bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial and temporal patterns of disease burden attributable to high BMI in Belt and Road Initiative countries, 1990–2019
Authors: Xu Yaxin , Wang Qizhe , Yu Tao , Han Yan , Dai Wei , Jiang Sunfang , Li Xiaopan 
Published: June 2024

Abstract

Objective:
This study aimed to analyse the spatial and temporal patterns of disease burden attributed to high BMI (DB-hBMI) from 1990 to 2019 in Belt and Road Initiative (BRI) countries, in light of increasing hBMI prevalence worldwide.

Design:
The study was a secondary analysis of Global Burden of Disease 2019 (GBD 2019) that analysed (using Joinpoint regression analysis) numbers and the age-standardised rate of mortality and disability-adjusted life years (DALY) of hBMI-induced diseases and their trends from 1990 to 2019 and in the final decade.

Setting:
GBD 2019 study data for BRI countries were categorised by country, age, gender and disease.

Participants:
GBD 2019 data were used to analyse DB-hBMI in BRI countries.

Results:
In 2019, China, India and Russia reported the highest mortality and DALY among BRI countries. From 1990 to 2019, the age-standardised DALY increased in Southeast Asia and South Asia, whereas many European countries saw declines. Notably, Bangladesh, Nepal and Vietnam showed the steepest increases, with average annual percentage change (AAPC) values of 4·42 %, 4·19 % and 4·28 %, respectively (all P < 0·05). In contrast, Israel, Slovenia and Poland experienced significant reductions, with AAPC values of –1·70 %, –1·63 % and –1·58 %, respectively (all P < 0·05). The most rapid increases among males were seen in Vietnam, Nepal and Bangladesh, while Jordan, Poland and Slovenia recorded the fastest declines among females. Across most BRI countries, the burden of diabetes and kidney diseases related to hBMI showed a significant uptrend.

Conclusion:
DB-hBMI varies significantly by region, age, gender and disease type across BRI countries. It can pose a substantial threat to public health.
Was there an enthusiasm gap? Examining support for Donald Trump among evangelicals and nonevangelicals
Authors: Pagán Márquez Alondra S. , Djupe Paul A. , Mettler Matthew , Mondak Jeffery J. 
Published: June 2024

AbstractEvangelicals arguably constitute an unexpected base of support for Donald Trump. One plausible account holds that evangelicals supported Trump reluctantly, backing him not because they strongly favored him, but rather because they viewed him as the least objectionable candidate. This perspective suggests a possible enthusiasm gap: among Donald Trump's supporters, nonevangelicals were more zealous while evangelicals were more tepid. We examine this account using data from March 2019, just past the midpoint of Trump's presidency, a period when any lack of enthusiasm with Trump among portions of his base should have been discernible. Our expansive analytical strategy, using OLS and matching, explores whether evangelicals offered Donald Trump more lukewarm support than did nonevangelicals, with support operationalized in six ways. Across 36 tests, no evidence of an enthusiasm gap between evangelicals and nonevangelicals is detected. Seen both in absolute terms and relative to nonevangelicals, evangelicals offered Donald Trump fervent support.
Breaking Internal Waves and Ocean Diapycnal Diffusivity in a High‐Resolution Regional Ocean Model: Evidence of a Wave‐Turbulence Cascade
Authors: Momeni Kayhan , Ma Yuchen , Peltier William R. , Menemenlis Dimitris , Thakur Ritabrata , Pan Yulin , Arbic Brian K. , Skitka Joseph , Alford Matthew H. 
Published: June 2024

AbstractIt is generally understood that the origin of ocean diapycnal diffusivity is primarily associated with the stratified turbulence produced by breaking internal (gravity) waves (IW). However, it requires significant effort to verify diffusivity values in ocean general circulation models in any particular geographical region of the ocean due to the scarcity of microstructure measurements. Recent analyses of downscaled IW fields from an internal‐wave‐admitting global ocean simulation into higher‐resolution regional configurations northwest of Hawaii have demonstrated a much‐improved fit of the simulated IW spectra to the in‐situ profiler measurements such as the Garrett‐Munk (GM) spectrum. Here, we employ this dynamically downscaled ocean simulation to directly analyze the nature of the IW‐breaking and the wave‐turbulence cascade in this region. We employ a modified version of the Kappa Profile Parameterization (KPP) to infer what the horizontally averaged vertical profile of diapycnal diffusivity should be, and compare this to the background profile that would be employed in the ocean component of a low‐resolution coupled climate model such as the Community Earth System Model (CESM) of the US National Center for Atmospheric Research (NCAR). In pursuing this goal, we also demonstrate that the wavefield in the high‐resolution regional domain is dominated by a well‐resolved spectrum of low‐mode IWs that are predictable by solving an appropriate eigenvalue problem for stratified flow. We finally suggest a new tentative approach to improve the KPP parameterization.
MicroRNA expression in JAG1/Notch-activated periodontal ligament stem cells
Authors: Kulthanaamondhita Promphakkon , Kornsuthisopon Chatvadee , Chansaenroj Ajjima , Trachoo Vorapat , Manokawinchoke Jeeranan , Samaranayake Lakshman , Srithanyarat Supreda Suphanantachat , Osathanon Thanaphum 
Published: June 2024

Abstract
Objectives
The study explored the expression profile of miRNAs in Notch-activated periodontal ligament stem cells (PDLSCs) and examined their potential cellular targets.

Methods
PDLSCs were cultured and treated with indirect immobilized Jagged1. The miRNA expression profile was examined using NanoString analysis. Bioinformatic analysis was performed together with enrichment, and miRNA expression was evaluated and validated using a quantitative polymerase chain reaction (qPCR).

Results
A total of 26 miRNAs were differentially expressed in Jagged1 treated PDLSCs compared with the controls. Pathway analysis revealed that altered miRNAs were significantly associated with the transforming growth factor β (TGF-β) signaling pathway. Target prediction analysis demonstrated that 11,170 genes as predictable targets of these altered miRNAs. Enrichment of predicted target genes revealed that they were related to ErbB, Ras and MAPK signaling pathways and small GTPase transduction.

Conclusions
The research concludes that several miRNAs are differentially expressed in jagged-1 treated PDLSCs. In translational terms the differential functionality of these miRNAs offer promise for the development of targeted regenerative materials that are necessary for managing lost tissue replacement in periodontal diseases.
Quality assurance for next-generation sequencing diagnostics of rare neurological diseases in the European Reference Network
Authors: Maver Aleš , Lohmann Katja , Borovečki Fran , Wolstenholme Nicola , Taylor Rachel L. , Spielmann Malte , Haack Tobias B. , Gerberding Matthias , Peterlin Borut , Graessner Holm 
Published: June 2024

AbstractIn the past decade, next-generation sequencing (NGS) has revolutionised genetic diagnostics for rare neurological disorders (RND). However, the lack of standardised technical, interpretative, and reporting standards poses a challenge for ensuring consistent and high-quality diagnostics globally. To address this, the European Reference Network for Rare Neurological Diseases (ERN-RND) collaborated with the European Molecular Genetics Quality Network (EMQN) to establish an external quality assessment scheme for NGS-based diagnostics in RNDs. The scheme, initiated in 2021 with a pilot involving 29 labs and followed by a second round in 2022 with 42 labs, aimed to evaluate the performance of laboratories in genetic testing for RNDs. Each participating lab analysed genetic data from three hypothetical cases, assessing genotyping, interpretation, and clerical accuracy. Despite a majority of labs using exome or genome sequencing, there was considerable variability in gene content, sequencing quality, adherence to standards, and clinical guidance provision. Results showed that while most labs provided correct molecular diagnoses, there was significant variability in reporting technical quality, adherence to interpretation standards, reporting strategies, and clinical commentary. Notably, some labs returned results with the potential for adverse medical outcomes. This underscores the need for further harmonisation, guideline development, and external quality assessment in the evolving landscape of genomic diagnostics for RNDs. Overall, the experience with the scheme highlighted the generally good quality of participating labs but emphasised the imperative for ongoing improvement in data analysis, interpretation, and reporting to enhance patient safety.
Microbiota regulates the TET1-mediated DNA hydroxymethylation program in innate lymphoid cell differentiation
Authors: Zhang Xusheng , Gao Xintong , Liu Zhen , Shao Fei , Yu Dou , Zhao Min , Qin Xiwen , Wang Shuo 
Published: June 2024

AbstractInnate lymphoid cell precursors (ILCPs) develop into distinct subsets of innate lymphoid cells (ILCs) with specific functions. The epigenetic program underlying the differentiation of ILCPs into ILC subsets remains poorly understood. Here, we reveal the genome-wide distribution and dynamics of the DNA methylation and hydroxymethylation in ILC subsets and their respective precursors. Additionally, we find that the DNA hydroxymethyltransferase TET1 suppresses ILC1 but not ILC2 or ILC3 differentiation. TET1 deficiency promotes ILC1 differentiation by inhibiting TGF-β signaling. Throughout ILCP differentiation at postnatal stage, gut microbiota contributes to the downregulation of TET1 level. Microbiota decreases the level of cholic acid in the gut, impairs TET1 expression and suppresses DNA hydroxymethylation, ultimately resulting in an expansion of ILC1s. In adult mice, TET1 suppresses the hyperactivation of ILC1s to maintain intestinal homeostasis. Our findings provide insights into the microbiota-mediated epigenetic programming of ILCs, which links microbiota-DNA methylation crosstalk to ILC differentiation.
A candidate sex determination locus in amphibians which evolved by structural variation between X- and Y-chromosomes
Authors: Kuhl Heiner , Tan Wen Hui , Klopp Christophe , Kleiner Wibke , Koyun Baturalp , Ciorpac Mitica , Feron Romain , Knytl Martin , Kloas Werner , Schartl Manfred , Winkler Christoph , Stöck Matthias 
Published: June 2024

AbstractMost vertebrates develop distinct females and males, where sex is determined by repeatedly evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW♀/ZZ♂), is known across >8740 species of amphibians. In this study, by combining chromosome-scale female and male genomes of a non-model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing, we reveal a candidate master locus, governing a male-heterogametic system (XX♀/XY♂). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5′-regulatory region of the gene bod1l, where a Y-specific non-coding RNA (ncRNA-Y), only expressed in males, suggests that this locus initiates sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads. This coincided with differential H3K4me-methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination.
The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease
Authors: Choi Eun-Kyung , Rajendiran Thekkelnaycke M. , Soni Tanu , Park Jin-Ho , Aring Luisa , Muraleedharan Chithra K. , Garcia-Hernandez Vicky , Kamada Nobuhiko , Samuelson Linda C. , Nusrat Asma , Iwase Shigeki , Seo Young Ah 
Published: June 2024

AbstractThe metal ion transporter SLC39A8 is associated with physiological traits and diseases, including blood manganese (Mn) levels and inflammatory bowel diseases (IBD). The mechanisms by which SLC39A8 controls Mn homeostasis and epithelial integrity remain elusive. Here, we generate Slc39a8 intestinal epithelial cell-specific-knockout (Slc39a8-IEC KO) mice, which display markedly decreased Mn levels in blood and most organs. Radiotracer studies reveal impaired intestinal absorption of dietary Mn in Slc39a8-IEC KO mice. SLC39A8 is localized to the apical membrane and mediates 54Mn uptake in intestinal organoid monolayer cultures. Unbiased transcriptomic analysis identifies alkaline ceramidase 1 (ACER1), a key enzyme in sphingolipid metabolism, as a potential therapeutic target for SLC39A8-associated IBDs. Importantly, treatment with an ACER1 inhibitor attenuates colitis in Slc39a8-IEC KO mice by remedying barrier dysfunction. Our results highlight the essential roles of SLC39A8 in intestinal Mn absorption and epithelial integrity and offer a therapeutic target for IBD associated with impaired Mn homeostasis.
Bactericidal effect of tetracycline in E. coli strain ED1a may be associated with ribosome dysfunction
Authors: Khusainov Iskander , Romanov Natalie , Goemans Camille , Turoňová Beata , Zimmerli Christian E. , Welsch Sonja , Langer Julian D. , Typas Athanasios , Beck Martin 
Published: June 2024

AbstractRibosomes translate the genetic code into proteins. Recent technical advances have facilitated in situ structural analyses of ribosome functional states inside eukaryotic cells and the minimal bacterium Mycoplasma. However, such analyses of Gram-negative bacteria are lacking, despite their ribosomes being major antimicrobial drug targets. Here we compare two E. coli strains, a lab E. coli K-12 and human gut isolate E. coli ED1a, for which tetracycline exhibits bacteriostatic and bactericidal action, respectively. Using our approach for close-to-native E. coli sample preparation, we assess the two strains by cryo-ET and visualize their ribosomes at high resolution in situ. Upon tetracycline treatment, these exhibit virtually identical drug binding sites, yet the conformation distribution of ribosomal complexes differs. While K-12 retains ribosomes in a translation-competent state, tRNAs are lost in the vast majority of ED1a ribosomes. These structural findings together with the proteome-wide abundance and thermal stability assessments indicate that antibiotic responses are complex in cells and can differ between different strains of a single species, thus arguing that all relevant bacterial strains should be analyzed in situ when addressing antibiotic mode of action.
MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes
Authors: Jungnickel Katharina Esther Julia , Guelle Océane , Iguchi Miharu , Dong Wentao , Kotov Vadim , Gabriel Florian , Debacker Cécile , Dairou Julien , McCort-Tranchepain Isabelle , Laqtom Nouf N. , Chan Sze Ham , Ejima Akika , Sato Kenji , Massa López David , Saftig Paul , Mehdipour Ahmad Reza , Abu-Remaileh Monther , Gasnier Bruno , Löw Christian , Damme Markus 
Published: June 2024

AbstractThe lysosomal degradation of macromolecules produces diverse small metabolites exported by specific transporters for reuse in biosynthetic pathways. Here we deorphanized the major facilitator superfamily domain containing 1 (MFSD1) protein, which forms a tight complex with the glycosylated lysosomal membrane protein (GLMP) in the lysosomal membrane. Untargeted metabolomics analysis of MFSD1-deficient mouse lysosomes revealed an increase in cationic dipeptides. Purified MFSD1 selectively bound diverse dipeptides, while electrophysiological, isotope tracer and fluorescence-based studies in Xenopus oocytes and proteoliposomes showed that MFSD1–GLMP acts as a uniporter for cationic, neutral and anionic dipeptides. Cryoelectron microscopy structure of the dipeptide-bound MFSD1–GLMP complex in outward-open conformation characterized the heterodimer interface and, in combination with molecular dynamics simulations, provided a structural basis for its selectivity towards diverse dipeptides. Together, our data identify MFSD1 as a general lysosomal dipeptide uniporter, providing an alternative route to recycle lysosomal proteolysis products when lysosomal amino acid exporters are overloaded.
Fine-scale contemporary recombination variation and its fitness consequences in adaptively diverging stickleback fish
Authors: Venu Vrinda , Harjunmaa Enni , Dreau Andreea , Brady Shannon , Absher Devin , Kingsley David M. , Jones Felicity C. 
Published: June 2024

AbstractDespite deep evolutionary conservation, recombination rates vary greatly across the genome and among individuals, sexes and populations. Yet the impact of this variation on adaptively diverging populations is not well understood. Here we characterized fine-scale recombination landscapes in an adaptively divergent pair of marine and freshwater populations of threespine stickleback from River Tyne, Scotland. Through whole-genome sequencing of large nuclear families, we identified the genomic locations of almost 50,000 crossovers and built recombination maps for marine, freshwater and hybrid individuals at a resolution of 3.8 kb. We used these maps to quantify the factors driving variation in recombination rates. We found strong heterochiasmy between sexes but also differences in recombination rates among ecotypes. Hybrids showed evidence of significant recombination suppression in overall map length and in individual loci. Recombination rates were lower not only within individual marine–freshwater-adaptive loci, but also between loci on the same chromosome, suggesting selection on linked gene ‘cassettes’. Through temporal sampling along a natural hybrid zone, we found that recombinants showed traits associated with reduced fitness. Our results support predictions that divergence in cis-acting recombination modifiers, whose functions are disrupted in hybrids, may play an important role in maintaining differences among adaptively diverging populations.
Thromboembolic events and vascular dementia in patients with atrial fibrillation and low apparent stroke risk
Authors: Mobley Alastair R. , Subramanian Anuradhaa , Champsi Asgher , Wang Xiaoxia , Myles Puja , McGreavy Paul , Bunting Karina V. , Shukla David , Nirantharakumar Krishnarajah , Kotecha Dipak 
Published: June 2024

AbstractThe prevention of thromboembolism in atrial fibrillation (AF) is typically restricted to patients with specific risk factors and ignores outcomes such as vascular dementia. This population-based cohort study used electronic healthcare records from 5,199,994 primary care patients (UK; 2005–2020). A total of 290,525 (5.6%) had a diagnosis of AF and were aged 40–75 years, of which 36,340 had no history of stroke, a low perceived risk of stroke based on clinical risk factors and no oral anticoagulant prescription. Matching was performed for age, sex and region to 117,298 controls without AF. During 5 years median follow-up (831,005 person-years), incident stroke occurred in 3.8% with AF versus 1.5% control (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.91–2.21; P < 0.001), arterial thromboembolism 0.3% versus 0.1% (HR 2.39, 95% CI 1.83–3.11; P < 0.001), and all-cause mortality 8.9% versus 5.0% (HR 1.44, 95% CI 1.38–1.50; P < 0.001). AF was associated with all-cause dementia (HR 1.17, 95% CI 1.04–1.32; P = 0.010), driven by vascular dementia (HR 1.68, 95% CI 1.33–2.12; P < 0.001) rather than Alzheimer’s disease (HR 0.85, 95% CI 0.70–1.03; P = 0.09). Death and thromboembolic outcomes, including vascular dementia, are substantially increased in patients with AF despite a lack of conventional stroke risk factors.
Whole genome sequences of 70 indigenous Ethiopian cattle
Authors: Ayalew Wondossen , Xiaoyun Wu , Tarekegn Getinet Mekuriaw , Naboulsi Rakan , Sisay Tessema Tesfaye , Van Damme Renaud , Bongcam-Rudloff Erik , Chu Min , Liang Chunnian , Edea Zewdu , Enquahone Solomon , Ping Yan 
Published: June 2024

AbstractIndigenous animal genetic resources play a crucial role in preserving global genetic diversity and supporting the livelihoods of millions of people. In Ethiopia, the majority of the cattle population consists of indigenous breeds. Understanding the genetic architecture of these cattle breeds is essential for effective management and conservation efforts. In this study, we sequenced DNA samples from 70 animals from seven indigenous cattle breeds, generating about two terabytes of pair-end reads with an average coverage of 14X. The sequencing data were pre-processed and mapped to the cattle reference genome (ARS-UCD1.2) with an alignment rate of 99.2%. Finally, the variant calling process produced approximately 35 million high-quality SNPs. These data provide a deeper understanding of the genetic landscape, facilitate the identification of causal mutations, and enable the exploration of evolutionary patterns to assist cattle improvement and sustainable utilization, particularly in the face of unpredictable climate changes.
Haplotype-resolved chromosome-level genome assembly of Ehretia macrophylla
Authors: Cheng Shiping , Zhang Qikun , Geng Xining , Xie Lihua , Chen Minghui , Jiao Siqian , Qi Shuaizheng , Yao Pengqiang , Lu Mailin , Zhang Mengren , Zhai Wenshan , Yun Quanzheng , Feng Shangguo 
Published: June 2024

AbstractEhretia macrophylla Wall, known as wild loquat, is an ecologically, economically, and medicinally significant tree species widely grown in China, Japan, Vietnam, and Nepal. In this study, we have successfully generated a haplotype-resolved chromosome-scale genome assembly of E. macrophylla by integrating PacBio HiFi long-reads, Illumina short-reads, and Hi-C data. The genome assembly consists of two haplotypes, with sizes of 1.82 Gb and 1.58 Gb respectively, and contig N50 lengths of 28.11 Mb and 21.57 Mb correspondingly. Additionally, 99.41% of the assembly was successfully anchored into 40 pseudo-chromosomes. We predicted 58,886 protein-coding genes, of which 99.60% were functionally annotated from databases. We furthermore detected 2.65 Gb repeat sequences, 659,290 rRNAs, 4,931 tRNAs and 4,688 other ncRNAs. The high-quality assembly of the genome offers a solid basis for furthering the fields of molecular breeding and functional genomics of E. macrophylla.
A cell atlas of the adult female Aedes aegypti midgut revealed by single-cell RNA sequencing
Authors: Wang Shunlong , Huang Ying , Wang Fei , Han Qian , Ren Nanjie , Wang Xiaoyu , Cui Yingjun , Yuan Zhiming , Xia Han 
Published: June 2024

AbstractAedes aegypti is a primary vector for transmitting various arboviruses, including Yellow fever, dengue and Zika virus. The mosquito midgut is the principal organ for blood meal digestion, nutrient absorption and the initial site of arbovirus infection. Although a previous study delineated midgut’s transcriptome of Ae. aegypti at the single-nucleus resolution, there still lacks an established protocol for isolating and RNA sequencing of single cells of Ae. aegypti midgut, which is required for investigating arbovirus-midgut interaction at the single-cell level. Here, we established an atlas of the midgut cells for Ae. aegypti by single-cell RNA sequencing. We annotated the cell clusters including intestinal stem cells/enteroblasts (ISC/EB), cardia cells (Cardia), enterocytes (EC, EC-like), enteroendocrine cells (EE), visceral muscle (VM), fat body cells (FBC) and hemocyte cells (HC). This study will provide a foundation for further studies of arbovirus infection in mosquito midgut at the single-cell level.