bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating Human Astrocyte Differentiation: Direct and Rapid one-step Differentiation of Induced Pluripotent Stem Cells to Functional Astrocytes Supporting Neuronal Network development
Authors: Schuurmans Imke M.E. , Mordelt Annika , Linda Katrin , Puvogel Sofia , Duineveld Denise , Hommersom Marina P. , Rahm Lisa , Dyke Emma , Scholten Gijs-Jan , Knorz Caroline , Oudakker Astrid , van Bokhoven Hans , de Witte Lot D. , van Karnebeek Clara D.M. , Garanto Alejandro , Kasri Nael Nadif 
Published: March 2024

AbstractAstrocytes play a pivotal role in neuronal network development. Despite the well-known role of astrocytes in the pathophysiology of neurologic disorders, the utilization of human induced pluripotent stem cell (hiPSC)-derived astrocytes in neuronal networks remains limited. Here, we present a streamlined one-step protocol for the differentiation of hiPSCs directly into functional astrocytes without the need for ectopic gene expression or neural progenitor cell generation. We found that culturing hiPSCs directly in commercial astrocyte medium, was sufficient to differentiate hiPSCs into functional astrocytes within five weeks. Validation to varying extents across thirty hiPSC-lines demonstrated consistent astrocyte differentiation with minimal batch-to-batch variability. We confirmed astrocyte identity and functionality of the hiPSC-astrocyte monocultures by immunofluorescence, flowcytometry, RNA sequencing, glutamate uptake assays and calcium signaling recordings. Optimization of the protocol enabled co-culture of hiPSC-astrocytes with Ngn2 hiPSC-derived neurons (iNeurons), promoting neuronal differentiation and synapse formation. Lastly, we used single-cell electrophysiology and multi-electrode arrays to confirm robust neuronal network development in 5-week-old hiPSC-astrocyte and iNeuron co-cultures. This protocol offers a rapid and efficient method to establish all-human astrocyte-neuron co-cultures, facilitating the investigation of cell-type-specific contributions to disease pathogenesis. While validated across multiple hiPSC lines, we actively encourage researchers to test and provide feedback on this protocol to enhance its validation for future iterations.
Mitogenomics, phylogenetic position, and updated distribution ofErgasilus kandti, an ergasilid copepod parasitizing African cichlid fishes
Authors: Jansen Dries , Vanhove Maarten P. M. , Makasa Lawrence , Vorel Jiří , Kmentová Nikol , Cruz-Laufer Armando J. 
Published: March 2024

AbstractErgasilidae are a family of globally distributed copepods parasitizing freshwater fish. Despite their widespread occurrence, their phylogeographic patterns are poorly understood, specifically in the African Great Lakes. Here, we aim to provide an update on distribution ofErgasilus kandti,a copepod species infectingTylochromis polylepis,an endemic cichlid fish species in Lake Tanganyika, and the phylogenetic relationship of African ergasilids. We present the first record ofE. kandtiparasitizing the gills ofT. polylepisin Lake Tanganyika proper, identified through light microcopy and, for the first time for any ergasilid, confocal laser scanning microscopy. We suggest that this technique adds spatial context to characters and are hardly visible while using light microscopy. Phylogenetic analyses based on ribosomal DNA fragments suggest two monophyletic groups of African ergasilids. However, the phylogenetic relationships ofErgasilusremain unresolved, possibly because of the insufficient resolution of these widely used phylogenetic markers and low taxonomic coverage. A comparison of ergasilid mitochondrial genomes highlights traits found in other parasite lineages including genome shrinkage and low evolutionary rates of thecox1gene. This study presents the most extensive molecular characterization of any ergasilid species to date.
Independent size regulation of bones and appendages in zebrafish
Authors: Aramaki Toshihiro , Kondo Shigeru 
Published: March 2024

AbstractVertebrate appendages vary in length among species, despite a low divergence in bone configuration. In this study, we assessed whether the total sizes of anatomical features are constrained by the lengths of individual bones during development. We examined size control by expressing mutant genes related to allometric growth in zebrafish fins under cell type-specific promoters. Hyperactive potassium channel (kcnk5bW169L) or dominant-negative gap junction protein connexin (Cx43T154A) expression in epidermal cells increased or decreased fin size, respectively, but did not influence the lengths of fin bone segments. Osteoblast expression of these mutant genes altered fin bone segment length but not total fin size. The combination of kcnk5bW169Lin epidermal cells and Cx43T154Ain osteoblasts resulted in transgenic fish with large fins and short bone segments, and vice versa. These results clearly indicate that fin size and bone segment length are determined separately by independent regulatory systems, despite the use of the same genes. These findings shed new light on the evolution of allometric traits.
Cladribine tablets in Relapsing-Remitting Multiple Sclerosis preferentially target B-cells
Authors: Ammoscato Francesca , Aboulwafa Mohammad , Skonieczna Justyna , Bestwick Jonathan , Monero Rosemary , Andrews Michael , Trane Stefania De , Holden David , Adams Ashok , Bianchi Lucia , Turner Ben , Marta Monica , Schmierer Klaus , Baker David , Giovannoni Gavin , Gnanapavan Sharmilee 
Published: March 2024

AbstractRecently it has been shown that treatments targeting B cells in multiple sclerosis (MS) are effective in controlling disease activity. B cells contribute to the pathogenesis of MS via antigen presentation, T cell activation, and antibody production. In the chronic progressive cladribine trial, some patients treated with cladribine had a significant decline in oligoclonal band number. However, the mode of action of cladribine tablets (CladT) on peripheral immune cells and its biological activity within the CNS remains to be determined further.The CladB study is a longitudinal prospective investigation of CladT treatment in relapsing-remitting MS (RRMS). Blood was sampled at Day 0, 1, 5, then once a week for 8 weeks, fortnightly up to 24 weeks, and once a month till 96 weeks for immune cells. This was compared to a historical cohort of alemtuzumab treated samples for one month. Paired cerebrospinal fluid (CSF) and blood were also taken at Day 0, 48 and 96 weeks after initiating CladT for Kappa and Lambda-free light chain (кFLC, λFLC) index, oligoclonal bands (OCBs), immunoglobulin indices, inflammatory mediators and neurofilament light chain (NfL). Participants also underwent clinical and magnetic resonance imaging brain assessments.Ten participants (3 male, 7 female, mean age 35.9 ± 10.5 (SD) and Expanded disability Status Scale 2.5 (range 0-6) at baseline were enrolled. B cells, in particular memory B cells, were heavily depleted by CladT. Alemtuzumab, conversely rapidly depleted both T and B cells. Although still present, reduction in OCB numbers were observed in 4/10 participants and кFLC index reduced from mean 164.5 ± 227.1 (SD) at baseline to 71.3 ± 84.7 at 48 weeks (p=0.002) and 64.4 ± 67.3 at 96 weeks (p=0.01). This coincided with reduction in IgG index [1.1 ± 0.5 (SD) at baseline, 0.8 ± 0.4 (p=0.014) at 48 weeks and 0.8 ± 0.3 (P=0.02) at 96 weeks] and CSF CXCL-13 [88.6± 68.4 (SD) pg/mL, 39.4 ± 35.2 mg/mL (p=0.037) at 48 weeks and 19.1 ± 11.7pg/ml at 96 weeks (p=0.027)]. CSF NfL levels were reduced at 48 weeks only (p=0.01).In conclusion, our study supports the view that CladT treatment works primarily by depleting memory B-cells and antibody-secreting cell precursors in RRMS leading to sustained effects on intrathecal antibody production and total IgG associated with a reduction in the B-cell chemoattractant CXCL-13 in the CSF.
Inequalities in behavioural risk factor prevalence between five post-war generational cohorts of working age, England
Authors: Bajekal Madhavi , Scholes Shaun 
Published: March 2024

AbstractBackground and objectivesLong-term trends in health risk factor prevalence, and in inequalities, are often summarised using age-standardised point prevalence to allow for age distribution changes over time and between groups. Policies to effectively promote health require the decomposition of social change into its age-period-cohort components. As a first step, we provide a descriptive age-cohort analysis to identify patterns of generational change in key behavioural risk factors between and within post-war cohorts of working age in England.DataCross-sectional Health Survey for England data for participants aged 25-60 years was pooled between 1994-2019 (n=153,172) to construct five decennial cohorts (1940s, 1950s, 1960s, 1970s, 1980s). Socioeconomic status was classified by neighbourhood deprivation quintiles using the Index of Multiple Deprivation. Five behavioural risk factors were analysed: cigarette smoking (current-and heavy-smoking); alcohol consumption (frequency and heavy drinking); obesity; meeting recommended levels of physical activity and fruit and vegetables consumption.MethodsSex-specific analyses were conducted. Log-binomial regression models quantified the magnitude and direction of change in (i) prevalence ratios (PRs) between cohorts adjusting for age and deprivation and (ii) deprivation-specific PRs within- and between-cohorts to examine changes in absolute and relative inequalities between generations.ResultsIn more recent cohorts, decreases in prevalence, independent of age and deprivation, were observed for current smoking, frequency of alcohol consumption and heavy drinking, resulting in decreasing absolute inequalities. However, obesity levels, particularly among females, reached their highest levels in the youngest 1980s cohort.Relative inequalities in current smoking (most-versus least-deprived quintiles) peaked in the 1950s cohort (Males: PR 2.79 (95% CI:2.57-3.04); Females: PR 2.81; 95% CI: 2.60-3.05)), decreased in the 1960s cohort (M: PR 2.00 (95% CI:1.70-2.34); F: PR 2.58 (95% CI:2.40-2.77)), and remained stable thereafter. Inequalities in heavy smoking persisted over time among current smokers.Higher obesity levels in the most-versus least-deprived quintiles were generally persistent across all five cohorts, albeit with some suggestion of widening inequalities in the younger-versus older-cohorts in females (1940s cohort: PR 1.55 (95% CI:1.40-1.72); 1960s cohort: PR 1.87 (95% CI: 1.73-2.01)). This pattern was also observed for mean body mass index (BMI).For heavy drinking, relative inequality remained stable. Relative inequalities in fruit and vegetable consumption were lower in more recent cohorts. Physical activity levels were similar across cohorts, with little evidence of inequalities.ConclusionOur analysis of generational change reveals credible signals of behavioural risk factor changes in levels and in inequalities over successive post-war cohorts of working age.
Applications of Large Language Models in Psychiatry: A Systematic Review
Authors: Omar Mahmud , Soffer Shelly , Charney Alexander W , Landi Isotta , Nadkarni Girish N , Klang Eyal 
Published: March 2024

AbstractBackgroundWith their unmatched ability to interpret and engage with human language and context, large language models (LLMs) hint at the potential to bridge AI and human cognitive processes. This review explores the current application of LLMs, such as ChatGPT, in the field of psychiatry.MethodsWe followed PRISMA guidelines and searched through PubMed, Embase, Web of Science, and Scopus, up until March 2024.ResultsFrom 771 retrieved articles, we included 16 that directly examine LLMs’ use in psychiatry. LLMs, particularly ChatGPT and GPT-4, showed diverse applications in clinical reasoning, social media, and education within psychiatry. They can assist in diagnosing mental health issues, managing depression, evaluating suicide risk, and supporting education in the field. However, our review also points out their limitations, such as difficulties with complex cases and potential underestimation of suicide risks.ConclusionEarly research in psychiatry reveals LLMs’ versatile applications, from diagnostic support to educational roles. Given the rapid pace of advancement, future investigations are poised to explore the extent to which these models might redefine traditional roles in mental health care.
Assessing Post-TAVR Cardiac Conduction Abnormalities Risk Using a Digital Twin of a Beating Heart
Authors: Reza Symon , Kovarovic Brandon , Bluestein Danny 
Published: March 2024

AbstractTranscatheter aortic valve replacement (TAVR) has rapidly displaced surgical aortic valve replacement (SAVR). However, certain post-TAVR complications persist, with cardiac conduction abnormalities (CCA) being one of the major ones. The elevated pressure exerted by the TAVR stent onto the conduction fibers situated between the aortic annulus and the His bundle, in proximity to the atrioventricular (AV) node, may disrupt the cardiac conduction leading to the emergence of CCA. In his study, anin-silicoframework was developed to assess the CCA risk, incorporating the effect of a dynamic beating heart and pre-procedural parameters such as implantation depth and preexisting cardiac asynchrony in the new onset of post-TAVR CCA. A self-expandable TAVR device deployment was simulated inside an electro-mechanically coupled beating heart model in five patient scenarios, including three implantation depths, and two preexisting cardiac asynchronies: (i) a right bundle branch block (RBBB) and (ii) a left bundle branch block (LBBB). Subsequently, several biomechanical parameters were analyzed to assess the post-TAVR CCA risk. The results manifested a lower cumulative contact pressure on the conduction fibers following TAVR for aortic deployment (0.018 MPa) compared to baseline (0.29 MPa) and ventricular deployment (0.52 MPa). Notably, the preexisting RBBB demonstrated a higher cumulative contact pressure (0.34 MPa) compared to the baseline and preexisting LBBB (0.25 MPa). Deeper implantation and preexisting RBBB cause higher stresses and contact pressure on the conduction fibers leading to an increased risk of post-TAVR CCA. Conversely, implantation above the MS landmark and preexisting LBBB reduces the risk.
Acute and Longitudinal Effects of Sport-related Concussion on Reactive Balance
Authors: Monoli Cecilia , Morris Amanda , Crofts Regan , Fino Nora F. , Petersell Tessa L. , Jameson Trevor , Dibble Leland E. , Fino Peter C. 
Published: March 2024

ABSTRACTPostural instability is a common observation after concussions, with balance assessments playing a crucial role in clinical evaluations. Widely used post-concussion balance tests focus primarily on static and dynamic balance, excluding the critical aspect of reactive balance. This study investigated the acute and longitudinal effects of concussion on reactive balance in collegiate athletes. The assessments were conducted at pre-season baseline and 4 post-concussion timepoints: acute, pre-return-to-play, post-return-to-play, and six months post-concussion. The instrumented-modified Push and Release test measured reactive balance. Longitudinal effects of concussions on time to stability and step latency metrics were investigated applying Generalized Estimating Equations. Acutely after concussion, athletes demonstrated impaired reactive balance, indicated by longer times to stability, in dual-task conditions (p= 0.004). These acute impairments were transient and recovered over time. Exploratory analyses revealed that athletes who sustained their first lifetime concussion exhibited both acute (p= 0.037) and longitudinal (p= 0.004 at post-return-to-play) impairments in single– and dual-task compared to controls with no lifetime concussion. This comprehensive evaluation provides insights into the multifaceted nature of post-concussion impairments and emphasizes the importance of considering cognitive demand and history of concussions in assessing athletes’ balance.
Effectiveness of Autumn 2023 COVID-19 vaccination and residual protection of prior doses against hospitalisation in England, estimated using a test-negative case-control study
Authors: Møller Kirsebom Freja Cordelia , Stowe Julia , Bernal Jamie Lopez , Allen Alex , Andrews Nick 
Published: March 2024

AbstractIntroductionThe last COVID-19 vaccine offered to all adults in England became available from November 2021. The most recent booster programme commenced in September 2023. Bivalent BA.4-5 or monovalent XBB.1.5 boosters were given. During the study period, the JN.1 variant became dominant in England.MethodsVaccine effectiveness against hospitalisation was estimated throughout using the test-negative case-control study design where positive PCR tests from hospitalised individuals are cases and comparable negative PCR tests are controls. Multivariable logistic regression was used to assess vaccine effectiveness against hospitalisation with the test result as the outcome, vaccination status as the primary exposure variable of interest and confounder adjustment.ResultsThere was no evidence of residual protection for boosters given as part of previous campaigns. There were 28,916 eligible tests included to estimate the effectiveness of the autumn 2023 boosters in those aged 65 years and older. VE peaked at 50.6% (95% CI: 44.2-56.3%) after 2-4 weeks, followed by waning to 13.6% (95% CI: -11.7-33.2%). Estimates were generally higher for the XBB.1.5 booster than the BA.4-5 booster, but this difference was not statistically significant. Point estimates were highest against XBB sub-lineages. Effectiveness was lower against both JN.1 and EG.5.1 variants with confidence intervals non-overlapping with the effectiveness of the XBB sub-lineages at 2-4 weeks for EG.5.1 where VE was 44.5% (95% CI: 20.2-61.4%) and at 5-9 weeks for JN.1 where VE was 26.4% (95%CI: -3.4-47.6%).ConclusionsThe recent monovalent XBB.1.5 and bivalent BA.4-5 boosters provided comparable and good protection against hospitalisation, however there was evidence of lower VE against hospitalisation of these boosters against JN.1.
Nuclear blebs are associated with destabilized chromatin packing domains
Authors: Pujadas Liwag Emily M. , Acosta Nicolas , Almassalha Luay Matthew , Su Yuanzhe (Patrick) , Gong Ruyi , Kanemaki Masato T. , Stephens Andrew D. , Backman Vadim 
Published: March 2024

ABSTRACTDisrupted nuclear shape is associated with multiple pathological processes including premature aging disorders, cancer-relevant chromosomal rearrangements, and DNA damage. Nuclear blebs (i.e., herniations of the nuclear envelope) have been induced by (1) nuclear compression, (2) nuclear migration (e.g., cancer metastasis), (3) actin contraction, (4) lamin mutation or depletion, and (5) heterochromatin enzyme inhibition. Recent work has shown that chromatin transformation is a hallmark of bleb formation, but the transformation of higher-order structures in blebs is not well understood. As higher-order chromatin has been shown to assemble into nanoscopic packing domains, we investigated if (1) packing domain organization is altered within nuclear blebs and (2) if alteration in packing domain structure contributed to bleb formation. Using Dual-Partial Wave Spectroscopic microscopy, we show that chromatin packing domains within blebs are transformed both by B-type lamin depletion and the inhibition of heterochromatin enzymes compared to the nuclear body. Pairing these results with single-molecule localization microscopy of constitutive heterochromatin, we show fragmentation of nanoscopic heterochromatin domains within bleb domains. Overall, these findings indicate that translocation into blebs results in a fragmented higher-order chromatin structure.SUMMARY STATEMENTNuclear blebs are linked to various pathologies, including cancer and premature aging disorders. We investigate alterations in higher-order chromatin structure within blebs, revealing fragmentation of nanoscopic heterochromatin domains.
Single-Molecule Imaging Reveals the Mechanism of Bidirectional Replication Initiation in Metazoa
Authors: Terui Riki , Berger Scott , Sambel Larissa , Song Dan , Chistol Gheorghe 
Published: March 2024

SummaryMetazoan genomes are copied bidirectionally from thousands of replication origins. Replication initiation entails the assembly and activation of two CMG (Cdc45•Mcm2-7•GINS) helicases at each origin. This requires several firing factors (including TopBP1, RecQL4, DONSON) whose exact roles remain unclear. How two helicases are correctly assembled and activated at every single origin is a long-standing question. By visualizing the recruitment of GINS, Cdc45, TopBP1, RecQL4, and DONSON in real time, we uncovered a surprisingly dynamic picture of initiation. Firing factors transiently bind origins but do not travel with replisomes. Two Cdc45 simultaneously arrive at each origin and two GINS are recruited together, even though neither protein can dimerize. The synchronized delivery of two GINS is mediated by DONSON, which acts as a dimerization scaffold. We show that RecQL4 promotes DONSON dissociation and facilitates helicase activation. The high fidelity of bidirectional origin firing can be explained by a Hopfield-style kinetic proofreading mechanism.
Construction of Animal Models Based on Exploring Pathological Features and Mechanisms of Different Locations in the Progression of DVT-APTE-CTEPD/CTEPH
Authors: Lin Qinghuang , Wang Wenfeng , Chen Xiaoyun , Liu Jixiang , Shao Nan , Wu Qiuxia , Lai Xingyue , Chen Maohe , Chen Min , Wu Yijin , Wu Dawen , Li Hongli , Yang Peiran , Zhang Yunxia , Zhang Zhu , Zhai Zhenguo , Deng Chaosheng 
Published: March 2024

AbstractBackgroundChronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) are sequelae of acute pulmonary embolism (APE) and severely affect patients’ health and quality of life. The treatment of these conditions is challenging, and their underlying mechanisms remain unclear. The main reason for this is the lack of an animal model that can fully simulate the entire chain of DVT-APTE-CTEPD/CTEPH progression. The objective of this study is to construct an ideal animal model that simulates the major pathological changes of DVT-APTE-CTEPD/CTEPH and can be used for mechanistic exploration. We aim to compare the advantages and disadvantages of different modeling approaches and provide an experimental basis for investigating the mechanisms of pulmonary embolism chronicization at different stages of evolution.Methods and MaterialsWe first evaluated the pathological changes in the pulmonary arterial intima stripping tissue of CTEPH patients. Animal models were established by multiple injections of thrombus columns through the internal jugular vein to simulate distal remodeling of the pulmonary artery. To simulate significant remodeling and fibrosis in the middle and distal segments of the pulmonary artery, thrombus columns were injected along with splenectomy. A CTEPD model with intimal fibrosis remodeling was successfully established by selectively injecting large thromboemboli into the pulmonary artery sites in large animals (dogs). A rat model with pathological manifestations of intimal fibrosis remodeling in the proximal end of the pulmonary artery was constructed using large thrombi combined with nitric oxide synthase inhibitors. An animal model of DVT was established using the inferior vena cava ligation method.ResultsAccording to the different pathological features and mechanisms observed in the progression of human DVT-APTE-CTEPD/CTEPH, we constructed animal models that conform to these pathological manifestations and mechanisms, each with its own advantages. Furthermore, the different methods used to construct animal models can be integrated and applied together.ConclusionAnimal models constructed using different modeling methods can effectively simulate the pathological and physiological manifestations of the corresponding stages of chronic pulmonary embolism. Researchers can select the aforementioned models according to their specific research purposes, directions, and requirements.