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Purpose: Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been noted to face increased cancer incidence. Yet, the impact of concomitant renal dysfunction on acute outcomes following elective surgery for cancer remains to be elucidated., Methods: All adult hospitalizations entailing elective resection for lung, esophageal, gastric, pancreatic, hepatic, or colon cancer were identified in the 2016-2020 National Inpatient Sample. Based on stage of renal dysfunction, CKD patients were sub-classified as CKD1-3, CKD4-5, or ESRD (others: Non-CKD). Multivariable regression models were developed to assess the association of comorbid CKD/ESRD with in-hospital mortality, perioperative complications, and resource utilization., Results: Of ~515,145 patients, 32,195 (6.2%) had CKD (5.1% CKD1-3, 0.7% CKD4-5, 0.5% ESRD). The incidence of CKD among patients undergoing cancer resection increased from 5.3% in 2016 to 7.3% in 2020 (P<0.001). Following risk adjustment, CKD1-3 and CKD4-5 remained linked with similar likelihood of mortality and hospitalization costs, but greater need for blood transfusion (CKD1-3 AOR 1.21, CI 1.09-1.35; CKD4-5 AOR 1.73 CI 1.38-2.18). CKD4-5 was also associated with greater odds of infection (AOR 1.88, CI 1.34-2.62) and respiratory sequelae (AOR 1.36, CI 1.05-1.77). Further, ESRD was linked with greater odds of in-hospital mortality (AOR 2.74, CI 1.69-4.45), infection (AOR 2.31, CI 1.62-3.30) and respiratory complications (AOR 1.72, CI 1.31-2.26), as well as greater resource utilization, relative to Non-CKD., Conclusion: Comorbid renal dysfunction was linked with inferior clinical and financial outcomes following elective cancer resection. Future work is needed to develop optimal management strategies and recovery pathways for this complex cohort., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Sakowitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This paper introduces a novel framework for evaluating phenotype algorithms (PAs) using the open-source tool, Cohort Diagnostics., Materials and Methods: The method is based on several diagnostic criteria to evaluate a patient cohort returned by a PA. Diagnostics include estimates of incidence rate, index date entry code breakdown, and prevalence of all observed clinical events prior to, on, and after index date. We test our framework by evaluating one PA for systemic lupus erythematosus (SLE) and two PAs for Alzheimer's disease (AD) across 10 different observational data sources., Results: By utilizing CohortDiagnostics, we found that the population-level characteristics of individuals in the cohort of SLE closely matched the disease's anticipated clinical profile. Specifically, the incidence rate of SLE was consistently higher in occurrence among females. Moreover, expected clinical events like laboratory tests, treatments, and repeated diagnoses were also observed. For AD, although one PA identified considerably fewer patients, absence of notable differences in clinical characteristics between the two cohorts suggested similar specificity., Discussion: We provide a practical and data-driven approach to evaluate PAs, using two clinical diseases as examples, across a network of OMOP data sources. Cohort Diagnostics can ensure the subjects identified by a specific PA align with those intended for inclusion in a research study., Conclusion: Diagnostics based on large-scale population-level characterization can offer insights into the misclassification errors of PAs., Competing Interests: All authors were employees of Janssen Research & Development, LLC, and shareholders of Johnson & Johnson (J&J) stock at the time of manuscript conceptualization, drafting, editing, and initial approval for submission. All authors except AM continue to be employees of J&J. Author AM changed affiliation after the initial submission and is currently affiliated with VNS Health. This competing interest does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2025 Rao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Speculations on the evolution of language have invoked comparisons across human and non-human primate communication. While there is widespread support for the claim that gesture plays a central, perhaps a predominant role in early language development and that gesture played the foundational role in language evolution, much empirical information does not accord with the gestural claims. The present study follows up on our prior work that challenged the gestural theory of language development with longitudinal data showing early speech-like vocalizations occurred more than 5 times as often as gestures in the first year of life. Now we bring longitudinal data on the second year (13, 16 and 20 mo), showing again that vocalizations predominated, and especially in conventional (learned) communication; > 9 times more spoken words were observed than gestures that could be viewed as functionally equivalent to words (i.e., signs). Our observations also showed that about ¾ of gestures across these second-year data were deictics (primarily pointing and reaching), acts that while significant in supporting the establishment of referential vocabulary in both spoken and signed languages, are not signs, but have single universal deictic functions in the here and now. In contrast, words and signs, the primary semantic components of spoken and signed languages, are functionally flexible, making possible reference to abstractions that are not bound to any particular illocutionary force nor to the here and now., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Burkhardt-Reed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In low- and middle-income countries, trauma is the leading cause of death among youth and it is also a major cause of disability. Globally, more than 1,600 children and adolescents below the age of 19-years die every day from preventable injuries. Traffic-related injuries, falls, sports-related injuries, assaults, burns, and drownings are the most commonly reported causes of traumatic mortality among children. The mechanism of injury is always diverse in different contexts due to the differences in social determinants of health., Objectives: To determine the epidemiological pattern of trauma among children 0-9 years in Cameroon., Methods: This is a retrospective analysis of prospectively collected data from the Cameroon Trauma Registry currently running in 10 pilot sites across seven of the ten regions of Cameroon. We retrieved data for all children aged 0-9 years from June 2022 to August 2023. Data was analyzed with respect to the demographics, injury characteristics and outcomes., Results: Of the 5,439 patients captured in the trauma registry, 267 (4.9%) were children aged 0-9 years. Over 50% (152/267) of the patients were males with 35% (93/267) from rural settings. The top injury mechanism was road traffic injuries (RTI) [137(52.1%)]. These injuries occurred on the streets [142(53.4%)] during leisure activities [205(78.5%)]. Majority of children [104(39%)] involved in RTI injuries were pedestrians and no prehospital care offered to 216(82.8%) of injured children. A total of 39 (16.9%) were discharged with major disability, 111 (48.1%) had limited ability to move and 5 (2.2%) demised or succumbed to their injuries. There was a significant association between injury activity and gender (P = 0.006). Unlike the females, majority of the males were discharged with major disability [21 (53.8%)]., Conclusion: This preliminary analysis highlights the burden of trauma among children aged 0-9 years and its contribution to the proportion of disabled persons in Cameroon. Leisure activities on the streets increased the number of pediatric injuries especially among males. It is therefore imperative to put in place or reinforce environmental interventions to reduce the burden of pediatric injuries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The main objective of this qualitative analysis is to increase the quality of Traditional Chinese Medicine (TCM) research education. Subject matter experts and stakeholders were sent a list of possible topics to include in a research course and were asked to comment on it, add or subtract topics, and suggest appropriate research papers to use, lessons learned in their topic areas and possible stand-alone topics for inclusion in other courses. Their feedback was used to revise the topic list, create a list of foundational research papers to include in a research course and devise a list of stand-alone topics that could be included in the general TCM research curriculum. The result is a TCM research course curriculum that will improve the teaching of evidence-based medicine (EBM) practices to TCM students. This will help TCM faculty and program directors improve existing courses, develop new courses and strengthen EBM education., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Most et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Evolution is an important part of biology education, but many college biology students do not accept important components of evolution, like the evolution of humans. Practices that reduce perceived conflict between religion and evolution have been proposed to increase student evolution acceptance. This study investigates college student experiences of conflict reducing practices in evolution education and how these experiences are related to their gains in acceptance of human evolution during evolution instruction. We measured the natural variation in student experiences of conflict reducing practices among 6,719 college biology students in 55 courses and 14 states including (1) their experiences of an instructor demonstrating religion-evolution compatibility by presenting examples of religious leaders and scientists who accept evolution and (2) their experiences of an instructor emphasizing students' autonomy in their own decision to accept evolution or not. We also measured student acceptance of human evolution before and after instruction so that we could test whether any changes in evolution acceptance were associated with student experiences of the conflict reducing practices. Linear mixed models showed that highly religious Christian students accepted evolution more when they perceived more compatibility practices. Further, students from all religious and non-religious affiliations accepted human evolution more after instruction when they perceived more autonomy practices. These results indicate that integrating examples of religion compatibility in evolution education will positively impact Christian students' views on evolution and that emphasizing students' autonomy over their decision to accept evolution may be important for students more broadly. If instructors incorporate practices that emphasize compatibility and one's personal choice to accept or not accept evolution, then these results suggest that students will leave their college biology classes accepting evolution more. Perhaps by using more conflict reducing practices, instructors can help increase evolution acceptance levels that have remained low in the United States for decades., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Increasing HIV testing and treatment coverage among people living with HIV (PLHIV) is essential for achieving global HIV epidemic control. However, compared to women, cis-gender heterosexual men living with HIV are significantly less likely to know their HIV status, initiate anti-retroviral therapy (ART) and achieve viral suppression. This is particularly true in South Africa, where men are also at increased risk of mortality resulting from AIDS-related illnesses. While there is growing knowledge of Treatment as Prevention or the concept Undetectable = Untransmittable (U = U) among PLHIV in Western and high-income countries, the reach and penetration of the U = U message in sub-Saharan Africa remains limited, and few studies have evaluated the impact of accessible and relatable U = U messages on ART initiation and adherence. To address these gaps, rigorous evaluations of interventions that incorporate U = U messages are needed, especially among men in high prevalence settings., Methods: Building on our U = U messages that we previously developed for men using behavioral economics insights and a human-centered design, we will conduct two sequential hybrid type 1 effectiveness-implementation trials to evaluate the impact of U = U messages on men's uptake of community-based HIV testing and ART initiation (Trial 1), and retention in care and achievement of viral suppression (Trial 2). For trial 1, a cluster randomized trial will be implemented with HIV testing service site-days (each day at one testing site) randomized to U = U or standard-of-care (SoC) messages inviting men to test for HIV. For trial 2, an individual-level randomized control trial will be implemented, with men initiating ART at six government clinics randomized to receive U = U counselling or SoC treatment adherence messaging. We will incorporate a multi-method evaluation to inform future implementation of U = U messaging interventions. The study will be conducted in the Buffalo City Metro Health District of the Eastern Cape Province and in the Cape Town Metro Health District in the Western Cape Province in South Africa., Discussion: These trials are the first to rigorously evaluate the impact of U = U messaging on HIV testing uptake, ART initiation and achievement of viral suppression among African men. If effective, these messaging interventions can shape global HIV testing, treatment and adherence counselling guidelines and practices., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Medina-Marino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Until the COVID-19 pandemic, it had not been possible to examine the effect of rapid policy changes surrounding telemental health on patient-reported mental health care access, costs, symptoms, and functioning. Sizable variation in telemental health use by patient race-ethnicity, age, and rurality, and in its adoption across healthcare settings, underscores the need to study equitable dissemination and implementation of high-quality telemental health services in the real world. This protocol describes an explanatory sequential mixed-methods study that aims to examine the effects of state telemental health policy expansion on patient-reported mental health outcomes, as well as the policy-to-practice pathway from the perspectives of state leaders, clinicians, and staff who care for underserved patients., Methods: This study uses legal mapping research methods to characterize the effective dates and specific provisions of telemental health policies (e.g., Medicaid reimbursement, private payer laws, professional licensure requirements) before and during the COVID-19 pandemic in all 50 U.S. states and Washington, D.C. Then, we will examine state factors (e.g., COVID-19 cases, broadband internet access) explaining these telemental health policies using discrete-time hazard models. The primary quantitative analysis employs a difference-in-difference approach to predict effects on outcome measures using a nationally representative survey of individuals. Using the Medical Expenditure Panel Survey, we will examine policy effects on (a) access to, use of, and expenditures related to mental health care and (b) mental health outcomes, functioning, and employment. Finally, qualitative methods will be used to obtain feedback from state leaders, administrators, clinicians, and clinic staff members on how state telemental health policy expansion influenced mental health services delivery during the pandemic, with a focus on improving safety-net care. We will use a positive deviance approach to select key partners from 6 "high" and 6 "low" telehealth expansion states for interviews and focus groups., Discussion: The overall study goal is to better understand the effect of pandemic-related state policy changes around telehealth on patient-reported mental health care access, costs, symptoms, and functioning. By characterizing variations in telehealth policies and their downstream effects, this mixed-methods study aims to inform equitable dissemination, implementation, and sustainment of high-quality telemental health services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The relationship between community-based healthcare barriers and risk of recurrent hospital-based care among persons with chronic liver disease (CLD) is understudied. We aimed to uncover distinct groups among adults in the United States with CLD based on healthcare barriers and risk-stratify recurrent acute care use by group., Methods: Using National Health Interview Survey (2011 to 2017) data, we performed latent class analysis (LCA) to uncover groups experiencing distinct sets of healthcare barriers. We assessed sociodemographic and health characteristics and probabilities of recurrent acute care use by group., Results: The sample included 5,062 (estimated 4.7 million) adults with CLD (median [range] age 55 [18-85]). LCA modeling differentiated 4 groups: minimal barriers (group 1) (n = 3,953; 78.1%), unaffordability (group 2) (n = 540; 10.7%), care delays (group 3) (n = 328; 6.5%), and inability to establish care (group 4) (n = 240; 4.8%). Group 2 had the most uninsured persons (n = 210; 38.9%), whereas group 3 was mostly insured (n = 305; 93.1%). Group 4 included the most adults under 65 years old (n = 220; 91.7%), females (n = 156; 65.1%), and persons with unemployment (n = 169; 70.6%) and poverty (n = 85; 35.3%). Compared to group 1, the likelihood of recurrent acute care use was highest for group 4 (aOR, 1.85; 95% CI, 1.23-2.79 followed by group 3 (aOR, 1.50; 95% CI, 1.07-2.11) and group 2 (aOR, 1.48; 95% CI, 1.11-1.97)., Conclusion: US adults with CLD can be categorized into 4 distinct groups based on healthcare barriers, which are associated with different probabilities of recurrent acute care use. Findings from this study are important for future interventions to reduce potentially avoidable hospital-based care among the highest-risk persons with CLD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Metarhizium anisopliae (Metschnikoff) Sorokin and Beauveria bassiana (Balsamo) Vuillemin are entomopathogenic fungi commonly used in microbial control of arthropods. In this study, we evaluated the insecticidal potential of six isolates of B. bassiana (BIITAC10.3.3, BIITAC6.2.2, and BIITAC8.1.5) and M. anisopliae (MIITAC11.3.4, MIITAC6.2.2, and MIITAC6.4.2) from Cameroon, against the banana aphid Pentalonia nigronervosa Coquerel, the vector of the banana bunchy top virus (BBTV). Pathogenicity tests were initially conducted using B. bassiana and M. anisopliae isolates at a concentration of 3.2 × 106 conidia/ml on P. nigronervosa adults sourced from four agroecologies in Cameroon. Four isolates (BIITAC6.2.2, BIITAC10.3.3, BIITAC8.1.5, and MIITAC6.2.2) were highly pathogenic, causing greater than 75% aphid mortality in all populations. A significant decrease in aphid fecundity was observed with BIITAC6.2.2, MIITAC6.2.2, and BIITAC10.3.3. These three isolates were in a test of a series of four fungal concentrations (3.2 × 101, 3.2 × 102, 3.2 × 104, and 3.2 × 106 conidia/ml). produced LC50 of 1.31 × 101 and 3.12 × 10-2 for BIITAC10.3.3 and MIITAC6.2.2, respectively. MIITAC6.2.2 had the lowest LC90 (1.55 × 103). Our results strongly support the continued development of biopesticides based on one or more of the three fungal entomopathogens for the control of banana aphids as a component of an Integrated Pest Management (IPM) strategy for the reduction of the prevalence and transmission of BBTV under field conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Enoh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Preventing Adverse Childhood Experiences (ACEs) is a public health priority, and the perinatal period is a sensitive life stage when preventive interventions could be particularly effective. Protecting and buffering pregnant persons and infants from exposure to adversity can optimize children's development and health trajectories, reduce future morbidity and mortality, and even break intergenerational cycles of adversity, but no study has synthesized experimental evidence on effectiveness of interventions to address ACEs in the perinatal period., Objectives: To (1) identify perinatal ACE prevention interventions, tested in high quality randomized control trials, with a dyadic perspective examining outcomes for mother and child; (2) describe their (a) place on the public health prevention continuum and (b) incorporation of life course characteristics that aim to optimize life health trajectories; and (3) determine which interventions show evidence of effectiveness., Methods: We undertook a scoping review, using a modified PRISMA-Sc approach, of articles published in English between January 2000 and November 2023 identified through Psych info and PubMed using search terms for a broad range of adversities, with additional capture of articles from relevant reference lists. Interventions were included if they targeted an identified ACEs exposure or risk; were tested in randomized controlled trials (RCTs); reported outcome measures for both mother and child and were initiated during pregnancy. Interventions were further analyzed using the public health prevention continuum and Life Course Intervention Research (LCIR) characteristics frameworks. A two-tailed t test was used to ascertain the association between LCIR characteristics, and the outcomes achieved., Results: Of 2148 articles identified, 57 were in scope for detailed analysis, yielding 53 unique interventions. Overall, 42 (74%) reported some positive impact; 37 (65%) for mothers; 37 (65%) for the child, and 32 (56%) for both. Interventions with the strongest evidence based on study quality and reported outcomes were co-parenting programs designed to improve the quality and function of the co-parenting relationship, home visiting interventions, and integrative health interventions incorporating baby massage and/or yoga. Half of effective interventions were secondary prevention focused. The mean number of life course characteristics was significantly higher in the studies that reported a positive impact on the mother and/or child (p = 0.003)., Conclusions: Few studies specifically addressed ACEs as a defined set of adversities, yet a range of perinatal interventions showed positive impacts on individual ACE risks or exposures. Intentional incorporation of life course characteristics and bundling of evidence-based components into comprehensive perinatal interventions hold promise for future ACEs prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kinsey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Whether attending college, entering the workforce, or finding a romantic partner, single emerging adults navigate a pivotal stage of their lives. The present cross-sectional study sought to examine the heterogeneity in happiness of single emerging adults (N = 1,073) with a person-centered, group-differential approach. Using five predictors of life satisfaction (friendship satisfaction, family satisfaction, self-esteem, neuroticism, and extraversion) as indicators in latent profile analysis (LPA), we identified five distinct profiles (or groups) of young singles. The profiles, ordered from favorable to unfavorable indicator patterns, presented diverse shape and level differences that corresponded to varying happiness levels. Singles in Profile 1 with the most favorable indicator patterns (e.g., high friendship satisfaction, low neuroticism) were the happiest, while those in Profile 5 with the least favorable indicator patterns (e.g., low friendship satisfaction, high neuroticism) were the unhappiest. In the middle profiles, singles often offset disadvantages in one area (e.g., high neuroticism) with advantages in others (e.g., high friendship satisfaction) to achieve average to somewhat high levels of happiness. Importantly, friendship satisfaction emerged as a vital indicator, often distinguishing which singles were happy or not. Covariate analyses further validated the profiles and revealed additional profile differences (e.g., gender, anxiety, depression). Overall, our findings underscore the essential role of satisfying friendships in promoting the well-being of single emerging adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Walsh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS., Methods and Analysis: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines., Ethics and Dissemination: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals., Trial Registration: This study was registered on ClinicalTrials.gov (NCT04469439)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JAA is a consultant for OptiNose and Medtronic; on a speaker panel GSK; on GlycoMira board and is an equity holder. PHH is a consultant for Stryker, Medtronic, Slate Therapeutics; and Equity ownership in Sound Health Systems. AJK is a consultant for Acclarent. ZMS is a consultant for OptiNose, Regeneron, SanofiGenzyme, and Lyra; and on Medical Directory for Healthy Humming. Unrelated to this work, NIC has received grant support from the Burroughs Welcome Fund, American Rhinologic Society, and the National Cancer Institute. In the last 36 months, CHG has received grants from the National Institutes of Health, the Cystic Fibrosis Foundation, the Federal Drug Administration unrelated to this work. CHG has received fees from Enterprise Therapeutics for providing clinical trial design advice. He received honoraria from Gilead Sciences to serve as grant review committee chair and from Vertex Pharmaceuticals for speaking at the UK LEAD conference. He served as a DSMB Chair for a trial supported by Novartis and the European Commission. He serves as the Deputy Editor of the Annals of the American Thoracic Society. CHG has stock in Air Therapeutics. JLTC reports personal financial relationships with commercial interests relevant to medicine within the past 3 years: As faculty in an institution that is part of the CF TDN, she have been site Pl on studies for Vertex, 4DMT, and Eloxx; she have done consulting/provided clinical trial design advice for Vertex and 4DMT; she served as Chair of a Data Monitoring Committee for AbbVie. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: she have received grant funding from the CFF and NIH. Professional Memberships include CFF Clinical Research Executive Committee; CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING); ATS International Conference Committee Chair and Respiratory Health Awards Committee Member (Scientific Grant Review and Clinical Problems Programming Committee-complete); National Institutes of Health/National Heart, Blood, Lung Institute Clinical Trials Review Study Section. MTS receives funding from Cystic Fibrosis Foundation unrelated to this work. In the last 36 months, DMB has received grant support from CF Foundation related to this work as well as unrelated to this work. Unrelated to this work, DMB has received grant support from the International Society of Inflammation and Allergy of the Nose and the American Rhinologic Society, honoraria, and consulting fees from Amgen, on medicolegal cases, and at Garner Health (equity). CML, JLF, TEB, NIC, AEG, JCM, TLS have disclosed no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Transgender women (hereafter "trans women") face social marginalization, stigma, and discrimination and experience a high burden of HIV. More recently, trans women have been identified as having a high risk for hepatitis C (HCV) infection. The interaction between these two diseases and the risks for HIV/HCV co-infection among trans women are understudied., Objective: To characterize epidemiological, behavioral, and socio-structural interactions between HIV and HCV infections among trans women., Methods: This cross-sectional study examined data from a community-based survey of trans women in San Francisco recruited through respondent-driven sampling (RDS) in 2019/2020. Face-to-face interviews collected data on demographics, medical history, drug injection practices, sexual behavior, and socio-structural factors (e.g., poverty, housing insecurity, incarceration, social support). HIV and HCV antibodies were detected using oral fluid rapid tests and prior diagnosis and treatment were collected by self-report. Blood specimens were collected to confirm antibodies using ELISA. Multinomial logistic regression analysis characterized factors associated with HIV infection alone, HCV infection alone, and HIV/HCV co-infection compared to neither infection., Results: Among 201 trans women recruited, HIV prevalence was 42.3%; HCV infection by history or current seroprevalence was 28.9%; evidence for both HIV and HCV infection was present for 18.9%. Two-thirds of trans women (67.2%) had been incarcerated; 30.8% had ever injected drugs. History of injection drug use and receiving emotional support from family were factors found in common for HIV infection, HCV infection, and HIV/HCV co-infection compared to no infection. Having a sexual partner who injects drugs was associated with HIV infection alone. Not lacking care due to cost and older age were associated with co-infection. Older age was also associated with HCV infection. Of trans women with HIV infection, 91.8% had accessed HIV care, whereas only 62% with HCV had accessed some form of care., Conclusions: Our study found high levels of HIV, HCV, and HIV/HCV co-infection among trans women in San Francisco. We found common associations between HIV and HCV through injection practices and emotional support, but having a sexual partner who injects drugs was not associated with HCV infection alone or co-infection. We note a substantial gap in the treatment of HCV for trans women, including those in HIV care, that needs to be urgently addressed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Frequent hemodialysis provided more than three times per week may lower mortality and improve health-related quality of life. Yet, the evidence is inconclusive. We evaluated the benefits and harms of frequent hemodialysis in people with kidney failure compared with standard hemodialysis., Methods: We performed a systematic review of randomized controlled trials including adults on hemodialysis with highly sensitive searching in MEDLINE, Embase, CENTRAL, and Google Scholar on 3 January 2024. Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. We adjudicated evidence certainty using GRADE., Results: From 11,142 unique citations, only seven studies involving 518 participants proved eligible. The effects of frequent hemodialysis on physical and mental health were imprecise due to few data. Frequent hemodialysis probably had uncertain effect on death from all cause compared with standard hemodialysis (relative risk 0.79, 95% confidence interval 0.33-1.91, low certainty evidence). Data were not reported for death from cardiovascular causes, major cardiovascular events, fatigue or vascular access., Conclusion: The evidentiary basis for frequent hemodialysis is incomplete due to clinical trials with few or no events reported for mortality and cardiovascular outcome measures and few participants in which patient-reported outcomes including health-related quality of life and symptoms were reported., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Natale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Loneliness has been linked to a host of harmful physical and mental health outcomes, detrimental effects that may stem from increases in threat-responding caused by altered fear learning in lonely individuals. In particular, the heightened threat-vigilance that is a hallmark of loneliness may augment the processes by which fear learning occurs, ultimately resulting in a greater number of perceived threatening cues in the environment. However, almost no research has examined how loneliness alters fear learning processes in humans. Here, we investigated the effect of loneliness on fear learning during an evaluative learning procedure in which participants (n = 782) were taught to associate fearful, positive, or neutral control stimuli with neutral images. Results showed that reduced extinction of evaluative fear associations occurred in high (vs. low) lonely individuals, but there was no difference in extinction of evaluative appetitive (also known as positive or reward) associations, suggesting this effect is specific to fear learning. In addition to shedding light on the link between loneliness and poor health, these results represent an important step forward in the growing understanding of the powerful impact of social bonds on fear learning processes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hornstein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Africa, humans and large carnivores compete over access to resources, including prey. Disturbance by humans to kills made by carnivores, often for purposes of obtaining all or portions of the carcass, constitutes a form of human-wildlife conflict. However the occurrence of this practice, known as human kleptoparasitism, and its impact on carnivores has received little scientific attention. We obtained expert opinions from African lion researchers and stakeholders via a standardized questionnaire to characterize the geographic extent and frequency of human kleptoparasitism as it occurs in modern times. Our survey found modern human kleptoparasitism on kills made by lions, and possibly other large carnivores in Africa, to be geographically more widespread than previously reported. Meat lost to humans requires carnivores to hunt and kill additional prey thereby causing stress, increasing their energetic costs and risks of natural injury, and exposing them to risk of direct injury or death from human usurpers. Because of their conspicuous behaviors and tendency towards killing large-bodied prey, lions are particularly susceptible to humans detecting their kills. While human kleptoparasitism was geographically widespread, socio-economic factors influenced the frequency of occurrence. Prey type (wild game or domestic livestock) influenced human attitudes towards meat theft; ownership allows for legal recovery of livestock carcasses, while possessing wild game meat is mostly illegal and may incur penalties. Meat theft was associated with other illegal activities (i.e., illegal mining) and most prevalent among people of low income, including underpaid game scouts. Despite quantifiable costs to carnivores of human disturbance to their kills, the majority of experts surveyed reported a lack of knowledge on this practice. We propose that human disturbance at kills, especially loss of prey through human kleptoparasitism, constitutes an important anthropogenic threat that may seriously impact energy budgets of individual lions and other scavengers when meat and carcasses are removed from the ecosystem, and that the costs incurred by carnivores warrants further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 White et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Extracorporeal membrane oxygenation (ECMO) represents an important but limited treatment for patients with severe COVID-19. We assessed the effects of an educational intervention on a person's ECMO care preference and examined whether patients and providers had similar ECMO preferences., Methods: In the Video+Survey group, patients watched an educational video about ECMO's purpose, benefits, and risks followed by an assessment of ECMO knowledge and care preferences in seven scenarios varying by hypothetical patient age, function, and comorbidities. Patients in the Survey Only group and providers didn't watch the video. Logistic regression was used to estimate the probability of agreement for each ECMO scenario between the two patient groups and then between all patients and providers., Results: Video+Survey patients were more likely (64% vs. 17%; p = 0.02) to correctly answer all ECMO knowledge questions than Survey Only patients. Patients in both groups agreed that ECMO should be considered across all hypothetical scenarios, with predicted agreement above 65%. In adjusted analyses, patients and providers had similar predicted agreement for ECMO consideration across six of the seven scenarios, but patients showed greater preference (84% vs. 41%, p = 0.003) for the scenario of a functionally dependent 65-year-old with comorbidities than providers., Discussion and Conclusions: An educational video increased a person's ECMO knowledge but did not change their ECMO preferences. Clinicians were less likely than patients to recommend ECMO for older adults, so advanced care planning discussion between patients and providers about treatment options in critically ill patients with COVID-19 is critical., Competing Interests: Dr. Borre reports funding from the National Institutes of Health. Dr. Maciejewski reports research grants from the Veterans Affairs Health Services Research and Development Service (VA HSR&D, RCS 10-391), and ownership of Amgen stock due to his spouse’s employment. Dr. Fan reports personal fees from Alung Technologies, Aerogen, Baxter, GE Healthcare, Inspira, and Vasomune outside the submitted work. Dr. Zhang reports funding from the Duke National Clinician Scholar Program and the Durham Veteran’s Affairs. All other authors have no conflicts of interest to disclose., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work. The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed a baseline and three-month electronic survey. At three months post-infection, 40.8% of participants reported at least one SARS-CoV-2 symptom and 9.6% of participants reported five or more SARS-CoV-2 symptoms. When asked about missed work due to their SARS-CoV-2 infection at three months, 7.2% of participants reported missing ≥10 workdays and 13.9% of participants reported not returning to work since their infection. At three months, participants with ≥5 symptoms had a higher adjusted odds ratio of missing ≥10 workdays (2.96, 95% CI 1.81-4.83) and not returning to work (2.44, 95% CI 1.58-3.76) compared to those with no symptoms. Prolonged SARS-CoV-2 symptoms were common, affecting 4-in-10 participants at three-months post-infection, and were associated with increased odds of work loss, most pronounced among adults with ≥5 symptoms at three months. Despite the end of the federal Public Health Emergency for COVID-19 and efforts to "return to normal", policymakers must consider the clinical and economic implications of the COVID-19 pandemic on people's employment status and work absenteeism, particularly as data characterizing the numerous health and well-being impacts of Long COVID continue to emerge. Improved understanding of risk factors for lost work time may guide efforts to support people in returning to work., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AHI receives research grant funding from the University of Texas Southwestern Medical Center outside of the submitted work. AKV receives grants from the Agency for Healthcare Research and Quality and the SAEM Foundation outside the submitted work. ESS receives grant funding from the National Heart, Lung, and Blood Institute (R01HL151240), and the Patient Centered Outcomes Research Institute (HM-2022C2-28354). JCCM receives research grant funding from SAMHSA (1H79TI084428-01 and 1H79TI085981-01, PI LeSaint), FDA (75F40122C00116, PI Anderson), NIH-NINDS (U24NS129501, PI Rodriguez) outside the submitted work. JE is Editor-in-chief of the Adult Primary Care topics at UpToDate. KLR receives research grant funding from Abbott Diagnostics, DermTech, MeMed, Prenosis, Siemens Healthcare Diagnostics, PROCOVAXED funded by NIAID 1R01AI166967, and PREVENT funded by CDC U01CK00048 outside the submitted work. KNO receives research grant funding for PROCOVAXED funded by NIAID R01 AI166967, PI: Rodriguez outside the submitted work. MG receives grant funding from the Biomedical Advanced Research and Development Authority Research Grant, the Bill and Melinda Gates Foundation, and the Society of Directors of Research in Medical Education Grant outside the submitted work. MJH receives research grant funding from an Investigator Award from Merck, MISP 100099, PI: Hill outside the submitted work. The following authors have declared that no competing interests exist: HY, KAS, RAW. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Venkatesh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The placenta is a transient organ critical for fetal development. Disruptions of normal placental functions can impact health throughout an individual's entire life. Although being recognized by the NIH Human Placenta Project as an important organ, the placenta remains understudied, partly because of a lack of non-invasive tools for longitudinally evaluation for key aspects of placental functionalities., Objective: Our goal is to create a non-invasive preclinical imaging pipeline that can longitudinally probe murine placental health in vivo. We use advanced imaging processing schemes to establish functional biomarkers for non-invasive longitudinal evaluation of placental development., Methodology: We implement dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and analysis pipeline to quantify uterine contraction and placental perfusion dynamics. We use optic flow and time-frequency analysis to quantify and characterize contraction-related placental motion. Our novel imaging and analysis pipeline uses subcutaneous administration of gadolinium for steepest slope-based perfusion evaluation, enabling non-invasive longitudinal monitoring., Results: We demonstrate that the placenta exhibits spatially asymmetric contractile motion that develops from E14.5 to E17.5. Additionally, we see that placental perfusion, perfusion delivery rate, and substrate delivery all increase from E14.5 to E17.5, with the High Perfusion Chamber (HPC) leading the placental changes that occur from E14.5 to E17.5., Discussion: We advance the placental perfusion chamber paradigm with a novel, physiologically based threshold model for chamber localization and demonstrate spatially varying placental chambers using multiple functional metrics that assess mouse placental development and remodeling throughout gestation., Conclusion: Our pipeline enables the non-invasive, longitudinal assessment of multiple placenta functions from a single imaging session. Our pipeline serves as a key toolbox for advancing research in mouse models of placental disease and disorder., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cortes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Alcohol use disorder (AUD) is a major economic and healthcare burden in the United States. While there is evidence-based medication-assisted treatment (MAT) for AUD, few physicians implement these therapies on a regular basis., Objective: To determine the impact of a pharmacy-guided AUD discharge planning workflow on the rate of MAT prescriptions and inpatient readmissions., Methods: This was a single-centered pre-and-post intervention study over a 6-month period, with a 90-day pre-intervention period and a 90-day post-intervention period. The study included all patients over the age of 18 years admitted to a medicine or surgery floor bed who presented with alcohol withdrawal at any point during their hospital course. The intervention involved a pharmacy workflow, in which a list of patients admitted with alcohol withdrawal was automatically generated and referred to pharmacists, who then provided recommendations to the primary physician regarding prescriptions for naltrexone, acamprosate, and/or gabapentin. The patients were then contacted within 30 days after discharge for post-hospitalization follow-up. Our outcome measures were change in prescription rate of MATs, change in total and alcohol-related 90-day readmission rates, and change in total and alcohol-related 90-day emergency department (ED) visit rates., Results: The pre-intervention period consisted of 49 patients and the post-intervention period consisted of 41 patients. Our workflow demonstrated a 195% increase in the prescription rate of MATs at discharge (p < 0.001), 61% reduction in 90-day total readmission rate (p < 0.05), 40% reduction in 90-day total ED visit rate (p = 0.09), 92% reduction in 90-day alcohol-related readmission rate (p < 0.05), and 88% reduction in 90-day alcohol-related ED visit rate (p < 0.05)., Conclusions: Our intervention demonstrated that a pharmacy-based AUD discharge planning workflow has the potential to reduce inpatient readmissions and ED visits for patients with AUD, thus demonstrating improved patient outcomes with the potential to reduce healthcare costs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abiri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Weight stigma is highly prevalent. However, existing weight stigma interventions are only modestly effective at reducing anti-fat attitudes. The current research proposes a novel approach using a loving kindness meditation (LKM). Experiment 1 tests whether random assignment to the LKM intervention reduces explicit and implicit anti-fat bias and increases empathy based on the LKM recipient with higher weight (close other vs. stranger). Experiment 2 tests whether LKM outperforms an empathy intervention or control to increase empathy or reduce stigmatizing behavior. Results revealed that the LKM increased empathic care but did not reduce anti-fat bias compared to control; the LKM intervention, but not the empathy intervention, reported greater empathy compared to control in unadjusted analyses; and participants in the LKM and empathy interventions (vs. control) were more likely to engage in stigmatizing behavior. These findings suggest that the LKM may not be effective at reducing weight stigma despite increasing empathy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Small extracellular vesicles (sEVs) are cell-released vesicles ranging from 30-150nm in size. They have garnered increasing attention because of their potential for both the diagnosis and treatment of disease. The diversity of sEVs derives from their biological composition and cargo content. Currently, the isolation of sEV subpopulations is primarily based on bio-physical and affinity-based approaches. Since a standardized definition for sEV subpopulations is yet to be fully established, it is important to further investigate the correlation between the biomolecular composition of sEVs and their physical properties. In this study, we employed a platform combining single-vesicle surface-enhanced Raman spectroscopy (SERS) and machine learning to examine individual sEVs isolated by size-exclusion chromatography (SEC). The biomolecular composition of each vesicle examined was reflected by its corresponding SERS spectral features (biomolecular "fingerprints"), with their roots in the composition of their collective Raman-active bonds. Origins of the SERS spectral features were validated through a comparative analysis between SERS and mass spectrometry (MS). SERS fingerprinting of individual vesicles was effective in overcoming the challenges posed by EV population averaging, allowing for the possibility of analyzing the variations in biomolecular composition between the vesicles of similar and/or different sizes. Using this approach, we uncovered that each of the size-based fractions of sEVs contained particles with predominantly similar SERS spectral features. Indeed, more than 84% of the vesicles residing within a particular group were clearly distinguishable from that of the other EV sub-populations, despite some spectral variations within each sub-population. Our results suggest the possibility that size-based EV fractionation methods produce samples where similarly eluted sEVs are correlated with their respective biochemical contents, as reflected by their SERS spectra. Our findings therefore highlight the possibility that the biogenesis and respective biological functionalities of the various sEV fractions may be inherently different., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Y.H. Xie is a scientific advisor of Nurlabs. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Globally, the prevalence of chronic non-communicable diseases (C-NCDs) and occurrence of multi-morbidity specifically, has been increasing and will continue to rise as life expectancy increases. The burden of mental health disorders has also been rising globally. In sub-Saharan Africa (SSA), literature on these health issues, which are interrelated, is scarce. This study assesses the prevalence of C-NCDs, and depressive and anxiety symptomology and examines the relationship between these issues among a sample of older adults in Uganda., Methods: Between 2021-2022, 604 consenting adults aged 35 years and older were surveyed on a broad range of health issues for the ongoing AMBSO Population Health Surveillance (APHS) cohort study in Wakiso district. Descriptive analyses were performed to characterize the burden of C-NCDs (e.g. diabetes, hypertension), depression (PHQ-9 using a cutoff of <5 scores for minimal/no and 5+ for mild to severe symptomology) and anxiety (GAD-7 using a cutoff of 5+ scores for mild to severe symptomology). Bivariate analysis and multivariable logistic regression models were built using STATA software version 16.0 to examine associations between mental health disorders and having at least one C-NCD. Our exposures of interest were depressive and anxiety symptoms and our outcomes of interest was presence of C-NCDs., Results: Majority of participants were females (63.6%), median age was 46 (IQR: 39-54). Any C-NCDs prevalence was 18.7%, while 18.9% and 11.4%, had screening scores indicative of depressive and anxiety symptomology, respectively. Three percent (3.2%) had PHQ-9 scores indicative of moderate to severe depressive symptomology. In models adjusted for sociodemographic characteristics, there was 12% increased odds of suffering from C-NCDs for every unit increase in PHQ-9 score (AOR = 1.12, 95% CI: 1.10-1.20). Participants with any anxiety symptoms had 2.1 greater odds of suffering from C-NCD compared to those who did not have anxiety symptoms (AOR = 2.10, 95% CI: 1.21-3.70)., Conclusion: C-NCDs were prevalent in older adults, particularly among those experiencing mental health symptoms. Screening for C-NCDs and mental health disorders should be integrated into routine health care for older adults in the country. Early screening and identification of these health issues through primary health care could significantly reduce the public health burden attributable to mental health disorders and the incidence of multi-morbidity in Uganda., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Bulamba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Literature regarding the impact of esophagectomy approach on hospitalizations costs and short-term outcomes is limited. Moreover, few have examined how institutional MIS experience affects costs. We thus examined utilization trends, costs, and short-term outcomes of open and minimally invasive (MIS) esophagectomy as well as assessing the relationship between institutional MIS volume and hospitalization costs., Methods: All adults undergoing elective esophagectomy were identified from the 2016-2020 Nationwide Readmissions Database. Multiple regression models were used to assess approach with costs, in-hospital mortality, and major complications. Additionally, annual hospital MIS esophagectomy volume was modeled as a restricted cubic spline against costs. Institutions performing > 16 cases/year corresponding with the inflection point were categorized as high-volume hospitals (HVH). We subsequently examined the association of HVH status with costs, in-hospital mortality, and major complications in patients undergoing minimally invasive esophagectomy., Results: Of an estimated 29,116 patients meeting inclusion, 10,876 (37.4%) underwent MIS esophagectomy. MIS approaches were associated with $10,600 in increased incremental costs (95% CI 8,800-12,500), but lower odds of in-hospital mortality (AOR 0.76; 95% CI 0.61-0.96) or major complications (AOR 0.68; 95% CI 0.60, 0.77). Moreover, HVH status was associated with decreased adjusted costs, as well as lower odds of postoperative complications for patients undergoing MIS operations., Conclusion: In this nationwide study, MIS esophagectomy was associated with increased hospitalization costs, but improved short-term outcomes. In MIS operations, cost differences were mitigated by volume, as HVH status was linked with decreased costs in the setting of decreased odds of complications. Centralization of care to HVH centers should be considered as MIS approaches are increasingly utilized., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mallick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the context of emerging international trade regulations on deforestation-free commodities, the drivers of households' deforestation in conservation landscapes are of interest. The role of households' livelihood strategies including cocoa production, and the effects of human-elephant conflict are investigated. Using a unique dataset from a survey of 1035 households in the Tridom landscape in the Congo basin, the spatial autoregressive model shows that: (1) Households imitate the deforestation decisions of their neighbors; (2) A marginally higher income from cocoa production-based livelihood portfolios is associated with six to seven times higher deforestation compared to other livelihood strategies with a significant spillover effect on neighboring households' deforestation. The increase in income, mainly from cocoa production-based livelihoods in open-access systems can have a negative effect on forests. Households with a higher share of auto-consumption are associated with lower deforestation. If economic development brings better market access and lower auto-consumption shares, this is likely to positively influence deforestation. Without proper land use planning/zoning associated with incentives, promoting sustainable agriculture, such as complex cocoa agroforestry systems, may lead to forest degradation and deforestation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ngouhouo-Poufoun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Cholecystectomy remains the standard management for acute cholecystitis. Given that rates of nonoperative management have increased, we hypothesize the existence of significant hospital-level variability in operative rates. Thus, we characterized patients who were managed nonoperatively at normal and lower operative hospitals (>90th percentile)., Methods: All adult admissions for acute cholecystitis were queried using the 2016-2019 Nationwide Readmissions Database. Centers were ranked by nonoperative rate using multi-level, mixed effects modeling. Hospitals in the top decile of nonoperative rate (>9.4%) were classified as Low Operative Hospitals (LOH; others:nLOH). Separate regression models were created to determine factors associated with nonoperative management at LOH and nLOH., Results: Of an estimated 418,545 patients, 9.9% were managed at 880 LOH. Multilevel modeling demonstrated that 20.6% of the variability was due to hospital factors alone. After adjustment, older age (Adjusted Odds Ratio [AOR] 1.02/year, 95% Confidence Interval [CI] 1.01-1.02) and public insurance (Medicare AOR 1.31, CI 1.21-1.43 and Medicaid AOR 1.43, CI 1.31-1.57; reference: Private Insurance) were associated with nonoperative management at LOH. These were similar at nLOH. At LOH, SNH status (AOR 1.17, CI 1.07-1.28) and small institution size (AOR 1.20, CI 1.09-1.34) were associated with increased odds of nonoperative management., Conclusion: We noted a significant variability in the interhospital variation of the nonoperative management of acute cholecystitis. Nevertheless, comparable clinical and socioeconomic factors contribute to nonoperative management at both LOH and non-LOH. Directed strategies to address persistent non-clinical disparities are necessary to minimize deviation from standard protocol and ensure equitable care., Competing Interests: P. Benharash serves as a proctor for AtriCure. The content of this manuscript is unrelated to this work. The others authors have no disclosures. All authors declare no competing interests., (Copyright: © 2024 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In response to biodiversity loss and biotic community homogenization in urbanized landscapes, there are increasing efforts to conserve and increase biodiversity within urban areas. Accordingly, around the world, previously extirpated species are (re)colonizing and otherwise infiltrating urban landscapes, while other species are disappearing from these landscapes. Tracking the occurrence of traditionally urban intolerant species and loss of traditionally urban tolerant species should be a management goal of urban areas, but we generally lack tools to study this phenomenon. To address this gap, we first used species' occurrences from iNaturalist, a large collaborative dataset of species observations, to calculate an urban association index (UAI) for 967 native animal species that occur in the city of Los Angeles. On average, the occurrence of native species was negatively associated with our composite measure of urban intensity, with the exception of snails and slugs, which instead occur more frequently in areas of increased urban intensity. Next, we assessed 8,348 0.25 x 0.25 mile grids across the City of Los Angeles to determine the average grid-level UAI scores (i.e., a summary of the UAIs present in a grid cell, which we term Community Urban Tolerance Index or CUTI). We found that areas of higher urban intensity host more urban tolerant species, but also that taxonomic groups differ in their aggregate tolerance of urban areas, and that spatial patterns of tolerance vary between groups. The framework established here has been designed to be iteratively reevaluated by city managers of Los Angeles in order to track the progress of initiatives to preserve and encourage urban biodiversity, but can be rescaled to sample different regions within the city or different cities altogether to provide a valuable tool for city managers globally., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Curti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Disaggregated data is a cornerstone of precision health. Vietnamese Americans (VietAms) are the fourth-largest Asian subgroup in the United States (US), and demonstrate a unique burden of disease and mortality. However, most prior studies have aggregated VietAms under the broader Asian American category for analytic purposes. This study examined the leading causes of death among VietAms compared to aggregated Asian Americans and non-Hispanic Whites (NHWs) during the period 2005-2020., Methods: Decedent data, including underlying cause of death, were obtained from the National Center for Health Statistics national mortality file from 2005 to 2020. Population denominator estimates were obtained from the American Community Survey one-year population estimates. Outcome measures included proportional mortality, age-adjusted mortality rates per 100,000 (AMR), and annual percent change (APC) in mortality over time. Data were stratified by sex and nativity status. Due to large differences in age structure, we report native- and foreign-born VietAms separately., Findings: We identified 74,524 VietAm decedents over the study period (71,305 foreign-born, 3,219 native-born). Among foreign-born VietAms, the three leading causes of death were cancer (26.6%), heart disease (18.0%), and cerebrovascular disease (9.0%). Among native-born VietAms the three leading causes were accidents (19.0%), self-harm (12.0%), and cancer (10.4%). For every leading cause of death, VietAms exhibited lower mortality compared to both aggregated Asians and NHWs. Over the course of the study period, VietAms witnessed an increase in mortality in every leading cause. This effect was mostly driven by foreign-born, male VietAms., Conclusions and Relevance: While VietAms have lower overall mortality from leading causes of death compared to aggregated Asians and NHWs, these advantages have eroded markedly between 2005 and 2020. These data emphasize the importance of racial disaggregation in the reporting of public health measures., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The population with serious mental illness has high risk for hospitalization or death due to unhealthy behaviors and inadequate medical care, though the level of risk varies substantially. Programs that integrate medical and psychiatric services improve outcomes but are challenging to implement and access is limited. It would be useful to know whether benefits are confined to patients with specific levels of risk., Methods: In a population with serious mental illness and increased risk for hospitalization or death, a specialized medical home integrated services and improved treatment and outcomes. Treatment quality, chronic illness care, care experience, symptoms, and quality of life were assessed for a median of 385 days. Analyses examine whether improvements varied by baseline level of patient risk., Results: Patients with greater risk were more likely to be older, more cognitively impaired, and have worse mental health. Integrated services increased appropriate screening for body mass index, lipids, and glucose, but increases did not differ significantly by level of risk. Integrated services also improved chronic illness care, care experience, mental health-related quality of life, and psychotic symptoms. There were also no significant differences by risk level., Conclusions: There were benefits from integration of primary care and psychiatric care at all levels of increased risk, including those with extremely high risk above the 95th percentile. When developing integrated care programs, patients should be considered at all levels of risk, not only those who are the healthiest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Transcatheter mitral valve replacement (TMVR) has garnered interest as a viable alternative to the traditional surgical mitral valve replacement (SMVR) for high-risk patients requiring redo operations. This study aims to evaluate the association of TMVR with selected clinical and financial outcomes., Methods: Adults undergoing isolated redo mitral valve replacement were identified in the 2016-2020 Nationwide Readmissions Database and categorized into TMVR or SMVR cohorts. Various regression models were developed to assess the association between TMVR and in-hospital mortality, as well as additional secondary outcomes. Transseptal and transapical catheter-based approaches were also compared in relation to study endpoints., Results: Of an estimated 7,725 patients, 2,941 (38.1%) underwent TMVR. During the study period, the proportion of TMVR for redo operations increased from 17.8% to 46.7% (nptrend<0.001). Following adjustment, TMVR was associated with similar odds of in-hospital mortality (AOR 0.82, p = 0.48), but lower odds of stroke (AOR 0.44, p = 0.001), prolonged ventilation (AOR 0.43, p<0.001), acute kidney injury (AOR 0.61, p<0.001), and reoperation (AOR 0.29, p = 0.02). TMVR was additionally correlated with shorter postoperative length of stay (pLOS; β -0.98, p<0.001) and reduced costs (β -$10,100, p = 0.002). Additional analysis demonstrated that the transseptal approach had lower adjusted mortality (AOR 0.44, p = 0.02), shorter adjusted pLOS (β -0.43, p<0.001), but higher overall costs (β $5,200, p = 0.04), compared to transapical., Conclusions: In this retrospective cohort study, we noted TMVR to yield similar odds of in-hospital mortality as SMVR, but fewer complications and reduced healthcare expenditures. Moreover, transseptal approaches were associated with lower adjusted mortality, shorter pLOS, but higher cost, relative to the transapical. Our findings suggest that TMVR represent a cost-effective and safe treatment modality for patients requiring redo mitral valve procedures. Nevertheless, future studies examining long-term outcomes associated with SMVR and TMVR in redo mitral valve operations, are needed., Competing Interests: Dr. Peyman Benharash received proctor fees from Atricure as a proctor. This manuscript does not discuss any Atricure products or services. Other authors report no conflicts., (Copyright: © 2024 Le et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The prediction of depression is a crucial area of research which makes it one of the top priorities in mental health research as it enables early intervention and can lead to higher success rates in treatment. Self-reported feelings by patients represent a valuable biomarker for predicting depression as they can be expressed in a lower-dimensional network form, offering an advantage in visualizing the interactive characteristics of depression-related feelings. Furthermore, the network form of data expresses high-dimensional data in a compact form, making the data easy to use as input for the machine learning processes. In this study, we applied the graph convolutional network (GCN) algorithm, an effective machine learning tool for handling network data, to predict depression-prone patients using the network form of self-reported log data as the input. We took a data augmentation step to expand the initially small dataset and fed the resulting data into the GCN algorithm, which achieved a high level of accuracy from 86-97% and an F1 (harmonic mean of precision and recall) score of 0.83-0.94 through three experimental cases. In these cases, the ratio of depressive cases varied, and high accuracy and F1 scores were observed in all three cases. This study not only demonstrates the potential for predicting depression-prone patients using self-reported logs as a biomarker in advance, but also shows promise in handling small data sets in the prediction, which is critical given the challenge of obtaining large datasets for biomarker research. The combination of self-reported logs and the GCN algorithm is a promising approach for predicting depression and warrants further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dynamic functional connectivity investigates how the interactions among brain regions vary over the course of an fMRI experiment. Such transitions between different individual connectivity states can be modulated by changes in underlying physiological mechanisms that drive functional network dynamics, e.g., changes in attention or cognitive effort. In this paper, we develop a multi-subject Bayesian framework where the estimation of dynamic functional networks is informed by time-varying exogenous physiological covariates that are simultaneously recorded in each subject during the fMRI experiment. More specifically, we consider a dynamic Gaussian graphical model approach where a non-homogeneous hidden Markov model is employed to classify the fMRI time series into latent neurological states. We assume the state-transition probabilities to vary over time and across subjects as a function of the underlying covariates, allowing for the estimation of recurrent connectivity patterns and the sharing of networks among the subjects. We further assume sparsity in the network structures via shrinkage priors, and achieve edge selection in the estimated graph structures by introducing a multi-comparison procedure for shrinkage-based inferences with Bayesian false discovery rate control. We evaluate the performances of our method vs alternative approaches on synthetic data. We apply our modeling framework on a resting-state experiment where fMRI data have been collected concurrently with pupillometry measurements, as a proxy of cognitive processing, and assess the heterogeneity of the effects of changes in pupil dilation on the subjects' propensity to change connectivity states. The heterogeneity of state occupancy across subjects provides an understanding of the relationship between increased pupil dilation and transitions toward different cognitive states., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Shared decision-making (SDM) refers to a collaborative process in which clinicians assist patients in making medically informed, evidence-based decisions that align with their values and preferences. There is a paucity of literature on SDM in dermatology., Objective: We aim to assess whether male and female psoriasis patients evaluate their clinicians' engagement in SDM differently across different age groups., Methods: Cross-sectional study using data from the 2014-2017 and 2019 Medical Expenditure Panel Surveys (MEPS)., Results: A weighted total of 7,795,608 psoriasis patients were identified. SDM Scores ranged from 1 to 4, with 4 representing the most favorable patient evaluation of their clinicians' engagement in SDM. We conducted multivariate linear regression to compare mean SDM Scores in male psoriasis patients versus female psoriasis patients across different patient age groups. Female patients ages 60-69 perceived significantly greater clinician engagement in SDM compared to age-matched male patients (female patient perception of SDM 3.65 [95%CI:3.61-3.69] vs. male patient perception of SDM 3.50 [95%CI:3.43-3.58], p<0.005). The same trend of older female patients evaluating their clinicians' engagement in SDM significantly higher than their age-matched male counterparts exists for the age group >70 (p<0.005). No significant differences between male and female patients' evaluations of their clinicians' engagement in SDM were demonstrated in subjects younger than 60. All calculations were adjusted for demographic and clinical factors., Conclusions: Compared to older male psoriasis patients, older female psoriasis patients evaluated their clinicians to be more engaged in shared decision-making., Competing Interests: Authors RK, PK, MTO, HT, RY, AH, SB, KS, LG, and DY have no conflicts of interest to disclose. AWA has served as a research investigator, scientific advisor, or speaker to AbbVie, Amgen, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho, Sun, Dermavant, Dermira, Sanofi, Takeda, Organon, Regeneron, Pfizer and Ventyx. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Kikuchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Metastasis is the most dreaded outcome after a breast cancer diagnosis, and little is known regarding what triggers or promotes breast cancer to spread distally, or how to prevent or eradicate metastasis effectively. Bilateral breast cancers are an uncommon form of breast cancers. In our study, a percentage of bilateral breast cancers were clonally related based on copy number variation profiling. Whole exome sequencing and comparative sequence analysis revealed that a limited number of somatic mutations were acquired in this "breast-to-breast" metastasis that might promote breast cancer distant spread. One somatic mutation acquired was SIVA-D160N that displayed pro-metastatic phenotypes in vivo and in vitro. Over-expression of SIVA-D160N promoted migration and invasion of human MB-MDA-231 breast cancer cells in vitro, consistent with a dominant negative interfering function. When introduced via tail vein injection, 231 cells over-expressing SIVA-D160N displayed enhanced distant spread on IVIS imaging. Over-expression of SIVA-D160N promoted invasion and anchorage independent growth of mouse 4T1 breast cancer cells in vitro. When introduced orthotopically via mammary fat pad injection in syngeneic Balb/c mice, over-expression of SIVA-D160N in 4T1 cells increased orthotopically implanted mammary gland tumor growth as well as liver metastasis. Clonally related bilateral breast cancers represented a novel system to investigate metastasis and revealed a role of SIVA-D160N in breast cancer metastasis. Further characterization and understanding of SIVA function, and that of its interacting proteins, may elucidate mechanisms of breast cancer metastasis, providing clinically useful biomarkers and therapeutic targets., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: Community-based health interventions often demonstrate efficacy in clinical trial settings but fail to be implemented in the real-world. We sought to identify the key operational and contextual elements of the Los Angeles Barbershop Blood Pressure Study (LABBPS), an objectively successful community-based health intervention primed for real-world implementation. LABBPS was a cluster randomized control trial that paired the barbers of Black-owned barbershops with clinical pharmacists to manage uncontrolled hypertension in Black male patrons, demonstrating a substantial 21.6 mmHg reduction in systolic blood pressure. Despite this success, the LABBPS intervention has not expanded beyond the original clinical trial setting. The aim of this study was to determine the facilitating and limiting factors to expansion of the LABBPS intervention., Methods: We undertook a qualitative assessment of semi-structured interviews with study participants performed after trial completion. Interviews included a total of 31 participants including 20 (6%) of the 319 LABBPS program participants ("patrons"), 10 (19%) barbers, and one (50%) clinical pharmacist. The semi-structured interviews were focused on perceptions of the medical system, study intervention, and influence of social factors on health., Results: Several common themes emerged from thematic analysis of interview responses including: importance of care provided in a convenient and safe environment, individual responsibility for health and health-related behaviors, and engagement of trusted community members. In particular, patrons reported that receiving the intervention from their barber in a familiar environment positively influenced the formation of relationships with clinical pharmacists around shared efforts to improve medication adherence and healthy habits. All interviewee groups identified the trust diad, comprising the familiar environment and respected community member, as instrumental in increasing health-related behaviors to a degree not usually achieved by traditional healthcare providers., Discussion: In conclusion, participants of an objectively successful community-based intervention trial consistently identified key features that could facilitate wider implementation and efficacy: social trust relationships, soliciting insights of trust bearers, and consistent engagement in a familiar community setting. These findings can help to inform the design and operations of future community-based studies and programs aiming to achieve a broad and sustainable impact., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kohrman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults., Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science., Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions., Clinical Trials.gov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Brett Anderson reported receiving direct support for work not related to RECOVER work/publications from Genentech and the National Institute of Allergy and Immunology. Walter Dehority reported receiving grant support from Merck and participating in research for the Moderna COVID-19 pediatric vaccine trial and the Pfizer Paxlovid trial. Alex Fiks reported receiving support from NJM insurance and personal consulting fees not related to this paper from Rutgers University and the American Academy of Pediatrics. Ashraf Harahsheh reported serving as a scientific advisory board member unrelated to this paper for OP2 DRUGS. Lawrence Kleinman reported serving as an unpaid member of the Board of Directors for the DARTNet Institute, as a principle investigator at Quality Matters, Inc., and as the Vice Chair for the Borough of Metuchen Board of Health. Dr. Kleinman also reported grant support for work not related to RECOVER work/publications from NIH, HRSA, and the Robert Wood Johnson Foundation. Dr. Kleinman also reported minority individual stock ownership in Apple Computer, Sanofi SA, Experion, GlaxoSmithKline, Magyar Bank, Regeneron Pharmaceuticals, JP Morgan Chase, and Amgen Inc. Torri Metz reported participating as a Principle Investigator in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She is also a principle investigator for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Joshua Milner reported serving as a member of the Scientific Advisory Board for Blueprint Medicines, in a capacity unrelated to RECOVER work/publications. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Gross et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Though rod and cone photoreceptors use similar phototransduction mechanisms, previous model calculations have indicated that the most important differences in their light responses are likely to be differences in amplification of the G-protein cascade, different decay rates of phosphodiesterase (PDE) and pigment phosphorylation, and different rates of turnover of cGMP in darkness. To test this hypothesis, we constructed TrUx;GapOx rods by crossing mice with decreased transduction gain from decreased transducin expression, with mice displaying an increased rate of PDE decay from increased expression of GTPase-activating proteins (GAPs). These two manipulations brought the sensitivity of TrUx;GapOx rods to within a factor of 2 of WT cone sensitivity, after correcting for outer-segment dimensions. These alterations did not, however, change photoreceptor adaptation: rods continued to show increment saturation though at a higher background intensity. These experiments confirm model calculations that rod responses can mimic some (though not all) of the features of cone responses after only a few changes in the properties of transduction proteins., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Morshedian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diabetes mellitus (DM) is a severe metabolic disease that can have significant consequences for cognitive health. Bioflavonoids such as Trifolium alexandrinum (TA), quercetin (Q), and Biochanin-A (BCA) are known to exert a wide range of pharmacological functions including antihyperglycemic activity. This study aimed to investigate the neurotherapeutic effects of quercetin-loaded nanoparticles (Q-LNP) and BCA extracted from TA against diabetes-induced cerebral cortical damage through modulation of PI3K/Akt/GSK-3β and AMPK signaling pathways. Adult male Wistar albino rats (N = 25) were randomly assigned to one of five groups: control, diabetics fed a high-fat diet (HFD) for 2 weeks and intraperitoneally (i.p.) injected with STZ (40 mg/kg), and diabetics treated with Q-LNP (50 mg/kg BW/day), BCA (10 mg/kg BW/day), or TA extract (200 mg/kg BW/day). Treatments were applied by oral gavage once daily for 35 days. Diabetic rats treated with Q-LNP, BCA, and TA extract showed improvement in cognitive performance, cortical oxidative metabolism, antioxidant parameters, and levels of glucose, insulin, triglyceride, and total cholesterol. In addition, these treatments improved neurochemical levels, including acetylcholine, dopamine, and serotonin levels as well acetylcholinesterase and monoamine oxidase activities. Furthermore, these treatments lowered proinflammatory cytokine production for TNF-α and NF-κB; downregulated the levels of IL-1β, iNOS, APP, and PPAR-γ; and attenuated the expressions of PSEN2, BACE, IR, PI3K, FOXO 1, AKT, AMPK, GSK-3β, and GFAP. The histopathological examinations of the cerebral cortical tissues confirmed the biochemical results. Overall, the present findings suggest the potential therapeutic effects of TA bioflavonoids in modulating diabetes-induced cerebral cortical damage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Newairy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)