bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of virulence- and antibiotic resistance-associated genotypes and phenotypes in Staphylococcus aureus strains from the food sector compared to clinical and cow mastitis isolates
Authors: Jurado Andrea , Fernández Lucía , Rodríguez Ana , García Pilar 
Published: January 2024

BackgroundInfections by the pathogen Staphylococcus aureus currently represent one of the most serious threats to human health worldwide, especially due to the production of enterotoxins and the ability to form biofilms. These structures and the acquisition of antibiotic resistance limit the action of antibiotics and disinfectants used to combat this microorganism in the industry and the clinic.MethodsThis work reports a comparative phenotypic and genotypic study of 18 S. aureus strains from different origins: clinical samples, milk from mastitic cows and food industry surfaces, most of which were isolated in Northern Spain.ResultsGenetically, the strains were very diverse but, in most cases, a closer proximity was observed for those from the same source. Notably, the average number of virulence genes was not significantly different in strains from the food sector. Of the 18 strains, 10 coded for at least one enterotoxin, and four of them carried 6 or 7 enterotoxin genes. The latter were all veterinary or clinical isolates. Most strains carried prophages, plasmids and/or pathogenicity islands. Regarding antibiotic resistance, although phenotypically all strains showed resistance to at least one antibiotic, resistance genes were only identified in 44.5% of strains, being mastitis isolates those with the lowest prevalence. Virulence-related phenotypic properties such as haemolytic activity, staphyloxanthin production, biofilm-forming capacity and spreading ability were widely distributed amongst the isolates.ConclusionsOur results indicate that production of virulence factors, antibiotic resistance and biofilm formation can be found in S. aureus isolates from diverse environments, including the food industry, although some of these traits are more prevalent in strains isolated from infections in cows or humans. This emphasizes on the importance of monitoring the spread of these determinants not only in samples from the clinical environment, but also along the food chain, a strategy that falls under the prism of a one-health approach.
Associations between urinary phthalate concentrations and antral follicle count among women undergoing in vitro fertilization
Authors: Yao Yangcheng , Du Yaoyao , Guo Na , Liu Fenghua , Deng Taoran , Li Yufeng 
Published: January 2024

BackgroundPhthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF).MethodsWe collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (&lt; 35 years) and an older group (≥ 35 years) to explore the potential effect modification by age. We also performed sensitivity analyses by restricting our analyses to only infertile women diagnosed with tubal factor infertility to test the robustness of the results.ResultsSignificant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses.ConclusionWe found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.
A conceptual framework to mitigate the adverse effects of surface urban heat islands through urban acupuncture: a two-phase scenario of diagnosis and prescription at the neighborhood scale
Authors: Moussavi A. S. Mohammad Reza , Lak Azadeh , Tabrizi Nasibeh 
Published: January 2024

Rising temperatures, a major global environmental challenge, negatively impact health, the environment, society, and the economy. Surface Urban Heat Islands (SUHI), exacerbated by urbanization and climate change, intensify vulnerabilities for urban areas and residents. Urban planning and design aime to reduce these vulnerabilities through large-scale and small-scale interventions. However, addressing the significance of the capillary effects resulting from small-scale interventions and bottom-up community engagement is important. Urban acupuncture (UA) is an emerging approach in contemporary urban planning and design that focuses on small-scale interventions to mitigate the effects of SUHIs at the community level. This study develops a framework for mitigating the impacts of SUHIs through UA implementation in urban design. The proposed framework consists of two key phases: diagnosis and prescription. During the diagnosis phase, we analyzed heat-vulnerable points to identify indicators contributing to the development and exacerbation of the SUHIs. Then, we employed the Matrix of Cross Impact Multiplications Applied to a Classification (MICMAC) technique to comprehensively assess 75 influential indicators related to urban structure across various aspects and scales, focusing on the mesoscale. Among them, 30 leading indicators were identified, of which environmental and morphological indicators emerged as significant catalysts. Moving on to the prescription phase, we developed a UA-based framework called the “5 Wh Question” which addresses five fundamental questions: why, who, what, how, and where. Our findings can provide comprehensive solutions for policymakers and urban planners to address the identified heat-vulnerable points.
Evaluation of genetic variants related to lipid levels among the North Indian population
Authors: Walia Gagandeep Kaur , Panniyammakal Jeemon , Agarwal Tripti , Jalal Ruchita , Gupta Ruby , Ramakrishnan Lakshmy , Tandon Nikhil , Roy Ambuj , Krishnan Anand , Prabhakaran Dorairaj 
Published: January 2024

Background: A heavy burden of cardiometabolic conditions on low- and middle-income countries like India that are rapidly undergoing urbanization remains unaddressed. Indians are known to have high levels of triglycerides and low levels of HDL-C along with moderately higher levels of LDL-C. The genome-wide findings from Western populations need to be validated in an Indian context for a better understanding of the underlying etiology of dyslipidemia in India.Objective: We aim to validate 12 genetic variants associated with lipid levels among rural and urban Indian populations and derive unweighted and weighted genetic risk scores (uGRS and wGRS) for lipid levels among the Indian population.Methods: Assuming an additive model of inheritance, linear regression models adjusted for all the possible covariates were run to examine the association between 12 genetic variants and total cholesterol, triglycerides, HDL-C, LDL-C, and VLDL-C among 2,117 rural and urban Indian participants. The combined effect of validated loci was estimated by allelic risk scores, unweighted and weighted by their effect sizes.Results: The wGRS for triglycerides and VLDL-C was derived based on five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs2293889 at TRPS1, rs4148005 at ABCA8, and rs4420638 at APOC1), which was associated with 36.31 mg/dL of elevated triglyceride and VLDL-C levels (β = 0.95, SE = 0.16, p &lt; 0.001). Similarly, every unit of combined risk score (rs2293889 at TRPS1 and rs4147536 at ADH1B) was associated with 40.62 mg/dL of higher total cholesterol (β = 1.01, SE = 0.23, p &lt; 0.001) and 33.97 mg/dL of higher LDL-C (β = 1.03, SE = 0.19, p &lt; 0.001) based on its wGRS (rs2293889 at TRPS1, rs4147536 at ADH1B, rs4420638 at APOC1, and rs660240 at CELSR2). The wGRS derived from five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs4148005 at ABCA8, rs4420638 at APOC1, and rs7832643 at PLEC) was associated with 10.64 mg/dL of lower HDL-C (β = −0.87, SE = 0.14, p &lt; 0.001).Conclusion: We confirm the role of eight genome-wide association study (GWAS) loci related to different lipid levels in the Indian population and demonstrate the combined effect of variants for lipid traits among Indians by deriving the polygenic risk scores. Similar studies among different populations are required to validate the GWAS loci and effect modification of these loci by lifestyle and environmental factors related to urbanization.
Risk and protection of different rare protein-coding variants of complement component C4A in age-related macular degeneration
Authors: Seddon Johanna M. , De Dikha , Casazza William , Cheng Shun-Yun , Punzo Claudio , Daly Mark , Zhou Danlei , Coss Samantha L. , Atkinson John P. , Yu Chack-Yung 
Published: January 2024

Introduction: Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. One-third of the genetic contribution to this disease remains unexplained.Methods: We analyzed targeted sequencing data from two independent cohorts (4,245 cases, 1,668 controls) which included genomic regions of known AMD loci in 49 genes.Results: At a false discovery rate of &lt;0.01, we identified 11 low-frequency AMD variants (minor allele frequency &lt;0.05). Two of those variants were present in the complement C4A gene, including the replacement of the residues that contribute to the Rodgers-1/Chido-1 blood group antigens: [VDLL1207-1210ADLR (V1207A)] with discovery odds ratio (OR) = 1.7 (p = 3.2 × 10−5) which was replicated in the UK Biobank dataset (3,294 cases, 200,086 controls, OR = 1.52, p = 0.037). A novel variant associated with reduced risk for AMD in our discovery cohort was P1120T, one of the four C4A-isotypic residues. Gene-based tests yielded aggregate effects of nonsynonymous variants in 10 genes including C4A, which were associated with increased risk of AMD. In human eye tissues, immunostaining demonstrated C4A protein accumulation in and around endothelial cells of retinal and choroidal vasculature, and total C4 in soft drusen.Conclusion: Our results indicate that C4A protein in the complement activation pathways may play a role in the pathogenesis of AMD.
Development and validation of a new diagnostic prediction model of ENHO and NOX4 for early diagnosis of systemic sclerosis
Authors: Zheng Leting , Wu Qiulin , Chen Shuyuan , Wen Jing , Dong Fei , Meng Ningqin , Zeng Wen , Zhao Cheng , Zhong Xiaoning 
Published: January 2024

ObjectiveSystemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis. The challenge of early diagnosis, along with the lack of effective treatments for fibrosis, contribute to poor therapeutic outcomes and high mortality of SSc. Therefore, there is an urgent need to identify suitable biomarkers for early diagnosis of SSc.MethodsThree skin gene expression datasets of SSc patients and healthy controls were downloaded from Gene Expression Omnibus (GEO) database (GSE130955, GSE58095, and GSE181549). GSE130955 (48 early diffuse cutaneous SSc and 33 controls) were utilized to screen differentially expressed genes (DEGs) between SSc and normal skin samples. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) were performed to identify diagnostic genes and construct a diagnostic prediction model. The results were further validated in GSE58095 (61 SSc and 36 controls) and GSE181549 (113 SSc and 44 controls) datasets. Receiver operating characteristic (ROC) curves were applied for assessing the level of diagnostic ability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to verify the diagnostic genes in skin tissues of out cohort (10 SSc and 5 controls). Immune infiltration analysis were performed using CIBERSORT algorithm.ResultsA total of 200 DEGs were identified between SSc and normal skin samples. Functional enrichment analysis revealed that these DEGs may be involved in the pathogenesis of SSc, such as extracellular matrix remodeling, cell-cell interactions, and metabolism. Subsequently, two critical genes (ENHO and NOX4) were identified by LASSO and SVM-RFE. ENHO was found down-regulated while NOX4 was up-regulated in skin of SSc patients and their expression levels were validated by above three datasets and our cohort. Notably, these differential expressions were more pronounced in patients with diffuse cutaneous SSc than in those with limited cutaneous SSc. Next, we developed a novel diagnostic model for SSc using ENHO and NOX4, which demonstrated strong predictive power in above three cohorts and in our own cohort. Furthermore, immune infiltration analysis revealed dysregulated levels of various immune cell subtypes within early SSc skin specimens, and a negative correlation was observed between the levels of ENHO and Macrophages M1 and M2, while a positive correlation was observed between the levels of NOX4 and Macrophages M1 and M2.ConclusionThis study identified ENHO and NOX4 as novel biomarkers that can be serve as a diagnostic prediction model for early detection of SSc and play a potential role in the pathogenesis of the disease.
Germline DNA damage response gene mutations as predictive biomarkers of immune checkpoint inhibitor efficacy
Authors: Dennis Michael J. , Bylsma Sophia , Madlensky Lisa , Pagadala Meghana S. , Carter Hannah , Patel Sandip P. 
Published: January 2024

BackgroundImpaired DNA damage response (DDR) can affect immune checkpoint inhibitors (ICI) efficacy and lead to heightened immune activation. We assessed the impact of pathogenic or likely pathogenic (P/LP) germline DDR mutations on ICI response and toxicity.Materials and methodsA retrospective analysis of 131 cancer patients with germline DNA testing and ICI treatment was performed.ResultsNinety-two patients were DDR-negative (DDR-), and 39 had ≥1 DDR mutation (DDR+). DDR+ patients showed higher objective response rates (ORRs) compared to DDR- in univariate and multivariable analyses, adjusting for age and metastatic disease (62% vs. 23%, unadjusted OR = 5.41; 95% CI, 2.41-12.14; adjusted OR 5.94; 95% CI, 2.35-15.06). Similar results were seen in mismatch repair (MMR), DDR pathways with intact MMR (DDR+MMRi), and homologous recombination (HR) subgroups versus DDR- (adjusted OR MMR = 24.52; 95% CI 2.72-221.38, DDR+MMRi = 4.26; 95% CI, 1.57-11.59, HR = 4.74; 95% CI, 1.49-15.11). DDR+ patients also had higher ORRs with concurrent chemotherapy (82% vs. 39% DDR-, p=0.03) or concurrent tyrosine kinase inhibitors (50% vs. 5% DDR-, p=0.03). No significant differences in immune-related adverse events were observed between DDR+ and DDR- cohorts.ConclusionP/LP germline DDR mutations may enhance ICI response without significant additional toxicity.
Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer’s disease
Authors: Srinivasan Sahana , Kancheva Daliya , De Ren Sofie , Saito Takashi , Jans Maude , Boone Fleur , Vandendriessche Charysse , Paesmans Ine , Maurin Hervé , Vandenbroucke Roosmarijn E. , Hoste Esther , Voet Sofie , Scheyltjens Isabelle , Pavie Benjamin , Lippens Saskia , Schwabenland Marius , Prinz Marco , Saido Takaomi , Bottelbergs Astrid , Movahedi Kiavash , Lamkanfi Mohamed , van Loo Geert 
Published: January 2024

BackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disorder affecting memory and cognition. The disease is accompanied by an abnormal deposition of ß-amyloid plaques in the brain that contributes to neurodegeneration and is known to induce glial inflammation. Studies in the APP/PS1 mouse model of ß-amyloid-induced neuropathology have suggested a role for inflammasome activation in ß-amyloid-induced neuroinflammation and neuropathology.MethodsHere, we evaluated the in vivo role of microglia-selective and full body inflammasome signalling in several mouse models of ß-amyloid-induced AD neuropathology.ResultsMicroglia-specific deletion of the inflammasome regulator A20 and inflammasome effector protease caspase-1 in the AppNL-G-F and APP/PS1 models failed to identify a prominent role for microglial inflammasome signalling in ß-amyloid-induced neuropathology. Moreover, global inflammasome inactivation through respectively full body deletion of caspases 1 and 11 in AppNL-G-F mice and Nlrp3 deletion in APP/PS1 mice also failed to modulate amyloid pathology and disease progression. In agreement, single-cell RNA sequencing did not reveal an important role for Nlrp3 signalling in driving microglial activation and the transition into disease-associated states, both during homeostasis and upon amyloid pathology.ConclusionCollectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation.
Overestimation of microbial community respiration caused by nitrification, and the identification of keystone groups associated with respiration
Authors: Zhang Lianbao , Zhou Wei , Wang Yanwei , Liu Yeping , Chen Junfeng , Li Bin , Su Bei , Song Hui 
Published: January 2024

InstructionMicrobial community respiration (MCR) strongly controls the fate of organic carbon in the ocean. The balance between MCR and primary production strongly determines whether the ocean is a net sink or source of CO2 to the atmosphere. Thus, it is necessary to estimate MCR to better understand the role of oceans in the global carbon cycle. Methods based on apparent oxygen utilization (AOU) are predominant while electron transport system (ETS) assay gets increasing attention. Although methods get developed, few studies on MCR have been performed on a seasonal cycle. Because MCR is strongly associated with the temperature which changes along with the succession of seasons, it is urgent to study the MCR on a seasonal cycle.MethodsThus, we measured MCR using in vivo tetrazolium salt 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride (INT) reduction rates (ETS) and oxygen-optode methods (AOU) simultaneously we measured the MCR based on AOU and ETS methods simultaneously from November 2020 to November 2021 in Aoshan Bay, China.ResultsThe highest AOU appeared in autumn, followed by summer, spring, and winter, whereas the highest ETS activity appeared in summer, followed by spring, autumn and winter. The seasonal trend of MCR estimated from AOU and ETS were not consistent, and further analysis indicated that oxygen consumption induced by nitrification caused the overestimation of MCR in autumn evaluated from AOU.DiscussionMicrobial groups that were strongly correlated with MCR estimated by ETS had the ability to degrade various substrates and could get energy directly from light. It should be careful to notice the deviation of assumed organic carbon demand based on ETS caused by the alternation of day and night. Furthermore, the pattern of bacterial groups associated with year-round MCR was distinct from season-specific MCR. This study raised a warning for caution when estimating MCR based on AOU and it was better to fully take the photoheterotrophy into account when assuming organic carbon remineralization based on ETS.
An observational study on treatment regimens and effectiveness for psoriasis in real-world settings among 407 patients in Southeast China
Authors: Huo Yuping , Huang Yike , Lee Tungchun , Lin Maoying , Chun Wenhung 
Published: January 2024

IntroductionWhile new targeted therapies have advanced psoriasis treatment, real-world data on comparative effectiveness is lacking. This study analyzed treatment regimens and response in an observational cohort, examining potential disparities between clinical trials and routine practice.MethodsData from the Psoriasis Standardized Diagnosis and Treatment Center registry were analyzed. Patients with ≥1 follow-up were included. Treatment response was assessed using PASI 50/90 criteria. Factors associated with response were analyzed.Results407 patients were included (46 first-time diagnosed, 361 previously diagnosed). A higher proportion of first-time diagnosed patients achieved treatment response than previously diagnosed (76.1% vs. 62.6%). Multivariable analysis identified factors associated with reduced response in previously treated patients.ConclusionThis real-world study found lower treatment response rates compared to clinical trials, especially in previously treated patients. Disparities highlight remaining unmet needs for psoriasis management. Combination and rotational strategies may improve outcomes in patients unresponsive to available therapies. Ongoing research on novel targets and pathways is warranted to address treatment gaps.