bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epiberberine Improves Hyperglycemia and Ameliorates Insulin Sensitivity in Type 2 Diabetic Mice
Authors: Ma Xiaohong , Shi Yufeng , Shang Zhitao 
Published: January 2025

ABSTRACTAimType 2 diabetes mellitus (T2DM) is a metabolic syndrome characterised by absolute or relative insufficiency of insulin secretion. The alkaloids from Rhizoma coptidis have potential hypoglycemic effects. Epiberberine (EPI), a protoberberine alkaloid extracted from Rhizome coptidis, has been found to regulate lipid metabolism. Our study aimed to investigate the antidiabetic effects of EPI on mice with T2DM, as well as its underlying mechanism.MethodsThe T2DM model in mice was established using a combination of high‐fat diet and streptozotocin. Animals were divided into the control, T2DM, EPI‐low dose (50 mg/kg EPI), EPI‐medium dose (100 mg/kg EPI), EPI‐high dose (200 mg/kg EPI) and metformin (MTF) (200 mg/kg MTF) groups. Body weight, water/food intake, serum lipids, blood glucose tolerance, insulin sensitivity, histopathological alterations, insulin signalling pathway and inflammation‐related pathways in each group were detected.ResultsEPI significantly reduced blood glucose levels and water/food intake in T2DM mice. EPI reduced the levels of total cholesterol, total triglyceride, low‐density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase, and elevated the levels of high‐density lipoprotein cholesterol in serum. EPI effectively improved oral glucose tolerance, alleviated hepatic insulin resistance, decreased glycosylated haemoglobin levels and increased liver glycogen content. EPI ameliorated the histopathological alterations of skeletal muscle and liver in T2DM mice. EPI stimulated the insulin signalling pathway by increasing glucose transporter type 4 levels and activating insulin receptor substrate‐1, phosphatidylinositol 3‐kinase and protein kinase B in skeletal muscle and liver. EPI reduced the levels of proinflammatory cytokine in serum and inhibited the activation of mitogen‐activated protein kinase signalling in skeletal muscle and liver of diabetic mice.ConclusionOverall, these data demonstrate that EPI alleviates the symptoms of T2DM, providing new insights into EPI as a therapeutic compound for the alleviation of T2DM.
Evolution and diversification of the momilactone biosynthetic gene cluster in the genus Oryza
Authors: Priego‐Cubero Santiago , Liu Youming , Toyomasu Tomonobu , Gigl Michael , Hasegawa Yuto , Nojiri Hideaki , Dawid Corinna , Okada Kazunori , Becker Claude 
Published: January 2025

Summary
Plants are master chemists and collectively are able to produce hundreds of thousands of different organic compounds. The genes underlying the biosynthesis of many specialized metabolites are organized in biosynthetic gene clusters (BGCs), which is hypothesized to ensure their faithful coinheritance and to facilitate their coordinated expression. In rice (Oryza sativa), momilactones are diterpenoids that act in plant defence and various organismic interactions. Many of the genes essential for momilactone biosynthesis are grouped in a BGC.
We applied comparative genomics of diploid and allotetraploid Oryza species to reconstruct the species‐specific architecture, evolutionary trajectory, and sub‐functionalisation of the momilactone biosynthetic gene cluster (MBGC) in the Oryza genus.
Our data show that the evolution of the MBGC is marked by lineage‐specific rearrangements and gene copy number variation, as well as by occasional cluster loss. We identified a distinct cluster architecture in Oryza coarctata, which represents the first instance of an alternative architecture of the MBGC in Oryza and strengthens the idea of a common origin of the cluster in Oryza and the distantly related genus Echinochloa.
Our research illustrates the evolutionary and functional dynamics of a biosynthetic gene cluster within a plant genus.
Intermittent theta burst stimulation for negative symptoms in schizophrenia patients with moderate to severe cognitive impairment: A randomized controlled trial
Authors: Li Jing , Jiang Dan , Huang Xingyu , Wang Xiao , Xia Tingting , Zhang Wei 
Published: January 2025

AimsThis study aims to assess the therapeutic effects of intermittent theta burst stimulation (iTBS) targeting the bilateral dorsomedial prefrontal cortex (DMPFC) on negative symptoms in patients with schizophrenia, utilizing functional near‐infrared spectroscopy for evaluation.MethodsThirty‐five schizophrenia patients with negative symptoms and moderate to severe cognitive impairment were randomly assigned to a treatment group (n = 18) or a control group (n = 17). The treatment group received iTBS via bilateral DMPFC. Negative symptoms, cognitive function, emotional state, and social function were assessed using Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Montreal Cognitive Assessment (MoCA), Calgary Depression Scale for Schizophrenia (CDSS), and Social Dysfunction Screening Questionnaire (SDSS) scales at pretreatment, posttreatment, and follow‐up at 4, 8, and 12 weeks. Brain activation in regions of interest (ROIs) was evaluated through verbal fluency tasks.ResultsPrior to treatment there was no significant difference in the two groups. After 20 iTBS sessions, a significant difference was observed in SANS total score, its related subscales, PANSS total score, and PANSS‐negative symptoms (all P < 0.05). The group‐by‐time interaction showed statistical significance, indicating improvements in negative symptoms and related dimensions over time, with therapeutic effects persisting for at least 8 weeks posttreatment. Prior to treatment, there were no significant differences in activation across all ROIs between the two groups. Posttreatment, the activation of right inferior frontal gyrus (t = 2.19, P = 0.036) and right frontal eye field (t = 2.14, P = 0.04) in the treatment group was significantly higher than in the control group.ConclusionsiTBS stimulation of bilateral DMPFC demonstrates therapeutic effects in improving negative symptoms in schizophrenia patients, and this treatment approach has the potential to enhance activation within the prefrontal cortex.
Associations Between Mental Disorders, Personality Disorders, and Filicide‐Suicide and Parental Suicide: A Nationwide Cohort Study
Authors: Yen Cheng‐Fang , Chen Yi‐Lung 
Published: January 2025

AimFilicide‐suicide represents a critical intersection of psychiatric and familial crises, yet the literature remains scant on differentiated risk profiles among family members. This study addresses a gap in understanding the specific mental health correlates of filicide‐suicide, especially within a comprehensive family context, distinct from traditional parental or child‐focused perspectives.MethodThis study used the Taiwan National Health Insurance Research Database to identify a nationally representative sample of families from 2004 to 2020, with continuous monitoring extending into 2021. Families were classified into those affected by filicide‐suicide, parental suicide, and those without such incidents. Multinomial logistic regression was conducted to explore the association between family status and mental health. Analyses of effect modification were conducted to evaluate whether low‐income status modified these relationships.ResultsThe study encompassed 1,898,299 families, revealing that filicide‐suicide is notably rare, with an incidence of 1.64 deaths per 100,000 newborn children from 2004 to 2020, with an increasing trend observed after 2014. Fathers and children in filicide‐suicide families had the highest prevalence of mental disorders, followed by those in parental‐suicide families and then other families (those where no child has been recorded as a homicide victim and no parent has committed suicide). There was a tendency for stronger associations between filicide‐suicide families and paternal schizophrenia as well as autistic spectrum disorder in children among low‐income families.ConclusionThe findings underscore the profound impact of severe mental disorders within the familial framework, emphasizing the need for an integrated approach to mental health care that considers the familial context in order to better predict and prevent such devastating events.
Goodness‐of‐fit testing based on graph functionals for homogeneous Erdös–Rényi graphs
Authors: Brune Barbara , Flossdorf Jonathan , Jentsch Carsten 
Published: January 2025

AbstractThe Erdös–Rényi graph is a popular choice to model network data as it is parsimoniously parameterized, straightforward to interpret and easy to estimate. However, it has limited suitability in practice, since it often fails to capture crucial characteristics of real‐world networks. To check its adequacy, we propose a novel class of goodness‐of‐fit tests for homogeneous Erdös–Rényi models against heterogeneous alternatives that permit nonconstant edge probabilities. We allow for both asymptotically dense and sparse networks. The tests are based on graph functionals that cover a broad class of network statistics for which we derive limiting distributions in a unified manner. The resulting class of asymptotic tests includes several existing tests as special cases. Further, we propose a parametric bootstrap and prove its consistency, which avoids the often tedious variance estimation for asymptotic tests and enables performance improvements for small network sizes. Moreover, under certain fixed and local alternatives, we provide a power analysis for some popular choices of subgraph counts as goodness‐of‐fit test statistics. We evaluate the proposed class of tests and illustrate our theoretical findings by simulations.
Collaborative global learning within an integrated STEM professional development using children's literature
Authors: Asim Sumreen , Haines Sarah , Wieselmann Jeanna , Menon Deepika 
Published: January 2025

AbstractElementary‐level teachers often express the need for assistance and support in teaching integrated science, technology, engineering, and mathematics (STEM) lessons. Many lack content knowledge in these disciplines, and many also report a lack of adequate opportunities to teach these subjects during their preservice programs or their in‐service careers. We addressed this need by offering online professional development (PD) opportunities in integrated STEM, using model lessons that are anchored in the BSCS 5E instructional model, also known as the learning cycle. Our broader goal is to establish a professional learning community for both preservice and in‐service elementary teachers focused on integrated STEM education. We based our design and implementation of an engineering‐focused PD sequence on research literature, integrating STEM content areas and emphasizing key factors for maximizing impact, such as active learning, content focus, coherence, duration, and participant engagement. In this article, we outline the structure and describe the activities we conducted over the summer, which included elements of collaboration, interaction, and reflection. Our team also chose to incorporate picture books featuring international STEM role models, like Zaha Hadid, in the book titled The World is not a Rectangle: A Portrait of Architect Zaha Hadid by Jeannette Winter. The insights gained from this iteration of the PD will inform the planning of future online PD offerings for elementary teachers.
Mean relative error and standard relative deviation
Authors: Chatfield Mark D. , Marquart‐Wilson Louise , Dobson Annette J. , Farewell Daniel M. 
Published: January 2025

AbstractStatistics on the natural log scale, such as differences, regression coefficients, and standard deviations, frequently arise when analyzing log‐transformed data or modeling binary, count, or time‐to‐event data. The statistical properties of log‐transformed estimators (for example, log odds ratio estimators) frequently appear in statistical articles. Understanding the magnitude of these quantities can be useful. Remarkably, many can be readily interpreted, without exponentiation. In this note, we introduce four new interpretations. While a log‐scale standard deviation can be interpreted as an approximate coefficient of variation describing variation about an arithmetic mean, we argue it can be more useful to interpret it exactly as a “standard relative deviation” describing variation about a geometric mean. For positive‐valued estimators, we show how the standard error of a log‐transformed estimator can be interpreted as the “standard relative error” describing the precision of the untransformed estimator. We also show how the bias and root mean squared error of a the log‐transformed estimator can be interpreted as the “mean relative error” and “root mean squared relative error” of the untransformed estimator. We illustrate the usefulness of our interpretations for (i) the usual scale parameter of a lognormal distribution, (ii) statistical properties of a log odds ratio estimator, and (iii) a single measure of the precision of an odds ratio estimator which agrees with its usual, asymmetric 95% confidence interval.
Physiological rhythms and metabolic regulation: Shining light on skeletal muscle
Authors: Betts James A. , Bowden Davies Kelly A. , Smith Harry A. , Hawley John A. 
Published: January 2025

AbstractMetabolic regulation is essential for maintaining homeostasis in response to fluctuating dietary nutrient availability. In this review, we explore how metabolic health can be affected by the temporal alignment between daily behavioural patterns (e.g., eating, physical activity and sleep) and recurring cycles in underlying physiology (e.g., ‘circadian’ rhythms). Misalignment within and/or between these patterns and cycles can lead to metabolic dysregulation, increasing the risk of chronic disease states such as obesity, type 2 diabetes and cardiovascular disease. Conversely, metabolic health can be improved by strategically aligning certain behavioural patterns with endogenous rhythms in physiology. Dietary interventions based upon this reasoning are referred to as chrono‐nutrition strategies. Skeletal muscle is an important tissue in relation to both whole‐body metabolism and behaviour and plays a central role in how physiological rhythms respond to the timing of nutrient delivery/availability. Few studies have examined rhythms in metabolism within human skeletal muscle, providing opportunities to advance current understanding of how nutrient timing affects muscle metabolism.
Cardiac muscle contracts more efficiently at lower contraction frequencies
Authors: Pham Toan , Taberner Andrew J. , Han June‐Chiew 
Published: January 2025

AbstractThis study investigated how contraction frequency impacts the mechano‐energetics of cardiac muscle performing mechanical work. Left‐ventricular trabeculae were isolated from rat hearts and mounted in our work‐loop calorimeter to assess their function at physiological temperature (37°C) across three stimulation frequencies, 2 Hz, 3.5 Hz and 5 Hz, in a randomised sequence. Each trabecula was subjected to two experimental protocols: work‐loop contractions under a range of afterloads and isometric contractions under a range of muscle lengths. Two contraction protocols allowed the partition of the various components of energy expenditure during cardiac contraction. By simultaneously measuring force–length work and heat output, mechanical efficiency was calculated over a range of afterloads to determine the peak value. Our findings revealed that force production, activation heat (energy associated with Ca2+ cycling) and cross‐bridge heat were unaffected by stimulation frequency. Trabeculae produced greater work output per twitch at 2 Hz and 3.5 Hz than at 5 Hz. Positive correlations among work output, shortening extent and mechanical efficiency were detected. From these findings it was concluded that the higher work output at lower frequencies is associated with greater extent of shortening, which correlates to greater mechanical efficiency. This study highlights the mechano‐energetic advantage of ventricular trabeculae in terms of increased work output and energy efficiency gained from operating at lower contraction frequencies, supporting the notion that heart rate reduction produces direct benefits on cardiac energetics.
‘Muscular wisdom’ revisited: Decaying rates of stimulation mitigate torque loss
Authors: Dudani Raaj A. , Zero Alexander M. , Rice Charles L. 
Published: January 2025

AbstractDuring a sustained high‐intensity isometric maximal voluntary contraction (MVC), declining motor unit firing rates (MUFRs) accompany torque loss. This decline (∼50% over 60 s) helps to maintain torque by preserving peripheral electrical propagation and matching the slowing contractile properties with torque loss (i.e., ‘muscular wisdom’). However, it has been suggested that reduced MUFRs contribute to torque loss. Here, we compared torque loss between constant and decaying rates of electrical stimulation to mimic MUFRs reported during MVCs. The dorsiflexors of 8 males and 5 females (21–30 years) underwent three 60 s muscle fatiguing conditions: (1) sustained MVC; (2) constant high‐frequency electrical stimulation (40 Hz); and (3) exponentially decaying stimulation rate (from 40 to 20 Hz). The decaying rate demonstrated less torque loss compared with the sustained high‐frequency stimulation and the MVC conditions (P < 0.01). Furthermore, torque increased (by ∼17%, P < 0.005) when the constant high‐frequency condition was switched to 20 Hz for 2 s at task termination. Conversely, torque loss was accelerated when the decaying stimulation rate was switched from 20 to 40 Hz for 2 s at task termination (by ∼16%, P < 0.001). Following all conditions, evoked twitch responses slowed (by 29%–77%, P < 0.01) but M‐wave amplitude was reduced only for the constant high‐frequency condition (by ∼23%, P < 0.01). Thus, the reduction in stimulation rates maintained optimal activation by matching the fatigue‐induced contractile slowing in combination with preserved peripheral electrical conductance. Therefore, reducing the activation rate preserves torque, rather than contributing to torque loss during high‐intensity contractions, thereby supporting the muscle wisdom hypothesis.
Exergetic Efficiency of Reverse Osmosis Desalination Systems: Definitions and Discussions
Authors: Wang Yongqing , Morosuk Tatiana , Cao Wensheng 
Published: January 2025

Abstract
Reverse osmosis (RO) desalination is the dominant desalination technology worldwide. The exergetic efficiency—which is recognized as a true measure from a thermodynamic viewpoint—of RO systems has been addressed by many researchers, but the inconsistencies in existing definitions prevent not only objective evaluation of the exergetic performance of an individual RO system, but also a logical comparison of the results among different systems and studies. Strictly following the thermodynamic and exergoeconomic principles, this study presents general and consistent definitions of exergetic efficiency for RO systems, aiming to promote uniformity in this important criterion. Considering the purpose and parametric features of RO systems, total exergy is decomposed into chemical and physical (mechanical plus thermal) exergies. The exergetic efficiencies of over 50 cases are calculated, and the results from different relationships and studies are compared and discussed. For the first time, the exergetic efficiency of thermally-enhanced RO systems is discussed, and the influence of thermal exergy consumption and the thermal exergy increments of permeate and brine is analyzed. Furthermore, the reasons behind the significant deviations in the results of some studies are revealed, and the defects or even mistakes in some of the existing definitions are pointed out. This work clarifies the definition and improves the understanding of the exergetic efficiency of RO desalination systems.
Physical Activity Habits and Incident First-Ever Stroke in Middle-Aged Adults—A Prospective Cohort Study
Authors: Vahlberg Birgit , Ribom Eva , Wennberg Patrik , Söderberg Stefan 
Published: January 2025

Background: Lifestyle affects the risk of cardiovascular events such as myocardial infarction and stroke. Several lifestyle factors, such as physical activity (PA), are modifiable, and in this study, we examined the association between leisure-time PA habits and the risk of a first-ever stroke. Methods: This prospective study included residents in Västerbotten, Sweden, who participated in the Västerbotten Intervention Programme at 40, 50, and 60 years of age. Altogether, 31,855 individuals (50.5% women, mean age: 42.6 [6.9] y at baseline) participated between 1989 and 2016. Leisure-time PA was categorized as irregular (never/now and then) or regular (once a week/2 or 3 times a week/more than 3 times a week). Changes in PA were compared between examinations (10 y apart). Cases of stroke were validated according to World Health Organization MONICA (Monitoring Trends and Determinants of Cardiovascular Disease) criteria. The risk related to changes in leisure-time PA was estimated using a multivariable Cox regression model. Results: During an average follow-up of 9.8 years (4.4), 609 incident first-ever stroke cases occurred (1.9%). A multivariable model showed that, compared with individuals with irregular PA at both examinations, those reporting regular PA over time had a lower risk of stroke (hazard ratio: 0.78, 95% CI, 0.61–0.99). Conclusion: Middle-aged adults who maintained regular PA during their leisure time over 10 years had a lower risk of a first-ever stroke. This association is probably partly mediated by lower body mass index and a reduced risk of hypertension and diabetes.