bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating spatial and single-cell transcriptomics reveals tumor heterogeneity and intercellular networks in colorectal cancer
Authors: Xiao Jing , Yu Xinyang , Meng Fanlin , Zhang Yuncong , Zhou Wenbin , Ren Yonghong , Li Jingxia , Sun Yimin , Sun Hongwei , Chen Guokai , He Ke , Lu Ligong 
Published: May 2024

AbstractSingle cell RNA sequencing (scRNA-seq), a powerful tool for studying the tumor microenvironment (TME), does not preserve/provide spatial information on tissue morphology and cellular interactions. To understand the crosstalk between diverse cellular components in proximity in the TME, we performed scRNA-seq coupled with spatial transcriptomic (ST) assay to profile 41,700 cells from three colorectal cancer (CRC) tumor-normal-blood pairs. Standalone scRNA-seq analyses revealed eight major cell populations, including B cells, T cells, Monocytes, NK cells, Epithelial cells, Fibroblasts, Mast cells, Endothelial cells. After the identification of malignant cells from epithelial cells, we observed seven subtypes of malignant cells that reflect heterogeneous status in tumor, including tumor_CAV1, tumor_ATF3_JUN | FOS, tumor_ZEB2, tumor_VIM, tumor_WSB1, tumor_LXN, and tumor_PGM1. By transferring the cellular annotations obtained by scRNA-seq to ST spots, we annotated four regions in a cryosection from CRC patients, including tumor, stroma, immune infiltration, and colon epithelium regions. Furthermore, we observed intensive intercellular interactions between stroma and tumor regions which were extremely proximal in the cryosection. In particular, one pair of ligands and receptors (C5AR1 and RPS19) was inferred to play key roles in the crosstalk of stroma and tumor regions. For the tumor region, a typical feature of TMSB4X-high expression was identified, which could be a potential marker of CRC. The stroma region was found to be characterized by VIM-high expression, suggesting it fostered a stromal niche in the TME. Collectively, single cell and spatial analysis in our study reveal the tumor heterogeneity and molecular interactions in CRC TME, which provides insights into the mechanisms underlying CRC progression and may contribute to the development of anticancer therapies targeting on non-tumor components, such as the extracellular matrix (ECM) in CRC. The typical genes we identified may facilitate to new molecular subtypes of CRC.
Confidence of Emergency Department doctors in managing ophthalmic emergencies: a systematic review
Authors: Mendall Jessica , Tolley Abraham , Parisi Veronica , Hornby Stella , Brown Ruth , Nowak Victoria 
Published: May 2024

Abstract
Background
Eye emergencies constitute a significant portion of attendances to general Emergency Departments (EDs) in the UK, therefore it is important to assess the confidence of doctors who work in this setting in managing these potentially sight- and life-threatening presentations. This systematic review aims to assess the confidence of UK doctors working in general EDs in managing ophthalmic emergencies.

Methods
MEDLINE (Ovid), EMBASE (Ovid), ProQuest Central and Web of Science databases and grey literature were searched from inception to 1 October 2022 for publications that (1) featured doctors working in UK general EDs, (2) assessed doctors’ confidence in managing ophthalmic emergencies, (3) contained original data, (4) were full-text, and (5) written in English. Methodological quality was assessed using the AXIS tool.

Results
462 articles were screened, and 7 papers included for data extraction, which collectively assessed the confidence of 956 doctors working in EDs in managing ophthalmic emergencies. There was a widespread lack of confidence amongst foundation doctors, which has worsened over time. Most doctors lacked confidence in performing funduscopy and using the slit-lamp, and considered formal ophthalmology training received in EDs to be inadequate.

Conclusions
Evidence suggests a lack of confidence amongst foundation doctors in managing ophthalmic emergencies. High-quality evidence investigating the confidence amongst more experienced Emergency Medicine (EM) physicians was lacking. It is important to assess why foundation doctors feel so ill-prepared to manage eye emergencies and develop further ophthalmic training for doctors working in EDs. Further investigation exploring the confidence of EM trainees and consultants is required.
Single-photon detection using large-scale high-temperature MgB2 sensors at 20 K
Authors: Charaev Ilya , Batson Emma K. , Cherednichenko Sergey , Reidy Kate , Drakinskiy Vladimir , Yu Yang , Lara-Avila Samuel , Thomsen Joachim D. , Colangelo Marco , Incalza Francesca , Ilin Konstantin , Schilling Andreas , Berggren Karl K. 
Published: May 2024

AbstractUltra-fast single-photon detectors with high current density and operating temperature can benefit space and ground applications, including quantum optical communication systems, lightweight cryogenics for space crafts, and medical use. Here we demonstrate magnesium diboride (MgB2) thin-film superconducting microwires capable of single-photon detection at 1.55  μm optical wavelength. We used helium ions to alter the properties of MgB2, resulting in microwire-based detectors exhibiting single-photon sensitivity across a broad temperature range of up to 20 K, and detection efficiency saturation for 1  μm wide microwires at 3.7 K. Linearity of detection rate vs incident power was preserved up to at least 100 Mcps. Despite the large active area of up to 400 × 400 μm2, the reset time was found to be as low as ~ 1 ns. Our research provides possibilities for breaking the operating temperature limit and maximum single-pixel count rate, expanding the detector area, and raises inquiries about the fundamental mechanisms of single-photon detection in high-critical-temperature superconductors.
Genetic and functional diversity of β-N-acetylgalactosamine-targeting glycosidases expanded by deep-sea metagenome analysis
Authors: Sumida Tomomi , Hiraoka Satoshi , Usui Keiko , Ishiwata Akihiro , Sengoku Toru , Stubbs Keith A. , Tanaka Katsunori , Deguchi Shigeru , Fushinobu Shinya , Nunoura Takuro 
Published: May 2024

Abstractβ-N-Acetylgalactosamine-containing glycans play essential roles in several biological processes, including cell adhesion, signal transduction, and immune responses. β-N-Acetylgalactosaminidases hydrolyze β-N-acetylgalactosamine linkages of various glycoconjugates. However, their biological significance remains ambiguous, primarily because only one type of enzyme, exo-β-N-acetylgalactosaminidases that specifically act on β-N-acetylgalactosamine residues, has been documented to date. In this study, we identify four groups distributed among all three domains of life and characterize eight β-N-acetylgalactosaminidases and β-N-acetylhexosaminidase through sequence-based screening of deep-sea metagenomes and subsequent searching of public protein databases. Despite low sequence similarity, the crystal structures of these enzymes demonstrate that all enzymes share a prototype structure and have diversified their substrate specificities (oligosaccharide-releasing, oligosaccharide/monosaccharide-releasing, and monosaccharide-releasing) through the accumulation of mutations and insertional amino acid sequences. The diverse β-N-acetylgalactosaminidases reported in this study could facilitate the comprehension of their structures and functions and present evolutionary pathways for expanding their substrate specificity.
The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis
Authors: Cooreman Michael P. , Butler Javed , Giugliano Robert P. , Zannad Faiez , Dzen Lucile , Huot-Marchand Philippe , Baudin Martine , Beard Daniel R. , Junien Jean-Louis , Broqua Pierre , Abdelmalek Manal F. , Francque Sven M. 
Published: May 2024

AbstractLanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.
Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes
Authors: Vieira Ana , Wan Yu , Ryan Yan , Li Ho Kwong , Guy Rebecca L. , Papangeli Maria , Huse Kristin K. , Reeves Lucy C. , Soo Valerie W. C. , Daniel Roger , Harley Alessandra , Broughton Karen , Dhami Chenchal , Ganner Mark , Ganner Marjorie A. , Mumin Zaynab , Razaei Maryam , Rundberg Emma , Mammadov Rufat , Mills Ewurabena A. , Sgro Vincenzo , Mok Kai Yi , Didelot Xavier , Croucher Nicholas J. , Jauneikaite Elita , Lamagni Theresa , Brown Colin S. , Coelho Juliana , Sriskandan Shiranee 
Published: May 2024

AbstractThe UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.
Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus
Authors: Benjamin Kynon J. M. , Arora Ria , Feltrin Arthur S. , Pertea Geo , Giles Hunter H. , Stolz Joshua M. , D’Ignazio Laura , Collado-Torres Leonardo , Shin Joo Heon , Ulrich William S. , Hyde Thomas M. , Kleinman Joel E. , Weinberger Daniel R. , Paquola Apuã C. M. , Erwin Jennifer A. 
Published: May 2024

AbstractSchizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.
Unconventional superconductivity without doping in infinite-layer nickelates under pressure
Authors: Di Cataldo Simone , Worm Paul , Tomczak Jan M. , Si Liang , Held Karsten 
Published: May 2024

AbstractHigh-temperature unconventional superconductivity quite generically emerges from doping a strongly correlated parent compound, often (close to) an antiferromagnetic insulator. The recently developed dynamical vertex approximation is a state-of-the-art technique that has quantitatively predicted the superconducting dome of nickelates. Here, we apply it to study the effect of pressure in the infinite-layer nickelate SrxPr1−xNiO2. We reproduce the increase of the critical temperature (Tc) under pressure found in experiment up to 12 GPa. According to our results, Tc can be further increased with higher pressures. Even without Sr-doping the parent compound, PrNiO2, will become a high-temperature superconductor thanks to a strongly enhanced self-doping of the Ni $${d}_{{x}^{2}-{y}^{2}}$$

d

x

2

−

y

2

orbital under pressure. With a maximal Tc of 100 K around 100 GPa, nickelate superconductors can reach that of the best cuprates.
High carbon dioxide emissions from Australian estuaries driven by geomorphology and climate
Authors: Yeo Jacob Z.-Q. , Rosentreter Judith A. , Oakes Joanne M. , Schulz Kai G. , Eyre Bradley D. 
Published: May 2024

AbstractEstuaries play an important role in connecting the global carbon cycle across the land-to-ocean continuum, but little is known about Australia’s contribution to global CO2 emissions. Here we present an Australia-wide assessment, based on CO2 concentrations for 47 estuaries upscaled to 971 assessed Australian estuaries. We estimate total mean (±SE) estuary CO2 emissions of 8.67 ± 0.54 Tg CO2-C yr−1, with tidal systems, lagoons, and small deltas contributing 94.4%, 3.1%, and 2.5%, respectively. Although higher disturbance increased water-air CO2 fluxes, its effect on total Australian estuarine CO2 emissions was small due to the large surface areas of low and moderately disturbed tidal systems. Mean water-air CO2 fluxes from Australian small deltas and tidal systems were higher than from global estuaries because of the dominance of macrotidal subtropical and tropical systems in Australia, which have higher emissions due to lateral inputs. We suggest that global estuarine CO2 emissions should be upscaled based on geomorphology, but should also consider land-use disturbance, and climate.
The translocation of a chloride channel from the Golgi to the plasma membrane helps plants adapt to salt stress
Authors: Rajappa Sivamathini , Krishnamurthy Pannaga , Huang Hua , Yu Dejie , Friml Jiří , Xu Jian , Kumar Prakash P. 
Published: May 2024

AbstractA key mechanism employed by plants to adapt to salinity stress involves maintaining ion homeostasis via the actions of ion transporters. While the function of cation transporters in maintaining ion homeostasis in plants has been extensively studied, little is known about the roles of their anion counterparts in this process. Here, we describe a mechanism of salt adaptation in plants. We characterized the chloride channel (CLC) gene AtCLCf, whose expression is regulated by WRKY transcription factor under salt stress in Arabidopsis thaliana. Loss-of-function atclcf seedlings show increased sensitivity to salt, whereas AtCLCf overexpression confers enhanced resistance to salt stress. Salt stress induces the translocation of GFP-AtCLCf fusion protein to the plasma membrane (PM). Blocking AtCLCf translocation using the exocytosis inhibitor brefeldin-A or mutating the small GTPase gene AtRABA1b/BEX5 (RAS GENES FROM RAT BRAINA1b homolog) increases salt sensitivity in plants. Electrophysiology and liposome-based assays confirm the Cl−/H+ antiport function of AtCLCf. Therefore, we have uncovered a mechanism of plant adaptation to salt stress involving the NaCl-induced translocation of AtCLCf to the PM, thus facilitating Cl− removal at the roots, and increasing the plant’s salinity tolerance.
A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues
Authors: Yan Ze , Yang Ji , Wei Wen-Tian , Zhou Ming-Liang , Mo Dong-Xin , Wan Xing , Ma Rui , Wu Mei-Ming , Huang Jia-Hui , Liu Ya-Jing , Lv Feng-Hua , Li Meng-Hua 
Published: May 2024

AbstractHigh-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.
Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
Authors: Kakaraskoska Boceska Biljana , Vilken Tuba , Xavier Basil Britto , Kostyanev Tomislav , Lin Qiang , Lammens Christine , Ellis Sally , O’Brien Seamus , da Costa Renata Maria Augusto , Cook Aislinn , Russell Neal , Bielicki Julia , Riddell Amy , Stohr Wolfgang , Walker Ann Sarah , Berezin Eitan Naaman , Roilides Emmanuel , De Luca Maia , Romani Lorenza , Ballot Daynia , Dramowski Angela , Wadula Jeannette , Lochindarat Sorasak , Boonkasidecha Suppawat , Namiiro Flavia , Ngoc Hoang Thi Bich , Tran Minh Dien , Cressey Tim R. , Preedisripipat Kanchana , Berkley James A. , Musyimi Robert , Zarras Charalampos , Nana Trusha , Whitelaw Andrew , da Silva Cely Barreto , Jaglal Prenika , Ssengooba Willy , Saha Samir K. , Islam Mohammad Shahidul , Mussi-Pinhata Marisa Marcia , Carvalheiro Cristina Gardonyi , Piddock Laura J. V. , Heath Paul T. , Malhotra-Kumar Surbhi , Sharland Michael , Glupczynski Youri , Goossens Herman 
Published: May 2024

AbstractGram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.
Overlooked shelf sediment reductive sinks of dissolved rhenium and uranium in the modern ocean
Authors: Hong Qingquan , Cheng Yilin , Qu Yang , Wei Lin , Liu Yumeng , Gao Jianfeng , Cai Pinghe , Chen Tianyu 
Published: May 2024

AbstractRhenium (Re) and uranium (U) are essential proxies in reconstructing past oceanic oxygenation evolution. However, their removal in continental shelf sediments, hotspots of early diagenesis, were previously treated as quantitatively unimportant sinks in the ocean. Here we examine the sedimentary reductive removal of Re and U and their coupling with organic carbon decomposition, utilizing the 224Ra/228Th disequilibria within the East China Sea shelf. We identified positive correlations between their removal fluxes and the rates of sediment oxygen consumption or organic carbon decomposition. These correlations enable an evaluation of global shelf reductive sinks that are comparable to (for Re) or higher than (~4-fold for U) previously established suboxic/anoxic sinks. These findings suggest potential imbalances in the modern budgets of Re and U, or perhaps a substantial underestimation of their sources. Our study thus highlights shelf sedimentary reductive removal as critical yet overlooked sinks for Re and U in the modern ocean.
TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia
Authors: Ma Jun-Kai , Su Li-Da , Feng Lin-Lin , Li Jing-Lin , Pan Li , Danzeng Qupei , Li Yanwei , Shang Tongyao , Zhan Xiao-Lin , Chen Si-Ying , Ying Shibo , Hu Jian-Rao , Chen Xue Qun , Zhang Qi , Liang Tingbo , Lu Xin-Jiang 
Published: May 2024

AbstractBleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.