bluuebunny/crossref_metadata_2025 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

Background

Infections 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.

Methods

This 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.

Results

Genetically, 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.

Conclusions

Our 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

Background

Phthalates 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).

Methods

We 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 (< 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.

Results

Significant 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.

Conclusion

We 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.
Novel insights into osteocyte and inter-organ/tissue crosstalk
Authors: Zhang Yan , Chen Qingchang
Published: January 2024

Osteocyte, a cell type living within the mineralized bone matrix and connected to each other by means of numerous dendrites, appears to play a major role in body homeostasis. Benefiting from the maturation of osteocyte extraction and culture technique, many cross-sectional studies have been conducted as a subject of intense research in recent years, illustrating the osteocyte–organ/tissue communication not only mechanically but also biochemically. The present review comprehensively evaluates the new research work on the possible crosstalk between osteocyte and closely situated or remote vital organs/tissues. We aim to bring together recent key advances and discuss the mutual effect of osteocyte and brain, kidney, vascular calcification, muscle, liver, adipose tissue, and tumor metastasis and elucidate the therapeutic potential of osteocyte.
Advances in the study of the correlation between insulin resistance and infertility
Authors: Lei Ruobing , Chen Shuyi , Li Weihong
Published: January 2024

This is a narrative review of the progress of research on the correlation between insulin resistance and infertility. Insulin resistance (IR) is not only involved in the development of various metabolic diseases, but also affects female reproductive function, and to some extent is closely related to female infertility. IR may increase the risk of female infertility by activating oxidative stress, interfering with energy metabolism, affecting oocyte development, embryo quality and endometrial tolerance, affecting hormone secretion and embryo implantation, as well as affecting assisted conception outcomes in infertile populations and reducing the success rate of assisted reproductive technology treatment in infertile populations. In addition, IR is closely associated with spontaneous abortion, gestational diabetes and other adverse pregnancies, and if not corrected in time, may increase the risk of obesity and metabolic diseases in the offspring in the long term. This article provides a review of the relationship between IR and infertility to provide new ideas for the treatment of infertility.
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 < 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 < 0.001) and 33.97 mg/dL of higher LDL-C (β = 1.03, SE = 0.19, p < 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 < 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 <0.01, we identified 11 low-frequency AMD variants (minor allele frequency <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

Objective

Systemic 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.

Methods

Three 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.

Results

A 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.

Conclusion

This 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.
Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application
Authors: Wang Rulan , Liu Zhenkun , Wang Ting , Zhang Jiabi , Liu Jiewei , Zhou Qinghua
Published: January 2024

Lung cancer poses a global threat to human health, while common cancer treatments (chemotherapy and targeted therapies) have limited efficacy. Immunotherapy offers hope of sustained remission for many patients with lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the adenosine (ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in lung cancer. As such, a timely review of the potential value of the ADO pathway in combination with immunotherapy strategies for lung cancer is warranted. This comprehensive review first describes the role of ADO in the formation of a lung tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of ADO inhibitors combined with immune checkpoint blockers to improve the lung cancer immunosuppressive microenvironment.
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

Background

Impaired 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 methods

A retrospective analysis of 131 cancer patients with germline DNA testing and ICI treatment was performed.

Results

Ninety-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.

Conclusion

P/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

Background

Alzheimer’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.

Methods

Here, we evaluated the in vivo role of microglia-selective and full body inflammasome signalling in several mouse models of ß-amyloid-induced AD neuropathology.

Results

Microglia-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.

Conclusion

Collectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation.
Impact of inflammation and Treg cell regulation on neuropathic pain in spinal cord injury: mechanisms and therapeutic prospects
Authors: Zhang Chunjia , Li Yan , Yu Yan , Li Zehui , Xu Xin , Talifu Zuliyaer , Liu Wubo , Yang Degang , Gao Feng , Wei Song , Zhang Liang , Gong Han , Peng Run , Du Liangjie , Li Jianjun
Published: January 2024

Spinal cord injury is a severe neurological trauma that can frequently lead to neuropathic pain. During the initial stages following spinal cord injury, inflammation plays a critical role; however, excessive inflammation can exacerbate pain. Regulatory T cells (Treg cells) have a crucial function in regulating inflammation and alleviating neuropathic pain. Treg cells release suppressor cytokines and modulate the function of other immune cells to suppress the inflammatory response. Simultaneously, inflammation impedes Treg cell activity, further intensifying neuropathic pain. Therefore, suppressing the inflammatory response while enhancing Treg cell regulatory function may provide novel therapeutic avenues for treating neuropathic pain resulting from spinal cord injury. This review comprehensively describes the mechanisms underlying the inflammatory response and Treg cell regulation subsequent to spinal cord injury, with a specific focus on exploring the potential mechanisms through which Treg cells regulate neuropathic pain following spinal cord injury. The insights gained from this review aim to provide new concepts and a rationale for the therapeutic prospects and direction of cell therapy in spinal cord injury-related conditions.
Bioinformatic analysis of defective viral genomes in SARS-CoV-2 and its impact on population infection characteristics
Authors: Xu Zhaobin , Peng Qingzhi , Song Jian , Zhang Hongmei , Wei Dongqing , Demongeot Jacques , Zeng Qiangcheng
Published: January 2024

DVGs (Defective Viral Genomes) are prevalent in RNA virus infections. In this investigation, we conducted an analysis of high-throughput sequencing data and observed widespread presence of DVGs in SARS-CoV-2. Comparative analysis between SARS-CoV-2 and diverse DNA viruses revealed heightened susceptibility to damage and increased sequencing sample heterogeneity within the SARS-CoV-2 genome. Whole-genome sequencing depth variability analysis exhibited a higher coefficient of variation for SARS-CoV-2, while DVG analysis indicated a significant proportion of recombination sites, signifying notable genome heterogeneity and suggesting that a large proportion of assembled virus particles contain incomplete RNA sequences. Moreover, our investigation explored the sequencing depth and DVG content differences among various strains. Our findings revealed that as the virus evolves, there is a notable increase in the proportion of intact genomes within virus particles, as evidenced by third-generation sequencing data. Specifically, the proportion of intact genome in the Omicron strain surpassed that of the Delta and Alpha strains. This observation effectively elucidates the heightened infectiousness of the Omicron strain compared to the Delta and Alpha strains. We also postulate that this improvement in completeness stems from enhanced virus assembly capacity, as the Omicron strain can promptly facilitate the binding of RNA and capsid protein, thereby reducing the exposure time of vulnerable virus RNA in the host environment and significantly mitigating its degradation. Finally, employing mathematical modeling, we simulated the impact of DVG effects under varying environmental factors on infection characteristics and population evolution. Our findings provide an explanation for the close association between symptom severity and the extent of virus invasion, as well as the substantial disparity in population infection characteristics caused by the same strain under distinct environmental conditions. This study presents a novel approach for future virus research and vaccine development.
Case report: A novel perspective on the treatment of primary tracheal small cell carcinoma: a patient’s experience with immuno-combined EP therapy and literature review
Authors: Chen Yu , Zhu Hongbin , Wang Danping , Ye Yalan , Gao Jianrong
Published: January 2024

Tracheal small cell carcinoma (SCC) is a rare malignancy, for which the optimal treatment strategy has yet to be determined. Currently, treatment largely aligns with the therapeutic guidelines established for small cell lung cancer, although numerous unresolved issues remain. This paper details a case study of a patient with Stage IIIB primary tracheal SCC, who was treated with an immune-combined etoposide-platinum(EP) regimen. This treatment offers valuable insights into innovative approaches for managing such malignancies. Furthermore, the study includes a comprehensive literature review to better contextualize the findings. The patient, admitted on May 2, 2023, had been experiencing persistent symptoms of airway discomfort for 15 days. A bronchoscopy performed on May 4 revealed tracheal SCC, classified as T4N2M0, IIIB. Following the CAPSTONE-1 study’s methodology, the patient underwent six cycles of PD-L1(adebrelimab) combined with EP therapy, leading to significant relief of symptoms and the eventual disappearance of the tracheal mass.
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

Instruction

Microbial 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.

Methods

Thus, 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.

Results

The 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.

Discussion

Microbial 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.
Wave energy converter with floating-point absorber and catenary mooring: dynamic coupling analysis
Authors: Zhang Dapeng , Zhao Bowen , Jiang Haoyu
Published: January 2024

Mooring design for floating wave energy converters (WECs) is crucial for station maintaining, efficient power collection, and economic concerns. In order to study the dynamic response of the floating-point absorber under the coupling action of the catenary in regular waves, this research presents the numerical modeling of the floating-point absorber alone with a catenary mooring system. Hydrodynamic behavior of the floating-point absorber is analyzed with respect to wave height, wave period, and current velocity. From the computational fluid dynamics (CFD) results, it can be deduced that the wave height has a much more pronounced impact on the longitudinal motion properties of WEC, such as the longitudinal force and the surge motion, and essentially no impact on the vertical force and the heave motion. The dynamic performance of the WEC under small wave periods are quite different from those under large wave periods. The current velocity also significantly affects the hydrodynamic performance of the WEC. The larger current velocity brings strong nonlinearity for the forces of the WEC. Under the combination of waves and current, the WEC and its mooring system will achieve a dynamic balance.
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

Introduction

While 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.

Methods

Data 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.

Results

407 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.

Conclusion

This 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.
Genomic and transcriptomic analysis of genes involved in exopolysaccharide biosynthesis by Streptococcus thermophilus IMAU20561 grown on different sources of nitrogen
Authors: Wang Yuenan , Peng Qingting , Liu Yang , Wu Na , He Yanyan , Cui Xinrui , Dan Tong
Published: January 2024

Exopolysaccharides (EPSs), which are produced by lactic acid bacteria, have been found to improve the texture and functionality of fermented dairy products. In a previous study, four nitrogen sources were identified as affecting the yield, molecular weight and structure of EPSs produced by Streptococcus thermophilus IMAU20561 in M17 medium. In this genomic and transcriptomics study, a novel eps gene cluster responsible for assembly of repeating units of EPS is reported. This eps cluster (22.3 kb), consisting of 24 open reading frames, is located in the chromosomal DNA. To explore the biosynthetic mechanisms in EPS, we completed RNA-seq analysis of S. thermophilus IMAU20561 grown in four different nitrogen sources for 5 h (log phase) or 10 h (stationary phase). GO functional annotation showed that there was a significant enrichment of differentially expressed genes (DEGs) involved in: amino acid biosynthesis and metabolism; ribonucleotide biosynthesis and metabolism; IMP biosynthesis and metabolism; and phosphorus metabolism. KEGG functional annotation also indicated enrichment of DEGs involved in amino acid biosynthesis, glycolysis, phosphotransferase system, fructose, and mannose metabolism. Our findings provide a better understanding the genetic traits of S. thermophilus, the biosynthetic pathways needed for the production of EPS, and a theoretical basis for screening dairy starter cultures.
Application of next-generation sequencing to identify different pathogens
Authors: Nafea Aljuboori M. , Wang Yuer , Wang Duanyang , Salama Ahmed M. , Aziz Manal A. , Xu Shan , Tong Yigang
Published: January 2024

Early and precise detection and identification of various pathogens are essential for epidemiological monitoring, disease management, and reducing the prevalence of clinical infectious diseases. Traditional pathogen detection techniques, which include mass spectrometry, biochemical tests, molecular testing, and culture-based methods, are limited in application and are time-consuming. Next generation sequencing (NGS) has emerged as an essential technology for identifying pathogens. NGS is a cutting-edge sequencing method with high throughput that can create massive volumes of sequences with a broad application prospects in the field of pathogen identification and diagnosis. In this review, we introduce NGS technology in detail, summarizes the application of NGS in that identification of different pathogens, including bacteria, fungi, and viruses, and analyze the challenges and outlook for using NGS to identify clinical pathogens. Thus, this work provides a theoretical basis for NGS studies and provides evidence to support the application of NGS in distinguishing various clinical pathogens.
Roles of Lipolytic enzymes in Mycobacterium tuberculosis pathogenesis
Authors: Lin Hong , Xing Jiayin , Wang Hui , Wang Shuxian , Fang Ren , Li Xiaotian , Li Zhaoli , Song Ningning
Published: January 2024

Mycobacterium tuberculosis (Mtb) is a bacterial pathogen that can endure for long periods in an infected patient, without causing disease. There are a number of virulence factors that increase its ability to invade the host. One of these factors is lipolytic enzymes, which play an important role in the pathogenic mechanism of Mtb. Bacterial lipolytic enzymes hydrolyze lipids in host cells, thereby releasing free fatty acids that are used as energy sources and building blocks for the synthesis of cell envelopes, in addition to regulating host immune responses. This review summarizes the relevant recent studies that used in vitro and in vivo models of infection, with particular emphasis on the virulence profile of lipolytic enzymes in Mtb. A better understanding of these enzymes will aid the development of new treatment strategies for TB. The recent work done that explored mycobacterial lipolytic enzymes and their involvement in virulence and pathogenicity was highlighted in this study. Lipolytic enzymes are expected to control Mtb and other intracellular pathogenic bacteria by targeting lipid metabolism. They are also potential candidates for the development of novel therapeutic agents.
Polyether ionophore resistance in a one health perspective
Authors: Frederiksen Rikki Franklin , Slettemeås Jannice Schau , Granstad Silje , Lagesen Karin , Pikkemaat Mariel G. , Urdahl Anne Margrete , Simm Roger
Published: January 2024

Antimicrobial resistance is a major threat to human health and must be approached from a One Health perspective. Use of antimicrobials in animal husbandry can lead to dissemination and persistence of resistance in human pathogens. Polyether ionophores (PIs) have antimicrobial activities and are among the most extensively used feed additives for major production animals. Recent discoveries of genetically encoded PI resistance mechanisms and co-localization of resistance mechanisms against PIs and antimicrobials used in human medicine on transferrable plasmids, have raised concerns that use of PIs as feed additives bear potential risks for human health. This review summarizes the current knowledge on PI resistance and discusses the potential consequences of PI-usage as feed additives in a One Health perspective.
Carbonic anhydrase, its inhibitors and vascular function
Authors: García-Llorca Andrea , Carta Fabrizio , Supuran Claudiu T. , Eysteinsson Thor
Published: January 2024

It has been known for some time that Carbonic Anhydrase (CA, EC 4.2.1.1) plays a complex role in vascular function, and in the regulation of vascular tone. Clinically employed CA inhibitors (CAIs) are used primarily to lower intraocular pressure in glaucoma, and also to affect retinal blood flow and oxygen saturation. CAIs have been shown to dilate vessels and increase blood flow in both the cerebral and ocular vasculature. Similar effects of CAIs on vascular function have been observed in the liver, brain and kidney, while vessels in abdominal muscle and the stomach are unaffected. Most of the studies on the vascular effects of CAIs have been focused on the cerebral and ocular vasculatures, and in particular the retinal vasculature, where vasodilation of its vessels, after intravenous infusion of sulfonamide-based CAIs can be easily observed and measured from the fundus of the eye. The mechanism by which CAIs exert their effects on the vasculature is still unclear, but the classic sulfonamide-based inhibitors have been found to directly dilate isolated vessel segments when applied to the extracellular fluid. Modification of the structure of CAI compounds affects their efficacy and potency as vasodilators. CAIs of the coumarin type, which generally are less effective in inhibiting the catalytically dominant isoform hCA II and unable to accept NO, have comparable vasodilatory effects as the primary sulfonamides on pre-contracted retinal arteriolar vessel segments, providing insights into which CA isoforms are involved. Alterations of the lipophilicity of CAI compounds affect their potency as vasodilators, and CAIs that are membrane impermeant do not act as vasodilators of isolated vessel segments. Experiments with CAIs, that shed light on the role of CA in the regulation of vascular tone of vessels, will be discussed in this review. The role of CA in vascular function will be discussed, with specific emphasis on findings with the effects of CA inhibitors (CAI).
Non-invasive in vivo imaging of brain and retinal microglia in neurodegenerative diseases
Authors: Etebar Fazeleh , Harkin Damien G. , White Anthony R. , Dando Samantha J.
Published: January 2024

Microglia play crucial roles in immune responses and contribute to fundamental biological processes within the central nervous system (CNS). In neurodegenerative diseases, microglia undergo functional changes and can have both protective and pathogenic roles. Microglia in the retina, as an extension of the CNS, have also been shown to be affected in many neurological diseases. While our understanding of how microglia contribute to pathological conditions is incomplete, non-invasive in vivo imaging of brain and retinal microglia in living subjects could provide valuable insights into their role in the neurodegenerative diseases and open new avenues for diagnostic biomarkers. This mini-review provides an overview of the current brain and retinal imaging tools for studying microglia in vivo. We focus on microglia targets, the advantages and limitations of in vivo microglia imaging approaches, and applications for evaluating the pathogenesis of neurological conditions, such as Alzheimer’s disease and multiple sclerosis.
Time-varying generalized linear models: characterizing and decoding neuronal dynamics in higher visual areas
Authors: Weng Geyu , Clark Kelsey , Akbarian Amir , Noudoost Behrad , Nategh Neda
Published: January 2024

To create a behaviorally relevant representation of the visual world, neurons in higher visual areas exhibit dynamic response changes to account for the time-varying interactions between external (e.g., visual input) and internal (e.g., reward value) factors. The resulting high-dimensional representational space poses challenges for precisely quantifying individual factors’ contributions to the representation and readout of sensory information during a behavior. The widely used point process generalized linear model (GLM) approach provides a powerful framework for a quantitative description of neuronal processing as a function of various sensory and non-sensory inputs (encoding) as well as linking particular response components to particular behaviors (decoding), at the level of single trials and individual neurons. However, most existing variations of GLMs assume the neural systems to be time-invariant, making them inadequate for modeling nonstationary characteristics of neuronal sensitivity in higher visual areas. In this review, we summarize some of the existing GLM variations, with a focus on time-varying extensions. We highlight their applications to understanding neural representations in higher visual areas and decoding transient neuronal sensitivity as well as linking physiology to behavior through manipulation of model components. This time-varying class of statistical models provide valuable insights into the neural basis of various visual behaviors in higher visual areas and hold significant potential for uncovering the fundamental computational principles that govern neuronal processing underlying various behaviors in different regions of the brain.
Comparing the efficacy of therapeutic Thai acupressure on plantar acupoints and laser cane therapy on freezing of gait in Parkinson’s disease: a randomized non-inferiority trial
Authors: Miyahara Yuka , Phokaewvarangkul Onanong , Kerr Stephen , Anan Chanawat , Toriumi Haruki , Bhidayasiri Roongroj
Published: January 2024

Background

ON-freezing of gait (ON-FOG) in Parkinson’s disease (PD), often resistant to medication, is linked to sensory deficits and proprioceptive impairment, and results in falls and reduced life quality. While visual cues from a laser cane (LC), which rapidly accesses the motor cortex, are commonly used to compensate for proprioceptive impairment, increased visual reliance may be affected by disease progression. Emerging evidence suggests that modulation of peripheral sensory processing may alleviate ON-FOG, and therapeutic Thai acupressure (TTA) may be a solution. This study aims to evaluate the effect of TTA in alleviating ON-FOG and compare its effectiveness to LC in patients with PD.

Methods

This open-label, non-inferiority trial randomized 90 PD patients with ON-FOG equally into three arms: TTA for plantar nerve stimulation for 96 s, LC for visual cueing, and sham control (SC). Stride length was the primary non-inferiority endpoint [non-inferiority margin: lower limit of 95% confidence interval (CI) above −10 cm in mean change difference in pre- and immediately post-intervention in TTA versus LC (one-sided)]. Secondary outcomes included FOG episodes, double support time, velocity, cadence, step length, timed up and go (TUG) test, and visual analog scale (VAS) score.

Results

TTA showed non-inferiority to LC in stride length (mean = −0.7 cm; 95% CI: −6.55; 5.15) (one-sided). The improvements with TTA and LC versus SC were comparable between (mean = 13.11 cm; 95% CI: 7.26; 18.96) and (mean = 13.8 cm; 95% CI: 7.96; 19.65) (one-sided). Secondary outcomes favored TTA and LC over SC with improved FOG, velocity, step length, and VAS scores, while only TTA resulted in improved double support time, cadence, and TUG test results. No complications occurred.

Conclusion

The efficacy of TTA, which improves stride length, is non-inferior to that of LC and consequently alleviates FOG comparable to LC. TTA might enhance proprioceptive function and reduce visual dependence. Therefore, TTA, characterized by its non-invasive, simple, and safe techniques, is a potential non-pharmacological alternative for ON-FOG treatment and might enhance overall quality of life. However, further research into the mechanism, efficacy, and utilization of TTA is essential.

Clinical trial registration

https://www.thaiclinicaltrials.org/show/TCTR20200317001, identifier TCTR20200317001.
Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Inderyas Maira , Thapaliya Kiran , Marshall-Gradisnik Sonya , Barth Markus , Barnden Leighton
Published: January 2024

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic condition with core symptoms of fatigue and cognitive dysfunction, suggesting a key role for the central nervous system in the pathophysiology of this disease. Several studies have reported altered functional connectivity (FC) related to motor and cognitive deficits in ME/CFS patients. In this study, we compared functional connectivity differences between 31 ME/CFS and 15 healthy controls (HCs) using 7 Tesla MRI. Functional scans were acquired during a cognitive Stroop color-word task, and blood oxygen level-dependent (BOLD) time series were computed for 27 regions of interest (ROIs) in the cerebellum, brainstem, and salience and default mode networks. A region-based comparison detected reduced FC between the pontine nucleus and cerebellum vermis IX (p = 0.027) for ME/CFS patients compared to HCs. Our ROI-to-voxel analysis found significant impairment of FC within the ponto-cerebellar regions in ME/CFS. Correlation analyses of connectivity with clinical scores in ME/CFS patients detected associations between FC and ‘duration of illness’ and ‘memory scores’ in salience network hubs and cerebellum vermis and between FC and ‘respiratory rate’ within the medulla and the default mode network FC. This novel investigation is the first to report the extensive involvement of aberrant ponto-cerebellar connections consistent with ME/CFS symptomatology. This highlights the involvement of the brainstem and the cerebellum in the pathomechanism of ME/CFS.