bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing femtosecond laser fabricating strategy of Nitinol hypotube for vascular interventional surgery
Authors: Song Yunfeng , Yang Zhiwei , Xu Tiangang , Xie Hao , Wang Depeng , Chen Lan , Yang Xusan 
Published: December 2024

AbstractGuidewires and catheters are essential in minimally invasive procedures, particularly in accessing targets within the vascular system for neuron surgery. Femtosecond lasers can precisely cut nickel-titanium micro tubes, known as Nitinol hypotubes, serving as the heads of micro guidewires while protecting their core tips. The quality and geometry of these hypotubes depend on the focus of the laser cutting system. We evaluated the cutting efficiency and quality of Nitinol hypotubes using objective lenses with three numerical apertures (NA). Quantitative analysis indicated that higher NA objectives yield better surface quality, resulting in lower debris. Additionally, cutting with high NA objectives produced significantly lower arithmetic mean surface roughness and enhanced mechanical properties. Using a two-temperature model, we simulated the interaction between femtosecond lasers and Nitinol, showing that higher NA objectives increase electron temperatures, thus improving material removal efficiency. This study also tested the optimized Nitinol hypotube prformance in simulations of invasive neuron surgery.
The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity
Authors: Fleming Andrew C. , Rao Nalini R. , Wright Matthew , Savas Jeffrey N. , Kiskinis Evangelos 
Published: December 2024

ABSTRACTThe degeneration of neurons in patients with amyotrophic lateral sclerosis (ALS) is commonly associated with accumulation of misfolded, insoluble proteins. Heat shock proteins (HSPs) are central regulators of protein homeostasis as they fold newly synthesized proteins and refold damaged proteins. Heterozygous loss-of- function mutations in theDNAJC7gene that encodes an HSP co-chaperone were recently identified as a cause for rare forms of ALS, yet the mechanisms underlying pathogenesis remain unclear. Using mass spectrometry, we found that the DNAJC7 interactome in human motor neurons (MNs) is enriched for RNA binding proteins (RBPs) and stress response chaperones. MNs generated from iPSCs with the ALS-associated mutation R156X inDNAJC7exhibit increased insolubility of its client RBP HNRNPU and associated RNA metabolism alterations. Additionally, DNAJC7 haploinsufficiency renders MNs increasingly susceptible to proteotoxic stress and cell death as a result of an ablated HSF1 stress response pathway. Critically, expression of HSF1 in mutant DNAJC7 MNs is sufficient to rescue their sensitivity to proteotoxic stress, while postmortem ALS patient cortical neurons exhibit a reduction in the expression of HSF1 pathway genes. Taken together, our work identifies DNAJC7 as a crucial mediator of HNRNPU function and stress response pathways in human MNs and highlights HSF1 as a therapeutic target in ALS.
The effects of varying intensities of unilateral handgrip fatigue on bilateral movement
Authors: Knorz Adrian L. , Andrushko Justin W. , Sporn Sebastian , Stagg Charlotte J. , Zich Catharina 
Published: December 2024

AbstractThe human ability to maintain adequate movement quality despite muscle fatigue is of critical importance to master physically demanding activities of daily life and for retaining independence following motor impairments. Many real-life situations call for asymmetrical activation of extremity muscles leading to unilateral manifestations of muscle fatigue. Repeated unilateral handgrip contractions at submaximal force have been shown to be associated with neural dynamics in both contralateral and ipsilateral cortical motor areas and improved response times of the contralateral, unfatigued homologue in a button-press task. However, it remains unclear whether the observed improvement in contralateral response latency translates into higher-level benefits in movement quality.To investigate this, 30 healthy participants underwent unilateral handgrip fatiguing tasks at 5%, 50%, and 75% of maximum voluntary contraction (MVC) force. Subsequently, bimanual movement quality was assessed in an object-hit task using a Kinarm robot.The protocol at 50% and 75% of MVC elicited clear signs of muscle fatigue compared to the control condition (5%) measured by a decline in force, post-exercise deterioration in MVC, characteristic changes in surface electromyography magnitudes, and increases in ratings of perceived exertion. No change was observed on kinematic measures in the object-hit task for both arms indicating that unilateral handgrip fatigue did not elicit measurable effects on higher-level movement quality on the ipsilateral or contralateral homologue. Previously reported improvements on contralateral response latency were not found to translate into advanced movement quality benefits.
Early prediction of preeclampsia using the first trimester vaginal microbiome
Authors: Kindschuh William F. , Austin George I. , Meydan Yoli , Park Heekuk , Urban Julia A. , Watters Emily , Pollak Susan , Saade George R. , Chung Judith , Mercer Brian M. , Grobman William A. , Haas David M. , Silver Robert M. , Serrano Myrna , Buck Gregory A. , McNeil Rebecca , Nandakumar Renu , Reddy Uma , Wapner Ronald J. , Kav Aya Brown , Uhlemann Anne-Catrin , Korem Tal 
Published: December 2024

AbstractPreeclampsia is a severe obstetrical syndrome which contributes to 10-15% of all maternal deaths. Although the mechanisms underlying systemic damage in preeclampsia—such as impaired placentation, endothelial dysfunction, and immune dysregulation—are well studied, the initial triggers of the condition remain largely unknown. Furthermore, although the pathogenesis of preeclampsia begins early in pregnancy, there are no early diagnostics for this life-threatening syndrome, which is typically diagnosed much later, after systemic damage has already manifested. Here, we performed deep metagenomic sequencing and multiplex immunoassays of vaginal samples collected during the first trimester from 124 pregnant individuals, including 62 who developed preeclampsia with severe features. We identified multiple significant associations between vaginal immune factors, microbes, clinical factors, and the early pathogenesis of preeclampsia. These associations vary with BMI, and stratification revealed strong associations between preeclampsia andBifidobacteriumspp.,Prevotella timonensis, andSneathia vaginalis. Finally, we developed machine learning models that predict the development of preeclampsia using this first trimester data, collected ~5.7 months prior to clinical diagnosis, with an auROC of 0.78. We validated our models using data from an independent cohort (MOMS-PI), achieving an auROC of 0.80. Our findings highlight robust associations among the vaginal microbiome, local host immunity, and early pathogenic processes of preeclampsia, paving the way for early detection, prevention and intervention for this devastating condition.
Optogenetically Induced Microtubule Acetylation Unveils the Molecular Dynamics of Actin-Microtubule Crosstalk in Directed Cell Migration
Authors: Deb Roy Abhijit , Saez Gonzalez Cristian , Shahid Farid , Yadav Eesha , Inoue Takanari 
Published: December 2024

AbstractMicrotubule acetylation is implicated in regulating cell motility, yet its physiological role in directional migration and the underlying molecular mechanisms have remained unclear. This knowledge gap has persisted primarily due to a lack of tools capable of rapidly manipulating microtubule acetylation in actively migrating cells. To overcome this limitation and elucidate the causal relationship between microtubule acetylation and cell migration, we developed a novel optogenetic actuator, optoTAT, which enables precise and rapid induction of microtubule acetylation within minutes in live cells. Using optoTAT, we observed striking and rapid responses at both molecular and cellular level. First, microtubule acetylation triggers release of the RhoA activator GEF-H1 from sequestration on microtubules. This release subsequently enhances actomyosin contractility and drives focal adhesion maturation. These subcellular processes collectively promote sustained directional cell migration. Our findings position GEF-H1 as a critical molecular responder to microtubule acetylation in the regulation of directed cell migration, revealing a dynamic crosstalk between the actin and microtubule cytoskeletal networks.
From Stability to Complexity: A Systematic Review Protocol on Long-term Divergence Exponents in Gait Analysis
Authors: Terrier Philippe 
Published: December 2024

ABSTRACTLong-term divergence exponents derived from nonlinear gait analysis (maximum Lyapunov exponent method) have recently been reinterpreted as measures of gait complexity rather than stability. This shift necessitates a comprehensive review of existing literature. This systematic review protocol aims to critically examine studies using long-term divergence exponents in gait analysis. The focus will be on reconciling previous findings with current understanding, evaluating methodological approaches, and synthesizing comparable results. We will search Web of Science (including MEDLINE) for peer-reviewed articles published between 2001 and 2024 that report long-term divergence exponents calculated using Rosenstein’s algorithm in human gait studies. Two independent reviewers will screen articles and extract data on study characteristics, methodological specifications, and result interpretations. Primary outcomes will include tracking how result interpretations have evolved over time and identifying potential reinterpretations based on current knowledge. Secondary outcomes will address methodological standardization. Data synthesis will primarily be narrative. Where possible, meta-analyses will be conducted for studies with comparable methods and objectives. Given the expected exploratory nature of many included studies, a narrative assessment of methodological quality will be performed instead of a formal risk of bias evaluation. This review will consolidate understanding of long-term divergence exponents as measures of gait complexity and automaticity, establish standardized computational methods, and inform future research and clinical applications in gait analysis.
DNA methylation in primary myelofibrosis is partly associated with driver mutations and distinct from other myeloid malignancies
Authors: Torlak Esra Dursun , Tharmapalan Vithurithra , Kricheldorf Kim , Schifflers Joelle , Caduc Madeline , Zenke Martin , Koschmieder Steffen , Wagner Wolfgang 
Published: December 2024

AbstractPrimary myelofibrosis (PMF) is a clonal blood disorder characterized by mutually exclusive driver mutations inJAK2,CALR, orMPLgenes. To explore the epigenetic impact of these mutations, we analyzed DNA methylation (DNAm) profiles from PMF patients. Notably, no differences were found in DNAm betweenJAK2andCALRmutated cases, whereasMPLmutations displayed slightly distinct patterns. Furthermore, induced pluripotent stem cell (iPSC) models withJAK2mutations indicated only a moderate association with PMF-related epigenetic changes, suggesting that these alterations may not be directly driven by the mutations themselves. Additionally, PMF-associated epigenetic changes showed minimal correlation with allele burden and were largely influenced by shifts in the cellular composition. PMF DNAm profiles compared with those from other myeloid malignancies - such as acute myeloid leukemia, juvenile myelomonocytic leukemia, and myelodysplastic syndrome – showed numerous overlapping changes, making it difficult to distinguish PMF based on individual CpGs. However, a PMF score created by combining five CpGs was able to discern PMF from other diseases in both training and validation datasets. These findings demonstrate that PMF driver mutations do not directly evoke epigenetic changes. While PMF shares certain epigenetic alterations with other myeloid malignancies, epigenetic signatures can distinguish between PMF and related diseases.
Adherence to Life’s Essential 8 is associated with delayed white matter aging
Authors: Feng Li , Ye Zhenyao , Pan Yezhi , McCoy Rozalina G. , Mitchell Braxton D. , Kochunov Peter , Thompson Paul M. , Chen Jie , Liang Menglu , Nguyen Thu T. , Shenassa Edmond , Li Yan , Canida Travis , Ke Hongjie , Lee Hwiyoung , Liu Song , Hong L. Elliot , Chen Chixiang , Lei David K.Y. , Chen Shuo , Ma Tianzhou 
Published: December 2024

AbstractImportanceThe American Heart Association introduced Life’s Essential 8 (LE8) as a checklist of healthy lifestyle factors to help older individuals maintain and improve cardiovascular health and live longer. How LE8 can foster healthy brain aging and interact with genetic risk factors to render the aging brain less vulnerable to dementia is not well understood.ObjectiveTo investigate the impact of LE8 on the white matter brain aging and the moderating effects of theAPOE4allele.Design, Setting, and ParticipantsThis cross-sectional study uses genetic, imaging, and other health-related data collected in the UK Biobank cohort. Participants included non-pregnant whites with LE8 variables, diffusion tensor imaging data, and genetic data onAPOE4available, and excluded the extreme white matter hyperintensities. The baseline assessment was performed from 2006 to 2010. The diffusion tensor imaging data were collected since 2014.ExposuresLE8 variables, encompassing diet, physical activity, smoking, sleep, body mass index, lipids, hemoglobin, and blood pressure.Main Outcomes and MeasuresThe white matter brain age was predicted from regional fractional anisotropy measures derived from diffusion tensor imaging data using the random forest regression method. The outcome white matter brain age gap was calculated by subtracting individuals’ chronological age from their predicted brain age.ResultsThe analysis included 9,430 women and 9,387 men (mean age 55.45 [SD: 7.46] years). Higher LE8 scores were associated with lower white matter brain age gap, indicating delayed brain aging. The findings are consistent for each of the individual LE8 variables. The effect was stronger among non-APOE4carriers (124 days younger per 10-point increase, 95% CI, 102 to 146 days; P<0.001) thanAPOE4carriers (84 days younger per 10-point increase, 95% CI, 47 to 120 days; P<0.001). Notably, early middle-aged women withAPOE4showed significant interactions between LE8 scores and brain aging (P interaction = 0.048), not observed in men.Conclusions and RelevanceAdherence to LE8 is associated with delayed brain aging, moderated by genetic factors such asAPOE4. These findings highlight the potential of behavioral and lifestyle interventions in reducing dementia risk, emphasizing tailored prevention plans for those with different genetic predispositions to dementia and sex.
Neurons of the human subthalamic nucleus engage with local delta frequency processes during action cancellation
Authors: Szabó Johanna Petra , Hegedüs Panna , Laszlovszky Tamás , Halász László , Miklós Gabriella , Király Bálint , Perczel György , Bokodi Virág , Entz Lászlo , Ulbert István , Tamás Gertrúd , Fabó Dániel , Erőss Loránd , Hangya Balázs 
Published: December 2024

AbstractThe subthalamic nucleus (STN) is a key regulator of inhibitory control, implicated in decision making under conflict and impulsivity. Delta frequency oscillations, both in the STN and in frontal cortices have been associated with such active decision processes. However, it is yet unclear how neurons of the human STN are linked to local delta frequencies during response inhibition. Here, we recorded STN neurons and local field potentials (LFP) in human patients with Parkinson’s disease (PD) while they performed a stop-signal reaction time task during deep brain stimulation implantation surgery. Delta band LFP activity increased during stimulus processing in the STN. We found that half of the STN neurons responded to a diverse set of behaviorally relevant events that included go and stop signals, with a subset of neurons showing differential responses in successful and unsuccessful attempts at response cancelling. Failure to stop was associated with stronger go signal-related firing increase of STN neurons and their stronger coupling to local delta band LFP activity. Furthermore, a specific population of bursting STN neurons showed increased delta coupling. These suggest that the STN integrates go and stop signal-related information. Increased engagement of STN neurons with local delta band activity during stimulus processing impaired the ability to cancel the ongoing response. This effect may be linked to the disease-related rise in STN neuronal bursting. These findings may shed light on a potential neuronal mechanism linking cortical delta band processes with STN activity, both of which are critical elements in inhibitory control.
Efficient and accurate simulation of infectious diseases on adaptive networks
Authors: Gubela Nils , von Kleist Max 
Published: December 2024

AbstractMathematical modelling of infectious disease spreading on temporal networks has recently gained popularity in complex systems science to understand the intricate interplay between social dynamics and epidemic processes. While analytic solutions for these systems can usually not be obtained, numerical studies through exact stochastic simulation has remained infeasible for large, realistic systems.Here, we introduce a rejection-based stochastic sampling algorithm with high acceptance probability (‘high-acceptance sampling’; HAS), tailored to simulate disease spreading on adaptive networks. We proof that HAS is exact and can be multiple orders faster than Gillespie’s algorithm. While its computational efficacy is dependent on model parameterization, we show that HAS is applicable regardless on whether contact dynamics are faster, on the same time-scale, or slower than the concurrent disease spreading dynamics. The algorithm is particularly suitable for processes where the spreading- and contact processes are co-dependent (adaptive networks), or when assumptions regarding time-scale separation become violated as the process unfolds. To highlight potential applications, we study the impact of diagnosis- and incidence-driven behavioural changes on virtual Mpox- and COVID-like epidemic and examine the impact of adaptive behaviour on the spreading processes.Author SummaryInfectious disease spreading is often affected by the dynamics of human-human contacts. These contact dynamics may change over time, and in direct response to infection kinetics, through e.g. self-isolation, risk-aversion, or anyadaptivebehaviour, which can generate complex dynamics as seen in recent outbreaks with e.g. COVID-19, as well as Mpox clade IIb (2022). Agent-based models (ABMs) are often derived and numerically simulated to study the complex interplay between epidemic- and contact dynamics and to derive insights for disease control. However, numerical simulation of these models denotes a computational bottleneck and limits the applicability of large ABMs. We introduce a novel numerical method called ‘high-acceptance sampling’ (HAS), which allows for the exact simulation of outbreaks withadaptivecontact behaviour. We proof that HAS is exact, show that it is faster, and that runtime grows with at least an order of magnitude less than state-of-the art exact simulation methods. This enables simulation of outbreaks on large populations, as well as parameter estimation for large systems. We apply HAS to study an Mpox- and COVID-like pandemic and the impact of adaptive behaviour on different time-evolving contact networks.
The Effect of Length of Stay in Hospital on Patients’ Health Outcomes: A Quasi-Experimental Study
Authors: Langenberger Benedikt , Worsham Christopher , Geldsetzer Pascal 
Published: December 2024

AbstractThe causal effect of hospital length of stay on crucial patient out-comes such as readmissions or mortality is under-investigated and therefore unknown for the vast majority of the US population. Existing evidence stems from association studies that are unable to draw causal conclusions. This study leverages Medicare’s two-midnight (2MN) and three-day (3D) rules as two natural experiments to establish causal rela-tionships between hospital length of stay (LOS) and patient outcomes. Using a quasi-experimental regression discontinuity design with data from a large US hospital, we find that the 2MN rule increases LOS by 0.10 days and the 3D rule by 0.21 days, confirming the validity of these rules as instruments for causal inference. However, despite these increases in LOS, there are no significant effects on 90-day mortality or 30-day readmission rates. These findings suggest that while the 2MN and 3D rules effectively extend hospital stays, they do not im-prove patient-related outcomes, indicating an inefficient use of hospital resources.
Shared tendencies between the adoption of masking sentiment and vaccine sentiment can determine the outcome of disease spread
Authors: Mehta Rohan S. 
Published: December 2024

AbstractIn the last two decades, the impact of human health-related behavior on the spread of the disease has increased in prominence due to the proliferation of sentiment against public health-promoting behaviors such as vaccination and mask-wearing. The recent SARS-COV-2 pandemic brought these effects into sharp focus. Recently, coupled-contagion epidemiological models have been used to study the joint impact of human behavior and disease. These models treat sentiment towards a particular public health intervention as a contagion spreading in parallel to the disease itself. In this paper, we use a coupled-contagion model to study the interaction of two different health behaviors—vaccination and mask-wearing. In particular, we study how a positive or negative association between these behaviors—e.g. a pro-vaccine person may be more likely to be pro-mask-wearing—affects disease dynamics. We find that the strength of such an association alone can determine the outcome of disease spread in the short term and the long term. In addition to studying human health-related behaviors separately, it is vitally important to understand how these behaviors are associated with each other and how these associations affect the outcomes of epidemics.