bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cohort profile: the Northwest China Real-world and Population-based Cohort
Authors: Huang Qi , Li Yanjun , Yin Bo , Wang Yaoguo , Yuan Yujuan , Guo Yanying , Gu Kuiying , Yang Yining , Di Qian 
Published: November 2024

Key FeaturesThe Northwest China Real-World and Population-based cohort is an ongoing prospective cohort with more than 25 million population, covering almost all residents across approximately 1.66 million square kilometers in northwest ChinaThe cohort integrates data from various sources, including health profiles, examination records, electronic health records, mortality records, statistical yearbooks, and environmental datasets, covering comprehensive health-related factors such as demographics, lifestyle factors, family medical history, living conditions, enrollment in national public health services, physical examinations, blood assay tests, diagnostic assessments, disease outcomes, and cause-specific mortality.This real-world dataset can evaluate clinical treatment effectiveness and prognosis, assess impact of health policy, and investigate the health effects of multiple risk factors .From January 2019 to December 2023, the cohort has included 13,634,481 participants, accumulating 47,050,707 person-years of follow-up, with 13,598,407 medical diagnosis records and 881,114 recorded deaths.Cohort data are available upon request. De-identified and anonymized data are stored on local servers and accessed through a data-sharing platform, enabling users to utilize the data without direct access to the raw information. A description of the proposed research can be sent to Yining Yang & Qian Di.
Higher burden of cerebral small vessel disease is associated with risk of incident stroke in community dwelling individuals
Authors: Pinheiro Adlin , Aparicio Hugo , Lioutas Vasileios , Beiser Alexa , Ekenze Oluchi , DeCarli Charles , Seshadri Sudha , Demissie Serkalem , Romero Jose R. 
Published: November 2024

AbstractBackgroundMild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple individual CSVD markers may better identify a person’s risk. We related a multi-marker CSVD score to risk of incident stroke and compared it with the Framingham Stroke Risk Profile (FSRP) in community-dwelling individuals.MethodsFramingham Heart Study participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used, assigning one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis. Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke.ResultsAmong 1,154 participants (46% male, mean age 70.9±8.7), 92 (8%) developed stroke over a median follow-up of 8.6 years (Q1-Q3: 5.1-12.5). In models adjusting for age, sex, time interval between clinic exam and MRI, FHS cohort, and FSRP, those with three or more markers had increased risk of stroke (HR: 2.62; 95% CI: 1.17-5.88). In comparison, a 5-percent increase in FSRP was also associated with increased risk (aHR: 1.16; 95% CI: 1.04-1.29). The FSRP and CSVD score had similar model discrimination metrics.InterpretationHigher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals for early implementation of preventive strategies.
Drivers of Depression in Chronic Post-Stroke Aphasia
Authors: Mathur Devna , Paul Sachi , DeMarco Andrew , Turkeltaub Peter 
Published: November 2024

AbstractBackgroundApproximately one third of stroke survivors develop post-stroke depression, which reduces quality of life. Previous studies have often focused on early phases of recovery and excluded people with significant aphasia. Here, we examine relationships of depression symptoms to demographic factors, and different types of stroke-related disability and impairment in adults with chronic left-hemisphere stroke and a history of aphasia.Methods92 chronic left-hemisphere stroke survivors with a history of aphasia and 70 controls participated in this cross-sectional study. The Beck Depression Inventory-II (BDI-II) measured depression symptoms. The Stroke Impact Scale 3.0 (SIS) assessed stroke-related disability in Cognitive, Physical, and Social Participation domains, as well as self-perceived Recovery. The Western Aphasia Battery Aphasia Quotient and the NIH Stroke Scale total motor score measured language and motor impairment. Spearman correlations examined bivariate relationships between variables. Ordinal regression models examined group differences in BDI-II scores (Model 1), and disability and impairment factors that predicted BDI-II scores (Model 2), accounting for demographic factors and antidepressant medication status.ResultsBDI-II scores were on average 3.4 points higher in stroke survivors than controls. Model 1 confirmed that this difference was significant, and found that age was inversely related to BDI-II scores. Bivariate correlations demonstrated that higher BDI-II scores were related to lower SIS Cognitive, Social Participation, and Recovery scores. Model 2 found that these three measures independently predicted BDI-II scores.ConclusionsThe factors related to depression may differ depending on the nature of the stroke, the types of deficits experienced, and the phase of recovery. In the chronic phase of left hemisphere stroke with aphasia, cognitive and communication disabilities, social participation, and self-perceived recovery are the primary correlates of depression symptoms. These findings highlight the importance of assessing for depression even long after left hemisphere stroke, and suggest potential targets for psychotherapy to improve depression.
Canonical Notch2 Signaling Regulates the Development of Iron-recycling Macrophages and Iron Homeostasis
Authors: Schroth Frauline Nicole , Kapanadze Tamar , Sablotny Stefan , Xu Yuangao , Chung Bo Mee , Deuper Lena , Kispert Andreas , Lochner Matthias , Kempf Tibor , Haller Hermann , Schmidt-Ott Kai M. , Gamrekelashvili Jaba , Limbourg Florian P. 
Published: November 2024

SummaryRed pulp macrophages (RPM) and bone marrow macrophages (BMM) are iron-recycling cells involved in iron homeostasis and erythropoiesis. Here, we show, using conditional deletion strategies of Notch signaling components, that the development of RPM and BMM is regulated by canonical Notch2 signaling. Loss of functionalNotch2, or its nuclear mediatorRbpj, causes impairment in RPM and BMM and iron overload in the spleen and bone marrow, while prototypic RPM genes required for iron handling are downregulated. This was accompanied by splenic extramedullary hematopoiesis and changes in splenic microarchitecture. Furthermore, early postnatal transfer of bone marrow and fetal liver progenitors rescued the defects in RPM and BMM and iron overload in aNotch2-dependent manner, demonstrating the potential to restore defective tissue resident macrophage niches by Notch-competent progenitors. Thus, canonicalNotch2is required for development and function of iron-recycling macrophages.
A genome-wide ATLAS of liver chromatin architecture reveals that sex dictates diet-induced nucleosome dynamics
Authors: Zhang Zhengyi , Su Vivien , Wiese Carrie B. , Cheng Lijing , Wang Dan , Cui Ya , Kim Jason , Wu Xiaohui , Tran Peter H. , Zhou Zhenqi , Casero David , Li Wei , Hevener Andrea L. , Reue Karen , Sallam Tamer 
Published: November 2024

AbstractThe three-dimensional organization of the genome plays an important role in cellular function. Alterations between open and closed chromatin states contributes to DNA binding, collaborative transcriptional activities and informs post-transcriptional processing. The liver orchestrates systemic metabolic control and has the ability to mount a rapid adaptive response to environmental challenges. We interrogated the chromatin architecture in liver under different dietary cues. Using ATAC-seq, we mapped over 120,000 nucleosome peaks, revealing a remarkably preserved hepatic chromatin landscape across feeding conditions. Stringent analysis of nucleosome rearrangements in response to diet revealed sex as the dominant factor segregating changes in chromatin accessibility. A lipid-rich diet led to a more accessible chromatin confirmation at promoter regions in female mice along with enrichment of promoter binding CCAAT-binding domain proteins. Male liver exhibited stronger binding for nutrient sensing nuclear receptors. Integrative analysis with gene expression corroborated a role for chromatin states in informing functional differences in metabolic traits. We distinguished the impact of gonadal sex and chromosomal sex as determinants of chromatin modulation by diet using the Four Core Genotypes mouse model. Our data provide mechanistic evidence underlying the regulation for the critical sex-dimorphic GWAS gene,Pnpla3. In summary, we provide a comprehensive epigenetic resource in murine liver that uncovers the complexity of chromatin dynamics in response to diet and sex.
A single cysteine residue in vimentin regulates long non-coding RNAXISTto suppress epithelial-mesenchymal transition and stemness in breast cancer
Authors: Usman Saima , Yeudall W. Andrew , Teh Muy-Teck , Ghloum Fatemah , Tummala Hemanth , Waseem Ahmad 
Published: November 2024

AbstractVimentin is a type III intermediate filament (IF) protein, that is induced in a large number of solid tumours. A single cysteine at position 328 in vimentin plays a crucial role in assembly, organisation and stability of IFs. However, its exact function during epithelial mesenchymal transition (EMT) and cancer progression has not been investigated. To investigate this, we have transduced wildtype (WT) and C328S vimentin separately in MCF-7 cells that lack endogenous vimentin. The expression of C328-VIM impacted vimentin-actin interactions and induced EMT-like features that include enhanced cell proliferation, migration, invasion accompanied by reduced cell adhesion when compared to the wildtype cells. Functional transcriptomic studies confirmed the upregulation of EMT and mesenchymal markers, downregulation of epithelial markers as well as acquisition of signatures associated with cancer stemness (CD56, Oct4, PROCR and CD49f) thus transforming MCF-7 cells from oestrogen positive to triple reduced (ESR1, PGR, and HER2) status. We also observed a stark increase in the expression of long non-coding RNA,XISTin MCF-7 cells expressing C328-VIM. Targeting the mutant vimentin orXISTby RNA interference partially reversed the phenotypes in C328-VIM expressing MCF-7 cells. Furthermore, introduction of C328-VIM cells into nude mice promoted tumour growth by increasing cancer stemness in an oestrogen independent manner. Altogether, our studies provide insight into how cysteine 328 in vimentin dictates mechano-transduction signals to remodel actin cytoskeleton and protect against EMT and cancer growth via modulating lncRNAXIST. Therefore, targeting vimentin and/orXISTvia RNA interference should be a promising therapeutic strategy for breast cancer treatment.Abstract Figure
Universal base editing for hemophilia B
Authors: Baatartsogt Nemekhbayar , Kashiwakura Yuji , Hiramoto Takafumi , Ito Rina , Sato Rikako , Nagao Yasumitsu , Naruoka Hina , Takata Haruka , Hayakawa Morisada , Batjargal Khishigjargal , Togashi Tomoki , Hoshino Atsushi , Shimizu Taro , Sato Yusuke , Ishida Tatsuhiro , Nureki Osamu , Ohmori Tsukasa 
Published: November 2024

AbstractThe repair of pathological gene variants is an ultimate aim for treating genetic diseases; however, it is not practical to develop different therapeutic reagents for each of the many variants that can occur in a gene. Here, we investigated whether base editing to induce a gain-of-function variant in blood coagulation factor IX (FIX) can increase FIX activity as a treatment strategy for hemophilia B. We engineered a G:C to A:T substitution at c.1151 ofF9by cytosine base editing to generate R338Q, known as the ShanghaiF9variant, which markedly potentiates coagulation factor activity. An adeno-associated virus vector harboring the base editor converted more than 60% of the target G:C to A:T and increased FIX activity in HEK293 cells harboring patient-derivedF9variants, as well as in knock-in mice harboring a humanF9cDNA. Furthermore, administration of lipid nanoparticles embedded with the base editor mRNA and gRNA increased FIX activity in mice. These data indicate that cytosine base editing to generate R338Q in FIX can become a universal genome editing strategy for hemophilia B.
Alveolar macrophages initiate the spatially targeted neutrophil recruitment during nanoparticle inhalation
Authors: Liu Qiongliang , Yang Lin , Li Chenxi , Zhou Qiaoxia , Han Lianyong , Schröppel Andreas , Kutschke David , Secklehner Judith , Yldirim Ali Önder , Zeuschner Dagmar , Carlin Leo M. , Sperandio Markus , Schmid Otmar , Stoeger Tobias , Rehberg Markus 
Published: November 2024

AbstractExposure to air pollution, including nanoparticles (NPs), is a major health concern associated with various diseases, triggered by subtle inflammatory responses in the lung. To investigate the dynamic immune response in vivo, lung intravital microscopy (L-IVM), was used to analyze the behavior of alveolar macrophages (AMs) and neutrophils, combined with ventilator-assisted inhalation of nebulized NPs in mice. Inhalation of fluorescent quantum dot NPs (cQDs) and soot-like carbon black NPs (CNPs, ambient pollutants), led to rapid spatially focused recruitment of neutrophils near alveolar deposited NPs. Neutrophil recruitment was initiated by NPs uptake by AMs, dependent on AM motility and AM NP surface recognition. Prior airway application of neutralizing antibodies against alveolar ICAM-1 and LFA-1, leading to reduced AM motility, inhibition of C5aR1 and FcγRI receptor mediated NPs uptake by AMs, as well as neutralizing of TNFα and application of a cellular degranulation inhibitor, abolished the early immune response induced by NPs. Overall, our data demonstrates the crucial role of AM activity (migration, phagocytosis, cytokine release) in the rapid and site-specific recruitment of neutrophils during the early phase of particle inhalation, suggesting these processes to be key events in mounting the immune response upon NP inhalation in the lung.Graphical abstract
Meta-omic insights into active bacteria mediating N2O mitigation and dissimilatory nitrate reduction to ammonium in an ammonia recovery bioreactor
Authors: Phan Hop V. , Yasuda Shohei , Oba Kohei , Tsukamoto Hiroki , Hori Tomoyuki , Kuroiwa Megumi , Terada Akihiko 
Published: November 2024

AbstractShifting from ammonia removal to recovery is the current strategy in wastewater treatment management. We recently developed a microaerophilic activated sludge (MAS) system for retaining ammonia while removing organic carbon with minimal N2O emissions. A comprehensive understanding of nitrogen metabolisms in the MAS system is essential to optimize system performance. Here, we employed metagenomics and metatranscriptomics analyses to characterize the microbial community structure and activity during the transition from a microaerophilic to an aerobic condition. A hybrid approach of high-quality Illumina short reads and Nanopore long reads recovered medium-to high-quality 98 non-redundant metagenome-assembled genomes (MAGs) from the MAS communities. The suppressed bacterial ammonia monooxygenase (amoA) expression was upregulated after shifting from a microaerophilic to an aerobic condition. The 73 MAGs (>74% of the total) from 11 bacterial phyla harbored genes encoding proteins involved in nitrate respiration; 39 MAGs (∼53%) carried N2O reductase (nosZ) genes with the predominance of clade IInosZ(31 MAGs), and 24 MAGs (∼33%) possessed nitrite reductase (ammonia forming) genes (nrfA). Clade IInosZandnrfAgenes exhibited the highest and second-highest expressions among nitrogen metabolism genes, indicating robust N2O consumption and ammonification. Non-denitrifying clade IInosZbacteria,Cloacibacteriumspp., in the most abundant and active phylum Bacteroioda, were likely major N2O sinks. Elevated dissolved oxygen (DO) concentration inhibited clade IInosZexpression but notnrfAexpression, potentially switching phenotypes from N2O reduction to ammonification. Collectively, the multi-omics analysis illuminated vital bacteria responsible for N2O reduction and ammonification in microaerophilic and aerobic conditions, facilitating high-performance ammonia recovery.
In vitroFLASH irradiation of A549 lung cancer cells and IMR90 healthy human fibroblasts in the synchrocyclotron room of a clinical proton therapy system
Authors: Zazpe Adrián , del Monte-García Inés , Palao Nerea , Cerrón Fernando , Cueto-Remacha Mateo , Linzoain-Agos Paula , Iniesta-González Minerva , Quartieri Martina , Cuesta Ángel M. , España Samuel , Velasco Guillermo , Vera-Sánchez Juan Antonio , Fraile Luis Mario , Mazal Alejandro , Udías José Manuel , Porras Almudena , Bragado Paloma , Gutierrez-Uzquiza Álvaro , Sánchez-Parcerisa Daniel 
Published: November 2024

AbstractPurposeThis study aims to investigate the FLASH irradiation effect on lung tumor (A549) and healthy fibroblast (IMR90) cell lines using an irradiation station installed at the synchrocyclotron room of a clinical proton facility without any permanent beamline modifications.Methods and MaterialsAn irradiation system composed of a lead scatterer and 3D-printed positioning system was designed and fabricated to operate within the beamline gap of the IBA Proteus One proton therapy facility after the extraction of the beam from the synchrocyclotron. A dosimetric analysis of the produced irradiation field was carried out using radiochromic films. FLASH and conventional-rate irradiations were conducted on relevant cell lines for lung cancer at the isocenter of the treatment room. Biological assessments post-irradiation included clonogenic and viability assays for cell survival, immunofluorescence analysis of p21 protein expression, and flow cytometry analysis for cell cycle arrest evaluation.ResultsThe irradiation system successfully delivered homogeneous and repeatable FLASH dose rates (>900 Gy/s) with a positioning accuracy of 1 mm and dose uniformity within 10%. Clonogenic assays revealed no statistically significant differences in survival between FLASH and conventional dose rates for both A549 and IMR90 cell lines, although a trend towards higher viability was observed in IMR90 cells under FLASH conditions. Flow cytometry demonstrated significant differences in cell cycle arrest patterns at doses above 7 Gy, with FLASH-irradiated cells exhibiting a decrease in G2/M phase arrest compared to conventional rates. Immunofluorescence analysis of p21 expression showed no significant differences between irradiation modalities.ConclusionsThe developed irradiation station effectively facilitates FLASH radiotherapy experiments in a clinical proton facility, achieving the necessary dose rates without hardware modification or extra tuning of the facility. Our analysis reported notable alterations in cell cycle dynamics suggesting distinct biological responses between FLASH and conventional rates in both healthy and tumor cells. These findings contribute to the emerging understanding of the FLASH effect and support the potential for its differential impact on cancerous versus healthy tissues.
Fast-Part: Fast and Accurate Data Partitioning for Biological Sequence Analysis
Authors: Ahmed Shafayat , Emon Muhit Islam , Moumi Nazifa Ahmed , Zhang Liqing 
Published: November 2024

AbstractDeveloping effective machine learning models for classifications of biological sequences depends heavily on the quality of the training and test datasets split. Existing tools are either computationally expensive, unable to maintain the desired level of similarity between the training and test datasets, or unable to retain training: test ratio stratification. Here, we present Fast-Part, a fast and accurate sequence data partitioning tool that ensures strict homology separation between the training and test datasets and the best possible training: test stratification ratio, and at the same time is computationally fast. Evaluation of Fast-Part on multiple protein sequence datasets shows that it performs data partitioning with exceptional speed and maintains strict partitioning compared to the existing tools. Fast-Part can handle massive datasets like CD-HIT[1] and MMseq[2] and maintain strict homology partitioning like GraphPart[3].
Basal cell of origin resolves neuroendocrine–tuft lineage plasticity in cancer
Authors: Ireland Abbie S. , Hawgood Sarah B. , Xie Daniel A. , Barbier Margaret W. , Lucas-Randolph Scarlett , Tyson Darren R. , Zuo Lisa Y. , Witt Benjamin L. , Govindan Ramaswamy , Dowlati Afshin , Moser Justin C. , Puri Sonam , Rudin Charles M. , Chan Joseph M. , Elliott Andrew , Oliver Trudy G. 
Published: November 2024

Summary paragraphNeuroendocrine and tuft cells are rare, chemosensory epithelial lineages defined by expression of ASCL1 and POU2F3 transcription factors, respectively1,2. Neuroendocrine cancers, including small cell lung cancer (SCLC), frequently display tuft-like subsets, a feature linked to poor patient outcomes3–13. The mechanisms driving neuroendocrine–tuft tumour heterogeneity, and the origins of tuft-like cancers are unknown. Using multiple genetically-engineered animal models of SCLC, we demonstrate that a basal cell of origin (but not the accepted neuroendocrine origin) generates neuroendocrine–tuft-like tumours that highly recapitulate human SCLC. Single-cell clonal analyses of basal-derived SCLC further uncovers unexpected transcriptional states and lineage trajectories underlying neuroendocrine–tuft plasticity. Uniquely in basal cells, introduction of genetic alterations enriched in human tuft-like SCLC, including high MYC, PTEN loss, and ASCL1 suppression, cooperate to promote tuft-like tumours. Transcriptomics of 944 human SCLCs reveal a basal-like subset and a tuft-ionocyte-like state that altogether demonstrate remarkable conservation between cancer states and normal basal cell injury response mechanisms14–18. Together, these data suggest that the basal cell is a plausible origin for SCLC and other neuroendocrine-tuft cancers that can explain neuroendocrine–tuft heterogeneity—offering new insights for targeting lineage plasticity.