bluuebunny/crossref_metadata_2025 huggingface dataset:
Urea/Thiourea Imine Linkages Provide Accessible Holes in Flexible Covalent Organic Frameworks and Dominates Self‐Adaptivity and Exciton Dissociation
Authors: Qin Chencheng , Wu Xiaodong , Zhou Wenyan , Li Miao , Bi Shuai , Tang Lin , Huang Hao , Tu Wenguang , Yuan Xingzhong , Ang Edison Huixiang , Sun Weiling , Chen Long , Liu Zhaoli , He Bing , Lyu Lai , Wu Yan , Liu Wen , Wang Hou
Published: November 2024

Unraveling the robust self‐adaptivity and minimal energy‐dissipation of soft reticular materials for environmental catalysis presents a compelling yet unexplored avenue. Herein, a top‐down strategy, tailoring from the unique linkage basis, flexibility degree, skeleton electronics to trace‐guest adaptability, is proposed to fill the understanding gap between micro‐soft covalent organic frameworks (COFs) and photocatalytic performance. The thio(urea)‐basis‐dominated linkage within benzotrithiophene‐based COFs induce the framework contraction/swelling (intralayer micro‐flexibility) in response to tetrahydrofuran or water. Adaptability of micro‐flexible thiourea‐COF with pore hydrophilicity not only contributes to the favorable mass transfer, but also enhances the accessible redox active sites, culminating in nearly 100 % removal of micropollutant with low‐energy dissipation in wastewater. The incorporating urea/thiourea into imine linkage facilitates polarization reduction and exciton dissociation within skeleton wall, inducing strong localization for holes. This transformation facilitates interchain charge transport and unbalanced distribution conducive to oxidative holes‐mediated micropollutant decomposition.
Food for thought: Nutrient metabolism controlling early T cell development
Authors: Werlen Guy , Hernandez Tatiana , Jacinto Estela
Published: November 2024

T cells develop in the thymus by expressing a diverse repertoire of either αβ‐ or γδ‐T cell receptors (TCR). While many studies have elucidated how TCR signaling and gene expression control T cell ontogeny, the role of nutrient metabolism is just emerging. Here, we discuss how metabolic reprogramming and nutrient availability impact the fate of developing thymic T cells. We focus on how the PI3K/mTOR signaling mediates various extracellular inputs and how this signaling pathway controls metabolic rewiring during highly proliferative and anabolic developmental stages. We highlight the role of the hexosamine biosynthetic pathway that generates metabolites that are utilized for N‐ and O‐linked glycosylation of proteins and how it impacts TCR expression during T cell ontogeny. We consider the dichotomy in metabolic needs during αβ‐ versus γδ‐T cell lineage commitment as well as how metabolism is also coupled to molecular signaling that controls cell fate.
Geographic variations of floral traits and pollinator guilds in a specialized pollination mutualism, Kadsura longipedunculata and gall midges
Authors: Hao Kai , Wu You‐Heng , Sun Qi‐Lin , Dong Wen‐Cai , Luo Shi‐Xiao
Published: November 2024

Floral traits exhibit variations in response to both biotic and abiotic factors, potentially leading to dynamic interactions between plants and pollinators. Little is known about whether these geographic variations in floral traits influence species–specific interactions in obligate mutualisms. In this study, variations in flower morphology, color and scent were investigated within and among Kadsura longipedunculata populations. Local midge pollinators across three populations were sampled to examine the plant‐insect dynamics at the geographic scale. Our results suggested dimorphism in androecium color within and among populations. Floral scent analyses suggested quantitative differences in major compounds (terpenes) among populations and between individuals with differing colors, but similar composition of volatile compounds between different color morphs. Stamen chamber size did not differ between different color morphs within the Xinning population. However, it was significantly larger in the Xinning population compared to the Hengshan population. Totally, four pollinating and ovipositing gall midge species were identified in these three populations with shared Resseliella kadsura between the Xinning and Hengshan population and shared Resseliella sp. between the Xinning and Lushan population. The variations in floral traits and pollinator guilds provide new empirical evidence for the dynamic interactions at geographic scales within specialized pollination mutualisms, potentially supporting the geographic mosaic theory of coevolution.
Prehabilitative/rehabilitative exercise, nutrition, and psychological support for bladder cancer: A scoping review of randomized clinical trials
Authors: Briggs Logan G. , Parke Sara C. , Beck Kelsey L. , Sinha Debarshi , Gill Vikram , Van Ligten Matthew J. , Bain Paul A. , Tyson Mark D. , Abdul‐Muhsin Haidar M. , Quillen Jaxon K. , Dodoo Christopher A. , De Luigi Arthur J. , Branstiter Nikki L. , Trinh Quoc‐Dien , Psutka Sarah P.
Published: November 2024

The study of prehabilitation and rehabilitation ([p]rehabilitation) to alleviate the sequelae of bladder cancer and its treatment has generated numerous opportunities to improve the quality of life of bladder cancer survivors. The authors conducted a scoping review of randomized clinical trials (RCTs) to identify knowledge gaps in and research directions for (p)rehabilitative support for those affected by bladder cancer. The authors systematically searched six databases and synthesized key findings from RCTs conducted from January 1, 2004, through March 15, 2022, that enrolled participants with bladder cancer, survivors, or caregivers in outpatient (p)rehabilitative programs (e.g., exercise, nutrition, or psychological support). Outcomes were characterized according to eight prespecified, clinically relevant categories. The search retrieved 10,968 records, 27 of which met the inclusion criteria, and 24 described unique RCTs with 2471 enrolled participants. Of 24 interventions, 17 (71%) yielded statistically significant results for the outcome of interest. Only one RCT included a cost‐effectiveness analysis, and only two characterized the efficacy of interventions for caregivers. Of 11 RCTs involving psychological support, eight yielded statistically significant results, as did nine of 11 RCTs with physical exercise interventions, three of four RCTs with educational interventions, three of four RCTs with nutritional support interventions, one of two RCTs with pharmacologic medications, and zero of one RCT with physical therapy. The most promising interventions for inclusion in multimodal, personalized (p)rehabilitation programs included exercise, stress management training, cognitive training, smoking and alcohol cessation counseling, immunonutrition, stoma education, and penile rehabilitation. Further studies of the cost effectiveness and efficacy for caregivers of such interventions are needed.

Plain Language Summary

In a scoping review of all randomized clinical trials involving prehabilitative or rehabilitative diet, exercise, and psychological support interventions for patients with bladder cancer, survivors, and their caregivers, 17 of 24 (71%) interventions yielded statistically significant improvements in the outcome of interest.

Clinicians should consider implementing such interventions for those affected by bladder cancer.
Enhancing Li+ Transportation at Graphite‐Low Concentration Electrolyte Interface Via Interphase Modulation of LiNO3 and Vinylene Carbonate
Authors: Quan Yin , Cui Xiaoling , Hu Ling , Kong Yueqin , Zhang Xiaojuan , Liang Hongcheng , Zhu Yu , Wang Caiyun , Zhang Ningshuang , Li Shiyou
Published: November 2024

The solvent‐rich solvent sheath in low‐concentration electrolytes (LCEs) not only results in high desolvation energy of Li+, but also forms organic‐rich solid electrolyte interface film (SEI) with poor Li+ conductivity, which hinders Li+ transport at the electrode‐electrolyte interface and greatly limits the application of LCEs. Here, the electrochemical performance of the LCEs is enhanced by dual interfacial modification with LiNO3 and vinylene carbonate (VC) additives. Results show that LiNO3 is preferentially reduced at about 1.65 V to form an inorganic‐rich but incomplete SEI inner layer. The formation of Li3N and LiNxOy inorganic components helps to achieve rapid Li+ transport in the SEI film, and the bare electrode surface caused by the incomplete SEI inner layer provides a place for the subsequent decomposition of VC. Then, at a lower potential of about 0.73 V, VC is reduced to generate the poly(VC)‐rich SEI outer layer, which provides lithium‐philic sites and greatly weakens the interaction between Li+ and ethylene carbonate (EC). The interaction modulates the Li+ solvation structure at the interface and reduces the desolvation energy of Li+. This ingenious design of the bilayer SEI film greatly enhances Li+ transport and inhibits the decomposition of traditional carbonate solvents and the swelling of graphite. As a result, the electrochemical performance of the battery using 0.5 M LiPF6 EC/diethyl carbonate (DEC) + 0.012 M LiNO3 + 0.5 vt% VC is improved to a higher level than the one using 1.0 M LiPF6 EC/DEC electrolyte. This research expands the design strategy and promising applications of LCEs by constructing a favorable SEI to enhance Li+ transport at the electrode‐electrolyte interface.
Sex‐Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans
Authors: Blöcher Jonas A. , Meyer‐Tönnies Marleen J. , Morof Felix , Rönnpagel Vincent , Bethmann Jonas , Vollmer Marcus , Engeli Stefan , Tzvetkov Mladen V.
Published: November 2024

An over‐the‐counter product berberine (a major alkaloid in goldenseal) is a substrate of the uptake transporter OCT1 and the metabolizing enzyme CYP2D6. The two genes exhibit common functional polymorphisms. Approximately 9% of Europeans and white Americans are either poor CYP2D6 metabolizers or poor OCT1 transporters. In this study, we investigated the effects of OCT1 and CYP2D6 polymorphisms on berberine pharmacokinetics in humans. We confirmed in vitro that berberine is an OCT1 substrate (KM of 7.0 μM, CLint of 306 ± 29 μL/min/mg). Common OCT1 alleles *3 to *6 showed uptake reduced by at least 65% and Oct1/2 knockout mice showed 3.2‐fold higher AUCs in liver perfusion experiments. However, in humans, poor OCT1 transporters did not show any differences in berberine pharmacokinetics compared with reference participants. In contrast, CYP2D6 polymorphisms significantly affected berberine metabolism, but exclusively in females. Females who were poor CYP2D6 metabolizers had an 80% lower M1‐to‐berberine ratio. General linear model analyses suggest strong synergistic, rather than additive, effects between female sex and CYP2D6 genotype. Overall, berberine displayed low oral bioavailability, yet females had a 2.8‐fold higher AUC and a 3.6‐fold higher Cmax than males (P < 0.001). These effects were only partially attributable to the sex‐CYP2D6 genotype interaction. In conclusion, despite berberine being an OCT1 substrate, OCT1 deficiency did not affect berberine pharmacokinetics in humans. In contrast, CYP2D6 emerges as a critical enzyme for berberine metabolism in females, but not in males, highlighting sex‐specific differences. We suggest that factors beyond CYP2D6 metabolism are determining berberine's systemic exposure, especially in males (NCT05463003).
Call Blocking Estimation Using Adaptive Channel Reservation for Hand‐Off Calls in Wireless Cellular Network
Authors: Sahu Promod Kumar , Pati Hemanta Kumar , Pradhan Sateesh Kumar
Published: November 2024

The wireless cellular network (WCN) provides services to many users with limited radio resources. In WCN, resource allocation is important to provide the desired quality of service (QoS). Among the two possible types of calls in WCN, hand‐off calls (HCs) have higher priority than new calls (NCs). In this paper, we developed a mathematical model to estimate call blocking using an optimal number of guard channel (GC) for HCs by considering target hand‐off call dropping probability (HCDP). We named this model the optimal guard channel reservation (OCR) policy. This analytical model assumes the long‐term average of the traffic parameters and so is far from making any correlation with the operation of the existing system. In real, the traffic parameters are dynamic. Further, we proposed an optimal adaptive guard channel reservation (OACR) policy to obtain optimal performance. It adjusts the GCs dynamically w.r.t the traffic conditions to keep HCDP below the target. We have implemented the OACR scheme by using a test bed. Finally, we have applied both mathematical model (i.e., OCR policy) and OACR policy to a wireless cellular network, that is, Global System for Mobile Communication (GSM) 900 system.
PARP7i Clinical Candidate RBN‐2397 Exerts Antiviral Activity by Modulating Interferon‐β Associated Innate Immune Response in Macrophages
Authors: Du Xiaoli , Zhou Jiawei , Zhou Yi , Chen Yulong , Kang Yanhua , Zhao Dongjiu , Ye Xiang‐Yang , Wang Liwei , Xie Tian , Zhang Hang
Published: November 2024

Polyadenosine diphosphate‐ribose polymerase 7 (PARP7) acts as a suppressor of the type I interferon (IFN) signaling pathway via suppressing TANK‐binding protein 1 (TBK1). Research study indicates that inhibition of PARP7 could potentially regulate tumor immunity. However, the effect of PARP7 inhibition on innate antiviral immunity in macrophages as well as the underlying mechanism have not been demonstrated else well. We report herein that PARP7 inhibitor clinical candidate RBN‐2397 could augment type I interferon (IFN‐I) production in macrophages by elevating retinoic acid‐inducible gene I (RIG‐I) and stimulator of interferon genes (STING) signaling pathways. Treatment with RBN‐2397 leads to increased pattern recognition ligands‐induced interferon‐β production in primary bone marrow‐derived macrophages (BMDM) and RAW264.7 cells. Additionally, RBN‐2397 suppresses viral replication efficiency in macrophages infected by vesicular stomatitis virus (VSV) and amplifies the expression of interferon‐stimulated chemokine genes (ISGs). Mechanistically, RBN‐2397 promotes TBK1 phosphorylation, consequently leading to the amplified activation of RIG‐I and STING signaling pathways. Furthermore, RBN‐2397 enhances the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2 induced by IFN‐α/β and the expression of chemokine genes in macrophages in response to IFN stimulation. In vivo experiments demonstrated that RBN‐2397 enhances innate antiviral immunity in mice infected with VSV, resulting in increased serum IFN‐β levels, reduced viral loads, and alleviated pulmonary inflammatory responses of the VSV‐infected mice. In conclusion, our findings highlight the potential of RBN‐2397 as a promising antiviral therapeutic agent for enhancing the IFN‐relative antiviral immune defense in host.
Prediction Study of Solid Oxide Fuel Cell Performance Degradation Using Data‐Driven Approaches
Authors: Huo Haibo , Chen Yu , Afun Gifty Pamela , Kuang Xinghong , Xu Jingxiang , Li Xi
Published: November 2024

Performance degradation in solid oxide fuel cells (SOFCs) leads to shorter service life and unexpected downtime. To reduce economic losses and accelerate commercialization, accurately predicting the degradation is conducted in this study. First, a comprehensive analysis of performance degradation through experiments on a real SOFC system is investigated. Then, three dada‐driven robust models, that is, vector autoregressive moving average (VARMA), radial basis function neural network (RBFNN), and neural basis expansion analysis for time series (N‐BEATS) models are proposed to predict the SOFC's performance degradation. Herein, the top 60–90% of the experimental datasets are used for training and the bottom 40–10% for testing. After training, the prediction performance testing of these 3 models is compared with that of the bi‐long short‐term memory networks (bi‐LSTM) and bi‐gated recurrent units (bi‐GRU) models. Simulation results show that both the VARMA and N‐BEATS models are superior to the bi‐LSTM and bi‐GRU models in predicting the performance degradation of the SOFC. While the test performance of the RBFNN model is worst, especially under the top 60% training datasets condition. These indicate it is feasible to respectively establish the VARMA model and the N‐BEATS model for predicting the SOFC's performance degradation.
High‐Entropy Perovskite Oxides for Thermochemical Solar Fuel Production
Authors: Betti Luca Angelo , Bosetti Aldo , Malavasi Lorenzo
Published: November 2024

The increasing global demand for energy, coupled with the need to mitigate climate change, has spurred significant interest in renewable energy sources. Among these, solar energy holds particular promise due to its abundance and potential to be converted into clean fuels through thermochemical cycles. High‐entropy perovskite oxides (HEPOs) have emerged as promising materials for solar thermochemical hydrogen (STCH) production, offering advantages over traditional materials like ceria due to their enhanced thermal stability, flexibility in composition, and lower operating temperatures. Herein, the advantages of HEPOs, including their stability under extreme thermal conditions which is critical for repeated redox cycling in H2 production, are highlighted. The inherent configurational entropy allows for a broader range of element incorporation, leading to improved tunability of physical properties. However, challenges remain, particularly in terms of cost and scalability. To address this, strategies such as the use of more abundant elements and optimized synthesis are discussed. Additionally, the future potential of HEPOs, including their integration into advanced solar reactors, is explored, and how computational methods can be employed to predict new high‐entropy compositions with improved performance is examined. The development of HEPOs for STCH offers a promising pathway toward sustainable hydrogen production, addressing both environmental and economic challenges.
Turning Corn Stalk Trashes into a Photothermal Agent for Interfacial Solar Water Evaporation for Sustainable Water Purification
Authors: Lv Bowen , Yang Shu
Published: November 2024

Biomass‐based photothermal materials have a higher photothermal conversion efficiency and contribute significantly to improved solar water evaporation systems. This work aims to transform corn stalk (CS) trash into efficient photothermal materials with centralized and less‐contact area water supply systems to achieve enhanced interfacial heat accumulation. We successfully synthesized cornstalk biochar synthesized via pyrolysis to maintain the environmental concern and is deposited onto a scalable, and cost‐effective (<1$) polyurethane foam (triangle shape, where the tip plays the wick and centralized water supply). The detailed characterizations validate the porous structure of CS biochar‐coated PU foam (CSB@PU), and enhance interfacial heat accumulation up to 47.8 °C under 1 kW m−2 solar irradiation which is endowed via thermal management of polystyrene foam (PS). This reproducible interfacial heat accumulation and sustainable evaporator bestow a water evaporation rate of up to 1.38 kg m−2 h−1, and solar‐to‐vapor conversion efficiency (84%) under one sun which is more efficient than other biomass‐derived evaporators. Inductively coupled plasma‐optical emission spectroscopy analysis validates the reductions of primary (Na+, K+, Mg2+, and Ca2+) and heavy metal ion (Fe3+, Hg2+, Cd2+, and Pb2+) concentrations in condensate, insights the potential of CSB@PU to advance the water treatment technologies.
Simultaneous Primer Coating for Fast Drying of Battery Electrodes
Authors: Burger David , Keim Noah , Shabbir Junaid , Gao Yuhao , Müller Marcus , Bauer Werner , Hoffmann Alexander , Scharfer Philip , Schabel Wilhelm
Published: November 2024

Primers are used to promote adhesion and reduce electrical interface resistance. Normally, the process of applying primer and electrode coating happens in two separate, sequential steps. Herein, primer and electrode are applied simultaneously, wet‐in‐wet. For fast drying of electrode coatings, a binder‐redistribution by binder migration happens. A normally unwanted binder migration is tried to be utilized. The goal is to use less binder in the electrode coating and dry it faster without losses in adhesion and performance. By using simultaneous primer coatings incorporating LAPONITE, the adhesion can be promoted by over 200%. This allows to eliminate the styrene‐butadiene‐rubber‐binder in the electrode slurry, saving in total of 70% of the binder. For eight times faster drying up to 30% improved specific capacity at 2C can be shown. This promising approach shows potential for any materials that lack adhesion, extending it, e.g., to porous, nanostructured particles and materials used in sodium‐ion batteries.
CHD2‐related epilepsy with eyelid myoclonia: Report of three cases
Authors: Padilla Hannah , Pinto e Vairo Filippo , Wirrell Elaine C. , Wong‐Kisiel Lily C. , Fine Anthony L. , Lanpher Brendan C. , Smith Kelsey M.
Published: November 2024

The aim of this study is to report three cases of epilepsy with eyelid myoclonia (EEM) with CHD2 pathogenic variants. A database of 134 patients with EEM evaluated at Mayo Clinic sites was searched to identify patients with CHD2 variants. The medical records of those identified were reviewed to describe their presentation, treatment, and clinical course. Three patients (2 males, 1 female) with EEM were found to harbor de novo CHD2 pathogenic variants (c.2636C>T p.(Ala879Val), c.3734delA p. (Lys1245Asnfs*4), and c.3896delTinsCG p. (Val1299Alafs*5)). All three patients had comorbid autism spectrum disorder (ASD), intellectual disability (ID), and attention deficit disorder (ADHD). Eyelid myoclonia was a prominent seizure type that persisted in the three patients despite trials of multiple antiseizure medications. Generalized tonic–clonic seizures occurred in two of the patients but were controlled with antiseizure medications. Genetic testing should be considered in patients presenting with EEM, especially when ADHD, ID, ASD, and drug‐resistant seizures are present. Further understanding of the relationship between CHD2 variants and epileptogenesis may provide important insights into the pathogenesis of EEM.
Recent advances in anion exchange membrane technology for water electrolysis: a review of progress and challenges
Authors: Qayoom Abdul , Ahmad Muhammad Shakeel , Fayaz H. , Qazi Atika , Selvaraj Jeyraj , Zainul Rahadian , Krismadinata  , Rahim Nasrudin Abd , Atamurotov Farruh , Tran Thien Khanh , Souayeh Basma , Benti Natei Ermias
Published: November 2024

Clean energy and environmental pollution are two key concerns of modern society and are pivotal necessities for the economic, social, and sustainable development of the world. Today around 80% of energy is generated using nonrenewable resources and fossil fuels (oil, gas, coal) which ultimately results in hazardous global emissions. As a clean substitute for fossil fuels, hydrogen has emerged as a promising and renewable energy resource. Utilization of this energy resource requires the development of active, stable, low‐cost environmentally friendly techniques. Water splitting electrolysis is a method for producing clean and efficient hydrogen using an environmentally benign technique that is currently at its most mature stage. Electrolysis is attracting ever‐increasing attention, as it is a promising electrochemical device for hydrogen production from water due to the high conversion efficiency and relatively low energy input required when compared to thermochemical and photocatalytic methods. This paper will outline the need, performance, and insight of anion exchange membrane (AEM) electrolyzer. Recent developments in the design and preparation of AEM. New strategies for activity, stability, and efficiency improvement of AEM. Membrane types, and factors affecting AEM performance in an electrolyzer. This review also discusses the effects, operating characteristics, and energy consumption of electrocatalysts in the AEM electrolyzer. Hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) pathways and mechanisms in acidic and alkaline media. This study seeks to provide a detailed overview of recent accomplishments in the field of the hydrogen economy, particularly electrolysis, to inspire further research and development to address the technology's obstacles.
Association of Changes in Relevant Indicators With Cardiovascular Disease and Osteoporosis in Perimenopausal and Postmenopausal Women
Authors: Luo Xiaoyan , Zhang Jun , Guo Yichuan , Xu Liangzhi
Published: November 2024

The essence of menopause is ovarian failure, decreased estrogen volatility, and deficiency leading to multiple related symptoms and an increased risk of metabolic disease in women, such as cardiovascular disease and osteoporosis. This study screened 773 eligible postmenopausal and perimenopausal women from an initial pool of 1187 participants, and various physiological and biochemical indices were measured and analyzed to assess differences across three age groups (40–44 years, 45–49 years, 50–54). We found no significant difference in the rate of cardiovascular disease between postmenopausal and perimenopausal women, while the rate of osteoporosis was higher in postmenopausal women compared to perimenopausal women. The disease of osteoporosis in postmenopausal women was associated with age (p < 0.05). We also found that postmenopausal women and perimenopausal women had significant effects on follicle‐stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), total cholesterol (TC), lumbar spine BMD (T1), femoral neck BMD, The bone density (T2) of the right femur was significantly affected. There are significant differences in FSH, LH, E2, TC, low‐density lipoprotein (LDL), L2–L4, T1, Neck of femur decrease, and T2 in women of different ages. Furthermore, the correlation analysis between age and E2 and metabolic indicators showed that age has a greater impact on the risk of postmenopausal and perimenopausal females. This study can help further understand the mechanisms of cardiovascular disease and osteoporosis in perimenopausal and menopausal women.
Gallstones increase the risk of nonalcoholic fatty liver: A case‐control study
Authors: Sheibani Abdolreza , Reihani Hamid , shoja Ahmad , Gharibvand Mohammad M. , Hanafi Mohammad G.
Published: November 2024

Background

Nonalcoholic fatty liver disease (NAFLD) and gallstones are generally seen together, and many of the risk factors for fatty liver and gallstones are common and similar. Therefore, this study aims to investigate the relationship between NAFLD and gallstones.

Methods

This case‐control study was conducted in patients referred to Imam Khomeini and Golestan hospitals of Ahvaz University of Medical Sciences in 2023, whose ultrasound showed fatty liver. Patients who were diagnosed with NAFLD by ultrasound were considered as the case group, and patients who did not have diagnostic findings of fatty liver in ultrasound were considered as the control group. Finally, the information recorded in the checklists was statistically analyzed using SPSS version 26 (SPSS Inc.).

Results

Three hundred patients were included in our study, 150 as cases and 150 as controls. There was no significant difference between the groups in terms of gender and age (gender P‐value: 0.817/age P‐value: 0.102). A statistically significant relationship was found between obesity, diabetes mellitus (DM), the presence of gallstones, and NAFLD (weight p‐value < 0.001/DM p‐value < 0.001/gallstones P‐value: 0.03). In addition, based on binary logistic regression analysis, the presence of gallstones increases the odds of NAFLD by 2.33 times (P‐value: 0.035). Furthermore, having DM and increasing each BMI unit increases the odds of NAFLD by 16 times and 30%, respectively (BMI p‐value < 0.001/DM p‐value < 0.001).

Conclusion

Based on the results of our study, gallstones are an important risk factor for NAFLD. The possible mechanisms are the existence of common risk factors between gallstones and NAFLD and the reduction of motility and flow of bile in the bile ducts with the presence of gallstones.
Self‐reported physical activity and gait in older adults without dementia: A longitudinal study
Authors: Krell‐Roesch Janina , Syrjanen Jeremy A. , Moeller Tobias , Krafft Jelena , Barisch‐Fritz Bettina , Kremers Walter K. , Ali Farwa , Knopman David S. , Petersen Ronald C. , Stein Thorsten , Woll Alexander , Vassilaki Maria , Geda Yonas E.
Published: November 2024

Background and Aims

Physical activity (PA) is associated with higher gait speed. We aimed to examine the associations between PA and change in spatial and temporal gait measures as well as fall risk in community‐dwelling individuals free of dementia.

Methods

Longitudinal study among 4173 individuals aged ≥50 years (mean age 71 years; 2078 males; median follow‐up 4 years) enrolled in the Mayo Clinic Study of Aging. Self‐reported late‐life PA was used to calculate overall PA and moderate‐vigorous PA (MVPA) scores. Gait was assessed using GAITRite® and Zeno™ systems. Incident falls information was based on diagnostic codes retrieved from medical records. We ran linear mixed effects models to examine associations between z‐scored PA variables and longitudinal gait parameters, adjusted for age, sex, education, body mass index (BMI), medical comorbidities, and including interactions between PA and time since baseline. In secondary analyses, we calculated Cox Proportional hazard models with age as time scale predicting incident falls by PA, adjusting for sex, education, BMI, medical comorbidities, and falls history.

Results

At baseline, higher PA was associated with higher velocity (overall PA: estimate 2.9935; MVPA: 2.2961; p < 0.001), higher cadence (overall PA: 1.0665; MVPA: 0.9073; p < 0.001), greater stride length (overall PA: 2.0805; MVPA: 1.4726; p < 0.001), shorter double support time (overall PA: −0.0257; MVPA: −0.0205; p < 0.001), and lower stance time variability (overall PA: −0.0204, p < 0.001; MVPA: −0.0152; p = 0.006). Overall PA was longitudinally associated with less decline in cadence, and MVPA with less increase in intraindividual stance time variability. Overall PA (Hazard ratio 0.892, 95% confidence interval 0.828–0.961, p = 0.003) and MVPA (HR 0.901; 95% CI 0.835–0.973, p = 0.008) were associated with a decreased risk of incident falls.

Conclusion

Late‐life PA was associated with favorable gait outcomes and decreased risk of incident falls. Thus, late‐life PA may help to maintain gait performance and decrease fall risk in old age.
Longitudinal relationship between adolescent emotional self‐regulation and prosocial behavior toward powerful people: Disentangling between‐person differences from within‐person effects
Authors: Li Xiaoxu , Fu Xinyuan , Wang Yue , Liu Chuanjun
Published: November 2024

Introduction

This study investigated the longitudinal effects between adolescent emotional self‐regulation and prosocial behavior toward powerful people (i.e., actions aimed at benefiting or supporting individuals who hold significant influence or authority within a group or society), based on the perspective of positive socialization cycle.

Methods

We recruited 543 Chinese adolescents (284 girls, M age at Time 1 = 11.27 years) and collected three waves of data over 3 years, each approximately 1 year apart (n Time 2 = 449, n Time 3 = 417). Traditional cross‐lagged panel model was conducted to test the longitudinal relationship between emotional self‐regulation and prosocial behavior toward powerful people. Then, a random‐intercept cross‐lagged panel model was performed to disentangle the between‐person differences from the within‐person predictive processes.

Results

The results showed that, emotional self‐regulation in the previous year was positively associated with prosocial behavior toward powerful people in the next year, whereas earlier prosocial behavior toward powerful people was not predictive of subsequent emotional self‐regulation.

Conclusions

Findings advocate the domain‐specific nature of self‐regulation and prosocial behavior and deepen our understanding of the relationship between the two from the culture‐specific perspective. This study also highlights the value of emotional self‐regulation intervention as a viable way to promote adolescent prosocial development. Theoretical and empirical implications are discussed.
Overexpression of Nfs1 Cysteine Desulphurase Relieves Sevoflurane‐Induced Neurotoxicity and Cognitive Dysfunction in Neonatal Mice Via Suppressing Oxidative Stress and Ferroptosis
Authors: Zhang Yang , Liu Xinru , Xie Lijuan , Hong Jin , Zhuang Qin , Ren Li , Li Xiaohong , Zhang Congli
Published: November 2024

Clinical evidence suggests that multiple exposures to sevoflurane in young people may be detrimental to cognitive development. Iron accumulation in the hippocampus is associated with sevoflurane‐induced neurotoxicity and cognitive deficits. The cysteine desulphurase, Nfs1, the rate‐limiting enzyme for the biosynthesis of iron–sulphur clusters, plays a role in cellular iron homeostasis. However, the impact of Nfs1‐mediated ferroptosis on sevoflurane‐induced neurotoxicity and cognitive impairments in neonatal mice remains undetermined. Neonatal mice at postnatal Day 6 received 3% sevoflurane daily for 3 consecutive days. Cognitive function was assessed using the Morris water maze test, and neurotoxicity was evaluated through terminal deoxynucleotidyl transferase dUTP nick end labeling and immunofluorescence staining. Here, HT22 hippocampal neurons were employed for in‐vitro experiments, and Fe2+ accumulation was measured. Ferroptosis‐related genes, including glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1) and ferritin, in the hippocampus and HT22 cells were observed, along with oxidative stress‐related indicators such as reactive oxygen species (ROS), methionine adenosyltransferase (MAT), glutathione (GSH) and lipid peroxidation (LPO). Transmission electron microscopy was utilized to examine the mitochondrial microstructure. Sevoflurane exposure significantly decreased Nfs1 expression in the hippocampus of mice and HT22 cells. This exposure resulted in cognitive impairments and neuronal damage in the hippocampus, which were alleviated by overexpression of Nfs1. Intracellular and mitochondrial iron accumulation occurred in HT22 cells following sevoflurane treatment. Sevoflurane exposure also significantly reduced GSH levels and increased levels of malondialdehyde, ROS and LPO in the hippocampus or HT22 cells. Additionally, sevoflurane exposure decreased GPX4 expression but increased TFR1 and ferritin expression in the hippocampus or HT22 cells. Overexpression of Nfs1 reversed the sevoflurane‐induced alterations in ferroptosis‐related genes and oxidative stress‐related indicators. Furthermore, overexpression of Nfs1 alleviated sevoflurane‐induced mitochondrial dysfunction. However, Nfs1 knockdown alone did not result in cognitive impairments, ferroptosis or oxidative stress. The overexpression of Nfs1 mitigated sevoflurane‐induced neurotoxicity and cognitive impairment by modulating oxidative stress and ferroptosis through the regulation of iron metabolism and transport.
Single‐cell transcriptomics reveals IRF7 regulation of the tumor microenvironment in isocitrate dehydrogenase wild‐type glioma
Authors: Li Jinwei , Long Shengrong , Yang Zhang , Wei Wei , Yu Shuangqi , Liu Quan , Hui Xuhui , Li Xiang , Wang Yinyan
Published: November 2024

Mutations in isocitrate dehydrogenase (IDH) are important markers of glioma prognosis. However, few studies have examined the gene expression regulatory network (GRN) in IDH‐mutant and wild‐type gliomas. In this study, single‐cell RNA sequencing and spatial transcriptome sequencing were used to analyze the GRN of cell subsets in patients with IDH‐mutant and wild‐type gliomas. Through gene transcriptional regulation analysis, we identified the M4 module, whose transcription factor activity is highly expressed in IDH wild‐type gliomas compared to IDH‐mutants. Enrichment analysis revealed that these genes were predominantly expressed in microglia and macrophages, with significant enrichment in interferon‐related signaling pathways. Interferon regulatory factor 7 (IRF7), a transcription factor within this pathway, showed the highest percentage of enrichment and was primarily localized in the core region of wild‐type IDH tumors. A machine‐learning prognostic model identified novel subgroups within the wild‐type IDH population. Additionally, IRF7 was shown to promote the proliferation and migration of T98G and U251 cells in vitro, and its knockdown affected glioma cell proliferation in vivo. This study systematically established the regulatory mechanism of IDH transcriptional activity in gliomas at the single‐cell level and drew a corresponding cell map. The study presents a transcriptional regulatory activity map for IDH wild‐type gliomas, involving single‐cell RNA sequencing and spatial transcriptomics to identify gene regulatory networks, machine learning models for IDH subtyping, and experimental validation, highlighting the role of IRF7 in glioma progression.
An inflammatory cytokine signature predicts IgA nephropathy severity and progression
Authors: Chen Lei , Chen Xizhao , Cai Guangyan , Jiang Hongli , Chen Xiangmei , Zhang Min
Published: November 2024

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, resulting in end‐stage renal disease and increased mortality rates. Prognostic biomarkers reflecting molecular mechanisms for effective IgAN management are urgently needed. Analysis of kidney single‐cell transcriptomic sequencing data demonstrated that IgAN expressed high‐expression levels of inflammatory cytokines TNFSF10, TNFSF12, CCL2, CXCL1, and CXCL12 than healthy controls (HCs). We also measured the urine proteins in 120 IgAN (57 stable and 63 progressive) and 32 HCs using the proximity extension assay (PEA), and the multivariable and least absolute shrinkage and selection operator (LASSO) logistic regression analysis both revealed that CXCL12, MCP1 were the prognostic significant variables to predict IgAN progression severity. These two proteins exhibited negative correlation with the estimated glomerular filtration rate (eGFR) and patients with higher expression levels of these two proteins had a higher probability to have poorer renal outcome. We further developed a risk index model utilizing CXCL12, MCP1, and baseline clinical indicators, which achieved an impressive area under the curve (AUC) of 0.896 for prediction of IgAN progression severity. Our study highlights the significance of the inflammatory protein biomarkers for noninvasive prediction of IgAN severity and progression, offering valuable insights for clinical management.
Immunometabolism: signaling pathways, homeostasis, and therapeutic targets
Authors: Xu Rongrong , He Xiaobo , Xu Jia , Yu Ganjun , Wu Yanfeng
Published: November 2024

Immunometabolism plays a central role in sustaining immune system functionality and preserving physiological homeostasis within the organism. During the differentiation and activation, immune cells undergo metabolic reprogramming mediated by complex signaling pathways. Immune cells maintain homeostasis and are influenced by metabolic microenvironmental cues. A series of immunometabolic enzymes modulate immune cell function by metabolizing nutrients and accumulating metabolic products. These enzymes reverse immune cells’ differentiation, disrupt intracellular signaling pathways, and regulate immune responses, thereby influencing disease progression. The huge population of immune metabolic enzymes, the ubiquity, and the complexity of metabolic regulation have kept the immune metabolic mechanisms related to many diseases from being discovered, and what has been revealed so far is only the tip of the iceberg. This review comprehensively summarized the immune metabolic enzymes’ role in multiple immune cells such as T cells, macrophages, natural killer cells, and dendritic cells. By classifying and dissecting the immunometabolism mechanisms and the implications in diseases, summarizing and analyzing advancements in research and clinical applications of the inhibitors targeting these enzymes, this review is intended to provide a new perspective concerning immune metabolic enzymes for understanding the immune system, and offer novel insight into future therapeutic interventions.
Arthroplasty Follow‐Up Pathways: A Qualitative Study of Current Practice and Healthcare Professionals' Attitudes and Motivations for Change
Authors: Hill Kate , Czoski‐Murray Carolyn , Smith Lindsay K. , Stone Martin , Conaghan Philip G. , Kingsbury Sarah R.
Published: November 2024

Background

There is considerable diversity in arthroplasty follow‐up pathways. This qualitative study aimed to understand healthcare professionals' practice and attitude to follow‐up, their motivation for change and what evidence they considered before implementing new pathways.

Methods

The main UKSAFE study enroled 38 centres providing revision procedures across the United Kingdom. A purposive sample of professional leads and service managers was identified from site contacts. Individual interviews were conducted by telephone, transcribed verbatim and analysed using a theoretical framework derived from current evidence and the data collected in our previous studies.

Results

We found that there had been a shift away from bringing patients back into the clinic for repeat follow‐up assessments, but that this was not universal, and some centres had long‐established care pathways that involved long‐term follow‐up. The way in which those services were provided might be different or have common features, but centres were likely to face common problems including large patient numbers and funding restraints.

Conclusion

The reliability of newer prosthetics and surgical skill has influenced some changes by increasing confidence in a pathway which does not routinely provide long‐term follow‐up. Service commissioners also have a role to play in how follow‐up care pathways are configured, but scrutiny of the ratio of new to follow‐up appointments can put pressure on clinical staff to follow‐up only patients with identified clinical need. Virtual clinics can provide a service to patients and use scarce resources efficiently, but NHS IT systems that would be needed to support more remote working, for example, telemedicine and plans to collect PROMS data online from patients to assist with monitoring were not advanced.
Impact of Age in Single‐Level Versus Multilevel Airway Compromise: A Multi‐Institutional Review
Authors: Laohakittikul Chanticha , Khalsa Inderpreet Kaur , Rao Shambavi J. , Stockton Steven D. , Madden Lyndsay L. , Cates Daniel J. , Young VyVy N.
Published: November 2024

Objective

Examine the association between age and treatment outcomes in conditions causing single‐ versus multilevel airway restriction.

Study Design

Multi‐institutional retrospective cohort study.

Setting

Tertiary laryngology centers.

Methods

Participants included younger (18‐64 years) and geriatric (≥65 years) adults with posterior glottic stenosis (PGS), multilevel airway stenosis (MLAS), and bilateral vocal fold paralysis (BVFP). Subgroup demographics, comorbidities, type, and etiology of airway compromise were described. Associations between age and primary outcome variables (i.e., tracheostomy and decannulation rates, number of surgeries performed, time between surgeries, and change in quality‐of‐life patient‐reported outcome measures [PROMs]) were evaluated. Statistical analyses included independent t tests, χ2, Fisher's exact, or Mann‐Whitney tests.

Results

In 158 patients [96 younger (30 PGS, 29 MLAS, 37 BVFP) and 62 geriatric (24 PGS, 9 MLAS, 29 BVFP)], age differences were not significant for gender (P = .990), tracheostomy placement (70% vs 66%, P = .629), or decannulation success (40% vs 24%, P = .091) in younger versus geriatric groups, respectively. In younger patients, MLAS was more common (30.2% vs 14.5%, P = .024), and BVFP patients were more likely to decannulate (50% vs 12%, P = .017). Geriatric patients were more likely to have a history of prior radiation (26% vs 10%, P = .016), stenosis due to malignancy (23% vs 9%, P = .022), and fewer overall surgeries (median 1 vs 3, P = .003). Median PROMs were comparable between age subgroups (P > .05).

Conclusion

Younger adults underwent more surgeries, but overall comorbidities, tracheostomy decannulation rates, and PROMs were comparable between groups. Age does not negatively impact treatment outcomes and should not be a deterrent in treatment decision‐making.
Finite element modeling of concentrated impact loads on the masticatory muscles at the head
Authors: Wang Zechang , Behrens Roland , Juhre Daniel , Elkmann Norbert
Published: November 2024

Numerical simulation has great potential to provide a more comprehensive understanding of human impact response to injury mechanisms. Finite Element (FE) models are used as a tool to study human injuries in greater detail, for example, the THUMS (Total Human Model Safety of TOYOTA) model, which is widely used as a reliable human model in different fields to predict human injuries such as fractures, internal organ damage, and brain tissue injuries. However, no available FE model can be used to simulate human‐robot collisions based on standards ISO/TS 15066 and the biomechanical characteristics of human soft tissues in vivo. The authors have developed a head model based on the structures (dimensions and anatomy) of the THUMS head model, specifically designed to simulate impact loads on the masticatory muscles. Based on medical imaging (MRI) data, the soft tissues at the location of the masticatory muscles in the THUMS head are transformed from monolayer to multilayer, that is, a composite geometry of skin‐fat‐muscle each with its own material model and parameters. The model was optimized and validated using the experimental data from the Fraunhofer IFF subjects study, which determined biomechanical thresholds for specific body locations in ISO/TS 15066 under dynamic collisions.
Long‐term renal outcomes of children with cancers treated with platinum‐based chemotherapy: A retrospective chart analysis
Authors: Kan Adrian , Marokakis Sarah , Ward James H. , Kim Siah , Gabriel Melissa , Durkan Anne M.
Published: November 2024

Purpose

Platinum‐based chemotherapy is a mainstay of treatment for many childhood cancers but is associated with acute nephrotoxicity and long‐term ototoxicity. There is emerging evidence of long‐term renal complications. This study aimed to assess the prevalence of chronic kidney disease (CKD) in children treated with platinum chemotherapy (cisplatin and carboplatin) and identify potential risk factors for the development of CKD.

Methods

We conducted a retrospective review of children diagnosed with hepatoblastoma, osteosarcoma, neuroblastoma, or medulloblastoma who received platinum chemotherapy over a 16 year timeframe. Patients were excluded if they did not have at least 3 years follow up data, died within 3 years of platinum chemotherapy, or if they relapsed. Clinical data were collected at baseline (first dose), 1 year, and at most recent follow up.

Results

Of 328 treated patients, 147 met the inclusion criteria and were followed for a mean of 8.1 years (range 3–15.7 years). The median age at first dose was 3.7 years (IQR 1.7–9.6 years). CKD ≥grade 2 was present in 53(36%) at last follow up and 15(10%) had tubular dysfunction. A history of acute kidney injury at any time during treatment was associated with CKD (OR 3.12 CI 1.07–9.12, p =0.04). On multivariable analysis older age at platinum therapy (OR 1.2, CI 1.1–1.4, p = 0.004) and a high aminoglycoside or vancomycin trough level (OR 4.3, CI 1.9–9.7, p < 0.001) were risk factors for CKD.

Conclusion

The high rate of CKD in children treated with platinum chemotherapy warrants long‐term follow‐up and screening for progressive disease.