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    Fidelity Sub-Study - Sub-Saharan Africa Regional Partnership (SHARP) for Mental Health Capacity Building trial

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    ABSTRACT  Background: Depression is a leading cause of disability worldwide that disproportionately impacts low- and middle-income countries (LMICs). Evidence-based depression care options are often limited in LMICs and poorly integrated into existing healthcare systems. Improving such integration is crucial to improving patient outcomes and reducing disability.   Methods: In Malawi, a cluster-randomized trial of implementation strategies to integrate depression care into non-communicable disease clinics was conducted at 10 healthcare facilities from 2019 to 2021. Some clinics were highly successful in integrating depression care while others were less successful in both arms. This post-hoc mixed-methods analysis combined quantitative clinic performance indicators with qualitative endline key informant interview data to identify factors other than the tested implementation strategies that differentiated clinics that effectively integrated depression treatment from those that did not.   Results: Most participants reported several implementation barriers that were present across nearly all clinics. These pervasive barriers included access to resources, provider attitudes, and provider turnover. Differentiating factors, which when present allowed successful clinics to overcome pervasive barriers and when absent made the barriers difficult to overcome, included clinic coordinator engagement, management engagement, clinic ownership, and adequate training.   Discussion: Differentiating factors that facilitated implementation of depression care integration, even in the presence of commonly identified barriers, should be prioritized as targets for future implementation efforts. 

    Mortality Outcomes Surveillance, Part I: Ascertaining Decedents (2023 Update)

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    Mortality Outcomes Surveillance, Part I: Ascertaining Decedents (2023 Update) summarizes the data stemming from the protocol used to (1) trace sample members and then (2) screen, match, and score all decedents in the National Longitudinal Study of Adolescent to Adult Health (Add Health)

    PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2

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    In search for broad-spectrum antivirals, we discover a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrate selective inhibition of the lipid kinases PIP4K2C and PIKfyve by RMC-113 and target engagement by its clickable analog. Lipidomics analysis reveals alteration of SARS-CoV-2-induced phosphoinositide signature by RMC-113 and links its antiviral effect with functional PIP4K2C and PIKfyve inhibition. We identify PIP4K2C’s roles in SARS-CoV-2 entry, RNA replication, and assembly/egress, validating it as a druggable antiviral target. Integrating proteomics, single-cell transcriptomics, and functional assays, reveals that PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment. Promoting viral protein degradation by reversing autophagic flux impairment is a mechanism of antiviral action of RMC-113. These findings reveal virus-induced autophagy regulation via PIP4K2C, an understudied kinase, and propose dual PIP4K2C and PIKfyve inhibition as a candidate strategy to combat emerging viruses

    When Community Comes Together: A Literature Review of Digital Preservation in Community Archives

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    This literature review provides an overview of community archives and addresses digital preservation within these smaller archives. This review examines the common barriers faced by community archives as well as the solutions utilized to address their challenges. Additionally, this review considers the impact of COVID-19 on community archives as they implement or adjust digital preservation strategies.

    Cultural adaptation of a psychosocial screening tool for adolescents living with HIV/AIDS attending antiretroviral therapy program in Malawi

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    Background Adolescents living with HIV (ALHIV) face a higher risk of mental health problems than adolescents without HIV yet culturally appropriate mental health screening tools are lacking in settings like Malawi. This study aimed to culturally adapt the HEADSS (Home, Education, Activities, Drugs, Sexuality, Suicide/Depression) psychosocial screening tool for the Malawian context, as the original was previously found to be inappropriate. Methods The study was conducted between December 2021 and May 2022. We employed an adapted Heuristic Framework for cultural adaptation translations. Data was collected with Mental Health experts (n = 4), focus group discussions with ALHIV (n = 20), in-depth interviews with health care providers (HCPs) (n = 6) and key informants (n = 4). An iterative process of piloting and feedback guided the adaptation. Results The adaptation addressed conceptually difficult, unacceptable, or stigmatizing items. HCPs reported that the adapted HEADSS tool may effectively guide the examination of ALHIV challenges and simplify the identification of high-risk behaviors (e.g., early sexual debut, self-harm and substance abuse). The tool’s language was culturally accepted by ALHIV, as the screening questions were available in both the local language and English, and accurately reflected their daily challenges. Conclusions Developing easy-to-use, comprehensible, and locally appropriate mental health screening tools is crucial for detecting high-risk behaviors and psychosocial issues among ALHIV. To effectively meet ALHIVs’ needs within HIV services, mental health interventions are essential for improving adherence to antiretroviral therapy (ART). Therefore, training HCPs to address sensitive risk issues during routine care is highly recommended

    Patient satisfaction with healthcare services among health insurance program beneficiaries in Nepal: A cross-sectional study

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    Background Patient satisfaction, often assessed through clients’ experiences and opinions are vital for improving healthcare services, shaping health policies, and providing feedback on the quality, availability, and responsiveness of healthcare services. In this study, we assessed the healthcare satisfaction levels of insured patients with the health services provided under the National Health Insurance Program (NHIP) accredited health facilities. Methods We conducted a cross sectional study at 22 health facilities across 3 provinces of Nepal. We utilized client-exit interviews among 468 patients enrolled and utilizing the health services under NHIP. We used a validated Patient Satisfaction Questionnaire III (PSQ-III) developed by RAND Corporation including various contextual sociodemographic characteristics. We calculated mean score and percentages of satisfaction across seven dimensions of patient satisfaction. To determine the association between various dimensions of patient satisfaction and socio- demographic characteristics of the patients, we used generalized ordered logistic regressions. Results Among 468 patients, we observed a wide variation in patient satisfaction across seven dimensions. About 87% of the patients were satisfied in the domain of interpersonal manner, 83% in technical quality, 63% in accessibility and convenience and 60% in financial aspects. The overall satisfaction was observed as 74%. The patients having chronic diseases among the family members were more satisfied compared to those having no chronic disease in the family members (AOR:5.96; 95% CI: 2.65–13.39). Presence of chronic disease and subsidy status were found to be associated with patient satisfaction in most dimensions. Conclusions Patient satisfaction measures the gap between expected and actual service experience, tied to service quality, availability, accessibility, and financial aspects. While NHIP aims to provide quality services, the actual service quality mainly depends on the efforts of the health facilities. Therefore, strengthening the health system is crucial for improving service quality and ensuring user retention and satisfaction with NHIP

    SEPA+PrEP-BW intervention: A feasible and acceptable HIV prevention intervention for Black women

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    Although biomedical prevention strategies such as Pre-Exposure Prophylaxis (PrEP) are available, Black women (BW), who comprise less than 15% of the female population in the United States, account for 54% of new HIV infections among women. Many BW underestimate their HIV risk and face barriers to prevention, including traditional gender roles, racism, stigma, and medical mistrust. To address these challenges, we adapted SEPA+PrEP into SEPA+PrEP-BW, a novel biobehavioral HIV prevention intervention that integrates the empirically validated SEPA model (Salud/ Health, Educación/Education, Prevención/Prevention, Autocuidado/Self-Care) with PrEP education and culturally relevant components tailored to BW. Using a mixed methods approach, we collected and analyzed quantitative and qualitative data from 73 BW residing in Miami-Dade County, Florida. Results demonstrated high feasibility (94.5% retention rate), strong acceptability (94.2% satisfaction with content), and unanimous willingness to recommend the intervention. Participants expressed interest in becoming peer facilitators and emphasized the importance of culturally relevant education and safe spaces for discussion. These findings support SEPA+PrEP-BW as a promising, community-driven intervention to address critical gaps in HIV prevention among BW

    Structural connectome gradients and their relationship to IQ in childhood

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    The concept of connectome gradients, which represents the continuous spatial variation of brain connectivity, offers a robust framework for exploring the hierarchical organization of the cortex and its relationship with cognitive function. We hypothesize that structural gradients in frontal and parietal regions play a significant role in shaping individual cognitive abilities during early childhood. To evaluate this hypothesis, we identified macroscale structural connectome gradients in children aged 1–6 years, where the principal gradient exhibited a left-to-right axis, and the secondary gradient exhibited an anterior-to-posterior axis. Next, we employed machine learning approaches to predict the future cognitive outcomes assessed at ages 4, 6, and 8, specifically intelligence quotient (IQ), based on the structural connectome gradients measured at age 1. We achieved consistent and robust prediction results (mean Spearman's correlation > 0.25). The regional relevance maps highlighted regions in control network, and associated sensory processing networks. Our findings indicate that the structural connectome, which undergoes maturation during early childhood, plays a crucial role in the individual variability of IQ observed in early and middle childhood. Our approach underscores the utility of structural gradients as compact and interpretable representations of the brain's complex network architecture, effectively capturing individual differences that contribute to cognitive development

    The Cold Case Files of rAAV Capsid Influence on Transduction: New Leads

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    Adeno-associated virus (AAV) is a prevalent vector in viral gene therapy. Given its importance, significant efforts focus on engineering the capsid residues on the exterior surface to increase cell/tissue-specific binding to cellular receptors or to decrease immunogenicity. But there is also a need for stable transgene expression to achieve the desired therapeutic effect. For rAAV transgene regulation, all approaches to date utilize sequence elements within the transgene cassette to restrict the localization and level of transgene expression. However, there is accumulating evidence that rAAV transgene expression can be mediated by rAAV capsid residues distinct from cell receptor binding residues, but these reports have largely gone ‘cold’ due to a lack of a clear mechanism. Thus, these novel rAAV capsid elements may revise interpretation of both past and future rAAV capsid engineering. This review will coalesce the data supporting this novel rAAV capsid role and describe how the capsid influences transgene expression with a focus on interactions with the transgene, binding cellular proteins, and epigenetic modulation

    Turning Patients' Open-Ended Narratives of Chronic Pain Into Quantitative Measures: Natural Language Processing Study.

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    BACKGROUND: Subjective report of pain remains the gold standard for assessing symptoms in patients with chronic pain and their response to analgesics. This subjectivity underscores the importance of understanding patients' personal narratives, as they offer an accurate representation of the illness experience. OBJECTIVE: In this pilot study involving 20 patients with chronic low back pain (CLBP), we applied emerging tools from natural language processing (NLP) to derive quantitative measures that captured patients' pain narratives. METHODS: Patients' narratives were collected during recorded semistructured interviews in which they spoke about their lives in general and their experiences with CLBP. Given that NLP is a novel approach in this field, our goal was to demonstrate its ability to extract measures that relate to commonly used tools, such as validated pain questionnaires and rating scales, including the numerical rating scale and visual analog scale. RESULTS: First, we showed that patients' utterances were significantly closer in semantic space to anchor sentences derived from validated pain questionnaires than to their antithetical counterparts. Furthermore, we found that the semantic distances between patients' utterances and anchor sentences related to quality of life were strongly correlated with reported CLBP intensity on the numerical rating and visual analog scales. Consistently, we observed significant differences between individuals with low and high pain levels. CONCLUSIONS: Although our small sample size limits the generalizability of these findings, the results provide preliminary evidence that NLP can be used to quantify the subjective experience of chronic pain and may hold promise for clinical applications

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