bluuebunny/crossref_metadata_2025 huggingface dataset:
Double burden of vulnerability for refugees: conceptualization and policy solutions for financial protection in Iran using systems thinking approach
Authors: Shahabi Saeed , Etemadi Manal , Hedayati Maryam , Bagheri Lankarani Kamran , Jakovljevic Mihajlo
Published: September 2023

Introduction

Iran is host to one of the world’s largest and longest-standing refugee populations. Although Iran has initiated a basic health insurance scheme for refugees throughout the country since September 2015, the population coverage of this scheme is very low, and various factors have caused a significant percentage of refugees to still lack insurance coverage and often face financial hardships when receiving health services. In response, this study aimed to understand barriers to insurance coverage among refugees in Iran and propose effective policies that can address persistent gaps in financial protection.

Methods

This qualitative study was conducted in two phases. First, a review of policy documents and interviews with participants were conducted to investigate the common barriers and facilitators of effective insurance coverage for refugees in Iran. Then, a systems thinking approach was applied to visualize the common variables and interactions on the path to achieving financial protection for refugees.

Results

Findings showed that various factors, such as (1) household-based premium for refugees, (2) considering a waiting time to be eligible for insurance benefits, (3) determining high premiums for non-vulnerable groups and (4) a deep difference between the health services tariffs of the public and private service delivery sectors in Iran, have caused the coverage of health insurance for non-vulnerable refugees to be challenging. Furthermore, some policy solutions were found to improve the health insurance coverage of refugees in Iran. These included removing household size from premium calculations, lowering current premium rates and getting monthly premiums from non-vulnerable refugees.

Conclusions

A number of factors have caused health insurance coverage to be inaccessible for refugees, especially non-vulnerable refugees in Iran. Therefore, it is necessary to adopt effective policies to improve the health financing for the refugee with the aim of ensuring financial protection, taking into account the different actors and the interactions between them.
Cost-effectiveness analysis of robot-assisted gait training in patients with bilateral spastic cerebral palsy
Authors: Klobucká Stanislava , Klobucký Robert , Valovičová Katarína , Šiarnik Pavol , Kollár Branislav
Published: September 2023

Background

To date, there have been no published studies evaluating the cost-effectiveness of robot-assisted gait training (RAGT) in adolescent and adult patients with cerebral palsy (CP). The study´s aim was to analyse the cost-effectiveness of RAGT versus conventional kinesiotherapy (CON) from the health care provider’s perspective.

Methods

We expressed the cost-effectiveness of RAGT in the Lokomat® system after analysing the costs and effects of RAGT and conventional therapy through the Incremental Cost-Effectiveness Ratio (ICER) based on a bicentric randomized controlled study, in which we demonstrated that the intensive RAGT regimen is more effective than conventional therapy in terms of improvements in gross motor functions in adolescent and adult patients with bilateral spastic CP.

Results

According to the calculated ICER ratio for Lokomat®, an additional improvement per unit of effect (1% in GMFM), compared to conventional therapy, results in an average cost increase of EUR70.38 per patient in a therapeutic block consisting of 20 TUs (Therapeutic Units).

Conclusion

However, from the comprehensive analysis of the results and evaluation of the long-term effects, it follows that RAGT applied in adolescent and adult patients with bilateral spastic CP is not only more effective in terms of evaluation of monitored clinical parameters, but in the long term it is also more cost-effective compared to conventional therapy.
Tamoxifen exerts anti-peritoneal fibrosis effects by inhibiting H19-activated VEGFA transcription
Authors: Zhao Tingting , Sun Zhengyu , Lai Xueli , Lu Hongtao , Liu Lulu , Li Shuangxi , Yuan Ji-hang , Guo Zhiyong
Published: September 2023

Background

Peritoneal dialysis (PD) remains limited due to dialysis failure caused by peritoneal fibrosis. Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been reported to treat fibrosis, but the underlying mechanism remains unknown. In this study, we sought to explore whether tamoxifen played an anti-fibrotic role by affecting transcription factor ESR1.

Methods

ESR1 expression was detected in the human peritoneum. Mice were daily intraperitoneally injected with 4.25% glucose PD dialysate containing 40 mM methylglyoxal for 2 weeks to establish PD-induced peritoneal fibrosis. Tamoxifen was administrated by daily gavage, at the dose of 10 mg/kg. Chromatin immunoprecipitation (ChIP) and dual‐luciferase reporter assay were performed to validate ESR1 bound H19 promoter. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of H19 on the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells (HPMCs). Intraperitoneal injection of nanomaterial-wrapped 2′-O-Me-modified small interfering RNA was applied to suppress H19 in the mouse peritoneum. RNA immunoprecipitation and RNA pull-down assays demonstrated binding between H19 and p300. Exfoliated peritoneal cells were obtained from peritoneal dialysis effluent to analyze the correlations between ESR1 (or H19) and peritoneal solute transfer rate (PSTR).

Results

ESR1 was increased significantly in the peritoneum after long-term exposure to PD dialysate. Tamoxifen treatment ameliorated high glucose-induced MMT of HPMCs, improved ultrafiltration rate, and decreased PSTR of mouse peritoneum. Tamoxifen reduced the H19 level by decreasing the ESR1 transcription of H19. Depletion of H19 reversed the pro-fibrotic effect of high glucose while ectopic expression of H19 exacerbated fibrotic pathological changes. Intraperitoneal injection of nanomaterial-wrapped 2′-O-Me-modified siRNAs targeting H19 mitigated PD-related fibrosis in mice. RNA immunoprecipitation (RIP) and RNA pull-down results delineated that H19 activated VEGFA expression by binding p300 to the VEGFA promoter and inducing histone acetylation of the VEGFA promoter. ESR1 and H19 were promising targets to predict peritoneal function.

Conclusions

High glucose-induced MMT of peritoneal mesothelial cells in peritoneal dialysis via activating ESR1. In peritoneal mesothelial cells, ESR1 transcribed the H19 and H19 binds to transcription cofactor p300 to activate the VEGFA. Targeting ESR1/H19/VEGFA pathway provided new hope for patients undergoing peritoneal dialysis.

Graphic Abstract
Identification of potential drug targets for rheumatoid arthritis from genetic insights: a Mendelian randomization study
Authors: Cao Yu , Yang Ying , Hu Qingfeng , Wei Guojun
Published: September 2023

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory illness that mostly affects the joints of the hands and feet and can reduce life expectancy by an average of 3 to 10 years. Although tremendous progress has been achieved in the treatment of RA, a large minority of patients continue to respond poorly to existing medications, owing in part to a lack of appropriate therapeutic targets.

Methods

To find therapeutic targets for RA, a Mendelian randomization (MR) was performed. Cis-expression quantitative trait loci (cis-eQTL, exposure) data were obtained from the eQTLGen Consortium (sample size 31,684). Summary statistics for RA (outcome) were obtained from two largest independent cohorts: sample sizes of 97,173 (22,350 cases and 74,823 controls) and 269,377 (8279 cases and 261,098), respectively. Colocalisation analysis was used to test whether RA risk and gene expression were driven by common SNPs. Drug prediction and molecular docking was further used to validate the medicinal value of drug targets.

Results

Seven drug targets were significant in both cohorts in MR analysis and supported by localization. PheWAS at the gene level showed only ATP2A1 associated with other traits. These genes are strongly associated with immune function in terms of biological significance. Molecular docking showed excellent binding for drugs and proteins with available structural data.

Conclusion

This study identifies seven potential drug targets for RA. Drugs designed to target these genes have a higher chance of success in clinical trials and is expected to help prioritise RA drug development and save on drug development costs.
H3K18 lactylation of senescent microglia potentiates brain aging and Alzheimer's disease through the NFκB signaling pathway
Authors: Wei Lin , Yang Xiaowen , Wang Jie , Wang Zhixiao , Wang Qiguang , Ding Yan , Yu Aiqing
Published: September 2023

Cellular senescence serves as a fundamental and underlying activity that drives the aging process, and it is intricately associated with numerous age-related diseases, including Alzheimer's disease (AD), a neurodegenerative aging-related disorder characterized by progressive cognitive impairment. Although increasing evidence suggests that senescent microglia play a role in the pathogenesis of AD, their exact role remains unclear. In this study, we quantified the levels of lactic acid in senescent microglia, and hippocampus tissues of naturally aged mice and AD mice models (FAD4T and APP/PS1). We found lactic acid levels were significantly elevated in these cells and tissues compared to their corresponding counterparts, which increased the level of pan histone lysine lactylation (Kla). We aslo identified all histone Kla sites in senescent microglia, and found that both the H3K18 lactylation (H3K18la) and Pan-Kla were significantly up-regulated in senescent microglia and hippocampus tissues of naturally aged mice and AD modeling mice. We demonstrated that enhanced H3K18la directly stimulates the NFκB signaling pathway by increasing binding to the promoter of Rela (p65) and NFκB1(p50), thereby upregulating senescence-associated secretory phenotype (SASP) components IL-6 and IL-8. Our study provides novel insights into the physiological function of Kla and the epigenetic regulatory mechanism that regulates brain aging and AD. Specifically, we have identified the H3K18la/NFκB axis as a critical player in this process by modulating IL-6 and IL-8. Targeting this axis may be a potential therapeutic strategy for delaying aging and AD by blunting SASP.
Transcriptomics and translatomics identify a robust inflammatory gene signature in brain endothelial cells after ischemic stroke
Authors: Arbaizar-Rovirosa Maria , Gallizioli Mattia , Lozano Juan J. , Sidorova Julia , Pedragosa Jordi , Figuerola Sara , Chaparro-Cabanillas Nerea , Boya Patricia , Graupera Mariona , Claret Marc , Urra Xabier , Planas Anna M.
Published: September 2023

Vascular endothelial function is challenged during cerebral ischemia and reperfusion. The endothelial responses are involved in inflammatory leukocyte attraction, adhesion and infiltration, blood–brain barrier leakage, and angiogenesis. This study investigated gene expression changes in brain endothelial cells after acute ischemic stroke using transcriptomics and translatomics. We isolated brain endothelial mRNA by: (i) translating ribosome affinity purification, enabling immunoprecipitation of brain endothelial ribosome-attached mRNA for translatome sequencing and (ii) isolating CD31+ endothelial cells by fluorescence-activating cell sorting for classical transcriptomic analysis. Both techniques revealed similar pathways regulated by ischemia but they showed specific differences in some transcripts derived from non-endothelial cells. We defined a gene set characterizing the endothelial response to acute stroke (24h) by selecting the differentially expressed genes common to both techniques, thus corresponding with the translatome and minimizing non-endothelial mRNA contamination. Enriched pathways were related to inflammation and immunoregulation, angiogenesis, extracellular matrix, oxidative stress, and lipid trafficking and storage. We validated, by flow cytometry and immunofluorescence, the protein expression of several genes encoding cell surface proteins. The inflammatory response was associated with the endothelial upregulation of genes related to lipid storage functions and we identified lipid droplet biogenesis in the endothelial cells after ischemia. The study reports a robust translatomic signature of brain endothelial cells after acute stroke and identifies enrichment in novel pathways involved in membrane signaling and lipid storage. Altogether these results highlight the endothelial contribution to the inflammatory response, and identify novel molecules that could be targets to improve vascular function after ischemic stroke.
Making implementation science more efficient: capitalizing on opportunities beyond the field
Authors: Wensing Michel , Wilson Paul
Published: September 2023

Implementation researchers often find themselves as research partners in practice improvement projects, clinical trials or other applied health studies. The implementation science component in these projects can be described as supportive, descriptive or explanatory. This commentary reflects on the potential contributions of such projects to implementation science. They may provide evidence on implementation strategies, so it is essential to identify and evaluate these separately from the clinical and preventive interventions of interest. The use of theory on implementation processes and associated factors can contribute to knowledge accumulation, particularly if the focus is on what actually gets implemented when, why and how. The development and validation of relevant measures is a third potential contribution to implementation science. Although not all issues in implementation science can be addressed in this way, capitalization on the opportunities beyond the field can contribute to implementation science.
Impaction bone grafting for contained acetabular defects in total hip arthroplasty
Authors: Abu-Zeid Mohamed Yousry , Habib Mohamed El-Sawy , Marei Sameh Mohamed , Elbarbary Ahmed Nasr-Eldin , Ebied Ahmed Ali , Mesregah Mohamed Kamal
Published: September 2023

Background

Acetabular bone loss is a technical challenge in total hip arthroplasty (THA). This study sought to report the functional and radiological results of acetabular reconstruction using impaction bone grafting (IBG) in patients with acetabular bone deficiency undergoing primary or revision THA.

Methods

In this prospective study, full history taking, preoperative clinical and radiological evaluation, and preoperative planning and templating were performed. The Paprosky classification and the American Academy of Orthopaedic Surgeons classification were used to assess the acetabular deficiencies. Clinical outcomes were assessed utilizing the Harris hip score (HHS) and a 4-question satisfaction questionnaire. Graft incorporation was evaluated in the last follow-up X-rays.

Results

This study included 50 patients with a mean age of 46.7 ± 15.3 years. The THA was primary in 14 (28%) patients and revision in 36 (72%) patients. The mean HHS improved significantly from 28.8 ± 24.1 preoperatively to 76.6 ± 6.1, with a mean follow-up period of 23 months. Overall, 88% of patients were very satisfied. Complete radiological graft incorporation to host bone was achieved in 35 (70%) patients, and the remaining patients had partial incorporation. Complete graft incorporation was associated more frequently with primary THA, autografts, cementless cups, decreased defect size, and decreased graft layer thickness.

Conclusions

IBG for acetabular reconstruction in THA can achieve excellent clinical and radiological outcomes with a low complication rate.

Level of evidence

Level IV.
Arabic version of the Extended Nordic Musculoskeletal Questionnaire, cross-cultural adaptation and psychometric testing
Authors: Al Amer Hamad S. , Alharbi Ahmad A.
Published: September 2023

Background

The Extended Nordic Musculoskeletal Questionnaire (NMQ-E) had never been adapted into Arabic. We culturally adapted the NMQ-E to Arabic in five stages and investigated its psychometric properties.

Methods

After translating and cross-culturally adapting the NMQ-E into Arabic, through forward translation, translation synthesis, backward translation, expert committee review, and pilot testing, the psychometric properties were investigated. The construct validity was assessed by having the participants completing the Arabic version of the NMQ-E with four Arabic scales that measured musculoskeletal pain in all regions covered in the NMQ-E. Participants’ baseline records were also used to evaluate internal consistency (Cronbach’s α). Seven days later, participants completed the Arabic NMQ-E again to evaluate its test–retest reliability employing intraclass correlation coefficient (ICC) and standard error of measurement (SEM) for the age questions, and Cohen’s kappa coefficient (κ), the proportion of observed agreement (Po), the proportion of positive agreement (Ppos), and the proportion of negative agreement (Pneg) for the dichotomous items.

Results

A total of 127 participants, 70 males and 57 females with mean age 32.5 ± 12.2 years, were included. Significant differences were found between participants with and without musculoskeletal pain in the corresponding scales, signifying the content validity of the questionnaire. Cronbach’s α for both the prevalence and consequences pain sections combined ranged from 0.30 to 1.00. The test–retest reliability of the age questions was excellent, with ICC values ranging between 0.995 and 1.00. The SEM was 0.77 for the neck region and 0 for the rest of the regions. The prevalence questions demonstrated almost perfect agreement, with κ values ranging between 0.82 and 1.00, the Po between 0.94 and 1.00, the Ppos between 0.80 and 1.00, and the Pneg between 0.93 and 1.00. The consequences of pain questions showed moderate-to-perfect agreement, with κ values ranging between 0.57 and 1.00, between 0.83 and 1.00 for the Po, between 0.50 and 1.00 for the Ppos, and between 0.86 and 1.00 for the Pneg.

Conclusions

The results suggest that the Arabic NMQ-E is a valid and reliable tool that can be used to screen Arab adults for the prevalence and consequences of musculoskeletal pain.
Molecular and phenotypic spectrum of cardio-facio-cutaneous syndrome in Chinese patients
Authors: Feng Biyun , Li Xin , Zhang Qianwen , Wang Yirou , Gu Shili , Yao Ru-en , Li Zhiying , Gao Shiyang , Chang Guoying , Li Qun , Li Niu , Fu Lijun , Wang Jian , Wang Xiumin
Published: September 2023

Background

Cardio-facio-cutaneous (CFC) syndrome is a RASopathy subtype that presents with unique craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. This study describes the phenotypic spectrum of CFC in China and its association with CFC syndrome gene variants.

Results

Twenty Chinese CFC patients, aged 0.6–9.5 years old, were included in this study and their clinical phenotypic spectrum was compared with that of 186 patients with CFC from non-Chinese ethnicities. All 20 Chinese patients with CFC carried de novo heterozygous BRAF, MAP2K1, and MAP2K2 variants. Two novel variants were detected and consistently predicted to be deleterious using bioinformatic tools. The clinical features of CFC in the Chinese patients included hypertrophic cardiomyopathy (2/20, 10%), pulmonary valve stenosis (2/20, 10%), curly or sparse hair (7/20, 35%), epilepsy (1/20, 5%), and hypotonia (10/20, 50%); these features were less frequently observed in Chinese patients than non-Chinese patients (p < 0.05). In contrast, feeding difficulties (19/20, 95%) were more frequently observed in the Chinese patients. Absent eyebrows and severe short stature were more common in patients with BRAF variants than in those with MAP2K1/2 variants. Facial recognition software was used to recognize most CFC patients using artificial intelligence.

Conclusion

This study identified novel and common variants in our cohort of 20 Chinese patients with CFC. We uncovered differences in clinical features between Chinese and non-Chinese patients and detected genotype–phenotype correlations among the BRAF and MAP2K1/2 variant subgroups. This is the largest cohort of Chinese CFC patients to our knowledge, providing new insights into a subtype of RASopathy.
Metabolomic profiling of Wilson disease, an inherited disorder of copper metabolism, and diseases with similar symptoms but normal copper metabolism
Authors: Qiu Yijie , Su Mingchuan , Xiao Xina , Zhou Dingzi , Xie Linshen
Published: September 2023

Background

Wilson’s disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson’s disease patients (who exhibit similar symptoms but have normal copper levels).

Results

Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson’s disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson’s disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson’s disease).

Conclusions

Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.
COLLAGENE enables privacy-aware federated and collaborative genomic data analysis
Authors: Li Wentao , Kim Miran , Zhang Kai , Chen Han , Jiang Xiaoqian , Harmanci Arif
Published: September 2023

Growing regulatory requirements set barriers around genetic data sharing and collaborations. Moreover, existing privacy-aware paradigms are challenging to deploy in collaborative settings. We present COLLAGENE, a tool base for building secure collaborative genomic data analysis methods. COLLAGENE protects data using shared-key homomorphic encryption and combines encryption with multiparty strategies for efficient privacy-aware collaborative method development. COLLAGENE provides ready-to-run tools for encryption/decryption, matrix processing, and network transfers, which can be immediately integrated into existing pipelines. We demonstrate the usage of COLLAGENE by building a practical federated GWAS protocol for binary phenotypes and a secure meta-analysis protocol. COLLAGENE is available athttps://zenodo.org/record/8125935.
Coupling of co-transcriptional splicing and 3’ end Pol II pausing during termination in Arabidopsis
Authors: Zhou Sixian , Zhao Fengli , Zhu Danling , Zhang Qiqi , Dai Ziwei , Wu Zhe
Published: September 2023

Background

In Arabidopsis, RNA Polymerase II (Pol II) often pauses within a few hundred base pairs downstream of the polyadenylation site, reflecting efficient transcriptional termination, but how such pausing is regulated remains largely elusive.

Result

Here, we analyze Pol II dynamics at 3’ ends by combining comprehensive experiments with mathematical modelling. We generate high-resolution serine 2 phosphorylated (Ser2P) Pol II positioning data specifically enriched at 3’ ends and define a 3’ end pause index (3’PI). The position but not the extent of the 3’ end pause correlates with the termination window size. The 3’PI is not decreased but even mildly increased in the termination deficient mutant xrn3, indicating 3’ end pause is a regulatory step early during the termination and before XRN3-mediated RNA decay that releases Pol II. Unexpectedly, 3’PI is closely associated with gene exon numbers and co-transcriptional splicing efficiency. Multiple exons genes often display stronger 3’ end pauses and more efficient on-chromatin splicing than genes with fewer exons. Chemical inhibition of splicing strongly reduces the 3’PI and disrupts its correlation with exon numbers but does not globally impact 3’ end readthrough levels. These results are further confirmed by fitting Pol II positioning data with a mathematical model, which enables the estimation of parameters that define Pol II dynamics.

Conclusion

Our work highlights that the number of exons via co-transcriptional splicing is a major determinant of Pol II pausing levels at the 3’ end of genes in plants.
Evaluation of the socioprofessional consequences of thoracic outlet syndrome
Authors: Logiou Charlotte , Demondion Xavier , Tiffreau Vincent , Wieczorek Valérie , Thevenon André
Published: September 2023

Purpose

Thoracic outlet syndrome (TOS) is a ductal syndrome that can have a significant functional impact. Various studies have highlighted positional factors and repetitive movements as risk factors for the development of TOS. However, there are few literature data on the socioprofessional consequences of TOS.

Methods

We performed a prospective, cross-sectional, descriptive, multicentre study of workers having received a Doppler ultrasound diagnosis of TOS between December 17th, 2018, and March 16th, 2021. Immediately after their diagnosis, patients completed a self-questionnaire on the impact of TOS on their work activities. We assessed the frequency of TOS-related difficulties at work and the associated socioprofessional consequences. Trial Registration Number (TRN) is NCT03780647 and date of registration December 18, 2018.

Results

Eighty-two participants (95.3%) reported difficulties at work. Seventy-seven of the participants with difficulties (94%) worked in the tertiary sector; these difficulties were due to prolonged maintenance of a posture, carrying loads, and repetitive movements. Although the majority of participants experienced organizational problems and lacked support at work, few of them had approached support organizations, expert and/or healthcare professionals.

Conclusions

TOS was almost always associated with difficulties at work (95.3%). However, poor awareness of sources of help or a perceived lack of need may discourage people with TOS from taking steps to resolve these difficulties. It is clear that the socioprofessional management of TOS requires significant improvements.
In vitro activity of exebacase against methicillin-resistant Staphylococcus aureus biofilms on orthopedic Kirschner wires
Authors: Karau Melissa J. , Mandrekar Jay , Lehoux Dario , Schuch Raymond , Cassino Cara , Patel Robin
Published: September 2023

Orthopedic foreign body-associated infection can be difficult to treat due to the formation of biofilms protecting microorganisms from both antimicrobials and the immune system. Exebacase is an antistaphylococcal lysin (cell wall hydrolase) under consideration for local treatment for biofilm-based infections caused by methicillin-resistant Staphylococcus aureus (MRSA). To determine the activity of exebacase, we formed MRSA biofilms on orthopedic Kirschner wires and exposed them to varying concentrations (0.098, 0.98, 9.8 mg/ml) of exebacase and/or daptomycin over 24 h. The biofilm consisted of 5.49 log10 colony forming units (cfu)/K-wire prior to treatment and remained steady throughout the experiment. Exebacase showed significant biofilm reduction at all timepoints (up to 5.78 log10 cfu/K-wire; P < 0.0495) compared to the controls at all concentrations and all time points with bactericidal activity (> 3 log10 cfu/K-wire reduction) observed for up to 12 h for the 0.098 and 0.98 mg/ml concentrations and at 24 h for 9.8 mg/ml. Daptomycin showed significant biofilm reduction, although non-bactericidal, at all time points for 0.98 and 9.8 mg/ml and at 4 and 8 h with 0.098 mg/ml (P < 0.0495). This study supports further evaluation of local administration of exebacase as a potential treatment for orthopedic implant infections.
Effect of fenofibrate and selective PPARα modulator (SPPARMα), pemafibrate on KATP channel activity and insulin secretion
Authors: Kitamura Shigeki , Murao Naoya , Yokota Shoko , Shimizu Masaru , Ono Tomoyuki , Seino Yusuke , Suzuki Atsushi , Maejima Yuko , Shimomura Kenju
Published: September 2023

Objective

Insulin secretion is regulated by ATP-sensitive potassium (KATP) channels in pancreatic beta-cells. Peroxisome proliferator-activated receptors (PPAR) α ligands are clinically used to treat dyslipidemia. A PPARα ligand, fenofibrate, and PPARγ ligands troglitazone and 15-deoxy-∆12,14-prostaglandin J2 are known to close KATP channels and induce insulin secretion. The recently developed PPARα ligand, pemafibrate, became a new entry for treating dyslipidemia. Because pemafibrate is reported to improve glucose intolerance in mice treated with a high fat diet and a novel selective PPARα modulator, it may affect KATP channels or insulin secretion.

Results

The effect of fenofibrate (100 µM) and pemafibrate (100 µM) on insulin secretion from MIN6 cells was measured by using batch incubation for 10 and 60 min in low (2 mM) and high (10 mM) glucose conditions. The application of fenofibrate for 10 min significantly increased insulin secretion in low glucose conditions. Pemafibrate failed to increase insulin secretion in all of the conditions experimented in this study. The KATP channel activity was measured by using whole-cell patch clamp technique. Although fenofibrate (100 µM) reduced the KATP channel current, the same concentration of pemafibrate had no effect. Both fenofibrate and pemafibrate had no effect on insulin mRNA expression.
Revision of the Middle Triassic coelacanth Ticinepomis Rieppel 1980 (Actinistia, Latimeriidae) with paleobiological and paleoecological considerations
Authors: Ferrante Christophe , Furrer Heinz , Martini Rossana , Cavin Lionel
Published: September 2023

Coelacanths form today an impoverished clade of sarcopterygian fishes, which were somewhat more diverse during their evolutionary history, especially in the Triassic. Since the first description of the coelacanth Ticinepomis peyeri from the Besano Formation of the UNESCO World Heritage Site of Monte San Giorgio (Canton Ticino, Switzerland), the diversity of coelacanths in the Middle Triassic of this area of the western Paleo-Tethys has been enriched with discoveries of other fossil materials. At Monte San Giorgio, two specimens of Heptanema paradoxum and several specimens of the unusual coelacanth Rieppeliaheinzfurreri, have been reported from the Meride Limestone and the Besano Formation, respectively. Another unusual coelacanth, Foreyia maxkuhni, and two specimens referred to Ticinepomis cf. T. peyeri have been described from the isochronous and paleogeographical close Prosanto Formation at the Ducanfurgga and Strel sites (near Davos, Canton Graubünden). In the framework of the revision of the coelacanth material from the Besano Formation kept in the collection of the Paläontologisches Institut und Museum der Universität Zürich (Switzerland), we reviewed the genus Ticinepomis on the basis of the holotype and four new referred specimens. Several morphological traits that were little and/or not understood in T. peyeri are here clarified. We re-evaluate the taxonomic attribution of the material of Ticinepomis cf. T. peyeri from the Prosanto Formation. Morphological characters are different enough from the type species, T. peyeri, to erect a new species, Ticinepomis ducanensis sp. nov., which is shown to be also present in the Besano Formation of Monte San Giorgio, where it is represented by fragmentary bone elements. The recognition of a new coelacanth species indicates that the diversity of this slow-evolving lineage was particularly high in this part of the Western Tethys during the Middle Triassic, especially between 242 and 240 million years ago.
Microbial community coalescence and nitrogen cycling in simulated mortality decomposition hotspots
Authors: Keenan Sarah W. , Emmons Alexandra L. , DeBruyn Jennifer M.
Published: September 2023

Background

The pulsed introduction of dead plant and animal material into soils represents one of the primary mechanisms for returning organic carbon (C) and nitrogen (N) compounds to biogeochemical cycles. Decomposition of animal carcasses provides a high C and N resource that stimulates indigenous environmental microbial communities and introduces non-indigenous, carcass-derived microbes to the environment. However, the dynamics of the coalesced microbial communities, and the relative contributions of environment- and carcass-derived microbes to C and N cycling are unknown. To test whether environment-derived, carcass-derived, or the combined microbial communities exhibited a greater influence on C and N cycling, we conducted controlled laboratory experiments that combined carcass decomposition fluids and soils to simulate carcass decomposition hotspots. We selectively sterilized the decomposition fluid and/or soil to remove microbial communities and create different combinations of environment- and carcass-derived communities and incubated the treatments under three temperatures (10, 20, and 30 °C).

Results

Carcass-derived bacteria persisted in soils in our simulated decomposition scenarios, albeit at low abundances. Mixed communities had higher respiration rates at 10 and 30 °C compared to soil or carcass communities alone. Interestingly, at higher temperatures, mixed communities had reduced diversity, but higher respiration, suggesting functional redundancy. Mixed communities treatments also provided evidence that carcass-associated microbes may be contributing to ammonification and denitrification, but that nitrification is still primarily carried out by native soil organisms.

Conclusions

Our work yields insight into the dynamics of microbial communities that are coalescing during carcass decomposition, and how they contribute to recycling carcasses in terrestrial ecosystems.
Experimental Study of the Flexural Behaviour of RC Beams Made of Eco-friendly Sawdust Concrete and Strengthened by a Wooden Plate
Authors: Maglad Ahmed M. , Mansour Walid , Fayed Sabry , Tayeh Bassam A. , Yosri Ahmed M. , Hamad M.
Published: September 2023

In this paper, the effectiveness of the strengthening by a wooden plate for reinforced concrete (RC) beams that incorporate waste sawdust (SD) as a partial substitute for fine aggregate (sand) has been investigated. To this end, two types of concrete mixtures were made: normal concrete (NC) and sawdust concrete (SDC), which was made by substituting 15% of the volume of sand with SD. Five RC beams (100 mm in depth, 200 mm in width, and 1500 mm in length) were experimentally tested for flexural behavior under four-point loading. Three strengthening schemes were used in this study. The first scheme used a wooden plate that was only fixed by an adhesive layer. The second and third schemes were applied by a wooden plate, which was fixed by an adhesive layer and steel angles (two and eleven angles). The findings of the study indicate that although the concrete's workability, compressive, and splitting tensile strengths were reduced with the addition of SD, the ultimate load of the beam with SD was lower than that of the control beam, with a slight variation of approximately 4%. Moreover, strengthening the RC beam with a wooden plate and two steel angles yielded the highest load capacity among all tested beams, 20% higher than the control specimen. The study's findings offered useful information for developing eco-friendly sawdust concrete beams with efficient strengthening techniques for potential future uses.
Sulfur-cycling chemolithoautotrophic microbial community dominates a cold, anoxic, hypersaline Arctic spring
Authors: Magnuson Elisse , Altshuler Ianina , Freyria Nastasia J. , Leveille Richard J. , Whyte Lyle G.
Published: September 2023

Background

Gypsum Hill Spring, located in Nunavut in the Canadian High Arctic, is a rare example of a cold saline spring arising through thick permafrost. It perennially discharges cold (~ 7 °C), hypersaline (7–8% salinity), anoxic (~ 0.04 ppm O2), and highly reducing (~ − 430 mV) brines rich in sulfate (2.2 g.L−1) and sulfide (9.5 ppm), making Gypsum Hill an analog to putative sulfate-rich briny habitats on extraterrestrial bodies such as Mars.

Results

Genome-resolved metagenomics and metatranscriptomics were utilized to describe an active microbial community containing novel metagenome-assembled genomes and dominated by sulfur-cycling Desulfobacterota and Gammaproteobacteria. Sulfate reduction was dominated by hydrogen-oxidizing chemolithoautotrophic Desulfovibrionaceae sp. and was identified in phyla not typically associated with sulfate reduction in novel lineages of Spirochaetota and Bacteroidota. Highly abundant and active sulfur-reducing Desulfuromusa sp. highly transcribed non-coding RNAs associated with transcriptional regulation, showing potential evidence of putative metabolic flexibility in response to substrate availability. Despite low oxygen availability, sulfide oxidation was primarily attributed to aerobic chemolithoautotrophic Halothiobacillaceae. Low abundance and transcription of photoautotrophs indicated sulfur-based chemolithoautotrophy drives primary productivity even during periods of constant illumination.

Conclusions

We identified a rare surficial chemolithoautotrophic, sulfur-cycling microbial community active in a unique anoxic, cold, hypersaline Arctic spring. We detected Mars-relevant metabolisms including hydrogenotrophic sulfate reduction, sulfur reduction, and sulfide oxidation, which indicate the potential for microbial life in analogous S-rich brines on past and present Mars.
Translation and validation of a Chinese version of the body talk scale for women and men
Authors: He Jinbo , Lu Yining , Barnhart Wesley R. , Tang Chanyuan , Zhang Hengyue , Zhao Yiqing , Lin Linda
Published: September 2023

Body talk has received increasing research attention in recent years, with accumulating evidence supporting the link between body talk and eating and body image disturbances. However, research on body talk in China is still relatively scarce and generally focused on fat talk, especially in women, and much remains unknown about muscle talk and positive body talk for both Chinese women and men. To promote a better understanding of body talk in the Chinese context, the present study adapted the Body Talk Scale (BTS) into Chinese Mandarin (i.e., C-BTS) and evaluated the factor structure and psychometric properties of the C-BTS in Chinese adult women and men. The English version of the BTS was translated into Chinese Mandarin with standard procedures. With 300 Chinese women (Mage = 29.48 years, SD = 7.26) and 300 men (Mage = 29.36 years, SD = 6.81), we examined the factor structure and gender invariance of the C-BTS, as well as internal consistency reliability, test–retest reliability, and construct validity, including convergent, concurrent, and incremental validity of the C-BTS. The results indicated that, consistent with the development study of the BTS, the C-BTS had three subscales (i.e., Negative Fat Talk, Negative Muscle Talk, and Positive Body Talk) and good reliability and validity. The findings demonstrate that the C-BTS can be a useful measure of body talk in both Chinese women and men.
A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess
Authors: Koizumi Michihiro , Matsuda Akihisa , Yamada Takeshi , Morimoto Koji , Kubota Itaru , Kubota Yawara , Tamura Shuzo , Tominaga Kenta , Sakatani Takashi , Yoshida Hiroshi
Published: September 2023

Background

A long-standing (over 10 years) anal fistula is considered a fundamental cause of fistula-associated mucinous adenocarcinoma (FAMC). Perianal abscesses and anal fistulas are two sequential phases of the same anorectal infectious process. We experienced a case of FAMC which developed 3 years after the treatment of a perianal abscess.

Case presentation

A 68-year-old woman was admitted to our hospital because of progressive anal pain and a palpable tumor. She had a history of undergoing a drainage operation for a perianal abscess 3 years previously. A 15 × 15-mm tumor at the former drainage site was identified; transanal ultrasonography showed an intersphincteric fistula connecting to the tumor. A biopsy taken from the tumor demonstrated mucinous adenocarcinoma; the tumor was diagnosed as FAMC. Laparoscopic abdominoperineal resection was performed. Histopathology showed highly dysplastic cells lining the lumen of the anal fistula and poorly differentiated mucinous adenocarcinoma proliferating in the dermis and epidermis in the distal aspect of the fistula.

Conclusions

FAMC can develop within fewer than 3 years after the development of a perianal abscess and anal fistula.
Limited Effects of Inorganic Nitrate Supplementation on Exercise Training Responses: A Systematic Review and Meta-analysis
Authors: Hogwood Austin C. , Anderson Kara C. , Ortiz de Zevallos Joaquin , Paterson Craig , Weltman Arthur , Allen Jason D.
Published: September 2023

Background

Inorganic nitrate (NO3−) supplementation is purported to benefit short-term exercise performance, but it is unclear whether NO3− improves longer-term exercise training responses (such as improvements in VO2peak or time to exhaustion (TTE)) versus exercise training alone. The purpose of this systematic review and meta-analysis was to determine the effects of NO3− supplementation combined with exercise training on VO2peak and TTE, and to identify potential factors that may impact outcomes.

Methods

Electronic databases (PubMed, Medscape, and Web of Science) were searched for articles published through June 2022 with article inclusion determined a priori as: (1) randomized placebo-controlled trials, (2) exercise training lasted at least three weeks, (3) treatment groups received identical exercise training, (4) treatment groups had matched VO2peak at baseline. Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using restricted maximum likelihood estimation between pre- and post-training differences in outcomes. Moderator subgroup and meta-regression analyses were completed to determine whether the overall effect was influenced by age, sex, NO3− dosage, baseline VO2peak, health status, NO3− administration route, and training conditions.

Results

Nine studies consisting of eleven trials were included: n = 228 (72 females); age = 37.7 ± 21 years; VO2peak: 40 ± 18 ml/kg/min. NO3− supplementation did not enhance exercise training with respect to VO2peak (SMD: 0.18; 95% CI: -0.09, 0.44; p = 0.19) or TTE (SMD: 0.08; 95% CI: − 0.21, 0.37; p = 0.58). No significant moderators were revealed on either outcome. Subset analysis on healthy participants who consumed beetroot juice (BRJ) revealed stronger trends for NO3− improving VO2peak (p = 0.08) compared with TTE (p = 0.19), with no significant moderators. Sunset funnel plot revealed low statistical power in all trials.

Conclusions

NO3− supplementation combined with exercise training may not enhance exercise outcomes such as VO2peak or TTE. A trend for greater improvement in VO2peak in healthy participants supplemented with BRJ may exist (p = 0.08). Overall, future studies in this area need increased sample sizes, more unified methodologies, longer training interventions, and examination of sex as a biological variable to strengthen conclusions.
Impact of egg mass layers and scale thicknesses of the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), on the parasitic performance of Trichogrammatoidea bactrae (Hymenoptera: Trichogrammatidae)
Authors: Mohamed Hend O. , El-Heneidy A. H. , Dahi Hassan F.
Published: September 2023

Background

Fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is one of the new alien destructive pests of maize and other 350 economic crops. The majority of farmers are still depended upon chemical insecticides to suppress the pest, but S. frugiperda has succeeded to develop resistance against most of the chemical families. Improving an effective environmentally-friendly approach is highly recommended. Therefore, the egg parasitoids are the best weapon for managing the FAW in the early egg stage due to the feeding behavior of their larvae. In this regard, the impact of FAW egg mass layers and scale thicknesses, as physical barriers, on the parasitic performance of the egg-parasitoid species, Trichogrammatoidea bactrae Nagaraja (Hymenoptera: Trichogrammatidae), in non-choice and choice tests was assessed. Besides, the efficacy of FAW-produced adult wasps on the next generation based on the rates of parasitism, adults' emergence, and female progeny was determined.

Results

Obtained results exhibited that T. bactrae was able to parasitize all exposed FAW egg masses but with different rates related to the layers’ number and scales' thicknesses in both tests. One-layer (83.18, 78.24%) and two-layer egg masses (65.99, 76.42%) had significantly the highest parasitism rate, while three layers (42.15, 46.05%) was the least one, in both tests, respectively. All parasitoids emerged after 10–12 days with high rates (~ 88–98%) from all the tested egg masses, and the majority offspring were female-biased in both tests. Furthermore, parasitic performance in F1 progeny was similar with that recorded in parental generation in terms of parasitism rate, high parasitoid emergency (~ 87–95%), and strongly female-biased (~ 68–76%) in all the exposed egg masses.

Conclusions

The egg parasitoid, T. bactrae, could be an efficient and recommended bio-control agent against FAW as its greatest ability to overcome the layers’ number and scales’ thickness.