bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid detection of FAdV-4 by one-tube RPA-CRISPR/Cas12a assay
Authors: Ma Lei , Wang Xueping , Zhang Mingliang , Zhu Mengjie 
Published: February 2025

IntroductionFowl adenovirus serotype 4 (FAdV-4) is a highly contagious viral pathogen of global significance that affects various avian species. It primarily infects poultry and wild birds, leading to avian inclusion body hepatitis (IBH) and hepatitis-hydropericardium syndrome (HHS). The development of rapid diagnostic tools for detecting FAdV-4 is crucial for effective disease control and eradication efforts.MethodsIn this study, we developed a recombinase polymerase amplification (RPA) combined with CRISPR/Cas12a assay, specifically targeting the FAdV-4 Hexon gene. RPA and CRISPR/Cas12a reagents were added to the bottom and lid of the test tube at once, allowing the detection process to occur within a single reaction tube. This approach reduced contamination.ResultsThe RPA-CRISPR/Cas12a detection method can identify as few as 10 copies of the genome per reaction, demonstrating 100% sensitivity comparable to that of fluorescence PCR (qPCR). This approach exhibits high specificity for FAdV-4, with no cross-reactivity observed with other FAdV serotypes or common avian pathogens. Additionally, the agreement rate between the results of RPA-CRISPR/Cas12a and qPCR for detecting clinical samples is as high as 97.5%.DiscussionTherefore, the RPA-CRISPR/Cas12a assay presents a promising alternative for the simple, sensitive, and specific identification of FAdV-4.
Nomogram for predicting mild cognitive impairment in Chinese elder CSVD patients based on Boruta algorithm
Authors: Huang Yanzi , Huang Wendie , Ma Xiaoming , Zhao Guoyin , Kang Jingwen , Li Huajie , Li Jingwei , Sheng Shiying , Qian Fengjuan 
Published: February 2025

BackgroundThe number of patients with cerebral small vessel disease is increasing, especially among the elderly population. With the continuous improvement of detection techniques, the positivity rate keeps increasing. Our goal is to develop a nomogram for early identification of PSCI and PSCID in stroke patients.MethodsIn a retrospective cohort, chained data imputation was performed to ensure no statistical differences from the original dataset. Subsequently, Boruta algorithm was utilized for variable selection based on their importance, followed by logistic regression employing backward stepwise regression. Finally, the regression results were visualized as a Nomogram.ResultsThe nomogram chart in this study achieves clinical utility in a concise and user-friendly manner, passing the Hosmer-Lemeshow goodness-of-fit test. ROC and calibration curves indicate its high discriminative ability.ConclusionWhile CSVD is prevalent among middle-aged and older individuals, cognitive decline trajectories differ. Endocrine metabolic indicators like IGF-1 offer early predictive value. This study has produced a succinct nomogram integrating demographic and clinical indicators for medical application.
Stable improvement in hand muscle strength in incomplete spinal cord injury patients by long-term paired associative stimulation—a case series study
Authors: Holopainen Kirsi , Tolmacheva Aleksandra , Bersch Ines , Haakana Piia , Pohjonen Markus , Kirveskari Erika , Arokoski Jari , Shulga Anastasia 
Published: February 2025

IntroductionPaired associative stimulation (PAS) consists of high-intensity transcranial magnetic stimulation and high-frequency electric stimulation of the peripheral nerve (high-PAS) and can induce plastic changes in spared corticospinal connections in individuals with spinal cord injury (SCI), leading to the restoration of motor function. The objective of this study was to investigate the long-term effect of high-PAS on hand function and muscle strength.Materials and methodsHigh-PAS was applied to four patients with chronic, incomplete, cervical-level SCI multiple times a week for as long as hand muscle strength improved. The median, ulnar, and radial nerves of one hand chosen by the patient were stimulated. Patients underwent Medical Research Council (MRC) manual muscle testing monthly during the stimulation period and were followed for 12 months after the stimulation.ResultsStrength increased in both the stimulated and non-stimulated hands. In muscles innervated by stimulated nerves, strength increased on average by 24.5% from pre- to post-conditions (p = 0.013). The achieved strength level was maintained for a minimum of 6 months after completing the stimulations. Patients were also evaluated with motor point (MP) integrity testing to estimate the extent of lower motor neuron damage. High MP integrity testing scores (low extent of damage) correlated positively with good MRC outcomes of the stimulated hand after high-PAS (r = 0.52, p ≤ 0.001).ConclusionHigh-PAS may improve muscle strength of both the stimulated and contralateral sides. Stable results were achieved when stimulation was delivered as long as MRC score improved progressively. The optimal duration of high-PAS treatment remains unknown.Clinical trial registrationclinicaltrials.gov, identifier NCT03045744.
Clinical and biochemical characteristics for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome: a pilot observational study
Authors: Li Pei , Zhang Ye , Luo Li-Min , Wang Wen-Qing , Li Jing , Cheng Yan , Dang Xiao , Chen Yang , Jiang Wei 
Published: February 2025

BackgroundPolyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is rare life-threatening condition associated with a clonal plasma cell neoplasm.ObjectiveThe aim of this study is to investigate the clinical and biochemical features in patients with POEMS syndrome before and post-therapy.MethodsCharacteristics of demographic information, underlying diseases, clinical manifestations, laboratory indicators, and imaging examination were retrospectively collected when diagnosed and post-therapy in the patients POEMS syndrome between 2018 and 2024.ResultsNineteen newly-diagnosed, treatment-naïve patients with POEMS syndrome were enrolled. The diagnosis of POEMS syndrome was re-analyzed and matched the diagnostic criteria updated in 2023. All patients presented the symptoms of polyneuropathy and positive for M-protein. Most patients suffered with hyperpigmentation (n = 18), organomegaly (n = 18), elevated vascular endothelial growth factor (VEGF) (n = 17), extravascular volume overload (n = 15), sclerotic bone lesions (n = 11), and hypothyroidism (n = 10). Serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total protein, and albumin levels were down-regulated, while uric acid level was up-regulated in patients with POEMS syndrome. Reduced triiodothyronine, thyroxine, free triiodothyronine levels were negatively correlated with urea nitrogen, creatinine, and uric acid levels in patients with POEMS syndrome. VEGF level, which was negatively correlated with Ca2+ level (r = −0.56), was reduced in most patients with POEMS syndrome receiving bortezomib/ixazomib and lenalidomide/thalidomide therapy. Aspartate aminotransferase, total protein, and estimated glomerular filtration rate levels were increased, while creatinine and uric acid levels were reduced post-therapy in patients with POEMS syndrome.ConclusionPatients with POEMS syndrome had impaired liver and renal function, and effective therapy might partly repair the liver and renal dysfunction.
Dynamic functional connectivity patterns predict early antidepressant treatment response in drug-naïve, first-episode adolescent MDD
Authors: Ran Maojia , Zhang Hang , Jin Meijiang , Tao Yuanmei , Xu Hanmei , Zou Shoukang , Wang Zhujun , Deng Fang , Huang Lijuan , Zhang Hong , Tang Xiaowei , Wang Yanping , Fu Xia , Yin Li 
Published: February 2025

ObjectiveAdolescents with major depressive disorder (MDD) exhibit abnormal dynamic functional connectivity (dFC) patterns, but it remains unclear whether these aberrant dFC patterns are linked to antidepressant treatment. The aim of this study is to investigate whether dFC patterns will be changed by antidepressant treatment, as well as whether baseline dFC pattern could predict treatment response in adolescent MDD patients.MethodWe included 35 drug-naïve, first-episode MDD adolescents (age 14.40 ± 1.24; 8 males and 27 females) and 24 healthy controls (HCs, age 14.21 ± 1.41; 11 males and 13 females). All MDD adolescents received 6 weeks of antidepressant treatment. Resting state and T1 MRI data were collected in MDD adolescents before and after treatment and in HCs. Independent component analysis (ICA) was used to compare the different dFC pattern between MDD adolescents and HCs at baseline, as well as which between before and after treatment in MDD adolescents. Finally, Pearson correlation and multivariate linear regression analyses were used to explore the associations between dFC pattern and changed score of BDI in MDD adolescents.ResultsThe mean dFC value between right inferior frontal gyrus (IFG) and bilateral insular cortex (IC; right, r = −0.461, p-FDR = 0.012; left, r = −0.518, p-FDR = 0.007) at baseline were negatively correlated with BDI score reduction. The mean dFC value between left frontal pole (FP) and right superior parietal lobule (SPL) after treatment was positively correlated with BDI score reduction (r = 0.442, p-FDR = 0.014). And the mean dFC values between right IFG and bilateral IC (right, β = −1.563, p-FDR = 0.021; left, β = −1.868, p-FDR = 0.012) at baseline could predict antidepressant treatment response.ConclusionThese findings demonstrate that dFC patterns between some brain areas could be a prospective factor for predicting antidepressant treatment response.
Ketamine effects on resting state functional brain connectivity in major depressive disorder patients: a hypothesis-driven analysis based on a network model of depression
Authors: Recourt Kasper , Van Gerven Joop , Drenth Nadieh , van der Grond Jeroen , Nishigori Kantaro , Van Der Wee Nic J. , Jacobs Gabriël E. 
Published: February 2025

IntroductionKetamine demonstrates robust and rapidly occurring antidepressant effects in patients with difficult-to-treat major depressive disorder. Ketamine’s antidepressant effects and its impact on functional networks in non-resistant forms of major depressive disorder are expected to provide valuable insight into ketamine’s mechanism of action related to depression.MethodsThis study employs an existing network model of major depressive disorder to investigate the effects of ketamine on resting state connectivity in a therapy-non-resistant major depressive disorder population. In a randomized, double-blind, placebo-controlled, cross-over study, 0.5 mg/kg racemic ketamine or 0.9%NaCl was administered intravenously in 16 MDD patients. We applied resting-state functional magnetic resonance imaging (rs-fMRI) to explore changes in functional brain connectivity directly at 50, 80 and 165 min (acute) and 24 h (delayed) following ketamine administration. A clinician-rated 10-item scale (MADRS) was administered at 165 min and 24 h after ketamine administration. Connections-of-interest (COIs) were based on the previously published corticolimbic-insular-striatalpallidal-thalamic (CLIPST) circuitry model of major depressive disorder.ResultsCompared with placebo, ketamine significantly (p &lt; 0.0014) reduced the mean (SD) MADRS total score from 21.2 (5.9) pre-dose to 10.3 (4.6) 24 h post-dose. At both acute (p &lt; 0.0172) and delayed (p &lt; 0.0488) time points, significant rs-fMRI connectivity changes occurred only in MDD-related COIs as proposed by the CLIPST model. No changes in functional connectivity were found in non-CLIPST connections.DiscussionThis study demonstrates that ketamine specifically affects depression-related circuitry. Analyzing functional connectivity based on a neurocircuitry model of a specific CNS disease and drug action may be an effective approach that could result in a more targeted analysis in future pharmaco-fMRI studies in CNS drug development.
Short-term caloric restriction or resveratrol supplementation alters large-scale brain network connectivity in male and female rats
Authors: van Rooij Judith R. A. , van den Berg Monica , Vasilkovska Tamara , Van Audekerke Johan , Kosten Lauren , Bertoglio Daniele , Adhikari Mohit H. , Verhoye Marleen 
Published: February 2025

IntroductionDietary interventions such as caloric restriction (CR) exert positive effects on brain health. Unfortunately, poor compliance hinders the success of this approach. A proposed alternative is resveratrol (Rsv), a CR-mimetic known to promote brain health. Direct comparison between the effects of Rsv and CR on brain health is lacking, with limited knowledge on their sex-specific effects. Therefore, we aimed to compare and unravel the sex-specific impact of these dietary interventions on spontaneous brain activity.MethodsHere, we used resting-state fMRI to investigate functional connectivity (FC) changes in five prominent resting-state brain networks (RSNs) in healthy 4 month old male and female F344 rats supplemented to either 40% CR or daily Rsv supplementation (10 mg/kg, oral) for the duration of 1 month.ResultsOur results demonstrated a decreased body weight (BW) in CR rats, as well as an increase in body weight in male Rsv supplemented rats, compared to female Rsv supplemented rats, whereas this difference between sexes was not observed in the control or CR groups. Furthermore, we found that both CR or Rsv supplementation induce a female-specific decrease of FC between the subcortical network and hippocampal network, and between the subcortical network and lateral cortical network. Moreover, Rsv supplementation lowered FC within the hippocampal network and between the hippocampal and the default mode like network, the lateral cortical network and the sensory network—an effect not observed for the CR rats.DiscussionOur findings reveal that both CR and Rsv induce a similar female-specific decrease of FC in RSNs associated with memory and emotion, all the while CR and Rsv induce dissimilar changes in body weight and other within- and between-RSN FC measures. Altogether, this study provides insight into the effects and comparability of short-term CR and Rsv supplementation on brain connectivity within- and between-RSNs in both male and female F344 rats, providing a FC reference for future research of dietary effects.
Associations between the intake of single and multiple dietary vitamins and depression risk among populations with chronic kidney disease
Authors: Yu Chunli , Liu Kun , Yao Weiguo , Tang Dingzhong 
Published: February 2025

BackgroundThe effects of multivitamin exposure on depression among patients with chronic kidney disease (CKD) have not been thoroughly explored. This study aimed to explore the effects of individual vitamin intakes and the joint effect of the intake of multiple vitamins (including vitamins A, B1, B2, B6, B12, C, D, E, and K) on depression risk in participants with CKD.MethodsA total of 3,123 participants with CKD (weighted n = 25,186,480) from the National Health and Nutrition Examination Survey database from 2007 to 2014 were included. Weighted multivariate logistic regression models were utilized to analyze the associations of individual dietary vitamin intakes with depression risk. Additionally, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were performed to evaluate the joint effect of the intake of the nine vitamins on depression risk.ResultsThe overall prevalence of depression was approximately 11.3% in the study participants. In the fully adjusted model, high intakes of vitamin A (OR: 0.54, 95% CI: 0.40–0.74), vitamin B1 (OR: 0.67, 95% CI: 0.48–0.95), vitamin B6 (OR: 0.70, 95% CI: 0.49–0.99), vitamin D (OR: 0.67. 95% CI: 0.48–0.94), and vitamin K (OR: 0.61, 95% CI: 0.44–0.85) were associated with a reduced likelihood of depression. BKMR and WQS regression showed that the joint effect of the intake of the nine dietary vitamins had a significant negative effect on depression, with vitamin A intake being the largest contributor in the two models. Lastly, WQS regression reflected the total mixed exposure effect of the nine vitamins (OR: 0.82, 95% CI: 0.69–0.99).ConclusionHigh intakes of vitamins A, B1, B6, D, and K are associated with low depression risk in patients with CKD. Furthermore, co-exposure to the nine dietary vitamins is a crucial factor contributing to low depression risk in this population.
The association between eight complete blood count-derived inflammatory markers and muscle health
Authors: Zhang Jingyuan , Wang Yuqi , Liu Heng , Lei Zhuolin , Cheng Shouquan , Cao Hong 
Published: February 2025

BackgroundMost studies have evaluated sarcopenia and muscle health solely based on muscle mass. This study comprehensively examined the associations between eight inflammatory indicators and muscle mass and strength, with the aim of identifying an indicator capable of evaluating muscle health across multiple dimensions.MethodsThis study included 10,440 participants from the National Health and Nutrition Examination Survey (NHANES, 2011–2018) and 5,384 participants from NHANES (2011–2014). Multivariate logistic regression, smooth curve fitting, restricted cubic spline (RCS) analysis, subgroup analysis, and Spearman's correlation were used to comprehensively assess the associations between the eight inflammatory indicators and muscle mass and strength. Receiver operating characteristic (ROC) curves were used to compare the predictive abilities of the different indices for low muscle mass and muscle strength. Additionally, NHANES data were cross-validated with data from 554 patients at our hospital to evaluate the ability of the systemic immune inflammatory index (SII) to distinguish between low muscle mass and strength.ResultsAfter controlling for all potential confounding factors, multiple logistic regression analysis revealed that apart from the platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and derived NLR (dNLR), the neutrophil-to-monocyte-plus-lymphocyte ratio (NMLR), neutrophil-to-lymphocyte ratio (NLR), SII, systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV) were significantly negatively correlated with muscle mass and strength. However, NMLR and NLR were significantly associated with changes in muscle mass only in Q4 (P &lt; 0.05). In the stratified analysis by body mass index (BMI), only the SII, NLR, and NMLR were unaffected by BMI. In the cross-validation, the predictive performance of the SII for low muscle mass [area under the curve (AUC) = 0.699, 0.677, and 0.685] and low muscle strength (AUC = 0.857, 0.849, and 0.840) demonstrated a good reference value. RCS and smooth curve fitting analyses indicated that most inflammatory markers were linearly correlated with muscle health (P &lt; 0.05).ConclusionCompared with other inflammatory markers (e.g., PIV and dNLR), the SII demonstrated a more robust predictive ability, was less influence by covariates, and exhibited high generalization performance in internal and external validation. SII may be crucial in identifying “hidden sarcopenia” and the early stages of muscle functional decline.
Efficacy and safety of pembrolizumab in patients with advanced endometrial cancer: a systematic review and meta-analysis
Authors: Pan Biqiong , Lai Xiaojun , Lu Jiefang , Bao Xiaoyan , Fan Zengke , Sun Jie 
Published: February 2025

ObjectiveThis meta-analysis evaluated pembrolizumab monotherapy and combination therapy’s efficacy and safety in recurrent or advanced endometrial cancer (EC).MethodsWe utilized PubMed, Embase, Cochrane Library, and Web of Science databases to identify clinical trials that were used to search literature from July 2013 to July 2023 to evaluate the efficacy and safety of pembrolizumab in patients with advanced EC. Eight studies with 2,742 patients were included. Outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), complete remission (CR), and adverse events (AEs); a subgroup analysis was carried out based on combination treatment regimens. Quality assessment of the included studies was conducted using the Cochrane Risk of Bias Tool, the Newcastle–Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal checklist.ResultsPembrolizumab reduced progression risk [hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.44, 0.63; p &lt; 0.00001] and death risk when combined with lenvatinib (HR: 0.67; 95% CI: 0.59, 0.76; p &lt; 0.00001). Pembrolizumab monotherapy and lenvatinib combination achieved higher ORR (OR: 3.61; 95% CI: 2.12, 6.13; p &lt; 0.00001) and CR rates (OR: 2.7; 95% CI: 1.59, 4.57; p &lt; 0.05) than controls. Single-arm studies: 8% CR and 4% PR in pembrolizumab-treated patients. Pooled AE incidence: 86%, with 43% grade 3/4. Two randomized controlled trials (RCTs) found that the pembrolizumab group had a higher incidence of grade 3 or 4 AEs compared to the control group (OR: 2.23; 95% CI: 1.23, 4.04; p = 0.008).ConclusionPembrolizumab monotherapy or combination significantly improves survival in recurrent or advanced EC and has manageable toxicity albeit with a relatively high incidence of treatment-related AEs.
The prognostic utility of the ratio of lymphocyte to monocyte in patients with metastatic colorectal cancer: a systematic review and meta-analysis
Authors: Mei Pingping , Huang Li , Lin Lu , Chen Yan , Guo Xiutian 
Published: February 2025

BackgroundAlthough advancements in treatment have resulted in improved overall outcomes for patients diagnosed with colorectal cancer, the prognosis remains unfavorable for individuals with metastatic colorectal cancer (mCRC). The association between lymphocyte/monocyte ratio (LMR) and clinical outcomes in mCRC patients is a subject of controversy. To systematically evaluate the correlation between LMR and prognostic factors in individuals with mCRC, we conducted this meta-analysis.MethodsThe databases PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for all relevant studies from their inception until October 26, 2024. Study selection was conducted based on predetermined inclusion and exclusion criteria. The primary outcomes of interest included prognosis measures such as overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and cancer-specific survival (CSS) in patients with metastatic colorectal cancer. Random-effects models or fixed-effects models were used to determine the pooled risk ratio (HR) and corresponding 95% confidence interval (CI) for each outcome indicator. Additionally, the pooled odds ratio (OR) and its corresponding 95% CI were calculated for LMR and clinicopathological characteristics.ResultsFourteen studies involving 3,089 patients were included in the analysis. The pooled analysis found that high LMR was correlated with better OS (HR: 0.55, 95% CI: 0.49-0.62, p&lt;0.00001), PFS (HR: 0.68, 95% CI: 0.57-0.81, p&lt;0.0001) and CSS(HR: 0.55, 95% CI: 0.32-0.95, p=0.03),The prognostic value of high LMR values for DFS(HR: 0.93, 95% CI: 0.78-1.12, p=0.46) in patients with metastatic rectal cancer was not found to be significant. We performed subgroup analyses based on study characteristics to confirm the robustness of our findings. Further clinicopathological analysis showed no significant difference between patients with elevated LMR and those without elevated LMR.ConclusionsIn conclusion, the results demonstrate a robust correlation between elevated LMR levels and a favorable prognosis in terms of overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) among patients diagnosed with metastatic colorectal cancer. However, further high-quality prospective studies are warranted to validate our findings since the majority of current investigations have relied on retrospective study designs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024496467, identifier CRD42024496467.