bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinforcement Learning Is Impaired in the Sub-acute Post-stroke Period
Authors: Branscheidt Meret , Hadjiosif Alkis M. , Anaya Manuel A. , Keller Jennifer , Widmer Mario , Runnalls Keith D. , Luft Andreas R , Bastian Amy J. , Krakauer John W. , Celnik Pablo A. 
Published: January 2023

AbstractBackgroundNeurorehabilitation approaches are frequently predicated on motor learning principles. However, much is left to be understood of how different kinds of motor learning are affected by stroke causing hemiparesis. Here we asked if two kinds of motor learning often employed in rehabilitation, (1) reinforcement learning and (2) error-based adaptation, are altered at different times after stroke.MethodsIn a cross-sectional design, we compared learning in two groups of patients with stroke, matched for their baseline motor execution deficit on the paretic side. The early group was tested within 3 months following stroke (N = 35) and the late group was tested more than 6 months after stroke (N = 30). Two types of task were studied: one based on reinforcement learning and the other on error-based learning.ResultsWe found that reinforcement learning was impaired in the early but not the late group, whereas error-based learning was unaffected compared to controls. These findings could not be attributed to differences in baseline execution, cognitive impairment, gender, age, or lesion volume and location.ConclusionsThe presence of a specific impairment in reinforcement learning in the first 3 months after stroke has important implications for rehabilitation. It might be necessary to either increase the amount of reinforcement feedback given early or even delay onset of certain forms of rehabilitation training, e.g., like constraint-induced movement therapy, and instead emphasize others forms of motor learning in this early time period. A deeper understanding of stroke-related changes in motor learning capacity has the potential to facilitate the development of new, more precise treatment interventions.
Structural variation across 138,134 samples in the TOPMed consortium
Authors: Jun Goo , English Adam C , Metcalf Ginger A , Yang Jianzhi , Chaisson Mark JP , Pankratz Nathan , Menon Vipin K , Salerno William J , Krasheninina Olga , Smith Albert V , Lane John A , Blackwell Tom , Kang Hyun Min , Salvi Sejal , Meng Qingchang , Shen Hua , Pasham Divya , Bhamidipati Sravya , Kottapalli Kavya , Arnett Donna K. , Ashley-Koch Allison , Auer Paul L. , Beutel Kathleen M , Bis Joshua C. , Blangero John , Bowden Donald W. , Brody Jennifer A. , Cade Brian E. , Chen Yii-Der Ida , Cho Michael H. , Curran Joanne E. , Fornage Myriam , Freedman Barry I. , Fingerlin Tasha , Gelb Bruce D. , Hou Lifang , Hung Yi-Jen , Kane John P , Kaplan Robert , Kim Wonji , Loos Ruth J.F. , Marcus Gregory M , Mathias Rasika A. , McGarvey Stephen T. , Montgomery Courtney , Naseri Take , Nouraie S. Mehdi , Preuss Michael H. , Palmer Nicholette D. , Peyser Patricia A. , Raffield Laura M. , Ratan Aakrosh , Redline Susan , Reupena Sefuiva , Rotter Jerome I. , Rich Stephen S. , Rienstra Michiel , Ruczinski Ingo , Sankaran Vijay G. , Schwartz David A. , Seidman Christine E. , Seidman Jonathan G. , Silverman Edwin K. , Smith Jennifer A. , Stilp Adrienne , Taylor Kent D. , Telen Marilyn J. , Weiss Scott T. , Williams L. Keoki , Wu Baojun , Yanek Lisa R. , Zhang Yingze , Lasky-Su Jessica , Gingras Marie Claude , Dutcher Susan K. , Eichler Evan E. , Gabriel Stacey , Germer Soren , Kim Ryan , Viaud-Martinez Karine A. , Nickerson Deborah A. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Luo James , Reiner Alex , Gibbs Richard A , Boerwinkle Eric , Abecasis Goncalo , Sedlazeck Fritz J 
Published: January 2023

AbstractEver larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a balance between comprehensiveness and precision. Here we present a catalog of 355,667 SVs (59.34% novel) across autosomes and the X chromosome (50bp+) from 138,134 individuals in the diverse TOPMed consortium. We describe our methodologies for SV inference resulting in high variant quality and >90% allele concordance compared to long-read de-novo assemblies of well-characterized control samples. We demonstrate utility through significant associations between SVs and important various cardio-metabolic and hemotologic traits. We have identified 690 SV hotspots and deserts and those that potentially impact the regulation of medically relevant genes. This catalog characterizes SVs across multiple populations and will serve as a valuable tool to understand the impact of SV on disease development and progression.
Investigating the roles of reflexes and central pattern generators in the control and modulation of human locomotion using a physiologically plausible neuromechanical model
Authors: Russo Andrea Di , Stanev Dimitar , Sabnis Anushree , Danner Simon M. , Ausborn Jessica , Armand Stéphane , Ijspeert Auke 
Published: January 2023

AbstractStudying the neural components regulating movement in human locomotion is obstructed by the inability to perform invasive experimental recording. Neuromechanical simulations can provide insights by modeling the locomotor circuits. Past neuromechanical models proposed control of locomotion either driven by central pattern generators (CPGs) with simple sensory commands or by a purely reflex-based network regulated by state-machine mechanisms. However, the physiological interpretation of these state-machines remains unclear. Here, we present a physiologically plausible model to investigate spinal control and modulation of human locomotion. We propose a bio-inspired controller composed of two coupled central pattern generators (CPGs) that produce the rhythm and pattern and a reflex-based network simulating low-level reflex pathways and Renshaw cells. This reflex network is based on leaky-integration neurons, and the whole system does not rely on changing reflex gains according to the gait cycle state. The only component of the controller that maintains a state-machine mechanism is the balance controller of the trunk. The musculoskeletal model is composed of a skeletal structure and 9 muscles per leg generating movement in sagittal plane. After optimizing the open parameters, human locomotion replicating kinematics and muscle activation naturally emerged. Furthermore, when CPGs were not activated, no stable and physiologically plausible gaits could be achieved through optimization, suggesting the necessity of this component to generate rhythmic behavior without a state machine mechanism regulating reflex activation. The controller could reproduce a wide range of speeds from 0.3 to 1.9 m/s. The results also showed that the net influence of feedback on motoneurons during perturbed locomotion is predominantly inhibitory and that the CPG network provides the timing of motoneurons’ activation by exciting or inhibiting muscles in specific gait phases. The proposed bio-inspired controller could contribute to our understanding of locomotor circuits of the intact spinal cord and could be used to study neuromotor disorders.
Timing of behavioral responding to long-duration Pavlovian fear conditioned cues
Authors: Wright Kristina M. , Kantor Claire E. , Moaddab Mahsa , McDannald Michael A. 
Published: January 2023

AbstractBehavioral responding is most beneficial when it reflects event timing. Compared to reward, there are fewer studies on timing of defensive responding. We gave female and male rats Pavlovian fear conditioning over a baseline of reward seeking. Two 100-s cues predicted foot shock at different time points. Rats acquired timing of behavioral responding to both cues. Suppression of reward seeking was minimal at cue onset and maximal before shock delivery. Rats also came to minimize suppression of reward seeking following cue offset. The results reveal timing as a mechanism to focus defensive responding to shock-imminent, cue periods.
The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons
Authors: Zhang Chi , Yi Xianfu , Hou Mengfan , Li Qingyang , Li Xueying , Lu Lu , Qi Enling , Wu Mingxin , Qi Lin , Jian Huan , Qi Zhangyang , Lv Yigang , Kong Xiaohong , Bi Mingjun , Feng Shiqing , Zhou Hengxing 
Published: January 2023

ABSTRACTCerebral ischaemia‒reperfusion injury, during which neurons undergo oxygen-glucose deprivation/reoxygenation (OGD/R), is a notable pathological process in many neurological diseases. N1-methyladenosine (m1A) is an RNA modification that can affect gene expression and RNA stability. The m1A landscape and potential functions of m1A modification in neurons remain poorly understood. We explored RNA (mRNA, lncRNA, and circRNA) m1A modification in normal and OGD/R-treated neurons and the effect of m1A on diverse RNAs. We investigated the m1A landscape in primary neurons, identified m1A-modified RNAs, and found that OGD/R increased the number of m1A RNAs. m1A modification might also affect the regulatory mechanisms of noncoding RNAs, e.g., lncRNA–RBP interactions and circRNA translation. We showed that m1A modification mediates the circRNA/lncRNA‒miRNA–mRNA ceRNA mechanism and that 3’UTR methylation of mRNAs can hinder miRNA–mRNA binding. Three methylation patterns were identified, and genes with different patterns had intrinsic mechanisms with potential m1A-regulatory specificity. Systematic analysis of the m1A landscape in normal and OGD/R neurons lays a critical foundation for understanding RNA methylation and provides new perspectives and a theoretical basis for treating and developing drugs for OGD/R pathology-related diseases.
Loss of genital epithelial barrier function is greater with depot-medroxyprogesterone acetate than intravaginal rings that release etonogestrel and ethinyl estradiol
Authors: Liu Mohan , Vicetti Miguel Rodolfo D. , Quispe Calla Nirk E. , Aceves Kristen M. , Fritts Linda , Miller Christopher J. , Moss John A. , Baum Marc M. , Cherpes Thomas L. 
Published: January 2023

ABSTRACTThe injectable progestin depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in sub-Saharan Africa although mouse models indicate it weakens genital epithelial integrity and barrier function and increases susceptibility to genital infection. The intravaginal ring NuvaRing® is another contraceptive option that like DMPA suppresses hypothalamic pituitary ovarian (HPO) axis function with local release of progestin (etonogestrel) and estrogen (ethinyl estradiol). As we previously reported that treating mice with DMPA and estrogen averts the loss of genital epithelial integrity and barrier function induced by DMPA alone, in the current investigation we compared genital levels of the cell-cell adhesion molecule desmoglein-1 (DSG1) and genital epithelial permeability in rhesus macaques (RM) treated with DMPA or a NuvaRing®re-sized for RM (N-IVR). While these studies demonstrated comparable inhibition of the HPO axis with DMPA or N-IVR, DMPA induced significantly lower genital DSG1 levels and greater tissue permeability to intravaginally administered low molecular mass molecules. By identifying greater compromise of genital epithelial integrity and barrier function in RM administered DMPA vs. N-IVR, our results add to the growing body of evidence that indicate DMPA weakens a fundamental mechanism of anti-pathogen host defense in the female genital tract.
Hsf1 and the molecular chaperone Hsp90 support a “rewiring stress response” leading to an adaptive cell size increase in chronic stress
Authors: Maiti Samarpan , Bhattacharya Kaushik , Wider Diana , Hany Dina , Panasenko Olesya , Bernasconi Lilia , Hulo Nicolas , Picard Didier 
Published: January 2023

AbstractCells are exposed to a wide variety of internal and external stresses. Whereas many studies have focused on cellular responses to acute and severe stresses, little is known about how cellular systems adapt to sublethal chronic stresses. Using mammalian cells in culture, we discovered that they adapt to chronic mild stresses of up to two weeks, notably proteotoxic stresses such as heat, by increasing their size and translation, thereby scaling the amount of total protein. These adaptations render them more resilient to persistent and subsequent stresses. We demonstrate that Hsf1, well known for its role in acute stress responses, is required for the cell size increase, and that the molecular chaperone Hsp90 is essential for coupling the cell size increase to augmented translation. We term this translational reprogramming the “rewiring stress response”, and propose that this protective process of chronic stress adaptation contributes to the increase in size as cells get older, and that its failure promotes aging.
Evaluating the causal relationship between educational attainment and mental health
Authors: Demange Perline A. , Boomsma Dorret I. , van Bergen Elsje , Nivard Michel G. 
Published: January 2023

AbstractWe investigate the causal relationship between educational attainment (EA) and mental health using two research designs. First, we compare the relationship between EA and 18 psychiatric diagnoses within sibship in Dutch national registry data (N=1.7 million), thereby controlling for unmeasured familial factors. Second, we apply two-sample Mendelian Randomization, which uses genetic variants related to EA or psychiatric diagnosis as instrumental variables, to test whether there is a causal relation in either direction. Our results suggest that lower levels of EA causally increase the risk of MDD, ADHD, alcohol dependence, GAD and PTSD diagnoses. We also find evidence of a causal effect of ADHD on EA. For schizophrenia, anorexia nervosa, OCD, and bipolar disorder, results were inconsistent across the different approaches, highlighting the importance of using multiple research designs to understand complex relationships such as between EA and mental health.
Cleavable crosslinkers redefined by novel MS3-trigger algorithm
Authors: Kolbowski Lars , Fischer Lutz , Rappsilber Juri 
Published: January 2023

AbstractCrosslinking MS is currently transitioning from a routine tool in structural biology to enabling structural systems biology. MS-cleavable crosslinkers could substantially reduce the associated search space expansion by allowing an MS3-based approach for identifying crosslinked peptides. However, MS2-based approaches currently outperform approaches utilising MS3. We show here that MS3-trigger sensitivity and specificity were hampered algorithmically. Our four-step MS3-trigger algorithm greatly outperformed currently employed methods and comes close to reaching the theoretical limit.
Single cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration
Authors: Celotto Laura , Rost Fabian , Machate Anja , Bläsche Juliane , Dahl Andreas , Weber Anke , Hans Stefan , Brand Michael 
Published: January 2023

SUMMARYIn the lesioned zebrafish retina, Müller glia produce multipotent retinal progenitors that generate all retinal neurons, replacing lost cell types. To study the molecular mechanisms linking Müller glia reactivity to progenitor production and neuronal differentiation, we used single cell RNA sequencing of Müller glia, progenitors and regenerated progeny from uninjured and light-lesioned retinae. We discover an injury-induced Müller glia differentiation trajectory that leads into a cell population with a hybrid identity expressing marker genes of Müller glia and progenitors. A glial self-renewal and a neurogenic trajectory depart from the hybrid cell population. We further observe that neurogenic progenitors progressively differentiate to generate retinal ganglion cells first and bipolar cells last, similar to the events observed during retinal development. Our work provides a comprehensive description of Müller glia and progenitor transcriptional changes and fate decisions in the regenerating retina, which are key to tailor cell differentiation and replacement therapies for retinal dystrophies in humans.
How market orientation affects open innovation? Exploring the role of information and communication technology capability
Authors: Yin Miaomiao , Li Jiying 
Published: January 2023

PurposeBased on the organizational learning theory, this study regards market orientation as market-based learning and seeks to advance insight into how proactive and responsive market orientations affect two kinds of open innovation strategies, sourcing and selling. A firm’s information and communication technology (ICT) capability is considered an essential moderator in these relationships.Design/methodology/approachThis study adopted a quantitative design and used the questionnaire survey method to collect data. The authors finally collected data on samples in China. Multiple regression analysis was used to test the hypotheses.FindingsThe results show that proactive and responsive market orientations act as antecedents of open innovation, showing linear and curvilinear relationships between them. Specifically, responsive market orientation positively affects selling, and proactive market orientation positively affects sourcing. Responsive market orientation has an inverted U-shaped relationship with sourcing, and proactive market orientation has a U-shaped relationship with selling. In addition, ICT capability strengthens the positive effects of market orientation on open innovation and weakens the negative effects.Originality/valueDrawing on organizational learning theory, this study provides a novel perspective to explain the complex mechanism between market orientation and open innovation. This study also explores the moderating role of ICT capability in this process, which advances research on how to select open innovation strategies under different conditions.
Perceived importance of emotional support provided by health care professionals and social networks: Should we broaden our focus for the delivery of supportive care?
Authors: Taylor Jo , Fradgley Elizabeth A. , Clinton‐McHarg Tara , Hall Alix , Paul Christine L. 
Published: January 2023

AbstractIntroductionEmotional support provided by health care professionals (HCPs) for people diagnosed with cancer is associated with improved outcomes. Support via social networks may also be important.AimsTo report among a sample of distressed patients and caregivers, (1) the importance attributed to different sources of emotional support (HCPs and social networks) by distressed cancer patients and caregivers; (2) the proportion who indicate they did not receive sufficient levels of emotional support; and (3) potential associations between respondents’ demographic and clinical characteristics and reported lack of emotional support.MethodsThis study utilised cross‐sectional data from telephone interviews collected during the usual‐care phase of the Structured Triage and Referral by Telephone (START) trial. Participants completed a telephone interview 6 months after their initial call to the Cancer Council Information and Support service and included recall of importance and sufficiency of emotional support.ResultsMore than two‐thirds of patients (n = 234) and caregivers (n = 152) reported that family and friends were very important sources of emotional support. Nurses (69% and 42%) and doctors (68% and 47%) were reported very important, while a lower proportion reported that psychologists and psychiatrists were very important (39%, and 43%). Insufficient levels of support were reported by 36% of participants. Perceptions of insufficient support were significantly associated with distress levels (p < .0001) and not having a partner (p = .0115).ConclusionSocial networks, particularly family, are an important source of emotional support. Higher levels of distress, those without partners, and caregivers may require targeted interventions to increase their access to emotional support.
Total‐evidence phylogeny and evolutionary morphology of New World pitvipers (Serpentes: Viperidae: Crotalinae)
Authors: Carrasco Paola A. , Koch Claudia , Grazziotin Felipe G. , Venegas Pablo J. , Chaparro Juan C. , Scrocchi Gustavo J. , Salazar‐Valenzuela David , Leynaud Gerardo C. , Mattoni Camilo I. 
Published: January 2023

AbstractCrotalines (pitvipers) in the Americas are distributed from southern Canada to southern Argentina, and are represented by 13 genera and 163 species that constitute a monophyletic group. Their phylogenetic relationships have been assessed mostly based on DNA sequences, while morphological data have scarcely been used for phylogenetic inquiry. We present a total‐evidence phylogeny of New World pitvipers, the most taxon/character comprehensive phylogeny to date. Our analysis includes all genera, morphological data from external morphology, cranial osteology and hemipenial morphology, and DNA sequences from mitochondrial and nuclear genes. We performed analyses with parsimony as an optimality criterion, using different schemes for character weighting. We evaluated the contribution of the different sources of characters to the phylogeny through analyses of reduced datasets and calculation of weighted homoplasy and retention indexes. We performed a morphological character analysis to identify synapomorphies for the main clades. In terms of biogeography, our results support a single colonization event of the Americas by pitvipers, and a cladogenetic event into a Neotropical clade and a North American/Neotropical clade. The results also shed light on the previously unstable position of some taxa, although they could not sufficiently resolve the position of Bothrops lojanus, which may lead to the paraphyly of either Bothrops or Bothrocophias. The morphological character analyses demonstrated that an important phylogenetic signal is contained in characters related to head scalation, the jaws and the dorsum of the skull, and allowed us to detect morphological convergences in external morphology associated with arboreality.