bluuebunny/crossref_metadata_2025_split huggingface dataset:
NURSING PHILOSOPHY OF FAMILY SUPPORT FOR PATIENT CARE SKIZOFRENIA: A LITERATURE REVIEW
Authors: Halawa Aristina , Yusuf Ah. , Rumambo Pandin Moses Glorino 
Published: December 2024

ABSTRACTIntroductionThe emergence of deinstitutionalisation of people with mental disorders has led to the burden of patient care being shifted to families. Patients with schizophrenic disorders who live with their families account for up to 50%. Families play an important role in the lives of individuals living with mental illnesses such as schizophrenia. Caregivers often face economic burdens and challenges in managing daily household tasks, which can exacerbate stress and reduce their overall well-being. This family support is lacking as family caregivers often experience significant emotional and physical stress due to the high demands of caregiving. If an individual receives emotional, informational, or instrumental support from their family then they will likely have greater confidence, hope, and optimism to pursue recovery and live a fulfilling and meaningful life.MethodsThis research uses a literature review using the PICOS framework. The literature for the originality of this research uses articles in English from 4 databases: Science direct, Scopus, Sage and EBSCOhost. The keywords used in the literature search were: “family support” AND family AND support AND schizophrenia. The search was limited to publications from 2019-2024 and the articles retrieved were full articles not review articles. The strategy used to search for articles used the PICOS framework. Then selected using PRISMA diagram and obtained ten articles.ResultsThere are 10 articles obtained and all of them explain about family support in caring for schizophrenia patients both from factors that affect family support, forms of family support and the impact of family support on caregivers or family members and patients. Thus, family support is very important for the welfare of caregivers and for patients who experience schizophrenia disorders.ConclusionFamily support is essential in the care of patients with schizophrenia. There are several barriers that prevent families from accessing necessary resources and support, including stigma, lack of information, and limited contact with the healthcare team. Family Support provided to caregivers as well as to patients provides better outcomes for patients including increased independence and improved daily functioning, reduced caregiver burden and improved caregiver ability to provide care.
Diazepam modulates hippocampal CA1 functional connectivity in people at clinical high-risk for psychosis
Authors: Livingston Nicholas R. , Kiemes Amanda , O’Daly Owen , Knight Samuel R. , Lukow Paulina B. , Jelen Luke A. , Reilly Thomas J. , Dima Aikaterini , Nettis Maria Antonietta , Casetta Cecilia , Devenyi Gabriel A. , Spencer Thomas , De Micheli Andrea , Fusar-Poli Paolo , Grace Anthony A. , Williams Steve C.R. , McGuire Philip , Chakravarty M. Mallar , Egerton Alice , Modinos Gemma 
Published: December 2024

AbstractBackgroundPreclinical evidence suggests that diazepam enhances hippocampal γ-aminobutyric acid (GABA) signalling and normalises a psychosis-relevant cortico-limbic-striatal circuit. Hippocampal network dysconnectivity, particularly from the CA1 subfield, is evident in people at clinical high-risk for psychosis (CHR-P), representing a potential treatment target. This study aimed to forward-translate this preclinical evidence.MethodsIn this randomised, double-blind, placebo-controlled study, 18 CHR-P individuals underwent resting-state functional magnetic resonance imaging twice, once following a 5mg dose of diazepam and once following a placebo. They were compared to 20 healthy controls (HC) who did not receive diazepam/placebo. Functional connectivity (FC) between the hippocampal CA1 subfield and the nucleus accumbens (NAc), amygdala, and ventromedial prefrontal cortex (vmPFC) was calculated. Mixed-effects models investigated the effect of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on CA1-to-region FC.ResultsIn the placebo condition, CHR-P individuals showed significantly lower CA1-vmPFC (Z=3.17,PFWE=0.002) and CA1-NAc (Z=2.94,PFWE=0.005) FC compared to HC. In the diazepam compared to placebo condition, CA1-vmPFC FC was significantly increased (Z=4.13,PFWE=0.008) in CHR-P individuals, and both CA1-vmPFC and CA1-NAc FC were normalised to HC levels. In contrast, compared to HC, CA1-amygdala FC was significantly lower contralaterally and higher ipsilaterally in CHR-P individuals in both the placebo and diazepam conditions (lower: placeboZ=3.46,PFWE=0.002, diazepamZ=3.33,PFWE=0.003; higher: placeboZ=4.48,PFWE<0.001, diazepamZ=4.22,PFWE<0.001).ConclusionsThis study demonstrates that diazepam can partially restore hippocampal CA1 dysconnectivity in CHR-P individuals, suggesting that modulation of GABAergic function might be useful in the treatment of this clinical group.
Minority populations exhibit distinct clinical and genetic features of celiac disease in the United States
Authors: Karnati Hemanth , Ying Wenjing , Long Xin , Touma Mary-Joe , Smith Ioana , Lewis Suzanne , Xing Chao , Burstein Ezra , Bolze Alexandre , Green Peter HR , Alkalay Michele J. , Kong Xiao-Fei 
Published: December 2024

AbstractCeliac disease (CeD) is a heterogeneous autoimmune disorder influenced by genetic, environmental, and socioeconomic factors. However, little is known about clinical manifestations and genetic risks in minority populations. Using data from theAll of UsResearch Program, we analyzed 3,040 CeD patients, referred to as the AoU-CeD cohort, to identify clinical and genetic differences across racial and ethnic groups in the United States. CeD prevalence was highest among White individuals (1.08%) and significantly lower among Hispanic (0.36%) and Black (0.16%) populations. The majority of CeD patients were female (78.4%) and diagnosed between the ages of 18 and 64. Minority groups reported poorer physical and mental quality of life (QoL) and higher levels of pain. Ancestry-specific patterns emerged in CeD-associated conditions, with minorities more likely to report diarrhea and non-infectious gastroenteritis but less likely to have osteoporosis, hypothyroidism, chronic fatigue, or a family history of CeD. Compared to previously reported data showing that over 90% of CeD patients carry the HLA-DQ2.5 haplotype, genetic analysis revealed that only 49% of patients in the AoU-CeD cohort carried the high-risk HLA-DQ2.5 haplotype. Additionally, 16.5% lacked known HLA-DQ risk haplotypes, suggesting potential diagnostic or reporting inaccuracies. Minority groups exhibited higher rates of atypical symptoms, lower frequencies of the DQ2.5 haplotype, and distinct distributions of HLA-DQ genotypes. A long haplotype block spanning HLA-A1, B8, C7 and HLA-DQ2.5 was found in Europeans but absent in other ancestries. A genome-wide association study (GWAS) using over 11 million variants from whole-genome sequencing data identified 1,651 significant single-nucleotide polymorphisms (SNPs), primarily within the MHC locus, with the strongest signals observed predominantly among individuals of European ancestry. A predictive model incorporating HLA-DQ genotype, family history, and clinical features achieved 83% accuracy for identifying seropositive CeD. These results highlight the importance of ancestry-specific clinical presentations and genetic features in CeD.
Genomic Specificity of Anti-TCR mAbs determined by single-cell RNAseq
Authors: Magill Ian , Piekarsa Val , Kossida Sofia , Croteau Josh , Lee Amy , Balderas Robert , Zemmour David , Benoist Christophe ,   the immgenT Project
Published: December 2024

ABSTRACTT cells play a pivotal role in the immune system, relying on their somatically rearranged T cell receptor (TCR) to recognize peptide-MHC complexes. A comprehensive and extensively used set of monoclonal antibodies (mAbs) against TCR Variable regions was generated in the previous century. The separate identification of mAb-specific TCR-V proteins andTRVgenes has resulted in multiple nomenclatures, making their relationships unclear. To formally re-establish this link and determine patterns of reactivity withinTRVsubfamilies, we sorted T cells positive for any one of a panel of 22 anti-V mAbs and determined theirTRVgenes by single-cell TCRseq. RNAseq data revealed consistently higher expression of repeated elements from the ERV1-family LTR RLTR6Mm (mapping toGm20400) in cells utilizingTRBVsegments encoded within a 66kb genomic region betweenTRBV23andTRBV30. Our findings provide a comprehensive resource for anti-TCR mAb specificity and insight into V-gene usage biases and T cell function.
Characterizing psilocybin as an antidepressant for adolescence in male and female rats
Authors: García-Cabrerizo Rubén , Beruete-Fresnillo Itziar , García-Fuster M. Julia 
Published: December 2024

AbstractAdolescent depression is a significant public health concern, yet treatment options remain limited, particularly due to age- and sex-related differences in antidepressant efficacy. This study explored the rapid and long-lasting antidepressant-like potential of psilocybin in adolescent Sprague-Dawley rats, examining acute and repeated oral dosing effects while incorporating sex as a biological variable. An acute administration of psilocybin produced rapid antidepressant-like effects 30 minutes post-treatment in both male and female rats, demonstrated by reduced immobility and increased escape-related behaviour in the forced swim test. However, repeated daily administrations over 7 days revealed notable sex differences. In males, the antidepressant-like effects were sustained, at least, for up to 15 days post-treatment at both tested doses. In contrast, in females, the effects were dose-dependent and less enduring, persisting only up to 8 days at the highest dose tested. To the best of our knowledge, these results are the first ones to underscore psilocybin’s potential as a fast-acting and long-lasting antidepressant during adolescence, a developmental stage marked by high vulnerability to depression and reduced response to conventional treatments, while also emphasizing the importance of tailoring therapeutic approaches to individual biological factors such as sex.
Creating microbiome-model harmony between metaproteomics data and the ADM1da for a two-step anaerobic digester
Authors: Hellwig Patrick , Seick Ingolf , Meinusch Nicole , Benndorf Dirk , Wiese Jürgen , Reichl Udo , Heyer Robert 
Published: December 2024

AbstractThe effective operation, planning, and optimization of renewable energy production in anaerobic digestion (AD) plants relies on advanced process models, such as the Anaerobic Digestion Model No. 1 (ADM1). This study applies an ADM1-based model (ADM1da) to simulate a two-step digester in an industrial setting. The data demonstrate that 2.6% of the methane is lost as a result of open hydrolysis. Conversely, the incorporation of a hydrolysis fermenter enhances methane production by an average of 2.5%. Although ADM1-like models are widely recognized for accurately representing anaerobic digestion processes, mechanistic insights into the microbiome involved have been limited by the absence of tools to analyze microbial composition and functionality at the time these models were developed.To overcome this limitation, we utilized a metaproteomics approach to assess the abundance and biomass-correlated activity of microbial groups as defined by the model, aiming to bridge the gap between microbial ecology and bioprocess engineering in AD systems. We also developed and evaluated a series of rules for associating particular microbial species with functional groups of the model.Our analysis demonstrates that while the model supports the presence of a stable microbiome composition in the main fermenter, it is difficult to capture the dynamic behavior observed in the hydrolysis fermenter. Furthermore, the actual AD microbiome displays a greater versatility than the model assumes, with microorganisms performing multiple functions rather than being restricted to single roles.In conclusion, this study identifies options for improving AD models and integrating comprehensive biological knowledge to further optimize the performance of anaerobic digesters.HighlightsSimulations revealed 2.6 % methane volume loss attributed to open hydrolysisImplementation of a two-step process increased methane production by 2.5%Identification of rules to map metaproteomics data to ADM1daSimulations of ADM1da depict the dynamic in the main but not in the hydrolysis fermenterMicrobial species perform multiple functions not just one as assumed in the ADM1da
Development and early life stress sensitivity of the rat cortical microstructural similarity network
Authors: Smith Rachel L. , Sawiak Stephen J. , Dorfschmidt Lena , Dutcher Ethan G. , Jones Jolyon A. , Hahn Joel D. , Sporns Olaf , Swanson Larry W. , Taylor Paul A. , Glen Daniel R. , Dalley Jeffrey W. , McMahon Francis J. , Raznahan Armin , Vértes Petra E. , Bullmore Edward T. 
Published: December 2024

ABSTRACTThe rat offers a uniquely valuable animal model in neuroscience, but we currently lack an individual-level understanding of the in vivo rat brain network. Here, leveraging longitudinal measures of cortical magnetization transfer ratio (MTR) from in vivo neuroimaging between postnatal days 20 (weanling) and 290 (mid-adulthood), we design and implement a computational pipeline that captures the network of structural similarity (MIND, morphometric inverse divergence) between each of 53 distinct cortical areas. We first characterized the normative development of the network in a cohort of rats undergoing typical development (N=47), and then contrasted these findings with a cohort exposed to early life stress (ELS, N=40). MIND as a metric of cortical similarity and connectivity was validated by cortical cytoarchitectonics and axonal tract-tracing data. The normative rat MIND network had high between-study reliability and complex topological properties including a rich club. Similarity changed during post-natal and adolescent development, including a phase of fronto-hippocampal convergence, or increasing inter-areal similarity. An inverse process of increasing fronto-hippocampal dissimilarity was seen with post-adult aging. Exposure to ELS in the form of maternal separation appeared to accelerate the normative trajectory of brain development – highlighting embedding of stress in the dynamic rat brain network. Our work provides novel tools for systems-level study of the rat brain that can now be used to understand network-based underpinnings of complex lifespan behaviors and experimental manipulations that this model organism allows.Significance StatementNetwork models derived from neuroimaging have revolutionized our understanding of human brain development but need translation into animal models to interrogate their underlying mechanisms. Rats provide a valuable model due to their complex behaviors and biological similarities to humans; however, in vivo models of individual-level brain networks remain underdeveloped. In this study, we present a novel computational pipeline to construct such networks from in vivo rat structural neuroimaging data. Our findings highlight the dynamic development and experiential sensitivity of fronto-hippocampal systems in rats, offering a reference for cross-species comparisons and mechanistic insights into brain architecture. To support broader research efforts, we include an open release of code and data for rat MIND similarity network analysis.
The farnesyl transferase inhibitor KO-2806 re-sensitizes relapsing tumors to RAS inhibition
Authors: Patel Hetika Vora , Smith Alison Elizabeth , Chan Stacia , Gasendo Jovylyn Gatchalian , Samantaray Tejas , Kessler Linda , Mitra Amitava , Zhu Xuefeng , Liu Yahu A. , Burrows Francis , Malik Shivani 
Published: December 2024

AbstractResistance remains a key issue limiting the clinical benefit from RAS-targeting therapeutic agents and necessitates combination approaches. We identify persistent mTORC1 activity in preclinicalKRAS-mutant NSCLC and CRC models as a frequent, nongenetic driver of inherent and adaptive resistance to RAS inhibition. This vulnerability is targetable with the farnesyl transferase inhibitor KO-2806, which blocks mTORC1 activation via RHEB while sparing mTORC2 and its associated toxicities. The addition of KO-2806 to NSCLC or CRC tumors progressing on mutant-selective RAS inhibitors led to rapid and durable tumor regression. In contrast, switching from mutant-selective to pan-RAS inhibitor monotherapy resulted in only stasis of NSCLC tumors and had no effect on CRC tumor progression. Further, the addition of KO-2806 rescued sensitivity of progressing tumors to the pan-RAS inhibitor RMC-6236. Our results establish mTORC1 as an important mediator of escape from RAS inhibition and highlight KO-2806 as a promising RAS companion inhibitor in patients with prior RAS inhibitor exposure.SignificanceUtilizingin vivomodels of tumor relapse, we define a subset of RAS inhibitor-resistant tumors in which vertical inhibition of MAPK is insufficient to restore sensitivity. By controlling parallel mTORC1 activity, KO-2806 may expand utility of RAS inhibitors in patients that have progressed on RAS-targeted therapy, regardless of inhibitor class.
An epigenetic clock forXenopus tropicalisreveals age-associated sites enriched in H4K20me3-marked heterochromatin
Authors: Bennett Ronan , Morselli Marco , Peshkin Leonid , Pellegrini Matteo 
Published: December 2024

AbstractDNA methylation clocks have been widely used for accurate age prediction, but most studies have been carried out on mammals. Here we present a clock for the aquatic frogXenopus tropicalis, a widely used model organism in developmental biology and genomics. The clock, trained on targeted bisulfite sequencing data, achieved a cross-validation median absolute error of 0.70 years. To construct the clock, we collected DNA methylation data from 192 frogs at genomic regions containing CpG sites previously shown to have age-associated methylation inXenopus. We found that CpG sites with methylation levels significantly increasing or decreasing with age are enriched in heterochromatic regions marked with H4K20me3 and H3K9me3. CpG sites with positively age-associated methylation levels are enriched in bivalent chromatin and gene bodies with H3K36me3, and tend to be proximal to lowly expressed genes. These epigenetic features of aging are similar to those found in mammals, suggesting evolutionary conservation of epigenetic aging mechanisms. Our clock enables future aging biology experiments that leverage the unique properties of amphibians.
Spatiotemporal photocatalytic proximity labeling proteomics reveals ligand-activated extracellular and intracellular EGFR neighborhoods
Authors: Lin Zhi , Ngo Wayne , Chou Yu-Ting , Wu Harry , Susa Katherine J. , Jun Young-wook , Bivona Trever G. , Doudna Jennifer A. , Wells James A. 
Published: December 2024

AbstractPhoto-proximity labeling proteomics (PLP) methods have recently shown that the cell surface receptors can dynamically form lateral interactome networks. Here, we present a paired set of PLP workflows that simultaneously track neighborhood changes for oncogenic epidermal growth factor receptor (EGFR) with temporal resolution, both outside and inside of cells. We achieved this by augmenting the multiscale PLP workflow we call MultiMap, where three photo-probes with different labeling ranges were photo-activated by one photocatalyst, Eosin Y. By anchoring Eosin Y extracellularly and intracellularly on EGFR, we captured hundreds of proteins on both sides of the cell membrane that change in proximity to EGFR upon EGF activation. Neighbors engaged with EGFR within minutes to over an hour, reflecting dynamic interactomes during early, mid- and late-signaling including phosphorylation, internalization, degradation and transcriptional regulation. This rapid “photographic” labeling approach provides snapshots of signaling neighborhoods, revealing their dynamic nature, and potential for drug targeting.
Machine Learning Approaches to Predict Alcohol Consumption from Biomarkers in the UK Biobank
Authors: Hassan Mohammed F. , Gentry Amanda Elswick , Prom-Wormley Elizabeth C. , Peterson Roseann E. , Webb Bradley T. 
Published: December 2024

AbstractBackgroundMeasuring and estimating alcohol consumption (AC) is important for individual health, public health, and Societal benefits. While self-report and diagnostic interviews are commonly used, incorporating biological-based indices can offer a complementary approach.MethodsWe evaluate machine learning (ML) based predictions of AC using blood and urine-derived biomarkers. This research has been conducted using the UK Biobank (UKB) Resource. In addition to the prediction of the number of alcoholic Drinks Per Week (DPW), four other related phenotypes were predicted for performance comparison. Five ML models were assessed including LASSO, Ridge regression, Gradient Boosting Machines (GBM), Model Boosting (MBOOST), and Extreme Gradient Boosting (XGBOOST).ResultsAll five ML methods achieved moderate prediction of DPW (r2=0.304-0.356) with biomarkers significantly increasing prediction above using only known covariates and liver enzymes (r2=0.105). XGBOOST achieved the best prediction performance (r2=0.356, MAE=5.214) at the expense of increasing model complexity and training resources compared to other ML methods. All ML models were able to accurately predict if subjects were heavy drinkers (DPW>8 for women and DPW>15 for men) and produced explainable models that highlighted the role of biomarkers in predicting DPW. While phenotype correlations were similar across methods, XGBOOST produced similar heritability estimates for observed (h2=0.064) and predicted (h2=0.077) DPW. The estimated genetic correlation between observed and predicted DPW was 0.877.ConclusionsPredicting AC from ML-based biological measures provides an opportunity to identify individuals at increased risk of heavy AC, thereby offering complementary avenue for risk assessment beyond self-report, screening instruments, or structured interviews, which have some known biases. In addition, explainable AI tools identified a constellation of biomarkers associated with AC.