bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal approaches for inequality in kidney care: turning social determinants of health into opportunities
Authors: Purtell Louise , Bennett Paul , Bonner Ann 
Published: October 2023

Purpose of review
Kidney disease is associated with major health and economic burdens worldwide, disproportionately carried by people in low and middle socio-demographic index quintile countries and in underprivileged communities. Social determinants such as education, income and living and working conditions strongly influence kidney health outcomes. This review synthesised recent research into multimodal interventions to promote kidney health equity that focus on the social determinants of health.

Recent findings
Inequity in kidney healthcare commonly arises from nationality, race, sex, food insecurity, healthcare access and environmental conditions, and affects kidney health outcomes such as chronic kidney disease progression, dialysis and transplant access, morbidity and mortality. Multimodal approaches to addressing this inequity were identified, targeted to: patients, families and caregivers (nutrition, peer support, financial status, patient education and employment); healthcare teams (workforce, healthcare clinician education); health systems (data coding, technology); communities (community engagement); and health policy (clinical guidelines, policy, environment and research).

Summary
The engagement of diverse patients, families, caregivers and communities in healthcare research and implementation, as well as clinical care delivery, is vital to counteracting the deleterious effects of social determinants of kidney health.
Platelet mechanosensing as key to understanding platelet function
Authors: Schoen Ingmar , Kenny Martin , Patil Smita 
Published: October 2023

Purpose of review
This review highlights how the perception of platelet function is evolving based on recent insights into platelet mechanobiology.

Recent findings
The mechanosensitive ion channel Piezo1 mediates activation of free-flowing platelets under conditions of flow acceleration through mechanisms independent of adhesion receptors and classical activation pathways. Interference with the initiation of platelet migration or with the phenotypic switch of migrating platelets to a procoagulant state aggravates inflammatory bleeding. Mechanosensing of biochemical and biophysical microenvironmental cues during thrombus formation feed into platelet contractile force generation. Measurements of single platelet contraction and bulk clot retraction show promise to identify individuals at risk for hemorrhage.

Summary
New findings unravel novel mechanotransduction pathways and effector functions in platelets, establishing mechanobiology as a pivotal component of platelet function. These insights highlight limitations of existing treatments and offer new potential therapeutic approaches and diagnostic avenues based on mechanobiological principles. Further extensive research is required to distinguish between core hemostatic and pathological mechanisms influenced by platelet mechanosensing.
CellContrast: Reconstructing Spatial Relationships in Single-Cell RNA Sequencing Data via Deep Contrastive Learning
Authors: Li Shumin , Ma Jiajun , Zhao Tianyi , Jia Yuran , Liu Bo , Luo Ruibang , Huang Yuanhua 
Published: October 2023

AbstractA vast amount of single-cell RNA-seq (SC) data has been accumulated via various studies and consortiums, but the lack of spatial information limits its analysis of complex biological activities. To bridge this gap, we introduce cellContrast, a computational method for reconstructing spatial relationships among SC cells from spatial transcriptomics (ST) reference. By adopting a contrastive learning framework and training with ST data, cellContrast projects gene expressions into a hidden space where proximate cells share similar representation values. We performed extensive benchmarking on diverse platforms, including SeqFISH, Stereo-Seq, 10X Visium, and MERSCOPE, on mouse embryo and human breast cells. The results reveal that cellContrast substantially outperforms other related methods, facilitating accurate spatial reconstruction of SC. We further demonstrate cellContrast’s utility by applying it to cell-type co-localization and cell-cell communication analysis with real-world SC samples, proving the recovered cell locations empower novel discoveries and mitigate potential false positives.
TheR1441C-LRRK2mutation induces myeloid immune cell exhaustion in an age- and sex-dependent manner
Authors: Wallings Rebecca L. , McFarland Karen , Staley Hannah A. , Neighbarger Noelle , Schaake Susen , Brüggemann Norbert , Zittel Simone , Usnich Tatiana , Klein Christine , Sammler Esther M , Tansey Malú Gámez 
Published: October 2023

AbstractConsidering age is the greatest risk factor for many neurodegenerative diseases, aging, in particular aging of the immune system, is the most underappreciated and understudied contributing factor in the neurodegeneration field. Genetic variation around theLRRK2gene affects risk of both familial and sporadic Parkinson’s disease (PD). The leucine-rich repeat kinase 2 (LRRK2) protein has been implicated in peripheral immune signaling, however, the effects of an aging immune system on LRRK2 function have been neglected to be considered. We demonstrate here that theR1441Cmutation induces a hyper-responsive phenotype in macrophages from young female mice, characterized by increased effector functions, including stimulation-dependent antigen presentation, cytokine release, phagocytosis, and lysosomal function. This is followed by age-acquired immune cell exhaustion in a Lrrk2-kinase-dependent manner. Immune-exhausted macrophages exhibit suppressed antigen presentation and hypophagocytosis, which is also demonstrated in myeloid cells fromR1441CandY1699C-PD patients. Our novel findings thatLRRK2mutations confer immunological advantage at a young age but may predispose the carrier to age-acquired immune cell exhaustion have significant implications for LRRK2 biology and therapeutic development. Indeed, LRRK2 has become an appealing target in PD, but our findings suggest that more research is required to understand the cell-type specific consequences and optimal timing of LRRK2-targeting therapeutics.One Sentence SummaryTheR1441C-LRRK2mutation causes an age-acquired immune cell exhaustion in macrophages in a sex-dependent manner
Assessing the Population Consequences of Disturbance and Climate Change for the Pacific Walrus
Authors: Johnson Devin L. , Eisaguirre Joseph M. , Taylor Rebecca L. , Garlich-Miller Joel L. 
Published: October 2023

ABSTRACTClimate change and anthropogenic disturbance are increasingly affecting wildlife at a global scale. Predicting how varying types and degrees of disturbance may interact to influence population dynamics is a key management challenge. Population Consequences of Disturbance (PCoD) models provide a framework to link effects of anthropogenic disturbance on an individual’s behavior and physiology to population-level changes. Bioenergetic models often constitute the basis of these frameworks, wherein an individual’s daily energy balance is simulated over the course of its lifetime, allowing many individuals to be subjected to different environmental conditions and ultimately simulate population-level vital rates under varying degrees of disturbance. In the present study, we develop a Pacific walrus (Odobenus rosmarus divergens) PCoD model to encompass the population-level effects of both anthropogenic disturbance and climate change. Pacific walruses are an Arctic/subarctic ice-associated pinniped. As the Arctic has become increasingly ice-free with climate change, walruses spend more time on land-based (rather than ice-based) haulouts from which they must expend more energy to reach foraging areas, and where they have a greater risk of predation and disturbance-based mortalities. Concurrently, sea ice loss is increasing the anthropogenic footprint in Arctic regions (e.g., fisheries, shipping, energy exploration) which creates additional disturbance. We developed a bioenergetic Dynamic Energy Budget (DEB) model for the Pacific walrus and applied it to four scenarios (ranging from optimistic-pessimistic) which incorporate different global sea ice model projections along with varying degrees of anthropogenic disturbance. All scenarios indicated a decline in Pacific walrus carrying capacity and population growth rate (and thus overall abundance) to the end of the 21stcentury, but demonstrated that the intensity of that decline could be mitigated by global efforts to reduce carbon emissions (i.e., lessening the rate of sea ice loss) and local management and conservation efforts to protect sensitive habitat areas. In summary, we introduced a flexible PCoD modelling framework in a novel context which will prove useful to researchers studying walruses and other species similarly threatened by rapid environmental change.
A comparative study of algorithms detecting differential rhythmicity in transcriptomic data
Authors: Miao Lin , Weidemann Douglas E. , Ngo Katherine , Unruh Benjamin A. , Kojima Shihoko 
Published: October 2023

AbstractRhythmic transcripts play pivotal roles in driving the daily oscillations of various biological processes. Genetic or environmental disruptions can lead to alterations in the rhythmicity of transcripts, ultimately impacting downstream circadian outputs, including metabolic processes and even behavior. To statistically compare the differences in transcript rhythms between two or more conditions, several algorithms have been developed to analyze circadian transcriptomic data, each with distinct features. In this study, we compared the performance of seven algorithms that were specifically designed to detect differential rhythmicity. We found that even when applying the same statistical threshold, these algorithms yielded varying numbers of differentially rhythmic transcripts. Nevertheless, the set of transcripts commonly identified as differentially rhythmic exhibited substantial overlap among algorithms. Furthermore, the phase and amplitude differences calculated by these algorithms displayed significant correlations. In summary, our study highlights a high degree of similarity in the results produced by these algorithms. Furthermore, when selecting an algorithm for analysis, it is crucial to ensure the compatibility of input data with the specific requirements of the chosen algorithm and to assess whether the algorithm’s output fits the needs of the user.
Prior heat stress increases pathogen susceptibility in the model cnidarianExaptasia diaphana
Authors: Diaz de Villegas Sofia C. , Borbee Erin M. , Abdelbaki Peyton Y. , Fuess Lauren E. 
Published: October 2023

AbstractAnthropogenic climate change has significantly altered terrestrial and marine ecosystems globally, often in the form of climate-related events such as thermal anomalies and disease outbreaks. Although the isolated effects of these stressors have been well documented, a growing body of literature suggests that stressors often interact, resulting in complex effects on ecosystems, including coral reefs where sequential associations between heat stress and disease have had profound impacts. Here we used the model cnidarianExaiptasia diaphanato investigate mechanisms linking prior heat stress to increased disease susceptibility. We examined anemone pathogen susceptibility and physiology (symbiosis, immunity, and energetics) following recovery from heat stress. We observed significantly increased pathogen susceptibility in anemones previously exposed to heat stress. Notably, prior heat stress reduced anemone energetic reserves (carbohydrate concentration), and activity of multiple immune components. Minimal effects of prior heat stress on symbiont density were observed. Together, results suggest changes in energetic availability might have the strongest effect on pathogen susceptibility and immunity following heat stress. The results presented here provide critical insight regarding the interplay between heat stress recovery and pathogen susceptibility in cnidarians and are an important first step towards understanding temporal associations between these stressors.
A role for theC. elegansArgonaute protein CSR-1b isoform in small nuclear RNA 3’ processing
Authors: Waddell Brandon M. , Wu Cheng-Wei 
Published: October 2023

ABSTRACTThe Integrator is a multi-subunit protein complex that catalyzes the maturation of snRNA transcripts via 3’ cleavage, a step required for snRNA incorporation with snRNP for spliceosome biogenesis. Here we developed a GFP basedin vivosnRNA misprocessing reporter as a readout of Integrator function and performed a genome-wide RNAi screen for Integrator regulators. We found that loss of the Argonaute encodingcsr-1gene resulted in widespread 3’ misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing. Loss ofcsr-1down-regulates the germline expression of Integrator subunit-4 and is accompanied by a reduced protein translation efficiency of multiple Integrator catalytic and non-catalytic subunits. Through isoform analysis, we identify thatcsr-1bis specifically required for snRNA processing and this is dependent on its catalytic slicer activity. Moreover, mRNA-sequencing revealed high similarity in the transcriptome profile betweencsr-1and Integrator subunit knockdown via RNAi. Together, our findings revealcsr-1bas a new regulator of the Integrator complex and implicate a novel role of this Argonaute protein in snRNA 3’ processing.
Distinct resource utilization by introduced man-made grouper hybrid: an overlooked anthropogenic impact from a longstanding religious practise
Authors: Chung Arthur , Schunter Celia 
Published: October 2023

AbstractAnthropogenic activities, such as non-native aquaculture species introduction have been considerably altering trophic interactions in marine ecosystems. The hybrid grouper (TGGG), an aquaculture product originated from artificial F1 crossbreed betweenEpinephelus fuscoguttatusandE. lanceolatus, have been released in the wild through religious activities, raising concerns about this man-made introduced species. The carnivorous diet, together with large body size inherited from the parental species have made TGGG a candidate that could pose significant impacts to the marine ecosystem. Yet, little is known about the diet composition of TGGG upon release into the natural environment, and any dietary overlap or partition with closely related endemic species. Here, we deploy gut content DNA metabarcoding to determine the prey richness and dietary niche of wild caught TGGG and compare with four native grouper species (Epinephelus awoara, E. bleekeri, E. coioides and E. quoyanus). The TGGG exhibited six unique prey taxa with teleosts being the major taxa preyed upon followed by crustaceans and cephalopods and displayed significant lower mean number of pray taxa compared to other groupers. The TGGG exhibits a significantly different diet composition, possibly indicating a diet transitioning and acquiring new feeding behavior. This study provides a comprehensive analysis with high taxonomic resolution on the diet of artificial hybrids in the wild, suggesting possibility of introduction success if release events persist. Finally, these findings provide new information on how local trophic dynamics are impacted by under-investigated release of animals through religious practices.
Endocisternal interfaces for minimally invasive neural stimulation and recording of the brain and spinal cord
Authors: Chen Joshua C. , Dhuliyawalla Abdeali , Garcia Robert , Robledo Ariadna , Woods Joshua E. , Alrashdan Fatima , O’Leary Sean , Crosby Scott , Felicella Michelle M , Wakhloo Ajay K. , Karas Patrick , Goodman Wayne , Sheth Sameer A. , Sheth Sunil A. , Robinson Jacob T. , Kan Peter 
Published: October 2023

AbstractMinimally invasive neural interfaces can be used to diagnose, manage, and treat many disorders with substantially reduced risks of surgical complications. Endovascular neural interfaces implanted in the veins or arteries is one approach, but it requires prescriptions of anti-thrombotic medication and are likely not explantable after endothelialization. More critically, the approach is limited by the small size and location of blood vessels, such that many important cortical, subcortical, spinal targets cannot be reached. Here, we demonstrate a chronic endocisternal neural interface that approaches brain and spinal cord targets through inner and outer cerebral spinal fluid (CSF) spaces. These spaces surround the nervous system and lack the tortuosity of the circulatory system, giving us access to the entire brain convexity, deep brain structures within the ventricles, and the spinal cord from the spinal subarachnoid space. Combined with miniature magnetoelectric-powered bioelectronics, the entire wireless system is deployable through a percutaneous procedure. The flexible catheter electrodes can be freely navigated throughout the body from the spinal to cranial subarachnoid space, and from the cranial subarachnoid space to the ventricles. We show in a large animal model that we can also reposition the recording and stimulation electrodes or explant the neural interface after chronic implantation. This enables applications in therapies that require transient or permanent brain/machine interface such as stroke rehabilitation and epilepsy monitoring and opens a new class of minimally invasive endocisternal bioelectronics.
Force-field perturbations and muscle vibration strengthen stability-related foot placement responses during steady-state gait
Authors: van Leeuwen A.M. , Bruijn S.M. , Dean J.C. 
Published: October 2023

AbstractMediolateral gait stability can be maintained by coordinating our foot placement with respect to the center-of-mass (CoM) kinematic state. Neurological impairments can reduce the degree of foot placement control. For individuals with such impairments, interventions that could improve foot placement control could thus contribute to improved gait stability. In this study we aimed to better understand two potential interventions, by investigating their effect in neurologically intact individuals. The degree of foot placement control can be quantified based on a foot placement model, in which the CoM position and velocity during swing predict subsequent foot placement. Previously, perturbing foot placement with a force-field resulted in an enhanced degree of foot placement control as an after-effect. Moreover, muscle vibration enhanced the degree of foot placement control through sensory augmentation whilst the vibration was applied. Here, we replicated these two findings and further investigated whether Q1) sensory augmentation leads to an after-effect and Q2) whether combining sensory augmentation with force-field perturbations leads to a larger after-effect, as compared to force-field perturbations only. In addition, we evaluated several potential contributors to the degree of foot placement control, by considering foot placement errors, CoM variability and the CoM position gain (βpos) of the foot placement model, next to the R2measure as the degree of foot placement control. Sensory augmentation led to a higher degree of foot placement control as an after-effect (Q1). However, combining sensory augmentation and force-field perturbations did not lead to a larger after-effect, as compared to following force-field perturbations only (Q2). Furthermore, we showed that, the improved degree of foot placement control following force-field perturbations and during/following muscle vibration, did not reflect diminished foot placement errors. Rather, participants demonstrated a stronger active response (higher βpos) as well as higher CoM variability.
Single cell transcriptomic profiling identifies tumor-acquired and therapy-resistant cell states in pediatric rhabdomyosarcoma
Authors: Danielli Sara G , Wei Yun , Dyer Michael A , Stewart Elizabeth , Wachtel Marco , Schäfer Beat W , Patel Anand G , Langenau David M 
Published: October 2023

SUMMARYRhabdomyosarcoma (RMS) is a pediatric tumor that resembles undifferentiated muscle cells; yet the extent to which cell state heterogeneity and molecular features are shared with human development have not been fully ascribed. Here, we report a single-cell/nucleus RNA sequencing atlas derived from 72 datasets that includes patient tumors, patient-derived xenografts, primaryin vitrocultures, and established cell lines. We report four dominant muscle-lineage cell states in RMS: progenitors, proliferative, differentiated, and ground cells. We stratify these RMS cells along the continuum of human muscle development and show that RMS cells share expression patterns with fetal/embryonal myogenic precursors rather than postnatal satellite cells. Indeed, fusion-negative RMS (FN-RMS) have a discrete stem cell hierarchy that faithfully recapitulates fetal muscle development. We also identify therapy-resistant FN-RMS progenitor cells that share transcriptomic similarity with bipotent skeletal mesenchymal cells, while a subset of fusion-positive (FP) RMS have tumor-acquired cells states, including a neuronal cell state, that are not found in development. Chemotherapy induced upregulation of progenitor signatures in FN-RMS while the neuronal gene programs were retained after therapy in FP-RMS. Taken together, this work identifies new cell state heterogeneity including unique treatment-resistant and tumor-acquired cell states that differ across RMS subtypes.
Pervasive biases in proxy GWAS based on parental history of Alzheimer’s disease
Authors: Wu Yuchang , Sun Zhongxuan , Zheng Qinwen , Miao Jiacheng , Dorn Stephen , Mukherjee Shubhabrata , Fletcher Jason M. , Lu Qiongshi 
Published: October 2023

AbstractAlmost every recent Alzheimer’s disease (AD) genome-wide association study (GWAS) has performed meta-analysis to combine studies with clinical diagnosis of AD with studies that use proxy phenotypes based on parental disease history. Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and non-random participation of parental illness survey, which cause substantial discrepancies between AD GWAS and GWAX results. We demonstrate that current AD GWAX provide highly misleading genetic correlations between AD risk and higher education which subsequently affects a variety of genetic epidemiologic applications involving AD and cognition. Our study sheds important light on the design and analysis of mid-aged biobank cohorts and underscores the need for caution when interpreting genetic association results based on proxy-reported parental disease history.
Commissureless acts as a substrate adapter in a conserved Nedd4 E3 ubiquitin ligase pathway to promote axon growth across the midline
Authors: Sullivan Kelly G. , Bashaw Greg J. 
Published: October 2023

SUMMARYIn both vertebrates and invertebrates, commissural neurons prevent premature responsiveness to the midline repellant Slit by downregulating surface levels of its receptor Roundabout1 (Robo1). InDrosophila, Commissureless (Comm) plays a critical role in this process; however, there is conflicting data on the underlying molecular mechanism. Here, we demonstrate that the conserved PY motifs in the cytoplasmic domain of Comm are required allow the ubiquitination and lysosomal degradation of Robo1. Disruption of these motifs prevents Comm from localizing to Lamp1 positive late endosomes and to promote axon growth across the midlinein vivo. In addition, we conclusively demonstrate a role for Nedd4 in midline crossing. Genetic analysis shows thatnedd4mutations result in midline crossing defects in the Drosophila embryonic nerve cord, which can be rescued by introduction of exogenous Nedd4. Biochemical evidence shows that Nedd4 incorporates into a three-member complex with Comm and Robo1 in a PY motif-dependent manner. Finally, we present genetic evidence that Nedd4 acts with Comm in the embryonic nerve cord to downregulate Robo1 levels. Taken together, these findings demonstrate that Comm promotes midline crossing in the nerve cord by facilitating Robo1 ubiquitination by Nedd4, ultimately leading to its degradation.