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Abstract Background In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes. Methods Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion (SHP) clinic Hanoi, Vietnam. Participants: Sexually active MSM (n=564) who are newly initiating PrEP or re-initiating PrEP and have unhealthy alcohol use will be recruited and randomized 1:1 to the SOC or BAI arm. A subgroup of participants (n=20) in each arm will be selected for longitudinal qualitative interviews; an additional subset (n=48) in the BAI arm will complete brief quantitative and qualitative interviews after completion of the BAI to assess the acceptability of the intervention. Additional implementation outcomes will be assessed through interviews with clinic staff and stakeholders (n=35). Intervention: Study participants in both arms will receive standard care for PrEP clients. In the BAI arm, each participant will receive two face-to-face intervention sessions and two brief booster phone sessions, based on cognitive behavioral therapy and delivered in motivational interviewing informed style, to address their unhealthy alcohol use. Outcomes: Effectiveness (PrEP and alcohol use) and cost-effectiveness outcomes will be compared between the two arms. Intervention implementation outcomes (acceptability, feasibility, adoption) will be assessed among MSM participants, clinic staff, and stakeholders. Discussion This proposed trial will assess an alcohol intervention for MSM with unhealthy alcohol use who initiate or re-initiate PrEP, while simultaneously preparing for subsequent implementation. The study will measure the effectiveness of the BAI for increasing PrEP persistence through reducing unhealthy alcohol use in a setting where excessive alcohol consumption is a normative behavior. If effective, implementation-focused results will inform future scale-up of the BAI in similar settings. Trial registration NCT06094634 on clinicaltrials.gov. Registered 16 October 2023.

Abstract Background In Malawi, approximately 25% of adolescents living with HIV (ALWH) also suffer from depression. Not only is HIV stigma a major contributor to depression but it also adversely impacts HIV care engagement. ALWH can experience HIV stigma as stereotyping, social exclusion, low social support, and abuse, and these experiences are associated with poor mental health. Despite recognition of the deleterious effects of HIV stigma, we have limited knowledge of how stigma is experienced by ALWH with comorbid depression. Guided by the Health Stigma and Discrimination Framework, we describe stigma faced by ALWH and comorbid depression in Malawi and its implications for future interventions. Methods As part of a larger formative study to adapt a mental health counseling intervention, we conducted in-depth interviews, social support mapping sessions, and focus-group discussions with 25 ALWH, 4 caregivers of ALWH, 3 HIV providers, and 5 participants and 5 staff of a prior mental health counseling intervention. After analyzing the stigma codes, we used the Health Stigma and Discrimination Framework to organize the data into four key domains: drivers, manifestations, outcomes, and health and social impacts. Results Major drivers of HIV stigma included fear of HIV transmission, negative effects of antiretroviral therapy (ART), association with death, inaccurate knowledge, and negative attitudes towards ALWH. The most common manifestations of HIV stigma were gossip, insults and mocking, and physical and social distancing. Decreased ART adherence and missed HIV appointments were commonly cited outcomes of HIV stigma. Broader health impacts of HIV stigma were notable for mental health comorbidities including depression, anxiety, substance use, and suicidality. Identified resilience strategies included support for HIV care engagement and psychosocial support from family and friends. Conclusions This study systematically describes the stigmatization process faced by ALWH and experiencing depressive symptoms in Malawi. Notably, HIV stigma continues to disrupt HIV care and detrimentally impacts mental health during adolescent development. Further studies focused specifically on stigma are needed to better characterize this process and identify additional resilience factors. Investment in stigma-reduction interventions for ALWH is needed to avert poor mental health and HIV outcomes.

Abstract Background Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians’ attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians’ knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use. Methods Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians’ alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI. Participants: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months. Outcomes: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff’s alcohol use and clinic-level alcohol expectations in the EBAI arm. Discussion This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases. Trial Registration NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885 .

BACKGROUND: In the US, over 200 lives are lost from opioid overdoses each day. Accurate and prompt diagnosis of opioid use disorders (OUD) may help prevent overdose deaths. However, international classification of disease (ICD) codes for OUD are known to underestimate prevalence, and their specificity and sensitivity are unknown. We developed and validated algorithms to identify OUD in electronic health records (EHR) and examined the validity of OUD ICD codes. METHODS: Through four iterations, we developed EHR-based OUD identification algorithms among patients who were prescribed opioids from 2014 to 2017. The algorithms and OUD ICD codes were validated against 169 independent gold standard EHR chart reviews conducted by an expert adjudication panel across four healthcare systems. After using 2014-2020 EHR for validating iteration 1, the experts were advised to use 2014-2017 EHR thereafter. RESULTS: Of the 169 EHR charts, 81 (48%) were reviewed by more than one expert and exhibited 85% expert agreement. The experts identified 54 OUD cases. The experts endorsed all 11 OUD criteria from the Diagnostic and Statistical Manual of Mental Disorders-5, including craving (72%), tolerance (65%), withdrawal (56%), and recurrent use in physically hazardous conditions (50%). The OUD ICD codes had 10% sensitivity and 99% specificity, underscoring large underestimation. In comparison our algorithm identified OUD with 23% sensitivity and 98% specificity. CONCLUSIONS AND RELEVANCE: This is the first study to estimate the validity of OUD ICD codes and develop validated EHR-based OUD identification algorithms. This work will inform future research on early intervention and prevention of OUD.

Neoantigens are tumor-specific peptide sequences resulting from sources such as somatic DNA mutations. Upon loading onto major histocompatibility complex (MHC) molecules, they can trigger recognition by T cells. Accurate neoantigen identification is thus critical for both designing cancer vaccines and predicting response to immunotherapies. Neoantigen identification and prioritization relies on correctly predicting whether the presenting peptide sequence can successfully induce an immune response. Because most somatic mutations are single-nucleotide variants, changes between wild-type and mutated peptides are typically subtle and require cautious interpretation. A potentially underappreciated variable in neoantigen prediction pipelines is the mutation position within the peptide relative to its anchor positions for the patient's specific MHC molecules. Whereas a subset of peptide positions are presented to the T cell receptor for recognition, others are responsible for anchoring to the MHC, making these positional considerations critical for predicting T cell responses. We computationally predicted anchor positions for different peptide lengths for 328 common HLA alleles and identified unique anchoring patterns among them. Analysis of 923 tumor samples shows that 6 to 38% of neoantigen candidates are potentially misclassified and can be rescued using allele-specific knowledge of anchor positions. A subset of anchor results were orthogonally validated using protein crystallography structures. Representative anchor trends were experimentally validated using peptide-MHC stability assays and competition binding assays. By incorporating our anchor prediction results into neoantigen prediction pipelines, we hope to formalize, streamline, and improve the identification process for relevant clinical studies.

Abstract Background Mental disorders are common among people with HIV (PWH) and are associated with poor HIV outcomes. Despite high unmet mental health needs among PWH, use of evidence-based mental health screening and treatment protocols remains limited at HIV treatment facilities across low-resource settings. Integrating mental health services into HIV care can reduce this gap. This study’s objective was to explore factors that influence integration of mental health screening and treatment into HIV clinics in Cameroon. Methods We analyzed 14 in-depth interviews with clinic staff supporting PWH at three urban HIV treatment clinics in Cameroon. Interviews focused on current processes, barriers and facilitators, and types of support needed to integrate mental health care into HIV care. Interviews were recorded and transcribed. French transcripts were translated into English. We used thematic analysis to identify factors that influence integration of mental health screening and treatment into HIV care in these settings. Ethical review boards in the United States and Cameroon approved this study. Results Respondents discussed a lack of standardized mental health screening processes in HIV treatment facilities and generally felt ill-equipped to conduct mental health screening. Low community awareness about mental disorders, mental health-related stigma, limited physical space, and high clinic volume affected providers’ ability to screen clients for mental disorders. Providers indicated that better coordination and communication were needed to support client referral to mental health care. Despite these barriers, providers were motivated to screen clients for mental disorders and believed that mental health service provision could improve quality of HIV care and treatment outcomes. All providers interviewed said they would feel more confident screening for mental disorders with additional training and resources. Providers recommended community sensitization, training or hiring additional staff, improved coordination to manage referrals, and leadership buy-in at multiple levels of the health system to support sustainable integration of mental health screening and treatment into HIV clinics in Cameroon. Conclusions Providers reported enthusiasm to integrate mental health services into HIV care but need more support and training to do so in an effective and sustainable manner.

ABSTRACTMetastatic (m) colorectal cancer (CRC) is an incurable disease with a poor prognosis and thus remains an unmet clinical need. Immune checkpoint blockade (ICB)-based immunotherapy is effective for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC patients, but it does not benefit the majority of mCRC patients. NK cells are innate lymphoid cells with potent effector responses against a variety of tumor cells but are frequently dysfunctional in cancer patients. Memory-like (ML) NK cells differentiated after IL-12/IL-15/IL-18 activation overcome many challenges to effective NK cell anti-tumor responses, exhibiting enhanced recognition, function, and in vivo persistence. We hypothesized that ML differentiation enhances the NK cell responses to CRC. Compared to conventional (c) NK cells, ML NK cells displayed increased IFN-γ production against both CRC cell lines and primary patient-derived CRC spheroids. ML NK cells also exhibited improved killing of CRC target cells in vitro in short-term and sustained cytotoxicity assays, as well as in vivo in NSG mice. Mechanistically, enhanced ML NK cell responses were dependent on the activating receptor NKG2D as its blockade significantly decreased ML NK cell functions. Compared to cNK cells, ML NK cells exhibited greater antibody-dependent cytotoxicity when targeted against CRC by cetuximab. ML NK cells from healthy donors and mCRC patients exhibited increased anti-CRC responses. Collectively, our findings demonstrate that ML NK cells exhibit enhanced responses against CRC targets, warranting further investigation in clinical trials for mCRC patients, including those who have failed ICB.

BackgroundWe assessed built environment (residential density, landuse mix and aesthetics) and HIV linkage to care (LTC) among 1,681 (18-49 years-old) residents of 15 Mpumalanga villages, South Africa.MethodsMultilevel models (linear-binomial) were used for the association between built environment, measured using NEWS for Africa, and LTC from a clinical database of 9 facilities (2015-2018). Additionally, we assessed effect-measure modification by universal test-and-treat policy (UTT).ResultsWe observed, a significant association in the adjusted 3-month probability of LTC for residential density (risk difference (RD)%: 5.6, 95%CI: 1.2-10.1), however, no association for land-use mix (RD%: 2.4, 95%CI: -0.4, 5.2) and aesthetics (RD%: -1.2, 95%CI: -4.5-2.2). Among those diagnosed after UTT, residents of high land-use villages were more likely to link-to-care than those of low land-use villages at 12 months (RD%: 4.6, 95%CI: 1.1-8.1, p  0.10).ConclusionFindings suggest, better built environment conditions (adequate infrastructure, proximity to services etc.) help facilitate LTC. Moreover, UTT appears to have a protective effect on LTC.

Introduction: Agitation is frequently encountered in the emergency department (ED) and can range from psychomotor restlessness to overt aggression and violent behavior. Among all ED patients, 2.6% present with agitation or become agitated during their ED visit. We aimed to determine ED disposition for patients requiring agitation management with physical restraints.Methods: This was a retrospective cohort of all adult patients who presented to one of 19 EDs in a large integrated healthcare system and received agitation management with physical restraints between January 1, 2018–December 31, 2020. Categorical variables are presented as frequency and percentages, and continuous variables are presented as medians and interquartile range.Results: There were 3,539 patients who had agitation management with physical restraints included in this study. In total 2,076 (58.8%) were admitted to the hospital (95% CI [confidence interval] 0.572-0.605), and of those 81.4% were admitted to a primary medical floor and 18.6% were medically cleared and admitted to a psychiatric unit. Overall, 41.2% were able to be medically cleared and discharged from the ED. Mean age was 40.9 years, 2,140 were male (59.1%), 1,736 were White (50.3%), and 1,527 (43%) were Black. We found 26% had abnormal ethanol, (95% CI 0.245-0.274) and 54.6% had an abnormal toxicology screen (95% CI 0.529-0.562). A significant number were administered a benzodiazepine or antipsychotic in the ED (88.44%) (95% CI 0.874-0.895).Conclusion: The majority of patients who had agitation management with physical restraints were admitted to the hospital; of those patients, 81.4% were admitted to a primary medical floor and 18.6% were admitted to a psychiatric unit.

Resilience and optimism may not only have main effects on health outcomes, but may also moderate and buffer negative effects of stressors. We examined whether dispositional resilience and optimism moderate the associations between HIV-related stigma in health care settings and health-related outcomes (trust in HIV health care providers and depression symptoms) among women living with HIV (WLHIV). One thousand four hundred five WLHIV in nine US cities completed validated questionnaires for cross-sectional analyses. Higher self-reported experienced and anticipated stigma and lower resilience and optimism were associated with higher depression symptoms and with lower trust in HIV providers. Importantly, resilience moderated the effects of experienced stigma (but not of anticipated stigma): When resilience was high, the association of experienced stigma with higher depression symptoms and lower trust in HIV providers was weaker compared with when resilience was low. Further, significant moderation effects suggested that when optimism was high, experienced and anticipated stigma was both less strongly associated with depression symptoms and with lower trust in one's HIV care providers compared with when optimism was low. Thus, the effects of experienced stigma on depression symptoms and provider trust were moderated by both resilience and optimism, but the effects of anticipated stigma were moderated only by optimism. Our findings suggest that in addition to their main effects, resilience and optimism may function as buffers against the harmful effects of stigma in health care settings. Therefore, optimism and resilience may be valuable intervention targets to reduce depression symptoms or improve trust in providers among populations that experience or anticipate stigma, such as WLHIV.

Despite the current interest in Open Science in the scientific community, it is not clear if Open Science will succeed in higher education. Open Science is based on three basic ideas: open data, open results, and open publication. If these principles can be successfully implemented, it will allow for much greater participation in the scientific process, including, perhaps, broad public participation. In order for Open Science to be successful, it must be compatible with the practices of higher education. This will require significant adjustment. This article will discuss the pluses and minuses of Open Science in higher education.

Species lists play an important role in biology and practical domains like conservation, legislation, biosecurity and trade regulation. However, their effective use by non-specialist scientific and societal users is sometimes hindered by disagreements between competing lists. While it is well-known that such disagreements exist, it remains unclear how prevalent they are, what their nature is, and what causes them. In this study, we argue that these questions should be investigated using methods based on taxon concept rather than methods based on Linnaean names, and use such a concept-based method to quantify disagreement about bird classification and investigate its relation to research effort. We found that there was disagreement about 38% of all groups of birds recognized as a species, more than three times as much as indicated by previous measures. Disagreement about the delimitation of bird groups was the most common kind of conflict, outnumbering disagreement about nomenclature and disagreement about rank. While high levels of conflict about rank were associated with lower levels of research effort, this was not the case for conflict about the delimitation of bird groups. This suggests that taxonomic disagreement cannot be resolved simply by increasing research effort.

The participation of students with severe disabilities in school-based extracurricular activities provides students with opportunities to experience a full inclusive school event. Typically, however, students with severe disabilities remain underrepresented in extracurricular involvement as compared to their peers without disabilities (Agran et al., 2017; Cadwallader, et al., 2003). Understanding factors influencing students' decisions to participate, or not to participate, in extracurricular activities is a concept frequently investigated in the existing literature for students without disabilities; however, participating in extracurricular school events is seldom explored for students with disabilities. Research highlights two factors when considering participation by students without disabilities in why these students select extracurricular school activities; these factors include individual and social-environmental motivational influences.

In 1990, Salovey and Mayer introduced emotional intelligence (EI). Thirty-one years later, a proliferation of interventions to improve people's EI has taken place. A literature review of studies focused on enhancing the EI of college students revealed a notable gap. When educational material for training sessions included all of the skills in an EI model, researchers usually utilized lengthy durations (i.e., 11-56 h). Few successful investigations employed an ultra-brief (i.e., [less than or equal to] 1 h) approach. The present study examined the feasibility of training using a minimalistic timeframe and a sample of freshmen; their transitional challenges from high school to college mark them as an appropriate target population. Employing a quasi-experimental one-group pretest-posttest design, the recruited participants (n = 75) experienced an ultra-brief intervention highlighting the complete skill-set in the Ability Emotional Intelligence model. Findings from a one-way repeated measures MANOVA indicated improvement transpired in two of four MSCEIT scores (i.e., perception and facilitation). The merit of the present study is delineated using Orsmond and Cohn's five objectives for feasibility investigations. In addition, implications of the results and possible applications are proposed.

The IUPAC International Chemical Identifier (InChI) is a structure-based chemical identifier that encodes various aspects of a chemical structure into a hierarchically layered line notation. Because InChI is non-proprietary, open-source, and freely available to everyone, it is adopted in popular chemical information resources and software programs. This paper describes the InChI Open Education Resource (OER) (https://www.inchi-trust.org/oer/), designed to provide educators and other interested parties with resources, training material, and information related to InChI. Currently, the OER contains over 100 materials collected from various sources and provides users with search, filtering, and sorting functionalities to locate specific records. New relevant materials can be suggested by anyone, allowing the scientific community to share and find InChI-related resources. This paper will show how to use the InChI OER tag taxonomy to filter content and demonstrate two resources within the InChI OER; the ChemNames2LCSS Google Sheet and the InChILayersExplorer, an Excel spreadsheet that breaks an InChI into its layers. While the InChI OER is of value to a broader chemistry community, this paper seeks to reach out to chemical educators and provide them with an understanding of InChI and its role in the practice of science.

Abstract Background Low- and middle-income countries often lack access to mental health services, leading to calls for integration within other primary care systems. In sub-Saharan Africa, integration of depression treatment in non-communicable disease (NCD) settings is feasible, acceptable, and effective. However, leadership and implementation climate challenges often hinder effective integration and quality of services. The aim of this study was to identify discrete leadership strategies that facilitate overcoming barriers to the integration of depression care in NCD clinics in Malawi and to understand how clinic leadership shapes the implementation climate. Methods We conducted 39 in-depth interviews with the District Medical Officer, the NCD coordinator, one NCD provider, and the research assistant from each of the ten Malawian NCD clinics (note one District Medical Officer served two clinics). Based on semi-structured interview guides, participants were asked their perspectives on the impact of leadership and implementation climate on overcoming barriers to integrating depression care into existing NCD services. Thematic analysis used both inductive and deductive approaches to identify emerging themes and compare among participant type. Results The results revealed how engaged leadership can fuel a positive implementation climate where clinics had heightened capacity to overcome implementation barriers. Effective leaders were approachable and engaged in daily operations of the clinic and problem-solving. They held direct involvement with and mentorship during the intervention, providing assistance in patient screening and consultation with treatment plans. Different levels of leadership utilized their respective standings and power dynamics to influence provider attitudes and perceptions surrounding the intervention. Leaders acted by informing providers about the intervention source and educating them on the importance of mental healthcare, as it was often undervalued. Lastly, they prioritized teamwork and collective ownership for the intervention, increasing provider responsibility. Conclusion Training that prioritizes leadership visibility and open communication will facilitate ongoing Malawi Ministry of Health efforts to scale up evidence-based depression treatment within NCD clinics. This proves useful where extensive and external monitoring may be limited. Ultimately, these results can inform successful strategies to close implementation gaps to achieve integration of mental health services in low-resource settings through improved leadership and implementation climate. Trial registration These findings are reported from ClinicalTrials.gov, NCT03711786. Registered on 18/10/2018. https://clinicaltrials.gov/ct2/show/NCT03711786 .

Social workers are ethically bound to engage in political action. Serving in elected office is one influential way they can fulfill this responsibility. The purpose of this study was to identify ways social work education and professional organizations can support elected office as a social work career trajectory. Nine political social workers who held or campaigned for elected office in a Midwestern state were interviewed. Thematic analysis was used to identify and conceptualize four themes: politically focused coursework, government and legislative field placements, professional organization support, and peer support. Examples of existing supports are provided, followed by practical recommendations to increase support of elected office as a career trajectory at the program and organization level.

Chemical educators are facing a new generation of instructional technologies that impact classroom teaching. New technologies, like smartphones, cloud computing and artificial intelligence take learning beyond the classroom; 3D printing, virtual reality, and augmented reality provide new ways to teach the virtualization skills that are important for chemists. These technologies cause students to become more isolated, so students may not develop the social skills that they will need for today's workplace. Individualized learning may be beneficial to many students, but it will create challenges for faculty. Although this article focuses on chemistry education, it should be apparent that a similar argument could be made for other sciences, like physics and biology.

Using a convergent parallel mixed methods design, this exploratory study examined mathematics lessons in two third-grade classrooms to analyze the mathematical classroom discourse when using tutorial instructional software. A chi-square test for independence revealed statistically significant correlations between teachers use of the focusing and revoicing talk moves and student discourse levels of generalization and justification. The qualitative analysis found two major themes: (1) responsive teaching with technology, and (2) using digital representations to question students. From this analysis, the Facilitating Mathematical Discourse with Technology framework emerges connecting three key elements of instruction with technology: the students, the teacher, and the instructional software. The relationships among these elements illustrate the classroom interactions when using technology to enhance classroom mathematical discourse.

Regulatory agencies require data on genetic stability as part of the safety assessment for biotech crops, even though the genetic stability of a plant is not necessarily an environmental, human or animal health safety concern. While sexual reproduction has the potential to introduce genomic variation in conventionally bred and biotech crops, vegetative propagation is genetically stable. In vegetatively propagated crops, meiosis does not occur thus limiting the number of homologous recombination events that could lead to chromosomal rearrangements in progeny plants. Genetic stability data is often, but should not be, an automatic requirement for the safety assessment of vegetatively propagated biotech crops. Genetic stability data from biotech potato events has demonstrated that vegetative propagation of potato tubers does not affect the stability of introduced DNA sequences or lead to loss of trait efficacy. The knowledge and experience gained from over 30 years of assessing the safety of biotech crops can be used by regulatory authorities to eliminate data requirements that do not address environmental, food or feed safety concerns. As a first step, regulators should consider removing requirements for genetic stability as part of the safety review for vegetatively propagated biotech crops.