Fatigue is a common, often disabling symptom in myasthenia gravis (MG), distinct from muscle fatigability, and strongly associated with reduced quality of life. This narrative review examines current evidence on fatigue in MG, its patient impact, and future research directions. Earlier studies, mostly small and heterogeneous, reported a highly variable prevalence of fatigue. Recent large registry-based studies have now established a more consistent prevalence around 60% and confirmed associations with disease severity, depressive symptoms, and physical inactivity. Fatigue has also been assessed as secondary endpoint in phase 3 trials of targeted immunotherapies, with improvements paralleling broader clinical benefits. In contrast, non-pharmacological approaches remain understudied; however, several studies have recently been initiated in which fatigue is a predefined outcome measure. Emerging biomarker evidence suggests that systemic low-grade inflammation may contribute to fatigue. Together, these insights highlight the need for targeted, multidimensional strategies to better understand and treat fatigue in MG.

Exploring students' perceived negotiation of critical thinking with teachers, peers, and AI in EFL learning.

Leukocyte trafficking in the efferent lymph of pigs - confirmation and extension of earlier observations.

Telehealth in pediatric physiotherapy presents both opportunities and challenges, particularly in lower-resource settings where health service access and equity remain concerns. Focus of attention (FOA) for instructions and feedback, which influences motor learning outcomes, may be crucial in this context. While earlier studies have relied mainly on self-reports, direct observation can identify physiotherapists' actual use of FOA in practice. This study used an exploratory observational design to examine pediatric physiotherapists' use of FOA when delivering instructions and feedback during telehealth. The study involved two therapy centers in the capital region. Six physiotherapists each selected two clients with neurodevelopmental disorders who received weekly telehealth physiotherapy. Three sessions per client were recorded via Zoom (n = 36). Physiotherapists completed the Developmental Profile-4th Edition forms assessing clients' physical and cognitive development. Transcriptions were coded as instructions, feedback, or general chatter and classified by focus, modality, and recipient. Frequencies were calculated to derive relative focus scores, indicating physiotherapists' FOA preference. Paired t tests revealed significant differences (p < .001) in physiotherapists' relative focus scores for instructions (mean 42.62 SD 25.03) and feedback (mean 58.98 SD 23.8). Pearson's correlations revealed that overall relative focus scores were significantly associated with clients' age (r = 0.396, p = .017), cognitive development (r = 0.552, p < .001), and physical development (r = 0.552, p < .001). Physiotherapists prefer an external FOA during instructions and an internal FOA during feedback. Relative focus scores were associated with clients' age and development levels. Given the heightened reliance on verbal instructions during telehealth, these findings offer baseline evidence to inform knowledge translation and context-specific application of FOA principles in pediatric physiotherapy practice.

Firebrands are glowing particles, typically millimeters to centimeters in size, that represent a common ignition source for structures in wildland-urban interface fires. In this work, three distinct types of ignitions of combustible substates by firebrands differing in mechanism have been identified through a review of the bench-scale wind tunnel experiments performed in earlier studies. A model for the most frequently observed type of ignition, preleading zone ignition, was developed. This model simulates a substrate’s response to firebrand exposure using a combination of an empirical firebrand pile heat feedback sub-model and a detailed pyrolysis model of the combustible substrate. Using the ignition model, an analysis of the experimentally observed preleading zone ignitions of Western Red Cedar, pressure-treated wood, and a wood-plastic composite at 0.9 – 2.7 m s -1 air flow velocities and 0.06 and 0.16 g cm -2 firebrand coverage densities was performed. It was determined that the attainment of the 10-s-averaged heat release rate of 120 kW m -2 or higher, computed under the assumption of complete combustion of the gaseous pyrolyzate, was a reliable predictor of the ignition occurrence. It was also found that the same critical heat release rate value can be used to predict the preleading zone ignition time. • Three ignition types of combustible substrates by firebrands were identified • Detailed pyrolysis modeling was used to analyze most common type of ignition • Heat-release-rate-based criterion for the ignition was derived

Class I cyclic nucleotide phosphodiesterases (PDEs) form a family of enzymes that hydrolyze the signaling molecules cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Highly potent and selective inhibitors of mammalian PDEs have been developed, demonstrating that this enzyme family is eminently druggable. The genomes of the free-living nematode and model organism Caenorhabditis elegans and those of related parasitic nematodes possess six PDE genes representing six of the eleven PDE families found in mammals. Here, we expressed the C. elegans PDEs or their catalytic domains in the fission yeast Schizosaccharomyces pombe and screened a collection of small molecule inhibitors of mammalian PDEs obtained from our previous high throughput screens for ones with activity against one or more C. elegans PDEs. Consistent with an earlier study, the C. elegans PDE-4 enzyme is relatively insensitive to mammalian PDE4 inhibitors such as Rolipram, as are PDE-4 enzymes from three parasitic nematodes. Much of this is due to a single amino acid difference between mammalian PDE4s and nematode PDE4, as replacing arginine 580 with threonine in C. elegans PDE-4 restores substantial sensitivity to Rolipram. Finally, several of the most effective C. elegans PDE inhibitors were tested for their impact on C. elegans growth and fertility, two of which displayed toxic effects on C. elegans viability and fecundity using two different assessment methods, while a third showed a significant effect on fecundity. The strategy described herein offers an approach for discovery of novel anthelmintic and nematicidal compounds targeting parasitic nematode PDEs.

Childhood adversity and adolescent motherhood: A cross-sectional study of trauma, partner age gaps, and parenting in the Dominican Republic.

Iron metabolism plays a vital role in maintaining physiological homeostasis, and its dysregulation is implicated in a range of pathological consequences and illnesses, including Alzheimer's disease (AD). Prior studies have demonstrated that Tau protein and amyloid precursor protein are involved in iron homeostasis disorder. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a key contributor to AD pathogenesis and a promising therapeutic target. Acyl-CoA synthetase long-chain family 4 (ACSL4) is a lipid metabolizing enzyme that enhances ferroptosis sensitivity by promoting the incorporation of oxidizable polyunsaturated fatty acids into membrane phospholipids. Beyond ferroptosis, ACSL4 also plays crucial roles in neuroinflammation and oxidative stress, which are implicated in AD progression. Therefore, targeting ACSL4 is fantastic and has a lot of promise for treating AD. Nevertheless, the precise mechanisms through which ACSL4 contributes to AD pathology have yet to be fully elucidated. This review reveals a potentially vital role of ACSL4 in AD, focusing on its involvement in ferroptosis, oxidative stress, and neuroinflammation. Additionally, we describe some natural and synthetic compounds targeting ACSL4 with therapeutic potential in AD. Building on the theoretical findings of earlier studies about focused interventions of the ACSL4 path, our evaluation provided a broad basis for the clinical transformation in the treatment of AD strategies.

Pathological platelet activation is central to cardiovascular disorders. Glycoprotein VI (GPVI), a pivotal collagen receptor, is a promising antithrombotic target. While earlier studies focused on the downstream effects of peroxisome proliferator-activated receptor γ (PPARγ) ligands, we recently identified the proximal PPARγ-Src family kinase (SFK) interaction as a key regulatory node. KR-62980 is a novel non-thiazolidinedione (non-TZD) PPARγ modulator designed to minimize traditional TZD-associated adverse effects. Here, we investigated whether KR-62980 operates through this "proximal mechanism." We found that KR-62980 dose-dependently inhibited collagen-induced human platelet aggregation in both washed platelets and platelet-rich plasma. Notably, KR-62980 exhibited a predominant sensitivity toward the collagen-GPVI axis compared to thrombin-induced protease-activated receptor signaling. Mechanistically, KR-62980 targeted the top of the GPVI signaling hierarchy by disrupting the physical and functional association between PPARγ and SFKs (Lyn and Fyn). This blockade suppressed SFK autophosphorylation and dismantled the LAT signalosome, preventing the recruitment of Gads, SLP-76, Btk, and PLCγ2. These findings confirm that the "proximal interaction" paradigm is a universal feature of PPARγ-mediated antiplatelet action, regardless of the agonist's chemical structure. In vivo, oral administration of KR-62980 significantly prolonged thrombotic occlusion time in a mouse carotid artery thrombosis model. Importantly, at therapeutic doses, KR-62980 did not significantly affect tail bleeding time, demonstrating a favorable safety profile with a wide therapeutic window. These findings confirm that the "proximal interaction" paradigm is a universal feature of PPARγ-mediated antiplatelet action and suggest that KR-62980 is a promising candidate for safe antithrombotic therapy.

A well-powered test of task difficulty effects on cardiovascular indicators of mental effort.

ABSTRACT Earlier studies have documented psychoactive substance use and nicotine exposure among commercial drivers in Ghana. However, those studies relied solely on self-reported questionnaires, which are prone to recall and response bias. This study aimed to provide a more accurate estimate by using a chromatographic immunoassay urine drug test. This exploratory cross-sectional study was conducted between January and August 2024 in the Tamale metropolitan area of Ghana. The study included 70 consenting commercial drivers aged from 26 to 78 years. Sociodemographic, anthropometric and occupational factors were collected using a semi-structured questionnaire. Urine samples were then obtained from the participants and tested for Amphetamine (AMP), Barbiturates (BAR), Benzodiazepines (BZO), Cocaine (COC), Tetrahydrocannabinol (THC), Morphine (MOP), Opiates (OPI), nicotine exposure using Cotinine (COT), Tramadol (TML), and Tricyclic Antidepressants (TCA) using the 10-panel Multi-Drug One Step chromatographic immunoassay test kit. The total urine prevalence of psychoactive substances and nicotine exposure was 61.4%, consisting of COT (37.1%), THC (24.3%), BZO (11.4%), Tramadol (5.7%) and AMP (2.9%). While the self-reported smoking prevalence was 10%, the urine cotinine prevalence was 37.1%. In addition, 14(20%) of the urine samples tested positive for two substances. Contrary to expectations, commercial drivers with no history of accident were more likely to test positive for TML [AOR = 8.667(95%CI: 1.025–73.249)], or two substances [AOR = 5.000(95%CI: 1.051–23.789)]. The urine samples of commercial drivers tested positive for psychoactive substances and nicotine exposure. However, positivity for a psychoactive substance or nicotine exposure may not be associated with a history of road traffic accidents. Further studies are recommended.

This review aims to examine the role of probiotics in modulating the gut-derived incretin peptide axis in type 2 diabetes (T2D), with emphasis on GLP-1, related gut peptides such as GLP-2, microbial metabolite signaling, and both conventional and engineered probiotic approaches. Narrative synthesis of literature from PubMed, Scopus, and Google Scholar, using search terms such as 'probiotics', 'GLP-1', 'type 2 diabetes', and 'gut microbiota'. Recent literature from 2015 to 2025 was prioritized, including randomized controlled trials, meta-analyses, systematic reviews, and relevant preclinical studies. Earlier landmark studies were included only when they established foundational mechanisms related to incretin biology, SCFA-FFAR signaling, or GLP-1 secretion physiology. Probiotics promote GLP-1 secretion via SCFAs binding to FFAR2/3 receptors, leading to improved glycemic control in meta-analyses, though with heterogeneity. Engineered probiotics like LgsGPA show superior preclinical efficacy in alleviating hyperglycemia and restoring β-cell function. While conventional probiotics offer benefits, engineered systems represent a promising advancement, requiring further clinical and regulatory development for personalized T2D therapy.

We investigate effects of the density of states of condensed matter on the electronic excitations triggered by penetrating keV ions, in a systematic study of energy deposition along multiple well-defined channeling trajectories. We measure the specific energy deposition of ions with keV energies transmitted through Si-a band gap material-in the form of single-crystalline, self-supporting membranes. Energy transfers observed for Ne ions along the 〈100〉, 〈211〉, and 〈111〉 channeling orientations agree well in magnitude with predictions from density functional theory for the expected unperturbed electron densities in an electron gas. This agreement indicates that, along channeling trajectories, the interaction is dominated by conduction and valence electrons, with atomic (core-electron) processes largely suppressed. In contrast, for H and He ions, the predicted values are found systematically higher than the measured values. Non-linearities in the energy dependence of the specific energy deposition of Ne ions are found along all studied low-index orientations, with an inverted behavior observable for random in comparison to channeling orientation. In this context, we discuss the experimental challenges of limiting selected trajectories for the lowest velocities studied, which can mask effects of electronic excitation thresholds in the target electronic system. The new insights shed also light on earlier studies reporting a complex scaling of energy deposition with excitation thresholds, or even their apparent absence.

Short-TE Proton Magnetic Resonance Spectroscopy (SPMRS) allows non-invasive, radiation-free detection of biomolecules including key brain metabolic biomarkers for neurological diseases. However, SPMRS also contains signals from macromolecules, lipids and baseline. Existing Deep Learning (DL) quantification methods for SPMRS overlook baseline interference. To address this, we proposed a novel DL quantification incorporating macromolecules, lipids and baseline (called background signal). First, background signal generators were built by capturing feature distributions of 200 in vivo background signals. Then, the synthetic SPMRS spectra were generated, composed of synthetic metabolite components based on the quantum mechanical and exponential models, background signal generated by the background generator and noise. Finally, the synthetic SPMRS were used to train the advanced DL quantification model QNet (our earlier study). The proposed DL method was validated on a large-scale healthy human brain dataset (BigGABA) and our collected data from different manufacturers (totaling 216 spectra). Furthermore, it was applied to classification of minimal hepatic encephalopathy (totaling 176 spectra), highlighting its clinical potential. We proposed and validated a novel deep learning-based quantification method for SPMRS which is explicitly taken into account the background effect. The proposed method is incorporated the background effect into the DL framework of SPMRS quantification, and DL quantification of SPMRS is utilized for the clinical diagnosis of minimal hepatic encephalopathy.

ABSTRACT Aim To update the Asia‐Pacific League of Associations for Rheumatology (APLAR) treatment recommendations for rheumatoid arthritis (RA) by incorporating new evidence and reassessing the validity of previous guidance: Methods A literature search for relevant publications from January 2018 to August 2023 was conducted, supplemented by earlier studies where relevant. Recommendations were formulated based on this evidence and refined through a modified‐Delphi process during a series of online meetings. The quality of evidence and strength of recommendations were assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results This update comprises 14 statements that achieved consensus during the meetings. Topics covered include measurement of disease activity and treatment response, the use of conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs), the use of targeted therapies, vaccination and screening for infections and the use of DMARDs during pregnancy. The recommendations address the selection of disease activity scores, initiation and intensification of therapy using csDMARDs and targeted therapies, and management of RA in patients at risk of reactivation of infectious diseases. These recommendations are discussed in the context of the clinical landscape encountered in the Asia‐Pacific region. Conclusion These updated recommendations complement previous APLAR guidelines and aim to support best practice management of RA across the Asia‐Pacific region. They provide a practical framework for national rheumatology associations to develop local guidelines adapted to their specific needs and clinical practice.

ABSTRACT Introduction Earlier studies focusing on global self-esteem in pregnant women have identified a number of risk factors for low global self-esteem and have compared global self-esteem during pregnancy and after childbirth. However, there is a lack of research on the specific self-esteem components except for body image. This study compared global self-esteem, specific self-esteem components, and identity integration in pregnant and non-pregnant women, and examined selected correlates of these variables. Methods The study included 394 women: 285 non-pregnant women aged 18–65 (M = 34.93; SD = 9.23), and 109 pregnant women aged 22–41 (M = 30.49; SD = 3.50). The assessments were performed using the Multidimensional Self-Esteem Inventory developed by O’Brien and Epstein, and enabling measurement of global self-esteem, eight specific self-esteem components, and identity integration. Independent-samples t tests and correlational analyses were used, with supplementary ANCOVAs adjusting for age, BMI, and motherhood history. Results Pregnant women scored higher than non-pregnant women on global self-esteem, identity integration, and several specific self-esteem components. After adjustment, pregnancy status remained significant for global self-esteem, competence, lovability, likeability, moral self-approval, and identity integration, but not for body appearance, body functioning, or self-control. In the pregnant group, higher pre-pregnancy BMI was associated with less favourable body-related self-evaluations, self-control, and defensiveness. Pre-pregnancy physical activity was associated with higher body appearance, self-control, likeability, and body functioning. Discussion The present study suggests there are significant differences in self-esteem and identity integration between pregnant and non-pregnant women and highlights the importance of multidimensional measurement of self-esteem in pregnant women.

Electron bifurcation networks split electron pairs into strongly and weakly reducing pools at low thermodynamic cost. Bifurcating enzymes typically use two-electron cofactors with inverted reduction potentials. The advantages of inverted potentials remain unclear, as earlier studies on generic free energy landscapes showed that both normal and inverted potentials can support efficient steady-state bifurcation and confurcation. Here, we examine how potential inversion affects steady-state and pre-steady-state bifurcation and confurcation kinetics by modeling redox substrates as finite pools, to better represent finite biological systems. We confirm that both potential orderings support efficient steady-state bifurcation and confurcation. However, only inverted potentials suppress short-circuiting and reduce energy dissipation in the pre-steady-state regime of bifurcation and confurcation when the transport network is launched in an electron-depleted state. These findings suggest that when metabolism switches frequently between bifurcation and confurcation, where steady state is not maintained, inverted potentials at the bifurcating site confer an energetic advantage.

To update previous meta-analyses by evaluating the association between body mass index (BMI) categories (underweight, overweight, and obesity) and gallbladder cancer (GBC) risk, and to compare findings between earlier and more recent studies. A systematic search of PubMed and Web of Science identified 10 observational studies published between January 2017 and May 2025. Studies reporting risk ratios (RRs), hazard ratios, or odds ratios with 95% confidence intervals (CIs) for GBC by BMI category were included. Pooled RRs were calculated using fixed- and random-effects models, and heterogeneity was assessed using I2 statistics. Subgroup analyses compared older with newer studies, and men with women. Twenty-four studies (14 previous, 11 new) were included. The underweight group showed a a 5% increased possible risk of GBC (fixed-effects RR = 1.05, 95% CI: 0.89-1.24), but there was no clear evidence as statistical significance was not demonstrated. The overweight group was associated with a 19% increased risk (random-effects RR = 1.19, 95% CI: 1.11-1.27), and obesity with a 69% increased risk (random-effects RR = 1.69, 95% CI: 1.51-1.88). Recent studies reported higher RRs for the overweight and obesity groups compared with earlier studies. Excess body weight is significantly associated with increased GBC risk, with stronger associations reported in recent studies. Underweight also suggests a possible positive association. These findings emphasize the importance of weight management in GBC prevention strategies. Prospero registration ID: CRD420251089832.

ABSTRACT The origins of the large form of the land snail Cornu aspersum known in the snail breeding industry as ‘Helix aspersa maxima’ remain enigmatic. Here, we tested the hypothesis that it is a distinct subspecies of C. aspersum, which represents a mitochondrial lineage sister of all remaining haplotypes in this species. We analysed 2-gene and mitogenomic alignments of a representative set of C. aspersum lineages. We show that there is no evidence for a split between ‘maxima’ and the typical C. aspersum in the mitochondrial data. Instead, the sister relationship recovered in an earlier study was a phylogenetic artifact caused by an extremely elevated mitochondrial substitution rate of ‘maxima’. The sequences of ‘maxima’ are in fact nested among those of typical C. aspersum. Based on the origin of the sequences most similar to that of ‘maxima’, and considering available information on the origins of its heliciculture stock, we suggest that ‘maxima’ in the sense of a large-bodied C. aspersum with black mantle margins has originated from the northeast of Morocco.

Academic anxiety negatively impacts students' performance and well-being. Although AI technologies are increasingly used in education, findings on their effectiveness in reducing academic anxiety remain mixed. This meta-analysis quantified the overall effect of AI interventions on academic anxiety and identified potential moderators. A systematic search identified 22 studies with 30 independent effect sizes. Robust variance estimation with random-effects models was used. Subgroup analyses and Q-tests were conducted. AI interventions showed a significant moderate overall effect on reducing academic anxiety (g = - 0.65, 95% CI [- 1.07, - 0.22], p < .01). Moderator analyses revealed: (a) test anxiety and general academic anxiety had significant effects, whereas mathematics, foreign language, and learning anxiety did not; (b) intelligent tutoring systems and robotics produced significant effects, but chatbots and virtual technology did not; (c) primary and middle school effects were marginally significant, university effects non‑significant; (d) Eastern cultural context showed a significant effect, Western and Islamic contexts did not; (e) effects sustained from immediate to delayed posttests; (f) post‑2022 studies yielded larger effects than earlier studies (marginally significant difference); (g) smaller‑sample studies tended to produce larger effect sizes. However, Q‑tests for most moderators were non‑significant (p > 0.05), indicating observed differences are descriptive rather than statistically robust. AI interventions significantly reduce academic anxiety with a moderate effect size. Although efficacy varies descriptively across several factors, most subgroup differences are not statistically significant. Future research should employ rigorous experimental designs, longer follow‑ups, and meta‑analytic structural equation modeling to test underlying mechanisms.