bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐dose vitamin D supplementation in patients with COVID‐19: A meta‐analysis of randomized controlled trials
Authors: Zhong Zhaoshuang , Zhao Long , Zhao Yan , Xia Shuyue 
Published: December 2023

AbstractThe efficacy of administering high doses of vitamin D to patients diagnosed with COVID‐19 remains uncertain. We conducted a comprehensive search across multiple databases (PubMed, EMBASE, Cochrane Library, and ISI Web of Science) from inception until August 2022, with no limitations on language, to locate randomized controlled trials (RCTs) that investigated the impact of high‐dose vitamin D supplementation (defined as a single dose of ≥100,000 IU or daily dose of ≥10,000 IU reaching a total dose of ≥100,000 IU) on COVID‐19 patients. Risk ratios (RR) with 95% confidence intervals (CI) and weighted mean differences (WMD) with 95% CI were calculated. Our meta‐analysis included 5 RCTs with a total of 834 patients. High‐dose vitamin D supplementation did not show any significant benefits for mortality (I2 = 0.0%, p = .670; RR 1.092, 95% CI 0.685–1.742, p = .711) or intensive care unit (ICU) admission (I2 = 0.0%, p = .519; RR 0.707, 95% CI 0.454–1.102, p = .126) in COVID‐19 patients compared to the control group. However, it was found to be safe and well‐tolerated (I2 = 0.0%, p = .887; RR 1.218, 95% CI 0.930–1.594, p = .151). Subgroup analysis also showed no benefits in overall mortality, including for patients with vitamin D deficiency (I2 = 0.0%, p = .452; RR 2.441, 95% CI 0.448–13.312, p = .303) or compared to the placebo (I2 = 0.0%, p = .673; RR 1.666, 95% CI 0.711–3.902, p = .240). Our research indicates that there is no evidence to support the efficacy of high‐dose vitamin D supplementation in improving clinical outcomes among individuals with COVID‐19, in line with previous studies focused on contexts including rickets. Considering the limitations of the study, additional research may be required.
The role of the primary sensorimotor system in generalized epilepsy: Evidence from the cerebello–cerebral functional integration
Authors: Chen Junxia , Jiang Sisi , Lu Bao , Liao Jiangyan , Yang Zhihuan , Li Hechun , Pei Haonan , Li Jianfu , Iturria‐Medina Yasser , Yao Dezhong , Luo Cheng 
Published: December 2023

AbstractThe interaction between cerebellum and cerebrum participates widely in function from motor processing to high‐level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic–clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello–cerebral circuit is still poorly understood. Resting‐state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel‐based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello–cerebral functional integration on the voxel‐based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello–cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients.
HPV‐negative head and neck cancers with adverse pathological features carry specific molecular changes that are associated with survival
Authors: Kim Hugh Andrew Jinwook , Zeng Peter Y. F. , Cecchini Matthew , Shaikh Mushfiq Hassan , Laxague Francisco , Deng Xiaoxiao , Jarycki Laura , Ryan Sarah Elizabeth Belle , Dawson Alice , Liu Mu Han , Palma David A. , Patel Krupal , Mundi Neil , Barrett John W. , Mymryk Joe S. , Boutros Paul C. , Nichols Anthony C. 
Published: December 2023

AbstractBackgroundAdverse pathological features following surgery in head and neck squamous cell carcinoma (HNSCC) are strongly associated with survival and guide adjuvant therapy. We investigated molecular changes associated with these features.MethodsWe downloaded data from the Cancer Genome Atlas and Cancer Proteome Atlas HNSCC cohorts. We compared tumors positive versus negative for perineural invasion (PNI), lymphovascular invasion (LVI), extracapsular spread (ECS), and positive margins (PSM), with multivariable analysis.ResultsAll pathological features were associated with poor survival, as were the following molecular changes: low cyclin E1 (HR = 1.7) and high PKC‐alpha (HR = 1.8) in tumors with PNI; six of 13 protein abundance changes with LVI; greater tumor hypoxia and high Raptor (HR = 2.0) and Rictor (HR = 1.6) with ECS; and low p38 (HR = 2.3), high fibronectin (HR = 1.6), low annexin A1 (HR = 3.1), and high caspase‐9 (HR = 1.6) abundances with PSM.ConclusionsPathological features in HNSCC carry specific molecular changes that may explain their poor prognostic associations.
Decreased fetal movements: Report from the International Stillbirth Alliance conference workshop
Authors: Bradford Billie F. , Hayes Dexter J. L. , Damhuis Stefanie , Shub Alexis , Akselsson Anna , Radestad Ingela , Heazell Alexander E. P. , Flenady Vicki , Gordijn Sanne J. 
Published: December 2023

AbstractMaternal reports of decreased fetal movement (DFM) are a common reason to present to maternity care and are associated with stillbirth and other adverse outcomes. Promoting awareness of fetal movements and prompt assessment of DFM has been recommended to reduce stillbirths. However, evidence to guide clinical management of such presentations is limited. Educational approaches to increasing awareness of fetal movements in pregnant women and maternity care providers with the aim of reducing stillbirths have recently been evaluated in a several large clinical trials internationally. The International Stillbirth Alliance Virtual Conference in Sydney 2021 provided an opportunity for international experts in fetal movements to share reports on the findings of fetal movement awareness trials, consider evidence for biological mechanisms linking DFM and fetal death, appraise approaches to clinical assessment of DFM, and highlight research priorities in this area. Following this workshop summaries of the sessions prepared by the authors provide an overview of understandings of fetal movements in maternity care at the current time and highlights future directions in fetal movement research.
Legislation expanding pharmacist scope of practice to furnish Human Immunodeficiency Virus pre‐exposure prophylaxis: A content analysis
Authors: Cocohoba Jennifer , Tweedie Lauren , Frank Michael , McElya Brad , Witt Ed 
Published: December 2023

AbstractIntroductionApproximately 1.2 million persons in the United States have indications for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP) yet utilization remains low. Alternative models for PrEP access, such as community pharmacy programs where pharmacists may prescribe and dispense HIV PrEP medications, may help improve rates of utilization. Individual states have begun to pass laws governing expanded pharmacist practice for provision of PrEP.MethodsAn internet search was conducted from January 2022 to June 2023 to identify United States legislative bills which support the independent provision of PrEP by pharmacists. A content analysis was conducted of the bill text to conceptualize key components, compare these across states, and hypothesize implications for implementation and pharmacy practice.ResultsTwelve states (Arkansas, California, Colorado, Nevada, Utah, New Mexico, Virginia, Oregon, Illinois, Maine, Rhode Island, and Connecticut) with legislation supporting pharmacist‐furnished HIV PrEP were identified. Content analysis revealed differences in required pharmacist training, conditions for furnishing PrEP, total amount of PrEP permitted for dispensing, and discussions of pharmacist‐provided laboratory testing and reimbursement.ConclusionPharmacist‐furnished PrEP is rapidly gaining support as a means to expand access to HIV prevention tools. State‐to‐state differences in legislation will have an impact on implementation and scalability of these models. It will be important to observe states that were early adopters of this type of legislation and who experienced challenges in implementing such programs in order to refine the new legislation being presented in other states.
Sleep duration and cardiorespiratory fitness in adolescents: Longitudinal analysis from the LabMed study
Authors: Sousa‐Sá Eduarda , Fonseca Ana Paula , Lopes Luís , Abreu Sandra , Moreira Carla , Agostinis‐Sobrinho César , Oliveira André , Azevedo Carolina , Santos Rute 
Published: December 2023

AbstractPurposeWe aimed to investigate longitudinal associations between sleep duration and cardiorespiratory fitness, in adolescents.MethodsSleep duration was self‐reported and cardiorespiratory fitness was assessed by the 20 m shuttle run test, both at baseline and follow‐up (2‐year follow‐up). Participants were 734 Northern Portuguese adolescents (349 girls), aged 14.6 ± 1.8 years, from the LabMed study.ResultsSignificant decreases were found between baseline and follow‐up for sleep duration, whereas for cardiorespiratory fitness there was an increase. Adolescents with short sleep duration at baseline had lower cardiorespiratory fitness at follow‐up, comparing to those meeting the sleep guidelines (odds ratio [OR] = 0.506, 95% confidence interval [CI]: 0.326–0.785; p = .002 for whole week; OR = 0.597, 95% CI: 0.407–0.875; p = .008 for weekdays). Girls who were short sleepers at baseline had lower odds of having a healthy cardiorespiratory fitness at follow‐up, comparing to those meeting the sleep guidelines (OR = 0.311, 95% CI: 0.158–0.613; p < .001 for whole week; OR = 0.469, 95% CI: 0.262–0.838; p = .011 for weekdays). No significant associations between sleep duration and cardiorespiratory fitness were found for boys.DiscussionThere was a significant longitudinal association between short sleep duration and lower cardiorespiratory fitness levels, particularly in girls. Future interventions targeting adolescents' sleep duration should acknowledge behavioral differences between genders, as well as different behaviors adopted by boys ang girls, specifically on weekends.
Effects of CYP2D6 *10 and *41 Variants in Healthy Chinese Men on the Pharmacokinetics of Dapoxetine
Authors: Wang Zhipeng , Gao Yuan , Ji Xingfang , Wu Tong , Pu Libin , Qiu Wen 
Published: December 2023

AbstractDapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), and is mainly metabolized by CYP2D6, CYP3A4, and flavin‐containing monooxygenase 1. The purpose of the study was to evaluate the effect of CYP2D6 polymorphism on the pharmacokinetics of dapoxetine in healthy Chinese men. Thirty‐nine subjects who received a single oral dose of 30 mg dapoxetine hydrochloride were classified based on their CYP2D6 genotype: *1/*1 (n = 9), *1/*41 (n = 1), *1/*10 (n = 12), *10/*41 (n = 3), or *10/*10 (n = 14). The difference in pharmacokinetic parameters between different genotype groups was analyzed and then scored according to the activity score system. Compared with the wild‐type subjects of CYP2D6 *1/*1, the peak plasma concentration (Cmax) and the area under the plasma drug concentration‐time curve (AUCinf) of dapoxetine in the *10/*10 and *10/*41 groups were notably increased (P ≤ .05). Significant differences in Cmax, AUC, volume of distribution/bioavailability (V/F) and clearance/bioavailability (CL/F) were observed among dapoxetine activity score groups (P ≤ .05). The AUCinf was increased significantly (154% and 89.73%, P ≤ .05) and the Cmax was increased significantly (73.45% and 42.67%, P ≤ .05) in CYP2D6 *10/*41 subjects, compared with CYP2D6 *1/*1 and *1/*10 subjects. The results obtained indicated that CYP2D6 *10 and *41 polymorphisms have significant effects on the pharmacokinetic properties of dapoxetine.
DBC1 maintains skeletal muscle integrity by enhancing myogenesis and preventing myofibre wasting
Authors: Liang Na , He Jia , Yan Jiaqi , Han Xueying , Zhang Xiaoqian , Niu Yamei , Sha Wuga , Li Jun 
Published: December 2023

AbstractBackgroundSkeletal muscle atrophy, particularly ageing‐related muscular atrophy such as sarcopenia, is a significant health concern. Despite its prevalence, the underlying mechanisms remain poorly understood, and specific approved medications are currently unavailable. Deleted in breast cancer 1 (DBC1) is a well‐known regulator of senescence, metabolism or apoptosis. Recent reports suggest that DBC1 may also potentially regulate muscle function, as mice lacking DBC1 exhibit weakness and limpness. However, the function of DBC1 in skeletal muscle and its associated molecular mechanisms remain unknown, thus prompting the focus of this study.MethodsTibialis anterior (TA) muscle‐specific DBC1 knockdown C57BL/6J male mice were generated through a single injection of 2.00 E + 11 vg of adeno‐associated virus 9 delivering single‐guide RNA for DBC1. Grip strength and endurance were assessed 2 months later, followed by skeletal muscle harvest. Muscle atrophy model was generated by cast immobilization of the mouse hindlimb for 2 weeks. Molecular markers of atrophy were probed in muscles upon termination. Cardiotoxin (CTX) was injected in TA muscles of DBC1 knockdown mice, and muscle regeneration was assessed by immunohistochemistry, quantitative PCR and western blotting. DBC1 knockdown C2C12 cells and myotubes were investigated using immunofluorescence staining, Seahorse, immunohistology, fluorescence‐activated cell sorting and RNA‐sequencing analyses.ResultsDBC1 knockdown in skeletal muscle of young mice led to signatures of muscle atrophy, including a 28% reduction in muscle grip force (P = 0.023), a 54.4% reduction in running distance (P = 0.002), a 14.3% reduction in muscle mass (P = 0.007) and significantly smaller myofibre cross‐sectional areas (P < 0.0001). DBC1 levels decrease in age‐related or limb immobilization‐induced atrophic mouse muscles and overexpress DBC1‐attenuated atrophic phenotypes in these mice. Muscle regeneration was hampered in mice with CTX‐induced muscle injury by DBC1 knockdown, as evidenced by reductions in myofibre cross‐sectional areas of regenerating myofibres with centralized nuclei (P < 0.0001), percentages of MyoG+ nuclei (P < 0.0001) and fusion index (P < 0.0001). DBC1 transcriptionally regulated mouse double minute 2 (MDM2), which mediated ubiquitination and degradation of forkhead box O3 (FOXO3). Increased FOXO3 proteins hampered myogenesis in DBC1 knockdown satellite cells by compromising around 50% of mitochondrial functions (P < 0.001) and exacerbated atrophy in DBC1 knockdown myofibres by activating the ubiquitin–proteasome and autophagy–lysosome pathways.ConclusionsDBC1 is essential in maintaining skeletal muscle integrity by protecting against myofibres wasting and enhancing muscle regeneration via FOXO3. This research highlights the significance of DBC1 for healthy skeletal muscle function and its connection to muscular atrophy.
Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics
Authors: Liu Shuaiyuan , Han Yibo , Kong Lingwen , Wang Guixue , Ye Zhiyi 
Published: December 2023

AbstractDespite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that “force” represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM.Research HighlightsBy examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.
Natural male hybrid common shrews with a very long chromosomal multivalent at meiosis appear not to be completely sterile
Authors: Matveevsky Sergey N. , Kolomiets Oxana L. , Shchipanov Nikolay A. , Pavlova Svetlana V. 
Published: December 2023

AbstractAmong 36 known chromosomal hybrid zones of the common shrew Sorex araneus, the Moscow–Seliger hybrid zone is of special interest because inter‐racial complex heterozygotes (F1 hybrids) produce the longest meiotic configuration, consisting of 11 chromosomes with monobrachial homology (undecavalent or chain‐of‐eleven: CXI). Different studies suggest that such a multivalent may negatively affect meiotic progression and in general should significantly reduce fertility of hybrids. In this work, by immunocytochemical and electron microscopy methods, we investigated for the first time chromosome synapsis, recombination and meiotic silencing in pachytene spermatocytes of natural inter‐racial heterozygous shrew males carrying CXI configurations. Despite some abnormalities detected in spermatocytes, such as associations of chromosomes, stretched centromeres, and the absence of recombination nodules in some arms of the multivalent, a large number of morphologically normal spermatozoa were observed. Possible low stringency of pachytene checkpoints may mean that even very long meiotic configurations do not cause complete sterility of such complex inter‐racial heterozygotes.
Akkermansia muciniphila might improve anti‐PD‐1 therapy against HCC by changing host bile acid metabolism
Authors: Lan Xiucai , Ma Jiaming , Huang Zhipeng , Xu Yuzhen , Hu Yaomin 
Published: December 2023

AbstractPD‐1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD‐1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD‐1mAb against HCC in a tumor‐bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+T proportion in the tumor microenvironment. Additionally, AKK downregulates PD‐L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD‐1mAb against HCC through its impact on bile acid metabolism.
Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel‐Based Analysis and Neurite Orientation Dispersion and Density Imaging
Authors: Xu Rui , Wang Ximing , Zhu Sijia , Jiang Bin , Wan Jiayi , Ma Jiali , Yu Yixing , Yu Liqiang , Fang Qi , Hu Chunhong , Zhu Mo 
Published: December 2023

BackgroundPrevious studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses.PurposeTo detect WM microstructural changes in ALS patients using fixel‐based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI.Study TypeProspective.PopulationThirty‐six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years).Field Strength/Sequence3 T; NODDI and FBA (b‐values = 0, 1000, and 2500 seconds/mm2).AssessmentSubgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS‐ci/ALS‐nci). Fiber density (FD), fiber‐bundle cross‐section (FC), combined fiber density and cross‐section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined.Statistical TestingChi‐square test, Mann–Whitney U test, two‐sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P‐value <0.05 was considered significant.ResultsALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS‐ci than ALS‐nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = −0.408).Data ConclusionFBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.
Rapid HIV‐1 genotyping assay for the detection of capsid mutations
Authors: Margot Nicolas , Naik Vidula , Nekkalapudi Anurag , Boopathy Archana , Falkard Brie , Callebaut Christian 
Published: December 2023

AbstractHuman immunodeficiency virus (HIV) capsid is one of the most recent viral proteins successfully targeted for the development of antiretrovirals. Lenacapavir is a first in class HIV‐1 capsid inhibitor that was recently approved for the treatment of highly treatment‐experienced people with HIV in combination with other anti‐HIV drugs. Owing to the novelty of the viral target, methods to characterize the potential resistance‐associated mutations present in capsid upon treatment failure have not been fully established yet. Here, we describe a rapid and simple method to amplify capsid fragments and to determine their sequence from various clinical samples including diverse HIV‐1 subtypes. These methods could easily be implemented in laboratories, including hospital laboratories often caring for this patient population.