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+ + + ++Although various COVID-19 vaccines have shown efficacy against placebo in randomized clinical trials, no head-to-head comparisons are yet available. This study aims to compare the efficacy of available COVID-19 vaccines. Vaccine trials searched in May 2021 were included. Data were extracted from Kaplan-Meier (KM) curves using the WebPlotDigitizer program for the individual participant (IP) data simulation. A mixed-effect acceleration failure model with log-logistic and Weibull distributions was used to estimate relative effects for individual vaccines as well as grouped by class: inactivated virus, mRNA, and viral vector. Primary studies were considered as the random effect in the model. Hazard ratios (HR) were estimated and compared across vaccine groups. All vaccines were efficacious in lowering symptomatic infection compared to placebo. CoronaVac, Ad26.COV2.S, ChAdOx1 nCoV-19, rAd26/rAd5, WIV04, HB02, and BNT162b2 showed 7.61 (4.50, 12.87), 6.77 (4.08, 11.24), 5.01 (2.93, 8.57), 4.50 (2.52, 8.01), 3.90 (2.04, 7.45), 3.18 (1.62, 6.21), and 2.15 (1.22, 3.78) times significantly higher risk of infection than mRNA-1273. mRNA vaccines were the most efficacious vaccine group compared to inactivated virus and viral vectors with HRs (95% CI) of 0.27 (0.20, 0.37) and 0.28 (0.21, 0.37), respectively. Although all vaccines showed significant protection compared to no vaccination. mRNA vaccines, including mRNA-1273 and BNT162b2, showed the highest efficacy in preventing symptomatic COVID-19 infection. Simulated IP data from the KM curve might allow treatment comparison when there is no primary study comparing active treatments. +
++We report SARS-CoV-2 neutralizing antibody titers in sera of triple-vaccinated individuals who received a booster dose of an original monovalent or a bivalent BA.1- or BA.4/BA.5-adapted vaccine, or had a breakthrough infection with Omicron variants BA.1, BA.2 or BA.4/BA.5. A bivalent BA.4/BA.5 booster or Omicron-breakthrough infection induced increased Omicron-neutralization titers compared with the monovalent booster. The XBB.1.5 variant effectively evaded neutralizing-antibody responses elicited by current vaccines and/or infection with previous variants. +
++This study investigated temporal variational structures of the COVID-19 pandemic in Japan using a time series analysis incorporating maximum entropy method (MEM) spectral analysis, which produces power spectral densities (PSDs). This method was applied to daily data of COVID-19 cases in Japan from January 2020 to February 2023. The analyses confirmed that the PSDs for data in both the pre- and post-Tokyo Olympics periods show exponential characteristics, which are universally observed in PSDs for time series generated from nonlinear dynamical systems, including the so-called susceptible/exposed/infectious/recovered (SEIR) model, well-established as a mathematical model of temporal variational structures of infectious disease outbreaks. The magnitude of the gradient of exponential PSD for the pre-Olympics period was smaller than that of the post-Olympics period, because of the relatively high complex variations of the data in the pre-Olympics period caused by a deterministic, nonlinear dynamical system and/or undeterministic noise. A 3-dimensional spectral array obtained by segment time series analysis indicates that temporal changes in the periodic structures of the COVID-19 data are already observable before the commencement of the Tokyo Olympics and immediately after the introduction of mass and workplace vaccination programs. Lessons from theoretical studies for measles control programs may be applicable to COVID-19. +
++Objectives: This study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on the long-term risk of digestive diseases in the general population. Design: Large-scale population-based cohort study based on a prospective cohort. Setting: UK Biobank cohort linked to multiple nationwide electronic health records databases. Participants: The cohort consisted of 112,311 individuals who survived the initial 30 days following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as two control groups: a contemporary group (n = 359,671) without any history of COVID-19, and a historical control group (n = 370,979) that predated the COVID-19 outbreak. Main outcome measures: Main outcomes were predefined digestive diseases. Hazard ratios and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. Results: Compared with the contemporary control group, patients with previous COVID-19 infection had higher risks of digestive diseases, including functional gastrointestinal disorders (hazard ratios [HR] 1.95 (95% CI 1.62 to 2.35)); peptic ulcer disease (HR 1.27 (1.04 to 1.56)); gastroesophageal reflux disease (GERD) (HR 1.46 (1.34 to 1.58)); inflammatory bowel diseases (HR 1.40 (1.02 to 1.90)); gallbladder disease (HR 1.28 (1.13 to 1.46)); severe liver disease (HR 1.46 (1.12 to 1.90)); non-alcoholic liver disease (HR 1.33 (1.15 to 1.55)); and pancreatic disease (HR 1.43 (1.17 to 1.74)). The risks of GERD were stepwise increased with severity of the acute phase of COVID-19 infection. The results were consistent when using the historical cohort as the control group. Conclusions: Our study provides important insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing gastrointestinal disorders, with stepwise increased risk with the severity and persisting even after one year follow-up. +
++Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents. +
++Background: The COVID-19 pandemic, extreme weather events, and the Russian invasion of Ukraine have highlighted global food system vulnerabilities and a lack of preparedness and prospective planning for increasingly complex disruptions. This has spurred an interest in food system resilience. Despite the elevated interest in food system resilience, there is a lack of comparative analyses of national-level food system resilience efforts. An improved understanding of the food system resilience landscape can support and inform future policies, programs, and planning. Methods: We conducted a cross-country comparison of national-level food system resilience activities from Australia, Aotearoa (New Zealand), Sweden, and the United States. We developed upon and adapted the resilience framework proposed by Harris and Spiegel to compare actions derived from thirteen national food system resilience documents. We coded the documents based on how the governments determined actions by food system resilience attribute utilized, part of the food supply chain, specific shocks or stressors, implementation level, the temporal focus of action, and the expected impact on food security. We analyzed and compared countries coded categories, subcategories, and category combinations. Results: The results showed that countries are using multi-pronged policy actions to address food system resilience issues and are focused on both retrospective reviews and prospective models of disruptive events to inform their decisions. Some work has been done towards preparing for climate change and other natural disasters, but not as much for other shocks or stressors. Conclusions: The analysis identified potential gaps, concentrations, and themes in national food systems resilience. The framework can be applied to augment existing policy, create new policy, as well as to supplement and complement other existing frameworks. +
++Background: Parkinson’s disease has been identified as a risk factor for severe Coronavirus disease 2019 (COVID-19) outcomes. However, whether the significant high risk of death from COVID-19 in people with Parkinson’s disease is specific to the disease itself or driven by other concomitant and known risk factors such as comorbidities, age, and frailty remains unclear. Objective: To investigate clinical profiles and outcomes of people with Parkinson’s disease and atypical parkinsonian syndromes who tested positive for COVID-19 in the hospital setting in a multicentre UK-based study. Methods: A retrospective cohort study of Parkinson’s disease patients with a positive COVID-19 test admitted to hospital between February 2020 and July 2021. An online survey was used to collect data from clinical care records, recording patient, Parkinson’s disease and COVID-19 characteristics. Associations with time-to-mortality and severe outcomes were analysed using either the Cox proportional hazards model or logistic regression models, as appropriate. Results: Data from 552 admissions were collected: 365 (66%) male; median (inter-quartile range) age 80 (74-85) years. The 34-day mortality rate was 38.4%; male sex, increased age and frailty, Parkinson’s dementia syndrome, requirement for respiratory support and no vaccination were associated with increased mortality risk. Community-acquired COVID-19 and co-morbid chronic neurological disorder were associated with increased odds of requiring respiratory support. Hospital-acquired COVID-19 and delirium were associated with requiring an increase in care level post-discharge. Conclusions: This first, multicentre, UK-based study on people with Parkinson’s disease or atypical parkinsonian syndromes, hospitalised with COVID-19, adds and expands previous findings on clinical profiles and outcomes in this population. +
++Background Data suggest that vaccine effectiveness against Covid-19-associated hospital admission and mortality is augmented with booster doses, but the benefit wanes within several months. However, the CDC recently concluded that second doses of bivalent vaccines this Spring were not warranted because existing data were insufficient to analyze the benefits of such a strategy. Therefore, our objective was to assess whether routinely boosting high-risk populations at least every 6 months may be warranted, depending on age and immune status. Methods Utilizing a database of 3,574,243 members of Clalit Health Services (CHS), we analyzed the medical records of individuals who received none, or at least one dose of the BNT162b2 mRNA COVID-19 vaccine between January 1, 2021, and April 5, 2022. We examined the risk of moderate-to-severe Covid-19 hospitalization or death stratified by age group, immune status and time since receipt of the last vaccine dose during the early Omicron wave in Israel (December 20, 2021 to April 5, 2022). The number needed to vaccinate (NNV) was calculated as the inverse of the absolute risk reduction for various subgroups and Covid-19 waves. Results Eligibility criteria were met by 3,381,480 CHS members. The absolute risk of Covid-19 moderate-to-severe hospitalization or death during the Omicron wave increased with age, immunocompromised status, and time since receipt of the last vaccine dose. The NNVs varied greatly by age and immune status and were contingent on various disease prevalence scenarios. Among the severely immunocompromised, boosting at the start of the Omicron wave had an NNV ranging from 87 (95% CI 70-109) in persons ages ≥80 to 1,037 (95% CI 999 -1,513) in persons ages 12-59. In the lower-prevalence periods, the NNV for 6-month booster cadencing remained favorable for immunocompromised people in all age groups and immunocompetent people ages ≥60. Conclusions Our study provides evidence for the potential benefit of a routine 6-month cadence for Covid-19 boosters for the highest-risk groups, and possibly more frequently, even during relatively lower Covid-19 prevalence. +
++Background: Artificial intelligence (AI) technologies can help solve the significant problem of missed findings in radiology studies. An important issue is assessing the economic benefits of implementing AI. Aim: to evaluate the frequency of missed pathologies detection and the economic potential of AI technology for chest CT, validated by expert radiologists, compared with radiologists without access to AI in a private medical center. Methods: An observational, single-center retrospective study was conducted. The study included chest CTs without IV contrast performed from 01.06.2022 to 31.07.2022 in “Yauza Hospital” LLC, Moscow. The CTs were processed using a complex AI algorithm for ten pathologies: pulmonary infiltrates, typical for viral pneumonia (COVID-19 in pandemic conditions); lung nodules; pleural effusion; pulmonary emphysema; thoracic aortic dilatation; pulmonary trunk dilatation; coronary artery calcification; adrenal hyperplasia; osteoporosis (vertebral body height and density changes). Two experts analyzed CTs and compared results with AI. Further routing was determined according to clinical guidelines for all findings initially detected and missed by radiologists. The lost potential revenue (LPR) was calculated for each patient according to the hospital price list. Results: From the final 160 CTs, the AI identified 90 studies (56%) with pathologies, of which 81 studies (51%) were missing at least one pathology in the report. The “second-stage” LPR for all pathologies from 81 patients was RUB 2,847,760 ($37,251 or CNY 256,218). LPR only for those pathologies missed by radiologists but detected by AI was RUB 2,065,360 ($27,017 or CNY 185,824). Conclusion: Using AI for chest CTs as an “assistant” to the radiologist can significantly reduce the number of missed abnormalities. AI usage can bring 3.6 times more benefits compared to the standard model without AI. The use of complex AI for chest CT can be cost-effective. +
++The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the cellular disease dynamics remains limited. In our unique COVID-19 human challenge study we used single cell genomics of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in 16 seronegative individuals challenged with preAlpha-SARS-CoV-2. Our analyses revealed rapid changes in cell type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific timepoints or infection status. We observed that the interferon response in blood precedes the nasopharynx, and that nasopharyngeal immune infiltration occurred early in transient but later in sustained infection, and thus correlated with preventing sustained infection. Ciliated cells showed an acute response phase, upregulated MHC class II while infected, and were most permissive for viral replication, whilst nasal T cells and macrophages were infected non-productively. We resolve 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our novel computational pipeline (Cell2TCR) identifies activated antigen-responding clonotype groups and motifs in any dataset. Together, we show that our detailed time series data (covid19cellatlas.org) can serve as a 9Rosetta stone9 for the epithelial and immune cell responses, and reveals early dynamic responses associated with protection from infection. +
++The COVID-19 pandemy has created a radically new situation where most countries provide raw measurements of their daily incidence and disclose them in real time. This enables new machine learning forecast strategies where the prediction might no longer be based just on the past values of the current incidence curve, but could take advantage of observations in many countries. We present such a simple global machine learning procedure using all past daily incidence trend curves. Each of the 27,418 COVID-19 incidence trend curves in our database contains the values of 56 consecutive days extracted from observed incidence curves across 61 world regions and countries. Given a current incidence trend curve observed over the past four weeks, its forecast in the next four weeks is computed by matching it with the first four weeks of all samples, and ranking them by their similarity to the query curve. Then the 28 days forecast is obtained by a statistical estimation combining the values of the 28 last observed days in those similar samples. Using comparison performed by the European Covid-19 Forecast Hub with the current state of the art forecast methods, we verify that the proposed global learning method, EpiLearn, compares favorably to methods forecasting from a single past curve. +
+Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19 - Condition: Omicron Variant of COVID-19
Intervention: Drug: Nirmatrelvir/Ritonavir
Sponsor: Xiangao Jiang
Completed
A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 - Condition: COVID-19
Interventions: Biological: mRNA-1283.222; Biological: mRNA-1273.222
Sponsor: ModernaTX, Inc.
Recruiting
Postoperative Sugammadex After COVID-19 - Conditions: General Anesthesia; COVID-19
Interventions: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg
Sponsor: Korea University Ansan Hospital
Not yet recruiting
Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19 - Condition: COVID-19
Interventions: Device: RD-X19; Device: Sham
Sponsor: EmitBio Inc.
Recruiting
Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes. - Condition: COVID-19
Interventions: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth
Sponsors: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation
Active, not recruiting
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) - Condition: COVID-19
Interventions: Drug: Azeliragon; Drug: Placebo
Sponsor: Salim S. Hayek
Recruiting
To Evaluate the Safety and Efficacy of Meplazumab in Treatment of Post-COVID-19 - Condition: Post-COVID-19
Interventions: Biological: Meplazumab for injection; Other: Normal saline
Sponsor: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
Recruiting
Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors - Condition: Post Acute COVID-19 Syndrome
Intervention: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)
Sponsor: Azienda Socio Sanitaria Territoriale di Lecco
Recruiting
Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome - Condition: Post-COVID-19 Syndrome
Intervention: Dietary Supplement: PS23 heat-treated
Sponsors: Mackay Memorial Hospital; Bened Biomedical Co., Ltd.
Recruiting
A Coping and Resilience Intervention for Adolescents - Condition: COVID-19 Pandemic
Interventions: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents
Sponsor: Taipei Medical University
Enrolling by invitation
Effect of Telerehabilitation Practice in Long COVID-19 Patients - Conditions: Long COVID-19; Long COVID; Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome
Interventions: Behavioral: Telerehabilitation; Behavioral: Standard rehabilitation care
Sponsor: Indonesia University
Recruiting
The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants - Condition: COVID-19 (Coronavirus Disease 2019)
Interventions: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10
Sponsor: Guangdong Raynovent Biotech Co., Ltd
Completed
Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints - Conditions: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired
Intervention: Device: RehaCom
Sponsor: Erasmus Medical Center
Not yet recruiting
Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial - Condition: COVID-19
Interventions: Drug: abatacept infusion; Drug: Placebo group
Sponsor: University of Minnesota
Not yet recruiting
A Study of Silmitasertib (CX-4945) in Healthy Subject - Condition: COVID-19
Intervention: Drug: CX-4945
Sponsor: Senhwa Biosciences, Inc.
Active, not recruiting
RAAS inhibition and beyond-cardiovascular medications in patients at risk of or affected by COVID-19 - The COVID-19 pandemic led to an enormous burden on healthcare systems worldwide. Causal therapy is still in its infancy. Contrary to initial views that the use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARBs) may increase the risk for a deleterious disease course, it has been shown that these agents may actually be beneficial for patients affected by COVID-19. In this article, we provide an overview of the three most commonly used classes of drugs in…
Identification and Comparison of the Sialic Acid-Binding Domain Characteristics of Avian Coronavirus Infectious Bronchitis Virus Spike Protein - Infectious bronchitis virus (IBV) infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host factors and fuses the viral and cell membranes. The N-terminal domain of the S1 subunit of IBV S protein binds to sialic acids, but the precise location of the sialic acid binding domain (SABD) and the role of the SABD in IBV-infected chickens remain unclear. Here, we identify the S1 N-terminal amino acid (aa) residues 19 to 227 (209 aa total) of IBV strains SD (GI-19) and…
Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus - Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which…
The human E3 ligase RNF185 is a regulator of the SARS-CoV-2 envelope protein - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks multiple human proteins during infection and viral replication. To examine whether any viral proteins employ human E3 ubiquitin ligases, we evaluated the stability of SARS-CoV-2 proteins with inhibition of the ubiquitin proteasome pathway. Using genetic screens to dissect the molecular machinery involved in the degradation of candidate viral proteins, we identified human E3 ligase RNF185 as a regulator of protein stability for…
Production and optimization of novel Sphorolipids from Candida parapsilosis grown on potato peel and frying oil wastes and their adverse effect on Mucorales fungal strains - CONCLUSION: The findings demonstrated the potential application of the SLs produced economically from agricultural waste as an effective and safer alternative for the treatment of infection caused by black fungus.
Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2 - Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC(50) = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC(50))….
Hemoptysis after COVID-19 and the importance of differential diagnosis: Birt-Hogg-Dubé syndrome - Birt-Hogg-Dubé syndrome is a genodermatosis of autosomal dominant inheritance characterized by mutations in the folliculin (FLCN) gene. There is an inappropriate inhibition/activation of a protein, the foliculin, which may cause tumor lesions in skin, renal and lung lesions; they could have more risk of developing pneumothorax compared to the normal population. A 38-year-old male patient with bronchial asthma who consulted for hemoptysis three weeks after recovery from COVID-19 infection. A…
Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19 - The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory…
Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions - The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a ‘cytokine storm’, during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or ’combination…
Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N-(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies - In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a-g) were assessed in Vero E6 cells via MTT assay to calculate the CC(50) and inhibitory concentration 50 (IC(50)) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with…
Barriers to recruiting primary care practices for implementation research during COVID-19: A qualitative study of practice coaches from the Stop Unhealthy (STUN) Alcohol Use Now trial - Background: The COVID-19 pandemic has brought widespread change to health care practice and research. With heightened stress in the general population, increased unhealthy alcohol use, and added pressures on primary care practices, comes the need to better understand how we can continue practice-based research and address public health priorities amid the ongoing pandemic. The current study considers barriers and facilitators to conducting such research, especially during the COVID-19 pandemic,…
Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury - INTRODCUTION: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary.
An Azapeptide Platform in Conjunction with Covalent Warheads to Uncover High-Potency Inhibitors for SARS-CoV-2 Main Protease - Main protease (M (Pro) ) of SARS-CoV-2, the viral pathogen of COVID-19, is a crucial nonstructural protein that plays a vital role in the replication and pathogenesis of the virus. Its protease function relies on three active site pockets to recognize P1, P2, and P4 amino acid residues in a substrate and a catalytic cysteine residue for catalysis. By converting the P1 Cα atom in an M (Pro) substrate to nitrogen, we showed that a large variety of azapeptide inhibitors with covalent warheads…
Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147 - Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers of drugs are discovered to treat COVID-19 patients. Even worse, the rapid mutations of SARS-CoV-2 compromise the effectiveness of existing vaccines and neutralizing antibodies due to the increased viral transmissibility and immune escape. CD147-spike protein, one of the entries of SRAR-CoV-2 into host cells, has been reported as a…
The 3’UTR region of the DNA repair gene PARP-1 May increase the severity of COVID-19 by altering the binding of antiviral miRNAs - COVID-19 may cause the release of systemic inflammatory cytokines resulting in severe inflammation. PARP-1 has been identified as a nuclear enzyme that is activated by DNA strand breaks. It has been suggested that PARP-1 has a role in the cytokine storm shown as a cause of mortality in COVID-19, and its inhibition may adversely affect the replication of SARS -CoV-2. We aimed to investigate the relationship between PARP-1 gene polymorphisms and the clinical severity of COVID-19. rs8679 TT…
A Heat Shield for the Most Important Ice on Earth - Engineers might be able to protect Arctic ice by coating it with tiny glass bubbles. Should they? - link
The World According to Tucker Carlson - Donald Trump had the raw power on the right. But it was Carlson who set the ideological agenda. - link
After the Shooting in Kansas City - Ralph Yarl is part of a tight-knit community of Liberian immigrants, many of whom fled violence to come to America. - link
India’s Quest to Build the World’s Largest Solar Farms - Pavagada Ultra Mega Solar Park, a clean-power plant the size of Manhattan, could be a model for the world—or a cautionary tale. - link
It Doesn’t Matter Who Replaces Tucker Carlson - Perhaps more than those of any other network on television, the stars of Fox News are more or less interchangeable. - link
+De-extinction isn’t worth the ethical cost. +
++On January 6, 2000, the bucardo (also known as the Pyrenean ibex, a subspecies of wild mountain goat) was confirmed extinct — for the first time, at least. Conservationists mourned when Celia, as the final bucardo was known, was found crushed beneath a tree in northeast Spain. +
++But scientists had removed some of Celia’s cells the year before her death, freezing them for preservation. In 2003 came attempts at cloning: Copies of her cell nucleus, containing her DNA, were implanted into 782 eggs taken from domestic goats (a close enough relative to be compatible with the bucardo nucleus). From these eggs, 407 embryos developed, about half of which the team transferred into the wombs of 57 surrogate goat mothers. Of these, seven turned into pregnancies, and one was born successfully. +
++The bucardo became the first species to return from extinction — but only for a moment. The baby’s lung was misshapen, and she suffocated within minutes. For the second time in three years, the bucardo was gone. +
++Celia’s story illuminates at least three realities facing “de-extinction,” a scientific pursuit aimed at using advanced cloning to resurrect extinct species. First, de-extinction seems technically possible — in fact, it has already been done once, if only briefly. Second, it won’t be easy. And third, there will be blood. +
++When people talk about de-extinction today, they’re looking at something much more headline-worthy than Spanish goats. Colossal Biosciences, a buzzy de-extinction company founded in 2021 by Harvard geneticist George Church and tech entrepreneur Ben Lamm, has chosen three species to pursue: the woolly mammoth, an elephant species gone for thousands of years; the Tasmanian tiger, or thylacine, an Australian marsupial believed extinct since the 1930s; and the dodo, a large flightless bird from the island of Mauritius that died out in the 17th century. +
++For the first two, Colossal claims de-extinction could bring ecological benefits. With the dodo, a species synonymous with the concept of extinction, it hopes to create “a symbol of hope” for conservation. The company also believes that techniques developed to bring these animals back could then be applied to help protect present-day endangered species. +
++It’s an exciting idea — after all, who wouldn’t thrill at an Ice Age symbol lumbering through Siberian snow? But while the technical challenges are enormous, the ethical ones are even more so. De-extinction raises fundamental questions about conservation’s priorities, why species matter, and the risks of scientific progress. And as the bucardo shows, one of the most intractable problems is the harm to individual animals: Both the surrogate parents and newborn clones face a risk of suffering and trauma, used as mere instruments in a research project of unclear benefit. +
++Church has been planning to bring back the mammoth for more than a decade, working on the problem at his Harvard lab and with the company Revive and Restore before launching Colossal. The project is fueled in part by mammoths’ fame and charisma — the species no doubt generates more funding and interest than, say, bringing back the extinct Christmas Island rat. +
++But cloning a mammoth will be even harder than the failed effort to clone a bucardo. The goat-cloning scientists had used a still-living cell nucleus from Celia, but no living mammoths remain to harvest cells from, so we have no intact mammoth nucleus, no complete mammoth DNA, and thus no obvious way to transform an elephant egg into a mammoth embryo. Instead, researchers will have to make their own mammoth DNA. +
++Scientists have already pieced together the species’ genome from fragments of mammoth DNA unearthed from ice, so they have a map for what they are trying to recreate. Colossal’s plan is to use CRISPR gene-editing technology to modify the DNA of an Asian elephant, the mammoth’s closest living relative, inserting specific genes that they consider most essential to being a mammoth: in particular, the hair and other adaptations enabling cold-weather living. The result would not be genetically identical to the mammoths that roamed the planet during the last ice age, but rather a mammoth-ified elephant, a hybrid approximation. +
++Colossal declares on its website that it’s trying to create a better world “for the planet, for the animals, for the future.” But for many animals, this brave new world could be bleak. +
++The most direct ethical problems concern the mammoths themselves. The bucardo’s lung deformity was not a fluke. “Rapid aging, ongoing health problems and premature death” are common among cloned animals, philosopher Heather Browning wrote in her 2019 article “Won’t Somebody Please Think of the Mammoths? De-extinction and Animal Welfare.” Many new mammoth babies would likely suffer and die young in the early stages of de-extinction. +
++The cloning stage also carries risks for the surrogate mothers, who will have no choice about their participation in the project. To gestate a whole herd of mammoths, many elephants would likely have to live in at least partial captivity and deal with the potential trauma of repeated miscarriages. The mother may need a C-section for the birth, as woolly mammoths are larger than Asian elephants — and surgery on an elephant isn’t easy. She would then be confronted by a strange, hairy child whom she may or may not accept. +
++“Elephants are normally really excited and happy when there’s a new birth,” Matthew Cobb, a biologist and author of As Gods, a book on the ethics of genetic engineering, said in an interview for my podcast, Storytelling Animals. “But they’re going to have this thing that is completely different. … It will smell different. It will behave different.” What if the elephant herd rejects the baby, leaving it alone and orphaned, like a real-life Frankenstein’s monster? “I can’t begin to get over quite how miserable that could be,” Cobb said. +
++Colossal Biosciences suggests on its website that while the base DNA will come from an Asian elephant, the mammoth embryos will be implanted into African elephants, which are larger and so may handle the birth better. The company also wishes to “eliminate any extra pressure” on the Asian elephant, as it is endangered while the African elephant, the site says, is considered merely “threatened.” That information is outdated, however, as African elephants were upgraded to endangered status in March 2021 (and elsewhere on its site, Colossal does acknowledge that African elephants are endangered). +
++“The ethical considerations these projects require … are definitely important,“ says Matt James, Colossal’s chief animal officer, in an email to Vox. “We continue to pivot and optimize on a daily basis.” Colossal didn’t respond to questions about the African elephant’s conservation status. +
++To avoid the complications of animal surrogacy, and to allow for faster breeding, Church has previously declared his intent to develop an artificial womb to gestate the mammoths, a technology that does not yet exist. Even if a synthetic womb were possible, it would only exacerbate the challenge facing the newborn woolies: How will they be raised, with neither a mother nor a father? +
++Elephants are highly social, culturally complex creatures who live in tight-knit matriarchal bands. Without such a community, “the first few individual wooly mammoths born would be some of the loneliest creatures imaginable,“ philosopher Christopher Preston writes in his book The Synthetic Age. +
++The first generation of mammoths would likely grow up in captivity, but we have little idea how best to raise them. While paleontological evidence gives some sense of their diet and behavior, the new creatures will be genetically distinct from their wild ancestors, and meeting their exact nutritional and social needs will be guesswork. Normal elephants are hard enough to keep in captivity — the small, enclosed spaces wreak havoc on their bodies and minds, and many zoos have stopped keeping elephants for ethical reasons. Now imagine trying to care for an elephant when we aren’t even sure of basic things like what to feed them. +
++In response to these and other worries, James explained, Colossal Biosciences has developed a team “tasked with developing not just animal care strategies but socialization plans to rear animals in a healthy setting, even if they are the first of their species to be restored.” +
++Such planning no doubt can help, but nothing can eliminate the risks and uncertainties of keeping a brand new species in captivity. “Just raising [mammoths] to an age that they are suitable for release [into the wild] may prove to be impossible,” Browning writes, “and the animals are likely to be malnourished and in poor health, with potential psychological and behavioral deficits.” +
++If scientists do succeed at keeping resurrected mammoths alive, they will eventually have to release them. Modern elephants are dependent on intergenerational knowledge transfer to learn the best watering holes and safest migration routes, but how will the first mammoths learn to survive with no generation above them? +
++Colossal Biosciences hopes that some combination of genetic instinct, surrogate elephant parents, and “on-the-ground animal behavior specialist teams” can teach the mammoths necessary survival skills. But reintroducing captive animals into the wild often fails even under far less exotic circumstances. +
++Paleontologist Steve Brusatte points out in The Rise and Reign of the Mammals that climate change could also be a hurdle. Mammoths are adapted to Ice Age climates with average temperatures up to 10 degrees Fahrenheit colder than today. If they return, they would be facing temperatures “much warmer than any mammoth ever experienced,” Brusatte writes. +
++Suppose that mammoths could overcome these obstacles, forging their own path and establishing themselves on the steppe as a happy community. To a hypothetical world of wild mammoths, we’d first have to be willing to put thinking, feeling beings through stress, pain, and often early death. For some animal rights advocates, this alone is enough to oppose de-extinction projects: they believe that nonhuman animals are not mere means to our ends. +
++For others, the ethical calculus may change if de-extinction brought about sufficient benefit. Perhaps the planet is made richer, in some small way, with one more species in it — one more unique way of the universe knowing itself. The full, joyful lives of some future mammoth herd could arguably justify the sacrifices along the way; we may even owe it to these future mammoths. +
++The problem with this thinking, write environmental journalist Emma Marris and philosopher Yasha Rohwer, “is that it doesn’t seem like one can have actual moral obligations to what doesn’t exist.” If we create new mammoths, we’ll also be creating immense ethical responsibilities to them. But so long as we don’t, we can focus our moral attention on the living. +
++Traditionally, conservation biology has not evinced much concern for the well-being of individual animals, instead prioritizing biodiversity — the health of whole species and ecosystems. Under this framework, a new mammoth population could be justified if it creates concrete benefits for the broader ecosystem. +
++Mammoths indeed once played a key role as ecosystem engineers: They snapped trees, trampled grasses and mosses, created depressions that became ponds, and otherwise transformed the steppe grasslands in ways that could theoretically help today’s endangered inhabitants such as the reindeer and Saiga antelope. +
++But a resurrected mammoth would not fix what has primarily been killing these creatures, namely hunting, disease, and the loss of habitat through the expansion of grazing and industry. De-extinction or not, addressing threats like these should be the most urgent conservation priority. In fact, introducing mammoths might invite even heavier human presence to the region: Church himself speculated in a 2019 interview with Harvard Magazine that mammoths could support “business models” including “tourism, meat, hair (following a sheep model of seasonal removal), and maybe legal ivory.” Church didn’t respond to a request for comment about these statements. +
++Another potential mammoth benefit is fighting climate change: Some scientists believe that mammoths’ compaction of soil could slow the thawing of Arctic permafrost, which releases the greenhouse gas methane. But it could take decades or more to breed enough mammoths to impact a sizable chunk of the permafrost, considering their slow reproductive process. +
++Even if the benefit were significant, Browning said in an email, it seems unlikely that bringing back a long-extinct creature is the best way to reduce methane emissions. If humans are creative enough to bring back the mammoth, surely we’re creative enough to find other ways of dealing with the permafrost. +
++De-extincting other animals is no less fraught. Different species present overlapping but distinct scientific and moral challenges, and de-extinction candidates may best be judged on a case-by-case basis. +
++“Mammoths seem to me to be the worst candidates due to their size and the likely complexity of their behavioral and social needs,” Browning said in an email, but species that went extinct more recently, she believes, may be easier to resurrect, because we may know more about their dietary and habitat requirements, and to at least some extent their original ecosystems still exist. +
++But in most cases, those ecosystems would hardly be safe. Most of the serious de-extinction candidates were wiped out due to human impact such as overhunting or habitat destruction. These pressures would likely still exist should they be resurrected. Philosopher Thom van Dooren and anthropologist Deborah Bird Rose wrote of de-extincting the thylacine, or Tasmanian tiger: “What sense does it make to dream of returning the thylacine when we cannot even ask people to make room for dingoes? How have the sheep farmers that once played a pivotal role in the extinction of the thylacine in Tasmania so changed their ways that this resurrection will be a success?” Without a protected area to return to, de-extinct animals might be relegated to zoo curiosities or exotic pets. +
++Ethicist T.J. Kasperbauer raises similar worries about the passenger pigeon, which the company Revive and Restore is attempting to revive. The North American bird once flew in flocks of hundreds of thousands, but might again be hunted and treated as a pest if it reaches its former numbers. Kasperbauer also cites some scientists’ fears that passenger pigeon flocks are not self-sustaining beneath a certain size — that is, we would need to breed a truly ginormous number of birds to be able to successfully release them into the wild. +
++Alex Lee, a philosopher at Alaska Pacific University, is most concerned about the moral hazard: If de-extinction technology becomes developed and widely accessible, will people become less worried about extinction in general? After all, why go through too much trouble to save a dying species when we could just bring them back a few years later? Empirical research is still needed to figure out how people’s attitudes are changed by the prospect of de-extinction, Rohwer and Marris suggest. Perhaps a newborn mammoth could inspire a sense of awe and wonder at the natural world that drives people to fight harder for all life, rather than seeing it as expendable. +
++For Beth Shapiro, a scientist involved in both Colossal and Revive and Restore, de-extinction itself is not really the point. Instead, she explains in her book, How to Clone a Mammoth, the scientific tools developed to resurrect dodos or mammoths could be used to help other creatures. Colossal’s James told Vox that the company is partnered with several elephant conservation organizations, and that its “advancements in assisted reproductive technologies,” “genetic engineering for disease resistance,” and more will benefit both de-extinction and existing wild elephant populations. +
++For instance, the company explains on its site, Colossal researchers are investigating how to insert genes into Asian elephants that would instill resistance to deadly elephant herpesviruses. De-extinction technology could also bring back species we lose in the future. While this at least seems ethically preferable to mammoth de-extinction, any potentially invasive research program involving sentient beings should inspire caution. +
++James said that much of the company’s testing is being done using AI or in vitro cell cultures, rather than in live animals. If and when live animals do become involved, he says, “whether that be a lab mouse or an elephant,” the company has bioethicist advisers, an independent Institutional Animal Care and Use Committee (IACUC), and an internal review process “to decide if and how we should pursue every aspect of our work. … Animal welfare, well-being, and health are at the forefront of our minds.” +
++These considerations are encouraging — but they can’t indicate that a research project is ethical because the Animal Welfare Act, which governs animal testing in the US, is highly limited and says little about what can be done to animals in experiments themselves, as Vox has reported. Most animal research facilities have an IACUC, but they do little to prevent research that many find unjustifiable. +
++The ethical issues raised by cloning, captive breeding, wildlife reintroductions, and animal experimentation writ large are not unique to de-extinction, and de-extinction is far from the worst threat to animal well-being today. But they still matter, and they can force us to consider our relationship with animals more broadly. When we imagine a lonely newborn mammoth, we might be moved to consider an individual animal’s welfare and subjective well-being in other decisions around wildlife. +
++Just as important: Who is the “we” who makes these decisions? Decisions about the dodo, for instance, should be made in concert with the people of Mauritius, where the bird’s ancestors lived for potentially millions of years, not solely by scientists thousands of miles away. Colossal “understand[s]…the importance [of] building mechanisms to give a voice to the local communities that co-exist with these animals,” James said. But mammoth expert Tori Herridge thinks more must be done to democratize the process. After declining a position on the company’s advisory board, she wrote in Nature, “The ethical road to de-extinction has to include informed citizen voices. … Let the people decide the future world they want to build.” +
++How to do this, exactly, will be difficult. But modern genetic technologies are too powerful to be controlled even by well-intentioned scientists, let alone for-profit corporations — some deliberative democratic process is needed. And more complicated still, that democracy must strive to represent non-human voices. Any decision on resurrecting species must consider the needs and desires of the elephants, pigeons, and other creatures whose lives would be upended, constrained, created, and destroyed to make de-extinction a reality. +
++One day, new knowledge or technology may allow us to avoid de-extinction’s ethical costs. But until then, the woolly mammoth should remain nothing more or less than a memory. +
++Dayton Martindale is a freelance writer and editor covering climate, ecology, animals, and politics. He hosts Storytelling Animals, an environmental books podcast, and serves as editor-at-large for the rural news publication Barn Raiser. This year, he will begin a PhD program in environmental studies at the University of Colorado Boulder, studying the ethics, politics, and policy of human-nonhuman interaction. +
+Borrowing money is just a few taps away. What could go wrong? +
++Do you want the company that makes your phone to be your bank, too? That’s the question some people are surely asking themselves now that Apple has rolled out its new Apple Card savings account, which comes with a 4.15 percent interest rate — well above what most traditional banks are offering. +
++It’s also not traditional because, unlike any other savings accounts out there, this one is baked into the operating system of your phone, as is the Apple Card, the credit card you must have in order to get the savings account. Thanks to digital banking and financial technology, or fintech, financial services have become so easy and frictionless that you can make important decisions about a lot of your money with just a few taps. Those could be applying for a credit card, sending money to friends, or using buy now, pay later services. +
++That’s a winning feature for some people. For others, it’s another way to lose. If you’re in a precarious financial situation and really shouldn’t be spending money, these tools can be hard to resist and make things worse. While Apple always frames its products as promoting financial health and adds tools that are supposed to help users make responsible decisions, it’s also giving them very prominent placement on the devices people use all the time. +
++For Apple, this is a way to lock customers in and make more money from them while also entrenching and expanding its dominance. It’s also a way to get money out of the companies it takes fees from in exchange for providing the services their customers want. These include some services that Apple also gets to be the exclusive provider of. +
++“Apple sees the value of owning the payment relationship. … If your financial life is on the iPhone, you’re not going to switch to a Samsung phone,” said Matt Stoller, research director of antitrust advocacy group American Economic Liberties Project. “If you’re a vendor and taking the iPhone for payment is easier, Apple is now your boss. It’ll be Apple’s America, we just live here.” +
++For some Apple users, of course, it’s also a good deal. +
++Me, for instance. Full disclosure, I signed up for an Apple savings account the day it became available because it was simple to do but mostly because it offered me nearly 10 times more interest than I got from the “high yield” savings account my real bank offered. And I was lucky to get that because big banks like Chase and Bank of America offer just 0.01 percent interest, while also often requiring mandatory minimums and sometimes charging monthly fees. After a week with my Apple savings account, it all seems to be working as advertised. +
++At a time when many people are reconsidering who they bank with, thanks to a few recent bank failures, Apple is offering something better than most traditional savings accounts. But it’s also new ground for Big Tech, and that may cause some new problems. +
++A few years ago, I never would have expected to give part of my financial life to the company that makes my computer and my phone. But Apple has steadily upped its presence in an ever-growing market of fintech services over the years. The internet makes online banking and transactions easy, mobile devices make them even easier, and tech companies are in a great position to provide it all. Apple, which is increasingly a services company, can do technology pretty well. More than half of American smartphone owners use an iPhone, giving Apple a large and loyal customer base to pull from. The world’s most valuable company also has an entire ecosystem built around it that no other American company can match. +
++So Apple has been more than happy to jump into the fintech game. It launched its mobile payments service Apple Pay in 2014, Apple Cash in 2017, and the Apple Card in 2019. In the last month, Apple has launched its take on the buy now, pay later craze — Apple Pay Later — and, now, the savings account. Both the credit card and savings account work through a partnership with Goldman Sachs, while Apple Cash is backed by Green Dot, a payments platform with its own bank. Apple does provide those Pay Later loans through its Apple Financing, LLC subsidiary. But Apple itself is not a bank. +
++“This is Apple becoming more of a fintech-type company, and shows their seriousness about being that entire suite or package when it comes to the fintech space,” Angelo Zino, a senior equity analyst at CFRA Research, said. +
++As with almost everything else it does, Apple takes advantage of the control it has over its devices to push these products on its users. You’ll find ads for them in your Wallet app, which integrates these features in a way that’s not available to Apple’s competitors. The Apple credit card has a little control panel in Apple Wallet, for instance, while other cards in Wallet will only show you your past transactions. Apple also makes sure to link all of these services to each other. And again, in order to get an Apple savings account, you have to have an Apple Card. To get an Apple Credit Card, you have to have an iPhone. All these seamless integrations make the products easy to use, which makes them that much more appealing. +
++Case in point: After an unfortunate period called “my mid-20s,” when I had multiple credit cards and multiple outstanding balances on them, I decided it was best to be a one-credit-card woman. Then my iPhone died. When I went to buy a new one, there was Apple waving interest-free payments and 3 percent cash back if I just signed up for an Apple Card and used it to buy my iPhone 14 Pro. I was approved quickly and could start using my card immediately after I added it to Wallet, an app I previously only used to hold airplane tickets. +
++Now I have two credit cards, but only one of them lets me see my balance, get cash rewards, and make payments right from the Wallet app on my iPhone. Since the Apple Card gives me extra cash if I use it with Apple Pay, I’ve also been using Apple Pay. The Apple savings account was also advertised to me in the Apple Card app, which it now exists within. My Apple Card cash rewards are automatically deposited into the savings account a day after I earn them, so I’ll probably be using the Apple Card even more, and my other credit card less. +
++So even though I thought I was getting an Apple Card just to buy a single Apple product, Apple has since become a significant part of my financial life. The company is offering me something better than what everyone else had and something that no one else could. I’m still not sure if this is a good thing for everyone in the long run. +
++“It’s really just this broader strategy to increase activation and engagement in terms of their actual physical hardware products and their software products,” Kevin Kennedy, an analyst at Third Bridge, said. “It’s all in the realm of driving more engagement in their core business.” +
++It’s not necessarily illegal for a company to make products that its customers want and that work well with other offerings. But Apple is a massive company with an incredible amount of control over its users as well as the companies many of its services compete with. +
++You can see why its expansion into finance would make antitrust advocacy groups wary. The American Economic Liberties Project warned against Google’s (now shelved) plans to launch some kind of bank account service in 2020. The organization said at the time that “the continuing push by Big Tech deeper and deeper into banking is at once alarming and totally unsurprising. It is a nightmarish example of the ways monopolies like Google can bully their way into new industries and it will open the door to all kinds of abuse.” Those concerns apply to Apple, too. +
++“There’s a reason we have traditionally separated out commerce and banking,” Stoller said. +
++Apple is hardly the only player in the fintech game, however. There’s a huge industry built around making your mobile device your financial hub, and to make spending money as frictionless as possible so you’ll do it more. It’s no coincidence that Elon Musk keeps bringing up “payments” as an essential part of his plan to turn Twitter into a “super app” called X. +
++Peer-to-peer payment apps — think Paypal, Venmo, Cash App, and Apple Cash — have become big business, with the majority of smartphone owners in the US using them to send money to friends or pay for services. They’re easy, fast, and convenient. That also makes them highly susceptible to scams and mistakes. With fewer protections than you’ll find in more traditional payment methods, there’s often no way to get your money back once it’s gone. You may be spending a lot more than you think in exchange for the ability to pay your friend back for those drinks almost instantaneously. +
++If you don’t have the money to spend or send immediately, there’s also a growing industry trying to solve that problem — but only temporarily, and there are strings attached. Buy now, pay later, or BNPL, apps like Klarna, Affirm, and Apple Pay Later typically operate by giving you a loan to buy a specific product, for which you can be approved in moments. You then pay the service back in installments. Some offer interest-free and fee-free plans, but you have to pay in full on time. +
++This allows people to buy things they otherwise couldn’t afford up front, or makes things seem cheaper than they are — which, in turn, makes people more likely to buy them. And people aren’t just using BNPL for frivolous or unnecessary expenses, either. People can and are using it for things like groceries. When it comes time to pay up, some people can’t. That subjects them to late fees or interest. Apple Pay Later doesn’t charge fees or interest, but it does require you to link the loan to a debit card, so the issuing bank of that card might hit you with an overdraft fee, and Apple may not be so quick to let you borrow from them next time. BNPL providers are incentivized to provide as many loans to as many people as possible, as they make money by charging retailers a fee (which may well translate to raising the prices for everyone) for each purchase financed through BNPL and through late fees and interest charges that some subject customers to. +
++“Currently, there are no requirements for underwriting for buy now, pay later,” Nadine Chabrier, senior policy counsel at the Center for Responsible Lending, said. “So there’s no analysis required — although some companies do — about whether this person has the ability to repay this loan.” +
++According to the Consumer Financial Protection Bureau, BNPL services approved 73 percent of applicants in 2021, and 10.5 percent of people who took out those loans paid a late fee. Chabrier said BNPL users tend to be younger, to have worse credit, and to be people of color. They’re also more likely to overdraft. +
++“People aren’t getting the protections that they want or need at times with these types of products,” Chabrier said. “People want the ‘frictionless process’ … and businesses want that because you can lose someone if there’s a roadblock in the way. But ultimately, it’s important to have consumer protections so that you’re not hurting consumers in the process.” +
++I don’t use BNPL, and I don’t intend to use Pay Later, even as Apple keeps reminding me in the Wallet app that I have the option to do so. Of course, I didn’t see myself getting an Apple Card either, nor did I think Apple would have savings accounts. So I guess the door’s still open. And while Apple’s offerings may be good for me directly, they do have indirect harms. Rewards credit cards come with high swipe fees (and Apple’s is higher than most), which means merchants have to pay more, and then they pass that down to their customers. People who pay with cash end up subsidizing people who pay through cards. BNPL services often promote themselves as being free to the consumer, but they may charge merchants fees, which many are fine with paying because BNPL services mean more purchases are being made. They may also raise their prices for everyone to compensate for what they lose to BNPL providers. +
++And then. again, there is the issue of Apple having that much more to do with that many more parts of my life and that many more parts of the economy, not only in the iPhone ecosystem Apple created but also, increasingly, well beyond it. Maybe I’ve put too many eggs in Apple’s basket, and I’ve made it that much harder to get out of. +
++On the other hand, that basket is a deep purple iPhone 14 Pro, available through 24 small interest-free monthly installments on my Apple Card, with a 3 percent Daily Cash back bonus that’s deposited into a savings account with a 4.15 percent interest rate. I’m not complaining — yet. +
+The ridiculous but important Twitter check mark fiasco, explained. +
++It didn’t take long for Elon Musk to weaponize his shiny new $44 billion toy. In less than six months since he took over Twitter, he’s laid off thousands of people, cut Twitter’s valuation in half, released cherry-picked “Twitter files” that purportedly show how pre-Musk Twitter was biased against conservatives, welcomed formerly banned accounts back into the fold, made a few changes to the product, and promised many more. +
++But the most controversial Twitter product update so far is what he’s done to verification. Verification used to be a way for users to know that a profile belonged to the person or organization it purported to be. It was reserved for the accounts that would need such an indicator, including those of famous people, companies, and journalists, who got blue check marks appended to their profiles to make that verification easy for everyone to see. +
+ ++It has now become a symbol of who is willing to pay $8 a month for “Twitter Blue” — or whomever Musk decides to give a free check to, whether they want one or not. Or, in the case of organizations, a symbol of who is willing to pay at least $1,000 a month. +
++On April 20, Twitter finally went through with the long-threatened removal of pre-Musk “legacy” blue checks. That means Musk’s Twitter Blue, which hasn’t gotten much traction so far, will truly be put to the test. How many people and companies are willing to pay for the check mark they used to get for free? And will more regular users want to pay once they see their favorite celebrities and brands are, too — assuming, that is, that any celebrities or brands actually do decide to pay for their checks? +
++The results so far haven’t been promising. Only a fraction of Twitter users have subscribed to Twitter Blue and their checks have become so much of a stigma that, a few days after taking free checks away, Twitter gave them back to accounts that had at least 1 million followers, possibly to encourage more accounts to sign up. +
++Musk’s big gamble may yet pay off. Platforms like Meta are even following his lead. For now, however, Twitter’s verification system has become a confusing mess of shifting timelines, “verified” fake accounts, and an ever-deteriorating experience for most of Twitter’s users by design — all to “democratize” whatever verification is now and squeeze money out of Twitter’s users and Musk’s biggest fans. +
++A few weeks after he took control of Twitter, Musk turned its Blue paid subscription service, which allowed users to get a few special features like the ability to edit tweets and a special profile photo shape for their NFTs, into a way for users to get blue checks on their profiles. He also said he would take blue checks away from accounts that didn’t pay up. Twitter Blue is $7 a month for people who sign up for an entire year, $8 a month on a per-month basis, and $11 a month if people sign up through Apple’s App Store or Google Play. The higher app store price is because Musk got mad that the app stores take a commission, although the extra $3 a month amounts to far more money than the app stores’ 15 to 30 percent commissions. +
++Musk framed the move as a way to open up Twitter’s blue checks, which to some had become a symbol of unfair and much-desired privilege that was bestowed upon people they didn’t like. +
+ ++The rollout has not been smooth, to say the least. Musk has been forced to suspend and delay it several times. An early attempt resulted in what should have been a predictable flood of “verified” impersonators of everyone from LeBron James announcing he wanted to be traded to Eli Lilly saying its insulin products were now free. Twitter has implemented new guardrails to try to prevent these issues every time a new one pops up. But the core problem remains that Twitter is no longer verifying the identity of users who get a blue check, nor is it a symbol of authenticity. Anyone who has a phone number and a credit card can appear “verified,” though Twitter supposedly vets accounts to ensure they’re not pretending to be someone else when they initially sign up, and temporarily takes their blue check away if they change their names or profile photos. +
++For the first few months of the new program, Twitter was also differentiating between the blue checks that were given to Twitter Blue subscribers and which were given to notable accounts before Musk’s takeover. You could click the check mark to see a prompt explaining which category a given user fell into. But being labeled a paid account soon became a source of shame. On April 1, the date that Musk once said Twitter would be removing blue checks from legacy accounts, the prompt changed to say that the check meant that an account was either subscribed to Twitter Blue or was a legacy account. On April 20, after the legacy checks were removed, the prompt changed again to say that the account was subscribed to Twitter Blue and had “verified their phone number.” +
+ ++Musk has also introduced a rainbow of check marks. Blue checks are for individuals. Government accounts get a gray check. Organizations get a square profile photo and gold check. Accounts that are associated with organizations get little icons with that organizations’ logo. But that’s only if those organizations are willing to pay a hefty price: the gold check is $1,000 a month, plus another $50 for each associated account. +
++Why would anyone pay for any of this? Increasingly, Musk has made paid Twitter about more than just the checks. The benefits from the previous Twitter Blue subscription are still there, and now you can tweet up to 10,000 characters, use bold and italics, and upload longer videos. You should see fewer ads, too. Twitter is also taking things that used to be free for all accounts and limiting them to just the paid ones to make the service seem more valuable. Two-factor authentication through text messages is now only given to paid accounts (the rest have to use an authenticator app). Musk said that the ability to vote in polls would be restricted to verified accounts on April 15, though this does not appear to have happened yet. He also said that only verified accounts will be shown in the For You tab, which replaced the Home tab in January. And verified accounts get prominence in replies and search, too. That could be a good thing if you like what those accounts have to say. It’s annoying and makes Twitter even less fun if you don’t. +
++It’s likely that, as time goes on, more and more features will be taken away from free accounts, and new features will be made available only to paid accounts, as Musk seems determined to make Twitter’s subscription-based business model work and ad revenues plunge. So far, only a fraction of Twitter accounts have subscribed. Now that Musk is forcing legacy accounts to pay up to stay verified, however, those numbers may change. That’s assuming, of course, that being on Twitter and having that prominence continues to be as valuable as it was before Musk bought it. +
++Many legacy check holders have already said it isn’t. Celebrities including William Shatner, Jason Alexander, and LeBron James (the real LeBron James this time) said they wouldn’t pay, as did several media outlets. This seems to have annoyed Musk, who personally requested that the gold check be removed from the main New York Times account after it was brought to his attention that the newspaper had said it would not pay for it. +
++But many of those celebrities and organizations won’t have to pay at all. According to the New York Times, Twitter will allow its 500 top advertisers and 10,000 most-followed organizations to keep their checks. And, with the reinstatement of free checks for accounts with more than 1 million followers, many celebrities and organizations already have their checks back. Including the New York Times. Oh, that’s right — just a few days after Musk “democratized” Twitter by making everyone pay for checks, no exceptions, Twitter gave a bunch of free checks back to accounts with big followings. This appears to be a response to a campaign called “Block the Blue,” which called for Twitter users to block any user with a paid blue check. +
++Musk quickly suspended the @BlockTheBlue account and gave free checks to accounts with more than 1 million followers, which came as a surprise (in some cases an unwelcome one) to many of those account holders. Some of them even changed their profile photos to make the checks go away, though, as per Twitter’s rules, the effect should only be temporary. Almost as temporary as Musk’s promises that Twitter Blue would be a great equalizer. +
++If you’re one of the many people in the world who don’t use Twitter, you may not understand exactly what a blue check is, why you should care about it, or why it seems to be so crucial to Musk’s business plan for Twitter. You may think none of this applies to you. Directly, it probably doesn’t. +
++But the blue checks were about more than just a badge next to a name. (Also: The blue checks are actually white checks inside a blue circle with scalloped borders.) Like many of Twitter’s best and most enduring features, the verification badges were an attempt to solve a problem Twitter also created. +
++Twitter began verifying accounts in 2009 to settle a lawsuit from famous baseball guy Tony La Russa over a fake Tony La Russa account. Back then, it was relatively easy to squat on a famous person’s name and make a fake account pretending to be them. That’s why Donald Trump had to go with “@realDonaldTrump” when he joined Twitter; someone had already taken @donaldtrump and made it a Trump parody account. Tina Fey says she’s never been on Twitter, but a lot of people sure thought @TinaFey (now @NotTinaFey) was her. And then there are the many, many Fake Will Ferrell Twitter accounts. That said, like most things Twitter, verification isn’t perfect: Author Cormac McCarthy’s fake account was somehow verified as recently as 2021. +
+ ++Twitter first doled out the checks to high-profile and official accounts, then expanded the program to accounts that weren’t necessarily celebrities. That group included accounts run by the people and institutions they claimed to be associated with — namely, politicians, brands, and journalists. +
++To give you an idea of what Twitter was like back when those blue checks were harder to come by, and the world we may return to now that “verification” can only be bought: Back in 2012 or so, the process for being verified was even more opaque and arbitrary than it is today. You got verified if you were famous enough that someone at Twitter decided you needed it, or if you knew someone at Twitter, or if the publication you worked for had an in with Twitter’s small Journalism & News team. Back then, a blue check was kind of special because it was rarer and you had to be somebody or know somebody to get it. +
++In 2016, Twitter let people apply to be verified. Now there were many more blue checks out there, although some people who probably should have gotten blue checks were denied and some people who really shouldn’t have gotten them were accepted. When people started asking why white supremacists were getting blue check marks, Twitter revoked the badges and closed down the verification application process altogether. The company only reopened it in 2021. +
++Before Musk’s changes, there were about 425,000 verified accounts, according to @verified, which used to follow all verified accounts but recently unfollowed everyone. That was enough for the blue check to no longer be the exclusive special symbol it was once seen as, but it was also a small percentage of Twitter’s total user base, which, before Musk’s takeover, Twitter put at 240 million monetizable (as in, actual people and not bots) daily active users. +
++So why are blue checks so important to Musk? Likely because he assigns a value to them that he thinks the vast majority of Twitter’s users share, and so they would be willing to pay for it as soon as they were given the chance. Plus, messing with them is a great way to hurt journalists, a profession he really doesn’t like, especially when he thinks it’s being mean to him. It’s also a way to appeal to the right-wing base to which he’s become some kind of savior. +
++Before Musk’s reign at Twitter, the right wing had also made “blue check” into a pejorative, using it to collectively describe and dismiss supposed liberal elites — especially journalists and supposedly woke SJW celebrities. (Some of the same people who make fun of blue checks also have blue checks, but somehow theirs don’t count.) Then there’s the fact that Twitter “punished” certain accounts by taking away their blue checks, which upset one blue check-loser so much that he tried to tell on Twitter to the White House. +
++To some, blue checks were seen as a mark of privilege, something they couldn’t have that was possessed by people they didn’t like. There was a sense that being verified was extremely important to the ego-driven, left-wing elitist journalist, and that they couldn’t live without their little badges or the thought of the unwashed masses having them, too. So if you’re Elon Musk and looking for a way to make money, stick it to people you don’t like, and please your adoring fans, charging for a blue check might seem like a great way to accomplish all three in one fell swoop. Bonus points for framing it as a way to “bring power to the people” and get rid of Twitter’s “current lords and peasants system” … as long as, you know, the peasants can pay $8 a month to become a lord. It also means compromising one of the very things the verification system was designed for. +
+ ++Musk says this method of verification is “the only way to defeat the bots and trolls” because it will cost them too much to create accounts that will either lose their blue check or be banned for violating Twitter’s rules. But Twitter still has a free tier, and if the vast majority of Twitter users won’t pay for Twitter, that’s where most of the action will stay. That could be a real problem for Twitter. If the pool of paid accounts is limited to a few hundred thousand or million Musk fans, right wingers, toxic users, and crypto bros, then that blue check will be even less desirable. And Twitter the platform, with only a select group of people being amplified, won’t be much fun either. +
++For people who aren’t verified and have always wanted to be, it’s understandable why getting a blue check, even by paying for it, is so attractive. But Musk and his acolytes, who seem to think blue checks are only about status, don’t seem to get why the company has, over the years, chosen who and what the platform should verify and amplify (or suppress). Twitter is a business, and it made business decisions to minimize objectionable and harmful users and content. That includes things like misinformation, racial slurs, conspiracy theories, state-sponsored propaganda campaigns, and calls to violence. +
++It never did those things perfectly, but it knew why it had to try: Users generally didn’t want to see that stuff, advertisers didn’t want their products featured alongside it, and it’s a really bad look for a company to be seen as a purveyor of harmful content, to the point that it’s partially blamed for a genocide — you can look at Facebook as an example that Twitter shouldn’t want to follow. +
++Musk appears to be throwing all of that away rather than learning from it and continuing to improve the company he’s already sunk so much of his money and reputation into. +
++It’s not just a matter of people who spread harmful content getting verified and being able to spread it even more widely. It’s also a matter of a lot of accounts that were verified for good reason losing that status because they understandably don’t want to or can’t pay for it. Their posts will be shoved down under those of the paid users, and that’s if they continue to use the service at all. +
++Meanwhile, people are willing to pay a little more to spread misinformation, and Twitter no longer has rules against that, nor does it have the content moderators needed to remove it at scale. Twitter is sure to become an even greater amplifier of harmful lies than it already is. Musk doesn’t seem to care about that aspect of verification or see why it’s important. When blue checks are solely about getting more money, it doesn’t really matter who is willing to pay or why. +
++There’s reason to believe that the blue check won’t be much of a status symbol — if it ever was one — now that the legacy checks are gone and anyone who has $8 to spare can get their own. (Dr. Seuss taught us this a long time ago.) But hey, this is the guy who built a reusable rocket, thanks in part to his vision but mostly to SpaceX’s talented engineers and massive government subsidies. He may well see something in Twitter and blue check payola that the rest of us don’t. Perhaps all of these seemingly spur-of-the-moment decisions were actually carefully considered and months in the making. +
++Now, though, the blue check only signifies that the name it’s next to was willing to pay for something that used to be free. As Musk himself tweeted, “you get what you pay for.” Now we’ll see what it’s actually worth. +
++Update, April 25, 2023, 5:20 pm ET: This story was originally published on November 4, 2022, and has been updated several times to include changes to Twitter Blue, that the legacy checkmarks have been removed, and that some of them came back. +
Wrestlers to PM Modi: please listen to our ‘Mann Ki Baat’ - Tokyo Games bronze medallist Bajrang also appealed to Prime Minister Narendra Modi
IPL 2023 | Jofra Archer undergoes minor elbow surgery, fit to play vs Rajasthan Royals on Sunday - The surgery in Belgium is Archer’s fifth in 25 months
Odisha beats Bengaluru FC in Super Cup summit to win first title - Diego Mauricio scored two goals in the first half in Odisha’s 2-1 win over Bengaluru FC in the Super Cup
IPL 2023 | It’s a little disappointing, says Rohit Sharma after big loss to Gujarat Titans - Set a stiff target of 208, MI were stopped at 152 for nine in the stipulated 20 overs.
Taty Castellanos scores four goals as Girona beats Real Madrid - Castellanos, playing on a one-season loan from New York City FC, scored twice in each half to help the Catalan club stun the defending league champions.
Centre targets ‘obscenity’ on streaming platforms, despite few complaints - The government is considering tightening rules for streaming platforms, though user complaints via established channels remain low, and two High Courts have stayed the Code of Ethics in the IT Rules, 2021
All about Kochi Water Metro, the first in India -
Defamation case | Gujarat HC judge recuses from hearing Rahul Gandhi’s appeal against sessions court order - Rahul Gandhi’s has challenged the order of the Surat sessions court that declined to stay his conviction in a criminal defamation case over his “Modi surname” remark
Wrestlers to PM Modi: please listen to our ‘Mann Ki Baat’ - Tokyo Games bronze medallist Bajrang also appealed to Prime Minister Narendra Modi
K.T. Rama Rao expects Telangana Assembly polls in December - It was revealed that the BRS was going in the right direction and emerged stronger after name change.
Zelensky holds first war phone call with China’s Xi - Ukraine’s president says his first call with China’s leader since the Russian invasion was “meaningful”.
Norway criticises Sweden’s response after research rocket goes awry - Oslo says it was not properly informed after a research rocket accidentally hit its territory.
Statue mocking Spain’s ex-king Juan Carlos appears in Madrid - The statue of the ex-king pointing a rifle at a sculpture of a bear mocks his love of hunting.
Der Spiegel: India anger over ‘racist’ German magazine cartoon on population - A cartoon by Der Spiegel on India overtaking China as the most populous nation has sparked sharp reactions.
Ukraine rapidly expanding its ‘Army of Drones’ for front line - The country increases its drone production after millions of pounds are raised through donations.
UK government blocks Microsoft’s proposed Activision purchase - Gov. group says deal would “substantially lessen competition” in cloud gaming. - link
Remember the EV Honda is building with GM? It goes on sale in 2024 - Two Ultium-based EVs arrive next year, an in-house EV follows in 2025. - link
Melatonin in sleep-aid gummies can be off by up to 350%, study finds - JAMA study highlights quality control issues common in dietary supplements. - link
ChatGPT now allows disabling chat history, declining training, and exporting data - Unsaved chats will be retained 30 days for “abuse monitoring” before permanent deletion. - link
GOP releases AI-generated ad to fearmonger over Biden’s reelection bid - RNC calls Biden “out of touch” for asking voters to let him “finish the job!” - link
A man with a great dane and a man with a Chihuahua go to a bar, but it says “no pets allowed” -
++One man says to the other “how will we bring our dogs inside?” The second man gives the first a pair of very dark sunglasses and says “do what I do.” He goes inside and the manager says “Sorry, no pets allowed.” The man says “You don’t understand. This is my guide dog.” “A great dane? Really?” Says the manager. “Yeah, they just got them into service. He’s great at protecting me, and his sense of smell allows me to easily find my way around the city” The manager decides to let him in. The man with the Chihuahua was watching carefully, and goes “how hard can this be?” So he puts on his sunglasses and goes to the bar. The manager sees him and says once again: “sorry sir, not pets allowed.” You don’t understand, this is my guide dog.” “A chihuahua?” “A CHIHUAHUA?! THEY GAVE ME A CHIHUAHUA?!” +
+ submitted by /u/Boeing307
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While in China, an American man is very sexually promiscuous and does not use a condom the entire time he is there. -
++A week after arriving back home in the States, he wakes one morning to find his penis covered with bright green and purple spots. +
++Horrified, he immediately goes to see a doctor. The doctor, never having seen anything like this before, orders some tests and tells the man to return in two days for the results. +
++The man returns a couple of days later and the doctor says, “I’ve got bad news for you, you’ve contracted Mongolian VD. It’s very rare and almost unheard of here in the US , we know very little about it.” +
++The man looks a little perplexed and says, “Well, give me a shot or something and fix me up, Doc.” +
++The doctor answers, “I’m sorry, there’s no known cure. We’re going to have to amputate your penis.” +
++The man screams in horror, “Absolutely not! I want a second opinion!!!” +
++The doctor replies, “Well, it’s your choice. Go ahead, if you want but surgery is your only option.” +
++The next day, the man seeks out a Chinese doctor, figuring that he’ll know more about the disease. +
++The Chinese doctor examines his penis and proclaims, “Ah, yes, Mongolian VD. Very rare disease.” +
++The guy says to the doctor, “Yeah, yeah, I already know that, but what can we do? My American doctor wants to cut off my penis!” +
++The Chinese doctor shakes his head and laughs. “Stupid American doctors, always want to amputate. Make more money that way. No need to amputate!” +
++“Oh, thank God!” the man exclaims. +
++“Yes,” says the Chinese doctor. “Wait two weeks. Fall off by itself!” +
+ submitted by /u/big_banana_6969
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What is a kidnappers favorite type of shoes? -
++White vans. +
+ submitted by /u/Griftimus
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I just graduated with a degree in Egyptology. -
++So now I am qualified to teach more students Egyptology. I’m beginning to think this is some sort of pyramid scheme. +
+ submitted by /u/Firegoat1
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Cop asks a guy..how high are you? -
++Guy: no officer, it’s hi, how are you. +
+ submitted by /u/Different-Tie-1085
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