bluuebunny/crossref_metadata_2025 huggingface dataset:
ACSM5 inhibits ligamentum flavum hypertrophy by regulating lipid accumulation mediated by FABP4/PPAR signaling pathway
Authors: Cao Yanlin , Li Jianjun , Qiu Sujun , Ni Songjia , Duan Yang
Published: November 2023

Background

Ligamentum flavum (LF) hypertrophy is the main cause of lumbar spinal canal stenosis (LSCS). Previous studies have shown that LF hypertrophy tissue exhibits abnormal lipid accumulation, but the regulatory mechanism remains unclear. The objective of this study was to explore the function and potential mechanism of ACSM5 in LF lipid accumulation.

Methods

To assess the ACSM5 expression levels, lipid accumulation and triglyceride (TG) level in LF hypertrophy and normal tissue, we utilized RT-qPCR, western blot, oil red O staining, and TG assay kit. The pearson correlation coefficient assay was used to analyze the correlation between ACSM5 levels and lipid accumulation or TG levels in LF hypertrophy tissue. The role of ACSM5 in free fatty acids (FFA)-induced lipid accumulation in LF cells was assessed in vitro, and the role of ACSM5 in LF hypertrophy in mice was verified in vivo. To investigate the underlying mechanisms of ACSM5 regulating lipid accumulation in LF, we conducted the mRNA sequencing, bioinformatics analysis, and rescue experiments.

Results

In this study, we found that ACSM5, which was significantly down-regulated in LF tissues, correlated with lipid accumulation. In vitro cell experiments demonstrated that overexpression of ACSM5 significantly inhibited FFA-induced lipid accumulation and fibrosis in LF cells. In vivo animal experiments further confirmed that overexpression of ACSM5 inhibited LF thickening, lipid accumulation, and fibrosis. Mechanistically, ACSM5 inhibited lipid accumulation of LF cells by inhibiting FABP4-mediated PPARγ signaling pathway, thereby improving hypertrophy and fibrosis of LF.

Conclusions

our findings elucidated the important role of ACSM5 in the regulation of LF lipid accumulation and provide insight into potential therapeutic interventions for the treatment of LF hypertrophy. This study further suggested that therapeutic strategies targeting lipid deposition may be an effective potential approach to treat LF hypertrophy-induced LSCS.
Effect of the telemedicine-supported multicomponent exercise therapy in patients with knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Feng Yuan , Wu Yan , Liu Huizhen , Bao Tianjie , Wang Chongyang , Wang Zezhang , Huang Jielei , Jiang Yiwei , He Chengqi , Zhu Siyi
Published: November 2023

Introduction

The rising prevalence of knee osteoarthritis is placing a considerable strain on the global healthcare system. To address this issue, telemedicine-supported multicomponent exercise therapy has emerged as a promising approach. This therapy combines exercise, patient education, and health coaching to empower knee osteoarthritis patients to manage their condition from the comfort of their homes. Nevertheless, there are some existing limitations in the current research on this approach, including challenges related to patient compliance and the absence of objective evaluation methods.

Methods and analysis

Patients diagnosed with knee osteoarthritis, who have not undergone knee surgery in the past year, will be recruited for a randomized controlled trial. The trial will include an intervention group and a control group. The intervention group will receive an mHealth app-based multicomponent exercise therapy, consisting of exercise therapy, patient education, and health coaching. Meanwhile, the control group will receive usual care, involving drug therapy and patient education. The primary outcome of the trial will be the measurement of pain intensity, assessed using a visual analog scale at baseline and at 4, 8, and 12 weeks of the post-intervention. To analyze the data, a two-factor, four-level repeated measures ANOVA will be used if the assumptions of homogeneity of variance and sphericity are met. If not, a mixed effects model will be employed.

Discussion

The aim of the study is to evaluate the effectiveness of multicomponent exercise therapy aimed at enhancing pain self-management for knee osteoarthritis patients in the comfort of their own homes. The intervention incorporate wearable devices equipped with advanced deep learning systems to monitor patients' adherence to the prescribed at-home exercise regimen, as well as to track changes in outcomes before and after the exercise sessions. The findings from this trial have the potential to enhance both the accessibility and quality of care provided to knee osteoarthritis patients, offering valuable insights for future improvements in their treatment and management.

Trial registration

Chinese Clinical Trials Registry, ChiCTR2300073688. Registered on 19 July 2023, https://www.chictr.org.cn/bin/project/edit?pid=199707. World Health Organization International Clinical Trials Registry Platform, https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300073688.
Multiple cardiometabolic diseases enhance the adverse effects of hypoalbuminemia on mortality among centenarians in China: a cohort study
Authors: Li Haowei , Wang Shengshu , Yang Shanshan , Liu Shaohua , Song Yang , Chen Shimin , Li Xuehang , Li Zhiqiang , Li Rongrong , Zhao Yali , Zhu Qiao , Ning Chaoxue , Liu Miao , He Yao
Published: November 2023

Background

Although hypoalbuminemia was associated with high risk of mortality in community-dwelling older adults, as well as in the hospitalized older adults, little is known among centenarians. And there are limited data on whether having cardiometabolic diseases (CMDs) is associated with additive effects.

Methods

Baseline examinations including a determination of albumin levels were performed in 1002 Chinese centenarians from January 2014 through to December 2016, and the survival status was subsequently ascertained until 31 May 2021. Cox proportional risk model was performed to assess the risk of all-cause mortality associated with albumin levels and hypoalbuminemia combined with CMDs.

Results

Of 1002 participants included in the analysis, the mean level of albumin was 38.5 g/L (± standard deviation, 4.0 g/L), and 174 (17.4%) had hypoalbuminemia (albumin < 35 g/L). The multivariable analyses showed that albumin level was negatively associated with all-cause mortality (Ptrend < 0.05). Compared to normoalbuminemia, hypoalbuminemia was associated with an increased mortality risk in the overall participants (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.22–1.97). Furthermore, the HR (95% CI) of hypoalbuminemia combined with multiple CMDs was 2.15 (1.14–4.07). There was evidence of an additive deleterious dose effect of an increasing number of CMDs (Ptrend = 0.001).

Conclusions

Hypoalbuminemia is associated with an increased risk of all-cause mortality in Chinese centenarians, and this risk is more pronounced among centenarians with multiple cardiometabolic diseases. Our findings suggest that older adults with hypoalbuminemia, especially comorbid multiple CMDs warrant early identification and management.
Do cool shirts make a difference? The effects of upper body garments on health, fluid balance and performance during exercise in the heat
Authors: Engeroff L. , Niederer D. , Groneberg D. , Vogt L. , Engeroff Tobias
Published: November 2023

Objectives

Due to climate change and major sport events in hot climate, temperature regulation during exercise is gaining relevance in professional and amateur sports. This study compares the effects of an upper body garment with water-soaked inlays, of a synthetic- and of a cotton shirt on health, fluid balance and performance during a high intensity exercise session in the heat.

Methods

32 healthy participants (age 25 ± 4 years; 15 women) were assigned to one of three upper body garments (cotton-shirt, synthetic-fiber-shirt, cooling-vest with water-soaked inlays) and underwent a high intensity steady state ergometer exercise test (Temperature 30.5 °C, frontal airflow 20 km/h, relative air-humidity 43 ± 13%). Time to exhaustion, physiologic parameters (inner ear temperature, heart rate, relative oxygen uptake, body weight, garment weight) and subjective data (perceived exertion, thermal sensation, skin wettedness, clothing humidity, feeling scale) were assessed. Time to exhaustion was analyzed using a survival time analysis. Other outcomes were evaluated using Kruskal-Wallis Tests and 95%-confidence-intervals.

Results

Time to exhaustion was not different between groups. Cooling-vests were heavier and led to lower inner ear temperature, lower thermal- and higher clothing-humidity-sensation at the start of exercise. Physiologic and subjective parameters showed no group differences at exercise termination.

Conclusions

In a realistic setting including frontal airflow, synthetic and cotton-fiber shirts reach comparable effects on health and thermoregulation and are perceived as equally comfortable. Although inducing a small pre-exercise cooling effect, a water-soaked garment induces a weight penalty and creates a less comfortable situation.
Oligodendrocyte progenitor cells in Alzheimer’s disease: from physiology to pathology
Authors: Zou Peibin , Wu Chongyun , Liu Timon Cheng-Yi , Duan Rui , Yang Luodan
Published: November 2023

Oligodendrocyte progenitor cells (OPCs) play pivotal roles in myelin formation and phagocytosis, communicating with neighboring cells and contributing to the integrity of the blood–brain barrier (BBB). However, under the pathological circumstances of Alzheimer’s disease (AD), the brain’s microenvironment undergoes detrimental changes that significantly impact OPCs and their functions. Starting with OPC functions, we delve into the transformation of OPCs to myelin-producing oligodendrocytes, the intricate signaling interactions with other cells in the central nervous system (CNS), and the fascinating process of phagocytosis, which influences the function of OPCs and affects CNS homeostasis. Moreover, we discuss the essential role of OPCs in BBB formation and highlight the critical contribution of OPCs in forming CNS-protective barriers. In the context of AD, the deterioration of the local microenvironment in the brain is discussed, mainly focusing on neuroinflammation, oxidative stress, and the accumulation of toxic proteins. The detrimental changes disturb the delicate balance in the brain, impacting the regenerative capacity of OPCs and compromising myelin integrity. Under pathological conditions, OPCs experience significant alterations in migration and proliferation, leading to impaired differentiation and a reduced ability to produce mature oligodendrocytes. Moreover, myelin degeneration and formation become increasingly active in AD, contributing to progressive neurodegeneration. Finally, we summarize the current therapeutic approaches targeting OPCs in AD. Strategies to revitalize OPC senescence, modulate signaling pathways to enhance OPC differentiation, and explore other potential therapeutic avenues are promising in alleviating the impact of AD on OPCs and CNS function. In conclusion, this review highlights the indispensable role of OPCs in CNS function and their involvement in the pathogenesis of AD. The intricate interplay between OPCs and the AD brain microenvironment underscores the complexity of neurodegenerative diseases. Insights from studying OPCs under pathological conditions provide a foundation for innovative therapeutic strategies targeting OPCs and fostering neurodegeneration. Future research will advance our understanding and management of neurodegenerative diseases, ultimately offering hope for effective treatments and improved quality of life for those affected by AD and related disorders.
Single-cell sequencing reveals the reproductive variations between primiparous and multiparous Hu ewes
Authors: Ge Ting , Wen Yifan , Li Bo , Huang Xiaoyu , Jiang Shaohua , Zhang Enping
Published: November 2023

Background

In the modern sheep production systems, the reproductive performance of ewes determines the economic profitability of farming. Revealing the genetic mechanisms underlying differences in the litter size is important for the selection and breeding of highly prolific ewes. Hu sheep, a high-quality Chinese sheep breed, is known for its high fecundity and is often used as a model to study prolificacy traits. In the current study, animals were divided into two groups according to their delivery rates in three consecutive lambing seasons (namely, the high and low reproductive groups with ≥ 3 lambs and one lamb per season, n = 3, respectively). The ewes were slaughtered within 12 h of estrus, and unilateral ovarian tissues were collected and analyzed by 10× Genomics single-cell RNA sequencing.

Results

A total of 5 types of somatic cells were identified and corresponding expression profiles were mapped in the ovaries of each group. Noticeably, the differences in the ovary somatic cell expression profiles between the high and low reproductive groups were mainly clustered in the granulosa cells. Furthermore, four granulosa cell subtypes were identified. GeneSwitches analysis revealed that the abundance of JPH1 expression and the reduction of LOC101112291 expression could lead to different evolutionary directions of the granulosa cells. Additionally, the expression levels of FTH1 and FTL in mural granulosa cells of the highly reproductive group were significantly higher. These genes inhibit necroptosis and ferroptosis of mural granulosa cells, which helps prevent follicular atresia.

Conclusions

This study provides insights into the molecular mechanisms underlying the high fecundity of Hu sheep. The differences in gene expression profiles, particularly in the granulosa cells, suggest that these cells play a critical role in female prolificacy. The findings also highlight the importance of genes such as JPH1, LOC101112291, FTH1, and FTL in regulating granulosa cell function and follicular development.
Poor removal of tedizolid during continuous hemodiafiltration: experiments using an in vitro continuous hemodiafiltration model
Authors: Yoshikawa Satoshi , Yoshikawa Shinichi , Sato Akira , Matsumoto Tsukasa
Published: November 2023

Background

Tedizolid is an oxazolidinone anti-MRSA drug with included in the National Health Insurance Drug Price List in 2018. The effect of hemodialysis on tedizolid phosphate concentrations has been reported; pre-dialysis concentrations decreased by 10% compared to post- dialysis concentrations. However, the material of the dialysis membrane remains unknown. In addition, there have been no reports on the effects of continuous hemodiafiltration. In this study, we investigated the effects of continuous hemodiafiltration on tedizolid using two types of dialysis membranes made of different materials.

Methods

The adsorption of tedizolid, linezolid, and vancomycin to two different dialysis membranes was investigated, and the clearance of each drug was calculated by experiments using an in vitro continuous hemodiafiltration model.

Results

The adsorption of tedizolid, linezolid, and vancomycin on the dialysis membranes was examined, and no adsorption was observed. Experimental results from the continuous hemodiafiltration model showed that linezolid and vancomycin concentrations decreased over time: after two hours, the respective decreases were 26.48 ± 7.14% and 28.51 ± 2.32% for polysulfone membranes, respectively. The decrease was 23.57 ± 4.95% and 28.73 ± 5.13% for the polymethylmethacrylate membranes, respectively. These results suggested that linezolid and vancomycin were eliminated by continuous hemodiafiltration. In contrast, tedizolid phosphate and tedizolid concentrations decreased slightly in the polysulfone and polymethylmethacrylate membranes. The decrease in concentrations were 2.10 ± 0.77% and 2.97 ± 0.60% for the polysulfone membranes, respectively. For the polymethylmethacrylate membranes, the decrease in concentration were 2.01 ± 0.88% and 1.73 ± 0.27%, respectively.

Conclusion

These results suggested that tedizolid should not be considered for dose control during continuous hemodiafiltration.
Tracking-dispatch of a combined wind-storage system based on model predictive control and two-layer fuzzy control strategy
Authors: Yang Jingyu , Yang Tongguang , Luo Longfu , Peng Li
Published: November 2023

To maximize improving the tracking wind power output plan and the service life of energy storage systems (ESS), a control strategy is proposed for ESS to track wind power planning output based on model prediction and two-layer fuzzy control. First, based on model predictive control, a model with deviations of grid-connected power from the planned output and the minimum deviation of the remaining capacity of the ESS from the ideal value is established as the target. Then, when the grid-connected power exceeds the allowable deviation band of tracking, the weight coefficients in the objective function are adjusted by introducing the first layer of fuzzy control rules, combining the state of charge (SOC) of the ESS with the dynamic tracking demand of the planned value of wind power. When the grid-connected power is within the tracking allowable deviation band, the second layer of fuzzy control rules is used to correct the charging and discharging power of the ESS to improve its ability to track the future planned deviation while not crossing the limit. By repeatedly correcting the charging and discharging power of the ESS, its safe operation and the multitasking execution of the wind power plan output tracking target are ensured. Finally, taking actual data from a wind farm as an example, tests on a simulation platform of a combined wind-storage power generation system verify the feasibility and superiority of the proposed control strategy.
Qualitative and psychometric evaluation of the PROMIS®-Fatigue SF-7a scale to assess fatigue in patients with moderately to severely active inflammatory bowel disease
Authors: Feagan Brian G. , Sandborn William J. , Sands Bruce E. , Liu Yan , Vetter Marion , Mathias Susan D. , Huang Kuan-Hsiang Gary , Johanns Jewel , Germinaro Matthew , Han Chenglong
Published: November 2023

Background

This study evaluated the content validity and psychometric properties of the Patient-Reported Outcomes Measurement Information System® (PROMIS)-Fatigue Short Form 7a (SF-7a) v1.0 scale to determine its suitability in clinical trials to assess fatigue in patients with moderately to severely active Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

A qualitative interview assessed patients’ experience living with CD (N = 20) and UC (N = 19). The contents of the SF-7a scale were cognitively debriefed to evaluate content validity. A psychometric evaluation was performed using data from clinical trials of patients with CD (N = 360) and UC (N = 214). Correlations with Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn’s Disease Activity Index (CDAI; CD only), and Mayo score (UC only) determined validity. The Patient Global Impression of Change (PGIC) was used to evaluate reliability and responsiveness to change. Using PGIC as an anchor, a preliminary threshold for clinically meaningful change was identified to define fatigue response in both CD and UC patients.

Results

All patients reported fatigue as a common symptom. Patients confirmed SF-7a items were relevant to assessing fatigue, instructions and response options were clear, and its 7-day recall period was appropriate. Higher SF-7a scores were associated with higher disease activity (CDAI and Mayo score) and lower health-related quality of life (IBDQ), confirming known groups validity. The correlation of the SF-7a scale was higher with fatigue-related items. (rs ≥ -0.70) than with items not directly associated with fatigue. Test-retest reliability was moderate to good (0.54–0.89) among patients with stable disease, and responsiveness to change in disease severity was demonstrated from baseline to Week 12. A ≥7point decrease was identified as a reasonable threshold to define clinically meaningful improvement.

Conclusion

The SF-7a scale is a valid, reliable, and sensitive measure of fatigue in patients with moderately to severely active IBD and can be used to evaluate treatment response.
Employment of patients with rheumatoid arthritis - a systematic review and meta-analysis
Authors: Kirkeskov Lilli , Bray Katerina
Published: November 2023

Background

Patients with rheumatoid arthritis (RA) have difficulties maintaining employment due to the impact of the disease on their work ability. This review aims to investigate the employment rates at different stages of disease and to identify predictors of employment among individuals with RA.

Methods

The study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines focusing on studies reporting employment rate in adults with diagnosed RA. The literature review included cross-sectional and cohort studies published in the English language between January 1966 and January 2023 in the PubMed, Embase and Cochrane Library databases. Data encompassing employment rates, study demographics (age, gender, educational level), disease-related parameters (disease activity, disease duration, treatment), occupational factors, and comorbidities were extracted. Quality assessment was performed employing Newcastle–Ottawa Scale. Meta-analysis was conducted to ascertain predictors for employment with odds ratios and confidence intervals, and test for heterogeneity, using chi-square and I2-statistics were calculated. This review was registered with PROSPERO (CRD42020189057).

Results

Ninety-one studies, comprising of a total of 101,831 participants, were included in the analyses. The mean age of participants was 51 years and 75.9% were women. Disease duration varied between less than one year to more than 18 years on average. Employment rates were 78.8% (weighted mean, range 45.4–100) at disease onset; 47.0% (range 18.5–100) at study entry, and 40.0% (range 4–88.2) at follow-up. Employment rates showed limited variations across continents and over time. Predictors for sustained employment included younger age, male gender, higher education, low disease activity, shorter disease duration, absence of medical treatment, and the absence of comorbidities.

Notably, only some of the studies in this review met the requirements for high quality studies. Both older and newer studies had methodological deficiencies in the study design, analysis, and results reporting.

Conclusions

The findings in this review highlight the prevalence of low employment rates among patients with RA, which increases with prolonged disease duration and higher disease activity. A comprehensive approach combining clinical and social interventions is imperative, particularly in early stages of the disease, to facilitate sustained employment among this patient cohort.
Biocontrol potential of native entomopathogenic nematodes against Gonioctena fornicata (Brüggemann, 1873) (Coleoptera, Chrysomelidae) in alfalfa
Authors: Barış Aydemir
Published: November 2023

Background

Gonioctena fornicata (Brüggemann, 1873) (Coleoptera: Chrysomelidae) inflicts substantial crop damage by consuming alfalfa leaves. The main aim of the study was to develop an efficient, sustainable control method against the pest, considering entomopathogenic nematodes (EPNs) as a potential control agent against soil-dwelling insect pests. This study investigated the impact of two native entomopathogenic nematodes (EPNs), Heterorhabditis bacteriophora (isolate Z-1) and Steinernema feltiae (isolate A-16), on mature larvae and adults of G. fornicata. Concentrations of 250, 500, and 1000 IJs/ml were used for adult and larval stages, and mortality rate was determined at the end of 144 h for larvae and 240 h for adults.

Results

The highest effect was 94.7% at 120 h for isolate Z-1 and 91.0% at 168 h for isolate A-16 at a concentration of 1000 IJs/ml for adult stages. The highest effect on larval stage was 97.6% at 96 h for isolate Z-1 and 85.8% at 120 h for isolate A-16 at the concentration of 1000 IJs/ml. On the adult stage, isolate Z-1 showed 50.0–67.1% effect at concentrations of 250 and 500 IJs/ml, respectively, while isolate A-16 showed an effect ranging from 46.7 to 63.6%. In the larval stage, isolate Z-1 caused 39.7–77.6% mortality at 250 and 500 IJs/ml concentrations, respectively, while the rate was 32.9–63.9% for isolate A-16. In the trial, isolate Z-1 showed a high efficacy in both stages of G. fornicata.

Conclusions

This study represents the first laboratory investigation encompassing both adult and mature larval stages of G. fornicata. The obtained data offer valuable insights for alternative control strategies targeting G. fornicata.
Preliminary species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi in the Dabie Mountains, Central China reveal unexpected richness
Authors: Liu Xiang-Yang , Liu Shi-Liang , Wei Hao-Wen , Wang Xue-Wei , Yu Jia , Shen Shan , Zhou Li-Wei
Published: November 2023

Wood-inhabiting fungi have important economic values as well as playing a major ecological role in forest ecosystem cycles. The Dabie Mountains, at the junction of Henan, Hubei, and Anhui Provinces, Central China, provide an ideal climate and favorable niches for the speciation and diversification of various forms of life including fungi. We studied the species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi that revealed 175 wood-inhabiting basidiomycetous species, of which 20 represented unidentified species, based on morphological and phylogenetic analyses of 575 specimens collected from ten sampling sites. These species belonged to two classes, 11 orders, 42 families, and 106 genera of Basidiomycota, and included 12 edible species, 28 medicinal species, four poisonous species, and seven forest pathogens. Four types of fungal distribution pattern at the genus level were recognized for 65 genera, while another 41 genera could not be placed in any known distribution pattern. The five sampling sites in the eastern part of the Dabie Mountains had significantly higher species diversity and phylogenetic diversity of wood-inhabiting basidiomycetous fungi than those in the western part, and thus deserve priority in terms of conservation. The community of wood-inhabiting basidiomycetous fungi in the Dabie Mountains is generally affected by a combination of habitat filtering and competitive exclusion. This study provides a basis on which to build actions for the comprehensive recognition, utilization, and conservation of wood-inhabiting basidiomycetous fungi in the region.
How to classify antipsychotics: time to ditch dichotomies?
Authors: McCutcheon Robert A. , Cannon Alistair , Parmer Sita , Howes Oliver D.
Published: November 2023

The dichotomies of ‘typical/atypical’ or ‘first/second generation’ have been employed for several decades to classify antipsychotics, but justification for their use is not clear. In the current analysis we argue that this classification is flawed from both clinical and pharmacological perspectives. We then consider what approach should ideally be employed in both clinical and research settings.
Using Machine Learning to Leverage Biomarker Change and Predict Colorectal Cancer Recurrence
Authors: Rodriguez Patricia J. , Heagerty Patrick J. , Clark Samantha , Khor Sara , Chen Yilin , Haupt Eric , Hahn Erin E. , Shankaran Veena , Bansal Aasthaa
Published: November 2023

Using machine learning to leverage CEA biomarker change and predict colorectal cancer recurrence.
Testosterone Replacement Therapy in Klinefelter Syndrome—Follow-up Study Associating Hemostasis and RNA Expression
Authors: Chang Simon , Just Jesper , Skakkebæk Anne , Johannsen Emma B , Fedder Jens , Gravholt Claus H , Münster Anna-Marie B
Published: November 2023

Background

Men with Klinefelter syndrome (KS) develop hypergonadotropic hypogonadism, are in need of testosterone replacement therapy (TRT), and present with a more than 4-fold increased risk of thrombosis. TRT in KS has the potential to modify thrombotic risk, but data are scarce.

Aim

To assess effects of 18 months of TRT on hemostasis in KS and identify genes associated with the prothrombotic phenotype.

Methods

Untreated and TRT-treated men with KS were included at baseline and matched to healthy controls. TRT was initiated in untreated KS and all groups were reassessed after 18 months of follow-up. Thrombin generation was evaluated with or without thrombomodulin, and fibrin clot lysis was evaluated by turbidity measurements. RNA expression was assessed in blood, fat, and muscle tissue of patients with TRT-treated KS and controls.

Results

Thrombin generation with thrombomodulin was slightly increased in untreated KS, but overall KS was not associated with a hypercoagulable state. KS presented with fibrinolytic impairment associated with higher body fat and higher levels of fibrinogen. Eighteen months of TRT in KS was associated with a reduction in body fat and fibrinogen, attenuating the prothrombotic profile. The expression of ENPP4 was higher in men with KS and served as a key player among a group of genes associated with impaired fibrinolysis.

Conclusion

KS is associated with a specific expression profile contributing to fibrinolytic impairment and increased thrombotic risk in the patients. TRT in patients with KS has the potential for alleviating the prothrombotic phenotype, in particular by reducing body fat and fibrinogen.
Epigenome-wide Association Study Shows Differential DNA Methylation of MDC1, KLF9, and CUTA in Autoimmune Thyroid Disease
Authors: Lafontaine Nicole , Shore Christopher J , Campbell Purdey J , Mullin Benjamin H , Brown Suzanne J , Panicker Vijay , Dudbridge Frank , Brix Thomas H , Hegedüs Laszlo , Wilson Scott G , Bell Jordana T , Walsh John P
Published: November 2023

Context

Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto disease (HD), which often run in the same family. AITD etiology is incompletely understood: Genetic factors may account for up to 75% of phenotypic variance, whereas epigenetic effects (including DNA methylation [DNAm]) may contribute to the remaining variance (eg, why some individuals develop GD and others HD).

Objective

This work aimed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) comparing GD to HD.

Methods

Whole-blood DNAm was measured across the genome using the Infinium MethylationEPIC array in 32 Australian patients with GD and 30 with HD (discovery cohort) and 32 Danish patients with GD and 32 with HD (replication cohort). Linear mixed models were used to test for differences in quantile-normalized β values of DNAm between GD and HD and data were later meta-analyzed. Comb-p software was used to identify DMRs.

Results

We identified epigenome-wide significant differences (P < 9E-8) and replicated (P < .05) 2 DMPs between GD and HD (cg06315208 within MDC1 and cg00049440 within KLF9). We identified and replicated a DMR within CUTA (5 CpGs at 6p21.32). We also identified 64 DMPs and 137 DMRs in the meta-analysis.

Conclusion

Our study reveals differences in DNAm between GD and HD, which may help explain why some people develop GD and others HD and provide a link to environmental risk factors. Additional research is needed to advance understanding of the role of DNAm in AITD and investigate its prognostic and therapeutic potential.
Discontinuation of Drug Treatment in Cushing's Disease Not Cured by Pituitary Surgery
Authors: Ghalawinji Adel , Drezet Lucas , Chaffanjon Philippe , Muller Marie , Sturm Nathalie , Simiand Anna , Lazard Arnaud , Gay Emmanuel , Chabre Olivier , Cristante Justine
Published: November 2023

Objective

When transsphenoidal surgery (TSS) does not cure Cushing's disease (CD), 4 treatments are available: drug treatment (DT), second TSS (2nd TSS), bilateral adrenalectomy (BA), and pituitary radiotherapy (PR). DT is attractive but supposes long-term continuation, which we aimed to evaluate.

Design and Methods

Retrospective study, in a center prioritizing 2nd TSS, of 36 patients, including 19 with TSS failure and 17 with recurrence, out of 119 patients with CD treated by a first TSS, average follow-up 6.1 years (95% confidence interval 5.27-6.91). Control was defined as normalization of urinary free cortisol (UFC) and final treatment (FT) as the treatment allowing control at last follow-up. We also analyzed discontinuation rates of DT in published CD prospective clinical trials.

Results

Control was achieved in 33/36 patients (92%). DT was initiated in 29/36 patients (81%), allowing at least 1 normal UFC in 23/29 patients (79%) but was discontinued before last follow-up in 18/29 patients (62%). DT was FT in 11/29 patients (38%), all treated with cortisol synthesis inhibitors. Second TSS was FT in 8/16 (50%), BA in 14/14 (100%), and PR in 0/5. In published trials, discontinuation of DT was 11% to 51% at 1 year and 32% to 74% before 5 years.

Conclusion

DT allowed at least 1 normal UFC in 23/29 patients (79%) but obtained long-term control in only 11/29 (38%), as discontinuation rate was high, although similar to published data. Interestingly, a successful 2nd TSS was the cause for discontinuing efficient and well-tolerated DT in 5 patients. Further studies will show whether different strategies with cortisol synthesis inhibitors may allow for a lower discontinuation rate in patients not candidates for a 2nd TSS so that BA may be avoided in these patients.
Higher Plasma Levels of Endocannabinoids and Analogues Correlate With a Worse Cardiometabolic Profile in Young Adults
Authors: Di Xinyu , Martinez-Tellez Borja , Krekels Elke H J , Jurado-Fasoli Lucas , Osuna-Prieto Francisco J , Ortiz-Alvarez Lourdes , Hankemeier Thomas , Rensen Patrick C N , Ruiz Jonatan R , Kohler Isabelle
Published: November 2023

Context

The endocannabinoid system (ECS) is a signaling system composed of endocannabinoids (eCBs), their receptors, and the enzymes involved in their synthesis and metabolism. Alterations in the ECS are linked to the development of cardiometabolic diseases.

Objective

Here, we investigated the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors.

Methods

The study included 133 young adults (age 22.1 ± 2.2 years, 67% women). Fasting plasma levels of eCBs and their analogues were measured using liquid chromatography-tandem mass spectrometry. Body composition, brown adipose tissue (BAT) volume, glucose uptake, and traditional cardiometabolic risk factors were measured.

Results

Plasma levels of eCBs and several eCB analogues were positively correlated with adiposity and traditional cardiometabolic risk factors (eg, serum insulin and triacylglyceride levels, all r ≥ 0.17 and P ≤ .045). Plasma levels of 2-arachidonoyl glycerol and N-pentadecenoylethanolamine were negatively correlated with BAT volume and glucose uptake (all r ≤ −0.17 and P ≤ .047). We observed that the plasma levels of eCBs and their analogues were higher in metabolically unhealthy overweight–obese participants than in metabolically healthy overweight–obese participants.

Conclusion

Our findings show that the plasma levels of eCBs and their analogues are related to higher levels of adiposity and worse cardiometabolic profile.
Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes
Authors: Dietsche Katrina B , Magge Sheela N , Dixon Sydney A , Davis Faith S , Krenek Andrea , Chowdhury Aruba , Mabundo Lilian , Stagliano Michael , Courville Amber B , Yang Shanna , Turner Sara , Cai Hongyi , Kasturi Kannan , Sherman Arthur S , Ha Joon , Shouppe Eileen , Walter Mary , Walter Peter J , Chen Kong Y , Brychta Robert J , Peer Cody , Zeng Yi , Figg William , Cogen Fran , Estrada D Elizabeth , Chacko Shaji , Chung Stephanie T
Published: November 2023

Objective

Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and β-cell function after therapy in AA Y-T2D.

Methods

In this parallel randomized clinical trial, 22 youth with Y-T2D—age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years—were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. β-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test.

Results

At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (−2.0 ± 1.3 vs −0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs −0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: −0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI.

Conclusion

Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance β-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.
A search tool based on language modelling developed for The Index of Middle English Prose
Authors: HONKAPOHJA Alpo , Thaisen Jacob , Nøklestad Anders
Published: November 2023

Non-standardised early vernaculars present a problem for search tools due to the high degree of variation. The challenge lies in the variation found in orthography, syntax, and lexicon between titles, incipits, and explicits in manuscript copies of the same work. Traditional search methods relying on exact string matching or regular expressions fail to address these variations comprehensively. This project presents a web-based search tool specifically designed to handle linguistic and textual variation. The software is made available as a part of the Index of Middle English Prose (IMEP). The search tool addresses the issue of variation by utilizing a database of incipits and explicits, character-based n-gram language models (LMs) built with the Stanford Research Institute Language Modelling (SRILM) toolkit, and a fuzzy search script (IMEP: FSS) written in Python. The tool optimizes for recall, retrieving multiple potential matches for a search string, without attempting to identify the ‘correct’ one. The search process involves looking up exact matches in the database while simultaneously using the fuzzy search script to evaluate the incipits and explicits against a model of the search string, followed by a match of the search string against models of the incipits and explicits. This two-step process shortens the processing time, which would otherwise be unreasonably long, because while using SRILM to match the search string against each incipit or explicit in the IMEP for precision could be time-consuming, running a first step where all texts are matched against a single LM built from the search string allows for faster processing. A web application, built using Django and Docker, combines the results of the direct database lookup and the fuzzy search script, presenting them as a list with exact matches followed by fuzzy matches ordered by increasing model perplexity. The tool is made available Open Access and can be adapted to other datasets.
ПРОГНОЗИРОВАНИЕ СОЦИАЛЬНО-ПСИХОЛОГИЧЕСКИХ ПРОЦЕССОВ
Authors:   University of Tyumen, Dolganov Dmitry
Published: November 2023

В данной работе, рассматривается вопрос о прогнозировании как методе анализа данных в эмпирических исследования в психологии. В работе представлены примеры использования алгоритмов статистического анализа позволяющего выделять скрытые, сложные связи переменных. Также приводятся примеры использования техник предиктивной аналитики позволяющих строить непосредственные прогнозы изменения зависимых переменных.
A possible new direction for employment strategies in rural areas: theoretical foundation for the assessment of employability
Authors: Tésits Róbert , Alpek Levente , Hovanyi Gabor , Lendvai Tamas
Published: November 2023

The aim of this study is to develop a theoretical framework for measuring an important segment of labour economics, namely the spatial structure of employability, especially for disadvantaged groups and regions. Based on secondary sources, it summarises the main factors of employability, providing a starting point for researchers working on the econometric branch of social sciences to develop an employability index using this conceptual background. The base of the primary research is the complex questionnaire survey administered to a group of the most disadvantaged job seekers. The study evaluates the factors hindering the employability of human resources that can be activated in the most disadvantaged districts. The research results are useful for those who are interested in increasing employment and reducing the impact of employability-limiting factors.
Investigation of conceptual networks related to climate change among inhabitants: A case study in Eastern Hungarian settlements with word association method
Authors: Kiss Emőke , Fazekas István , Balla Dániel
Published: November 2023

In this study, the word association method was applied in relation to municipalities in Eastern Hungary (Hajdú-Bihar county), where the Sustainable Energy and Climate Action Plan (SECAP) already exists, and where the SECAP has not yet been introduced. In addition to the six municipalities examined, Debrecen, a county seat with the SECAP, was also included in the survey. The aim was to explore the conceptual networks related to climate change and the strength of the relationship between the stimulus word and the associated concepts. The associations representing a common meaning were categorised. The results show that the distribution of conceptual networks and that of categories related to climate change exhibit a similar picture in the group of municipalities with (3 villages) and without the SECAP (3 villages), although significant differences were found when the settlements were examined separately (7 municipalities). Studying the distribution of categories by demographic groups, it was found that educational attainment determines, to the greatest extent, the answers.
Possibilities for paranormal tourism development in Serbia
Authors: Obradović Sanja , Pivac Tatjana , Besermenji Snežana , Tešin Aleksandra
Published: November 2023

This paper aims to identify possibilities for paranormal tourism development in Serbia and to determine domestic tourists’ interest in participating in paranormal tourism. Paranormal places and bizarre rituals have been defined as potential paranormal tourism localities and events. Paranormal tourism is one of the new forms of special interest tourism. It is evident that paranormal tourism is a result of the expansion of other related types of tourism, such as dark tourism, ghost tourism, spiritual tourism, cultural tourism, ethnological tourism, new age tourism and pilgrimage tourism. It is defined by tourists’ interest in topics which challenge realist ontologies and representational epistemologies. The present study examines responses from 405 Serbia residents (potential tourists). After using descriptive statistics, Independent Samples T-Test and ANOVA, the study finds that potential tourists are interested in visiting certain paranormal places, and there is a possibility to develop this type of tourism in Serbia. The current work is the first study of paranormal tourism in Serbia and one of the few studies in the world.
EFFECT OF ULTRASONIC WELDING PROCESS PARAMETERS ON THE CRYSTALLINITY OF GF/MWCNT/PP COMPOSITES
Authors: ULLAH MD ASMAT , I LI WENCAI , PALARDY GENEVIEVE
Published: November 2023

Ultrasonic welding (USW) is a rapid and efficient joining method for thermoplastic polymer composites. This joining technique offers a high bonding strength between composite materials to form lightweight, durable structures in a costeffective way, compared to other traditional joining methods. Crystallinity at the bond line can influence mechanical properties and chemical resistance. However, despite technological development of the USW process, the underlying crystallization mechanisms at the welded interface are still insufficiently understood. This paper explores the use of polypropylene (PP) and multifunctional multi-walled carbon nanotube (MWCNT/PP) films to perform USW between glass fiber (GF)/PP adherends and the resulting effect of welding parameters on the crystallinity degree at the bonded interface. After the USW process, PP and MWCNT films were isolated from glass fiber laminates using Kapton tapes. The effect of MWCNT content (0, 5, 10, 15, 20, 25 wt.%) and welding parameters on the crystallinity of the films and the welded interface was analyzed using differential scanning calorimetry (DSC) and Scanning electron microscopy (SEM), respectively. It was found that increasing MWCNT percentage resulted in a lower degree of crystallinity (44-34%) for the films and for the welded composite interface (23-9%). Four sets of different parameters (welding force and vibration amplitude) were used in this experiment, (500N, 38.1μm), (500N, 54.0μm), (1500N, 38.1μm), and (1500N, 54.0μm), representing different welding times. It was found that increasing force and amplitude resulted in a higher and lower degree of crystallinity, respectively, at the welded interface. Thus, it is expected that the change of crystallinity during USW may be partially attributed to strain-induced crystallization mechanisms.
MOLECULAR DYNAMICS INVESTIGATION OF THE EFFECTS OF DEFECTS AND TRANSVERSE PRESSURE ON THE AXIAL TENSILE BEHAVIORS OF POLYETHYLENE CRYSTALS AND FIBRILS
Authors: DEWAPRIYA M. A. N. , CHOWDHURY S. C. , GILLESPIE JR. J. W.
Published: November 2023

Experimental AFM images have revealed that the structure of ultra-high molecular weight polyethylene (UHMWPE) is porous at the fibril length scale. However, the effects of voids on the mechanical properties of PE fibers are not well understood. We employ molecular dynamics (MD) simulations to investigate the behavior of porous PE crystals under transverse pressure, which can be manifested during processing or transverse impact. We first focused on investigating the influence of the cut-off function in the Reactive Empirical Bond Order potential on the predicted properties of polyethylene crystals. Our objective was to identify the most accurate and computationally efficient implementation of the cut-off function. Through our investigation, we discovered that modifying the lower cut-off radius of the existing cutoff function yields reliable results while maintaining computational efficiency. Building upon this, we conducted MD simulations to analyze the behavior of polyethylene crystals with voids under transverse compression. Our simulations revealed that the collapse of voids is influenced by their state, whether they are vented or closed. Moreover, the strain rate significantly influences the process of void collapse. The outcomes of this study lay a solid foundation for future research endeavors, particularly in exploring the response of porous UHMWPE structures to transverse compression and axial tensile loading.