bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of Central Post-Stroke Pain: Systematic Review and Meta-Analysis
Authors: Tamasauskas Arnas , Marshall Andrew , Silva-Passadouro Barbara , Fallon Nichollas , Frank Bernhard , Laurinaviciute Svajune , Keller Simon 
Published: January 2024

AbstractCentral post stroke pain (CPSP) is a neuropathic pain condition prevalent in 8% to 35% of stroke patients. This systematic review and meta-analysis aimed to provide insight in the effectiveness of available pharmacological, physical, psychological, and neuromodulation intervention in reducing pain in CPSP patients. Secondary outcomes included mood, sleep, global impression of change, and physical responses. Data extraction included participant demographics, stroke aetiology, pain characteristics, pain reduction scores, and secondary outcome metrics. Forty two original studies were included with a total of 1451 participants. Twelve studies met requirements for a random-effects meta-analysis which found: neuromodulation to be the most effective with a moderate effect on pain scores (SMD = -0.60, 95% confidence interval [-0.97, -0.23]), followed by physical interventions with moderate effect (SMD = -0.55, [-1.28, 0.18), and pharmacological interventions with a small effect on pain (SMD = -0.36, [-0.68, -0.03]). Fourteen studies were included in proportional meta-analysis with pharmacological studies having a moderate effect (58.34% mean reduction, [36.50, 80.18]), and neuromodulation studies a small effect (31.70% mean reduction, [21.44, 41.96]). Sixteen studies were included in the narrative review. While the overall medium risk of bias limits generalisation of findings, fluvoxamine and repetitive transcranial magnetic stimulation was found to have consistently good pain alleviation and relatively low risk of side effects. Anticonvulsants were found to have a significant effect on pain reduction, but were found to have the most side effects. Virtual reality and acupuncture show promising results, but lack rigorous methodological investigation to understand their full effect.
Trajectories in county-level Low Birthweight Rates and Associated Contextual Factors in the United States, 2016-2021
Authors: Dwivedi Pallavi , Nguyen Thu T. , He Xin , Nguyen Quynh C. 
Published: January 2024

ABSTRACTIntroductionInfants with low birthweight (less than 2500 grams) have greater risk of mortality, long-term neurologic disability and chronic diseases such as diabetes and cardiovascular disease as compared to infants with normal birthweight. This study examined the trajectories of low birthweight rate in the U.S. across the metropolitan and non-metropolitan counties over the time period of 2016-2021 and the associated contextual factors.MethodsThis longitudinal study utilized data on 21,759,834 singleton births across 3,108 counties. Data on birthweight and maternal sociodemographic and behavioral characteristics was obtained from the National Center for Health Statistics. A generalized estimating equations model was used to examine the association of county-level contextual variables with low birthweight rates.ResultsA significant increase in low birthweight rates was observed across the counties over the duration of the study. Large metro and small metro counties had significantly higher low birthweight rates as compared to non-metro counties. High percentage of Black women, underweight women, age more than 35 years, lack of prenatal care, uninsured population, and high violent crime rate was associated with an increase in low-birth-weight rates. Other contextual characteristics (percentage of married women, American Indian/Alaskan Native women, and unemployed population) differed in their associations with low birthweight rates depending on county metropolitan status.ConclusionsOur study findings emphasize the importance of developing interventions to address geographical heterogeneity in low birthweight burden, particularly for metropolitan areas and communities with vulnerable racial/ethnic and socioeconomic groups.
Contrasting methods of measurement of antibiotic exposure in clinical research: a real-world application predicting hospital-associatedClostridioides difficileinfection
Authors: Webster Jessica L. , Eppes Stephen , Lee Brian K , Harrington Nicole S. , Goldstein Neal D. 
Published: January 2024

ABSTRACTThe goal of this article is to summarize common methods of antibiotic measurement used in clinical research and demonstrate analytic methods for selection of exposure variables. Variable selection was demonstrated using three methods for modeling exposure, using data from a case-control study onClostridioides difficileinfection in hospitalized patients: 1) factor analysis of mixed data, 2) multiple logistic regression models, and 3) Least Absolute Shrinkage and Selection Operator (LASSO) regression. The factor analysis identified 9 variables contributing the most variation in the dataset:any antibiotic treatment;number of classes;number of treatments;dose; and classesmonobactam, β-lactamβ-lactamase inhibitors,rifamycin,carbapenem, andcephalosporin. The regression models resulting in the best model fit used predictorsany antibiotic exposureandproportion of hospitalization on antibiotics. The LASSO model selected 22 variables for inclusion in the predictive model, exposure variables including:any antibiotic treatment; classes β-lactamβ-lactamase inhibitors,carbapenem,cephalosporin,fluoroquinolone,monobactam,rifamycin,sulfonamides, andmiscellaneous; andproportion of hospitalization on antibiotics. Investigators studying antibiotic exposure should consider multiple aspects of treatment informed by their research question and the theory on how antibiotics may impact the distribution of the outcome in their target population.
A tripartite organelle platform links growth factor receptor signaling to mitochondrial metabolism
Authors: Mesa Deborah Salvi , Barbieri Elisa , Raimondi Andrea , Freddi Stefano , Miloro Giorgia , Jendrisek Gorana , Caldieri Giusi , Quarto Micaela , Lomoriello Irene Schiano , Malabarba Maria Grazia , Bresci Arianna , Manetti Francesco , Vernuccio Federico , Abdo Hind , Scita Giorgio , Polli Dario , Tacchetti Carlo , Pinton Paolo , Bonora Massimo , Di Fiore Pier Paolo , Sigismund Sara 
Published: January 2024

AbstractOne open question in the biology of growth factor receptors is how a quantitative input (i.e.,ligand concentration) is decoded by the cell to produce specific response(s). Here, we show that an EGFR endocytic mechanism, non-clathrin endocytosis (NCE), which is activated only at high ligand concentrations and targets receptor to degradation, requires a tripartite organelle platform involving the plasma membrane (PM), endoplasmic reticulum (ER) and mitochondria. At these contact sites, EGFR-dependent, ER-generated Ca2+oscillations are sensed by mitochondria, leading to increased metabolism and ATP production. Locally released ATP is required for cortical actin remodeling and EGFR-NCE vesicle fission. The same biochemical circuitry is also needed for an effector function of EGFR, i.e., collective motility. The multiorganelle signaling platform herein described mediates direct communication between EGFR signaling and mitochondrial metabolism, and is predicted to have a broad impact on cell physiology as it is activated by another growth factor receptor, HGFR/MET.
Targeting ductal-endothelial crosstalk alleviate pancreatitis
Authors: Gao Rong-rong , Ma Lan-yue , Chen Jian-wei , Wang Yu-xiang , Li Yu-yan , Zhou Zi-yuan , Deng Zhao-hua , Zhong Jing , Shu Ya-hai , Liu Yang , Chen Qi 
Published: January 2024

AbstractPancreatitis are common gastrointestinal disorders that cause hospitalization with significant morbidity and mortality. The mechanistic pathophysiology of pancreatitis is complicated, which greatly limits the discovery of pharmacological intervention methods. Here, we show that administration of antagonist of Integrin-α5, significantly mitigates the pathological condition of acute pancreatitis. In caerulein-induced acute pancreatitis model, the newly emergent CK19 positive cells are highly vascularized with significant increase of vascular density and endothelial cell number. Single cell RNA sequencing analysis shows ductal and endothelial cells are intimate interacting partners. Pancreatitis dramatically reduce the crosstalk in ductal-endothelial interface but promote the integrin-α5 signaling. Blocking this signaling significantly reduce acinar-to-ductal metaplasia, pathological angiogenesis and restore other abnormal defects induced by caerulein. Our work reveals a therapeutic potential of targeting integrin-α5 as uncharacterized pharmacological method to alleviate the symptom of pancreatitis.
Requirements for the Biogenesis of [2Fe-2S] Proteins in the Human and Yeast Cytosol
Authors: Braymer Joseph J. , Stehling Oliver , Stümpfig Martin , Rösser Ralf , Spantgar Farah , Blinn Catharina M. , Mühlenhoff Ulrich , Pierik Antonio J. , Lill Roland 
Published: January 2024

ABSTRACTThe biogenesis of iron-sulfur (Fe/S) proteins entails the synthesis and trafficking of Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, the multiple steps of biogenesis are accomplished by complex protein machineries in both mitochondria (ISC) and cytosol (CIA). The underlying biochemical pathways have been elucidated over the past decades, yet the mechanisms of cytosolic [2Fe-2S] protein assembly have remained ill-defined. Similarly, the precise site of glutathione (GSH) requirement in cytosolic and nuclear Fe/S protein biogenesis is unclear, as is the molecular role of the GSH-dependent cytosolic monothiol glutaredoxins (cGrxs). Here, we investigated these questions in human and yeast cells by variousin vivoapproaches. [2Fe-2S] cluster assembly of cytosolic target apoproteins required the mitochondrial ISC machinery, the ABC transporter Atm1/ABCB7 and GSH, yet occurred independently of both the CIA system and cGrxs. This mechanism was strikingly different from the ISC-, Atm1/ABCB7-, GSH-, and CIA-dependent assembly of cytosolic-nuclear [4Fe-4S] proteins. One notable exception to this newly defined cytosolic [2Fe-2S] protein maturation pathway was the yeast protein Apd1 which used the CIA system via binding to the CIA targeting complex through its C-terminal tryptophan. cGrxs, although attributed as [2Fe-2S] cluster chaperones or trafficking proteins, were not essentialin vivofor deliver ing [2Fe-2S] clusters to either CIA components or apoproteins. Finally, GSH function was assigned to Atm1-dependent export, i.e. a step before GSH-dependent cGrxs function. Our findings extend the general model of eukaryotic Fe/S protein biogenesis by adding the molecular requirements for cytosolic [2Fe-2S] protein maturation.
Structural and sequential regularities modulate phrase-rate neural tracking
Authors: Zhao Junyuan , Martin Andrea E. , Coopmans Cas W. 
Published: January 2024

AbstractElectrophysiological brain activity has been shown to synchronize with the quasi-regular repetition of grammatical phrases in connected speech – so-called phrase-rate neural tracking. Current debate centers around whether this phenomenon is best explained in terms of the syntactic properties of phrases or in terms of syntax-external information, such as the sequential repetition of parts of speech. As these two factors were confounded in previous studies, much of the literature is compatible with both accounts. Here, we used electroencephalography (EEG) to determine if and when the brain is sensitive to both types of information. Twenty native speakers of Mandarin Chinese listened to isochronously presented streams of monosyllabic words, which contained either grammatical two-word phrases (e.g., catch fish, sell house) or non-grammatical word combinations (e.g., full lend, bread far). Within the grammatical conditions, we varied two structural factors: the position of the head of each phrase and the type of attachment. Within the non-grammatical conditions, we varied the consistency with which parts of speech were repeated. Tracking was quantified through evoked power and inter-trial phase coherence, both derived from the frequency-domain representation of EEG responses. As expected, neural tracking at the phrase rate was stronger in grammatical sequences than in non-grammatical sequences without syntactic structure. Moreover, it was modulated by both attachment type and head position, revealing the structure-sensitivity of phrase-rate tracking. We additionally found that the brain tracks the repetition of parts of speech in non-grammatical sequences. These data provide an integrative perspective on the current debate about neural tracking effects, revealing that the brain utilizes regularities computed over multiple levels of linguistic representation in guiding rhythmic computation.
The molecular basis for the increased stability of the FUS-LC fibril at the anionic membrane- and air-water interfaces
Authors: Paul Sanjoy , Mondal Sayantan , Shenogina Irina , Cui Qiang 
Published: January 2024

AbstractSelf-organization of biomolecules can lead to the formation of liquid droplets, hydrogels, and irreversible aggregates that bear immense significance in biology and diseases. Despite the considerable amount of studies conducted on biomolecular condensation in bulk solution, there is still a lack of understanding of how different surfaces regulate the condensation process. In this context, recent studies showed that, in contrast to zwitterionic lipid membranes, anionic membranes promoted the production of liquid droplets of FUsed in Sarcoma Low Complexity domain (FUS-LC) despite exhibiting no specific protein-lipid interactions. Moreover, the air-water interface led to a solid fibril-like aggregate of FUS-LC. The molecular mechanism of condensation/aggregation of proteins in response to surfaces of various charged states or levels of hydrophobicity remains to be better elucidated. Here, we address this question by investigating the stability of a smallβfibril state of FUS-LC in bulk solution vs. membrane- and air-water interfaces. Our study demonstrates the stability of the FUS-LC fibril in the presence of anionic membranes over 1µs timescale while the fibril falls apart in bulk solution. We observe that a zwitterionic membrane does not enhance the stability of the fibril and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) has a higher propensity to stabilize the fibril than dioleoylphosphatidylglycerol (DOPG), in qualitative agreement with experiments. We further show that the fibril becomes more stable at the air-water interface. We pinpoint interfacial solvation at the membrane- and air-water interfaces as a key factor that contributes to the stabilization of the peptide assembly.
Multiomic Data Integration Reveals Microbial Drivers of Aetiopathogenesis in Mycosis Fungoides
Authors: Licht Philipp , Mailänder Volker 
Published: January 2024

AbstractBackgroundMycosis fungoides (MF) represents the most prevalent entity of cutaneous T cell lymphoma (CTCL). The MF aetiopathogenesis is incompletely understood, due to strong transcriptomic heterogeneity and opposing perspectives on the initial oncologic transformation mapping the event to both early thymocytes and mature, effector memory T cells. Recently, using clinical specimen, our group showed that the skin microbiome aggravates disease course, mainly driven by an outgrowing, pathogenicS. aureusstrain carrying the virulence factor spa, which reportedly activates the T cell signalling pathway NF-κB.MethodsTo further investigate the role of the skin microbiome in MF aetiopathogenesis, we here performed RNA sequencing, multiomic data integration of the skin microbiome and skin transcriptome using Multi-Omic Factor Analysis (MOFA), virome profiling, and T cell receptor (TCR) sequencing in 10 MF patients representing a subset of our previous study cohort.ResultsWe observed that inter-patient transcriptional heterogeneity may be largely driven by differential activation of T cell signalling pathways. Strikingly, the MOFA model resolved the heterogenous activation pattern of T cell signalling after denoising the transcriptome from microbial influence. The MOFA model showed that the outgrowingS. aureusstrain evoked signalling by non-canonical NF-κB and IL-1B, which likely fuelled the aggravated disease course. Further, the MOFA model revealed aberrant pathways of early thymopoiesis alongside enrichment of antiviral innate immunity. In line, viral prevalence, particularly of Epstein-Barr virus (EBV), trended higher in both lesional skin and the blood compared to nonlesional skin. Additionally, TCRs in both MF skin lesions and the blood were significantly more likely to recognize EBV peptides involved in latent infection.ConclusionsFirst, our findings suggest thatS. aureuswith its virulence factor spa fuels MF progression trough non-canonical NF-κB and IL-1B signalling. Second, our data provide insights into the potential role of viruses in MF aetiology. Last, we propose a model of microbiome-driven MF aetiopathogenesis: Thymocytes undergo initial oncologic transformation, potentially caused by viruses. After maturation and skin infiltration, an outgrowing, pathogenicS. aureusstrain evokes activation and maturation into effector memory T cells, resulting in aggressive disease.
NRV: An open framework for in silico evaluation of peripheral nerve electrical stimulation strategies
Authors: Couppey Thomas , Regnacq Louis , Giraud Roland , Romain Olivier , Bornat Yannick , Kölbl Florian 
Published: January 2024

AbstractElectrical stimulation of peripheral nerves has been used in various pathological contexts for rehabilitation purposes or to alleviate the symptoms of neuropathologies, thus improving the overall quality of life of patients. However, the development of novel therapeutic strategies is still a challenging issue requiring extensivein vivoexperimental campaigns and technical development. To facilitate the design of new stimulation strategies, we provide a fully open source and self-contained software framework for thein silicoevaluation of peripheral nerve electrical stimulation. Our modeling approach, developed in the popular and well-established Python language, uses an object-oriented paradigm to map the physiological and electrical context. The framework is designed to facilitate multi-scale analysis, from single fiber stimulation to whole multifascicular nerves. It also allows the simulation of complex strategies such as multiple electrode combinations and waveforms ranging from conventional biphasic pulses to more complex modulated kHz stimuli. In addition, we provide automated support for stimulation strategy optimization and handle the computational backend transparently to the user. Our framework has been extensively tested and validated with several existing results in the literature.Author summaryElectrical stimulation of the peripheral nervous system is a powerful therapeutic approach for treating and alleviating patients suffering from a large variety of disorders, including loss of motor control or loss of sensation. Electrical stimulation works by connecting the neural target to a neurostimulator through an electrode that delivers a stimulus to modulate the electrical activity of the targeted nerve fiber population. Therapeutic efficacy is directly influenced by electrode design, placement, and stimulus parameters. Computational modeling approaches have proven to be an effective way to select the appropriate stimulation parameters. Such an approach is, however, poorly accessible to inexperienced users as it typically requires the use of multiple commercial software and/or development in different programming languages. Here, we describe a Python-based framework that aims to provide an open-source turnkey solution to any end user. The framework we developed is based on open-source packages that are fully encapsulated, thus transparent to the end-user. The framework is also being developed to enable simulation of granular complexity, from rapid first-order simulation to the evaluation of complex stimulation scenarios requiring a deeper understanding of the ins and outs of the framework.
High-content phenotypic analysis ofa C. elegansrecombinant inbred population identifies genetic and molecular regulators of lifespan
Authors: Gao Arwen W. , Alam Gaby El , Zhu Yunyun , Li Weisha , Katsyuba Elena , Sulc Jonathan , Li Terytty Y. , Li Xiaoxu , Overmyer Katherine A. , Lalou Amelia , Mouchiroud Laurent , Sleiman Maroun Bou , Cornaglia Matteo , Morel Jean-David , Houtkooper Riekelt H. , Coon Joshua J. , Auwerx Johan 
Published: January 2024

AbstractLifespan is influenced by complex interactions between genetic and environmental factors. Studying those factors in model organisms of a single genetic background limits their translational value for humans. Here, we mapped lifespan determinants in 85 genetically diverseC. elegansrecombinant intercross advanced inbred lines (RIAILs). We assessed molecular profiles – transcriptome, proteome, and lipidome – and life-history traits, including lifespan, development, growth dynamics, and reproduction. RIAILs exhibited large variations in lifespan, which positively correlated with developmental time. Among the top candidates obtained from multi-omics data integration and QTL mapping, we validated known and novel longevity modulators, includingrict-1,gfm-1andmltn-1. We translated their relevance to humans using UK Biobank data and showed that variants inRICTORandGFM1are associated with an elevated risk of age-related heart disease, dementia, diabetes, kidney, and liver diseases. We organized our dataset as a resource (https://lisp-lms.shinyapps.io/RIAILs/) that allows interactive explorations for new longevity targets.
Circadian regulation of CaV1.2 expression by RORα in the mouse heart
Authors: Personnic Estelle , Gerard Garance , Poilbout Corinne , Jetten Anton M. , Gómez Ana Maria , Benitah Jean-Pierre , Perrier Romain 
Published: January 2024

AbstractBackgroundIn addition to show autonomous beating rhythmicity, the physiological functions of the heart present daily periodic oscillations. Notably the ventricular repolarization itself varies throughout the circadian cycle which was mainly related to the periodic expression of K+channels. However, the involvement of the L-type Ca2+channel (CaV1.2 encoded byCacna1cgene) in these circadian variations remains elusive.MethodsWe used a transgenic mouse model (PCa-luc) that expresses the luciferase reporter under the control of the cardiacCacna1cpromoter and analyzed promoter activity by bioluminescent imaging, qPCR, immunoblot, Chromatin immunoprecipitation assay (ChIP) and CaV1.2 activity.ResultsUnder normal 12:12h light-dark cycle, we observedin vivoa biphasic diurnal variation of promoter activities peaking at 9 and 19.5 Zeitgeber time (ZT). This was associated with a periodicity ofCacna1cmRNA levels preceding 24-h oscillations of CaV1.2 protein levels in ventricle (with a 1.5 h phase shift) but not in atrial heart tissues. The periodicity of promoter activities and CaV1.2 proteins, which correlated with biphasic oscillations of L-type Ca2+current conductance, persisted in isolated ventricular cardiomyocytes from PCa-Luc mice over the course of the 24-h cycle, suggesting an endogenous cardiac circadian regulation. Comparison of 24-h temporal patterns of clock gene expressions in ventricles and atrial tissues of the same mice revealed conserved circadian oscillations of the core clock genes except for the retinoid-related orphan receptor α gene (RORα), which remained constant throughout the course of a day in atrial tissues.In vitrowe found that RORα is recruited to two specific regions on theCacna1cpromoter and that incubation with specific RORα inhibitor disrupted 24-h oscillations of ventricular promoter activities and CaV1.2 protein levels. Similar results were observed for pore forming subunits of the K+transient outward currents, KV4.2 and KV4.3.ConclusionsThese findings raise the possibility that the RORα-dependent rhythmic regulation of cardiac CaV1.2 and KV4.2/4.3 throughout the daily cycle may play an important role in physiopathology of heart function.