bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myelination Trajectory and Microglial Dynamics Following Repeated Sevoflurane Exposure in Developing Brain
Authors: Che Ji , Wu Yuanyuan , Dong Jing , Jiang Xuliang , Yang Li , Chen Yali , Zhang Jun 
Published: February 2025

ABSTRACTThe myelination is a critical process during brain development. This study aimed to explore the impact of volatile anesthetic sevoflurane on developing myelination and the role of microglial activation in this process. Neonatal C57BL/6J mice were exposed to sevoflurane at their postnatal 6–8 days. Neurobehavioral tests were used to assess fine motor and cognitive functions. Myelination of hippocampus (HC) and corpus callosum (CC), as well as microglial activation, were determined by western blotting and immunostaining. Lipid droplets were assessed by Oil‐Red‐O and Bodipy staining. Further, primary microglia were co‐cultured with oligodendrocyte precursor cell (OPC) to determine the role of microglia in the proliferation and differentiation of OPC. And microglial inhibitor minocycline and CSF1R inhibitor PLX5622 were administered to assess the effects of microglial activation on developing myelination. The results showed that repeated sevoflurane exposure impaired both fine motor and cognitive functions and induced abnormal expressions of myelin‐related proteins myelin basic protein (MBP) and platelet‐derived growth factor α receptor (PDGFR‐α). And accumulations of lipid droplets were found in the microglia of HC and CC after sevoflurane exposure. Further, the spatiotemporal response to repeated sevoflurane exposure in glial cells exhibited an aberrant myelination process and microglial polarization. The conditioned medium from sevoflurane‐treated microglia inhibited the OPC proliferation and differentiation, while minocycline or PLX5622 alleviated sevoflurane‐induced neuroinflammation and hypomyelination. Therefore, repeated sevoflurane exposure negatively affected OPC differentiation and myelination trajectory through hyperactivating microglia in developing brain, leading to motor and cognitive impairments, while microglial inhibition/depletion could protect against sevoflurane‐induced damage on developing myelination.
AA147 Alleviates Symptoms in a Mouse Model of Multiple Sclerosis by Reducing Oligodendrocyte Loss
Authors: Aksu Metin , Kaschke Kevin , Podojil Joseph R. , Chiang MingYi , Steckler Ian , Bruce Kody , Cogswell Andrew C. , Schulz Gwen , Kelly Jeffery W. , Wiseman R. Luke , Miller Stephen D. , Popko Brian , Chen Yanan 
Published: February 2025

ABSTRACTInflammation‐induced oligodendrocyte death and CNS demyelination are key features of multiple sclerosis (MS). Inflammation‐triggered endoplasmic reticulum (ER) stress and oxidative stress promote tissue damage in MS and in its preclinical animal model, experimental autoimmune encephalitis (EAE). Compound AA147 is a potent activator of the ATF6 signaling arm of the unfolded protein response (UPR) that can also induce antioxidant signaling through activation of the NRF2 pathway in neuronal cells. Previous work showed that AA147 protects multiple tissues against ischemia/reperfusion damage through ATF6 and/or NRF2 activation; however, its therapeutic potential in neuroinflammatory disorders remains unexplored. Here, we demonstrate that AA147 ameliorated the clinical symptoms of EAE and reduced ER stress, oligodendrocyte loss, and demyelination. Additionally, AA147 suppressed T cells in the CNS without altering the peripheral immune response. Importantly, AA147 significantly increased the expressions of Grp78, an ATF6 target gene, in oligodendrocytes, while enhancing levels of Grp78 as well as Ho‐1, an NRF2 target gene, in microglia. In cultured oligodendrocytes, AA147 promoted nuclear translocation of ATF6, but not NRF2. Intriguingly, AA147 altered the microglia activation profile, possibly by triggering the NRF2 pathway. AA147 was not therapeutically beneficial during the acute EAE stage in mice lacking ATF6 in oligodendrocytes, indicating that protection primarily involves ATF6 activation in these cells. Overall, our results suggest AA147 as a potential therapeutic opportunity for MS by promoting oligodendrocyte survival and regulating microglia status through distinct mechanisms.
Glaucoma Disease‐Specific Adherence Measurement Tools Validated for Measuring Adherence to Glaucoma Medications: A Systematic Review
Authors: Abaidoo B. , Mashige K. P. , Govender‐Poonsamy P. , Tagoe N. N. , Essuman V. A. , Adam S. Y. 
Published: February 2025

ABSTRACTBackgroundReviewing validated glaucoma disease‐specific tools for measuring adherence could encourage adherence monitoring to avoid progressive visual field losses in people living with glaucoma.AimTo review the literature on validated disease‐specific tools for measuring adherence to glaucoma medications.MethodsRelevant peer‐reviewed publications from the year 2000 to 2022 from PubMed, EMBASE, Scopus, and PROquest were retrieved. For each search conducted, the name of the search engine used, date of search, number of publications retrieved, and keywords used were documented. The selected articles were reviewed for inclusion and assessed for biases and quality. Each tool was described by the type of measurement, technique for measurement, strengths and weaknesses, and method of validation, respectively.ResultsOut of the 10 included articles, seven glaucoma disease‐specific tools were identified namely; Glaucoma Treatment Compliance Assessment Tool‐Short form (GTCAT‐S), Glaucoma Treatment Compliance Assessment Tool‐Long form (GTCAT‐L), Travatan Dosing Aid (TDA), Eye‐Drop Satisfaction Questionnaire (EDSQ), Glaucoma Adherence Questionnaire‐Revised (GAQ‐R), Glaucoma Adherence Questionnaire‐Old (GAQ‐O), and Schwartz Adherence Questionnaire (SAQ). Three studies had a low risk of bias, and seven recorded a moderate risk of bias. The TDA, GTCAT‐S, and GTCAT‐L were rated as high‐quality tools.ConclusionsSeven glaucoma disease‐specific tools for measuring adherence were found. Integration of regular measurement of medication adherence as part of care for glaucoma patients would be beneficial for both patients and providers of eye care.
Factors Associated With Low Tuberculosis Case Detection and Investigation in Public Health Facilities (PHFs) in Bududa District, Uganda: A Cross‐Sectional Study
Authors: Tumuhairwe Imelda , Komuhangi Alimah , Okello Alfred , Ayebale Apolo , Buyinza Ambrose Wabwire , Bwire Godfrey 
Published: February 2025

ABSTRACTBackground and AimsDespite global efforts to combat tuberculosis (TB), Uganda bears a high burden, with an annual incidence of 200 per 100,000 and a mortality rate of 35 per 100,000 persons. This study investigates TB prevalence, detection rates, and associated factors in public health facilities (PHFs) in Bududa district.MethodsA cross‐sectional study employing Mixed Methods Research (MMR) was conducted in November 2019 on respondents with symptoms suggestive of TB and key informants overseeing TB care in Bududa district, Uganda.ResultsOnly 18.8% (46/245) of respondents who reported symptoms suggestive of TB were investigated for infection. The majority, 87.4%, never had sputum requested and 91.7% never had a chest X‐ray done. Participants from rural areas were 26% less likely to be screened for TB than their urban counterparts (PR = 1.26, 95% CI [1.16–1.38]). Challenges for TB care included staffing shortages and inadequate medical supplies and equipment.ConclusionThis study highlights the disparity between high TB burden and low detection rates in Bududa district. The Government of Uganda and stakeholders should invest in solving the challenges identified by this study.
Simulation and Optimization of Finned and Twisted Double‐Tube Heat Exchanger Using Neural Network Algorithm
Authors: Chegini Javid Nezamivand , Javaherdeh Kourosh , Seddigh Alireza Asadi 
Published: February 2025

ABSTRACTCreating a high heat transfer flux is not a common phenomenon and occurs only when a source of heat production (or consumption) is placed in a small volume; in precision casting systems, heat transfer should be done at a high velocity due to the presence of thin molten branches. Nanofluids present a significant opportunity to improve the thermal efficiency. In this research, a combination of different solutions to enhance heat transfer has been evaluated simultaneously. For this purpose, in the current research, aluminum oxide non‐Newtonian nanofluid in volume percentages of 0, 0.5, 1.5, and 2 has been investigated in a torsional heat exchanger with a rotating triangular blade around the tube. The base fluid of this non‐Newtonian nanofluid consists of water with 0.1% mass of carboxymethyl cellulose. In this study's results, the heat exchanger's performance has been predicted. Combining neural network optimization code with the numerical simulation of the double‐tube spiral geometry and using non‐Newtonian nanofluid to increase the heat transfer and improve the performance of the heat exchanger is the innovation of the present research.
Numerical Simulation on the Impact Cooling of Multi‐Nozzle Jet for Hot‐Rolled L‐Beam and Industrial Test
Authors: Li Jie , Zhao Xianming 
Published: February 2025

ABSTRACTThe consistency of cooling greatly influences the quality of L‐beams. In this paper, the process of cooling high‐temperature L‐beams by multi‐jet impingement is numerically simulated. The VOF model and Realizable k–ε turbulence model were used, and the reliability of the Realizable k–ε turbulence model was verified using experiments. The jet flow rate is mainly 3–11 L/min. Numerical simulation calculations were used to obtain the distribution law of pressure, streamline, and wall shear of the flow field of the multi‐nozzle jet impinging on the surface of the L‐beam, as well as the distribution of Nusselt number of the L‐beam and the temperature distribution at 1/2 thickness. The results suggest that the cooling uniformity of the L‐beam can be enhanced by extending the cooling duration of the short edge or by concurrently increasing the water flow and time of the short edge. Based on the above strategy, a relevant industrial test program was developed. After the jet impingement cooling experiment, the L‐beam's surface temperature differential decreased by 43.9°C, and the bending of the L‐beam was decreased by 10.4 cm. The maximum value of the magnetic field gradient associated with the stress in the L‐beams was reduced by up to 80.2%.
Modelling Count Data in Psychological Research: An Applied Tutorial
Authors: Too Miranda A. , Alter Udi , Flora David B. 
Published: February 2025

ABSTRACTAcross subfields of psychology, researchers frequently encounter count variables (i.e., non‐negative integer values, which result from counted measurements). Although count variables are common in psychological research (e.g., frequency of behaviours or symptoms), researchers may not be aware of appropriate statistical procedures for modelling and drawing inferences from count data. Specialised regression techniques (i.e., generalised linear models and zero‐augmented models) have been developed for the unique properties of count data, but they can seem inaccessible to non‐technical audiences because of their departure from more familiar methods. Assuming a basic knowledge of linear regression, this tutorial aims to demystify count regression approaches and empower researchers to apply these methods to their own count data, using free, open‐source statistical software (i.e., R). This tutorial takes researchers step‐by‐step through the implementation of count regression methods in applied research, imparting them with the knowledge to confidently implement these techniques.
Enhanced BoxInst for Weakly Supervised Liver Tumor Instance Segmentation in CT Images
Authors: Li Shanshan , Zhang Yuhan , Zhang Lingyan , Chen Wei 
Published: February 2025

ABSTRACTAccurate liver tumor detection and segmentation are essential for disease diagnosis and treatment planning. While traditional methods rely on pixel‐level mask annotations in fully supervised training, weakly supervised techniques are gaining attention due to their reduced annotation requirements. In this study, we propose an enhanced version of BoxInst, called Enhanced BoxInst, which incorporates two key innovations: the position activation (PA) Module and the progressive mask generation (PMG) Module. The PA Module utilizes a Spatial Awareness (SA) Block to accurately locate tumor regions and encodes the location information to the segmentation branch through the Spatial Interaction Encoding (SIE) mechanism, thereby achieving cross‐spatial feature interaction and ultimately improving the segmentation accuracy of liver tumors. Additionally, the PMG Module employs a feature decomposition scheme to refine tumor masks progressively from coarse to fine, accurately restoring the overall layout and boundary details of the tumor mask. Extensive experiments on the LiTS, AMU‐Liver, and 3DIRCADb datasets demonstrate that Enhanced BoxInst outperforms existing methods in liver tumor instance segmentation. These results highlight the potential of our approach for practical use in medical image analysis, especially when only box annotations are available. The code is available at https://github.com/ssli23/Enhanced_BoxInst.
Parent and child gender effects in the relationship between attachment and both internalizing and externalizing problems of children between 2 and 5 years old: A dyadic perspective
Authors: Matetovici Magda , Spruit Anouk , Colonnesi Cristina , Garnier‐Villarreal Mauricio , Noom Marc 
Published: February 2025

AbstractAcknowledging that the parent–child attachment is a dyadic relationship, we investigated differences between pairs of parents and preschool children based on gender configurations in the association between attachment and problem behavior. We looked at mother–daughter, mother–son, father–daughter, and father–son dyads, but also compared mothers and fathers, daughters and sons, and same versus different gender pairs. We employed multigroup structural equation modeling to explore moderation effects of gender in a sample of 446 independent pairs of parents and preschool children (2–5 years old) from the Netherlands. A stronger association between both secure and avoidant attachment and internalizing problems was found for father–son dyads compared to father–daughter dyads. A stronger association between both secure and avoidant attachment and externalizing problems was found for mother–son dyads compared to mother–daughter and father–daughter dyads. Sons showed a stronger negative association between secure attachment and externalizing problems, a stronger positive association between avoidant attachment and externalizing problems, and a stronger negative association between secure attachment and internalizing problems compared to daughters. These results provide evidence for gender moderation and demonstrate that a dyadic approach can reveal patterns of associations that would not be recognized if parent and child gender effects were assessed separately.
METTL3‐mediated NFAT5 Upregulation Promotes Cervical Cancer Progression Through Enhancing the Mitochondrial Function by Transcriptional Regulation of PRDX1
Authors: He Yanli , Ge Junli , Zhao Shuhua , Zhou Fuxing , Zou Wei , Gao Yan , Liu Shujuan , Zhang Wei 
Published: February 2025

ABSTRACTNuclear factor of activated T‐cells 5 (NFAT5) is recognized as an oncogene in a variety of tumors. However, the role of NFAT5 in cervical cancer (CC) cell phenotypic alterations remains to be elucidated. Here, we demonstrated that NFAT5 expression was elevated in CC samples and cells using quantitative real‐time reverse transcription PCR, Western blot analysis, and immunohistochemistry assays, and high NFAT5 expression showed a poor prognosis. After C‐33A cells were transfected with pcDNA‐NFAT5 or NFAT5‐short hairpin RNA (shRNA), cell proliferation, invasion, and apoptosis were evaluated using CCK‐8 and EdU assays, transwell assays, and flow cytometry, respectively. Biomarkers indicating mitochondrial function, including the expression of the d‐loop, ATP levels, and mitochondrial membrane potential, were detected. NFAT5 knockdown restrained cell proliferation and invasion, impaired mitochondrial function, and increased the ratio of cell apoptosis; however, NFAT5 overexpression showed the opposite results. RNA immunoprecipitation (RIP) and methylated RIP (MeRIP) assays were performed to identify interactions among NFAT5, methyltransferase‐like 3 (METTL3), and insulin‐like growth factor 2 mRNA‐binding protein 3 (IGF2BP3). Chromatin immunoprecipitation and dual‐luciferase reporter gene assays demonstrated that NFAT5 binds to the peroxiredoxin 1 (PRDX1) promoter to drive PRDX1 transcription. METTL3 enhanced NFAT5 mRNA stability through IGF2BP3‐mediated N6‐Methyladenosine (m6A) modification, and NFAT5 transcriptionally regulated PRDX1 expression. Moreover, the reintroduction of METTL3 or PRDX1 promoted cell growth and mitochondrial function damage in NFAT5‐silenced cells. In vivo experiments further demonstrated that NFAT5 promotes CC tumor growth. Taken together, NFAT5 upregulation mediated by the METTL3/IGF2BP3 complex in an m6A‐dependent manner facilitates CC cell growth by transcriptionally regulating PRDX1 expression, providing a novel target for CC therapy.
Indication‐Specific Dosing and Dose‐Evaluation Strategies in New Indications for Non‐Oncology Monoclonal Antibodies
Authors: Tawfik Sherouk M. , Tang Fei 
Published: February 2025

AbstractCompared to traditional small molecule drugs, monoclonal antibodies (mAbs) often display more complex pharmacokinetic (PK) and pharmacodynamic (PD) properties that may be impacted by disease‐specific factors. For mAbs in non‐oncology indications, where the same drug might be used for conditions involving different organ systems and/or having different degrees of severity, the need for indication‐specific dosing and/or tailored dose evaluation strategies is more evident. However, a comprehensive analysis on this topic has not been conducted for approved non‐oncology therapies. In this work, we extracted literature information for non‐oncology mAbs approved in the past 20 years to provide a comprehensive exploration of indication‐specific dosing and dose evaluation strategies in the new indications. Our analysis included 21 mAbs with 50 supplemental approvals for new indications. Indication‐specific dosing was prevalent, with 15 out of 21 mAbs having different recommended dosing regimens across two or more indications. The majority of the new indications were supported by Phase 2 dose‐ranging studies and/or Phase 3 studies that evaluated more than one dosing regimen. Importantly, our analysis uncovered a relationship between indication‐specific dosing, dose evaluation strategies, and organ system classification of the original versus the new indication. We delved into dose justification supporting the new indications, including the types of data and modeling approaches used or considered. Through case studies, we highlighted factors that may influence dose selection in new indications, such as target expression levels, disease severity, and benefit–risk profile. Lastly, we made practical recommendations regarding dose optimization approaches in clinical drug development across multiple indications.
One‐stage minced cartilage autograft with platelet‐rich plasma improves early clinical outcomes: A multicentric retrospective study
Authors: Barbaret Arthur , Wein Frank , Jacquet Christophe , Ollivier Matthieu 
Published: February 2025

AbstractPurposeKnee cartilage defects are a therapeutic challenge, often requiring multiple costly procedures with modest improvements. This study evaluates whether a one‐stage minced cartilage autograft with platelet‐rich plasma (PRP) improves clinical and radiological outcomes after at least 1 year.MethodsA multicentric, non‐randomized, retrospective analysis was conducted using data from two sports medicine centres. Sixty‐six patients aged 18–50 years with symptomatic International Cartilage Repair Society Grade III/IV chondral defects underwent the minced cartilage autograft and PRP procedure between January 2021 and April 2023. The minimum follow‐up was 1 year. Clinical scores for Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) Score and Self Knee Value (SKV) were collected from medical records and by an independent examiner at the latest follow‐up. Magnetic resonance imaging (MRI) assessments using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 scoring system were performed at the latest follow‐up in 46 patients (70%).ResultsThe mean follow‐up was 20.5 ± 7.5 months. The study demonstrated significant improvements in knee function and pain relief following the minced cartilage autograft with the PRP procedure. The mean KOOS total score started from 45.3 to 71.5 points, mean KOOS pain started from 51.9 to 80.4 points, mean KOOS activities of daily living started from 62.1 to 85.3 points, mean KOOS symptoms started from 53.1 to 79 points, mean KOOS sports started from 38.7 to 74.8 points, mean KOOS quality of life started from 43.3 to 73.7 points. The mean IKDC score improved by 27.7 ± 15.7 points. All these scores have been significantly improved (p < 0.05). MRI assessments confirmed the successful integration of repair tissue with a mean MOCART 2.0 score of 80.5 ± 12.5 points.ConclusionThe minced autograft cartilage technique with PRP provides favourable early clinical and radiological outcomes for limited chondral defects in the knee. This method offers a single‐procedure approach with minimal grafting requirements and does not necessitate a laboratory or specialized personnel, unlike other techniques.Level of EvidenceLevel III retrospective multicentric study.
Comparison of coronal and sagittal alignment in patients without osteoarthritis but with knee complaints
Authors: Handa Mikiko , Takahashi Tsuneari , Saitsu Akihiro , Iguchi Masaki , Takeshita Katsushi 
Published: February 2025

AbstractPurposeThis study aimed to clarify lower limb alignment characteristics and the relationship between coronal and sagittal lower limb alignment in Japanese patients with knee complaints but without knee osteoarthritis (KOA).MethodsThis retrospective study included 200 knees from Japanese patients with knee complaints but without KOA aged 60 years and under presenting with knee complaints between May 2020 and May 2023. We assessed coronal parameters, including mechanical hip knee angle (mHKA), arithmetic HKA (aHKA) mechanical lateral distal femoral angle and medial proximal tibial angle (MPTA), and sagittal parameters, such as medial posterior tibial slope (MPTS) and lateral posterior tibial slope (LPTS). In addition, we compared differences between CPAK types.ResultsA weak positive correlation was found between mHKA and MPTS, but not with aHKA. Moderate negative and moderate positive correlations were found between mHKA and MPTA and between medial and LPTS, respectively.ConclusionsLittle correlation was found between the coronal and sagittal parameters in patients with knee complaints but without KOA.Level of EvidenceLevel Ⅲ.
Anterolateral corner of knee: Current concepts
Authors: Meena Amit , Attri Manish , Farinelli Luca , Campos Vicente , Rajpal Karan , D'Ambrosi Riccardo , Malik Shahbaz , de Sa Darren , Fink Christian , Tapasvi Sachin 
Published: February 2025

AbstractThe anatomy of the antero‐lateral corner (ALC) has been the topic of recent interest, as evidenced by the increasing number of publications. Knowledge needs to be improved amongst clinicians regarding the anatomy and biomechanical function of this vital structure and its implications on the rotational stability of the knee. There has yet to be a consensus on the role of surgical procedures and their indications for addressing the instability associated with the injury to these structures. Through this article, the authors have tried to outline the existing literature regarding Anterolateral knee instability, the associated structures, and the management of its injuries, emphasising the role of the anterolateral capsule and reconstructive procedures in combined ligamentous knee injuries.