bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Hope for the Patients of Non‐Alcoholic Steatohepatitis: FDA Gives Green Signal for Resmetirom Use
Authors: Hasan Abdul Haseeb , Abid Muhammad Ali , Abid Muhammad Hafi , Suhail Laiba , Nazir Abubakar 
Published: January 2025

ABSTRACTBackground and AimsNon‐Alcoholic Steatohepatitis (NASH), a severe form of Non‐Alcoholic Fatty Liver Disease (NAFLD), is characterized by inflammation and fibrosis in the liver, often progressing to cirrhosis and hepatocellular carcinoma. Despite its rising prevalence and significant disease burden, effective pharmacological treatments have been limited to lifestyle modifications and surgical interventions. Recently, resmetirom, a thyroid hormone receptor‐β agonist, received FDA approval for treating NASH, offering new hope to patients. This review explores the current understanding of NASH and the role of resmetirom as a breakthrough therapeutic option.MethodsThis study is a comprehensive literature review analyzing peer‐reviewed articles, clinical trial data, and public health reports. No original analyses were conducted, and no statistical software was utilized in this review.ResultsResmetirom demonstrated efficacy in resolving NASH without fibrosis progression and improving fibrosis scores in patients with biopsy‐confirmed NASH. In a randomized Phase 3 trial, significant histological improvements were observed in 25.9% and 29.9% of patients receiving 80 and 100 mg doses, respectively, compared to 9.7% in the placebo group. Similar trends were noted in fibrosis improvement, with 24.2% and 25.9% of patients showing ≥ 1 stage improvement compared to 14.2% in the placebo group. Adverse effects, including nausea and diarrhea, were reported more frequently in the treatment groups, but the rates of serious adverse events were comparable across groups.ConclusionThe approval of resmetirom marks a significant advancement in the treatment of NASH, addressing the limitations of lifestyle‐based interventions. As the obesity epidemic drives the increasing prevalence of NASH, resmetirom provides a promising therapeutic option, paving the way for improved patient outcomes and future research.
Enhanced River Connectivity Assessment Across Larger Areas Through Deep Learning With Dam Detection
Authors: Zhang Xiao , Liu Qi , Gui Dongwei , Zhao Jianping , Chen Yu , Liu Yunfei , Martínez‐Valderrama Jaime 
Published: January 2025

ABSTRACTMonitoring river connectivity across large regions is essential for understanding hydrological processes and environmental management. However, comprehensive assessments of river connectivity are often hindered by inaccurate dam databases, which are biased towards larger dams while overlooking smaller or low‐head dams. To enhance the accuracy of river connectivity assessments, we developed three advanced convolutional neural networks (CNNs; YOLOv5, Advance‐You Only Look Once [YOLO], and Faster R‐CNN) to accurately classify dams and evaluate river connectivity using high‐resolution (1 m) remote sensing imagery. The evaluation results showed that Advance‐YOLO performs best with an average mean average precision (mAP) of 86.6%, while Faster R‐CNN performs mediocrely with an average mAP of 77.9%. Applying the well‐trained model in the Tarim River Basin (China), one of the largest inland river basins around the globe, we found that there are currently 135 dams in total on the Tarim River and its sources. Conversely, the existing public dam database underestimates 85.9% of the dams. Notably, we found a 14.3% decline in river connectivity of the Tarim River over the past decade, and the current dam density of the Tarim River and its four source rivers is 1.12 per 10 000 km2. However, the existing public dam database overestimated river connectivity by 83.9%. The model developed here enhances river connectivity assessment across larger areas over a long period, thereby fostering more advanced research on hydrological processes and effective water resource management.
Toward Automated Scientific Discovery in Hydrology: The Opportunities and Dangers of AI Augmented Research Frameworks
Authors: Eythorsson Darri , Clark Martyn 
Published: January 2025

ABSTRACTThis commentary explores the potential of artificial intelligence (AI) to transform hydrological modelling workflows. We introduce a prototype AI‐assisted framework called INDRA (Intelligent Network for Dynamic River Analysis) that leverages a multi‐agent architecture composed of specialised large language models (LLMs) to assist in model conceptualization, configuration, execution, and interpretation. INDRA integrates with CONFLUENCE, a comprehensive modelling framework, to provide context‐aware guidance and automation throughout the modelling process. We discuss the opportunities and dangers of AI‐augmented research frameworks, emphasising the importance of maintaining human oversight while harnessing AI's potential to enhance efficiency, reproducibility, and scientific understanding. We argue that AI‐assisted workflows could democratise advanced hydrological modelling, enabling researchers worldwide to address critical water resources challenges, particularly in understudied regions. While acknowledging potential biases and risks, we advocate for responsible AI integration to catalyse a new paradigm in hydrological science.
Impact of the WHO safe childbirth checklist on birth attendant behavior and maternal‐newborn outcomes: A systematic review and meta‐analysis
Authors: Fernández‐Elorriaga María , Fifield Jocelyn , Semrau Katherine E. A. , Lipsitz Stuart , Tuller Danielle E. , Mita Carol , Cho Chelsea , Scott Heather , Taha Ayda , Dhingra‐Kumar Neelam , Moran Allisyn , Molina Rose L. 
Published: January 2025

AbstractBackgroundThe intrapartum period is critical for reducing maternal and perinatal morbidity and mortality. The WHO's Safe Childbirth Checklist (SCC) was designed as a reminder of the most critical, evidence‐based practices (EBPs) to improve quality care and reduce preventable complications and deaths.ObjectiveTo assess the impact of SCC on birth attendant behavior and maternal and newborn health outcomes.Search StrategyA systematic review and meta‐analysis was performed searching across five databases from 2009 to 2023.Selection CriteriaWe included randomized controlled trials, quasi‐experimental studies, and pre/post studies.Data AnalysisA meta‐analysis yielded a pooled estimate of relative risk (RR) for adherence to and effectiveness of the SCC.Main ResultsOf 1070 articles identified, 16 were included. Use of the SCC increased adherence to EBPs by 65% (RR 1.65; 95% confidence interval [CI] 1.34–2.02). The behaviors that improved the most were danger sign counseling (RR 12.37; 95% CI 1.95–78.52; P = 0.008) and pre‐eclampsia management (RR 3.43; 95% CI 1.33–8.88; P = 0.011). There was moderate evidence for stillbirth reduction (RR 0.89; 95% CI 0.80–0.99; P = 0.034).ConclusionThere is moderate evidence demonstrating the effectiveness of the SCC in reducing stillbirths and improving adherence to EBPs.
Photobiomodulation Combined With Human Umbilical Cord Mesenchymal Stem Cells Modulates the Polarization of Microglia
Authors: Ma Chunyan , Zhu Hongyu , Cai Yuanhao , Li Na , Han Zhibo , Wu Huancheng , Chen Hongli 
Published: January 2025

ABSTRACTNeuroinflammation plays a key role in the development of neurodegenerative diseases, with microglia regulating this process through pro‐inflammatory M1 and anti‐inflammatory M2 phenotypes. Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) modulate neuroinflammation by secreting anti‐inflammatory cytokines. Photobiomodulation (PBM), a non‐invasive therapy, has demonstrated significant potential in alleviating neuroinflammation. This study examines the combined effects of PBM and hUCMSCs in an in vitro microglial inflammation model and an LPS‐induced mouse model. The results show that PBM‐pretreated hUCMSCs promoted M2 polarization and improved cognitive function in mice by downregulating the Notch signaling pathway, suggesting a promising new approach for treating neurodegenerative diseases.
Biomechanical comparison of all‐inside meniscal suture configurations for posterior root tear: Three conventional stitches versus delta‐grip stitch
Authors: Ishibashi Kyohei , Ishibashi Kyota , Tsushima Takahiro , Sasaki Eiji , Yamauchi Shohei , Kimura Yuka , Ishibashi Yasuyuki 
Published: January 2025

AbstractPurposeThis study aimed to compare the biomechanical properties of four meniscal suture configurations—two simple sutures (TSS), two cinch sutures, a locking loop stitch (LLS), and a delta‐grip stitch (DGS)—for transtibial pullout repair of medial meniscus posterior root tears (MMPRTs) using porcine menisci.MethodsForty porcine menisci were randomly assigned to each suture configuration with all‐inside repair. All specimens were subjected to cyclic loading for 1000 cycles, followed by a load‐to‐failure test. We evaluated displacement after cyclic loading, the ultimate failure load and the mode of failure.ResultsNo significant differences in displacement were observed between the configurations (p = 0.709). The DGS exhibited significantly higher ultimate failure loads (281.4 ± 53.5 N) compared to TSS (166.8 ± 84.5 N) and the LLS (119.7 ± 46.7 N) (p = 0.006 and p < 0.001, respectively). Suture breakage was observed in the DGS group, while meniscus cutout was observed in the other suture configuration models.ConclusionThe results suggest that the DGS provides superior fixation strength and enhances MMPRT repair outcomes.Level of EvidenceLevel IV.
Uncovering a new family of conserved virulence factors that promote the production of host‐damaging outer membrane vesicles in gram‐negative bacteria
Authors: Goman Audrey , Ize Bérengère , Jeannot Katy , Pin Camille , Payros Delphine , Goursat Cécile , Ravon‐Katossky Léa , Murase Kazunori , Chagneau Camille V. , Revillet Hélène , Taieb Frédéric , Bleves Sophie , David Laure , Meunier Etienne , Branchu Priscilla , Oswald Eric 
Published: January 2025

AbstractCprA is a short‐chain dehydrogenase/reductase (SDR) that contributes to resistance against colistin and antimicrobial peptides. The cprA gene is conserved across Pseudomonas aeruginosa clades and its expression is directly regulated by the two‐component system PmrAB. We have shown that cprA expression leads to the production of outer membrane vesicles (OMVs) that block autophagic flux and have a greater capacity to activate the non‐canonical inflammasome pathway. In a murine model of sepsis, a P. aeruginosa strain deleted for cprA was less virulent than the wild‐type (WT) strain. These results demonstrate the important role of CprA in the pathogenicity of P. aeruginosa. It is worth noting that CprA is also a functional ortholog of hemolysin F (HlyF), which is encoded by virulence plasmids of Escherichia coli. We have shown that other cryptic SDRs encoded by mammalian and plant pathogens, such as Yersinia pestis and Ralstonia solanacearum are functional orthologs of CprA and HlyF. These SDRs also induce the production of OMVs which block autophagic flux. This study uncovers a new family of virulence determinants in Gram‐negative bacteria, offering potential for innovative therapeutic interventions and deeper insights into bacterial pathogenesis.
A Non‐Centrifugation Method to Concentrate and Purify Extracellular Vesicles Using Superabsorbent Polymer Followed by Size Exclusion Chromatography
Authors: Bergqvist Markus , Lässer Cecilia , Crescitelli Rossella , Park Kyong‐Su , Lötvall Jan 
Published: January 2025

ABSTRACTExtracellular vesicles (EVs) can be isolated and purified from cell cultures and biofluids using different methodologies. Here, we explored a novel EV isolation approach by combining superabsorbent polymers (SAP) in a dialysis membrane with size exclusion chromatography (SEC) to achieve high concentration and purity of EVs without the use of ultracentrifugation (UC). Suspension HEK293 cells transfected with CD63 coupled with Thermo Luciferase were used to quantify the EV yield and purity. The 500 mL conditioned medium volume was initially reduced by pressure ultrafiltration, followed by UC, SAP or a centrifugal filter unit (CFU). Using either of these methods, the EVs were concentrated to a final volume of approximately 1 mL, with retained functionality. The yield, quantified by luciferase activity, was highest with UC (70%–80%), followed by SAP (60%–70%) and CFU (50%–60%). Further purification of the EVs was performed by iodixanol density cushion (IDC) or SEC (Sepharose CL‐2B or 6B, in either 10 or 20 mL columns). Although the IDC and Sepharose CL‐2B (10 mL) achieved the highest yields, the purity was slightly higher (30%) with IDC. In conclusion, combining SAP concentration with CL‐2B SEC is an alternative and efficient way to isolate EVs without using UC.
Revealing the Complex Interaction of Noncoding RNAs, Sirtuin Family, and Mitochondrial Function
Authors: Yuan Ludong , Yin Leijing , Lin Xiaofang , Li Jing , Liang Pengfei , Jiang Bimei 
Published: January 2025

ABSTRACTMitochondria are key organelles that perform and coordinate various metabolic processes in the cell, and their homeostasis is essential for the maintenance of eukaryotic life. To maintain mitochondrial homeostasis and cellular health, close communication between noncoding RNAs (ncRNAs) and proteins is required. For example, there are numerous crosstalk between ncRNAs and the sirtuin (SIRT1–7) family, which is a group of nicotinamide adenine dinucleotides (NAD(+))–dependent Type III deacetylases. NcRNAs are involved in the regulation of gene expression of sirtuin family members, and deacetylation of sirtuin family members can also influence the generation of ncRNAs. This review focuses on the relationship between the two mentioned above and summarizes the impact of their interactions on mitochondrial metabolism, oxidative stress, mitochondrial apoptotic pathways, mitochondrial biogenesis, mitochondrial dynamics, and other mitochondria‐related pathophysiological processes. Finally, the review also describes targeted and appropriate treatment strategies. In conclusion, we provide an overview of the ncRNA‐sirtuins/mitochondria relationship that could provide a reference for related research in the mitochondrial field and help the future development of new biomedical applications in this area.
Spermidine Recovers the Autophagy Defects Underlying the Pathophysiology of Cell Trafficking Disorders
Authors: Díaz‐Osorio Yaiza , Gimeno‐Agud Helena , Mari‐Vico Rosanna , Illescas Sofía , Ramos Jose Miguel , Darling Alejandra , García‐Cazorla Àngels , Oyarzábal Alfonso 
Published: January 2025

ABSTRACTCell trafficking alterations are a growing group of disorders and one of the largest categories of Inherited Metabolic Diseases. They have complex and variable clinical presentation. Regarding neurological manifestations they can present a wide repertoire of symptoms ranging from neurodevelopmental to neurodegnerative disorders. The study of monogenic cell trafficking diseases draws an scenario to understanding this complex group of disorders and to find new therapeutic avenues. Within their pathophysiology, alterations in autophagy outstand as a targetable mechanism of disease, ammended to be modulated through different strategies. In this work we have studied the pathophysiology of two cell trafficking disorders due to mutations in SYNJ1 and NBAS genes. Specifically, we have assesed the autophagic flux in primary fibroblast cultures of the patients and gender/age‐matched controls and whether it could be address with a therapeutic purpose. The results have shaped autophagy as one of the hallmarks of the disease. Moreover, we tested in vitro the effect of spermidine, a natural polyamine that acts as an autopagy inductor. Due to the positive results, its efficacy was evaluated later on the patients as well, in a series of n‐of‐1 clinical trials, achieving improvement in some clinical aspects related to motricity and cognition. Defining autophagy alterations as a common feature in the pathophysiology of cell trafficking disorders is a great step towards their treatment, as it represents a potential actionable target for the personalized treatement of these disorders.
Fractal Performance Under Magnetization Procedures of Fractional Memristive Wilson Neuron Dynamical Model
Authors: Abro Kashif Ali , Mahariq Ibrahim 
Published: January 2025

ABSTRACTThe non‐integer neuron dynamical models are feasible for accurate prediction and perfect estimation of magnetization and de‐magnetization in complicated physiological environments within reliable fractal‐fractional neuronal modeling. The memristive Wilson neuron model is proposed under the comparative performance of two types of fractal‐fractional differentials with two different types of kernels based on two different memories. The non‐classical memristive Wilson neuron model with and without magnetization is simulated for numerical schemes by means of linear multi‐step integration method. The numerical simulations are traced out by discretizing continuum processes of spatial and time domains for the sake of perfect approximations under singular and non‐singular kernel versus local and non‐local kernel. By applying the powerful methodology of fractal‐fractional differential and integral operators on the memristive Wilson neuron model, the antimonotonicity phenomenon and asymmetric coexisting electrical activities have been explored intensively to widen the neuron‐based engineering applications. Remarkably, our results based on magnetization and de‐magnetization procedures of Wilson neuron model have imitated the neuron activities under electrophysiological environment.
Intermittent Fasting Ameliorates β‐Amyloid Deposition and Cognitive Impairment Accompanied by Decreased Lipid Droplet Aggregation Within Microglia in an Alzheimer's Disease Model
Authors: Wu Liangwei , Zhao Yang , Gong Xiaokang , Liang Zheng , Yu Jing , Wang Jiaquan , Zhang Yuheng , Wang Xiaochuan , Shu Xiji , Bao Jian 
Published: January 2025

ABSTRACTScope: Alzheimer's disease (AD) is the most prevalent form of dementia, lack of effective therapeutic interventions. In this study, we investigate the impact of intermittent fasting (IF), an alternative strategy of calorie restriction, on cognitive functions and AD‐like pathology in a transgenic mouse model of AD. Methods and results: APP/PS1 mice at 6 months were randomly allocated to two dietary groups: one receiving ad libitum (AL) feeding and the other undergoing IF for 1 month. Y maze, Barnes maze, western blotting, and immunofluorescence were employed. Behavioral assessments revealed that the APP/PS1‐IF group demonstrated notable improvements in cognitive function compared to the AL group. Further analysis showed that microglia in the APP/PS1‐IF mice exhibited enhanced phagocytic activity, characterized by prominent enlargement of soma and reduced complexity of their processes. Importantly, IF significantly decreased the accumulation of lipid droplets (LDs) within microglia. These microglia with less LDs may contribute to enhanced β‐amyloid (Aβ) phagocytosis, thereby ameliorating Aβ deposition in the brains of APP/PS1‐IF mice. Conclusion: Our findings demonstrate that IF ameliorates amyloid deposition and cognitive deficits in the AD model mice, which is associated with the reduction of LDs within microglia, providing support for the use of the dietary intervention against AD pathology.
A Computationally Efficient Technique for Dynamic Sensitivity Filtering in Topology Optimization
Authors: Huang Hongbin , Wang Yiming , Wang Haoyin , Wu Bo , Hu Youmin 
Published: January 2025

ABSTRACTIn this paper, we present a novel approach: a dynamic sensitivity filtering technique designed for density‐based topology optimization. Sensitivity filtering methods have found extensive utility in mitigating numerical instabilities. Nevertheless, conventional sensitivity filtering can introduce numerous gray elements along the topology's boundaries, thereby impeding practical manufacturing within real‐world engineering applications. To address this challenge, we propose a dynamic sensitivity filter that adjusts the sensitivity at each iterative step based on the optimization outcomes of the preceding iteration. Through diverse test examples, our method demonstrates the capacity to effectively solve the numerical instability problem while concurrently achieving a nearly pure black and white design, characterized by significantly reduced computational expense and improved structural stiffness.
Structure Preserving Nodal Continuous Finite Elements via Global Flux Quadrature
Authors: Barsukow Wasilij , Ricchiuto Mario , Torlo Davide 
Published: January 2025

ABSTRACTNumerical methods for hyperbolic PDEs require stabilization. For linear acoustics, divergence‐free vector fields should remain stationary, but classical Finite Difference methods add incompatible diffusion that dramatically restricts the set of discrete stationary states of the numerical method. Compatible diffusion should vanish on stationary states, e.g., there should be a gradient of the divergence. Some Finite Element methods allow the natural embedding of this grad‐div structure, e.g., the SUPG method or OSS. We prove here that the particular discretization associated with them still fails to be stationarity preserving. We then introduce a new framework on Cartesian grids based on surface (volume in 3D) integrated operators inspired by Global Flux quadrature and related to mimetic approaches. We can construct constraint‐compatible stabilization operators (e.g., of SUPG‐type) and show that the resulting methods are stationarity and vorticity preserving. We show that the Global Flux approach is even super‐convergent on stationary states; we characterize the kernels of the discrete operators and provide projections onto them.
Isocaloric high‐fat diet decreases motivation in the absence of obesity
Authors: Arbuckle Kenny , Sharma Reema , Drake Frannie E. , Usiyevich Abigail , Usman Sarah , Matikainen‐Ankney Bridget A. 
Published: January 2025

AbstractObjectiveObesogenic diets induce persistent changes in physical activity and motivation. It remains unclear whether these behavioral changes are driven by weight gain or exposure to obesogenic diets themselves. We investigated how exposure to a high‐fat diet (HFD) in the absence of obesity affected physical activity, food motivation, and circadian patterns in mice.MethodsC57Bl6/J mice were given ~80% of their daily calories in an HFD, known as isocaloric feeding, along with ad libitum access to laboratory chow. Weekly weights, physical activity levels, circadian patterns, operant behavior, and peripheral blood metabolic markers were measured to determine how an isocaloric HFD affected behavior and physiology. Following this period, the same cohort was exposed to an ad libitum HFD to monitor changes in weight gain and physical activity.ResultsAn isocaloric HFD did not significantly increase weight or change physical activity levels. An isocaloric HFD decreased motivation for sucrose pellets but did not alter weight gain with ad libitum HFD exposure.ConclusionsAn isocaloric HFD was associated with decreased motivation for sucrose, as observed in reports of rodent models of obesity. These findings suggest that exposure to an obesogenic diet, even in the absence of significant weight gain, can induce behavioral changes associated with obesity.