bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of oxidative post-translational modifications in type 1 diabetes pathogenesis
Authors: Alhamar Ghadeer , Vinci Chiara , Franzese Valentina , Tramontana Flavia , Le Goux Nelig , Ludvigsson Johnny , Nissim Ahuva , Strollo Rocky
Published: February 2025

The pathogenesis of type 1 diabetes (T1D) involves a complex interplay of genetic predisposition, immune processes, and environmental factors, leading to the selective destruction of pancreatic beta-cells by the immune system. Emerging evidence suggests that intrinsic beta-cell factors, including oxidative stress and post-translational modifications (PTM) of beta-cell antigens, may also contribute to their immunogenicity, shedding new light on the multifaceted pathogenesis of T1D. Over the past 30 years, neoepitopes generated by PTMs have been hypothesized to play a role in T1D pathogenesis, but their involvement has only been systematically investigated in recent years. In this review, we explored the interplay between oxidative PTMs, neoepitopes, and T1D, highlighting oxidative stress as a pivotal factor in immune system dysfunction, beta-cell vulnerability, and disease onset.
Factor B as a therapeutic target for the treatment of complement-mediated diseases
Authors: Kavanagh David , Barratt Jonathan , Schubart Anna , Webb Nicholas J. A. , Meier Matthias , Fakhouri Fadi
Published: February 2025

The complement system, consisting of three initiating pathways—classical, lectin and alternative, is an important part of innate immunity. Dysregulation of the complement system is implicated in the pathogenesis of several autoimmune and inflammatory diseases. Therapeutic inhibition of the complement system has been recognized as a viable approach to drug development and has been successful with the approval of a small number of complement inhibitors for diseases such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, neuromyelitis optica, myasthenia gravis and geographic atrophy. More recently, therapies selectively targeting the alternative pathway (AP), which drives the amplification of the complement responses, are being evaluated for these complement-mediated diseases. Complement Factor B, a serine protease, is a unique component of the AP that is essential for the catalytic activity of AP C3 convertase and AP C5 convertase. Inhibition of Factor B blocks the activity of the alternative pathway and the amplification loop, and subsequent generation of the membrane attack complex downstream; however, it has no effect on the initial activation mediated by the classical and lectin complement pathways. Therefore, Factor B is an attractive target for diseases in which the AP is overactivated. In this review, we provide an overview of Factor B and its critical role in the AP, discuss the benefit-risk of Factor B inhibition as a targeted therapeutic strategy, and describe the various Factor B inhibitors that are approved and/or in clinical development.
Structurally modified tetrabromophthalic-based compounds as an anti-corrosion agent in microbial influenced saline systems
Authors: Vignesh Krishnan , Sujithra Sankar , Vajjiravel Murugesan , Santhosh Selvakumar , Narenkumar Jayaraman , AlSalhi Mohamad S. , Devanesan Sandhanasamy , Arunkumar Paulraj , Rajasekar Aruliah , Malik Tabarak
Published: February 2025

This study investigates the efficacy of synthesized corrosion inhibitors and evaluates them for microbial influenced corrosion (MIC) control in carbon steel API 5LX80 induced by Pseudomonas aeruginosa in 3.5 wt% NaCl. Tetrabromophthalic-based inhibitors (TBIs) have been synthesised and ascertained on the basis of spectral measurements determined by Fourier transform infrared spectroscopy (FTIR) and systematically evaluated for MIC. The results showed that this TBI effectively reduced biofilm formation at 200 ppm. FTIR and X-ray diffraction (XRD) observations confirmed that adsorption of a protective film over the surface of metal inhibited bacterial growth. FTIR analysis revealed the adhesion of the inhibitor over the metal surface. Polarization studies indicated that this inhibitor 1 decreased the corrosion current densities (1.4588 × 10−4A/cm2) by a mixed-mode mechanism (both anodic and cathodic) and exhibited 75% corrosion inhibition efficiency. Thus, the present investigation has gained significance in reporting about novel corrosion inhibitors possessing biocidal activity to control MIC in API 5LX80 carbon steel used in oil and pipeline transporting properties.
Relationship between elevated serum direct bilirubin and atrial fibrillation risk among patients with coronary artery disease
Authors: Song Yanbin , Li Wenhua
Published: February 2025

Background

Observational studies have shown that the direct bilirubin (DBIL) is correlated with metabolic syndrome and cardiovascular disease. However, it remains unclear whether DBIL is associated with atrial fibrillation (AF) risk in the patients with coronary artery disease (CAD). This study aimed to investigate the association between serum DBIL levels and AF in CAD patients.

Methods

A total of 937 patients diagnosed with CAD were retrospectively included. Serum total bilirubin (TBIL), DBIL, lipid profiles, and other data were collected and analyzed between the AF and non-AF groups. The characteristics of participants were compared based on their DBIL tertiles. Univariate and multivariate logistic regression models, as well as restricted cubic spline (RCS) regression, were used to explore the relationship between DBIL and AF.

Results

AF was observed in 72 (7.7%) patients. There was a significant higher level of DBIL in the AF patients compared to non-AF patients (p < 0.001). Individuals from the DBIL T3 group, when compared to those from the T1 or T2 groups, were more likely to have a higher proportion of AF and lower levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B) and triglyceride-glucose (TyG) (all p < 0.001). Univariate logistic regression showed that the OR for AF in patients in T3 was 2.796 (95% CI, 1.528–5.116, p = 0.001) compared with participants in T1. The result remained consistent in the multivariate logistic regression (T3 versus 1: adjusted OR: 2.239). The RCS curve demonstrated a significant nonlinear association between DBIL and AF. Subgroup analysis revealed that this association was significant among patients aged ≥65 years old, with body mass index (BMI) < 25, and with diabetes mellitus (DM).

Conclusion

The study suggested a robust relationship between higher levels of DBIL and an increased risk of AF in CAD patients. The association of elevated DBIL with the incidence of AF was higher in CAD patients older than 65 years, with a BMI < 25, and those with DM.
Assessing the impact of 25-hydroxyvitamin concentrations on mortality in chronic diarrhea: a cross-sectional analysis
Authors: Li Pengyu , Zou Menglong , Peng Ziming
Published: February 2025

Background

The aim of this study was to assess the relationship between serum 25-hydroxyvitamin levels and all-cause mortality in patients with chronic diarrhea.

Methods

We carried out a cross-sectional study using information drawn from the National Health and Nutrition Examination Survey (NHANES). To assess mortality outcomes, we compared our data with records from the National Death Index as of December 31, 2011. The NHANES data were used to determine mortality outcome. We used a Cox regression model-based approach to analyze the relationship between serum 25-hydroxyvitamin concentrations and mortality in chronic diarrhea patients.

Results

A total of 2,972 participants with chronic diarrhea were included in our study, 488 cases of all-cause mortality were recorded. The study showed an L-shaped relationship between 25-hydroxyvitamin concentrations and all-cause mortality with a threshold of 73.40 nmol/L. On the left side of the threshold, each 1-unit increase in 25-hydroxyvitamin concentrations was associated with a 2.2% reduction in the risk of all-cause mortality (HR 0.978; 95% CI: 0.969, 0.987); however, on the right side of the threshold, there was no significant correlation between 25(OH)D concentrations and all-cause mortality.

Conclusion

Serum 25-hydroxyvitamin D levels showed an L-shaped association with all-cause mortality in patients with chronic diarrhea, with 73.40 nmol/L as the potential threshold. However, because this was a cross-sectional study, only an association, not a causal relationship, can be inferred. Further prospective studies are needed to confirm these findings and explore the potential impact of vitamin D supplementation on mortality outcomes.
Advances in kidney disease: pathogenesis and therapeutic targets
Authors: Boima Vincent , Agyekum Alex Baafi , Ganatra Khushali , Agyekum Francis , Kwakyi Edward , Inusah Jalil , Ametefe Elmer Nayra , Adu Dwomoa
Published: February 2025

Chronic kidney disease (CKD) is a global public health issue characterized by progressive loss of kidney function, of which end-stage kidney disease (ESKD) is the last stage. The global increase in the prevalence of CKD is linked to the increasing prevalence of traditional risk factors, including obesity, hypertension, and diabetes mellitus, as well as metabolic factors, particularly insulin resistance, dyslipidemia, and hyperuricemia. Mortality and comorbidities, such as cardiovascular complications, rise steadily as kidney function deteriorates. Patients who progress to ESKD require long-term kidney replacement therapy, such as transplantation or hemodialysis/peritoneal dialysis. It is currently understood that a crucial aspect of CKD involves persistent, low-grade inflammation. In addition, increased oxidative and metabolic stress, endothelial dysfunction, vascular calcification from poor calcium and phosphate metabolism, and difficulties with coagulation are some of the complex molecular pathways underlying CKD-related and ESKD-related issues. Novel mechanisms, such as microbiome dysbiosis and apolipoprotein L1 gene mutation, have improved our understanding of kidney disease mechanisms. High kidney disease risk of Africa has been linked to APOL1 high-risk alleles. The 3-fold increased risk of ESKD in African Americans compared to European Americans is currently mainly attributed to variants in the APOL1 gene in the chromosome 22q12 locus. Additionally, the role of new therapies such as SGLT2 inhibitors, mineralocorticoid receptor antagonists, and APOL1 channel function inhibitors offers new therapeutic targets in slowing down the progression of chronic kidney disease. This review describes recent molecular mechanisms underlying CKD and emerging therapeutic targets.
Elucidating the molecular docking and binding dynamics of aptamers with spike proteins across SARS-CoV-2 variants of concern
Authors: Quintela Irwin A. , Vasse Tyler , Jian Dana , Harrington Cameron , Sien Wesley , Wu Vivian C. H.
Published: February 2025

DNA aptamers with high binding affinity against SARS-CoV-2 spike proteins have been selected and analyzed. To better understand the binding affinities between DNA aptamers and spike proteins (S-proteins) of relevant variants of concerns (VOCs), in silico and in vitro characterization are excellent approaches to implement. Here, we identified and generated DNA aptamer sequences targeting the S-protein of SARS-CoV-2 VOCs through systematic evolution of ligands by exponential enrichment (SELEX). In silico, prediction of aptamer binding was conducted, followed by a step-by-step workflow for secondary and tertiary aptamer structures determination, modeling, and molecular docking to target S-protein. The in silico strategy was limited to only providing predictions of possible outcomes based on scores, and ranking was complemented by characterization and analysis of identified DNA aptamers using a direct enzyme-linked oligonucleotides assay (ELONA), which showed dissociation constants (Kd) within the 32 nM–193 nM range across the three significant VOCs. These three highly specific VOCs aptamers (Alpha Apt, Delta Apt, and Omicron Apt) can be further studied as potential candidates for both diagnostic and therapeutic applications.
Epidemic trend of Salmonella from swines and broilers in China from 2014 to 2023 and genetic evolution analysis of ESBLs-producing strains
Authors: Liu Yaopeng , Wang Lin , Wang Juan , Lu Mingzhe , Liu Na , Zhao Jianmei , Hu Fangyuan , Han Keguang , Liu Junhui , Wang Junwei , Qu Zhina
Published: February 2025

Introduction

In recent years, the epidemic trend and antimicrobial resistance of Salmonella from swines and broilers, especially the extended-spectrum β-lactamase (ESBLs)-producing Salmonella, pose a serious threat to human and animal health.

Methods

In this study, we employed serotype identification, drug sensitivity testing, detection of ESBL-producing strains, and whole genome sequencing to analyze the epidemiological trends and drug resistance of Salmonella isolates from swines and broilers, as well as the genetic evolutionary relationships of ESBL-producing strains in China from 2014 to 2023.

Results

The results showed that the most prevalent serotypes of Salmonella from swines and broilers in China in recent 10 years were S. Typhimurium (133/381, 34.91%) and S. Enteritidis (156/416, 37.50%), respectively. Overall, 80.58% strains from swines and 70.67% strains from broilers were multidrug resistant. The multidrug resistance rate (MDR) showed a downward trend. The types of drugs exhibiting an increasing trend in resistance rates among Salmonella from broilers (7) were significantly greater than those from swines (2). The detection rates of ESBLs-producing Salmonella from swines and broilers were 9.45 and 29.58%, respectively, with the former showing a downward trend and the latter showing an upward trend. The drug resistance phenotype of Salmonella produced in ESBLs from swines and broilers is consistent with the results of the resistance genes carried. Whole genome sequencing analysis revealed that 36 swine-derived ESBL-producing Salmonella strains contained 6 ST-types and 13 cgST-types, among which ST34 and ST17 were dominant ST-types; a total of 35 resistance genes across 11 classes, blaCTX-M-14, blaTEM-1B, and blaCTX-M-65 were the predominant subtypes of β-lactam resistance genes. 126 broiler-derived ESBL-producing Salmonella strains included 19 ST-types and 37 cgST-types, with ST17 and ST198 as the dominant ST-types; a total of 52 resistance genes belonging to 12 classes, blaCTX-M-55, blaCTX-M-65, blaTEM-1B, and blaOXA-1 identified as the major subtypes of β-lactam resistance genes.

Discussion

This suggests that we should thoroughly implement management policies aimed at reducing the use of veterinary antimicrobials. Additionally, we should enhance research on traceability technology and the abatement of resistance genes, thereby providing support for the effective prevention and control of the spread of Salmonella and its drug resistance.
PINNing cerebral blood flow: analysis of perfusion MRI in infants using physics-informed neural networks
Authors: Galazis Christoforos , Chiu Ching-En , Arichi Tomoki , Bharath Anil A. , Varela Marta
Published: February 2025

Arterial spin labelling (ASL) magnetic resonance imaging (MRI) enables cerebral perfusion measurement, which is crucial in detecting and managing neurological issues in infants born prematurely or after perinatal complications. However, cerebral blood flow (CBF) estimation in infants using ASL remains challenging due to the complex interplay of network physiology, involving dynamic interactions between cardiac output and cerebral perfusion, as well as issues with parameter uncertainty and data noise. We propose a new spatial uncertainty-based physics-informed neural network (PINN), SUPINN, to estimate CBF and other parameters from infant ASL data. SUPINN employs a multi-branch architecture to concurrently estimate regional and global model parameters across multiple voxels. It computes regional spatial uncertainties to weigh the signal. SUPINN can reliably estimate CBF (relative error −0.3±71.7), bolus arrival time (AT) (30.5±257.8), and blood longitudinal relaxation time (T1b) (−4.4 ± 28.9), surpassing parameter estimates performed using least squares or standard PINNs. Furthermore, SUPINN produces physiologically plausible spatially smooth CBF and AT maps. Our study demonstrates the successful modification of PINNs for accurate multi-parameter perfusion estimation from noisy and limited ASL data in infants. Frameworks like SUPINN have the potential to advance our understanding of the complex cardio-brain network physiology, aiding in the detection and management of diseases. Source code is provided at: https://github.com/cgalaz01/supinn.
Commercial immunoassays in paraneoplastic neurological syndromes: an Australian laboratory perspective
Authors: Ali Syed B. , Cecchin Amelia , Burfoot Rebecca , Chia Nicholas , Ravindran Janakan , Field Deborah , King Jovanka , Pucar Phillippa A. , Banovic Tatjana
Published: February 2025

Background

Paraneoplastic antibodies are implicated in heterogeneous clinical presentations. Commercial immunoassays include indirect immunofluorescence (IIF), and line immunoblot (LIB). LIB can be associated with false positives, and unfortunately, further confirmatory assays are not readily available in diagnostic laboratories.

Objectives

To determine frequency of positive LIB on serum or cerebrospinal fluid (CSF) using EUROLine paraneoplastic neurological syndromes (PNS) 12 Ag Test kit (EuroImmun, Germany) and establish concordance with IIF on Nova Lite kit (Inova Diagnostics, United States) and clinical presentation.

Methods

A retrospective analysis of all LIB performed over a four-year period was undertaken. Healthy control samples were also analysed with IIF and LIB.

Results

Two thousand and eighty-one LIB samples were processed, 91 (4.4%) were positive from 69 patients with a median age of 64 years. There were 37 females (53.6%). Some samples had two antibody specificities (n = 6, 6.6%). Of those with one antibody, GAD65 (n = 22), Yo (n = 19), SOX1 (n = 17) and amphiphysin (n = 14) were most frequent. Of the positive LIBs, 80 (87.9%) had concurrent IIF and eight samples (10%) had a typical IIF pattern. Clinical relevance of a positive LIB, irrespective of IIF, was seen in 15/91 samples (14.3%) from nine patients; GAD65 (n = 3), Hu (n = 2), amphiphysin (n = 1), Yo (n = 1), Tr (n = 1) and CV2 (n = 1). Of the 71 healthy controls, five (7.0%) had a positive LIB: medium band (n = 4, 5.6%: amphiphysin, CV2, SOX1 and Yo) and strong band (n = 1, 1.4%: Yo). All IIF were negative. On average, signal intensity (SI) was higher in those with disease (SI 77.3/very strong band) compared to those without (SI 28.6/strong band) and healthy controls (SI 2/negative band) (p < 0.0001).

Discussion

LIB has a high false positive rate, and in this cohort, there were more false than true positive results. The assay must be used in those with a high clinical suspicion for PNS. While the commercial IIF kit is a useful test, it is insufficient to be used as a screening strategy in isolation.
A high-throughput screening platform to identify MYCN expression inhibitors for liver cancer therapy
Authors: Xu Yali , Mishra Hricha , Furutani Yutaka , Yanaka Kaori , Nishimura Hajime , Furuhata Erina , Takahashi Masataka , Gailhouste Luc , Suenaga Yusuke , Hippo Yoshitaka , Yu Wenkui , Matsuura Tomokazu , Suzuki Harukazu , Qin Xian-Yang
Published: February 2025

MYCN, an oncogene implicated in hepatocellular carcinoma (HCC), is predominantly expressed in cancer stem-like HCC cells. It drives tumorigenicity, metastasis, and therapeutic resistance. In this study, we hypothesized that the pharmacological inhibition of MYCN could represent a novel therapeutic strategy for HCC. To identify inhibitors of MYCN expression, we developed an unbiased, high-throughput screening platform. With this platform, we identified MI202 as a potent inhibitor of MYCN expression. MI202 significantly reduced MYCN promoter activity and mRNA levels in HCC cells, inhibiting cell proliferation, spheroid formation, and colony growth and promoting apoptosis. Notably, MI202 selectively inhibited the proliferation of HCC cells but not of normal hepatic cells, highlighting its potential for HCC-specific therapy. Genome-wide CRISPR knockout screening has identified acyl-CoA thioesterase 2 (ACOT2), a key regulator of lipid metabolism, as a molecular target of MI202. ACOT2 downregulation by MI202 was associated with reduced MYCN expression, suggesting that ACOT2 may mediate MYCN-driven tumorigenesis through lipid desaturation. Overall, this study presents a robust high-throughput screening platform to identify MYCN inhibitors and highlights the potential of pharmacological downregulation of MYCN as a therapeutic strategy for targeting HCC.
The prognostic value of pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with esophageal cancer undergoing immunotherapy: a systematic review and meta-analysis
Authors: Deng Min , Qing Yun , Qiu Dan , Sheng Ya , Zhou Juan , Sun Lan
Published: February 2025

Background

Esophageal cancer (EC) is associated with a high morbidity and mortality rate. Immunotherapy has demonstrated effective antitumor activity in patients with EC, making it imperative to investigate easily accessible prognostic factors. Consequently, we conducted a meta-analysis to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in EC patients treated with immunotherapy.

Methods

The literature search was conducted across three databases: PubMed, Embase, and Web of Science. The primary deadline for literature retrieval was July 2024. Hazard ratio (HR) with a 95% confidence interval (CI) was utilized to assess the association between NLR or PLR and overall survival (OS) as well as progression-free survival (PFS). Statistical analysis was performed using Review Manager version 5.4 and STATA version 15.0.

Results

The meta-analysis included a total of 16 studies involving 1,481 patients. The results indicated a significant correlation between high pretreatment NLR and poor PFS (HR=1.76, 95%CI:1.38-2.25, p<0.001) as well as poor OS (HR=2.61,95%CI:1.86-3.67, p<0.001). Subgroup analyses based on tumor stage revealed that the association between elevated NLR and poor PFS was only observed in advanced EC patients. Regarding PLR, an increased PLR was found to be indicative of inferior PFS (HR=1.44, 95%CI: 1.20-1.72, p<0.001) and OS (HR=1.72,95%CI:1.08-2.74, p=0.020). However, the sensitivity analyses suggested that the observed increase in PLR lack robustness in terms of its impact on inferior OS.

Conclusion

Elevated NLR and PLR are associated with inferior PFS and OS in EC patients receiving immunotherapy. These findings suggest that NLR and PLR levels hold promise as prognostic biomarkers in clinical practice, offering valuable guidance for personalized immunotherapy strategies.

Systematic Review Registration

PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42024596737.
Methamphetamine self-administration causes neuronal dysfunction in rat medial prefrontal cortex in a sex-specific and withdrawal time-dependent manner
Authors: Chen Lihua , Kreko-Pierce Tabita , Cassoday Stefanie L. , Al-Harthi Lena , Hu Xiu-Ti
Published: February 2025

Methamphetamine (Meth) is one of the most widely used illicit drugs worldwide, exerting potent psychostimulant effects that fuels its highly addictive nature. Chronic Meth use is associated with severe cognitive impairments, particularly in executive functions, decision-making, and working memory, which persist long even after cessation of Meth use. These cognitive deficits are associated with dysfunction of glutamatergic pyramidal neurons in the medial prefrontal cortex (mPFC), which regulates addiction and cognition. Both human and animal studies highlight Meth-induced mPFC dysfunction that contributes to compulsive behaviors and relapse. Emerging evidence also highlights significant sex differences in Meth use disorder (MUD). Previous studies suggest that Meth-induced behavioral and neuronal dysfunctions are different between males and females, but the cellular and molecular mechanism are not fully understood. Using behavioral and electrophysiological approaches (whole-cell patching), this study determined certain sex differences in neuronal dysfunction in the mPFC of rats that self-administered Meth (Meth-SA) followed by a short (2–5 d) or long-term (≥30 d) withdrawal. We found that both male and female rats self-administered methamphetamine in a similar pattern; however, the resulting hypoactivity, hyperactivity, and calcium dysregulation in mPFC neurons differed between the sexes. Such sex-specific neuronal dysfunction was associated with, and depended on, short or long-term withdrawal, respectively. By understanding these sex-specific behavioral/neuronal differences following different Meth withdrawal period, our novel findings demonstrate the role of sex as a biological variable in Meth-use and relapse, and reveal the effects of drug-using environment on mPFC neuronal dysfunction during withdrawal, providing insights for gender-specific treatment strategies.
Cinnamic acid alleviates hypertensive left ventricular hypertrophy by antagonizing the vasopressor activity and the pro-cardiac hypertrophic signaling of angiotensin II
Authors: Cui Yimeng , Yang Yawei , Tang Xinmiao , Wang Peiwei , Cui Jingang , Chen Yu , Zhang Teng
Published: February 2025

Background

Hypertension is the most common cause of pathological left ventricular hypertrophy, a condition causally associated with debilitating heart failure and cardiovascular events in hypertensive patients. It is well recognized that the disease burden of hypertension-linked heart failure remains unabated with existing treatments. New therapies controlling hypertensive left ventricular hypertrophy are thus required to decelerate or prevent the development of heart failure. Our previous study has demonstrated that cinnamic acid, a naturally occurring monocarboxylic acid, mitigates transverse aortic constriction-induced pressure overload-mediated cardiac hypertrophy. However, whether cinnamic acid is effective at controlling hypertensive left ventricular hypertrophy remains unknown. Angiotensin II (ang II) plays a pivotal role in driving the pathogenesis of hypertensive left ventricular hypertrophy. The current work thus investigates the therapeutic potential and pharmacological mechanisms of cinnamic acid in the context of ang II-mediated hypertensive left ventricular hypertrophy.

Methods

Ang II-infused mice and cardiomyocytes were analyzed by histological, immunohistochemical, cellular and molecular biological methods to delineate the impact of cinnamic acid on hypertensive left ventricular hypertrophy.

Results

The results showed that cinnamic acid lowered blood pressure and attenuated left ventricular hypertrophic and fibrotic alterations in the ang II-infused mice. Cinnamic acid counteracted hypertrophic responses, impairment of the mitochondrial function and overproduction of mitochondrial reactive oxygen species (ROS) in the cardiomyocytes exposed to ang II. At the molecular level, cinnamic acid mitigated ang II-induced activation of signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2) in cardiomyocytes. Additionally, cinnamic acid blunted STAT3 and ERK1/2 activation as well as the hypertrophic responses in cardiomyocytes exposed to interleukin 6 (IL-6) as well.

Conclusion

In summary, this is the first study demonstrating that cinnamic acid is effective at mitigating hypertensive left ventricular hypertrophy. Cinnamic acid antagonizes the vasopressor activity of ang II at the systemic level and the ligand-dependent pro-hypertrophic signaling of ang II in cardiomyocytes. Furthermore, our present study presents new evidence supporting that cinnamic acid lessens the activation of STAT3 and ERK1/2, which may in part contribute to its anti-hypertrophic actions in cardiomyocytes.
A scoping review of longitudinal studies of athlete burnout
Authors: Dišlere Beate Evelīna , Mārtinsone Kristīne , Koļesņikova Jeļena
Published: February 2025

Introduction

Prior research has shown that increasing training and competition loads, along with associated stressors, can negatively impact athletes’ mental health and contribute to burnout. While athlete burnout can be associated with various negative sports-related consequences, such as withdrawal from sports or injuries. Although most studies on athlete burnout employ cross-sectional designs, longitudinal approaches could provide valuable insights into athlete burnout changes over time and potential causal relationships between variables and burnout. Therefore, this study aims to systematically examine longitudinal design studies to offer a comprehensive methodological, conceptual, and practical overview of athlete burnout and its associated factors.

Methods

Following PRISMA-ScR guidelines, this review explores what factors influence changes in burnout levels among athletes throughout a sports season. Therefore, studies were selected that examined athlete burnout across both genders, all age groups, and various sport types, using repeated measurements. Published articles from 2014 to 2024 were collected. Eligible studies were identified through three databases: PubMed, Scopus, and Web of Science.

Results

A total of 32 studies were analyzed. Quantitative mapping highlights study demographics, measurement approaches, and procedures, while qualitative mapping identifies 26 factors categorized as risk, protective, and factors influenced by burnout. The review highlights the use of tools like the Athlete Burnout Questionnaire and identifies optimal data collection intervals for tracking burnout dynamics.

Conclusion

This scoping review offers insights into the multidimensional and nonlinear nature of athlete burnout, emphasizing its development through longitudinal studies and the importance of monitoring specific dimensions. The findings revealed various athlete burnout influencing personal and sport-environmental factors, including risk factors like perfectionistic concerns and negative social interaction, protective factors such as resilience-related skills and relatedness, and social support. The study emphasizes the importance of early detection and longitudinal monitoring to prevent burnout and mitigate its impact on athletes’ mental health and performance. Further research is needed to explore additional risk and protective factors to develop effective interventions aimed at reducing the risk of burnout in athletes.
sunflower: an R package for handling multiple response attempts and conducting error analysis in aphasia and related disorders
Authors: Gutiérrez-Cordero Ismael , García-Orza Javier
Published: February 2025

Manual classification of production errors and the allocation of speech/spelling scores are time-consuming, laborious and error-prone tasks, even when conducted by clinicians and specialized researchers. Here we present sunflower, an R package developed to improve the analysis of language production quality for Spanish data. The package offers various functions, including (1) managing dataframes containing single responses and multiple-attempt responses, (2) conducting formal similarity analyses on words as well as positional accuracy data analyses within words, and (3) the classification of errors by considering lexicality, formal similarity and semantic similarity indexes, which are obtained by means of different algorithms and artificial intelligence techniques such as word2vec. The applications of sunflower, which is the first open-source package of its kind, include assessing whether production quality improves over the course of multiple attempts, and identifying which aspects of an individual’s productions are most impacted by their impairments. Other potential applications include the analysis of whether improvements arise in a patient’s production quality after a given treatment, distinguishing between cases of apraxia of speech and conduction aphasia, as well as simply using the package to improve and speed up the classification of speech/spelling errors with large datasets through automation.
Global burden and international disparities in NASH-associated liver Cancer: mortality trends (1990–2021) and future projections to 2045
Authors: Nie Qilong , Jiang Yongwen , Li Mingyang , Liang Qiuyan , Mo Xiaoai , Qiu Tengyu , Jiang Qunfang , Huang Kaizhou , Xie Youqing , Chen Ying , Ma Xiaojun , Li Jianhong , Jiang Kaiping
Published: February 2025

Background

NASH-associated liver cancer (NALC) is a significant contributor to global cancer mortality, closely linked to the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). This study comprehensively examines the global burden of NALC from 1990 to 2021.

Methods

This study used data from the Global Burden of Disease (GBD) 2021 database to analyze NALC death and age-standardized death rates (ASDR) globally and regionally from 1990 to 2021. We applied Joinpoint regression analysis to assess temporal trends, calculating the annual percent change (APC) and average annual percent change (AAPC). Decomposition analysis was performed to break down mortality changes into contributions from population aging, growth, and epidemiological changes. A frontier analysis was used to evaluate the relationship between NALC burden and sociodemographic development using the Socio-Demographic Index (SDI). Prediction analysis of NALC deaths and ASDR from 2021 to 2045 were estimated using the Nordpred model.

Results

From 1990 to 2021, the global burden of NALC deaths increased significantly, with the ASDR rising from 0.38 per 100,000 in 1990 to 0.48 per 100,000 in 2021. Age-specific data in 2021 revealed that NALC deaths peaked in the 65–69 age group for men and 70–74 age group for women. Decomposition analysis indicated that population growth was the most significant contributor to the global NALC death toll, followed by population aging and epidemiological changes. Frontier analysis showed that countries like Mongolia and Gambia were farthest from the disease burden frontier, while Morocco and Ukraine were closest. Prediction analysis suggest a significant increase in NALC deaths by 2045 compared to 2021, with a larger rise in deaths among women.

Conclusion

Through this study, a data-driven approach is provided to reduce the global disease burden of NALC. Essential data support for public health prevention strategies is offered, helping guide the development of targeted government interventions. Trends across global regions, countries, age groups, and genders have been analyzed, providing valuable insights for the formulation of evidence-based policies aimed at mitigating the impact of NALC worldwide.
“Know your medicines, know your health”—public perspectives on medicines and health awareness campaigns
Authors: Alhomoud Faten , Alameer Kawthar , Almousa Zahra’a , Almatar Manar , Alzlaiq Wafa , Alhomoud Farah Kais , Alsugeir Dana
Published: February 2025

Background

Irrational medication use is likely to result in therapeutic failure and disease progression. One way to increase public awareness about appropriate medication use is to design and deliver a public health medicine awareness campaign. This study aims to assess the public’s attitudes and experiences related to medication use and health awareness campaigns in Saudi Arabia.

Methods

This is a cross-sectional survey study. Participants were aged 18 or over and able to speak Arabic or English. An online survey was distributed to a convenient sample of 451 participants by email and social media via an internet link, leading to a web-based survey platform in QuestionPro. Bivariate and multivariate analyses were used to assess the associations.

Results

Three hundred and forty-seven participants (76% female, aged 18–85 years) were on a mean (SD) of two (1.86) prescription-only-medicines (POMs), and 225 were on non-prescription medicines. Seventy-one and 63 % of those surveyed consulted a doctor or a pharmacist, respectively, for advice about their medications. The participants were curious mainly about the side effects of treatment (79%), followed by drug interactions and contraindications (55%). Most participants agreed or strongly agreed that their medications were necessary to improve their condition (82%), prevent the progress of their condition (85%), and reduce the risk of complications (90%). Seventy-seven percent of participants reported seeing a public health campaign previously. TV (58%) and Twitter (55%) were reported as the most appropriate tools to help deliver a good public health campaign. Ninety-one percent believed that a public health campaign can increase people’s awareness about their lifestyle, and 73% declared that medication should be part of it.

Conclusion

The findings can be a foundation for developing and implementing medicines and health awareness campaigns to enhance public understanding of health and medication use.
Determining the meter of classical Arabic poetry using deep learning: a performance analysis
Authors: Mutawa A. M. , Alrumaih Ayshah
Published: February 2025

The metrical structure of classical Arabic poetry, deeply rooted in its rich literary heritage, is governed by 16 distinct meters, making its analysis both a linguistic and computational challenge. In this study, a deep learning-based approach was developed to accurately determine the meter of Arabic poetry using TensorFlow and a large dataset. Character-level encoding was employed to convert text into integers, enabling the classification of both full-verse and half-verse data. In particular, the data were evaluated without removing diacritics, preserving critical linguistic features. A train–test–split method with a 70–15–15 division was utilized, with 15% of the total dataset reserved as unseen test data for evaluation across all models. Multiple deep learning architectures, including long short-term memory (LSTM), gated recurrent units (GRU), and bidirectional long short-term memory (Bi-LSTM), were tested. Among these, the bidirectional long short-term memory model achieved the highest accuracy, with 97.53% for full-verse and 95.23% for half-verse data. This study introduces an effective framework for Arabic meter classification, contributing significantly to the application of artificial intelligence in natural language processing and text analytics.
The Emperor’s old clothes: a critical review of circular fashion in gray literature
Authors: Hussain Talia , Kuzmina Ksenija , Koria Mikko
Published: February 2025

A consensus across industry, academics, and policy-makers holds that a circular fashion system can reduce pollution and waste while producing continued economic growth. Gray literature, understood here as reports published outside of academic journals, has been foundational to describing and promoting circular economy and circular fashion. Yet, this literature is rarely subjected to critical scrutiny, allowing evidence, claims and methods to go unexamined. This review aims to understand how value and the market are conceptualized in a circular fashion system, and what are the implications of this. The study employs a problematizing review of 20 gray literature documents, including a key text of circular fashion: the Ellen MacArthur Foundation’s 2017 report A New Textiles Economy: Redesigning Fashion’s Future. Textual analysis is used to identify assumptions, inferences and problem framings in the texts. These are evaluated against academic understandings, demonstrating that core concepts of the circular fashion proposal are poorly defined and unconnected to existing theory and knowledge. Existing retail practices and consumer marketing messages are central to circular fashion, while the role of the market in setting prices is ignored. A $460 billion error is revealed, refuting the claim that a circular fashion system provides an opportunity for growth. We offer a critical perspective on the role of gray literature and gray publishers in shaping policy-making and, subsequently, academic research programs. We argue that new proposals for sustainable fashion are needed, based on established knowledge and validated models.
“They seemed to forget about us little people”: the lived experiences of personal care attendants during the COVID-19 pandemic
Authors: Wendel Carrie , Sullivan Darcy L. , Babitzke Jennifer , La Pierre Tracey A.
Published: February 2025

Background

Personal care attendants (PCAs) provided essential care and support to home care clients during the COVID-19 pandemic and thus were a vital part of the pandemic response in helping to keep older adults and individuals with disabilities out of nursing homes. Furthermore, they are one of the largest and fastest growing workforces in the United States. Yet this essential workforce received little attention during the pandemic. Guided by feminist theories on caregiving and the principles of community-based participatory research, this study examined the experiences of PCAs during the COVID-19 pandemic.

Methods

Data from 78 in-depth interview participants representing Medicaid-Funded Home and Community-Based Services (HCBS) PCAs, clients, family caregivers, and service providers in Kansas, United States, as well as additional data from 176 PCA survey participants were analyzed. Findings from this interactive, convergent, mixed-methods study were integrated by theme using the weaving approach.

Results

Four major themes emerged from the analysis: (1) PCAs remained in this field during the pandemic out of a commitment to their clients; (2) PCAs were undervalued and invisible as an essential workforce; (3) direct care work had an emotional toll on PCAs during the pandemic; and (4) PCAs have mixed feelings about their satisfaction with the job, and, as good workers quit, they were difficult to replace.

Discussion

PCAs held professional-level responsibilities without the recognition or pay of a professional. The pandemic had mixed impacts on job stress and satisfaction, suggesting that the intrinsic rewards of the job and social support had a protective impact. However, intrinsic rewards are not enough to retain this workforce, and the growing PCA workforce shortage leaves many clients having to choose between no care and poor care. Our findings indicate that institutions and systems must better support and recognize this essential workforce to build and maintain a quality in-home care services system.
High-level personal trainer perspective for industry practice and development in Serbia: a qualitative descriptive study
Authors: Curovic Ivan , Grecic David
Published: February 2025

Personal trainers (PTs) play a pivotal role in promoting positive gym experiences, implementing effective weight loss strategies, and influencing healthier lifestyle choices. In Serbia, however, the absence of national accrediting bodies for standardised qualifications has led to a lack of formal recognition of exercise professionals. The views of personal training clients regarding their training practices and experiences have been explored previously. Building on this, the current study investigated the perspectives of high-level Serbian PTs, examining their professional developmental journeys, educational background, coaching philosophies, professional needs and experiences. The aim was to provide insights for educational institutions and other practitioners to adopt successful approaches that inspire lifelong exercise and promote positive lifestyle changes for increasingly sedentary populations. Using a snowball sampling method, we interviewed 12 high-level PTs, selected for their exceptional practice as recognised by their peers. The findings suggest a need for a shift from traditional, physical performance-focused approaches toward a more holistic model that incorporates psychosocial support and a care for the whole person, fostering an appreciation for the concept of physical literacy. Additionally, the study identifies critical gaps in PTs education and training, particularly concerning the lack of focus on behavior change models and inquiry-based skills essential for their future self-directed learning. These areas were highlighted as vital for continued professional development after formal qualifications are obtained. In conclusion, this research underlines the need for holistic training approaches to improve clients' physical and health outcomes. The study offers guidance to shape industry standards, foster accreditation systems, and start the debate on how best to continually support PTs during their careers. Such action is essential if the evolving personal training profession in Serbia is to be equipped with the tools needed to promote long-term client engagement and achieve the health benefits for the wider Serbian population.
How does science and technology finance affect the agricultural green development: an interpretation from the perspective of rural human capital and agricultural industrial agglomeration
Authors: Yao Sheng , Wu Guosong , Zhang Shu
Published: February 2025

How to achieve a win-win situation between agricultural economic growth and environmental protection has become an urgent issue to be resolved. This study takes China as an example and employs econometric methods to explore the impact of science and technology finance on agricultural green development and its underlying mechanisms. The findings indicate that science and technology finance has a significant positive impact on agricultural green development and can effectively promote it. This conclusion remains robust after replacing the explained variables, adding control variables, removing samples from municipalities, and conducting endogeneity tests. The impact of science and technology finance on agricultural green development is significant across different regions, showing no obvious regional differences. Rural human capital acts as a mediator in the relationship between science and technology finance and agricultural green development, while agricultural industrial agglomeration has a certain “masking effect” on this relationship. The impact of science and technology finance on agricultural green development exhibits a complex non-linear relationship. When science and technology finance is used as a threshold variable, it shows a significant positive marginal effect that increases; however, when rural human capital and agricultural industrial agglomeration are used as threshold variables, it shows a significant positive marginal effect that decreases. Future research can be further expanded in three areas: first, using spatial econometric models to study the spatial spillover effects of science and technology finance on agricultural green development; second, identifying more mediating variables and incorporating them into the research framework to more comprehensively demonstrate the mechanisms through which science and technology finance affects agricultural green development; third, data at the municipal level are used for the relevant analysis to address the issue of insufficient detail in studies that rely on provincial-level data.
A Dual-Motor Actuator for Ceiling Lift with High-Force and High-Speed Capabilities
Authors: Lalonde Ian , Denis Jeff , Lamy Mathieu , Girard Alexandre
Published: February 2025

Patient transfer devices allow for passive movement of patients in hospitals and care centers. Instead of hoisting the patient, it would be beneficial in some cases to assist their movement, enabling them to move by themselves and reducing hospitalization time. However, patient assistance requires devices capable of precisely controlling output forces at significantly higher speeds than those used for patient transfers alone, and a single-motor solution would be over-sized and would show poor efficiency for accomplishing both functions. This paper presents a ceiling robot, using a dual-motor actuator and adapted control schemes, that can be used to transfer patients, assist patients in their movement, and help prevent falls. The prototype is shown to be able to lift patients weighing up to 318 kg and to assist a patient with a desired force of up to 100 kg with a precision of 7.8%. Also, a smart control scheme to manage falls is shown to be able to stop a patient who is falling by applying a desired deceleration.