bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between sarcopenic obesity and mortality in patients on peritoneal dialysis: a prospective cohort study
Authors: Shen Yiwei , Su Xinyu , Yu Zanzhe , Yan Hao , Ma Dahua , Xu Yimei , Yuan Jiangzi , Ni Zhaohui , Gu Leyi , Fang Wei 
Published: February 2024

BackgroundWhether sarcopenic obesity had unfavorable effect on survival of peritoneal dialysis (PD) patients is unknown. We aimed to investigate the association between sarcopenic obesity and survival in PD patients.MethodsThis was a prospective observational study. Eligible PD patients from November 2016 to December 2017 were enrolled and followed until August 31, 2023. Sarcopenia was defined following the recommendations of the Asian Working Group for Sarcopenia (AWGS) as low appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Obesity was defined using the percentage of body fat (PBF). Survival analysis was conducted using the Kaplan–Meier and log-rank test. The Cox regression and the cumulative incidence competing risk (CICR) analyzes were used to investigate the association between sarcopenic obesity and all-cause mortality.ResultsA total of 223 patients were enrolled with 133 (59.6%) males, a median age of 57.5 (44.6, 65.7) years, a median dialysis vintage of 20.3 (6.4, 57.7) months and 48 (21.5%) who had comorbid diabetes mellitus. Among them, 46 (20.6%) patients were sarcopenic, and 25 (11.2%) patients were diagnosed with sarcopenic obesity. After followed up for 51.6 (25.6, 73.9) months, the Kaplan–Meier curve showed the sarcopenic obesity (log-rank = 13.527, p &lt; 0.001) group had significant lower survival rate compared to the nonsarcopenic non-obesity group. For multivariate analysis, the CICR method showed patients with sarcopenic obesity had significantly higher mortality rate (HR: 2.190, 95% CI: 1.011–4.743, p = 0.047) compared to those with nonsarcopenic non-obesity.ConclusionSarcopenia is not uncommon in PD patients, with a considerable proportion having sarcopenic obesity. There is a significant association between sarcopenic obesity and an increased risk of mortality in PD patients.
A selective defect in the glial wedge as part of the neuroepithelium disruption in hydrocephalus development in the mouse hyh model is associated with complete corpus callosum dysgenesis
Authors: Rodríguez-Pérez Luis-Manuel , López-de-San-Sebastián Javier , de Diego Isabel , Smith Aníbal , Roales-Buján Ruth , Jiménez Antonio J. , Paez-Gonzalez Patricia 
Published: February 2024

IntroductionDysgenesis of the corpus callosum is present in neurodevelopmental disorders and coexists with hydrocephalus in several human congenital syndromes. The mechanisms that underlie the etiology of congenital hydrocephalus and agenesis of the corpus callosum when they coappear during neurodevelopment persist unclear. In this work, the mechanistic relationship between both disorders is investigated in the hyh mouse model for congenital hydrocephalus, which also develops agenesis of the corpus callosum. In this model, hydrocephalus is generated by a defective program in the development of neuroepithelium during its differentiation into radial glial cells.MethodsIn this work, the populations implicated in the development of the corpus callosum (callosal neurons, pioneering axons, glial wedge cells, subcallosal sling and indusium griseum glial cells) were studied in wild-type and hyh mutant mice. Immunohistochemistry, mRNA in situ hybridization, axonal tracing experiments, and organotypic cultures from normal and hyh mouse embryos were used.ResultsOur results show that the defective program in the neuroepithelium/radial glial cell development in the hyh mutant mouse selectively affects the glial wedge cells. The glial wedge cells are necessary to guide the pioneering axons as they approach the corticoseptal boundary. Our results show that the pioneering callosal axons arising from neurons in the cingulate cortex can extend projections to the interhemispheric midline in normal and hyh mice. However, pioneering axons in the hyh mutant mouse, when approaching the area corresponding to the damaged glial wedge cell population, turned toward the ipsilateral lateral ventricle. This defect occurred before the appearance of ventriculomegaly.DiscussionIn conclusion, the abnormal development of the ventricular zone, which appears to be inherent to the etiology of several forms of congenital hydrocephalus, can explain, in some cases, the common association between hydrocephalus and corpus callosum dysgenesis. These results imply that further studies may be needed to understand the corpus callosum dysgenesis etiology when it concurs with hydrocephalus.
RETRACTED: Comparison of the effects of EGF, FGF-b, and NGF on the proliferation, migration, and reprogramming of primary rat Müller cells
Authors: Liao Yanying , Wu Miaoqin 
Published: February 2024

PurposeDuring the healing process of full-thickness macular holes (FTMHs), the closure and recovery of the hole depend on the migration, proliferation, and activation of Müller cells to promote the closure of holes and restoration of the photosensitive layer. In this study, we investigated the ability of the epidermal growth factor (EGF), fibroblast growth factor-basic (FGF-b), and nerve growth factor (NGF) to influence this process by regulating proliferation, migration, and reprogramming of primary rat Müller cells.MethodsCell proliferation was measured using CCK8 [2- (2-Methoxy-4-nitrophenyl)-3- (4-nitrophenyl)-5- (2,4-disulfophenyl)-2H-tetrazolium Sodium Salt] colorimetric assays and EdU [5-Ethynyl-2′-deoxyuridine] assays over 48 h. Cell migration was measured using scratch-wound assays and transwell migration assays over 48 h. In addition, we conducted Western blot assays and immunofluorescence assays on cells that were specially treated for 1, 3, and 5 days for cell reprogramming. The percentage of EdU-positive cells in Nestin-positive have also been tested by co-immunofluorescence (Co-IF) staining.ResultsEGF and FGF-b significantly promoted the proliferation of Müller cells (p &lt; 0.05) at a concentration of 0–50 ng/mL, but NGF did not (p &gt; 0.05), compared to untreated controls. Exogenous FGF-b and EGF promote the reprogramming of primary rat Müller cells, significantly enhancing the neural stem cell marker Nestin after stimulation on the 1st, 3rd, and 5th days, respectively. The expression of Müller cell marker Vimentin was significantly (p &lt; 0.05) reduced during this period compared to the control group. However, there was no significant difference between the NGF and control groups. Furthermore, the EGF group expressed stronger Nestin expression than the SCM group. The Co-IF staining showed that early 50% of activated cells came from newly proliferating cells on the 5th day.ConclusionThese observations suggest that FGF-b can promote the activation of Müller cells in a short time and enhance the possessive features of neural stem cells, while EGF may act for a longer period of time. This may further the understanding of growth factor therapy in treating FTMHs, and Müller glia may be promising candidates for cell replacement therapy.
Motor and neurocognitive profiles of children with symptomatic spinal muscular atrophy type 1 with two copies of SMN2 before and after treatment: a longitudinal observational study
Authors: Bitetti Ilaria , Manna Maria Rosaria , Stella Roberto , Varone Antonio 
Published: February 2024

IntroductionSpinal muscular atrophy (SMA) is a neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. In clinical studies, gene replacement therapy with onasemnogene abeparvovec (formerly AVXS-101, Zolgensma®, Novartis) was efficacious in improving motor functioning in children with SMA. However, its effects on cognitive and language skills are largely unknown.MethodsThis longitudinal observational study evaluated changes in motor and neurocognitive functioning over a 1-year period after administration of onasemnogene abeparvovec in 12 symptomatic SMA type 1 patients with two copies of SMN2 aged 1.7–52.6 months at administration. Motor functioning was measured using the Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders (CHOP-INTEND) while neurocognitive assessment was measured using Griffiths III. Motor milestones and language ability were also assessed at each timepoint.Results and discussionStatistically significant increases in median CHOP-INTEND scores from baseline were observed at 1, 3, 6, and 12 months after onasemnogene abeparvovec administration (all p ≤ 0.005). Most (91.7%) patients were able to roll over or sit independently for &gt;1 min at 12 months. Significant increases in the Griffiths III Foundations of Learning, Language and Communication, Eye and Hand Coordination, and Personal-Social-Emotional subscale scores were observed at 12-months, but not in the Gross Motor subscale. Speech and language abilities progressed in most patients. Overall, most patients showed some improvement in cognitive and communication performance after treatment with onasemnogene abeparvovec in addition to significant improvement in motor functioning and motor milestones. Evaluation of neurocognitive function should be considered when assessing the global functioning of patients with SMA.
Optimizing adjuvant treatment options for patients with glioblastoma
Authors: Zhu Enzhao , Wang Jiayi , Shi Weizhong , Jing Qi , Ai Pu , Shan Dan , Ai Zisheng 
Published: February 2024

BackgroundThis study focused on minimizing the costs and toxic effects associated with unnecessary chemotherapy. We sought to optimize the adjuvant therapy strategy, choosing between radiotherapy (RT) and chemoradiotherapy (CRT), for patients based on their specific characteristics. This selection process utilized an innovative deep learning method.MethodsWe trained six machine learning (ML) models to advise on the most suitable treatment for glioblastoma (GBM) patients. To assess the protective efficacy of these ML models, we employed various metrics: hazards ratio (HR), inverse probability treatment weighting (IPTW)-adjusted HR (HRa), the difference in restricted mean survival time (dRMST), and the number needed to treat (NNT).ResultsThe Balanced Individual Treatment Effect for Survival data (BITES) model emerged as the most effective, demonstrating significant protective benefits (HR: 0.53, 95% CI, 0.48–0.60; IPTW-adjusted HR: 0.65, 95% CI, 0.55–0.78; dRMST: 7.92, 95% CI, 7.81–8.15; NNT: 1.67, 95% CI, 1.24–2.41). Patients whose treatment aligned with BITES recommendations exhibited notably better survival rates compared to those who received different treatments, both before and after IPTW adjustment. In the CRT-recommended group, a significant survival advantage was observed when choosing CRT over RT (p &lt; 0.001). However, this was not the case in the RT-recommended group (p = 0.06). Males, older patients, and those whose tumor invasion is confined to the ventricular system were more frequently advised to undergo RT.ConclusionOur study suggests that BITES can effectively identify GBM patients likely to benefit from CRT. These ML models show promise in transforming the complex heterogeneity of real-world clinical practice into precise, personalized treatment recommendations.
The efficacy of contralaterally controlled functional electrical stimulation compared to conventional neuromuscular electrical stimulation for recovery of limb function following a stroke: a systematic review and meta-analysis
Authors: Halawani Alhussain , Aljabri Ammar , Bahathiq Dena M. , Morya Roaa E. , Alghamdi Saeed , Makkawi Seraj 
Published: February 2024

IntroductionLimb paresis following a stroke is a common sequela that can impact patients’ quality of life. Many rehabilitation strategies targeting the restoration of motor function exist. This systematic review and meta-analysis aim to evaluate the effects of contralaterally controlled functional electrical stimulation (CCFES) as a modality for limb rehabilitation. Unlike conventional neuromuscular electrical simulation (NMES), the contra-laterality in CCFES is achieved by two methods a bend angle sensor or an electromyographic bridge (EMGB) method, both of which targets signals from the unaffected limb.MethodThis review study was performed following the preferred reporting item for systematic review and meta-analysis (PRISMA) guidelines. Records that met the inclusion criteria were extracted from the following databases: Medline, Embase, and Cochrane Register of Controlled Trials (CENTRAL). Additional articles were also retrieved from clinicaltrials.gov and China/Asia on Demand (CAOD). Only randomized controlled studies (RCTs) were included.ResultsSixteen RCTs met the inclusion criteria, and 14 of which were included in the quantitative analysis (meta-analysis). The results of the analysis show that when compared to conventional NMES, CCFES displayed a better improvement in the upper extremity Fugl–Meyer assessment (UEFMA) (SMD = 0.41, 95% CI: 0.21, 0.62, p-value &lt;0.0001, I2 = 15%, GRADE: moderate), box and blocks test (BBT) (SMD = 0.48, 95% CI: 0.10, 0.86, p-value = 0.01, I2 = 0%, GRADE: very low), modified Barthel index (mBI) (SMD = 0.44, 95% CI: 0.16, 0.71, p-value = 0.002, I2 = 0%, GRADE: moderate), active range of motion (AROM) (SMD = 0.61, 95% CI: 0.29, 0.94, p-value = 0.0002, I2 = 23%, GRADE: moderate), and surface electromyography (sEMG) scores (SMD = 0.52, 95% CI: 0.14, 0.90, p-value = 0.008, I2 = 0%, GRADE: low). The results of the subgroup analysis for the type of sensor used in CCFES shows that an EMGB (SMD = 0.58, 95% CI: 0.33, 0.84, p-value &lt;0.00001, I2 = 7%) is more effective than a bend angle sensor (SMD = 0.17, 95% CI: −0.12, 0.45, p-value = 0.25, I2 = 0%).ConclusionThe results of this study provide strong evidence that shows CCFES being a better electrical stimulation modality compared to conventional NMES. This could be explained by the fact that CCFES is bilateral in nature which offers a platform for better neuroplasticity following a stroke. There is still a need for high-quality studies with a standardized approach comparing CCFES to other treatment modalities.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=342670, identifier CRD42022342670.
Comparing feature selection and machine learning approaches for predicting CYP2D6 methylation from genetic variation
Authors: Fong Wei Jing , Tan Hong Ming , Garg Rishabh , Teh Ai Ling , Pan Hong , Gupta Varsha , Krishna Bernadus , Chen Zou Hui , Purwanto Natania Yovela , Yap Fabian , Tan Kok Hian , Chan Kok Yen Jerry , Chan Shiao-Yng , Goh Nicole , Rane Nikita , Tan Ethel Siew Ee , Jiang Yuheng , Han Mei , Meaney Michael , Wang Dennis , Keppo Jussi , Tan Geoffrey Chern-Yee 
Published: February 2024

IntroductionPharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related toCYP2D6in children from the GUSTO cohort.MethodsBuffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated withCYP2D6were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of theCYP2D6gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models’ performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites.ResultsOverall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model.DiscussionThe development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.
Design and motion control of exoskeleton robot for paralyzed lower limb rehabilitation
Authors: Zhu Zhiyong , Liu Lingyan , Zhang Wenbin , Jiang Cong , Wang Xingsong , Li Jie 
Published: February 2024

IntroductionPatients suffering from limb movement disorders require more complete rehabilitation treatment, and there is a huge demand for rehabilitation exoskeleton robots. Flexible and reliable motion control of exoskeleton robots is very important for patient rehabilitation.MethodsThis paper proposes a novel exoskeleton robotic system for lower limb rehabilitation. The designed lower limb rehabilitation exoskeleton robot mechanism is mainly composed of the hip joint mechanism, the knee joint mechanism and the ankle joint mechanism. The forces and motion of the exoskeleton robot were analyzed in detail to determine its design parameters. The robot control system was developed to implement closed-loop position control and trajectory planning control of each joint mechanism.ResultsMultiple experiments and tests were carried out to verify robot's performance and practicality. In the robot angular response experiments, the joint mechanism could quickly adjust to different desired angles, including 15°, 30°, 45°, and 60°. In the trajectory tracking experiments, the exoskeleton robot could complete tracking movements of typical actions such as walking, standing up, sitting down, go upstairs and go downstairs, with a maximum tracking error of ±5°. Robotic wearing tests on normal people were performed to verify the assistive effects of the lower limb rehabilitation exoskeleton at different stages.DiscussionThe experimental results indicated that the exoskeleton robot has excellent reliability and practicality. The application of this exoskeleton robotic system will help paralyzed patients perform some daily movements and sports.
Predictive value of controlling nutritional status score for prostate cancer diagnosis
Authors: Huang Jiaguo , Sun Ji , Hua Runmiao , Fan Yi , Wang Kai , Zheng Liying , Qian Biao 
Published: February 2024

ObjectiveThis study aims to explore the predictive value of the Controlling Nutritional Status (CONUT) score for prostate cancer (PCa) diagnosis.MethodsThe data of 114 patients who underwent prostate needle biopsies from June 2020 to December 2022 were retrospectively analyzed. The relationship between CONUT score and various clinical factors as well as PCa diagnosis was evaluated.ResultsThe pathological results classified patients into the PCa (n = 38) and non-PCa (n = 76) groups. Compared with the non-PCa group, the PCa group exhibited statistically significant differences in age, prostate-specific antigen (PSA), PSA density (PSAD), the proportion of PI-RADS ≥ 3 in mpMRI, and the CONUT score, prostate volume, lymphocyte count, and total cholesterol concentration (p &lt; 0.05). ROC curve analyses indicated the diagnostic accuracy as follows: age (AUC = 0.709), prostate volume (AUC = 0.652), PSA (AUC = 0.689), PSAD (AUC = 0.76), PI-RADS ≥ 3 in mpMRI (AUC = 0.846), and CONUT score (AUC = 0.687). When CONUT score was combined with PSA and PSAD, AUC increased to 0.784. The AUC of CONUT score combined with PSA, PSAD, and mpMRI was 0.881, indicates a higher diagnostic value. Based on the optimal cut-off value of CONUT score, compared with the low CONUT score group, the high CONUT score group has a higher positive rate of PCa diagnosis (p &lt; 0.05).ConclusionCONUT score is an excellent auxiliary index for PCa diagnosis in addition to the commonly used PSA, PSAD, and mpMRI in clinical practice. Further prospective trials with a larger sample size are warranted to confirm the present study findings.
Clinical analysis of 82 cases of acute promyelocytic leukemia with PML-RARα short isoform in children and adults
Authors: Huang Qiaolin , Zhang Yicheng , Zheng Miao 
Published: February 2024

BackgroundAcute promyelocytic leukemia (APL) with PML/RARα fusion gene is a distinct variant of acute myeloid leukemia. According to the different break sites of the PML gene, there are three transcripts: Long (bcr1), Variant (bcr2) and Short (bcr3).MethodsWe retrospectively analyzed 82 APL cases with PML-RARα short isoform.ResultsA total of 384 patients with APL were seen, of which 85(22.14%) had PML/RARα short isoform (bcr3) and 82 met the inclusion criteria. The median age was 33.5 years (range, 2-72 years). The incidences of hemorrhage in the intermediate- and high-risk group were higher, but only the incidence between medium and low risk differed statistically (P=0.006), and the incidences of fever, fatigue, splenomegaly, and lymph node enlargement and differentiation syndrome (DS) in those groups were not statistically significant (P&gt;0.05). FLT3 gene mutation rate and the mortality rate of the high-risk group were significantly higher than that of other groups (P=0.040 and P=0.004, P=0.041 and P=0.037, respectively). The mortality rate was lowest (4.26%) in the group treated with ATRA combined with arsenic and anthracycline. The 3-year OS and the 3-year DFS of the low and intermediate-risk group were better (P=0.019 and P=0.017, respectively).ConclusionsATRA combined with arsenic and anthracycline had significant impact on outcomes in APL with PML-RARα short isoform.