bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAR-T Therapy in HIV: Pioneering Advances and Navigating Challenges
Authors: Wang Xiao , Liu Jianyang , Hao Feike , Ajavavarakula Tatchapon , Shi Xuanling 
Published: July 2024

Abstract
Chimeric antigen receptor T (CAR-T) cell therapy, renowned for its successes in cancer treatment, is now entering the field of human immunodeficiency virus (HIV) therapy, presenting both opportunities and challenges. With the emergence of broadly neutralizing antibodies, multi-target CARs, and T cell receptor–like antibodies aimed at increasing specificity in targeting HIV reservoirs, CAR-T therapy is synergizing with other cutting-edge treatments, including gene-editing technologies, therapeutic vaccines, and latency-reversing agents, in pursuit of a potential functional cure. In this review, we delve into the role of CAR-T therapy in HIV treatment, highlighting its potential to overcome clinical obstacles. We discuss advancements in targeting strategies within CAR constructs and the intricate regulation of T cell proliferation and chemotaxis. Moreover, we explore the use of diverse immune cells, such as gamma-delta T cells and natural killer cells. We review advanced biotechnologies, manufacturing innovations, viral mechanisms, and immune microenvironments. We also discuss the current research landscape and potential future applications of CAR-T therapy against HIV, which remains a critical global health challenge.
Meeting the Health Needs of Society Through Curricular Innovation in Physical Therapist Education: Examples From 3 Entry-Level Programs
Authors: Magnusson Dawn M. , Judd Dana L. , Ambler Steven B. , Magee Julian , Collins Prisca , Kuba Elizabeth , Bilyeu Catherine 
Published: July 2024

Background and Purpose.
Entry-level physical therapist (PT) education programs play a critical role in inspiring future leaders to become moral change agents, capable of understanding and addressing evolving societal health needs. Social reconstructionism represents an educational philosophy focused on alleviating pervasive inequities and improving the health of society; however, its application in PT education is not well understood. The purpose of this article is to describe the approach 3 entry-level PT programs used to manifest social reconstructionism within their curricula to foster social consciousness and strengthen moral agency.

Method/Model Description and Evaluation.
The Framework for Educating Health Professionals to Address the Social Determinants of Health informed the development of a conceptual framework that illustrates the role of PT education programs in creating transformative learning environments and preparing learners to meet societal health needs. Concepts within this framework were operationalized according to 5 domains put forth by Jensen et al. and related competencies put forth by the Association of American Medical Colleges.

Outcomes.
Narratives from each program demonstrate how the design and implementation of curricula, grounded in social reconstructionism, can be accomplished through 1) ongoing modifications, 2) thoughtful reconstruction, and 3) initial design. Sample learning activities, objectives, and assessment strategies are provided.

Discussion and Conclusion.
The proposed method was effective in guiding meaningful objectives, learning activities, and assessment strategies grounded in social reconstructionism. Such findings can inform the design of curricula that inspire the next generation of transformative leaders who work to alleviate pervasive inequities and improve the health of society.
Prevalence and Type of HPV Genital Infection in Girls: A Systematic Review and Meta-Analysis
Authors: de Azevedo Bispo Raianne Kívia , Fonseca Marcelo Cunio Machado , de Góis Speck Neila Maria 
Published: July 2024

Objectives
This investigation explored the prevalence of human papillomavirus (HPV) infection by subtypes in girls aged up to 12.

Methods
Four indexed databases, PubMed, EMBASE, Cochrane, and LILACS, were evaluated. Twenty-nine observational studies published between 1992 and 2018 were included.

Results
The prevalence of genital condyloma acuminatum or HPV-positive serology due to prior infection among girls with suspected/confirmed sexual abuse was 25%, and without a history or information about abuse, 8%. The analysis indicated that low-risk HPV types were the most prevalent among this group, corresponding to 86.6% of the identified types. Human papillomavirus 6 and 11 were the most prevalent types, followed by HPV 16 and 2. Moreover, the analysis identified limited epidemiological data on genital warts in children up to 12 years. Several studies focused on convenience sampling, sexually abused girls, or failed to separate data by gender.

Conclusion
Findings of our systematic review and prevalence meta-analysis indicate that the occurrence of HPV infection in girls aged 12 or younger is relatively rare, underscoring the significance of understanding the prevalence of HPV in the pediatric population. However, it is essential to be cautious when applying these results to the pediatric population, given cases of girls who are suspected of or have suffered sexual abuse. There is a pressing need for further research to fill the information gap on HPV infection in this vulnerable group.
Multifaceted, Brief Intensive Home-Based Exposure Treatment in Patients with Obsessive-Compulsive Disorder Who are Nonresponsive to Regular Cognitive Behavior Therapy: An Uncontrolled Pilot Study
Authors: Remmerswaal Karin C.P. , Batelaan Neeltje M. , van Oppen Patricia , Scholten Willemijn D. , van Balkom Anton J.L.M. 
Published: July 2024

Objective:
To test a multifaceted treatment program for patients with obsessive-compulsive disorder (OCD) who did not respond to regular cognitive behavior therapy (CBT). The treatment addresses several factors that may play a role in maintaining OCD.

Methods:
We designed a treatment consisting of a 6-day intensive, individual exposure in vivo with response prevention (ERP) format, with 24 therapist-assisted treatment hours at the patient’s home and 12 self-controlled ERP hours, including behavioral activation and family interventions. Next, we investigated the effect (obsessive-compulsive symptoms, comorbidity, functioning, quality of life, OCD-related interaction patterns) and feasibility (dropout, treatment satisfaction, and organization) of this program using pre-post-tests, pre-follow-up tests, and qualitative data from patients, family members, and therapists.

Results:
In a sample of 22 participants, obsessive-compulsive symptoms (Y-BOCS pre: 28.7, post: 15.9; Wilcoxon S-R tests P<0.01) improved significantly, as did most other effect measures. Results were largely, but not completely, preserved at 3-month follow-up. There was only 1 dropout. Patients, family members, and therapists were satisfied with the treatment. Implementation of the treatment did not pose difficulties.

Conclusions:
In nonresponders with OCD, a multifaceted, brief, intensive home-based ERP program targeting factors maintaining OCD is promising and feasible. Extra care is needed to maintain improvement.
Assessing the Effectiveness of Simulation-Based Education in Emerging Infectious Disease Management
Authors: Yoon Sol , Kim Su Hyun 
Published: July 2024

Summary Statement
This systematic review and meta-analysis aimed to thoroughly examine the effectiveness of simulation-based education in the management of emerging infectious diseases, focusing on educational content and methods. Studies published between 2000 and 2022 were identified, and a meta-analysis was conducted using a random-effects model. The findings revealed that simulation-based education significantly enhances various competencies related to managing emerging infectious diseases, encompassing cognitive, negative-affective, positive-affective, and psychomotor outcomes. Subgroup analysis indicated that methods effective in improving competencies include the use of equipment with limited or full patient interaction, simulated or in situ settings, and scenarios involving some interruptions by educators or independent participation of trainees. This review underscores the importance of appropriate methodological considerations in simulation-based education, including equipment, settings, and scenario designs, to optimize educational outcomes in the management of emerging infectious diseases.
Associations of Resilience, Perceived Control of Health, and Depression with Geriatric Outcomes after Surgery
Authors: Miller Matthew J. , Cenzer Irena , Covinsky Kenneth E. , Finlayson Emily , Raue Patrick J. , Tang Vicky L. 
Published: July 2024

Objective:
To identify if depression, resilience, and perceived control of health are related to 2.5-year mortality and instrumental activities of daily living (IADL) decline among older adults after surgery

Summary Background Data:
The relationships of psychosocial factors with postoperative mortality and IADL decline among older adults are understudied.

Methods:
We identified 3778 community-dwelling older adults in the Health and Retirement Study (HRS) with Medicare claims for surgery (mean [SD] age: 75.4 [7.8] years, 53.9% women, and 86.0% non-Hispanic White). We assessed associations of depression, resilience, and perceived control of health with 2.5-year postoperative mortality and IADL decline using cox and modified Poisson regression analyses, adjusting for sociodemographic and health variables.

Results:
The incidence of 2.5-year postoperative mortality was 18.5% and IADL decline was 9.4%. Depression was associated with a higher incidence and adjusted hazard [95% CI] of mortality (26% vs. 16%, aHR:1.2[0.9, 1.5]), but high resilience was associated with a lower incidence and adjusted hazard of mortality (9% vs. 21%, aHR:0.6[0.5, 0.8]). Those with depression had higher incidence and adjusted relative risk [95% CI] of IADL decline (17% vs. 7%, aRR:1.6[1.2, 2.2]), but lower incidence and adjusted relative risk of IADL decline was identified for those with high resilience (4% vs. 11%, aRR:0.6[0.4, 1.0]) and high perceived control of health (7% vs. 10%, aRR:0.6[0.4, 1.0]).

Conclusion:
While depression confers greater risk of mortality and IADL decline, higher resilience and perceived control of health may be protective. Addressing psychosocial factors in the peri-operative period may improve outcomes among older adults.
The Genetic Architecture of the Human Corpus Callosum and its Subregions
Authors: Bhatt Ravi R. , Gadewar Shruti P. , Shetty Ankush , Ba Gari Iyad , Haddad Elizabeth , Javid Shayan , Ramesh Abhinaav , Nourollahimoghadam Elnaz , Zhu Alyssa H. , de Leeuw Christiaan , Thompson Paul M. , Medland Sarah E. , Jahanshad Neda 
Published: July 2024

AbstractThe corpus callosum (CC) is the largest set of white matter fibers connecting the two hemispheres of the brain. In humans, it is essential for coordinating sensorimotor responses, performing associative/executive functions, and representing information in multiple dimensions. Understanding which genetic variants underpin corpus callosum morphometry, and their shared influence on cortical structure and susceptibility to neuropsychiatric disorders, can provide molecular insights into the CC’s role in mediating cortical development and its contribution to neuropsychiatric disease. To characterize the morphometry of the midsagittal corpus callosum, we developed a publicly available artificial intelligence based tool to extract, parcellate, and calculate its total and regional area and thickness. Using the UK Biobank (UKB) and the Adolescent Brain Cognitive Development study (ABCD), we extracted measures of midsagittal corpus callosum morphometry and performed a genome-wide association study (GWAS) meta-analysis of European participants (combinedN= 46,685). We then examined evidence for generalization to the non-European participants of the UKB and ABCD cohorts (combinedN= 7,040). Post-GWAS analyses implicate prenatal intracellular organization and cell growth patterns, and high heritability in regions of open chromatin, suggesting transcriptional activity regulation in early development. Results suggest programmed cell death mediated by the immune system drives the thinning of the posterior body and isthmus. Global and local genetic overlap, along with causal genetic liability, between the corpus callosum, cerebral cortex, and neuropsychiatric disorders such as attention-deficit/hyperactivity and bipolar disorders were identified. These results provide insight into variability of corpus callosum development, its genetic influence on the cerebral cortex, and biological mechanisms related to neuropsychiatric dysfunction.
Ongoing local adaptation to climate change in yarrow (Achillea millefoliumL.)
Authors: Losapio Gianalberto , Doussot Baptiste , Araniti Fabrizio , Bruno Leonardo , Guevara Roger , Dirzo Rodolfo 
Published: July 2024

AbstractClimate change threatens biodiversity as populations can persist if they migrate or adapt to the rapidly changing conditions of the Anthropocene. However, little is known about the persistence of plant populations under the long-term trends of increasing temperature and drought. We explore whether historical populations of yarrow (Achillea millefoliumL.) surveyed in the 1920s have persisted locally or undergone local extinction after 100 years. We resurveyed historical sites spanning a broad climatic gradient (from 1 m to 3,200 m a.s.l.), examined to what extent plant growth signature (height) has changed over time, and analyzed metabolic diversity. Nine out of ten populations persisted locally and showed phenotypic and metabolic differentiation. The only population potentially extirpated is that of the hottest and driest site. Populations from warm sites in coastal and mountain regions had grown taller than 100 years ago. In contrast, populations from dry sites in lowlands and foothills became shorter. Furthermore, we document differentiation in metabolic diversity involving plant defenses and signaling. Ongoing local adaptation is constrained by changing both temperature and precipitation as well as by biotic interactions. Preserving locally adapted populations and metabolic diversity is key for conservation efforts.
Genomic prediction of metabolic content in rice grain in response to warmer night conditions
Authors: Bi Ye , Walia Harkamal , Obata Toshihiro , Morota Gota 
Published: July 2024

AbstractIt has been argued that metabolic content can be used as a selection marker to accelerate crop improvement because metabolic profiles in crops are often under genetic control. Evaluating the role of genetics in metabolic variation is a long-standing challenge. Rice, one of the world’s most important staple crops, is known to be sensitive to recent increases in nighttime temperatures. Quantification of metabolic levels can help measure rice responses to high night temperature (HNT) stress. However, the extent of metabolic variation that can be explained by regression on whole-genome molecular markers remains to be evaluated. In the current study, we generated metabolic profiles for mature grains from a subset of rice diversity panel accessions grown under optimal and HNT conditions. Metabolite accumulation was low to moderately heritable, and genomic prediction accuracies of metabolite accumulation were within the expected upper limit set by their genomic heritability estimates. Genomic heritability estimates were slightly higher in the control group than in the HNT group. Genomic correlation estimates for the same metabolite accumulation between the control and HNT conditions indicated the presence of genotype-by-environment interactions. Reproducing kernel Hilbert spaces regression and image-based deep learning improved prediction accuracy, suggesting that some metabolite levels are under non-additive genetic control. Joint analysis of multiple metabolite accumulation simultaneously was effective in improving prediction accuracy by exploiting correlations among metabolites. The current study serves as an important first step in evaluating the cumulative effect of markers in influencing metabolic variation under control and HNT conditions.Core ideasRice is sensitive to increases in nighttime and daytime temperaturesMetabolite accumulation from rice grains was low to moderately heritableNon-additive genomic prediction models improved prediction accuracy for some metabolitesResults shed new light on the utility of genomic predictions for metabolite accumulation from rice grains
Reduced perceptual error monitoring in autism
Authors: Zuk Nathaniel J. , Weiss Yarden , Akrami Athena , Ahissar Merav 
Published: July 2024

AbstractIndividuals with autism spectrum disorder (ASD) exhibit both slower updating of perceptual priors and reduced online error correction in motor tasks, leading to diminished behavioral flexibility. We hypothesized that these difficulties may be related to atypical activation of anterior cingulate cortex (ACC), known to produce a feedback-related negativity (FRN), measurable with EEG, following erred motor responses. We reasoned that ACC might also monitor perceptual performance and produce FRN following “incorrect” perceptual feedback. Participants performed a two-tone pitch discrimination task. Overall behavioral performance and EEG responses to stimuli did not differ between individuals with and without autism. However, almost all (33/35) non-autistics produced a clear perceptual FRN, while less than half (13/30) of autistic participants did. Behaviorally, non-autistics showed response slowing following incorrect trials, improved accuracy after difficult correct trials, and greater influence of perceptual priors following easy successful trials. In contrast, ASD participants did not exhibit these patterns. By examining FRN in a perceptual decision-making task involving feedback dependent choice updates, we demonstrated that FRN differs between ASD and non-autistic individuals and is associated with distinct behavioral differences. This study is the first to measure FRN in such a task, revealing significant disparities. Our findings suggest atypical ACC activation and insensitivity to feedback contribute to reduced behavioral flexibility in ASD, particularly when feedback is essential for performance update.Significance statementA characteristic of autism is cognitive “slowness” in updating expectations in new contexts. Our study shows that this cognitive difference is related to a reduced use of feedback, linked to atypical activity in a brain area involved in error detection and behavioral adjustment. Using EEG, we found that autistic individuals have weaker feedback-related signals and do not adjust their behavior as effectively as non-autistic individuals. This effect was significant enough to serve as a potential biomarker for autism. This is the first time such brain responses have been measured in a perceptual task requiring continuous adjustments. Understanding these brain mechanisms can inform strategies to enhance learning and adaptability in autism, providing new insights into the neural basis of behavioral flexibility.
Causal Estimands for Analyses of Averted and Avertible Outcomes due to Infectious Disease Interventions
Authors: Jia Katherine M , Boyer Christopher B , Wallinga Jacco , Lipsitch Marc 
Published: July 2024

ABSTRACTDuring the coronavirus disease (COVID-19) pandemic, researchers attempted to estimate the number of averted and avertible outcomes due to non-pharmaceutical interventions or vaccination campaigns to quantify public health impact. However, the estimands used in these analyses have not been previously formalized. It is also unclear how these analyses relate to the broader framework of direct, indirect, total, and overall causal effects of an intervention under interference. In this study, using potential outcome notation, we adjust the direct and overall effects to accommodate analyses of averted and avertible outcomes. We use this framework to interrogate the commonly-held assumption in empirical studies that vaccine-averted outcomes via direct impact among vaccinated individuals (or vaccine-avertible outcomes via direct impact among unvaccinated individuals) is a lower bound on vaccine-averted (or -avertible) outcomes overall. To do so, we describe a susceptible-infected-recovered-death model stratified by vaccination status. When vaccine efficacies wane, the lower bound fails for vaccine-avertible outcomes. When transmission or fatality parameters increase over time, the lower bound fails for both vaccine-averted and -avertible outcomes. Only in the simplest scenario where vaccine efficacies, transmission, and fatality parameters are constant over time, outcomes averted via direct impact among vaccinated individuals (or outcomes avertible via direct impact among unvaccinated individuals) is shown to be a lower bound on overall impact on vaccine-averted (or -avertible) outcomes. In conclusion, the lower bound can fail under common violations to assumptions on constant vaccine efficacy, pathogen properties, or behavioral parameters over time. In real data analyses, estimating what seems like a lower bound on overall impact through estimating direct impact may be inadvisable without examining the directions of indirect effects. By classifying estimands for averted and avertible outcomes and examining their relations, this study improves conduct and interpretation of research evaluating impact of infectious disease interventions.
Peer victimization in adolescence alters gene expression and cytokine profiles during transition to adulthood
Authors: Heumann Jens , Cole Steve W. , Eisner Manuel , Ribeaud Denis , Grünblatt Edna , Shanahan Michael J. 
Published: July 2024

ABSTRACTSocial adversity downregulates antiviral genes and upregulates inflammatory genes, altering cytokine levels. This study investigated the effects of peer victimization (PV) during adolescence on gene expression, cellular dynamics, and cytokine profiles in young adulthood. Data from the Zurich Brain and Immune Gene Study (z-GIG,n= 200; 47% female) captured PV between ages 11 and 20, with mRNA and plasma cytokines analyzed in 144 participants at age 22. A counterfactual design with genetically informed inverse probability weighting adjusted for baseline confounders in individual and environmental characteristics.In silicodeconvolution revealed altered leukocyte composition in victims, including an M2-like monocyte–skewed profile. Differentially expressed genes in victims were enriched in preselected Reactome pathways, includingInterferon signaling, MetabolismandSignal transduction. Exploratory Reactome-wide queries confirmed pathways in theImmune SystemandMetabolism, highlighted their downregulation, and identified additional pathways, such as those involved inChromatin organizationandMetabolism of proteins. Transcription factors STAT2, IRF2, and NF-κB emerged as key regulators in victims, with target genes prominently mapped to Interferon signaling and Chromatin organization pathways. Victims exhibited altered cytokine levels, including pro-inflammatory CCL4, TNF, CXCL9, and CXCL10. These findings suggest that adolescent PV can lead to changes in gene regulation and cytokine levels, potentially altering the immune profile into young adulthood. The results underscore the importance of health policies aimed at prevention, building resilience, and mitigating the long-term effects of PV.