Browse Articles
Discover research articles across all indexed journals
Elevated urinary phytoestrogens are associated with delayed biological aging: a cross-sectional analysis of NHANES data
Cobalt-Doped Ru@RuO<sub>2</sub> Core–Shell Heterostructure for Efficient Acidic Water Oxidation in Low-Ru-Loading Proton Exchange Membrane Water Electrolyzers
GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis
Abstract Sarcoidosis is a complex inflammatory disease with a strong genetic component. Here, we perform a genome-wide association study in 9755 sarcoidosis cases to identify risk loci and map associated genes. We then use transcriptome-wide association studies and enrichment analyses to explore pathways involved in sarcoidosis and use Mendelian randomization to examine associations with modifiable factors and circulating biomarkers. We identify 28 genomic loci associated with sarcoidosis, with the C1orf141-IL23R locus showing the largest effect size. We observe gene expression patterns related to sarcoidosis in the spleen, whole blood, and lung, and highlight 75 tissue-specific genes through transcriptome-wide association studies. Furthermore, we use enrichment analysis to establish key roles for T cell activation, leukocyte adhesion, and cytokine production in sarcoidosis. Additionally, we find associations between sarcoidosis and genetically predicted body mass index, interleukin-23 receptor, and eight circulating proteins.
The causal effects of inflammatory bowel disease on its ocular manifestations: A Mendelian randomization study
Background Observational studies have shown that ocular manifestations of inflammatory bowel disease (IBD) are common extraintinal manifestations, among which iridocyclitis, scleritis and episcleritis are the most common. However, whether there is a causal relationship between the two is unclear. The purpose of this study was to evaluate the causality of IBD on ocular manifestations using the mendelian randomization (MR) analysis. Methods We performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Results After false discovery rate (FDR) correction, genetically predicted IBD (IVW OR = 1.184, 95% CI: 1.125-1.247, P_FDR < 0.001), Crohn’s disease (CD, IVW OR = 1.082, 95% CI: 1.033-1.133, P_FDR = 0.007) and ulcerative colitis (UC, IVW OR = 1.192, 95% CI: 1.114-1.275, P_FDR < 0.001) were associated with an increased risk of iridocyclitis. Moreover, IBD (IVW OR = 1.128, 95% CI: 1.064-1.196, P_FDR = 0.001), CD (IVW OR = 1.077, 95% CI: 1.026-1.131, P_FDR = 0.019) and UC (IVW OR = 1.153, 95% CI: 1.069-1.243, P_FDR = 0.003) were associated with a higher risk of uveitis (uveitis includes iridocyclitis). Further sensitivity analyses validated the robustness of the above associations. However, IBD and its subtypes were not associated with scleritis, episcleritis, optic neuritis and corneal disease. Results of complementary methods were generally consistent with those of the IVW method. Conclusions Our study revealed genetically predicted associations of IBD, CD and UC on iridocyclitis and uveitis in European populations. However, IBD, CD, and UC are not causally related to scleritis, external scleritis, optic neuritis, and corneal disease.
Innovative art selection through neutrosophic hesitant fuzzy partitioned Maclaurin symmetric mean aggregation operator
Nickel-Catalyzed Asymmetric Homobenzylic Hydroamidation of Aryl Alkenes to Access Chiral β-Arylamides
Foxa2-dependent uterine glandular cell differentiation is essential for successful implantation
Combatting antibiotic resistance in Gardnerella vaginalis: A comparative in silico investigation for drug target identification
Gardnerella vaginalis is the most frequently identified bacterium in approximately 95% of bacterial vaginosis (BV) cases. This species often exhibits resistance to multiple antibiotics, posing challenges for treatment. Therefore, there is an urgent need to develop and explore alternative therapeutic strategies for managing bacterial vaginosis. The objective of this study was to identify virulence factors and potential drug targets against Gardnerella vaginalis by utilizing in silico methods, including subtractive and comparative genomics. These methods enabled the systematic comparison of genetic sequences to pinpoint specific features unique to G. vaginalis and crucial for its pathogenicity, which could then inform the development of targeted therapeutic strategies. The analysis of the pathogen's proteomic data aimed to identify proteins that fulfilled specific criteria. These included being non-homologous to human proteins, essential for bacterial survival, amenable to drug targeting, involved in virulence, and contributing to antibiotic resistance. Following these analyses and an extensive literature review, the phospho-2-dehydro-3-deoxyheptonate aldolase enzyme emerged as a promising drug target. To deepen our understanding of the biological function of the identified protein, comprehensive protein structural modeling, validation studies, and network topology analyses were conducted. The subsequent structural analysis, encompassing modeling, validation, and network topology assessment, is aimed at further characterizing the protein. Using a library of around 9,000 FDA-approved compounds from the DrugBank database, a virtual screening was conducted to identify potential compounds that could effectively target the proposed drug target. This approach facilitated the evaluation of existing drugs for their ability to inhibit the target, potentially offering an efficient pathway for developing new treatments against the pathogen. Leveraging the established efficacy, safety, pharmacokinetics, and pharmacodynamics of these compounds, the study suggests repurposing them for Gardnerella vaginalis infections. Among the screened compounds, five specific agents—DB03332, DB07452, DB01262, DB02076, and DB00727—were identified as cost-effective therapeutic options for treating infections related to Gardnerella vaginalis. These compounds were selected based on their efficacy in targeting the pathogen while maintaining economic feasibility. While the results indicate potential efficacy in treating infections caused by the pathogen, further experimental studies are essential to validate these findings.
Activin A affects colorectal cancer progression and immunomodulation in a stage dependent manner
Abstract Advanced colorectal cancer (CRC) continues to present with poor survival and treatment options remain limited. We have shown that increased activin A (activin) expression in the tumor microenvironment (TME) is associated with poor outcome in a cohort of stage III and IV CRC patients. Here, we hypothesized that activin promotes stage specific outcomes in CRC, enhancing metastasis and tolerance in late-stage CRC exclusively. We employed Digital Spatial Profiling (DSP) technology on a cohort of stage II and III CRC patient tissue samples obtained at the time of curative surgery to show that activin co-localization was associated with increased mitogenic signaling, proliferation, and immunosuppression in stage III, but not stage II, CRCs. Furthermore, we found strong linear correlations between markers of immunosuppression and signaling proteins in activin (+) areas, an effect that was not observed in activin (-) areas of tissue. Taken together these data suggest activin exerts pro-metastatic and immunosuppressive effects in stage III, but not stage II, CRC providing an attractive therapeutic target for advanced CRC.
An Operationally Unsaturated Iridium-Pincer Complex That C–H Activates Methane and Ethane in the Crystalline Solid-State
Insights into the compact CRISPR–Cas9d system
The efficacy of the corpus-based error correction method on revision in writing classrooms
Despite the growing interests in investigating the application of data-driven learning (DDL), much existing research remains outcome-oriented. Limited attention has been paid to learners’ interactions with corpora, especially the experiences of consulting corpora and decision-making processes during revision in second language (L2) writing. In this regard, this study investigates how corpora assist language learning during the revision process in a classroom-based foreign language learning context. We recruited 123 non-English major undergraduates from a university in China, learners’ revision behaviours and outcomes were analysed in each draft. To gather the learners’ experiences and perceptions of using the BAWE corpus for error correction, a stimulated recall interview was conducted using the revised drafts as stimuli. Quantitative results indicated that corpus consultation was highly effective for revising word form errors (93.6%), and participants were more likely to use the BAWE corpus to correct collocation and phrase errors (62.7%). Interview results demonstrated that the corpus-based error correction method was effective in enhancing correctness and facilitating language learning. Learners were able to utilise corpora to identify patterns, shape writing habits, and test linguistic hypothesis. The findings and the implications of this study also provide valuable insights for teachers into the potential role and implementation of corpora in designing classroom writing tasks.
Development of hybrid robust model based on computational modeling and machine learning for analysis of drug sorption onto porous adsorbents
Enantiopurity by Directed Evolution of Crystal Stabilities and Nonequilibrium Crystallization
Salt stress activates the CDK8-AHL10-SUVH2/9 module to dynamically regulate salt tolerance in Arabidopsis
Comparison between Go-GutDx, a novel diagnostic stool test kit with potential impact in low-income countries, and BioFire test
Introduction Infectious diarrheal diseases are one of the leading causes of worldwide morbidity and mortality. The incidence of diarrhea is higher in Low-Middle-Income Countries (LMIC), where more than 90% of deaths from diarrheal diseases occur. Diagnostic tests for infectious diarrhea are not readily available in Low-Middle-Income Countries. Our study evaluates a novel, cost-effective, easy-to-use DNA stool testing kit for infectious diarrhea that can easily be rolled out in low-resource settings and has comparable performance to current testing modalities in the USA in terms of diagnostic utility. Methods 435 stool samples were tested using the novel stool testing Kit (Go-GutDx®). The stool samples were in groups of 8 and were tested using floating microspheres DNA extraction followed by Recombinase Polymerase Amplification (RPA) and lateral flow assay detection. Pathogens tested include Clostridium difficile, Campylobacter jejuni, Salmonella enterica Typhimurium, Shigella spp., STEC (stx1, stx2), Vibrio spp., and Yersinia enterocolitica. The same samples were tested using BioFire GI Panel (gold standard), and the results were compared. Descriptive analysis was summarized as raw counts and frequencies and compared using Fisher’s exact test. We conducted specificity and sensitivity analysis of the two diagnostic tests using the diagnostic testing package in STATA. Graphical illustrations were conducted using two-way line graphs with custom margins and axis. All analyses with p-values ≤ 0.05 were significant. All analyses were conducted using STATA version 17. Results Results showed a sensitivity of 56.1% for C. difficile, and 58.6% for Campylobacter jejuni. 46.1% for STEC (stx1, stx2), 83.3% for Salmonella, 0% for Yersinia enterocolitica, 66.7% for Vibrio spp and 65.0% for Shigella spp. Specificities were > 97% for all pathogens. The positive predictive value was highest for Campylobacter jejuni 94.4%, followed by C. difficile 93.5%, Salmonella 86.2%, Shigella 76.5%, STEC (stx1, stx2) 50%, Vibrio spp 40%, and Yersinia 0%. The negative predictive value was 75.8% for C. difficile, with all other pathogens being above 98.3%. Table 3. The concordance between BioFire and Go-GutDx® for C. difficile testing was 80%. All other organisms showed a concordance of greater than 97% Table 2. Discussion Our study confirms that Go-GutDx® is a novel diagnostic tool for diarrheal pathogens with statistically comparable sensitivity, specificity, positive and negative predictive values with the current gold standard testing kit, BioFire. In addition, the simplicity of the technology and lower price both to healthcare systems and to patients makes Go-GutDx® an ideal diagnostic test to be implemented in low- and middle-income countries.
Publisher Correction: Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages
The relationship between diet, plasma glucose, and cancer prevalence across vertebrates
Coping with chronic periprosthetic joint infection after failed revision of total knee and hip arthroplasty: a qualitative study on patient’s experiences in treatment and healing
Periprosthetic joint infections (PJI), along with the extensive medical and surgical interventions required for treatment, impose a substantial psychological burden on patients. Given the need for patients to adapt to long-term physical limitations and ongoing medical challenges, this qualitative study aims to explore the nature of psychological coping amongst patients with chronic cases of PJI. A total of 18 patients (8 men and 10 women, aged 55 to 92) who underwent a total knee or hip arthroplasty revision due to chronic PJI were recruited at a single academic institution between August 2022 and July 2023. Semi-structured interviews were conducted at two timepoints and analyzed using thematic analysis. We identified the nature of coping with PJI as patients’ process-orientation towards healing. This encapsulates constant adaptation to challenges and losses in day-to-day life, managing expectations and proactively developing a sense of self-efficacy during treatment and healing. Patients expressed uncertainty and unpredictability to treatment trajectories and getting a feeling of being stuck, where health and well-being oscillates between progression and regression. These experiences contributed to unstable relationships with healthcare practitioners which were influenced by loss of trust and perceived treatment failures. A holistic view on patients, taking them seriously in their concerns and providing clear information were identified as crucial factors in shaping a positive patient-physician relationship. Acknowledging the fluctuating nature of chronic PJI treatment, physicians should adopt a process-oriented approach that promotes step-by-step healing while maintaining a positive patient-physician relationship. Recognizing the profound psychological impact, we propose the establishment of a new subdiscipline, namely ‘Psycho-Endoprosthetics’, to facilitate interdisciplinary collaborations for research and practice in septic surgery.