bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel MEIOB variants cause primary ovarian insufficiency and non-obstructive azoospermia
Authors: Wang Yurong , Liu Ling , Tan Chen , Meng Guiquan , Meng Lanlan , Nie Hongchuan , Du Juan , Lu Guang-Xiu , Lin Ge , He Wen-Bin , Tan Yue-Qiu 
Published: August 2022

Background: Infertility is a global health concern. MEIOB has been found to be associated with premature ovarian insufficiency (POI) and non-obstructive azoospermia (NOA), but its variants have not been reported in Chinese patients. The aim of this study was to identify the genetic aetiology of POI or NOA in three Han Chinese families.Methods: Whole-exome sequencing (WES) was used to identify candidate pathogenic variants in three consanguineous Chinese infertile families with POI or NOA. Sanger sequencing was performed to validate these variants in the proband of family I and her affected family members. In vitro functional analyses were performed to confirm the effects of these variants.Results: Two novel homozygous frameshift variants (c.258_259del and c.1072_1073del) and one novel homozygous nonsense variant (c.814C &gt; T) in the MEIOB gene were identified in three consanguineous Han Chinese families. In vitro functional analyses revealed that these variants produced truncated proteins and affected their function.Conclusion: We identified three novel MEIOB loss-of-function variants in local Chinese patients for the first time and confirmed their pathogenicity using in vitro functional analyses. These results extend the mutation spectrum of the MEIOB gene and have important significance for genetic counselling in these families.
Construction of a survival nomogram for gastric cancer based on the cancer genome atlas of m6A-related genes
Authors: Wang Xiaokang , Xu Kexin , Liao Xueyi , Rao Jiaoyu , Huang Kaiyuan , Gao Jianlin , Xu Gengrui , Wang Dengchuan 
Published: August 2022

Objective: Based on TCGA database, a prediction model for 1-, 3-, and 5-year overall survival rates of gastric cancer (GC) patients was constructed by analyzing the critical risk factors affecting the prognosis of gastric cancer patients.Method: Clinicopathological features as well as gene signature of GC patients were obtained from TCGA database. Patients were randomly divided into a training cohort and an internal validation cohort. Independent predictors of GC prognosis were analyzed by univariate and multivariate Cox analyses to construct nomogram. The accuracy and reliability of the model was further validated by calibration curves, ROC curves, and C-indexes, and the clinical utility of the model was analyzed by decision analysis curves.Result: Age, sex, N stage, M stage, METTL16, RBM15, FMR1, IGFBP1, and FTO were significantly associated with the prognosis of GC patients, and these predictors were further included in the construction of nomogram. The C-indexes for the training cohort and validation set were 0.735 and 0.688, respectively. The results of the ROC curve analysis indicated that the area under the curve (AUC) exceeded 0.6 in training and validation sets at 1, 3, and 5 years.Conclusion: We have constructed and validated a nomogram that provides individual survival condition prediction for GC patients. The prognostic model integrating gene signatures and clinicopathological characteristics would help clinicians determine the prognosis of patients with GC and develop individualized treatment plans.
Development of a prognostic model for children with neuroblastoma based on necroptosis-related genes
Authors: Jing Chu  
Published: August 2022

Background: Neuroblastoma (NBL) is a rare malignant tumor of the peripheral sympathetic nervous system in children with a low overall survival rate. Recent studies have revealed the important role of necroptosis in the occurrence and development of many kinds of tumors. In this study, a prognostic model based on necroptosis-related genes was constructed for NBL.Methods: Expression profiles and clinical information for patients with NBL were downloaded from TARGET. Data for necroptosis-related genes were extracted for Cox regression and lasso regression analyses to evaluate factors associated with prognosis and to construct a prognostic model. Data from the GEO datasets GSE62564 and GSE85047 were used for external verification. Associations between risk scores were calculated, and immune infiltration, drug sensitivity, and mutation analyses were conducted. Functional enrichment analyses of genes in the prognostic model were performed.Results: Six necroptosis-related genes (i.e., CYLD, JAK1, APC, ERH, CNBP, and BAX) were selected to construct a prognostic risk model. The risk score was highly correlated with levels of infiltration of multiple immune cells and sensitivity to common antineoplastic drugs. In addition, the risk score was identified as an independent prognostic factor for patients with NBL.Conclusion: We constructed and validated a prognostic model based on necroptosis-related genes, providing insights into the development and progression of NBL and a basis for improved management. In addition to providing a tool for clinical decision-making, these findings support the importance of necroptosis in NBL and may guide the development of therapeutic strategies targeting this process.
Screening of crosstalk and pyroptosis-related genes linking periodontitis and osteoporosis based on bioinformatics and machine learning
Authors: Liu Jia , Zhang Ding , Cao Yu , Zhang Huichao , Li Jianing , Xu Jingyu , Yu Ling , Ye Surong , Yang Luyi 
Published: August 2022

Background and objectiveThis study aimed to identify crosstalk genes between periodontitis (PD) and osteoporosis (OP) and potential relationships between crosstalk and pyroptosis-related genes.MethodsPD and OP datasets were downloaded from the GEO database and were performed differential expression analysis to obtain DEGs. Overlapping DEGs got crosstalk genes linking PD and OP. Pyroptosis-related genes were obtained from literature reviews. Pearson coefficients were used to calculate crosstalk and pyroptosis-related gene correlations in the PD and OP datasets. Paired genes were obtained from the intersection of correlated genes in PD and OP. PINA and STRING databases were used to conduct the crosstalk-bridge-pyroptosis genes PPI network. The clusters in which crosstalk and pyroptosis-related genes were mainly concentrated were defined as key clusters. The key clusters’ hub genes and the included paired genes were identified as key crosstalk-pyroptosis genes. Using ROC curve analysis and XGBoost screened key genes. PPI subnetwork, gene–biological process and gene-pathway networks were constructed based on key genes. In addition, immune infiltration was analyzed on the PD dataset using the CIBERSORT algorithm.ResultsA total of 69 crosstalk genes were obtained. 13 paired genes and hub genes TNF and EGFR in the key clusters (cluster2, cluster8) were identified as key crosstalk-pyroptosis genes. ROC and XGBoost showed that PRKCB, GSDMD, ARMCX3, and CASP3 were more accurate in predicting disease than other key crosstalk-pyroptosis genes while better classifying properties as a whole. KEGG analysis showed that PRKCB, GSDMD, ARMCX3, and CASP3 were involved in neutrophil extracellular trap formation and MAPK signaling pathway pathways. Immune infiltration results showed that all four key genes positively correlated with plasma cells and negatively correlated with T cells follicular helper, macrophages M2, and DCs.ConclusionThis study shows a joint mechanism between PD and OP through crosstalk and pyroptosis-related genes. The key genes PRKCB, GSDMD, ARMCX3, and CASP3 are involved in the neutrophil extracellular trap formation and MAPK signaling pathway, affecting both diseases. These findings may point the way to future research.
Prediction of conversion to dementia using interpretable machine learning in patients with amnestic mild cognitive impairment
Authors: Chun Min Young , Park Chae Jung , Kim Jonghyuk , Jeong Jee Hyang , Jang Hyemin , Kim Kyunga , Seo Sang Won 
Published: August 2022

PurposeAmnestic mild cognitive impairment (aMCI) is a transitional state between normal aging and Alzheimer’s disease (AD). However, not all aMCI patients are observed to convert to AD dementia. Therefore, developing a predictive algorithm for the conversion of aMCI to AD dementia is important. Parametric methods, such as logistic regression, have been developed; however, it is difficult to reflect complex patterns, such as non-linear relationships and interactions between variables. Therefore, this study aimed to improve the predictive power of aMCI patients’ conversion to dementia by using an interpretable machine learning (IML) algorithm and to identify the factors that increase the risk of individual conversion to dementia in each patient.MethodsWe prospectively recruited 705 patients with aMCI who had been followed-up for at least 3 years after undergoing baseline neuropsychological tests at the Samsung Medical Center between 2007 and 2019. We used neuropsychological tests and apolipoprotein E (APOE) genotype data to develop a predictive algorithm. The model-building and validation datasets were composed of data of 565 and 140 patients, respectively. For global interpretation, four algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) were compared. For local interpretation, individual conditional expectations (ICE) and SHapley Additive exPlanations (SHAP) were used to analyze individual patients.ResultsAmong the four algorithms, the extreme gradient boost model showed the best performance, with an area under the receiver operating characteristic curve of 0.852 and an accuracy of 0.807. Variables, such as age, education, the scores of visuospatial and memory domains, the sum of boxes of the Clinical Dementia Rating scale, Mini-Mental State Examination, and APOE genotype were important features for creating the algorithm. Through ICE and SHAP analyses, it was also possible to interpret which variables acted as strong factors for each patient.ConclusionWe were able to propose a predictive algorithm for each aMCI individual’s conversion to dementia using the IML technique. This algorithm is expected to be useful in clinical practice and the research field, as it can suggest conversion with high accuracy and identify the degree of influence of risk factors for each patient.
Quantitative susceptibility mapping and blood neurofilament light chain differentiate between parkinsonian disorders
Authors: Zhang Piao , Chen Junling , Cai Tongtong , He Chentao , Li Yan , Li Xiaohong , Chen Zhenzhen , Wang Lijuan , Zhang Yuhu 
Published: August 2022

ObjectivesWe employed quantitative susceptibility mapping (QSM) to assess iron deposition in parkinsonian disorders and explored whether combining QSM values and neurofilament light (NfL) chain levels can improve the accuracy of distinguishing Parkinson’s disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).Materials and methodsForty-seven patients with PD, 28 patients with MSA, 18 patients with PSP, and 28 healthy controls (HC) were enrolled, and QSM data were reconstructed. Susceptibility values in the bilateral globus pallidus (GP), putamen (PUT), caudate nucleus (CN), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) were obtained. Plasma NfL levels of 47 PD, 18 MSA, and 14 PSP patients and 22 HC were measured by ultrasensitive Simoa technology.ResultsThe highest diagnostic accuracy distinguishing MSA from PD patients was observed with increased susceptibility values in CN (AUC: 0.740). The susceptibility values in RN yielded the highest diagnostic performance for distinguishing PSP from PD patients (AUC: 0.829). Plasma NfL levels were significantly higher in the MSA and PSP groups than in PD and HC groups. Combining the susceptibility values in the RN and plasma NfL levels improved the diagnostic performance for PSP vs. PD (AUC: 0.904), whereas plasma NfL levels had higher diagnostic accuracy for MSA vs. PD (AUC: 0.877).ConclusionThe exploratory study indicates different patterns of iron accumulation in deep gray matter nuclei in Parkinsonian disorders. Combining QSM values with NfL levels may be a promising biomarker for distinguishing PSP from PD, whereas plasma NfL may be a reliable biomarker for differentiating MSA from PD. QSM and NfL measures appeared to have low accuracy for separating PD from controls.
Intraneural or extraneural ganglion cysts as a cause of cubital tunnel syndrome: A retrospective observational study
Authors: Yalikun Ainizier , Yushan Maimaiaili , Hamiti Yimurang , Lu Cheng , Yusufu Aihemaitijiang 
Published: August 2022

PurposeCubital tunnel syndrome caused by ganglion cysts has rarely been reported. The purpose of this study was to evaluate the surgical treatment outcomes of a patient diagnosed with cubital tunnel syndrome caused by intraneural or extraneural cysts and to summarize our experience.MethodIn total, 34 patients were evaluated retrospectively from January 2011 to January 2020 with a follow-up of more than 24 months. Preoperative data, such as demographic data, clinical symptoms, physical examination findings, and laboratory tests, were all recorded and pre-operative and post-operative data were compared. The function was evaluated by the modified Bishop scoring system and the McGowan grade at the last follow-up.ResultsImprovement of interosseous muscle strength, the Visual Analog Scale (VAS), 2-point discrimination (2-PD), electromyogram (EMG) result, Wartenberg sign, claw hand, and weakness could be clearly observed in all patients. Extraneural cysts were completely removed and the pedicles of the cysts were ligated. Intraneural cysts were incised and drained, and part of their cyst walls were removed using a microsurgical technique. All patients underwent anterior subcutaneous transposition (AST). At the last follow-up, McGowan's (0-IIa) grade increased from seven patients (20.6%) preoperatively to 27 patients (79.4%); the excellent and good rate according to the modified Bishop scoring system was 82.4% (28 patients), and all patients had no symptoms of recurrence after surgery.ConclusionThe treatment of cubital tunnel syndrome caused by intraneural or extraneural cysts achieved good long-term results through extraneural cyst resection or intraneural cyst incision and drainage combined with subcutaneous transposition. Early diagnosis and surgical treatment are essential for the patient's postoperative recovery.
The impact of cathodal tDCS on the GABAergic system in the epileptogenic zone: A multimodal imaging study
Authors: Abuhaiba Sulaiman I. , Duarte Isabel C. , Castelhano João , Dionísio Ana , Sales Francisco , Edden Richard , Castelo-Branco Miguel 
Published: August 2022

ObjectivesWe aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy.MethodsThis is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 × 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients.ResultsReal tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003).ConclusionThese results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges.
Early depression screening and short-term functional outcome in hospitalized patients for acute ischemic stroke
Authors: Baik Minyoul , Lee Hyungwoo , Lee Il Hyung , Heo JoonNyung , Nam Hyo Suk , Lee Hye Sun , Kim Young Dae 
Published: August 2022

BackgroundPatients with ischemic stroke are at high risk for post-stroke depression (PSD). There are limited data regarding the clinical impact of early PSD, assessed in hospitalized patients with acute ischemic stroke.MethodsThis hospital-based observational cohort study included consecutive patients with acute ischemic stroke or transient ischemic attack between July 2019 and June 2021. In the study hospital, all admitted patients were systematically screened for depression. The depression was screened using the Patient Health Questionnaire-9 (PHQ-9), and PHQ-9 positivity indicated early PSD, which was defined as a score of &gt;4. Logistic regression analyses were used to compare the rates of poor functional outcomes at 3 months in patients with and without PHQ-9 positivity.ResultsAmong 1339 patients admitted during the study period, 775 were included, with a median age of 68.0 years, and 316 (40.8%) were women. A total of 111 (14.3%) patients were PHQ-9 positive. History of cancer and early neurological deterioration were independently associated with PHQ-9 positivity. Poor functional outcomes at 3 months were observed in 147 patients (18.8%). PHQ-9 positivity independently showed a 2.2-fold increased risk of poor functional outcome at 3 months (Odds ratio 2.23; 95% confidence interval 1.05–4.73, P = 0.037).ConclusionsPatients with history of cancer and early neurological deterioration were at risk for early PSD. Early PSD was independently associated with poor functional outcomes at 3 months. The identification of early depression could offer opportunities for further questioning and exploration of symptoms, as well as interventions.
Effectiveness and safety of EVT in patients with acute LVO and low NIHSS
Authors: Kim Beom Joon , Menon Bijoy K. , Yoo Joonsang , Han Jung Hoon , Kim Bum Joon , Kim Chi Kyung , Kim Jae Guk , Kim Joon-Tae , Park Hyungjong , Baik Sung Hyun , Han Moon-Ku , Kang Jihoon , Kim Jun Yup , Lee Keon-Joo , Park Jong-Moo , Kang Kyusik , Lee Soo Joo , Cha Jae-Kwan , Kim Dae-Hyun , Jeong Jin-Heon , Park Tai Hwan , Park Sang-Soon , Lee Kyung Bok , Lee Jun , Hong Keun-Sik , Cho Yong-Jin , Park Hong-Kyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi-Sun , Kim Dong-Eog , Ryu Wi-Sun , Choi Kang-Ho , Choi Jay Chol , Kim Joong-Goo , Kwon Jee-Hyun , Kim Wook-Joo , Shin Dong-Ick , Yum Kyu Sun , Sohn Sung-Il , Hong Jeong-Ho , Kim Chulho , Lee Sang-Hwa , Lee Juneyoung , Almekhlafi Mohammed A. , Demchuk Andrew , Bae Hee-Joon 
Published: August 2022

Background and purposeThere is much uncertainty in endovascular treatment (EVT) decisions in patients with acute large vessel occlusion (LVO) and mild neurological deficits.MethodsFrom a prospective, nationwide stroke registry, all patients with LVO and baseline NIHSS &lt;6 presenting within 24 h from the time last known well (LKW) were included. Early neurological deterioration (END) developed before EVT was prospectively collected as an increasing total NIHSS score ≥2 or any worsening of the NIHSS consciousness or motor subscores during hospitalization not related to EVT. Significant hemorrhage was defined as PH2 hemorrhagic transformation or hemorrhage at a remote site. The modified Rankin Scale (mRS) was prospectively collected at 3 months.ResultsAmong 1,083 patients, 149 (14%) patients received EVT after a median of 5.9 [3.6–12.3] h after LKW. In propensity score-matched analyses, EVT was not associated with mRS 0-1 (matched OR 0.99 [0.63–1.54]) but increased the risk of a significant hemorrhage (matched OR, 4.51 [1.59–12.80]). Extraneous END occurred in 207 (19%) patients after a median of 24.5 h [IQR, 13.5–41.9 h] after LKW (incidence rate, 1.41 [95% CI, 1.23–1.62] per 100 person-hours). END unrelated to EVT showed a tendency to modify the effectiveness of EVT (P-for-interaction, 0.08), which decreased the odds of having mRS 0–1 in mild LVO patients without END (adjusted OR, 0.63 [0.40–0.99]).ConclusionsThe use of EVT in patients with acute LVO and low NIHSS scores may require the assessment of individual risks of early deterioration, hemorrhagic complications and expected benefit.
What names for covert awareness? A systematic review
Authors: Schnakers Caroline , Bauer Chase , Formisano Rita , Noé Enrique , Llorens Roberto , Lejeune Nicolas , Farisco Michele , Teixeira Liliana , Morrissey Ann-Marie , De Marco Sabrina , Veeramuthu Vigneswaran , Ilina Kseniya , Edlow Brian L. , Gosseries Olivia , Zandalasini Matteo , De Bellis Francesco , Thibaut Aurore , Estraneo Anna 
Published: August 2022

BackgroundWith the emergence of Brain Computer Interfaces (BCI), clinicians have been facing a new group of patients with severe acquired brain injury who are unable to show any behavioral sign of consciousness but respond to active neuroimaging or electrophysiological paradigms. However, even though well documented, there is still no consensus regarding the nomenclature for this clinical entity.ObjectivesThis systematic review aims to 1) identify the terms used to indicate the presence of this entity through the years, and 2) promote an informed discussion regarding the rationale for these names and the best candidates to name this fascinating disorder.MethodsThe Disorders of Consciousness Special Interest Group (DoC SIG) of the International Brain Injury Association (IBIA) launched a search on Pubmed and Google scholar following PRISMA guidelines to collect peer-reviewed articles and reviews on human adults (&gt;18 years) published in English between 2006 and 2021.ResultsThe search launched in January 2021 identified 4,089 potentially relevant titles. After screening, 1,126 abstracts were found relevant. Finally, 161 manuscripts were included in our analyses. Only 58% of the manuscripts used a specific name to discuss this clinical entity, among which 32% used several names interchangeably throughout the text. We found 25 different names given to this entity. The five following names were the ones the most frequently used: covert awareness, cognitive motor dissociation, functional locked-in, non-behavioral MCS (MCS*) and higher-order cortex motor dissociation.ConclusionSince 2006, there has been no agreement regarding the taxonomy to use for unresponsive patients who are able to respond to active neuroimaging or electrophysiological paradigms. Developing a standard taxonomy is an important goal for future research studies and clinical translation. We recommend a Delphi study in order to build such a consensus.