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Prevalence and risk factors of cholelithiasis in patients with spinal cord injury: A cross-sectional analysis
Objective The purpose of the present study was to investigate the incidence of cholelithiasis and evaluate the risk factors for cholelithiasis in patients with spinal cord injury (SCI). Methods We analyzed 1,530 SCI patients (1,186 males and 344 females) from the China Rehabilitation Research Center (2010–2019) and compared patients with cholelithiasis (n = 289) and without cholelithiasis. The variables included age, gender, marital status, blood glucose level, motor function, and American Spinal Injury Association (ASIA) Impairment Scale (AIS) score. Results A total of 1530 patients with SCI, including 1186 males and 344 females, were included in this study. The prevalence of cholelithiasis was 18.89%. Univariate analysis revealed significant differences in age (P < 0.001), marital status (P < 0.001), blood glucose level (P < 0.001), and preserved motor function (P = 0.033). Multivariate analysis revealed the following independent risk factors: age ≥ 50 years (OR=1.637; 95% CI = 1.016–2.639; P = 0.043), being married (OR=1.902; 95% CI = 1.061–3.411; P = 0.031), lack of motor function (OR=1.587; 95% CI = 1.194–2.111; P < 0.001), and hyperglycemia (OR=1.764; 95% CI = 1.164–2.673; P = 0.007). Gender, lipid levels, SCI segment, and AIS grade were not significantly different. Conclusion Patients with SCI have a higher incidence of gallstones. Multivariate logistic regression analysis revealed that the occurrence of cholelithiasis in patients with SCI is closely related to age, marital status, blood glucose level and motor function preservation. Tailored preventive and therapeutic approaches should be developed for SCI patients, with intensified monitoring and intervention for high-risk patients to significantly improve quality of life.
The problem with Canada’s plan to buy scientific prestige
ALYREF-mediated RNA 5-methylcytosine modification promotes laryngeal cancer progression via stabilizing DDX11 mRNA
4-Hydroxyphenanthrene exacerbates obesity by altering gut microbiota and bile acid metabolism
IRN2Vec: A representation learning model for road network intersections by integrating geospatial attributes and travel behaviors
The structural characterization of road networks serves as a critical foundation for enabling high performance in intelligent transportation systems. This paper proposes IRN2Vec, an intersection-oriented representation learning model that generates discriminative road intersection embeddings by integrating geospatial attributes, semantic homogeneity, and mobility behavior features through the LEIRN framework. The model employs a shortest-path sampling strategy to construct training data and adopts a multi-task learning approach to jointly optimize three types of relationships: geographical proximity, label consistency, and categorical similarity. Experiments conducted on real-world road network data from San Francisco, Porto, and Tokyo demonstrate that IRN2Vec achieves average improvements in F1-Score of 31.6%/25.1%, 16.2%/8.6%, and 27.8%/20.2% over UID, GCN, and GAT models, respectively, in traffic signal classification and pedestrian crossing classification tasks. In travel time estimation, it reduces the mean absolute error (MAE) by 12.2%–24.6%. The findings provide effective feature support for traffic state perception and road network optimization.
Briefing Chat: ‘Can it run Doom?’ — why scientists got brain cells and a satellite to play the classic game
CRISPR-based mutagenesis of lipopolysaccharide biosynthesis genes in Leptospira interrogans reveals gene essentiality and confirms the role of an O-antigen polymerase
Abstract Leptospirosis is a worldwide zoonosis caused by pathogenic bacteria of the genus Leptospira . Lipopolysaccharide (LPS) is an immunodominant and protective antigen for Leptospira , but its biosynthesis remains poorly understood. In this study, we employed CRISPR/Cas9-non-homologous end-joining and CRISPR-Prime Editing to mutate key genes within the rfb locus of L. interrogans , including those involved in core oligosaccharide assembly, and the biogenesis, polymerization, and ligation of O-antigen. Mutants were successfully generated in LIC11312 ( waaF , heptosyltransferase II) and LIC12137 ( wcaJ , undecaprenyl-phosphate glycosyltransferase) but yielded only in-frame deletions suggesting their essentiality. Mutants were also successfully generated in LIC12143, a putative O-antigen polymerase, which exhibited truncated LPS that failed to induce acute leptospirosis in hamsters but retained the ability to colonize kidneys. Mutation of LIC_RS09320, an O-antigen ligase, did not display a change in LPS phenotype. Bacterins prepared with either control wild-type or LIC12143 mutant cells conferred complete homologous protection with sterile immunity, though failed to protect against heterologous challenge. These findings confirm LIC12143 as a functional O-antigen polymerase and underscore the challenges in generating knockout mutants to understand LPS biosynthesis in leptospires.
A genus-wide interaction atlas across NS4B orthologues identifies a conserved role for UFMylation in orthoflavivirus replication
Abstract Orthoflavivirus infections represent an increasing public health burden, with several members of the genus emerging or re-emerging globally. Several pre-clinical studies identified the non-structural protein 4B (NS4B), as the most promising target for the development of potent direct-acting antivirals. However, its functional roles in viral replication are still elusive. Here, we employ an integrated proteomic approach to systematically identify cellular targets of NS4B across eight prototypic orthoflaviviruses and characterize their influence on the human proteome. Using this approach, we mapped high-confidence NS4B-interacting human proteins across the genus, underlying potentially divergent and convergent mechanisms of host adaptation across orthoflaviviruses spanning diverse pathologies and vector preferences. Among these, we unveil a novel function for UBA5, the E1-activating enzyme of the UFMylation pathway, in orthoflavivirus replication. Mechanistically, we map associations of distinct viral proteins with multiple members of the UFMylation pathway, which are selectively recruited to sites of viral replication to promote infectious particle production. Finally, we demonstrate that pharmacological inhibition of UFMylation exerts potent antiviral activity in vitro and in vivo. This integrative study provides a rational framework for a system-level understanding of orthoflavivirus NS4B effector functions and sheds light on a conserved and unconventional role for UFMylation in orthoflavivirus replication.
Expression of Concern: Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study
Reckoning with my ‘ghost years’: why a low publication rate doesn’t always reflect failure
Nervous networker or conference presenter? Just care less, says speech coach Susie Ashfield
‘Baked, not fried’: five highlights from nutrition research
Daily briefing: Vaccine-carrying mosquitoes could inoculate bats against rabies
Youthful antics predict lifespan — at least for these fish
No such thing as a shark? Genomes shake up ocean predator’s family tree
A niche for every stem cell in myeloproliferative neoplasms
‘Einstein’ bot sharpens debate over AI in the classroom
VEXAS anemia is a mosaic erythroblastopenia
Abstract VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently discovered autoinflammatory disorder linked to somatic mutations in the UBA1 gene, resulting in a profound cytoplasm-restricted defect in ubiquitylation. The disease is characterized by a macrocytic anemia that remains poorly understood. To investigate the erythroid lineage in VEXAS syndrome, we conducted a comprehensive study combining in vivo assessments of patients’ mature red cells and marrow erythroblasts, alongside in vitro base-editing models of erythropoiesis. Here, we show that mature red cells do not exhibit ubiquitylation defects, and patient-derived bone marrow erythroblasts lack UBA1 mutations beyond the basophilic stage of erythroid differentiation. In vitro base editing of UBA1 variants in CD34+ primary cells resulted in high mortality during early erythroid differentiation but not during monocytic differentiation. Edited erythroid precursors displayed TP53 overexpression linked to defective ubiquitylation and anomalies in ribosome biogenesis, reminiscent of Diamond-Blackfan anemia. We propose that VEXAS syndrome–associated anemia should be considered as a mosaic erythroblastopenia, in which the severity of anemia is influenced by the quality and quantity of the UBA1–wild-type compartment. Our findings offer new insights into the physiopathology of VEXAS syndrome and may suggest new potential therapeutic options.
Long-term follow-up of gastrointestinal CAR T-cell lymphoma: homing, clonal expansion, and response to cyclosporine
Abstract Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for hematological malignancies, yet its potential to drive lymphomagenesis poses significant clinical concerns. In this study, we investigated the mechanisms underlying CAR T-cell–associated lymphomagenesis in the gastrointestinal (GI) tract on a single case, focusing specifically on the role of integrin α4β7 expression and a predisposing somatic SH2B3 mutation. We observed oligoclonal CAR T cells homing to, and clonally expanding in, the GI tract, with the dominant expanded clone harboring both a pathogenic SH2B3 mutation and a CAR transgene integration within a TFCP2 locus. The clonal CAR T cells subsequently transitioned beyond the GI tract into the peripheral blood, suggesting a potential pathway for systemic dissemination. We found clinical, histological, and molecular evidence demonstrating the efficacy of cyclosporine in reducing the expanded malignant clone and achieving durable clinical remission for more than a year. Our findings highlight the complex interplay between CAR T-cell therapy, preexisting genetic vulnerabilities, and the GI microenvironment, emphasizing the need for vigilant monitoring and tailored therapeutic strategies to address the risks associated with CAR T-cell lymphomagenesis.