Search

Abstract This paper presents the development and functionalities of the AI-FEED web-based platform (ai-feed.ai), designed to address food and nutrition insecurity challenges within the food charity ecosystem. AI-FEED leverages advancements in artificial intelligence (AI) and blockchain technology to facilitate improved access to nutritious food and efficient resource allocation, aiming to reduce food waste and bolster community health. The initial phase involved comprehensive interviews with various stakeholders to gather insights into the ecosystem’s unique challenges and requirements. This informed the design of four distinct modules in the AI-FEED platform, each targeting the needs of one of four stakeholder groups (food charities, donors, clients, and community leaders). Prototyping and iterative feedback processes were integral to refining these modules. The food charity module assists charities in generating educational content and predicting client needs through AI-driven tools. Based on blockchain technology, the food donor module streamlines donation processes, enhances donor engagement, and provides donor recognition. The client module provides real-time information on food charity services and offers a centralized repository for nutritional information. The platform includes a comprehensive mapping and proposal system for community leaders to strategically address local food insecurity issues. AI-FEED’s integrated platform approach allows data sharing across modules, enhancing overall functionality and impact. The paper also discusses ethical considerations, potential biases in AI systems, and the transformation of AI-FEED from a research project to a sustainable entity. The AI-FEED platform exemplifies the potential of interdisciplinary collaboration and technological innovation in addressing societal challenges, particularly in improving food security and community health.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization. CDO-7N-1 shows highly attenuated replication and minimal or no lung pathology in vivo over multiple passages. It induces robust mucosal and systemic neutralizing antibody and T-cell subset responses, in mice (female K18-hACE2 and male HFH4-hACE2 mice), hamsters, and macaques triggered by a single immunization. Mice and hamsters vaccinated with CDO-7N-1 are protected from challenge with wild-type (WT) SARS-CoV-2 and other variants of concern. Serum from vaccinated animals neutralizes WT SARS-CoV-2, variants of concern (beta and delta), variants of interest (omicron XBB.1.5) and SARS-CoV-1. Antibody responses are sustained and enhanced by repeated immunization or infection with WT SARS-CoV-2. Immunity against all SARS-CoV-2 proteins by CDO-7N-1 should improve efficacy against future SARS-CoV-2 variants.

Abstract Background The growth of labour migration and associated risks of human trafficking and exploitation remain significant global human rights and health challenges. There is increasing policy interest in addressing structural determinants of adverse migration outcomes such as migrants’ use of informal employment recruiters. In Ethiopia, “safe migration” policies have introduced regulations for registered private employment agencies and penalties for anyone else placing migrants into work overseas. Yet migrants continue to use informal facilitators who are often demonised as traffickers without evidence of their motivations, experiences or perceptions. We conducted qualitative interviews with 28 informal facilitators as part of a study into how recruitment practices shape risks for female migrants seeking domestic work in the Middle East and Gulf States. We present the realities of irregular recruitment on the ground, and how these practices are affected by policies that dichotomise recruiters into legal/safe and illegal/unsafe categories. Results We identified four main themes. First, arranging migration from rural areas differs from in the capital, Addis Ababa, where laws and regulations originate. Outside Addis Ababa, registration was difficult for facilitators to arrange, with little incentive to do so due to its lack of importance to prospective migrants. Second, the ability to circumvent legal requirements was considered an advantage of informal facilitators because it reduced costs and expedited migrants’ departure. Third, facilitators did not work alone but operated in long “chains” of diverse actors. This meant migrants’ safety was not determined by any given individual, but spread across numerous people involved in sending a migrant abroad, some of whom might be registered and others not. And finally, facilitators did not believe they could realistically safeguard migrants once they were outside of Ethiopia and working under different laws and employers. Conclusions Findings from this study add to a growing body of work demonstrating the diversity of people involved in the migration process, and consequent oversimplification of popular policy solutions. A more effective approach might be to constructively engage informal facilitators and identify ways they could assist with referring migrant workers to registered agencies and safe employment, rather than criminalising their participation.

To evaluate the clinical efficacy, safety, and cost-effectiveness of endometrial ablation or resection (E:A/R) compared to hysterectomy for the treatment of heavy menstrual bleeding. Literature search was conducted, and randomized control trials (RCTs) comparing (E:A/R) versus hysterectomy were reviewed. The search was last updated in November 2022. Twelve RCTs with 2,028 women (hysterectomy: n=977 vs. [E:A/R]: n=1,051) were included in the analyzis. The meta-analysis revealed that the hysterectomy group showed improved patient-reported and objective bleeding symptoms more than those of the (E:A/R) group, with risk ratios of (mean difference [MD], 0.75; 95% confidence intervals [CI], 0.71 to 0.79) and (MD, 44.00; 95% CI, 36.09 to 51.91), respectively. Patient satisfaction was higher post-hysterectomy than (E:A/R) at 2 years of follow-up, but this effect was absent with long-term follow-up. (E:A/R) is considered an alternative to hysterectomy as a surgical management for heavy menstrual bleeding. Although both procedures are highly effective, safe, and improve the quality of life, hysterectomy is significantly superior at improving bleeding symptoms and patient satisfaction for up to 2 years. However, it is associated with longer operating and recovery times and a higher rate of postoperative complications. The initial cost of (E:A/R) is less than the cost of hysterectomy, but further surgical requirements are common; therefore, there is no difference in the cost for long-term follow-up.

OBJECTIVES/GOALS: Identify causes for clinical research professional turnover Define data collection methods for exit interviews Provide institutions with resources to collect and analyze exit interviews Employ strategies to maximize the impact of exit interviews on retention METHODS/STUDY POPULATION: The Clinical Research Professional Taskforce (CRPT) exit interview Subgroup has met monthly since January 2023. Action items were agreed to and minutes were kept and reviewed at subsequent virtual working meetings. All members were given opportunity to speak and contribute. After a landscape analysis, conducted via survey, five institutions agreed to provide examples of their exit interview questions. Members spoke at length about goals, methods, collection techniques, institutional involvement, lessons learned and practical applications that could become best practices. RESULTS/ANTICIPATED RESULTS: The Subgroup aggregated all questions into categories and developed sample questions incorporating all data without using any word for word. In order to allow for quantitative assessment and standardized reporting the Subgroup formulated questions to be responded to utilizing a Likert scale with free text fields for select questions where further information is needed. The Subgroup developed best practices describing decision-making metrics, understanding reasons for turnover and reporting data back to leadership. Practical aspects such as method and time of survey collection, anonymity, and training staff are also included. DISCUSSION/SIGNIFICANCE: We are hopeful that sample questions and best practices will be helpful and widely utilized. Understanding the causes and impacts of CRP turnover are critical to meeting the current needs of clinical research. Further work is being done to calculate the cost of turnover to make the business case.

Objectives This study reviewed existing recommendations for virtual mental healthcare services through the quadruple aim framework to create a set of recommendations on virtual healthcare delivery to guide the development of Canadian policies on virtual mental health services.Design We conducted a systematic rapid review with qualitative content analysis of data from included manuscripts. The quadruple aim framework, consisting of improving patient experience and provider satisfaction, reducing costs and enhancing population health, was used to analyse and organise findings.Methods Searches were conducted using seven databases from 1 January 2010 to 22 July 2022. We used qualitative content analysis to generate themes.Results The search yielded 40 articles. Most articles (85%) discussed enhancing patient experiences, 55% addressed provider experiences and population health, and 25% focused on cost reduction. Identified themes included: screen patients for appropriateness of virtual care; obtain emergency contact details; communicate transparently with patients; improve marginalised patients’ access to care; support health equity for all patients; determine the cost-effectiveness of virtual care; inform patients of insurance coverage for virtual care services; increase provider training for virtual care and set professional boundaries between providers and patients.Conclusions This rapid review identified important considerations that can be used to advance virtual care policy to support people living with mental health conditions in a high-income country.

Abstract We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C‐reactive protein (hs‐CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs‐CRP levels were not significantly higher in participants with mild cognitive impairment (n = 97) or dementia (n = 59), compared to those with normal cognitive function (n = 126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs‐CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs‐CRP levels, is unlikely to contribute significantly to cognitive decline.

Abstract Background The optimal duration of antipsychotic treatment following remission of first-episode psychosis (FEP) is uncertain, considering potential adverse effects and individual variability in relapse rates. This study aimed to investigate the effect of antipsychotic discontinuation compared to continuation on recovery in remitted FEP patients. Methods CENTRAL, MEDLINE (Ovid), Embase, and PsycINFO databases were searched on November 2, 2023, with no language restrictions. RCTs evaluating antipsychotic discontinuation in remitted FEP patients were selected. The primary outcome was personal recovery, and secondary outcomes included functional recovery, global functioning, hospital admission, symptom severity, quality of life, side effects, and employment. Risk of bias was assessed using the Cochrane risk-of-bias tool 2, and the certainty of evidence was evaluated with GRADE. Meta-analysis used a random-effect model with an inverse-variance approach. Results Among 2185 screened studies, 8 RCTs (560 participants) were included. No RCTs reported personal recovery as an outcome. Two studies measured functional recovery, and discontinuation group patients were more likely to achieve functional recovery (RR 2.19; 95% CIs: 1.13, 4.22; I2 = 0%; n = 128), although evidence certainty was very low. No significant differences were found in hospital admission, symptom severity, quality of life, global functioning, or employment between the discontinuation and continuation groups. Conclusions Personal recovery was not reported in any antipsychotic discontinuation trial in remitted FEP. The observed positive effect of discontinuation on functional recovery came from an early terminated trial and an RCT followed by an uncontrolled period. These findings should be interpreted cautiously due to very low certainty of evidence.

Background Evidence guiding the pre‐hematopoietic stem cell transplantation (HSCT) cardiovascular evaluation is limited. We sought to derive and validate a pre‐HSCT score for the cardiovascular risk stratification of HSCT candidates. Methods and Results We leveraged the CARE‐BMT (Cardiovascular Registry in Bone Marrow Transplantation) study, a contemporary multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019 (N=2435; mean age at transplant of 55 years; 4.9% Black). We identified the subset of variables most predictive of post‐HSCT cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, heart failure, stroke, atrial fibrillation or flutter, and sustained ventricular tachycardia. We then developed a point‐based risk score using the hazard ratios obtained from Cox proportional hazards modeling. The score was externally validated in a separate cohort of 919 HSCT recipients (mean age at transplant 54 years; 20.4% Black). The risk score included age, transplant type, race, coronary artery disease, heart failure, peripheral artery disease, creatinine, triglycerides, and prior anthracycline dose. Risk scores were grouped as low‐, intermediate‐, and high‐risk, with the 5‐year cumulative incidence of cardiovascular events being 4.0%, 10.3%, and 22.4%, respectively. The area under the receiver operating curves for predicting cardiovascular events at 100 days, 5 and 10 years post‐HSCT were 0.65 (95% CI, 0.59–0.70), 0.73 (95% CI, 0.69–0.76), and 0.76 (95% CI, 0.69–0.81), respectively. The model performed equally well in autologous and allogeneic recipients, as well as in the validation cohort. Conclusions The CARE‐BMT risk score is easy to calculate and could help guide referrals of high‐risk HSCT recipients to cardiovascular specialists before transplant and guide long‐term monitoring.

BackgroundAmerican Indian and Alaska Native peoples experience poor end-of-life care, including more hospitalizations and lower use of hospice and do-not-resuscitate orders. Although advance care planning (ACP) can improve end-of-life care, ACP rates are disproportionately low in American Indians and Alaska Natives. ObjectiveWe culturally tailored and delivered an existing evidence-based ACP program for an American Indian tribal community. Here, we present the protocol for assessing the intervention’s feasibility and efficacy. MethodsWe measured feasibility via participant recruitment, participants’ evaluation (acceptability, appropriateness, comprehension, and satisfaction), and intervention fidelity. Recruitment was measured with participant screening, eligibility, enrollment, and retention. Participant’s evaluation of the intervention was measured with surveys. Fidelity was measured with direct observation and the Make Your Wishes About You (MY WAY) Fidelity Checklist Tool. To assess the intervention’s efficacy, we used a quasi-experimental waitlist control design with 2 cohorts who were surveyed each on three separate occasions. The intervention’s efficacy was assessed by the following: ACP barriers and facilitators as well as ACP self-efficacy, readiness, and completion. ResultsA total of 166 participants were screened for eligibility; 11 were deemed ineligible, and 155 participants were enrolled in the study. Of those enrolled, 113 completed the intervention and will be included in subsequent analyses. We finalized data collection in January 2023, and analyses are underway. Study enrollment was successful, and we expect that participants will report high levels of acceptability, appropriateness, comprehension, and satisfaction with the intervention. We expect that the intervention was implemented with fidelity and will demonstrate decreases in ACP barriers and increases in ACP facilitators, self-efficacy, readiness, and completion. ConclusionsEnrolling over twice as many participants as we had hoped suggests that members of this tribal community are willing to engage in end-of-life ACP. We were able to implement a waitlist study design to show that a culturally tailored ACP program for a tribal community is feasible. Trial RegistrationClinicalTrials.gov NCT05304117; https://clinicaltrials.gov/study/NCT05304117 International Registered Report Identifier (IRRID)DERR1-10.2196/50654

Objectives Early identification of lung cancer on chest radiographs improves patient outcomes. Artificial intelligence (AI) tools may increase diagnostic accuracy and streamline this pathway. This study evaluated the performance of commercially available AI-based software trained to identify cancerous lung nodules on chest radiographs.Design This retrospective study included primary care chest radiographs acquired in a UK centre. The software evaluated each radiograph independently and outputs were compared with two reference standards: (1) the radiologist report and (2) the diagnosis of cancer by multidisciplinary team decision. Failure analysis was performed by interrogating the software marker locations on radiographs.Participants 5722 consecutive chest radiographs were included from 5592 patients (median age 59 years, 53.8% women, 1.6% prevalence of cancer).Results Compared with radiologist reports for nodule detection, the software demonstrated sensitivity 54.5% (95% CI 44.2% to 64.4%), specificity 83.2% (82.2% to 84.1%), positive predictive value (PPV) 5.5% (4.6% to 6.6%) and negative predictive value (NPV) 99.0% (98.8% to 99.2%). Compared with cancer diagnosis, the software demonstrated sensitivity 60.9% (50.1% to 70.9%), specificity 83.3% (82.3% to 84.2%), PPV 5.6% (4.8% to 6.6%) and NPV 99.2% (99.0% to 99.4%). Normal or variant anatomy was misidentified as an abnormality in 69.9% of the 943 false positive cases.Conclusions The software demonstrated considerable underperformance in this real-world patient cohort. Failure analysis suggested a lack of generalisability in the training and testing datasets as a potential factor. The low PPV carries the risk of over-investigation and limits the translation of the software to clinical practice. Our findings highlight the importance of training and testing software in representative datasets, with broader implications for the implementation of AI tools in imaging.

Introduction: Scenario-based learning and gamification have many advantages in comparison to traditional didactic teaching methods, including development of many higher-level skills such as analysis and evaluation. It is hoped that these simulations provide a real-world experience in a format accessible to students. Integration of these tools into teaching excelled during the COVID-19 pandemic, an event that completely changed education and initiated the greatest advancement in digital learning to date. We discuss our experiences using Resimion, a novel scenario-based learning tool that was adapted to biomedical science, both for teaching and assessment.Methods: Our cohort included 769 students studying BSc(Hons) Biomedical Science at the University of the West of England from 2020 to 2023. Data was obtained from assessments within four different modules, two at FHEQ level 5 and two at level 6. Students were grouped based on reasonable adjustment (RA) status, including physical issues, specific learning differences and neurodiversity, with differences between student groups and assessment types analysed by ANOVA.Results: Data clearly demonstrate good engagement from students utilising Resimion software, representing 18,436 student interactions in total, across both assessed and non-assessed activities. RAs of any type did not alter submission rates (p = 0.53) or student outcome in any of the assessment types analysed. However, submission rates for Resimion assessments were notably higher than for other assessment types (p = 0.002). Whist outcomes were not significantly different, students with RAs did take significantly longer to complete the Haematology and Transfusion assessments (p = 0.0012). Specifically, neurodiverse students and those with specific learning differences used on average 81% of their allocated time, students with other RAs used 76%, whereas students without RAs used just 56% (p ≤ 0.0001), highlighting the appropriate adjustment of extra time provided for these students. It was further observed that 1.3% of Resimion activities undertaken by students utilised the in-built inclusivity features in the software. Both students with known RAs, and those without, utilised these features, therefore also aiding students without a formal diagnosis.Conclusion: The scenario-based learning tool Resimion was successfully integrated into the teaching of biomedical science and provided an engaging platform for students, with comparable results to other traditional assessment types.

Abstract Background Patients undergoing hemodialysis have a high mortality rate and yet underutilize palliative care and hospice resources. The Shared Decision Making-Renal Supportive Care (SDM-RSC) intervention focused on goals of care conversations between patients and family members with the nephrologist and social worker. The intervention targeted deficiencies in communication, estimating prognosis, and transition planning for seriously ill dialysis patients. The intervention showed capacity to increase substantially completion of advance care directives. The HIGHway Project, adapted from the previous SDM-RSC, scale up training social workers or nurses in dialysis center in advance care planning (ACP), and then support them for a subsequent 9-month action period, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care. Methods We will train between 50–60 dialysis teams, led by social workers or nurses, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care. This implementation project uses the Knowledge to Action (KTA) Framework within the Consolidated Framework for Implementation Research (CFIR) to increase adoption and sustainability in the participating dialysis centers. This includes a curriculum about how to hold ACP conversation and coaching with monthly teleconferences through case discussion and mentoring. An application software will guide on the process and provide resources for holding ACP conversations. Our project will focus on implementation outcomes. Success will be determined by adoption and effective use of the ACP approach. Patient and provider outcomes will be measured by the number of ACP conversations held and documented; the quality and fidelity of ACP conversations to the HIGHway process as taught during education sessions; impact on knowledge and skills; content, relevance, and significance of ACP intervention for patients, and Supportive Kidney Care (SKC) App usage. Currently HIGHway is in the recruitment stage. Discussion Effective changes to advance care planning processes in dialysis centers can lead to institutional policy and protocol changes, providing a model for patients receiving dialysis treatment in the US. The result will be a widespread improvement in advance care planning, thereby remedying one of the current barriers to patient-centered, goal-concordant care for dialysis patients. Trial registration The George Washington University Protocol Record NCR213481, Honoring Individual Goals and Hopes: Implementing Advance Care Planning for Persons with Kidney Disease on Dialysis, is registered in ClinicalTrials.gov Identifier: NCT05324878 on April 11th, 2022.

Abstract Background There is increasing evidence of problematic rates of food insecurity among college students, yet few studies have gone beyond this to examine housing insecurity rates or rates of basic need insecurity (BNI), which is defined as having both food and housing insecurity, among the postsecondary population. BNI may have significant impacts on the mental and social health, and academic outcomes of college students, yet remains understudied. The researchers of this study are among the first to assess the prevalence of food insecurity, housing insecurity, and basic needs insecurity among college students enrolled at a large, public university in the Southeast and to identify factors associated with experiencing food, housing, and basic needs insecurity. Methods A cross-sectional online survey was conducted at a large, public university in the Southeast United States. All eligible, enrolled students (n = 23,444) were asked to complete an online survey, 2634 responded (11.2% response rate). Multivariate logistic regression models were used to assess relationships between demographic and financial factors and the outcomes of interest (food, housing, and basic needs insecurity). Results High rates of food insecurity (48.5%), housing insecurity (66.1%), and basic needs insecurity (37.1%) were identified. After controlling for confounders, factors that were significantly associated with increased odds of students having basic needs insecurity included previous food insecurity (p

Angiotensin-converting enzyme 2 (ACE2), part of the renin-angiotensin system (RAS), serves as an entry point for SARS-CoV-2, leading to viral proliferation in permissive cell types. Using mouse lines in which the Ace2 locus has been humanized by syntenic replacement, we show that regulation of basal and interferon induced ACE2 expression, relative expression levels of different ACE2 transcripts, and sexual dimorphism in ACE2 expression are unique to each species, differ between tissues, and are determined by both intragenic and upstream promoter elements. Our results indicate that the higher levels of expression of ACE2 observed in the lungs of mice relative to humans may reflect the fact that the mouse promoter drives expression of ACE2 in populous airway club cells while the human promoter drives expression in alveolar type 2 (AT2) cells. In contrast to transgenic mice in which human ACE2 is expressed in ciliated cells under the control of the human FOXJ1 promoter, mice expressing ACE2 in club cells under the control of the endogenous Ace2 promoter show a robust immune response after infection with SARS-CoV-2, leading to rapid clearance of the virus. This supports a model in which differential expression of ACE2 determines which cell types in the lung are infected, and this in turn modulates the host response and outcome of COVID-19.

OBJECTIVES:. Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN:. Multicenter cohort study. SETTING:. ICUs at 68 hospitals across the United States. PATIENTS:. A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity

Background Venous thromboembolism (VTE) contributes significantly to COVID‐19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID‐19. Whether suPAR levels identify patients with COVID‐19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID‐19 with suPAR and D‐dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine‐Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D‐dimer levels. There was a positive association between suPAR and D‐dimer (β=7.34; P=0.002). Adjusted for clinical covariables, including D‐dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51–4.75]; P

The purpose of this cross-sectional study was to understand the perceptions Extension professionals have about healthy food retail programs (HFRPs). Family and Consumer Science (FCS) agents from one state in the southeastern United States were interviewed about their definitions of HFRPs, what challenges and benefits existed, and strategies for successful HFRP implementation. Participants reported that HFRPs would bring immense benefits to their communities, including expanding the recognition of Extension. However, one specific suggestion that was identified was hands-on training needed before initiating HFRPs, particularly on strategies for relationship development with retail store owners.

This study investigated the concerns and perceptions associated with COVID-19 and its variants among faculty, students, staff, and administrators at an R2 research university. Participants: n = 189 participants from the university community. A Qualtrics™ survey was used to draw responses from the university community. The results of this study revealed that (1) Approximately 2/3 of survey respondents are concerned about the appearance of Delta and Omicron COVID-19 variants; (2) 53.7% of respondents were inclined to get vaccinated after the new COVID-19 variants surfaced; (3) 22.2% of respondents tested positive for COVID-19 after becoming fully vaccinated; (4) 70.4% of respondents said they would get the booster shot for COVID-19; (5) 77.2% of respondents felt that there would be a new COVID variant identified this year beyond Delta and Omicron; and (6) Less than 20% of survey respondents feel safe on campus during the prevailing COVID-19 pandemic. There remains a general feeling of vulnerability while on campus two years into the COVID-19 pandemic.

ABSTRACT Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.

Systematic screens for synthetic lethal gene pairs represent a powerful approach to define interactions that may be exploited in the clinic. Here, the authors use a dual-guide CRISPR screening approach to screen a curated selection of gene pairs across three cell lines and validate the Fam50a/Fam50b synthetic lethality was in isogenic cell models as well as in an in vivo setting.

Low-grade inflammation is emerging as a common feature of contemporary metabolic, psychiatric, and neurodegenerative diseases. Both physical inactivity and abdominal adiposity are associated with persistent systemic low-grade inflammation. Thus, the behavioral, biological, and physiological changes that cause a predisposition to obesity and other co-morbidities could have epigenetic underpinnings in addition to various evolutionary scenarios. A key assumption involves the potential for a mismatch between the human genome molded over generations, and the issue of adapting to the modern high calorie diet and common built environments promoting inactivity. This biological mismatch appears to have dire health consequences. Therefore, the goal of this article is to provide a brief overview on the importance of inflammation as part of human survival and how physical activity (PA) and physical inactivity are critical regulators of systemic inflammation. The review will highlight anti-inflammatory effects of PA and exercise training from a metabolic and systemic signaling perspective, which includes skeletal muscle to utilization of fatty acids, TLR4 signaling, and myokine/adipokine effects. The available evidence suggests that PA, regular exercise, and weight loss offer both protection against and treatment for a wide variety of chronic diseases associated with low-grade inflammation through an improved inflammatory profile. Keywords: Inflammation, Immunity, Myokines, Cytokines, Physical inactivity, Physical activity, Exercise, Obesity

Migratory species are the most important commercial fishes in the Amazon. They are also now the most threatened directly by some combination of overfishing, floodplain deforestation, and dam construction. Limited governmental monitoring and implemented regulations impede adequate management of the fisheries at adequate scale. We summarize the current stock status of the three most heavily exploited long-distance migratory species, which are two goliath catfishes (Brachyplatystoma rousseauxii and B. vaillantii) and the characiform Colossoma macropomum. In addition, we analyze impacts beyond overfishing on these species. Our results indicate: (i) the overfishing trends for these important species are either ominous or indicate the verge of collapse of the commercial fisheries based on them, and (ii) a dangerous synergy between overfishing, hydroelectric dams, and floodplain deforestation further challenge fisheries management of migratory species in the Amazon. We propose eight direct governmental actions as a proactive approach that addresses the main impacts on the fisheries. We consider that the most practical way to assess and manage overfishing of migratory species in the short run in an area as large as the main commercial fishing area in the Amazon is at market sites where enforced regulations can control fish catch. The management of the three species considered here has implications beyond just their sustainability. Their management would represent a paradigm shift where the governments assume their legal responsibilities in fishery management. These responsibilities include regulation enforcement, data collecting, inter-jurisdictional cooperation to protect migratory species at realistic life history scales, mitigation of the Madeira dams to assure goliath catfish passage to the largest western headwater region, and recognition of monitoring and managing wetland deforestation for the protection of fish and other aquatic and terrestrial biodiversity.

Chronic diseases are the leading cause of death worldwide with increasing prevalence in all age groups, genders, and ethnicities. Most chronic disease deaths occur in middle-to low-income countries but are also a significant health problem in developed nations. Multiple chronic diseases now affect children and adolescents as well as adults. Being physically inactive is associated with increased chronic disease risk. Global societies are being negatively impacted by the increasing prevalence of chronic disease which is directly related to rising healthcare expenditures, workforce complications regarding attendance and productivity, military personnel recruitment, and academic success. However, increased physical activity (PA) and exercise are associated with reduced chronic disease risk. Most physiologic systems in the body benefit positively from PA and exercise by primary disease prevention and secondary disease prevention/treatment. The purpose of this brief review is to describe the significant global problem of chronic diseases for adults and children, and how PA and exercise can provide a non-invasive means for added prevention and treatment. Keywords: Chronic disease, Noncommunicable diseases, Obesity, Diabetes, Cardiovascular disease, Cancer, Physical activity, Exercise

Background Use of angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) is thought to affect COVID‐19 through modulating levels of angiotensin‐converting enzyme 2, the cell entry receptor for SARS‐CoV2. We sought to assess the association between ACEi/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVID‐19. Methods and Results We leveraged the ISIC (International Study of Inflammation in COVID‐19), identified patients admitted for symptomatic COVID‐19 between February 1, 2020 and June 1, 2021 for COVID‐19, and examined the association between in‐hospital ACEi/ARB use and all‐cause death, need for ventilation, and need for dialysis. We estimated the causal effect of ACEi/ARB on the composite outcomes using marginal structural models accounting for serial blood pressure and serum creatinine measures. Of 2044 patients in ISIC, 1686 patients met inclusion criteria, of whom 398 (23.6%) patients who were previously on ACEi/ARB received at least 1 dose during their hospitalization for COVID‐19. There were 215 deaths, 407 patients requiring mechanical ventilation, and 124 patients who required dialysis during their hospitalization. Prior ACEi/ARB use was associated with lower levels of soluble urokinase plasminogen activator receptor and C‐reactive protein. In multivariable analysis, in‐hospital ACEi/ARB use was associated with a lower risk of the composite outcome of in‐hospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36–0.65]). Conclusions In patients hospitalized for COVID‐19, ACEi/ARB use was associated with lower levels of inflammation and lower risk of in‐hospital outcomes. Clinical trials will define the role of ACEi/ARB in the treatment of COVID‐19. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

BackgroundDespite unprecedented advances in worldwide access to the internet via smartphones, barriers to engaging hard-to-reach populations remain in many methods of health research. A potential avenue for conducting qualitative research is via participatory web-based media, including the free, popular social platform WhatsApp. However, despite the clear advantages of engaging with participants over a well-established web-based platform, logistical challenges remain. ObjectiveThis study aims to report evidence on the feasibility and acceptability of WhatsApp as a method to conduct focus groups. MethodsA pilot focus group was conducted with Spanish-speaking women near the US–Mexico border. The content focus was knowledge and perceived risks for exposure to the Zika virus during pregnancy. ResultsEvidence was obtained regarding WhatsApp as a low-cost, logistically feasible methodology that resulted in rich qualitative data from a population that is often reticent to engage in traditional research. A total of 5 participants participated in a focus group, of whom all 5 consistently contributed to the focus group chat in WhatsApp, which was conducted over 3 consecutive days. ConclusionsThe findings are noteworthy at a time when face-to-face focus groups, the gold standard, are risky or precluded by safe COVID-19 guidelines. Other implications include more applications and evaluations of WhatsApp for delivering one-on-one or group health education interventions on sensitive topics. This paper outlines the key steps and considerations for the replication or adaptation of methods.

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Hypothesis generation in observational, biomedical data science often starts with computing an association or identifying the statistical relationship between a dependent and an independent variable. However, the outcome of this process depends fundamentally on modeling strategy, with differing strategies generating what can be called "vibration of effects" (VoE). VoE is defined by variation in associations that often lead to contradictory results. Here, we present a computational tool capable of modeling VoE in biomedical data by fitting millions of different models and comparing their output. We execute a VoE analysis on a series of widely reported associations (e.g., carrot intake associated with eyesight) with an extended additional focus on lifestyle exposures (e.g., physical activity) and components of the Framingham Risk Score for cardiovascular health (e.g., blood pressure). We leveraged our tool for potential confounder identification, investigating what adjusting variables are responsible for conflicting models. We propose modeling VoE as a critical step in navigating discovery in observational data, discerning robust associations, and cataloging adjusting variables that impact model output.

Introduction: Older adults have the poorest coronavirus (COVID-19) prognosis with the highest risk of death due to complications, making their COVID-19 experiences particularly important. Guided by the stress-appraisal-coping theoretical model, we sought to understand COVID-related perceptions and behaviors of older adults residing in the United States.Materials and Methods: We used convenience sampling to recruit persons with the following inclusion criteria: Aged ≥ 65 years, English fluency, and U.S. residency. Semi structured in-depth interviews were conducted remotely and audio recorded between April 25, 2020 and May 7, 2020. Interviews were professionally transcribed with a final study sample of 43. A low-inference qualitative descriptive design was used to provide a situated understanding of participants' life experiences using their naturalistic expressions.Results: The mean age of participants was 72.4 ± 6.7. Slightly over half were female (55.8%), 90.6% were White, and 18.6% lived alone. The largest percentages of participants resided in a rural area (27.9%) or small city (25.6%). We identified four themes, including (1) risk perception, (2) financial impact, (3) coping, and (4) emotions. Most participants were aware of their greater risk for poor COVID-19 outcomes but many did not believe in their increased risk. Financial circumstances because of the pandemic varied with largely no financial impacts, while others reported negative impacts and a few reported positive impacts. Coping was problem- and emotion-focused. Problem-focused coping included precautionary efforts and emotion-focused coping included creating daily structure, pursuing new and/or creative activities, connecting with others in new ways, and minimizing news media exposure. Overall, emotional health was negatively affected by the pandemic although some participants reported positive emotional experiences.Conclusions: Perceiving themselves as high risk for COVID-19 complications, older adults used precautionary measures to protect themselves from contracting the virus. The precautionary measures included social isolation, which can negatively affect mental health. Older adults will need to be resourceful and draw on existing resources to cope, such as engaging in creative activities and new strategies to connect with others. Our findings underscore the importance of the preservation of mental health during extended periods of isolation by taking advantage of low-to-no-cost existing resources.

Abstract Background Insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are effective for malaria prevention and are designed to provide nearly 5 years of mosquito protection. However, many ITNs and LLINs become damaged and ineffective for mosquito bite prevention within 1 to 2 years in field conditions. Non-adherence to recommended bed net care and repair practices may partially explain this shortened net longevity. Methods Using data from a cross-sectional study, a net care adherence score was developed and adherence to net care practices described from two regions of western Kenya. Relationships between attitudes and environmental factors that influence net longevity were measured with adherence to bed net care practices. Results While overall care practices are highly adherent particularly in the highlands, practices related to daily storage, washing frequency, and drying location need improvement in the lowlands. Seventy-seven percent of nets in the lowlands were washed

Gene fusions are observed in many cancers but their link to tumour fitness is largely unknown. Here, transcriptomic analysis combined with pharmacological and CRISPR-Cas9 screening of cancer cell lines was used to evaluate the functional linkage between fusions and tumour fitness.

Introduction This article discusses the process of defining competencies and development of a best practices training course for investigators and clinical research coordinators who conduct social and behavioral research. Methods The first project phase established recommendations for training in Good Clinical Practice (GCP) and was done in conjunction with representatives from 62 Clinical and Translational Science Award (CTSA) hubs. Diversity in behavioral clinical trials and differences in regulation of behavioral trials compared with clinical trials involving drugs, devices, or biologics necessitated a separate Social and Behavioral Work Group. This group worked with CTSA representatives to tailor competencies and fundamental GCP principles into best practices for social and behavioral research. Results Although concepts underlying GCP were deemed similar across all clinical trials, not all areas were equally applicable and the ways in which GCP would be enacted differ for behavioral trials. It was determined that suitable training in best practices for social and behavioral research was lacking. Discussion Based on the training need, an e-learning course for best practices is available to all CTSA sites. Each institution is able to track outcomes for its employees to help achieve standardized competency-based best practices for social and behavioral investigators and staff.

يسعى التعليم الصحي المتداخل بين التخصصات إلى خلق بيئة يستطيع من خلالها الطلبة من مختلف التخصصات الصحية التعلم مع بعضهم, ومن بعضهم وحول بعضهم البعض لتحسين التعاون وجودة الرعاية المقدمة. تصف هذه المقالة إثنتا عشرة استراتيجية لإدخال التعليم المتداخل بين التخصصات للتسجيل المسبق لتعليم الصحة المهنية آخذة بالحسبان صعوبة تصميم ودمج التعليم المتداخل بين التخصصات في مختلف مناهج التخصصات الصحية. نؤكد المسئولية الجماعية بين الأكاديميين والشركاء مع الوضوح التام في تحديد الأهداف المعبر عنها في مخرجات التعليم وطرق التعلم. تؤكد هذه المقالة على أهمية إدارة عمل المجموعات الطلابية للتعليم والتعلم المتداخل بين التخصصات متطلعين لتأهيل الأكاديميين والطلبة. وقد أظهرت أيضا الأدلة المؤيدة من الأدبيات أن التعليم المتداخل بين التخصصات لتقييم الطالب وتقييم البرنامج يلعبان أدوارا رئيسة في نجاح أداء مقررات التعليم الصحي المتداخل بين التخصصات.

Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER)-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.