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<title>20 April, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Social identification and risk dynamics: how perceptions of (inter)personal and collective risk impact the adoption of COVID-19 preventative behaviours</strong> -
<div>
Public adoption of preventative behaviours to reduce the transmission of COVID-19 is crucial to managing the pandemic, and so it is vital to determine what factors influence the uptake of those behaviours. Previous studies have identified COVID-19 risk perceptions as a key factor, but this work has typically been limited both in assuming that risk means risk to the personal self, and in being reliant on self-reported data. Drawing on the social identity approach (Reicher, Spears and Haslam, 2010), we conducted two online studies in which we investigated the effects of two different types of risk on preventative measure taking: risk to the personal self and risk to the collective self (i.e. members of a group with which one identifies). Both studies involved behavioural measures using innovative interactive tasks. In Study 1 (n = 199; data collected 27 May 2021), we investigated the effects of (inter)personal and collective risk on physical distancing. In Study 2 (n = 553; data collected 20 September 2021), we investigated the effects of (inter)personal and collective risk on the speed at which tests are booked as COVID-19 symptoms develop. In both studies, we find that perceptions of collective risk, but not perceptions of (inter)personal risk, influence the extent to which preventative measures are adopted. We discuss the implications both conceptually (as they relate to both the conceptualisation of risk and social identity processes) and also practically (in terms of the implications for public health communications).
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/vw7ze/" target="_blank">Social identification and risk dynamics: how perceptions of (inter)personal and collective risk impact the adoption of COVID-19 preventative behaviours</a>
</div></li>
<li><strong>An ex vivo human precision-cut lung slice platform provides insight into SARS-CoV-2 pathogenesis and antiviral drug efficacy</strong> -
<div>
COVID-19 has claimed millions of lives since the emergence of SARS-CoV-2, and lung disease appears the primary cause of the death in COVID-19 patients. However, the underlying mechanisms of COVID-19 pathogenesis remain elusive, and there is no existing model where the human disease can be faithfully recapitulated and conditions for the infection process can be experimentally controlled. Herein we report the establishment of an ex vivo human precision-cut lung slice (hPCLS) platform for studying SARS-CoV-2 pathogenicity and innate immune responses, and for evaluating the efficacy of antiviral drugs against SARS-CoV-2. We show that while SARS-CoV-2 continued to replicate during the course of infection of hPCLS, infectious virus production peaked within 2 days, and rapidly declined thereafter. Although most proinflammatory cytokines examined were induced by SARS-CoV-2 infection, the degree of induction and types of cytokines varied significantly among hPCLS from individual donors, reflecting the heterogeneity of human populations. In particular, two cytokines (IP-10 and IL-8) were highly and consistently induced, suggesting a role in the pathogenesis of COVID-19. Histopathological examination revealed focal cytopathic effects late in the infection. Transcriptomic and proteomic analyses identified molecular signatures and cellular pathways that are largely consistent with the progression of COVID-19 in patients. Furthermore, we show that homoharringtonine, a natural plant alkaloid derived from Cephalotoxus fortunei, not only inhibited virus replication but also production of pro-inflammatory cytokines, and ameliorated the histopathological changes of the lungs caused by SARS-CoV-2 infection, demonstrating the usefulness of the hPCLS platform for evaluating antiviral drugs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.18.537373v1" target="_blank">An ex vivo human precision-cut lung slice platform provides insight into SARS-CoV-2 pathogenesis and antiviral drug efficacy</a>
</div></li>
<li><strong>COVID-19 and silent hypoxemia in a minimal closed-loop model of the respiratory rhythm generator</strong> -
<div>
Silent hypoxemia, or `happy hypoxia’, is a puzzling phenomenon in which patients who have contracted COVID-19 exhibit very low oxygen saturation (SaO280%) but do not experience discomfort in breathing. The mechanism by which this blunted response to hypoxia occurs is unknown. We have previously shown that a computational model (Diekman et al., 2017, J. Neurophysiol) of the respiratory neural network can be used to test hypotheses focused on changes in chemosensory inputs to the central pattern generator (CPG). We hypothesize that altered chemosensory function at the level of the carotid bodies and/or the nucleus tractus solitarii are responsible for the blunted response to hypoxia. Here, we use our model to explore this hypothesis by altering the properties of the gain function representing oxygen sensing inputs to the CPG. We then vary other parameters in the model and show that oxygen carrying capacity is the most salient factor for producing silent hypoxemia. We call for clinicians to measure hematocrit as a clinical index of altered physiology in response to COVID-19 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.19.536507v1" target="_blank">COVID-19 and silent hypoxemia in a minimal closed-loop model of the respiratory rhythm generator</a>
</div></li>
<li><strong>Frequency Of pRenatal CAre viSiTs (FORCAST): study protocol to develop a core outcome set for prenatal care schedules</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Abstract Background: Prenatal care, one of the most common preventive care services in the United States, endeavors to improve pregnancy outcomes through evidence-based screenings and interventions. Despite the prevalence of prenatal care and its importance to maternal and infant health, there are several debates about the best methods of prenatal care delivery, including the most appropriate schedule frequency and content of prenatal visits. Current U.S. national guidelines recommend that low-risk individuals receive a standard schedule of 12 to 14 in-office visits, a care delivery model that has remained unchanged for almost a century. Objectives: In early 2020, to mitigate individuals exposure to the SARS-CoV-2 virus, prenatal care providers implemented new paradigms that altered the schedule frequency, interval, and modality (e.g., telemedicine) of how prenatal care services were offered. In this manuscript, we describe development of a core outcome set (COS) that can be used to evaluate the effect of the frequency of prenatal care schedules on maternal and infant outcomes. Methods: We will systematically review the literature to identify previously reported outcomes important to individuals who receive prenatal care and the people who care for them. Stakeholders with expertise in prenatal care delivery (i.e., patients/family members, healthcare providers, and public health professionals and policymakers) will rate the importance of identified outcomes in an online survey using a three-round Delphi process. A virtual consensus meeting will be held for a group of stakeholder representatives to discuss and vote on the outcomes to include in the final COS. Results: The Delphi survey was initiated in July 2022 with 71 stakeholders invited. A virtual consensus conference was conducted on October 11, 2022. Data is currently under analysis. Conclusions: More research about the optimal schedule frequency and modality for prenatal care delivery is needed. Standardizing outcomes that are measured and reported in evaluations of the recommended prenatal care schedules will assist evidence synthesis and results reported in systematic reviews and meta-analyses. Overall, this COS will expand the consistency and patient-centeredness of reported outcomes for various prenatal care delivery schedules and modalities, hopefully improving the overall efficacy of recommended care delivery for pregnant people and their families.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.17.23288705v1" target="_blank">Frequency Of pRenatal CAre viSiTs (FORCAST): study protocol to develop a core outcome set for prenatal care schedules</a>
</div></li>
<li><strong>A Perspective on Mature Gratitude as a Way of Coping with COVID-19</strong> -
<div>
Aim and Method: This perspective searches presents evidence of mature gratitude as a way of coping with the threats and boundaries of COVID-19. This narrative, non-systematic review will be based on studies from the COVID-19 period in association with more general literature on the characteristics of mature gratitude related to good mental health. Results: The results from the literature suggest that a confrontation with our existential vulnerability during a pandemic is not only a crisis but also an opportunity to view our lives in a different way. Mature gratitude, as proposed in this perspective, can help us in coping with the threats and boundaries that are part of our lives due to the COVID-19 pandemic. This time of crisis gives us the opportunity to self-reflect on our current life and plans for the future and to reframe them through a positive lens which can encourage individuals to actively strengthen their psychological resilience and coping skills. Conclusion: Cultivating an attitude of mature gratitude through actions of kindness, expressing being thankful for life and God, and enjoying all the small things in life helps in coping with the current threats of COVID-19 and building lifelong resilience for the future Knowledge about these associations can help psychologists, counselors, and coaches to support people who experience psychological issues due to the current pandemic and all crises to come.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/b9zq4/" target="_blank">A Perspective on Mature Gratitude as a Way of Coping with COVID-19</a>
</div></li>
<li><strong>Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants</strong> -
<div>
Among the multiple SARS-CoV-2 variants recently reported, the Delta variant has generated most perilous and widespread effects. Another variant, Omicron, has been identified specifically for its high transmissibility. Omicron contains numerous spike (S) protein mutations and in numbers much larger than those of its predecessor variants. In this report we discuss some essential structural aspects and time-based structure changes of a selected set of spike protein mutations within the Delta and Omicron variants. The expected impact of multiple-point mutations within the spike protein’s receptor-binding domain (RBD) and S1 of these variants are examined. Additionally, RBD of the more recently emerged subvariants BA.4, BA.5 and BA.2.12.1 are discussed. Within the latter group, BA.5 represents globally, the most prevalent form of SARS-CoV-2 at the present time. Temporal mutation profile for the subvariant BF.7 and currently circulating variants of interest (VOI) and variants under monitoring (VUMs) including XBB.1.5, BQ.1, BA.2.75, CH.1.1, XBB and XBF are computationally explored here briefly with the expectation that these structural data will be helpful to identify drug targets and to neutralize antibodies for the evolving variants/subvariants of SARS-CoV-2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.25.493484v5" target="_blank">Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants</a>
</div></li>
<li><strong>Post-COVID-19 syndrome and insulin resistance 20 months after a mild COVID-19</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objective SARS-CoV-2 infection is associated with impaired glucose metabolism. Although the mechanisms are not fully understood, insulin resistance (IR) appears to be a central factor. Patients who had a severe acute phase, but even asymptomatic or with mild COVID-19, have an increased risk of T2DM. After the acute phase, post-COVID-19 syndrome (PCS) also seems to be related to this metabolic disturbance, but there is a paucity of studies. This study aims to evaluate a possible relationship between PCS and IR after mild COVID-19 and, if confirmed, whether there are differences by sex. Subjects and methods Retrospective observational cohort study including subjects who had mild COVID-19 between April and September 2020 in a community setting. None had been vaccinated against SARS-CoV-2 at inclusion, and previous T2DM and liver disease were exclusion criteria. Patients who met NICE criteria were classified as PCS+. Epidemiological and laboratory data were analysed. Three assessments were performed: 1E (pre-COVID-19, considered baseline and reference for comparisons), 2E (approximately 3 months after the acute phase), and 3E (approximately 20 months after the acute phase). A triglyceride-to-glucose (TyG) index ≥8.74 was considered IR. Albumin-to-globulin ratio (AGR) and lactate dehydrogenase (LDH) were assessed as inflammatory markers. Bivariate analyses were performed, using nonparametric and repeated measures tests. A subsample without metabolic disorder or CVD (age&lt; median, BMI&lt;25 kg/m^2, elevated AGR, TyG index=7.80 [0.5]) was generated to reasonably rule out prior baseline IR that could bias the results. The relationships between PCS and TyG in 3E (TyG3) were modeled in 8 multiple regressions, stratifying by sex and BMI combinations. Results A total of 112 subjects (median [IQR] of age= 44 [20] years; 65 women) were analysed. Up to 14.3% was obese and 17% was hypertensive. Significant increases between 1E and 3E were registered regarding (i) basal glycemia (BG), 87 [14] mg/dL vs. 89 [14]; p=0.014, (ii) TyG index (8.25 [0.8] vs. 8.32 [0.7]; p=0.002), and (iii) LDH in 3rd tertile (16.1% vs 32.1%; p=0.007). A total of 8 previously normoglycemic subjects, showed BG2 or BG3 &gt;126 mg/dL. The subgroups with IR highest prevalence at 3E were those of BMI ≥25 kg/m^2 and PCS+. The subgroup without CVD presented a significant increase in the TyG index (TyG1=7.80 [0.1] vs. TyG3= 8.28 [0.1]; p=0.017). LDH1 was significantly correlated with TyG3 in both sexes (rho=0.214 in women, rho=0.298 in men); in contrast, LDH2 and LDH3 did not present such an association. In multivariable analysis, PCS has shown to be an independent and predictive variable of TyG index in women with BMI&lt;25 kg/m^2, after adjustment for age, hypertension, BMI, Charlson comorbidity index, AGR1, AGR2, LDH1, number of symptoms of acute COVID-19, and number of days of the acute episode (beta coefficient=0.350; p=0.039). Conclusions PCS has played a secondary role in predicting IR, showing a modest effect compared to BMI or prior hypertension. A significant increase in IR has been noted 20 months after mild COVID-19, both in cases of previous baseline IR and in those without previous IR. Basal serum LDH has shown to be predictive of current TyG, regardless of elevated LDH after SARS-CoV-2 infection. There were profound differences between women and men, confirming the need for a sex-stratified analysis when addressing the relation between PCS and glycemic alterations.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.17.23288637v1" target="_blank">Post-COVID-19 syndrome and insulin resistance 20 months after a mild COVID-19</a>
</div></li>
<li><strong>Infection Risk Shifts of Protests During Pandemics</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This research article examines the dual impact of protests on COVID-19 spread, a challenge for policymakers balancing public health and the right to assemble. Using a game theoretical model, it shows that protests can shift infection risks between counties, creating a dilemma for regulators. The empirical study analyzes two German protests in November 2020 using proprietary data from a bus-shuttle service, finding evidence to support the assumption that protests can shift infection risks. The article concludes by discussing the implications of these findings for policymakers, highlighting that regulators9 individually rational strategic decisions may lead to inefficient outcomes.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.15.23288618v1" target="_blank">Infection Risk Shifts of Protests During Pandemics</a>
</div></li>
<li><strong>Bivalent mRNA-1273.214 vaccine effectiveness in Qatar</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Qatar introduced COVID-19 bivalent vaccination for persons ≥12 years old using the 50-μg mRNA-1273.214 vaccine combining SARS-CoV-2 ancestral and omicron BA.1 strains. We estimated effectiveness of this bivalent vaccine against SARS-CoV-2 infection using a matched, retrospective, cohort study. Matched cohorts included 10,886 persons in the bivalent cohort and 53,901 persons in the no-recent-vaccination cohort. During follow-up, 36 infections were recorded in the bivalent cohort and 211 were recorded in the no-recent-vaccination cohort. None progressed to severe, critical, or fatal COVID-19. Cumulative incidence of infection was 0.53% (95% CI: 0.35-0.79%) in the bivalent cohort and 0.55% (95% CI: 0.47-0.65%) in the no-recent-vaccination cohort, 105 days after the start of follow-up. Incidence during follow-up was dominated by omicron XBB* subvariants including XBB, XBB.1, XBB.1.5, XBB.1.9.1, and XBB.1.9.2. The adjusted hazard ratio comparing incidence of infection in the bivalent cohort to that in the no-recent-vaccination cohort was 0.75 (95% CI: 0.53-1.08). Bivalent vaccine effectiveness against infection was 24.7% (95% CI: -7.0-47.2%). Effectiveness was 16.4% (95% CI: -24.6-47.3%) among persons with no prior infection and 35.3% (95% CI: -12.6-63.4%) among persons with prior infection. mRNA-1273.214 reduced incidence of SARS-CoV-2 infection, but the protection was modest at only ~25%. The modest protection may have risen because of XBB* immune evasion or immune imprinting effects, or combination of both.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.15.23288612v1" target="_blank">Bivalent mRNA-1273.214 vaccine effectiveness in Qatar</a>
</div></li>
<li><strong>Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants</strong> -
<div>
Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with the emergence of variants of concern, the clinical profile induced by SARS-CoV-2 infection has changed, with anosmia being less frequent. Here, we assessed the clinical, olfactory and neuroinflammatory conditions of golden hamsters infected with the original Wuhan SARS-CoV-2 strain, its isogenic ORF7-deletion mutant and three variants: Gamma, Delta, and Omicron/BA.1. We show that infected animals developed a variant-dependent clinical disease including anosmia, and that the ORF7 of SARS-CoV-2 contributes to the induction of olfactory dysfunction. Conversely, all SARS-CoV-2 variants were found to be neuroinvasive, regardless of the clinical presentation they induce. Taken together, this confirms that neuroinvasion and anosmia are independent phenomena upon SARS-CoV-2 infection. Using newly generated nanoluciferase-expressing SARS-CoV-2, we validated the olfactory pathway as a major entry point into the brain in vivo and demonstrated in vitro that SARS-CoV-2 travels retrogradely and anterogradely along axons in microfluidic neuron-epithelial networks.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.31.505985v2" target="_blank">Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants</a>
</div></li>
<li><strong>Exploring Physical and Biological Manifestations of Burnout and Post-Traumatic Stress Disorder Symptoms in Healthcare Workers: A Scoping Review Protocol</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Introduction: The COVID-19 pandemic has strained the mental and physical well-being of healthcare workers (HCW). Increased work-related stress and limited resources has increased symptoms of anxiety, depression, insomnia, and post-traumatic stress disorder (PTSD) in this population. Stress-related disorders have been strongly associated with long-term consequences including cardiometabolic disorders, endocrine disorders and premature mortality. This scoping review aims to explore available literature on burnout, PTSD, and other mental health-associated symptoms in HCW to synthesize relationships with physiological and biological biomarkers that may be associated with increased risk of disease, creating an opportunity to summarize current biomarker knowledge and identify gaps in this literature. Methods and Analysis: This scoping review uses the Arksey and O,Malley six-step scoping review methodology framework. The research team will select appropriate primary sources using a search strategy developed in collaboration with a health sciences librarian. Three reviewers will initially screen the title and abstracts obtained from the literature searches, and two reviewers will conduct independent reviews of full-text studies for inclusion. The research team will be reviewing literature focusing on which burnout and/or PTSD-associated physiological and biological biomarkers have been studied, the methodologies used to study them and the correlations between the biomarkers and HCW experiencing burnout/PTSD. Data extraction forms will be completed by two reviewers for included studies and will guide literature synthesis and analysis to determine common themes. Ethics and Dissemination: This review does not require ethical approval. We expect results from this scoping review to identify gaps in the literature and encourage future research regarding improving biologic and physiologic biomarker research in HCW. Preliminary results and general themes will be communicated back to stakeholders. Results will be disseminated through peer-reviewed publications, policy briefs, and conferences, as well as presented to stakeholders to an effort to invest in HCW mental and physical health.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.16.23288657v1" target="_blank">Exploring Physical and Biological Manifestations of Burnout and Post-Traumatic Stress Disorder Symptoms in Healthcare Workers: A Scoping Review Protocol</a>
</div></li>
<li><strong>Antibody Correlates of Protection for COVID-19 Convalescent Plasma Associated with Reduced Outpatient Hospitalizations</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
SARS-CoV-2 antibody levels associated with reduced hospitalization risk remain undefined. Our outpatient COVID-19 convalescent plasma (CCP), placebo-controlled trial observed SARS-CoV-2 antibody levels decreasing 22-fold from matched donor units into post-transfusion seronegative recipients. Unvaccinated recipients were jointly stratified by a) early or late transfusion (&lt; 5 or &gt;5 days from symptom onset) and b) high or low post-transfusion SARS-CoV-2 antibody levels (&lt; or &gt; geometric mean). Early treatment with high post-transfusion antibody levels reduced hospitalization risk-0/102 (0%) compared to all other CCP recipients-17/370 (4.6%; Fisher exact-p-0.03) and to all control plasma recipients-35/461 (7.6%; Fisher exact p-0.001). A similar donor upper/lower half antibody level and early late transfusion stratified analyses indicated significant hospital risk reduction. Pre-transfusion nasal viral loads were similar in CCP and control recipients regardless of hospitalization outcome. Therapeutic CCP should comprise the upper 30% of donor antibody levels to provide effective outpatient use for immunocompromised and immunocompetent outpatients.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.13.23288353v1" target="_blank">Antibody Correlates of Protection for COVID-19 Convalescent Plasma Associated with Reduced Outpatient Hospitalizations</a>
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<li><strong>Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial</strong> -
<div>
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Background: Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic and haemodynamic effects. Methods: In this randomised, controlled, open-label trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus empagliflozin 10mg once daily for 28 days or until discharge using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. On 3 March the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on 7 March. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 8 July 2021 and 6 March 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Overall, 289 (14%) patients allocated to empagliflozin and 307 (14%) patients allocated to usual care died within 28 days (rate ratio 0.96; 95% confidence interval [CI] 0.82-1.13; p=0.64). There was no evidence of significant differences in duration of hospitalisation (median 8 days vs. 8 days) or the proportion of patients discharged from hospital alive within 28 days (79% vs. 78%; rate ratio 1.03; 95% CI 0.96-1.10; p=0.44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (16% vs. 17%; risk ratio 0.95; 95% CI 0.84-1.08; p=0.44). Interpretation: In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.13.23288469v1" target="_blank">Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial</a>
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<li><strong>VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis</strong> -
<div>
The liver is known for its remarkable regenerative ability through proliferation of hepatocytes. Yet, during chronic injury or severe hepatocyte death, proliferation of hepatocytes is exhausted. To overcome this hurdle, we propose vascular-endothelial-growth-factor A (VEGFA) as a therapeutic means to accelerate biliary epithelial cell (BEC)-to-hepatocyte conversion. Investigation in zebrafish establishes that blocking VEGF receptors abrogates BEC-driven liver repair, while VEGFA overexpression promotes it. Delivery of VEGFA via non-integrative and safe nucleoside-modified mRNA encapsulated into lipid-nanoparticles (mRNA-LNP) in acutely or chronically injured mouse livers induces robust BEC-to-hepatocyte conversion and reversion of steatosis and fibrosis. In human and murine diseased livers, we further identified VEGFA-receptor KDR-expressing BECs associated with KDR-expressing cell-derived hepatocytes. This defines KDR-expressing cells, most likely being BECs, as facultative progenitors. This study reveals novel therapeutic benefits of VEGFA delivered via nucleoside-modified mRNA-LNP, whose safety is widely validated with COVID-19 vaccines, for harnessing BEC-driven repair to potentially treat liver diseases.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.17.537186v1" target="_blank">VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis</a>
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<li><strong>Growth Hormone Accelerates Recovery From Acetaminophen-Induced Murine Liver Injury</strong> -
<div>
Background and Aims: Acetaminophen (APAP) overdose is the leading cause of acute liver failure, with one available treatment, N-acetyl cysteine (NAC). Yet, NAC effectiveness diminishes about ten hours after APAP overdose, urging for therapeutic alternatives. This study addresses this need by deciphering a mechanism of sexual dimorphism in APAP-induced liver injury, and leveraging it to accelerate liver recovery via growth hormone (GH) treatment. GH secretory patterns, pulsatile in males and near-continuous in females, determine the sex bias in many liver metabolic functions. Here, we aim to establish GH as a novel therapy to treat APAP hepatotoxicity. Approach and Results: Our results demonstrate sex-dependent APAP toxicity, with females showing reduced liver cell death and faster recovery than males. Single-cell RNA sequencing analyses reveal that female hepatocytes have significantly greater levels of GH receptor expression and GH pathway activation compared to males. In harnessing this female-specific advantage, we demonstrate that a single injection of recombinant human GH protein accelerates liver recovery, promotes survival in males following sub-lethal dose of APAP, and is superior to standard-of-care NAC. Alternatively, slow-release delivery of human GH via the safe non-integrative lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP), a technology validated by widely used COVID-19 vaccines, rescues males from APAP-induced death that otherwise occurred in control mRNA-LNP-treated mice. Conclusions: Our study demonstrates a sexually dimorphic liver repair advantage in females following APAP overdose, leveraged by establishing GH as an alternative treatment, delivered either as recombinant protein or mRNA-LNP, to potentially prevent liver failure and liver transplant in APAP-overdosed patients.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.17.537197v1" target="_blank">Growth Hormone Accelerates Recovery From Acetaminophen-Induced Murine Liver Injury</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 )</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Standard of Care + Quinine Sulfate;   Drug: Standard of Care<br/><b>Sponsors</b>:   Universitas Padjadjaran;   National Research and Innovation Agency of Indonesia;   Prodia Diacro Laboratories P.T.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19</strong> - <b>Condition</b>:   Long COVID-19 Syndrome<br/><b>Intervention</b>:   Biological: MSC-derived exosomes<br/><b>Sponsors</b>:   Huazhong University of Science and Technology;   REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19</strong> - <b>Condition</b>:   Omicron Variant of COVID-19<br/><b>Intervention</b>:   Drug: Nirmatrelvir/Ritonavir<br/><b>Sponsor</b>:   Xiangao Jiang<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: mRNA-1283.222;   Biological: mRNA-1273.222<br/><b>Sponsor</b>:   ModernaTX, Inc.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate the Safety and Efficacy of Meplazumab in Treatment of COVID-19 Sequelae</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Meplazumab for injection;   Other: Normal saline<br/><b>Sponsor</b>:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Device: RD-X19;   Device: Sham<br/><b>Sponsor</b>:   EmitBio Inc.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Ropeginterferon alfa-2b;   Procedure: SOC<br/><b>Sponsor</b>:   National Taiwan University Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: SCB-2019/Clover;   Biological: AstraZeneca/Fiocruz;   Biological: Pfizer/Wyeth<br/><b>Sponsors</b>:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Postoperative Sugammadex After COVID-19</strong> - <b>Conditions</b>:   General Anesthesia;   COVID-19<br/><b>Interventions</b>:   Drug: Sugammadex Sodium;   Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg<br/><b>Sponsor</b>:   Korea University Ansan Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Azeliragon;   Drug: Placebo<br/><b>Sponsor</b>:   Salim S. Hayek<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants</strong> - <b>Condition</b>:   COVID19 Testing<br/><b>Interventions</b>:   Behavioral: FABI tailored COVID-19 testing pamphlet;   Behavioral: Standard COVID-19 home-based test kit<br/><b>Sponsors</b>:   Texas Woman’s University;   National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors</strong> - <b>Condition</b>:   Post Acute COVID-19 Syndrome<br/><b>Intervention</b>:   Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)<br/><b>Sponsor</b>:   Azienda Socio Sanitaria Territoriale di Lecco<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Intervention</b>:   Dietary Supplement: PS23 heat-treated<br/><b>Sponsors</b>:   Mackay Memorial Hospital;   Bened Biomedical Co., Ltd.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>:   COVID-19;   Diagnostic Test<br/><b>Intervention</b>:   Device: Lollipop<br/><b>Sponsor</b>:   University of Wisconsin, Madison<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring the Effect of Video Interventions on Intentions for Continued COVID-19 Vaccination</strong> - <b>Conditions</b>:   Vaccine Refusal;   COVID-19<br/><b>Interventions</b>:   Behavioral: Informational Video;   Behavioral: Altruistic Video;   Behavioral: Individualistic Video<br/><b>Sponsor</b>:   Sir Mortimer B. Davis - Jewish General Hospital<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kinetics and ability of binding antibody and surrogate virus neutralization tests to predict neutralizing antibodies against the SARS-CoV-2 Omicron variant following BNT162b2 booster administration</strong> - CONCLUSIONS: This study showed a significant drop in humoral immunity 6 months after booster administration. Anti-RBD IgG and Omicron sVNT assays were highly correlated and could predict neutralizing activity with moderate performance.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis of SARS-CoV-2 M<sup>pro</sup> inhibitors bearing a cinnamic ester warhead with <em>in vitro</em> activity against human coronaviruses</strong> - COVID-19 now ranks among the most devastating global pandemics in history. The causative virus, SARS-CoV-2, is a new human coronavirus (hCoV) that spreads among humans and animals. Great efforts have been made to develop therapeutic agents to treat COVID-19, and among the available viral molecular targets, the cysteine protease SARS-CoV-2 M^(pro) is considered the most appealing one due to its essential role in viral replication. However, the inhibition of M^(pro) activity is an interesting…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diosmetin alleviates acute lung injury caused by lipopolysaccharide by targeting barrier function</strong> - Acute lung injury (ALI) is an acute and devastating disease caused by systemic inflammation e.g. patients infected with bacteria and viruses such as SARS-CoV-2 have an unacceptably high mortality rate. It has been well documented that endothelial cell damage and repair play a central role in the pathogenesis of ALI because of its barrier function. Nevertheless, the leading compounds that effectively accelerate endothelial cell repair and improve barrier dysfunction in ALI are largely unknown. In…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis</strong> - Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HRESIMS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3’-C-8’’) biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results</strong> - CONCLUSIONS: AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Awareness raising and dealing with methanol poisoning based on effective strategies</strong> - Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ferrocenoyl-substituted quinolinone and coumarin as organometallic inhibitors of SARS-CoV-2 3CLpro main protease</strong> - The 3-chymotrypsin-like protease 3CLpro from SARS-CoV-2 is a potential target for antiviral drug development. In this work, three organometallic ferrocene-modified quinolinones and coumarins were compared to their benzoic acid ester analogues with regard to inhibition of 3CLpro using a HPLC-based assay with a 15mer model peptide as the substrate. In contrast to FRET-based assays, this allows direct identification of interference of buffer constituents with the inhibitors, as demonstrated by the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transcription factor <em>Dmrt1</em> triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility</strong> - Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Selective translational control of cellular and viral mRNAs by RPS3 mRNA binding</strong> - RPS3, a universal core component of the 40S ribosomal subunit, interacts with mRNA at the entry channel. Whether RPS3 mRNA-binding contributes to specific mRNA translation and ribosome specialization in mammalian cells is unknown. Here we mutated RPS3 mRNA-contacting residues R116, R146 and K148 and report their impact on cellular and viral translation. R116D weakened cap-proximal initiation and promoted leaky scanning, while R146D had the opposite effect. Additionally, R146D and K148D displayed…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of Potent Pyrazoline-Based Covalent SARS-CoV-2 Main Protease Inhibitors</strong> - Among the various genes and proteins encoded by all coronaviruses, one particularly “druggable” or relatively easy-to-drug target is the coronavirus Main Protease (3CLproor Mpro), an enzyme that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro with a small-molecule antiviral would effectively stop the ability of the virus to replicate,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Omicsynin B4 potently blocks coronavirus infection by inhibiting host proteases cathepsin L and TMPRSS2</strong> - The emergence of SARS-CoV-2 variants represents a major threat to public health and requires identification of novel therapeutic agents to address the unmet medical needs. Small molecules impeding viral entry through inhibition of spike protein priming proteases could have potent antiviral effects against SARS-CoV-2 infection. Omicsynin B4, a pseudo-tetrapeptides identified from Streptomyces sp. 1647, has potent antiviral activity against influenza A viruses in our previous study. Here, we found…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of novel papain-like protease inhibitors for potential treatment of COVID-19</strong> - The recent emergence of different SARS-CoV-2 variants creates an urgent need to develop more effective therapeutic agents to prevent COVID-19 outbreaks. Among SARS-CoV-2 essential proteases is papain-like protease (SARS-CoV-2 PLpro), which plays multiple roles in regulating SARS-CoV-2 viral spread and innate immunity such as deubiquitinating and deISG15ylating (interferon-induced gene 15) activities. Many studies are currently focused on targeting this protease to tackle SARS-CoV-2 infection. In…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Esculin alleviates LPS-induced acute lung injury via inhibiting neutrophil recruitment and migration</strong> - CONCLUSIONS: Esculin inhibits β(2) integrin-dependent neutrophil migration and chemotaxis, blocks the cytoskeletal remodeling process required for neutrophil recruitment, thereby contributing to its protective effect against ALI. This study demonstrates the new therapeutic potential of esculin as a novel lead compound.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>FDA approved drugs with antiviral activity against SARS-CoV-2: From structure-based repurposing to host-specific mechanisms</strong> - The continuing heavy toll of the COVID-19 pandemic necessitates development of therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved drugs for inhibitory effects against main protease enzyme (Mpro) substrate-binding pocket of SARS-CoV-2 for non-covalent and covalent binding. Top candidates were screened against infectious SARS-CoV-2 in a cell-based viral replication assay. Promising candidates included atovaquone, mebendazole, ouabain, dronedarone, and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>4’-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses</strong> - Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4’-Fluorouridine (4’-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Stunning End of Dominion’s Case Against Fox News</strong> - The voting-machine company has agreed to a seven-hundred-million-dollar settlement in its defamation suit against Rupert Murdoch’s cable news network. - <a href="https://www.newyorker.com/news/annals-of-communications/the-stunning-end-of-dominions-case-against-fox-news">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Biden’s New Green Jobs Are Boosting Purple and Red States</strong> - Why the President’s industrial policy could be key to his reëlection bid. - <a href="https://www.newyorker.com/news/our-columnists/bidens-new-green-jobs-are-boosting-purple-and-red-states">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Christian’s Thoughts on the Problem of Christian Nationalism</strong> - The separation of church and state, though under attack from the right, is still ingrained in our national psyche. Who’s best positioned to keep it there? - <a href="https://www.newyorker.com/news/daily-comment/a-christians-thoughts-on-the-problem-of-christian-nationalism">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>When the Culture Wars Come for the Public Library</strong> - A Montana county’s battle shows how faith in public learning and public space is fraying. - <a href="https://www.newyorker.com/news/dispatch/when-the-culture-wars-come-for-the-public-library">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My Family and the Monterey Park Shooter</strong> - My mom and my uncle spent their evenings at the dance studios of the San Gabriel Valley. After a mass shooting, I finally saw what those studios looked like on the inside. - <a href="https://www.newyorker.com/news/essay/my-family-and-the-monterey-park-shooter">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>When your neighbors become your overlords</strong> -
<figure>
<img alt="Cartoon of a man peering through blinds with binoculars." src="https://cdn.vox-cdn.com/thumbor/hkxfXf4EZJhkEb_sgSct3nZWpyY=/950x0:6605x4241/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72198606/GettyImages_1222453075.0.jpg"/>
<figcaption>
In HOAs and condos, everybody’s a little bit hero, a little bit villain. | SIphotography via Getty Images/iStockphoto
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
How HOAs became an unnecessary necessary evil.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YHT0dz">
There are few things more delicious than a homeowners association horror story. All over the internet, you can find tales of people <a href="https://www.thedrive.com/news/rivian-r1t-owner-targeted-by-hoa-for-parking-in-their-driveway">getting fined</a> for parking their vehicles in their own driveways or <a href="https://www.reddit.com/r/fuckHOA/comments/hva2re/id_really_like_some_good_hoa_horror_stories/">having a potted tomato plant</a> on their back porches or <a href="https://www.tiktok.com/@rachonlife/video/7203005944580853038?lang=en&amp;q=hoa%20horror%20stories&amp;t=1681220811907">leaving a bottle of Gatorade out</a> for one day. In Tennessee, a man returned from vacation to discover his car was missing; he thought it had been stolen, but in reality, his HOA <a href="https://www.youtube.com/watch?v=P3h21yZGFbc&amp;t=121s">had towed it</a> because it had a flat tire. A Maryland HOA <a href="https://www.wmar2news.com/matterformallory/homeowner-fined-40-000-for-a-few-inches-of-fence-takes-hoa-to-court">fined a homeowner</a> $40,000 because the fence she built was 8 inches too long. A Missouri HOA <a href="https://www.kmbc.com/article/purple-playground-poses-problem-for-lee-s-summit-family/3689929">threatened a family with jail time</a> because they’d put up a play set that was — gasp! — purple.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4Pm087">
It’s easy to laugh at the inanity of so much of it … until you find yourself peeking through your curtains trying to catch your neighbor putting her trash can out five minutes early because last year she reported you to the HOA for leaving up your Christmas lights past the New Year.
</p>
<aside id="30EwJ8">
<div>
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</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZbQ0Q5">
HOAs, condo associations, and co-op boards — all private forms of governing what’s called common-interest communities — are increasingly becoming an inevitability of homeownership in America. According to a <a href="https://www.globenewswire.com/en/news-release/2020/09/22/2097611/0/en/NEW-HOUSING-REPORT-SHOWS-73-9-MILLION-AMERICANS-RESIDE-IN-HOMEOWNERS-ASSOCIATIONS-AND-CONDOMINIUM-COMMUNITIES.html">2020 report</a> by the Foundation for Community Association Research, some 73.9 million Americans — more than a quarter of the population — live under such an arrangement. More than 75 percent of new housing built for sale is part of a community association. In other words, if you own a home in the US today, you’ve got a one in four chance of living under an HOA. (For the purposes of this story, I’m going to use “HOA” as the umbrella term here.) And if you are buying a home, well, have fun meeting your new neighbor-overlords!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g890Au">
Not all HOAs are evil. With people living in such close proximity, it makes sense to set some general rules and guidelines for coexistence. But it’s hard not to look at their setup and think they’re at least suboptimal.
</p>
<div class="c-float-right">
<aside id="ib1wuM">
<q>“This is the most widespread, dramatic privatization of local government functions that has ever happened”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mtONBe">
HOAs exist in service of community well-being, which is often just code for preserving property values, making developers rich in the process. They have a <a href="https://kinder.rice.edu/urbanedge/hoas-are-spreading-what-cost-cities">history of being</a> discriminatory and exclusionary. They are micro-sized super-local governments that are largely left to their own devices by the actual government, giving them the ability to exercise an enormous amount of unchecked power. In a nutshell, HOAs are privatization on hyperdrive.
</p>
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“This is the most widespread, dramatic privatization of local government functions that has ever happened. That’s essentially what’s happened. These are private governments that are doing all the things that local governments traditionally do. And it’s unregulated,” said Evan McKenzie, a political science professor at the University of Illinois Chicago and the author of <a href="https://www.amazon.com/Privatopia-Homeowner-Associations-Residential-Government/dp/0300066384"><em>Privatopia: Homeowner Associations and the Rise of Residential Private Government</em></a>. “This is the Reagan-era idea, the market will solve all our problems. No, it won’t. It’s not going to solve everybody’s problems. It’ll work out for some people, and for some people, it will be a disaster.”
</p>
<h3 id="A7fjbz">
HOAs mean dollar signs for developers (and save dollars for cities)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ng0I7X">
Homeowners associations in the US have been on the rise since the 1960s, the result of the suburban housing development boom and, in some cases, a desire by certain communities to keep certain people — namely, Black people — out. That legacy persists today: <a href="https://www.businessinsider.com/personal-finance/homeowners-associations-black-americans-discriminaiton-2020-9">As Insider notes</a>, neighborhoods with HOAs have more white and Asian residents and fewer Black residents than non-HOA neighborhoods, and Black residents continue to face discrimination in such arrangements.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FQpsnc">
In modern-day America, HOAs — which are usually set up as not-for-profit private corporations — persist and have proliferated as part of a win-win deal for real estate developers and for cities. A developer goes to a city offering to put a new subdivision in, offering to build out private streets and put in a private pool and a sewer system and whatever else to try to attract buyers, who will subsequently wind up paying for those amenities through fees. The city, which is likely cash-strapped, likes the deal — that way it doesn’t have to put in the street or sewer system or deal with the pool.
</p>
<div class="c-float-right">
<aside id="bOwmiv">
<q>“Real estate developers and cities see dollar signs with private governments”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rBNW0B">
“Real estate developers and cities see dollar signs with private governments. If you create a private subdivision or ideally a condominium, you can get much greater density, and the developers can get more houses on less land,” McKenzie said. “Cities love this because they get a whole bunch of new taxpayers paying a full property tax and they don’t have to provide the services to them they have to provide to everybody else.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OhN1JL">
The deal is supposed to be good for homeowners, too. People get some rules of the road, like that their neighbors won’t be blasting music at 3 am, and get access to that private pool if there is one. HOA-governed properties can also be worth more — <a href="https://www.sciencedirect.com/science/article/abs/pii/S0094119019300300">one 2019 study</a> found that houses in such subdivisions are worth at least 4 percent more than similar houses outside of them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mP7Ujh">
“Being in an HOA actually makes your housing value go up,” said Wyatt Clarke, one of the authors of the paper. However, he acknowledged most of that value is captured by the developer, and that over time, that extra value diminishes as properties age and houses start to turn over. “The fact that you’re in this unit, over time, becomes less and less valuable,” he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3HaXtB">
Trying to keep that property value up is by and large the main function of the HOA, and the way it accomplishes that is, in part, by enforcing all sorts of rules. The underlying theory is that everything staying the same and sticking to the original plan is the best way to maintain property values, McKenzie explained, which is why the houses have to be some shade of beige and the curtains have to be visible from the street and the mailboxes have to be a certain color and the lawns have to be maintained and watered. “The idea is that this is good for property value,” he said.
</p>
<h3 id="ko9g14">
Don’t like your HOA? Good luck.
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lXBDel">
The big issue with HOAs is that if you’ve got a problem with them — or they’ve got a problem with you — it can be quite a dilemma. Association rules aren’t just kind little suggestions, they’re enforced through fines and <a href="https://www.investopedia.com/terms/l/lien.asp">liens</a> and in extreme cases even <a href="https://www.propublica.org/article/they-faced-foreclosure-not-from-their-mortgage-lender-but-from-their-hoa">foreclosures</a> on people’s properties. And if you want to fight back against your HOA, you might be out of luck.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9RiMQA">
States and courts are generally pretty hands-off when it comes to dealing with HOAs, explained Michael Pollack, a professor at Cardozo Law School specializing in property law who has written about the <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=2753371">way courts do — and don’t — handle HOA rules in the past</a>. “Most states have some statute on the books that says something about the circumstances under which a court should not enforce a particular HOA rule or something like that, but usually, those statutes are written to say something like a court should not enforce a restriction or the rule if it is totally arbitrary or against public policy, which is a very narrow set of things,” he said. “It’s almost unheard of for a court to intervene in the day-to-day.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dMeJuD">
Part of the philosophy here is that “the market” is supposed to address the problem on its own and will punish HOAs with bad rules or overzealous enforcement because people will not buy in those communities and will flee. But that’s not how it works in practice. A lot of the time, buyers don’t fully know the consequences of buying in a development ruled by an HOA or even see the rules and regulations ahead of time. Buyers trying to sell might not be so open about the association, nor will the broader community trying to keep property values up. And in many communities, HOAs are the only game in town. In New York City, for example, you’ve practically always got to buy an apartment in a condo or co-op building — and in a co-op, the board can turn prospective buyers down.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uDOMZF">
“Courts tend to take the view of, look, if you don’t like it, you can leave, or you can work within the community to change things, exercise your voice,” Pollack said. But it’s not so easy to pick up and go; it’s financially and emotionally costly to move. Being on an HOA isn’t a particularly rewarding or fun job, either. It’s unpaid, thankless, and can be a lot of work. Sometimes, the people on the boards are the ones who are most eager to impose rules on their neighbors. “That creates the sort of predictable consequences that we see, which are boards of similar compositions remaining in place with pretty unhappy communities,” he said.
</p>
<div class="c-float-right">
<aside id="KLLZCL">
<q>In an HOA situation, everybody’s a little bit hero, a little bit villain</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z9jhHy">
Scott, who asked to use a pseudonym to protect his privacy, says most of his experience serving on his HOA board about a decade ago in South Florida was pretty ho-hum, with the exception of what to do about invasive snakes and alligators living in the nearby Everglades, which some board members were “obsessed” with. “I felt the emphasis on large reptiles was quite unnecessary, but if it helped people feel safe, then who am I to complain about it,” Scott said, noting that he thinks just a few people had died as a result of alligator attacks in the area over the years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uu5nR1">
Apart from dealing with the reptile situation, board members would drive around once a week with a checklist to make sure everything in the 24-house subdivision was in order, making sure lawns were mowed, trash was in order, and driveways didn’t have any cracks. I asked Scott why a crack in the driveway would matter — it’s not like it affects anyone else. He responded that people could see it, and there were golf courses in the area, reassuring me that the weekly drive-by situation “really is not as bad as it sounds.” The potential killer alligator situation he’d seemingly minimized did sound quite bad in comparison to some driveway cracks, but we moved on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="twc1cw">
In an HOA situation, everybody’s a little bit hero, a little bit villain.
</p>
<h3 id="LNN6L7">
Unaccountable little local governments, maybe not great
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rJh4nF">
Whenever someone tells me a story about their homeowners association or co-op board, I send them this 2021 <a href="https://www.wsj.com/articles/joining-an-hoa-there-will-be-hell-to-pay-11618491620">Wall Street Journal gem</a> that likens co-op boards to “Ted Bundy, whoever designed Gmail, and bad paper cuts” and large condo boards to “airplane passengers who clip their nails in flight.” Going forward, I will also be sending them this <a href="https://www.youtube.com/watch?v=qrizmAo17Os"><em>Last Week Tonight </em>segment</a> with John Oliver on HOAs, in which he describes state postures toward people looking for legal remedies to deal with their associations as, “You’re fucked!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fwLPWV">
HOAs can do a lot of things that government can’t do. They can tell you what signs you can and can’t put outside of your home, because the First Amendment protects your right to free speech from being infringed upon by the government but not by a private entity. They can tell you that your truck has to be parked in the garage or not parked at all because they don’t want the neighborhood to look too “working class.” They can’t overtly say they don’t want people of color in the subdivision, but they can make it very hard for people of color to get in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OH5LLj">
There is no great fix to HOAs in the US, and truth be told, they’re not going away. But are there ways to make them better? Tighter regulations — which developers push hard to avoid — could be a start. There’s also a conversation to be had about why municipalities are so cash-strapped, which is part of what drives them to allow for more private subdivisions and condos in the first place.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3C64RE">
McKenzie pointed out that more attention needs to be paid to how much money these associations and boards have to make sure they’re able to make repairs when necessary and buildings don’t entirely go under. In some scenarios, condo associations wind up having to sell buildings off entirely. Or, in the most dire scenario, you end up with the Surfside condominium collapse in Florida in 2021, which killed nearly 100 people, after the building <a href="https://www.cnn.com/2021/07/08/us/surfside-collapse-condo-finances-invs/index.html">had trouble getting residents to put up funds to pay for repairs</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wHzsbB">
To put it short, these unaccountable little governments could stand to be held a little more accountable. “The only way to make it work in the long term is a little bit more assertive role of government,” McKenzie said. “But this really just epitomizes the whole era we’ve been in for the last 40 years: privatize everything, the market solves all our problems. I’m sorry, no.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5G5qzT">
<em>We live in a world that’s constantly trying to sucker us and trick us, where we’re always surrounded by scams big and small. It can feel impossible to navigate. Every two weeks, join Emily Stewart to look at all the little ways our economic systems control and manipulate the average person. Welcome to </em><a href="https://www.vox.com/the-big-squeeze"><em>The Big Squeeze</em></a><em>.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NF25sR">
<a href="http://vox.com/big-squeeze-newsletter"><em>Sign up to get this column in your inbox</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fEmYHz">
<em>Have ideas for a future column or thoughts on this one? Email </em><a href="mailto:emily.stewart@vox.com"><em>emily.stewart@vox.com</em></a>.
</p></li>
<li><strong>3 theories to explain why syphilis rates are exploding among women</strong> -
<figure>
<img alt="A woman stands in front of a graffitied wall holding a towel to her face." src="https://cdn.vox-cdn.com/thumbor/Np_lMXWk6WfuF4Bqd6YycqLnwgY=/167x0:2834x2000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72198371/820430806.0.jpg"/>
<figcaption>
A woman with substance use disorder pauses under the bridge where she lives in the Kensington section of Philadelphia, Pennsylvania, on July 21, 2017. Substance use disorder and homelessness are risk factors for syphilis. | Spencer Platt/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The trend is likely a symptom of failed drug, education, and health policy.
</p>
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</p>
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</p>
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</p>
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</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x13sRS">
For a big chunk of the past two decades, sexual health experts generally thought of syphilis as a disease of greatest concern to gay men and their sexual networks. In 2014, more than <a href="https://www.cdc.gov/nchhstp/newsroom/2015/std-surveillance-report.html">90 percent</a> of US cases were diagnosed in men, the vast majority of whom had sex with other men.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QtfzBI">
But in 2015, that began to change: Syphilis began ticking upward in heterosexual adults, too — especially among women. By 2021, women accounted for about a quarter of new syphilis cases; the Centers for Disease Control and Prevention recently released <a href="https://www.cdc.gov/std/statistics/2021/default.htm">data</a> detailing the dramatic rise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9KyMtM">
Syphilis causes skin rashes in its early stages and if untreated, in its later stages, can lead to complications ranging from neurologic problems to cardiovascular disease to death (in around <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743072/">10 percent</a> of cases).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tc6Okt">
Between 2017 and 2021, infection rates in women <a href="https://www.vox.com/science-and-health/23392423/std-syphilis-sti-maternal-prenatal-care-sexually-transmitted">rose</a> more than threefold, from two per 100,000 people to seven per 100,000 — a much larger increase than the rise among men, and larger still than the uptick in other sexually transmitted infections (STIs), like chlamydia and gonorrhea. (In absolute numbers, the majority of syphilis infections continue to occur among men who have sex with men, and their infection rates are rising, too. But that increase has been sluggish compared with the meteoric increase among women.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zBbvi4">
Syphilis is particularly concerning when it affects women of childbearing age because of the catastrophic effects it can have on pregnancy. Infections in pregnant people can lead to congenital infections in their newborns, placing them at <a href="https://www.cdc.gov/nchhstp/pregnancy/effects/syphilis.html">high risk</a> for stillbirth or severe disability. Indeed, congenital syphilis rates have risen <a href="https://www.cdc.gov/std/statistics/2021/default.htm#CongenitalSyphilisCases">precipitously</a> alongside rates in adult women over the past five years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P9pEKp">
The reasons for syphilis’s rising rates in women are complex. An unfortunate fact of biology likely plays a part: People with vaginas are <a href="https://www.cdc.gov/std/health-disparities/stds-women-042011.pdf">more susceptible</a> to STIs than those with penises.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="16Qly2">
But that anatomical reality, while extremely annoying, isn’t enough to explain why an <a href="https://www.cdc.gov/std/syphilis/stdfact-syphilis.htm">easily curable STI</a> (with just one dose of antibiotics!) is newly and uncontrollably surging among women. Rising syphilis rates in women — and their babies — signal that multiple societal failsafes have, in fact, failed. This is a big red flag that should provoke us to wonder what’s gone wrong, and to think urgently about fixes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="blUIwE">
Here are three theories for how social changes in the US might be contributing to syphilis’s shifting dynamics.
</p>
<h3 id="QUyZC8">
<ol type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Homelessness and substance abuse increase syphilis risk more for women — and those at highest risk are getting less of the care they need.
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J5AHF1">
<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915834/">Among both heterosexual men and women</a>, some of the biggest socioeconomic risk factors for syphilis include drug use — especially opioid, methamphetamine, and heroin use — <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595853/">poverty, homelessness, and transactional sex</a>. Several of these factors have been <a href="https://endhomelessness.org/homelessness-in-america/homelessness-statistics/state-of-homelessness/">on</a> <a href="https://www.vox.com/science-and-health/2017/8/3/16079772/opioid-epidemic-drug-overdoses">the rise</a> in recent years, and they often travel together.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wWTd7t">
Although these trends affect all genders, it’s among women where they most strongly translate into syphilis risk. Among youth, homelessness raised the risk of syphilis and other STIs <a href="https://www.jstor.org/stable/48512261">far more in girls than in boys</a>. And among people with substance use disorders, women in one study were nearly <a href="https://www.sciencedirect.com/science/article/abs/pii/S0749379722003889">twice as likely</a> to have transactional sex as men. That led to big negative consequences that fell largely to women: In the same study, people who had transactional sex were three times as likely to have syphilis as those who didn’t.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pMH45O">
Meanwhile, the safety-net sexual health services that are supposed to provide preventive care, testing, and treatment for uninsured Americans, including those at highest risk of syphilis, have dwindled. Since 2004, funding for STI prevention has fallen <a href="https://www.vox.com/science-and-health/23392423/std-syphilis-sti-maternal-prenatal-care-sexually-transmitted">41 percent</a>, and many counties <a href="https://pubmed.ncbi.nlm.nih.gov/32001050/">don’t have a safety-net sexual health clinic</a> at all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RiBZWu">
That means many women with the highest vulnerability and the lowest resources — and the men who are most likely to be their sources of infection — are facing bigger barriers than ever to getting tested and treated for syphilis. This is perhaps especially true in rural America. There, the disproportionate impact of the opioid epidemic raises the infection risk for a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595853/">higher proportion of women</a><strong> </strong>— and the disproportionate closure of health facilities more broadly reduces their access to care.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hFlSL6">
The declines in sexual health care have been going on for decades: Nearly 18,000 women got STI testing and treatment at publicly funded clinics in 2018 — about <a href="https://pubmed.ncbi.nlm.nih.gov/34735419/">half as many</a> as in 2010. Simultaneously, more people are getting STI care in <a href="https://www.sciencedirect.com/science/article/abs/pii/S0091743517301482">emergency rooms</a>, where providers often altogether skip testing for syphilis, Irene Stafford, an OB-GYN and syphilis researcher at the University of Texas Health Science Center at Houston, <a href="https://www.vox.com/science-and-health/23392423/std-syphilis-sti-maternal-prenatal-care-sexually-transmitted">told me</a> in an interview last fall.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uyr9vL">
In these settings, providers more often test patients for chlamydia and gonorrhea than for syphilis, she said, as they are more common.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ssa6bq">
Only about a third of women Stafford sees for syphilis infection complete their treatment, she said, largely because of a mix of socioeconomic challenges and despair. “We have patients who are already mistrusting the government, mistrusting health care, can’t get insured, the health clinics are closed, they’re being trafficked,” she said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bjgTg3">
Syphilis’s persistence and growth among women who are already so marginalized shows how poorly equipped the US health care system is for finding and treating disease in the most vulnerable Americans.
</p>
<h3 id="coaT91">
<ol start="2" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">It’s getting harder to access prenatal care, a key catch-and-treat point for syphilis.
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j68njf">
Rising syphilis rates in women may also be linked to another burgeoning crisis: declining access to maternal health care.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xHUNio">
Most states <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081215/#R8">require</a> some form of syphilis testing during pregnancy. For that reason, prenatal care is an important tool for catching and treating women’s syphilis infections — and a critical opportunity for preventing these infections from leading to devastating effects in newborns.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cTZW9p">
But prenatal care is becoming increasingly hard to find. Rural hospitals with birth centers —which usually also offer prenatal care — have been closing at an <a href="https://www.nytimes.com/2023/02/26/health/rural-hospitals-pregnancy-childbirth.html">astonishing rate</a>, and obstetricians have been leaving rural communities for urban centers.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y5sAga">
According to the March of Dimes, nearly <a href="https://www.marchofdimes.org/maternity-care-deserts-report">7 million women</a> of childbearing age have low or no access to maternity care, and the trend disproportionately affects rural parts of the South and the Plains states.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sd5BTW">
The lack of access is concerning considering that in 2021, one-fifth of women diagnosed with syphilis were pregnant. How many more cases might be caught if prenatal care access was closer to women in need?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KQ0sSH">
But it’s not just geographic distance that forms a barrier to accessing prenatal care. In 2020, about <a href="https://www.marchofdimes.org/peristats/assets/s3/reports/2022-Maternity-Care-Report.pdf">11 percent</a> of American women were uninsured — and women without health care coverage are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016223/">less likely</a> to seek prenatal care.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CgCY2I">
Additionally, while pregnant women who use drugs are at higher risk for getting infected with syphilis, they face state policies that harshly punish substance use during pregnancy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KjZPJS">
“Sometimes people are afraid to seek prenatal care because of the consequences,” said Robert McDonald, a medical epidemiologist who works on syphilis prevention efforts at the CDC, in an <a href="https://www.vox.com/science-and-health/23392423/std-syphilis-sti-maternal-prenatal-care-sexually-transmitted">interview</a> last fall.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0PTlvS">
<a href="https://www.guttmacher.org/state-policy/explore/substance-use-during-pregnancy">Twenty-four states</a> have laws on the books that consider drug use while pregnant to be child abuse. Several states go even further, allowing women to be jailed or involuntarily committed to rehabilitation if they are found to be using drugs during pregnancy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="54uFH3">
The result is that women at highest risk for having syphilis — those with substance use disorders — often avoid the very system that’s intended to protect themselves and their pregnancies.
</p>
<h3 id="bwoM7d">
<ol start="3" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">School sex education is failing to give young women practical STI-prevention tools.
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In an ideal world, people would learn how to keep themselves from catching syphilis before the opportunity to do so came up. But in many American classrooms, students are getting sex education that simply doesn’t prepare them to avoid STIs.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="esJyek">
Sex education in the US is quite the patchwork when it comes to scientific accuracy: Only <a href="https://www.guttmacher.org/state-policy/explore/sex-and-hiv-education?gclid=CjwKCAjw__ihBhADEiwAXEazJpPYkfu508r2KqcpIZgg0ax5CRTE3PAVyey3DyG4mDddKV-323_jtRoCcMoQAvD_BwE">17 states</a> require sex ed content to be medically accurate. Meanwhile, 19 states require programs to teach that sex should only happen within marriages, and 29 states require programs to emphasize sexual abstinence.
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Programs grounded in religious dogma rather than reality leave young people with more questions than answers about their bodies and about their own sexual health, and make many feel like they’ve done something wrong by being sexually active, or even having sexual thoughts. And their effects are particularly detrimental to young women.
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So-called “abstinence-only until marriage” (AOUM) programs reinforce gender stereotypes about passive women and aggressive men. Studies have shown that women<strong> </strong>who buy into these gender roles are <a href="https://pubmed.ncbi.nlm.nih.gov/16752117/">less likely</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12511212/">to use condoms</a>, making them more vulnerable to STIs, including syphilis. Studies also showed students who made virginity pledges had <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/jomf.12279">higher STI and non-marital pregnancy rates</a>, and were <a href="https://www.sciencedirect.com/science/article/abs/pii/S1054139X05000558">less likely</a> to use condoms and to be tested for STIs.
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Stigmatizing sexual activity among teens — whether intentionally or not — also <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334654/">reduces the likelihood</a> that a young woman with an STI will seek care for it. Because syphilis can hang around in the body for years before causing severe symptoms, that means the negative effects of low-quality sex ed in high school can lead to health problems that manifest well into adulthood.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fwjzpw">
It’s not like there’s no better way: Inclusive, medically accurate sex ed that includes education on healthy relationships and communication has been proven not only to reduce <a href="https://www.sciencedirect.com/science/article/abs/pii/S0749379711009068">STI rates</a>, but also to lead to lower rates of unwanted pregnancy.
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Effective sex ed goes well beyond teaching students the basics of sexual biology, said Michelle Slaybaugh, a former school sex educator who directs social impact and communications at <a href="https://siecus.org/about-siecus/">SIECUS</a>, a nonprofit comprehensive sex ed advocacy organization, in an interview last summer.
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“Students have to understand what it means to be turned on, what does pleasure feel like,” said Slaybaugh. “Then they can understand, when they are in those moments, how they need to move forward to safely protect themselves and their partners.”
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It’s wildly unlikely that such a nuanced brand of sex ed will hit all the US classrooms where it’s needed anytime soon.
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<h3 id="9oWxYF">
Punitive, stigmatizing policies make the situation worse — not better
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DmcbRQ">
What so many of the above trends have in common is that they result from policies attempting to incentivize desired behaviors by punishing or stigmatizing undesired ones.
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It’s clear in the case of opioids, where the strict punishments for abuse keep people from seeking care.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r1VyrJ">
Similarly, comprehensive sex education could actually reduce young women’s risk for syphilis. But a preference for programs that systematically stigmatize young people’s sexuality means many are deprived of the tools they need to negotiate safe sex.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qx6SgA">
These policies reduce women’s autonomy, their trust in health care providers, and their ability to get their needs met. Syphilis is just one signal of these punitive approaches’ harms — but it’s one we should heed.
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<li><strong>The devil lurking in the dust</strong> -
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<img alt="" src="https://cdn.vox-cdn.com/thumbor/tjg3z6GITFCmh7iGSKAM6F9O5YQ=/250x0:1750x1125/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72164762/MVP_VOX_LEDE_VALLEY_FEVER.0.jpg"/>
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Millie von Platen for Vox
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
How extreme weather is driving a deadly fungus further into the American West
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o6PZOV">
<em>Part of the issue </em><a href="https://www.vox.com/the-highlight/23682697/colorado-river-drought-100-year-old-mistake-thats-reshaping-the-american-west"><em><strong>The 100-year-old-mistake that’s reshaping the American West</strong></em></a><em> from </em><a href="https://www.vox.com/the-highlight?itm_campaign=hloct22&amp;itm_medium=article&amp;itm_source=intro"><em><strong>The Highlight</strong></em></a><em>, Vox’s home for ambitious stories that explain our world.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ty1VEu">
On a cloudless day in March, Marieke Ramsey crouches against the mossy wall of a shallow gulch just inside the Phoenix city limits. She brandishes a kitchen spoon — “Nothing really fancy with some of our tools,” she tells me — and motions toward a fist-sized crevice in a craggy section of the streambed.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YAUEy6">
It’s a rodent burrow, perhaps home to a <a href="https://www.desertmuseum.org/kids/oz/long-fact-sheets/krat.php">kangaroo rat</a> or a <a href="https://www.desertmuseum.org/kids/oz/long-fact-sheets/White-throated%20woodrat.php">white-throated woodrat</a>, although Ramsey isn’t sure. She stoops, awkwardly angling her wrist to scrape a few spoonfuls of loose dirt from just inside the burrow, then deposits it into a sterile plastic cup. “As minimal soil destruction as possible” helps preserve what is, after all, an animal’s home, she says: “Pack in, pack out.”
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In a few weeks, Ramsey — a graduate student in mycologist <a href="https://www.bridgetbarker.com/">Bridget Barker’s lab </a>at Northern Arizona University — will analyze this and other soil samples from other Phoenix-area sites to look for signs that Coccidioides<em>, </em>the fungus that causes Valley fever, is claiming new territory within a state it has already besieged.
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Valley fever — also called coccidioidomycosis, although both the disease and its cause are often shortened to “cocci” (rhymes with “foxy”) — can be serious and even fatal in humans and animals, and can cause disease ranging from flu-like illness to pneumonia to meningitis, a dangerous infection of the membranes surrounding the brain and spinal cord.
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The infection spreads when fungal spores packed into dry soil get swirled into the air by <a href="https://www.youtube.com/watch?v=3sv9ewx0NZg">dust storms</a> that periodically roar through the desert, or when <a href="https://pubmed.ncbi.nlm.nih.gov/29053941/">construction projects</a> tear into the ground. Ramsey is hunting for Cocci in rodent dwellings to better understand the link between these small mammals and the fungus’s presence in soil. Although scientists have for decades understood that small rodents carry the infection in areas where the fungus is endemic, they’re still struggling to explain why exactly rodents and Cocci so often <a href="https://www.mdpi.com/2309-608X/6/4/320">appear in the same places</a> — and what that portends for the future.
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Unlike respiratory diseases like the flu or Covid-19, where fresh air is often key to preventing infections, all a person needs to do to get Valley fever is breathe outdoor air in an endemic area. People have gotten infected while <a href="https://www.pcta.org/discover-the-trail/backcountry-basics/safety-tips/valley-fever/">hiking</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/24739339/">filming TV shows</a>, and <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5049a2.htm">flying model airplanes</a>, and those who <a href="https://www.cdc.gov/niosh/topics/valleyfever/risk.html">work outdoors in some way that disrupts soil</a> are at highest risk: construction workers, wildland firefighters, agricultural workers, archaeologists. And while most other fungal infections primarily impact immunocompromised people, Cocci is capable of causing disease in people with healthy immune systems.
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<q>Where there’s dust, there can be Valley fever</q>
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Cocci isn’t new: It’s thrived in the Americas’ hot, arid climates <a href="https://pubmed.ncbi.nlm.nih.gov/17256570/">for millennia</a>. In the United States, the hotbed has largely included a relatively narrow strip of land spanning what’s now the Southwest’s Four Corners region and parts of California and Texas.
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<img alt=" " src="https://cdn.vox-cdn.com/thumbor/5aOwnNApTpRyMoNUof-Ho9vGZR8=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24595615/Screenshot_2023_04_19_at_9.34.48_AM.png"/>
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Estimated areas with coccidioidomycosis (Valley fever) in the United States. (Source: <a class="ql-link" href="https://www.cdc.gov/fungal/diseases/coccidioidomycosis/maps.html" target="_blank">CDC</a>.)
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But now, that slim band is fast expanding. Researchers estimate that by 2095, the parts of the US where people will be most susceptible to Valley fever will more than <a href="https://agupubs.onlinelibrary.wiley.com/doi/epdf/10.1029/2019GH000209">double</a>, the risk encroaching to envelop almost the entire Western half of the country.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8EmOmi">
Scientists and public health experts are still working to understand this fungus and its life cycle. But what they’ve learned so far suggests it will spread because of complex and interconnected issues fueled by climate change — change we can already see.
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The Colorado River snakes through many of the states afflicted by Valley fever. This essential water source and the reservoirs it feeds are contracting at an alarming rate, making these regions dustier — and where there’s dust, there can be Valley fever.
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Right now, on a national scale, infections are rare. But where they do occur, they are highly consequential. In the early 2000s, researchers found Cocci caused <a href="https://wwwnc.cdc.gov/eid/article/12/6/06-0028_article">nearly a third of pneumonia cases</a> in an outpatient clinic network in Tucson, Arizona. Experts recently projected that climate change will drive cases up <a href="https://agupubs.onlinelibrary.wiley.com/doi/epdf/10.1029/2019GH000209">threefold</a> over the next 50 years.
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Although states <a href="https://www.mdpi.com/2309-608X/9/1/83">aren’t required to report</a> fungal infections to federal agencies, in 2019, the Centers for Disease Control and Prevention heard of about <a href="https://www.cdc.gov/fungal/diseases/coccidioidomycosis/statistics.html">20,000 Valley fever cases annually</a>, with about 200 of them fatal.
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The fungus’s incursion northward, past state lines and into new territory, will probably happen undetected, at least for a while. That’s partly because outside research laboratories like the one where Ramsey works, no one is systematically charting its spread through desert soil.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="H0Rhbt">
But it’s also because the US undercounts Valley fever cases on a grand scale. Even in places where Cocci is literally underfoot, health care providers simply <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875278/">don’t think to test for the infection</a> in people who show up sick. Some estimates place the true annual US incidence of Cocci upward of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749157/?report=reader">350,000 cases</a> — more than 17 times higher than what’s reported to the CDC — and suggest public health authorities are also broadly undercounting Cocci <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080208/">deaths</a>.
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For a pathogen with so much destructive potential, Cocci is shrouded in mystery. There’s no map to show, in real time, exactly where it’s lurking. We haven’t yet figured out how to vaccinate people against infection. And nobody’s certain how it spreads through the soil — which makes staying ahead of it a near-impossible task.
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Still, we know the fungus’s territory is growing, driven by extreme <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1257592/">dry-then-wet weather cycles</a> and, perhaps, by their influence on small rodent life. The point of Ramsey’s work is to alert both the general public and their health care providers to the risk that poses: “You can’t just read a textbook” to pinpoint where Cocci is a threat, she said. She and others are working to build something approximating a real-time map of where the fungus is, although “it’s super early days,” said Barker, her boss.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UBoIzV">
A growing community of scientists is fervently seeking answers to Cocci’s biggest questions, and answers are within reach. But as climate-driven changes to the soil of the American West speed the fungus’s life cycle into overdrive — and bureaucracy and outdated medical practices sluggishly evolve — can we outrun a pathogen that seems engineered to evade us?
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<h2 id="PgZAA8">
How is Cocci spreading?
</h2>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mjKLSf">
Starting from its discovery in the late 1800s, Cocci has perplexed scientists. When they first observed it under a microscope — after being isolated from the facial sores of an Argentine soldier in 1892 — scientists first mistook it for a parasite called Coccidia<em>. (</em>The mistake in the spherule’s original identification led to the organism’s name,<em> </em>Coccidioides<em>: </em>literally, “like a Coccidia.”)
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It turned out to be something from a completely different kingdom of life. In 1900, microbiologists realized the germ was actually a dimorphic fungus, so named because it takes one of two forms — small, round, thick-walled orbs called spherules or long, brittle chains of spores — depending on the moisture and temperature of its environment.
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The organism’s shape-shifting trick makes it an especially prodigious chaos agent: Inside the lung, it transforms into its brawny spherule form, too strong to be taken down by the immune system’s front-line fighters. That form then births hundreds of mini-spherules, replicants equipped to make mischief anywhere and everywhere else in the body.
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But before they get into our lungs, Cocci spores spend a lot of time living in the dirt.
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Scientists first realized soil was the source of Cocci infection in 1932, when two bacteriologists from the University of California Berkeley <a href="https://journals.sagepub.com/doi/abs/10.3181/00379727-29-6159?journalCode=ebma">isolated the fungus from soil</a> gathered near the barracks of a Kern County, California, ranch where four workers had fallen ill.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A3WK42">
This discovery only opened up more mysteries about the fungus. Cocci perplexed its observers by growing only sluggishly in soil. That raised a big question: How does an organism that can barely reproduce in the dirt get and stay there — and in quantities high enough to cause disease in people who are just passing by?
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Over the following near-century, several hypotheses came and went. Early on, Chester Emmons, the <a href="https://www.researchgate.net/publication/302139611_Cryptococcosis_From_Discovering_the_Natural_Reservoir_of_its_Etiology_to_the_Genetic_Manipulation_of_Cryptococcus_neoformans_Milestones_in_Cryptococcal_Research_by_Intramural_Investigators_at_NIAID/figures?lo=1">granddaddy of American medical mycology</a>, hypothesized rodents were the reservoir for the pathogen. That theory receded over the following years, until in 2009, graduate students working with John Taylor, a mycologist and fungal genomics specialist at UC Berkeley, had an epiphany: Cocci eats meat.
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“Almost all fungi eat plants. A very few fungi can eat animals,” said Taylor. But Cocci DNA lacked the genes that would have encoded plant-metabolizing enzymes, and were chock full of the <a href="https://pubmed.ncbi.nlm.nih.gov/19717792/">genetic markers of a carnivore</a>. “When we saw that, we went, ‘Emmons was right.’” Taylor said.
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The breakthrough helped explain two important things. First, how rodents get the fungus into the soil. And second, how climate change — and its drastic extremes of drought and wet weather — may be furthering Cocci’s spread.
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The unifying theory was called the <a href="https://pubmed.ncbi.nlm.nih.gov/30690603/">endozoan hypothesis</a>, which Taylor and Barker, the Northern Arizona University mycologist, proposed in 2019.
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<aside id="UxvauB">
<q>“I was shocked that it was projected to reach the US-Canadian border by year 2100”</q>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5IMgxw">
It goes like this: A rodent inhales a Cocci spore, and for a long time, nothing happens. Although the rodent doesn’t get sick, the fungus lives inside it in a dormant state — in other words, as an endozoan. When the rodent dies, the fungus “wakes up” and goes to work, eating it from the inside out.
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The strategy gives Cocci an enormous advantage over other microorganisms that eat dead animals. The fungus is first in the microbial chow line to devour this “wet bag of protein,” as Taylor put it — “a very good place to be if you’re patient.”
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Climate change fits into this picture because temperature and precipitation have direct effects on the rodent life cycle.
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Imagine, for example, what happens to a family of kangaroo rats during just one drought-flood cycle. The rats, named for their <a href="https://www.youtube.com/watch?v=-hyKWwiefF8">spring-loaded</a> hind legs and feet, depend on desert vegetation to survive, and during a drought, there’s less for them to eat — which means more of them die. In the <a href="https://eurekamag.com/research/025/512/025512662.php">quarter or so</a> of the rats whose lungs harbor dormant Cocci, the fungi, no longer constrained by the rodents’ immune systems, belly up to the all-you-can-eat carcass bar.
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The fungi prefer to grow in moist environments, so the feast is over once the carcass dries out. In its wake, kangaroo rat-shaped clusters of bones, skin, and brittle fungal spores are left behind. The more drought, the more half-eaten rat bodies there are scattered underground.
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But that’s not where it ends: Climate change could also increase the geographic region in which Cocci live — quite possibly, by driving migration of their rodent hosts.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="I71SQa">
Now, imagine that after several months of drought and death, big rains come. This pattern of drought followed by intense rains is sometimes called “<a href="https://www.vox.com/energy-and-environment/23550073/california-floods-rainfall-weather-climate-change-whiplash">weather whiplash</a>” — and some climate scientists expect more of it in the decades to come.
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During those rains, desiccated rat bodies rehydrate, and the Cocci consume what’s left of them, growing in number. Green shoots sprout where water has percolated into once-arid crevices, and the surviving kangaroo rats get fat amid the plenty: perfect conditions for making more of themselves. Rodent families multiply, perhaps to the point that their existing neighborhoods get crowded.
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Some of these young kangaroo rats will get infected with Cocci, although how that happens isn’t entirely clear.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TxHDso">
It’s plausible — although not officially part of the hypothesis — that the most adventurous of them, while migrating into heretofore unexplored territory, burrow past — whoops! — kangaroo rat-shaped clusters of spores and inhale a few of them. In this scenario, the newly infected (but still healthy-appearing) kangaroo rat now goes on to start the cycle all over again, only now in a new area.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XDVgcb">
If that’s indeed what’s happening, it could explain how heavy rains alternating with severe drought — all the result of a changing climate — drive Cocci’s expanding footprint.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MKFhbx">
Overall, the endozoan hypothesis is mostly still speculative, said Taylor. Proving rodents’ role in Cocci’s propagation could involve labeling rodents with tracking devices to figure out what’s going on underground, and perhaps sequencing Cocci genomes from different infected animals to see who infected whom. The field work would be quite a bit more complicated than Marieke Ramsey’s burrow floor sampling — although the lab work, like Ramsey’s, would need to be performed by trained personnel in high-level biosafety labs. None of this is impossible, but it is expensive.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bRduwe">
Meanwhile, other scientists’ work suggests the climate parameters feeding into the trends are all but inevitable. By warming and drying the soil throughout the Western US, temperature and precipitation changes will likely more than double the area of cocci’s potential habitat by 2090, said Morgan Gorris, an earth system scientist at Los Alamos National Laboratory in New Mexico. Gorris has created models that forecast both the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007157/">expansion of Cocci’s home region</a> and its <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311625/">economic impact to come</a>; she predicts costs associated with the infection will increase nearly 400 percent over the next 70 years.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uqw78V">
Gorris’s findings were surprising even to her — “I was shocked that it was projected to reach the US-Canadian border by year 2100,” she said. “That was an ‘aha’ moment because it really showed the necessity of … reaching out to these public health departments that may not have been considering Valley fever as a risk for their communities.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RpqMoL">
Even if scientists perfectly understood the Cocci life cycle and its interaction with weather, big knowledge gaps would remain. Existing maps of the fungus’s distribution are approximate at best, based as they are on people’s best guesses at where they got infected after being diagnosed with Valley fever, said Adrienne Carey, an infectious disease doctor who studies Cocci at the University of Utah School of Medicine.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7CEU2t">
“We, for the life of us, have a really hard time culturing the fungus in the soil,” Carey said. The organism is <a href="https://academic.oup.com/mmy/article/57/2/246/4925226">notoriously difficult to grow</a> from soil samples using standard microbiological methods. Molecular methods — like Barker’s lab uses — are better, but prohibitively expensive, at least for now. “When you can’t culture it in the soil, you have a hard time knowing where it is,” said Carey.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BdhTkx">
The endozoan hypothesis is not the only one going: Scientists also suspect dust storms and other regional wind patterns play a role in Cocci’s spread. A recent <a href="https://academic.oup.com/cid/article/56/6/847/310582">cluster of cases</a> in Washington state was <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584917/">linked</a> to organisms isolated from soil in the arid eastern part of the state, hundreds of miles from its usual geographic range; <a href="https://news.wsu.edu/press-release/2014/05/05/illness-causing-fungus-spreads-to-washington-state/">strong winds</a> might have played an important role in the pathogen’s migration.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pQcM4k">
Either way, mounting data suggests that, barring a dramatic reversal in the factors driving climate change and the weather changes it’s producing, Cocci’s march through the American West, overland and underground, is inevitable.
</p>
<h2 id="lO0IxA">
Who does Cocci hurt the most?
</h2>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9zfozv">
However many questions remain unanswered about how Cocci gets into and spreads through soil, we know what happens when it gets inside the lungs — for the most part.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TrJQGO">
Within the warm, wet, protein-rich embrace of a mammalian airway, a Cocci spore performs a feat that distinguishes it from other disease-causing fungi. Its cousins would, in this environment, round themselves into blobby single-cell organisms small enough to be fodder for the immune system’s macrophages (literally, “big eater” cells). But here, Cocci zags, hulking out into the massive spherules that earned it its name.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="prxJFD">
“Making a sphere is a good strategy for a lot of different problems” — at least from cocci’s perspective, said Barker. The fungus’s new shape and size render it inedible to macrophages. Plus, it’s ideal for germinating the hundreds of baby fungal cells, or endospores, that it readies to spread from the lung and raise hell elsewhere in the body. Spherulization is a tactic unique to Cocci: “There’s no other structure like that in this group,” Barker said, referring to the Onygenales<em> </em>order that includes a host of other fungal pathogens.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="I17Y8B">
Unable to destroy the spherule by chewing it up, the immune system instead tries to smother the burgeoning threat with white blood cells. In about <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749157/?report=reader">60 percent</a> of all human cases, the containment is successful, and happens so swiftly and quietly that the infection goes undetected and lies dormant — at least until the person dies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nytdy5">
In the other 40 percent, containment fails, and Cocci pushes past the body’s defenses. In this unlucky group, fungal spherules burst within a few weeks of inhaling the first spore, unleashing up to a thousand endospores into the blood and the neighboring lung tissue. Immunocompromised people are at particularly high risk for this scenario: Up to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324825/?report=reader">half</a> of all cases in people with suppressed immune systems disseminate beyond the lungs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mb9sU6">
As the immune system tries to contain the Valley fever infection, many people experience flu-like aches, fever, and fatigue. Symptoms of the fungus’s invasion of lung tissue, like cough and chest pain, are also common. Many patients report weird, often nodular rashes, and months to years later, a small minority develop even <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631225/">weirder rashes</a>, most commonly in the laugh lines of the face. These oddities, like Cocci-related meningitis and infections of the bones, brain, and gastrointestinal tract, signal disseminated disease — that is, the spread of infection outside the lungs to other parts of the body.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4SHMe2">
People with symptomatic infection often feel sick for weeks or months, even if their immune system is strong. And while many recover without treatment, <a href="https://www.idsociety.org/practice-guideline/coccidioidomycosis/#null">people with severe disease</a> usually end up taking variably unpleasant antifungal medications, whose temporary <a href="https://pubmed.ncbi.nlm.nih.gov/19836985/">side</a> <a href="https://www.drugs.com/sfx/fluconazole-side-effects.html">effects</a> range from nausea to blurry vision to neurologic problems, like numbness or weakness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zbAhFa">
Part of what makes Cocci infections last so long is that diagnosing them often takes a long time. Valley fever usually starts out looking like a respiratory infection, and often gets mistaken for more common bacterial and viral diseases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jORBjh">
Even in places where Cocci causes a significant proportion of pneumonias, the time between getting sick and getting diagnosed can be weeks or even months. Although blood tests can diagnose Valley fever in <a href="https://www.cdc.gov/fungal/diseases/coccidioidomycosis/diagnosis.html#:~:text=The%20most%20common%20way%20that,look%20for%20Valley%20fever%20pneumonia.">a few days</a>, patients at one Tucson clinic network waited a median of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711243/">three weeks</a> for a correct diagnosis, according to a study in <em>Emerging Infectious Diseases</em>, and a related analysis showed more than half waited anywhere between one and six months.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZhqsWT">
It’s worse outside of the Southwest. At Ohio’s Cleveland Clinic — one of the nation’s top diagnostic centers — people with Cocci waited a median of <a href="https://pubmed.ncbi.nlm.nih.gov/11316114/">three months</a> for doctors to figure out what was causing their symptoms.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="H1fdCt">
Scientists still don’t understand what distinguishes people who get sick from those who don’t, although Taylor thinks the quantity of spores the immune system has to contend with makes a difference. About three-quarters of people with symptomatic disease are men, and Filipino and Black people are more likely to have severe disease. That imbalance probably has something to do with exposure risk — people in these groups are more likely to do the outdoor work associated with infection — but there’s <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815636/">ongoing debate</a> about whether genetics also play a role.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kim8fy">
And it’s not just humans who are at risk: Cocci also causes a spectrum of disease in a variety of other vertebrates – most commonly <a href="https://pubmed.ncbi.nlm.nih.gov/18762558/">dogs and cats</a>, but also <a href="https://pubmed.ncbi.nlm.nih.gov/35879871/">horses</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/29790449/">llamas</a>,<a href="https://pubmed.ncbi.nlm.nih.gov/29790449/"> alpacas</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/9359077/">sea lions</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/9706575/">dolphins</a>, and other, less local species. “If you look at the records from the Phoenix Zoo — polar bears and kangaroos and wallabies and nonhuman primates — it’s kind of crazy how diverse the host range is,” said Barker.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GZcBVd">
Regardless of whether they have symptoms of their first infection, people who get infected with Cocci once don’t catch it again. “It’s a living vaccine,” said Taylor. But if the immune system of a person with a dormant Cocci infection gets distracted or disabled due to medications or disease, the fungus can wild out, bursting from its shell to wreak the havoc it failed to unleash on its first try.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AS6z07">
That creates particular urgency for finding ways to prevent Cocci infections from settling in to begin with.
</p>
<h2 id="uchRPw">
We know more Cocci is coming. How can we prepare?
</h2>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UWvuUk">
The most obvious way to protect people from an infection they can’t help but encounter is with a vaccine. But despite ongoing efforts to develop a vaccine since the 1960s, there is still no prototype effective at reducing Cocci’s effects on humans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZwTRpu">
Part of the challenge has to do with antibodies. Most vaccines are designed to get the body to generate neutralizing antibodies. But with Cocci, a different flank of the immune system, composed of T-cells, “is essential” for protecting people from repeat infection, said <a href="https://www.utsa.edu/sciences/molecular-microbiology-immunology/faculty/ChiungYuHung.html">Chiung-Yu Hung</a>, an immunologist at the University of Texas at San Antonio who’s working on a Cocci vaccine prototype.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JE2IfK">
The challenge: It’s hard to train up human T-cells without injecting a living but weakened version of the Cocci spherule, a so-called “live attenuated” vaccine. And that process comes with its own risks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D7rji0">
Live attenuated vaccines elicit a robust immune response — which includes T-cells. But many of them run the risk of <a href="https://www.hhs.gov/immunization/basics/types/index.html#:~:text=Subunit%2C%20recombinant%2C%20polysaccharide%2C%20and%20conjugate%20vaccines,-Subunit%2C%20recombinant%2C%20polysaccharide&amp;text=One%20limitation%20of%20these%20vaccines,Haemophilus%20influenzae%20type%20b)%20disease">replicating uncontrollably</a> in people with compromised immune systems. That’s not what anyone wants — especially since immunocompromised people would benefit the most from a Valley fever vaccine.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IDzJHe">
So a live Cocci vaccine would only be a realistic option if the version of the spherule it contained had zero risk of replicating once injected into a person’s body.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="78a9l4">
That concept is no longer in the realm of science fiction, said <a href="https://vfce.arizona.edu/profile/john-galgiani-md">John Galgiani</a>, an infectious disease doctor who directs the Valley Fever Center for Excellence at the University of Arizona’s medical school. In 2016, a team led by his colleague <a href="https://cals.arizona.edu/spls/content/marc">Marc Orbach</a> published a <a href="https://pubmed.ncbi.nlm.nih.gov/27481239/">method</a> for snipping out the gene that controls Cocci’s ability to multiply. A vaccine made from the resulting fungal mutant has been <a href="https://www.sciencedirect.com/science/article/pii/S0264410X21013499">remarkably effective</a> at reducing disease in dogs. The prototype is on track to be approved by the USDA for veterinary use in the first half of 2024.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3xDhaW">
Why isn’t the vaccine ready for human trials? “Well in my view, it is,” said Galgiani. But the manufacturing and licensing process for human vaccines is a completely different animal (sorry) than the one for veterinary vaccines — and the costs are much, much higher.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gKgTWz">
Shepherding the prototype through the Food and Drug Administration’s (FDA’s) hoops will probably take at least eight years, said Galgiani. And as with previous Cocci vaccine prototypes, there’s a chance that because relatively few people are currently at risk of infection — compared with, say, the global population-wide risk for polio or measles — the product’s modest profit potential would <a href="https://www.vox.com/science-and-health/2023/2/11/23592955/last-of-us-fungal-vaccines-infections-cordyceps">put off manufacturing partners</a>. Without their investment, no prototype would get past the finish line.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1znam2">
Other vaccines are also under development but don’t yet exist as prototypes. For example, Hung’s team is working on an mRNA vaccine packaged in a faux-fungal capsule that enables it to induce a T-cell response.
</p>
<div class="c-float-right">
<aside id="Fm6MYZ">
<q>“It’s the little dangers that get you. A mosquito, the Valley fever fungus. Not the wolf. Not the tiger.”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4upPYq">
This is where our lack of clarity on the true reach of Valley fever poses perhaps the clearest obstacle to doing something about it. If we’re massively undercounting cases, and if Cocci’s geographic intrusion into new regions is going undetected, we might be wildly underestimating the risk of the infection — and the benefit of a vaccine. Underinvesting in solutions now could leave us scrambling in an increasingly climate-weird future.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qww5uw">
And weird it shall be. Climate change is altering our world in a million small ways that have big consequences. It changes the land, which changes how and whether animals live in it, which embeds further changes in the land, which impacts our health.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="luRDrl">
The desert, the rodents, the fungus, and the weather were all here before we were. We’ve dug too indiscriminately into the land and <a href="https://www.vox.com/2022/9/23/23357093/colorado-river-drought-cuts">taken too much water</a> from its rivers — and now, we face invisible threats in the desert’s imbalance. The consequences of a changing climate are not all as obvious as ice melting: Our world is changing in other ways whose fallout we might not notice until it literally hits our lungs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AkyEjc">
The time to prepare for them is now.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bJjfda">
John Taylor, the Berkeley mycologist, was once the expert witness in a court case involving a <a href="https://www.dailyrepublic.com/all-dr-news/solano-news/fairfield/solano-jury-hits-caltrans-with-12m-verdict-in-valley-fever-suit/">Cocci cluster among construction workers</a> who built a culvert in California’s San Joaquin Valley — Valley fever’s namesake. Many became seriously ill; they hadn’t been informed of the Cocci risk, or told that respirator masks were necessary protective gear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hV9VDc">
The trial cost California taxpayers millions of dollars. Still, when Taylor drives through the Valley to collect soil samples, he sees workers without protection. Vaccinating at-risk workers would be the best defense against the coming rise of Cocci, he said, perhaps because it accounts for our tendency as a species to ignore that which we cannot see. Because even if we can’t see the threat in a speck of dust, it’s there.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zZrKNP">
“It’s the little dangers that get you,” he said, “a mosquito, the Valley fever fungus. Not the wolf. Not the tiger.”
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Four-stroke karting series to be held across six cities from April 29</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ARTEMIS, a football-playing humanoid robot, is ready for the pitch</strong> - “If your robot cannot even play a game of soccer, how would you be able to use these robots for more important things, such as saving people’s lives?” said Dennis Hong, professor of mechanical and aerospace engineering and director of the Robotics and Mechanisms Laboratory (RoMeLa) at UCLA, which developed ARTEMIS</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023 | Punjab Kings limit RCB to 174/4 after du Plessis-Kohli show</strong> - Arshdeep Singh and Curran employed the short-ball tactic against du Plessis and Kohli with the new ball but it did not work</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UCL 2022/23 | In last-4, Man City meets Real test, Inter sets up Milan clash</strong> - Manchester City will hope to continue good form against holders Real Madrid, while Inter will meet city rivals AC Milan in the first Milanese UCL semifinal after a decade</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023 | CSK hope for Stokes boost ahead of SRH clash</strong> - While the CSK batting unit has been finding the runs, the bowlers have been inconsistent and fielding below par</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Andhra Pradesh: Industries Minister asks TDP to make its stand clear on Visakhapatnam as Executive capital</strong> - The Chief Minister is at liberty to rule from anywhere in the State, and no political party, or system, can oppose it, asserts Industries Minister Gudivada Amarnath</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Santanu Bhattacharya takes charge as IISER Director</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engineering college students get placements</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Delay in capturing Arikompan gives sleepless nights to RRT members</strong> - RRT members have been reportedly ‘overworked’ for the past month</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Youth exhorted to become entrepreneurs</strong> -</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Turkey’s soft-spoken Kemal Kilicdaroglu takes on powerful Erdogan</strong> - Behind his calm nature, Kemal Kilicdaroglu has the first real chance of unseating Turkey’s leader.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Blinding flash over Kyiv was probably meteorite, says Ukraine space agency</strong> - Nasa denies the flash which lit up the sky was caused by a satellite falling to Earth.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New York woman sentenced for cheesecake murder plot</strong> - Viktoria Nasyrova lashes out at the judge as she is jailed for the “diabolical” identity theft plot.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: The Russian ships accused of North Sea sabotage</strong> - Disguised Russian ships are said to be preparing sabotage plans in case of war with Western powers.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Italian outcry over Lollobrigida ‘ethnic replacement’ remarks</strong> - In a speech about birth rates, the agriculture minister uses a phrase linked to white supremacists.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SpaceX to make a second attempt to launch its massive Starship rocket</strong> - The most likely outcome is that something goes wrong during this flight. - <a href="https://arstechnica.com/?p=1932986">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Twitter quietly edited its hateful conduct policy to drop transgender protections</strong> - Musk says his own tweets might be labeled under new hateful conduct policy. - <a href="https://arstechnica.com/?p=1933162">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Google Fi gets third rebrand in 8 years, adds free trial for eSim phones</strong> - There’s a new app coming and an option for a free phone after 24 months of service. - <a href="https://arstechnica.com/?p=1933098">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reddit will start charging AI models learning from its extremely human archives</strong> - LLMs can no longer lurk, learn, and profit from 18 years of links and chatter. - <a href="https://arstechnica.com/?p=1933080">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>First teaser for Star Trek: Strange New Worlds S2 is giving us all the feels</strong> - “The next great Age of Exploration starts with us.” - <a href="https://arstechnica.com/?p=1933065">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A beautiful woman walks into a bar. “What’ll it be?” asks the bartender. “I’ll have a double entendre,” she said…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So he gave it to her.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/_JackStraw_"> /u/<em>JackStraw</em> </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12simgs/a_beautiful_woman_walks_into_a_bar_whatll_it_be/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12simgs/a_beautiful_woman_walks_into_a_bar_whatll_it_be/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A man leaving his apartment building runs into his female neighbor on the elevator.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">“Good morning, what are you up to today?” he asks.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">She replies, “I’m going down to give blood.”</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">“How much do you get paid for giving blood?” he asks.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">“About $20 a pint.” she says.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">“Hmm …,” the man, says. “I’m going up to donate sperm, and the sperm bank pays $100 a tablespoon.”</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">The woman is left with a questioning expression on her face as the man leaves the elevator.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">The next day they meet in the elevator again.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">The man asks, “So, where you off to today?”</p>
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“Fmerm mank,” she says, with her mouth full.
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submitted by <a href="https://www.reddit.com/user/IloveRamen99"> /u/IloveRamen99 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12rvaza/a_man_leaving_his_apartment_building_runs_into/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12rvaza/a_man_leaving_his_apartment_building_runs_into/">[comments]</a></span></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Mormon and the Irishman</strong> - <!-- SC_OFF --></p>
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A Mormon was seated next to an Irishman on a flight from London to the US.<br/> After the plane was airborne, drink orders were taken. The Irishman asked for a whiskey, which was promptly brought and placed before him.
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The flight attendant then asked the Mormon if he would like a drink. He replied in disgust, “I’d rather be savagely raped by a dozen whores than let liquor touch my lips.”
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The Irishman then handed his drink back to the attendant and said, “Me, too, I didn’t know we had a choice.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Zulufepustampasic"> /u/Zulufepustampasic </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12sppz3/a_mormon_and_the_irishman/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12sppz3/a_mormon_and_the_irishman/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What do you call it when a group of cuddly adorable lesbians take over your country</strong> - <!-- SC_OFF --></p>
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A coochie coochie coup
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(I’ll see myself out…)
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/xxCorsicoxx"> /u/xxCorsicoxx </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12sfibf/what_do_you_call_it_when_a_group_of_cuddly/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12sfibf/what_do_you_call_it_when_a_group_of_cuddly/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Duck stands before the judge. Judge says “why are you here?”</strong> - <!-- SC_OFF --></p>
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Duck “I was caught blowing bubbles in the lake your honor”
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Judge “thats stupid, case dismissed”
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Next duck comes in.
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Judge “why are you here?”
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Duck “I was caught blowing bubbles in the lake your honor”
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Judge “thats stupid, case dismissed”
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Next duck comes in.
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Judge “let me guess, you were caught blowing bubbles in the lake?”
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Duck “no your honor! I am bubbles”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/islandrenaissance"> /u/islandrenaissance </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12sgut9/duck_stands_before_the_judge_judge_says_why_are/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12sgut9/duck_stands_before_the_judge_judge_says_why_are/">[comments]</a></span></p></li>
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