bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity, connectivity and negative interactions define robust microbiome networks across land, stream, and sea
Authors: Kajihara Kacie T. , Yuan Mengting , Amend Anthony S. , Cetraro Nicolas , Darcy John L. , Fraiola Kauaoa M.S. , Frank Kiana , McFall-Ngai Margaret , Medeiros Matthew C.I. , Nakayama Kirsten K. , Nelson Craig E. , Rollins Randi L. , Sparagon Wesley J. , Swift Sean O. I. , Téfit Mélisandre A. , Yew Joanne Y. , Yogi Danyel , Hynson Nicole A. 
Published: January 2025

AbstractIn this era of rapid global change, factors influencing the stability of ecosystems and their functions have come into the spotlight. For decades the relationship between stability and complexity has been investigated in modeled and empirical systems, yet results remain largely context dependent. To overcome this we leverage a multiscale inventory of fungi and bacteria ranging from single sites along an environmental gradient, to habitats inclusive of land, sea and stream, to an entire watershed. We use networks to assess the relationship between microbiome complexity and robustness and identify fundamental principles of stability. We demonstrate that while some facets of complexity are positively associated with robustness, others are not. Beyond positive biodiversityxrobustness relationships we find that the number of “gatekeeper” species or those that are highly connected and central within their networks, and the proportion of predicted negative interactions are universal indicators of robust microbiomes. With the potential promise of microbiome engineering to address global challenges ranging from human to ecosystem health we identify properties of microbiomes for future experimental studies that may enhance their stability. We emphasize that features beyond biodiversity and additional characteristics beyond stability such as adaptability should be considered in these efforts.
Biased sampling confounds machine learning prediction of antimicrobial resistance
Authors: Yu Yanying , Wheeler Nicole E , Barquist Lars 
Published: January 2025

AbstractAntimicrobial resistance (AMR) poses a growing threat to human health. Increasingly, genome sequencing is being applied for the surveillance of bacterial pathogens, producing a wealth of data to train machine learning (ML) applications to predict AMR and identify resistance determinants. However, bacterial populations are highly structured and sampling is biased towards human disease isolates, meaning samples and derived features are not independent. This is rarely considered in applications of ML to AMR. Here, we demonstrate the confounding effects of sample structure by analyzing over 24,000 whole genome sequences and AMR phenotypes from five diverse pathogens, using pathological training data where resistance is confounded with phylogeny. We show resulting ML models perform poorly, and increasing the training sample size fails to rescue performance. A comprehensive analysis of 6,740 models identifies species- and drug-specific effects on model accuracy. We provide concrete recommendations for evaluating future ML approaches to AMR.
Nonlinear effects of temperature on mosquito parasite infection across a large geographic climate gradient
Authors: Farner Johannah E. , Lyberger Kelsey P. , Couper Lisa I. , Cruz-Loya Mauricio , Mordecai Erin A. 
Published: January 2025

AbstractTemperature drives ectothermic host – parasite interactions, making them particularly sensitive to climatic variation and change. To isolate the role of temperature, lab-based studies are increasingly used to assess and forecast disease risk under current and future climate conditions. However, in the field, the effects of temperature on parasitism may be mediated by other sources of variation, including local adaptation. To address the key knowledge gaps of how temperature influences host – parasite interactions and whether thermal responses measured in controlled experiments capture infection across temperature gradients in nature, we paired an extensive field survey of parasitism—by the ciliateLambornella clarkion its tree hole mosquito host,Aedes sierrensis—with laboratory experiments describing parasitism thermal performance curves (TPCs) for six host populations from varying climates. We also investigated the mechanisms underlying the thermal biology of the host – parasite interaction by separately measuring TPCs for infection, host immunity, and parasite growth rates. Along the west coast of North America, across an 1100 km climate gradient spanning 12°C mean rainy season temperature variation, we found that parasitism peaked at intermediately cold temperatures, and was consistent both between field seasons and with the lab experiment results. The experiments produced no evidence of host intraspecific variation in temperature sensitivity to parasitism. Importantly, parasitism peaked at temperatures below the thermal optimum for free-livingL. clarkidue to the balance of temperature effects on parasite growth and reproduction against the strength of the host melanization immune response. The results suggest that nonlinear responses to temperature drive parasitism in nature, and that simple lab and field studies can accurately capture the thermal biology of multilayered host – parasite interactions.Data and code for this submission are provided on Dryad:http://datadryad.org/stash/share/CfZkk4LsJzljetJJnFZMDMrjuciTXMxrkrc95I2J3tA.
sCCIgen: A high-fidelity spatially resolved transcriptomics data simulator for cell-cell interaction studies
Authors: Song Xiaoyu , Chavez-Fuentes Joselyn C. , Ma Weiping , Fu Weijia , Wang Pei , Yuan Guo-Cheng 
Published: January 2025

AbstractSpatially resolved transcriptomics (SRT) provides an invaluable avenue for examining cell-cell interactions within native tissue environments. The development and evaluation of analytical tools for SRT data necessitate tools for generating synthetic datasets with known ground truth of cell-cell interaction induced features. To address this gap, we introduce sCCIgen, a novel real-data-based simulator tailored to generate high-fidelity SRT data with a focus on cell-cell interactions. sCCIgen preserves transcriptomic and spatial characteristics in SRT data, while comprehensively models various cell-cell interaction features, including cell colocalization, spatial dependence among gene expressions, and gene-gene interactions between nearby cells. We implemented sCCIgen as an interactive, easy-to-use, realistic, reproducible, and well-documented tool for studying cellular interactions and spatial biology.
Compensation of Hyperexcitability with Simulation-Based Inference
Authors: Müller-Komorowska Daniel , Fukai Tomoki 
Published: January 2025

AbstractThe activity of healthy neuronal networks is tightly regulated, and a shift towards hyperexcitability can cause various problems, such as epilepsies, memory deficits, and motor disorders. Numerous cellular, synaptic, and intrinsic mechanisms of hyperexcitability and compensatory mechanisms to restore healthy activity have been proposed. However, quantifying multiple compensatory mechanisms and their dependence on specific pathophysiological mechanisms has proven challenging, even in computational models. We use simulation-based inference to quantify the interactions of compensatory mechanisms in a spiking neuronal network model. Various parameters of the model can compensate for changes in other parameters to maintain baseline activity, and we rank them by their compensatory potential. Furthermore, specific causes of hyperexcitability - interneuron loss, excitatory recurrent synapses, and principal cell depolarization - have distinct compensatory mechanisms that can restore normal excitability. Our results show that spiking neuronal network simulators could provide the quantitative foundation for targeting pathophysiological network mechanisms with precise interventions.
Variants inNR6A1as a cause for congenital renal, vertebral and uterine anomalies
Authors: Jacquinet Adeline , Flasse Lydie , Dohet Manon , Vanhaeren Romane , Pendeville Hélène , Saunders Carol , Lehman Anna , Pienkowski Catherine , Morcel Karine , Guerrier Daniel , Bours Vincent , Peers Bernard 
Published: January 2025

ABSTRACTThe underlying cause for renal and uterine agenesis remains unknown in many cases, whereas recurrence in some families strongly suggests the involvement of genetic factors. Here, we identify 5 affected individuals from 3 families with phenotypes including bilateral or unilateral renal agenesis/hypoplasia, along with variable congenital uterine anomalies and costovertebral defects associated with heterozygous deleterious variants inNR6A1. The variant spectrum includes both inherited missense as well asde novoloss of function, with the latter associated with a perinatal lethal phenotype characterized by bilateral renal agenesis.In vitrostudies demonstrated partial loss-of-function for both missense variants. To investigate the role ofNR6A1in development, CRISPR-Cas9 knockout zebrafish models targeting the orthologuesnr6a1aandnr6a1bwere generated. Mutants recapitulate the human phenotype, exhibiting impaired kidney development, including pronephros segmentation defects and adult kidney hypoplasia, along with axial skeletal abnormalities, cloacal anomalies, and disrupted anteroposterior expression of posterior hox genes. This study provides strong evidence linkingNR6A1heterozygous loss-of-function variants to renal, uterine and costovertebral defects in humans.
Non communicable diseases and resistant tuberculosis, a growing burden among people living with HIV in Eastern Kenya
Authors: Muriuki Patrick Kiogora , Ngayo Musa Otieno , Njire Moses , Mungiria Juster , Nyanya Winnie , Owuor Daniel , Ndung’u Perpetual 
Published: January 2025

AbstractHuman Immunodeficiency Virus (HIV) and tuberculosis (TB) still poses a significant health burden in Kenya. Countries with the highest burden of people living with HIV (PLWH) have a substantial burden of non-communicable diseases (NCDs) including type 2 diabetes (T2D) and hypertension (HPT). This study evaluated the burden and predictors of T2D, HPT and TB including resistant strains among PLWH receiving antiretroviral therapy (ART) in Eastern Kenya. Blood and sputum samples were obtained from 280 consenting PLWH and a detailed sociodemographic questionnaire was administered. TB and rifampicin resistance was determined by Cepheid’s GeneXpert system while Glycated hemoglobin (HbA1c) was determined using SD A1cCare™ analyzer. Blood pressure (BP) measurements with systolic BP readings of≥140 mmHg and/or diastolic BP≥90 mmHg was considered hypertensive. The participants CD4 cell counts, plasma HIV-1 RNA, full blood cells and blood chemistry were also measured. The patients mean (SD) age was 35.6 (±9.8) years, with 169 (82.4%) being on the first line ART regimen and a median (IQR) duration living with of 7 (4 to 8) years. The majority of the patients 179 (63.9%) were HIV mono-infected. The dual coinfections reported included; 58 (20.7%) HIV/TB, 42 (15%) HIV/ T2D, 33 (11.8%) HIV/HPT. Triple coinfections included; 18 (6.4%) HIV/T2D/HPT, 9(3.2%) HIV/TB/T2D, 9 (3.2%) HIV/TB/HPT with quadruple coinfection of HIV/TB /T2 /HPT among 4 (1.4%) patients. Six 6 (2.1%) HIV patients were coinfected with multidrug resistant TB. In the multivariable model, being on ARV only (aOR 0.5; 95% CI 0.4 – 0.6, p = 0.0001) and virological suppression (aOR 0.8; 95% CI 0.6 – 0.9, p = 0.017) were protective to HIV/TB coinfection. Previously hospital admission (aOR 1.2; 95% CI 1.1 – 1.4, p = 0.049) and previous TB infection (aOR 1.6; 95%CI 1.0 – 3.0, p = 0.034) were associated with HIV/TB coinfection. This study shows that Eastern Kenya is experiencing a syndemic of NCDs and TB including resistant strains among PLWH denoting the need to integrate the management of NCDs among HIV and TB treatment programs in Kenya.
DNA Methylation Differences Stratified by Normalized Fetal/Placental Weight Ratios Suggest Neurodevelopmental Deficits in Neonates with Congenital Heart Disease
Authors: Jacobwitz Marin , Xie Michael , Catalano Jamie , Helbig Ingo , Gaynor J. William , Burnham Nancy , Linn Rebecca L. , Gebb Juliana , Russell Mark W. , Chaiyachati Barbara H. , Cristancho Ana G. 
Published: January 2025

AbstractBackgroundWe lack early biomarkers for predicting neurodevelopment (ND) outcomes in children with congenital heart disease (CHD). Placentas of fetuses with CHD have abnormalities, including unbalanced fetal/placental weight ratios (F/P). Although DNA methylation profiles have revealed insights into the maternal-fetal environment (MFE), it is unknown if DNA methylation correlates to normalized F/P weight ratio groups and how these differences relate to ND outcomes.MethodsWe prospectively recruited a cohort of pregnant women carrying a fetus with CHD. A subset of the cohort had DNA methylation performed on either umbilical cord blood or postnatal blood (45 full-term neonates). We calculated normalized F/P weight ratios, focusing on three normalized F/P ratio groups for analysis. We calculated differential methylation signals in eight ND disabilities-associated gene sets. Normalized F/P ratios were compared to 18-month Bayley Scales of Infant Development-III scores (BSID-III).ResultsUnbiased gene ontology enrichment analysis of differentially methylated regions revealed enrichment for brain development-related pathways. Although there were no significant differences between normalized F/P weight ratio groups and BSID-III, disease-associated gene set pathway analysis revealed significant methylation differences between the most severely unbalanced F/P weight ratio and normal F/P weight ratio groups.ConclusionGene ontology enrichment analysis of differential methylation regions revealed significant differences between normalized F/P weight ratio groups in neurogenesis genes. Furthermore, our data identified methylation differences between unbalanced and balanced normalized F/P weight ratio groups in gene pathways associated with ND dysfunction common in the aging CHD population suggesting converging pathways for ND disorders that should be investigated further.
Unique transcriptional profiles of adult human immature neurons in healthy aging, Alzheimer’s disease, and cognitive resilience
Authors: Tosoni G , Ayyildiz D , Penning A , Snoeck S , Santiago-Mujika E , Ruiz Ormaechea O , Lee H , Poovathingal SM , Davie K , Bryois J , Macnair W , Anink J , De Vries LE , Verhaagen J , Aronica E , Thuret S , Basak O , Roybon L , Fitzsimons CP , Lucassen PJ , Salta E 
Published: January 2025

AbstractThe existence and functional significance of immature neurons in the adult human brain, particularly in the context of neurodegenerative disorders, remain controversial. While rodent studies have highlighted active roles for adult-born immature neurons in the hippocampus under both healthy conditions and in Alzheimer’s disease (AD), evidence from the human brain is limited and lacks detailed molecular characterization. To address this gap, we performed single-nucleus RNA sequencing in aged healthy, AD and dementia-resilient human hippocampus to probe immature neuronal signatures and gene expression alterations associated with AD pathology and resilience. Employing a novel experimental and computational pipeline, we identified persistent populations of immature neurons across all donor groups, with transcriptional profiles distinct from both fetal counterparts and adult mature hippocampal neurons. These profiles were associated with ‘juvenile’ cellular functions, suggesting that the presence of these immature neuronal populationsper semay actively contribute to maintaining homeostasis within the aged human hippocampus, a role that may be disrupted in AD. In the resilient brain, immature neurons were involved in transcriptional programs and intercellular interactions associated with anti-inflammatory, neurotrophic, neuroprotective, myelinating, anti-apoptotic and anti-amyloidogenic signaling pathways, suggesting active roles for the immature cells in enhancing cognitive resilience in the presence of AD pathology. Our findings reveal novel, putative physiological roles for immature neurons in the healthy and resilient adult human brain, and offer a resource for probing new strategies with potential functional relevance in AD.
Deficiency ofShank3in the Nucleus Accumbens Reveals a Loss of Social-Specific Motivation
Authors: Folkes Oakleigh M. , Donahue Meaghan , Wang Sung Eun , Oo Nicole Xinyen , Qiao Sheng-nan , Wang Xiaoming , Negrón-Moreno Paola N. , Jiang Yong-hui 
Published: January 2025

ABSTRACTDeficits in social interaction are a hallmark symptom of autism and other neuropsychiatric disorders.SHANK3encodes a postsynaptic density scaffold protein and is one of the most common causal genes for autism. SHANK3 protein is highly expressed in the nucleus accumbens (NAc), a critical brain region underlying motivated behavior, including social motivation. We previously reported that globalShank3Δe4–22deletion mice have decreased motivation for palatable food, increased unilateral social investigation, and show a hypoactive NAc and NAc-connected circuits. We thus developed a newShank3flox/floxmouse tool to conditionally knockdown SHANK3 in a region-specific manner. We found that knockdown ofShank3in the NAc decreased social preference in the 3-chamber assay and decreased social motivation in the social conditioned place preference (sCPP) assay.Shank3-NAc deletion did not alter food reward seeking, reciprocal social investigation, or anxiety-like behaviors, that we report in globalShank3Δe4–22deletion mice. These data establish a novel and specific role ofShank3in the NAc on social motivation.
Mechanical impact on neural stem cell lineage decisions in human brain organoids
Authors: Lampersperger Hanna , Tranchina Michael , Meth Bastian , Han Dandan , Nayebzadeh Negar , Reiter Nina , Kuth Sonja , Lorke Markus , Boccaccini Aldo R , Budday Silvia , Karow Marisa , Falk Sven 
Published: January 2025

AbstractDuring neurodevelopment neural stem cells give rise to a spatially patterned tissue in which a regionally differentially regulated balance between proliferation and differentiation produces the fine-tuned number of neurons and macroglia necessary for a functional central nervous system. The cells driving these highly intricated developmental processes of patterning, growth and differentiation are constantly exposed to a mechanical environment that is however variable between different brain regions and along differentiation trajectories. Here we demonstrate that both, acute mechanical manipulations as well as a persistent change in the mechanical environment provided to human brain organoids, instruct neural stem cell lineage decisions. Furthermore, we dissect the underlying changes in the molecular program of organoid-resident cells by bulk- and single cell RNA-sequencing and reveal that mechanical manipulations impact on molecular programs governing early patterning events as well as cell-type specifically alter cellular metabolism. Thus, our results unravel a regulatory network linking mechanics and neural stem cell lineage decisions.
Intestinal RICT-1 regulates the larval germline progenitor pool via the vitellogenin VIT-3 inC. elegans
Authors: Kloock Anke , Hubbard E. Jane Albert 
Published: January 2025

ABSTRACTPopulations of proliferating cells such as stem cells and tumors are often nutrient responsive. Highly conserved signaling pathways communicate information about the surrounding environmental, organismal, and cellular nutrient conditions. One such pathway is the Target of Rapamycin (TOR) pathway. The TOR kinase exists in two complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TORC1 has been researched extensively and its regulation, particularly by amino acids, is well characterized. TORC1 activity promotes both stem cell fate and proliferation in theCaenorhabditis eleganshermaphrodite germline stem cell system to facilitate expansion of the larval germline Progenitor Zone (PZ) pool in response to nutrients. By contrast, a role for TORC2 in germline development has not been investigated. Here, we show that RICT-1, the sole ortholog of the TORC2-specific component RICTOR, also promotes expansion of the larval PZ, acting largely through SGK-1. Further, unlike the germline-autonomous role for TORC1 components, intestinalrict-1is both necessary and sufficient for full germline PZ pool establishment. Furthermore, neither DAF-2/IIS nor DAF-7/TGF-ß pathways mediate the effects of RICT-1. Rather, intestinal RICT-1 likely acts via vitellogenins, intestinally produced yolk proteins previously characterized for provisioning the adult germ line, but not previously characterized for a role in larval germ line development. By comparative RNA-seq on staged L4 larvae, we found vitellogenin genes among highly differentially abundant mRNAs. Genetic analysis supports a role forvit-3in germline development in a linear pathway withrict-1. Our results establish theC. elegansgerm line as a fruitful model for investigating TORC2 and its connection to stem cells and lipid biology.
A Heterozygous 9q34 deletion encompassing SPTAN1 as a cause of distal myopathy
Authors: Van de Vondel Liedewei , De Winter Jonathan , Monticelli Alice , Camacho Natacha , Deconinck Tine , Janssens Katrien , Malfroid Goedele , Alonso-Jiménez Alicia , Demidov German , Laurie Steven , De Ridder Willem , Ermanoska Biljana , Timmerman Vincent , Baets Jonathan 
Published: January 2025

AbstractWe report a family affected with childhood onset distal muscle weakness with a heterozygous chromosome 9q34 deletion encompassing theSPTAN1gene. The deletion was detected through exome-sequencing based copy number variant detection, segregates in four patients and is non-penetrant in two other relatives. Electromyography, muscle MRI and muscle biopsy revealed a myopathic disease phenotype. Cellular consequences of the deletion were investigated using qPCR and western blotting on patient-derived fibroblasts, which revealed a reduction of RNA but not protein levels. Immunocytochemistry was performed on muscle tissue which did not reveal reduction of α-II-spectrin.SPTAN1loss-of-function variants have previously been reported to cause distal hereditary motor neuropathy and recently distal myopathy. Here, we confirm the role ofSPTAN1haploinsufficiency as a cause of distal myopathy. We propose an age-dependent lack of α-II-spectrin and suggest CNV detection in repurposed exome sequencing as an important diagnostic tool.
Anatomic and Functional Outcomes of Lamellar Macular Hole Surgery: Predictive Factors and Associated Complications
Authors: Er-reguyeg Yosra , Doukkali Sihame , Hébert Mélanie , You Eunice Linh , Bourgault Serge , Caissie Mathieu , Tourville Éric , Dirani Ali 
Published: January 2025

ABSTRACTPurposeTo analyze the anatomic and functional outcomes of lamellar macular hole (LMH) surgery.Patients and methodsThis is a retrospective interventional cohort study of ninety patients with unilateral idiopathic LMH who underwent pars plana vitrectomy (PPV) with membrane peeling for LMH between 2014 and 2021. We evaluated the anatomic and functional success of PPV with membrane peeling for treating LMH, compared surgical outcomes between the two LMH subtypes (“true” LMH and epiretinal foveoschisis (ERMF)), and identified predictive factors for anatomical and functional success. Primary outcomes included final postoperative best-corrected visual acuity (BCVA) and LMH closure. Variables associated with final BCVA were assessed using a multiple linear regression model.Results51 subjects presented with ERMF, while 39 presented with “true” LMH. LMH closure occurred in 80 cases. “True” LMH cases had a lower rate of closure (“true” LMH closure rate: 76.9%, vs. ERMF closure rate: 94.2%, p=0.005) and were more at risk of developing a postoperative macular hole (p=0.008). A significant difference was observed between median [Q1, Q3] preoperative BCVA (0.42 [0.26, 0.61]) and final BCVA (0.31 [0.14, 0.48], p=0.024). “True” LMH without epiretinal proliferation (β=0.194, p=0.040) was associated with worse final BCVA in multivariate analysis.ConclusionResults support the effectiveness of PPV as a treatment for LMH. “True” LMHs had worse anatomic outcomes than ERMFs.