bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokinesis-dependent twisting of HMR-1/Cadherin regulates the first left-right symmetry-breaking event inCaenorhabditis elegans
Authors: Khor Mi Jing , Sangha Gaganpreet , Sugioka Kenji 
Published: December 2024

SummaryDiverse mechanisms for establishing cellular- and organismal-level left-right (L-R) asymmetry emerged during the evolution of bilateral animals, including cilia-based and actomyosin-dependent mechanisms. In pond snails andCaenorhabditis elegans, cell division plays a critical role in regulating both levels of L-R asymmetries. However, the precise mechanism by which cell division breaks cellular-level L-R symmetry remains elusive. Here, we show that cytokinesis-induced cortical flow twists the cell-cell adhesion pattern, which in turn controls the L-R asymmetrical constriction of the contractile ring, thereby breaking the first L-R body symmetry inC. elegans. During the second mitosis ofC. elegansembryos, we discovered the twisting of the HMR-1/cadherin patch at the cell-cell contact site. The HMR-1 patch twisting occurs within a few minutes upon cytokinesis onset, with individual cadherin foci within the patch exhibits directional flow and coalescence. This cell type exhibits chiral cortical flow, characterized by counter-rotational surface flows in the two halves of the dividing cell. We found that this chiral cortical flow plays a critical role in regulating HMR-1 patch twisting by inducing cadherin flow. As the HMR-1 patch twists, the contractile ring preferentially associates with HMR-1 on the right side of the embryo. We demonstrate that HMR-1 patch twisting regulates the L-R asymmetric ring closure. This study uncovers an interplay between three fundamental cellular processes—cell-cell adhesion, cytokinesis, and cell polarity— mediated by cadherin flow, shedding light on cadherin flow’s role in cellular patterning during development.
Men with long-term conditions in the Game of Stones text messaging and financial incentives trial: an exploratory mixed methods study
Authors: Macaulay Lisa , O’Dolan Catriona , Swingler James , Torrens Claire , MacLean Alice , Turner Katrina , Avenell Alison , Cotton Seonaidh , Dombrowski Stephan U , Gray Cindy M , Hunt Kate , Kee Frank , McKinley Michelle C , MacLennan Graeme , Hoddinott Pat 
Published: December 2024

AbstractMen living with multiple long-term conditions and obesity are under-represented in behavioural weight management trials. Within an effective text messaging and financial incentives trial, our aim was to explore retention, secondary mental health and wellbeing outcomes, and experiences of men with multiple long-term conditions.MethodsMixed methods process evaluation within a 3-group randomised controlled trial: behavioural text messages with financial incentives, texts alone and waiting-list control, for 583 of 585 men with obesity. Trial retention, mental health and wellbeing outcomes, and experiences were compared for 235 (40%) participants with multiple long-term conditions, 181 (31%) with single conditions, 167 (29%) with no conditions, and for 165 (29%) with disability. Semi-structured interviews, analysed using the Framework method, explored experiences with weight trajectories. Concurrent descriptive and qualitative analyses were undertaken.ResultsOf the 235 (40%) trial participants with multiple long-term conditions, 99 were disabled and 93 were living in deprived areas. Participants with multiple long-term conditions and/or disability were older, fewer had a degree level qualification, and fewer were in full time work. Retention at 12 months was higher for men with disability (76%) or no long-term conditions (75%), and lower for men with diabetes (65%). Self-reported weight stigma, wellbeing and quality of life scores improved or stayed the same for men living with multiple long-term conditions in the intervention groups, however, results for anxiety and depression screening scores were inconsistent. Participant experiences indicated complex dynamic health, social and life situations which could provide motivation to lose weight for some but not others. Hospitalisation and poor mobility, with inability to exercise, was de-motivating for making changes to reach weight loss targets.ConclusionMen with multiple long-term conditions varied from very successful weight loss and improved health, to not prioritising or feeling helped by the programme or disengagement due to immobility or diabetes.
‘It would nearly put the life back into you’ Older adults’ experiences of a Community Specialist Team for Older People (CSTOP) service model in Ireland: A Qualitative Descriptive Study
Authors: Condon Brian , Griffin Anne , Delvin Collette , Fitzgerald Christine , Shanahan Elaine , Glynn Liam , Couturier Yves , O’Connor Margaret , Hayes Christina , Manning Molly , Galvin Rose , Leahy Aoife , Robinson Katie 
Published: December 2024

AbstractIntroductionIn Ireland, there has been a substantial recent investment in the Community Specialist Team for Older People (CST OP) service model. This approach provides timely integrated assessment and intervention for older adults in the community by a specialist multidisciplinary team. To inform the ongoing development and refinement of the CST OP service model, and ensure it is responsive to the needs and preferences of older adults, it is important to understand how older adults experience this new model of care. This qualitative descriptive study aims to resolve a research gap by exploring older adults’ experiences of the CST OP service model.MethodsA qualitative descriptive study design was employed to explore older adults’ experiences of the CST OP service model. Purposive non-probability sampling was used to recruit 13 older adults who had completed intervention with a CST OP intervention. All interviews were completed in participants own homes, audio recorded and transcribed verbatim. A reflexive approach to thematic analysis guided data analysis.FindingsThree themes were identified; older adults were uncertain about what to expect from the CST OP service and encountered accessibility barriers (theme1); the CST OP team provided coordinated, comprehensive care and built strong relationships with older adults (theme 2); CST OP intervention enabled older adults to better manage everyday activities and long-term conditions, thereby improving their wellbeing (theme 3).Discussion/ conclusionOur findings highlight the importance of CGA in community-based care for older adults. Further research is needed to address access barriers and evaluate older adults’ experiences with case management and care coordination in the CST OP service model.
Nitrogen response and growth trajectory of sorghum CRISPR-Cas9 mutants using high-throughput phenotyping
Authors: Jin Hongyu , Park Alexa , Sreedasyam Avinash , Li Guangyong , Ge Yufeng , Swaminathan Kankshita , Schmutz Jeremy , Clemente Thomas E. , Schnable James C. , Yang Jinliang 
Published: December 2024

ABSTRACTInorganic nitrogen (N) fertilizer has emerged as one of the key factors driving increased crop yields in the past several decades; however, the overuse of chemical N fertilizer has led to severe ecological and environmental burdens. Understanding how crops respond to N fertilizer has become a central topic in plant science and plant genetics, with the ultimate goal of enhancing N use efficiency (NUE) in crop production. As one of the most essential macronutrients, N significantly influences crop performance across different developmental stages of plant, phenotypic traits result from the accumulative effects of genetic factors, prevailing environmental conditions (specifically N availability), and their complex interactions. To characterize the targeting N-responsiveness and growth trajectory, we employed CRISPR-Cas9 technique to generate sorghum mutants using CRISPR technology. Using a LemnaTec plant imaging system, we obtained time series imagery data from 29 to 130 days after sowing (DAS) for these CRISPR-edited mutants under high N and low N greenhouse conditions. After imagery data analysis, we extracted a number of morphological and greenness index traits as a proxy of plant growth and N responses. Subsequently, we employed two different methods to model the temporal N-responsive traits, allowing us to estimate seven key parameters from the growth curve. Our findings revealed that the wildtype and the edited sorghum lines exhibited differences in N responses for several of the key growth-related parameters. The high-throughput N phenotyping pipeline paves the way for a better understanding of the N responses of edited lines in a dynamic manner and sheds light on further improvements in crop NUE.
Emergence ofCandida aurisin Minas Gerais, Brazil: Genomic Surveillance to inform Rapid Public Health Responses
Authors: Tomé Luiz Marcelo Ribeiro , Camargo Dhian Renato Almeida , Bastos Rafael Wesley , dos Santos Sara Cândida Ferreira , Guimarães Natália Rocha , Pedroso Sílvia Helena Sousa Pietra , de Souza da Silva Paulo Eduardo , Góes-Neto Aristóteles , de Assis Figueredo Lida Jouca , da Côrte Castro Gabriella , Rodrigues Ana Maria Ribeiro Nunes , Cruzeiro Flavia Ribeiro Soares , Dutra Nádia Aparecida Campos , Moura Josiane Barbosa Piedade , de Carvalho Pereira Glauco , Faria Carmem Dolores , Giovanetti Marta , de Melo Iani Felipe Campos , Alcantara Luiz Carlos Júnior , Adelino Talita Émile Ribeiro 
Published: December 2024

AbstractCandida aurisposes a significant global health threat due to its multidrug-resistance and outbreak potential. In this study, we report its emergence in Minas Gerais, Brazil, supported by genomic surveillance that identified Clade-IV isolates, suggested a potential introduction from Colombia, and detected a missense mutation associated with azole resistance.
Global lymphatic filariasis post-validation surveillance activities in 2024: A systematic review protocol
Authors: Jian Holly , Lawford Harriet , McLure Angus , Lau Colleen , Craig Adam 
Published: December 2024

AbstractIntroductionLymphatic filariasis (LF) is a neglected tropical disease caused by infection with parasitic worms, spread by mosquitoes. In countries where LF is validated as eliminated as a public health problem by the World Health Organization (WHO), post-validation surveillance (PVS) is required to ensure recrudescence has not occurred and verify the sustained elimination of transmission. However, it is unclear what PVS strategies should be applied, how PVS strategies should be tailored to meet country capacity and need, and whether currently used approaches align with upcoming WHO guidelines.ObjectivesThis study will aim to review available evidence on PVS implementation in countries previously endemic for LF; examine barriers and facilitators to PVS implementation; critique alignment in PVS activities with international guidelines; and identify knowledge gaps in PVS implementation that may be addressed through further research.MethodsWe will search four databases (PubMed, Scopus, Embase and Web of Science) for peer-reviewed literature and the WHO Institutional Repository for Information Sharing (IRIS) database for grey literature. Documents published between January 1, 2007 and November 5, 2024 will be included. Two reviewers will independently screen studies based on a priori inclusion and exclusion criteria. The quality of included studies will be assessed using the Joanna Briggs Institute Critical Appraisal Checklist, and deductive content analysis will be conducted to synthesise data. The study will also examine alignment with upcoming WHO PVS guidelines.ConclusionThis review will systematically collate and analyse available literature on PVS of LF, which, to our knowledge, has not yet been conducted. Our study will synthesise knowledge in this field and provide an evidence base which may be used to guide the design of future PVS strategies.This protocol has been registered in PROSPERO (registration ID:CRD42024618436).
Sepsis induces long-term reprogramming of human HSPCs and drives myeloid dysregulation in sepsis survivors
Authors: De Zuani Marco , Lázničková Petra , Hortová Kohoutková Marcela , Bosáková Veronika , Andrejčinová Ivana , Vadovičová Natália , Tomášková Veronika , Mýtniková Alexandra , Štíchová Julie , Tomáš Tomáš , Hrdý Jiří , Boráková Kristýna , Uldrijan Stjepan , Vlková Marcela , Šrámek Vladimír , Helán Martin , Bendíčková Kamila , Frič Jan 
Published: December 2024

ABSTRACTSepsis is a life-threatening condition characterised by an overwhelming immune response and high fatality. While most research has focused on its acute phase, many sepsis survivors remain immunologically weakened leaving them susceptible to serious complications from even mild infections. The mechanisms underlying this prolonged immune dysregulation remain unclear, limiting effective interventions. Here, we analysed whether sepsis induced long-term “training” in hematopoietic stem and progenitor cells (HSPCs), imprinting changes that persist in their myeloid progeny. Peripheral blood analysis of 8 sepsis survivors, 12 patients with septic shock, and 10 healthy donors revealed a significant expansion of CD38+ progenitors in survivors, with increases in megakaryocyte-erythroid and granulocyte-monocyte progenitors, and reduced mature neutrophil counts. This shift suggests impaired granulopoiesis, favouring immature, immunosuppressive granulocytes. Differentiated macrophages from survivors’ HSPCs exhibited impaired metabolic pathways after lipopolysaccharide stimulation, with downregulation of tricarboxylic acid cycle and glycolysis genes, indicating altered immune metabolism. Pathway analysis revealed enhanced type-I interferon (IFN) and JAK-STAT signalling in survivors’ macrophages, reflective of potentially tolerance-prone reprogramming. Finally, exposing healthy donor HSPCs to IFNβ during macrophage differentiation reduced HSPC proliferation, increased apoptosis, and induced a metabolic shift towards glycolysis over mitochondrial respiration. Together, these findings suggest that sepsis induces lasting reprogramming in HSPCs leading to myeloid progeny with altered immune memory that might drive immune dysregulation in survivors. These data open avenues to explore potential targets to better manage long-term immune alterations in sepsis survivors.KEY POINTSSepsis induces long-term alterations in HSPCs, leading to the expansion of immature progenitors and metabolic dysregulation of their progeny.Type-I IFN signalling reprograms macrophage differentiation, affecting their metabolic function and reducing cell proliferation.
Controlled by disorder: phosphorylation modulates SRSF1 domain availability for spliceosome maturation
Authors: Fargason Talia , Powell Erin , De Silva Naiduwadura Ivon Upekala , Paul Trenton , Prevelige Peter , Zhang Jun 
Published: December 2024

ABSTRACTSerine/arginine-rich splicing factor 1 (SRSF1) is key in the mRNA lifecycle including transcription, splicing, nonsense-mediated decay, and nuclear export. Consequently, its dysfunction is linked to cancers, viral evasion, and developmental disorders. The functionality of SRSF1 relies on its interactions with other proteins and RNA molecules. These processes are regulated by phosphorylation of its unstructured arginine/serine-rich tail (RS). Here, we characterize how phosphorylation affects SRSF1’s protein and RNA interaction and phase separation. Using NMR paramagnetic relaxation enhancement and chemical shift perturbation, we find that when unphosphorylated, SRSF1’s RS interacts with its first RNA-recognition motif (RRM1). Phosphorylation of RS decreases its interactions with RRM1 and increases its interactions with the RNA-binding site. This change in SRSF1’s intramolecular interactions increases the availability of protein-interacting sites on RRM1 and weakens RNA binding of SRSF1. Phosphorylation alters the phase separation of SRSF1 by diminishing the role of arginine in intermolecular interactions. These findings provide an unprecedented view of how SRSF1 influences the early-stage spliceosome assembly.SUMMARYPhosphorylation of SRSF1 is pivotal in pre-mRNA processing and is dysregulated in various pathologies. Modeling of SRSF1 based on NMR restraints reveals phosphorylation alters the accessibility of protein-protein and protein-RNA interaction sites on SRSF1’s RRM1 domain, altering its binding preferences
Modeling Bias Toward Binding Sites in PDB Structural Models
Authors: Wankowicz Stephanie A. 
Published: December 2024

AbstractThe protein data bank (PDB) is one of the richest databases in biology. The structural models deposited have provided insights into protein folds, relationships to evolution, energy functions of structures, and most recently, protein structure prediction, connecting sequence to structure. However, the X-ray crystallography (and cryo-EM) models deposited in the PDB are determined by a combination of refinement algorithms and manual modeling. The intervention of human modeling leads to the possibility that within a single structure, there can be differences in how well parts of a structure are modeled and/or fit the underlying experimental data. We identified that small molecule binding sites are more carefully modeled and better match the underlying experimental data than the rest of the protein structural model. This trend persisted irrespective of the structure’s resolution or its overall agreement with the experimental data. The variation of modeling has implications for how we interpret protein structural models and use structural models in explaining mechanisms, structural bioinformatics, simulations, docking, and structure prediction, especially when drawing conclusions about binding sites compared to the rest of the protein.
Effects of a Water, Sanitation, and Hygiene Program on Diarrhea and Child Growth in the Democratic Republic of the Congo: A Cluster-Randomized Controlled Trial of the Preventative-Intervention-for-Cholera-for-7-Days (PICHA7) Program
Authors: George Christine Marie , Sanvura Presence , Bisimwa Jean-Claude , Endres Kelly , Namunesha Alves , Felicien Willy , Banywesize Blessing Muderhwa , Williams Camille , Perin Jamie , Sack David A , Boroto Raissa , Nsimire Gisèle , Rugusha Feza , Endeleya Freddy , Kitumaini Pacifique , Lunyelunye Claude , Buhendwa Emmanuel , Bujiriri Pascal Kitumaini , Tumusifu Jessy , Munyerenkana Brigitte , Caulfield Laura E. , Bengehya Justin , Maheshe Ghislain , Cikomola Cirhuza , Mwishingo Alain , Bisimwa Lucien 
Published: December 2024

AbstractBackgroundWe assessed whether the Preventative-Intervention-for-Cholera-for-7-Days (PICHA7) program reduced diarrhea and improved child growth in the Democratic Republic of the Congo (DRC).MethodsThe PICHA7 cluster-randomized controlled trial enrolled diarrhea patient households in urban Bukavu, DRC. Households were randomized into two arms: single in-person visit for the DRC government’s diarrhea patient standard message on oral rehydration solution use and a basic WASH message (standard arm); or this standard message and the PICHA7 program with quarterly in-person visits and weekly voice and text mobile health messages (mHealth) (PICHA7 arm). The primary outcome was diarrhea in the past two weeks assessed monthly for 12 months. Secondary outcomes were diarrhea with rice water stool, healthcare facility visits for diarrhea, stunting, underweight, and wasting over 12 months. Generalized estimating equations were used for regression models to account for clustering at the individual and household level.ResultsBetween December 2021 and December 2022, 2334 participants in 359 households were randomly allocated to two arms: 1138 standard arm and 1196 PICHA7 arm. Diarrhea prevalence during the 12 month surveillance period was significantly lower among PICHA7 arm participants (Prevalence Ratio: 0.39 (95% Confidence Interval (CI): 0.32, 0.48). PICHA7 arm participants had lower odds of diarrhea with rice water stool (Odds Ratio (OR): 0.48 (95% CI: 0.27, 0.86)), and lower odds of visiting a healthcare facility for diarrhea during the 12 month surveillance period (OR: 0.44 (95% CI: 0.25, 0.77)). PICHA7 arm children 0-4 were significantly less likely to be stunted (52% vs. 63% standard arm) (OR: 0.65 (95% CI: 0.43, 0.98)) at the 12 month follow-up. All WASH components had high adherence.ConclusionThe PICHA7 program which combines mHealth with quarterly in-person visits lowered diarrhea prevalence and stunting in the DRC.Clinical Trials RegistrationNCT05166850.Key PointsThe PICHA7 program combines mHealth with in-person visits and was assessed with a randomized controlled trial. Compared to the standard arm, the PICHA7 program lowered diarrhea prevalence for all ages and reduced stunting in children 0-4 years in the DRC.
Early brain changes in Lyme disease are associated with clinical outcomes
Authors: Marvel Cherie L. , Rebman Alison W. , Alm Kylie H. , Touradji Pegah , Bakker Arnold , Nadkarni Prianca A. , Bhattacharya Deeya , Morgan Owen P. , Mistri Amy , Sandino Christopher C. , Ecker Jonathan A. , Kozero Erica A. , Venkatesan Arun , Moghekar Abhay , Keeys Ashar A. , Aucott John N. 
Published: December 2024

AbstractBackground and ObjectivesIn Lyme disease (LD), 10-20% of patients develop persistent symptoms following antibiotic treatment (i.e., post-treatment Lyme disease (PTLD)), which often includes neurological symptoms. Little is known about how the brain is affected by LD. This study tested the hypothesis that brain changes occur early in LD and influence clinical outcomes.MethodsIn this case-control study, a working memory task was administered during functional MRI (fMRI), in conjunction with cognitive assessments and health surveys, in people with acute LD after antibiotic treatment [i.e., “baseline”] and six months later. A healthy control (HC) group was also assessed six months apart. The LD group was retrospectively categorized into those who returned to health (RTH) and those who reported persistent symptoms (sPTLD). FMRI data from both LD subgroups were compared to the HC group at both time points. Brain regions of interest (ROI) values were obtained from the fMRI results and correlated to cognitive performance and health survey scores.ResultsThere were no differences in demographic characteristics [n, % male, mean age (range), mean days after end of initial antibiotic treatment (range)] among RTH [11, 45%, 56.5 (28.4- 78.2), 16.9 (-1.0-51.0)], sPTLD (9, 67%, 47.1 (26.2-66.6), 13.0 (6.0-20.0), and HC [19, 32%, 46.5 (19.4-59.9)]. Baseline brain activity in RTH increased relative to sPTLD and HC, p <.0025 and p <.001, respectively. Notably, 64% of the RTH group’s activation clusters were in white matter, confirmed by segmentation analysis. ROIs created from the RTH vs. HC fMRI results, including white matter regions, correlated with higher (better) health survey scores. At the 6-month follow-up, most of the RTH group’s activity had normalized compared to HC. The sPTLD group showed few fMRI activation differences versus the HC group at either time point, and no significant associations were observed between ROI values and health survey scores.DiscussionIncreased brain activity in early LD was associated with better health survey scores and RTH status six months later. The absence of such brain changes was associated with persistent symptoms. Understanding how increased brain activity contributes to RTH in LD will aid early identification of those most vulnerable to developing PTLD and guide treatment intervention.