bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher–Neuhäuser Syndrome
Authors: He Junyu , Liu Xin , Liu Liyi , Zeng Shaohao , Shan Shuanghong , Liao Zhihong 
Published: February 2022

Background: Boucher–Neuhäuser syndrome (BNS, MIM 215470) is a rare autosomal recessive syndrome caused by mutations in the PNPLA6 gene. Few BNS cases have been reported for functional validation at the RNA level. Herein, we report on the family of a 17-year-old girl with clinical characteristics of BNS, genetic validation, and a systematic review of PNPLA6 variants related to BNS.Methods: Clinical data and blood samples were collected from the patient and their parents, and whole-exome sequencing was performed and confirmed by Sanger sequencing. RNA-sequencing (RNA-Seq) and quantitative RT-PCR (qRT-PCR) were performed, and the three-dimensional protein structures of the variants were predicted.Results: We report a 17-year-old female with progressive night blindness since the age of four, primary amenorrhea, and non-development of secondary sexual characteristics. Her impaired vision was diagnosed as retinal pigmentary degeneration of the retina. She had congenital hypogonadotropic hypogonadism (CHH) but no cerebellar ataxia at present. Two novel compound heterozygous variants (c.2241del/p.Met748TrpfsTer65 and c.2986A&gt;G/p.Thr996Ala) of the PNPLA6 gene (NM_006702.4) were identified by whole-exome sequencing. The former variant was carried from her healthy father and has not been reported previously. The latter was inherited from her healthy mother and was noted in a report without functional studies. The RT-PCR results showed that the mRNA expression of PNPLA6 was lower in this patient and her father than in the control group. She was diagnosed with BNS. Both variants (c.2241del and c.2986A&gt;G) were likely pathogenic according to the ACMG criteria. The novel variants in the PNPLA6 gene related to Boucher–Neuhäuser syndrome were summarized in this article.Conclusion: The possibility of Boucher–Neuhäuser syndrome should be considered when patients present with night blindness, impaired vision, and hypogonadotropic hypogonadism. Gene sequencing is currently the primary diagnostic method. Herein, novel compound heterozygous variants of PNPLA6 were identified in a BNS patient, and its function was verified at the RNA level. The PNPLA6 c.2241del variant is novel and potentially pathogenic, expanding the mutation spectrum in PNPLA6.
Cytotoxic B Cells in Relapsing-Remitting Multiple Sclerosis Patients
Authors: Boldrini Vinícius O. , Marques Ana M. , Quintiliano Raphael P. S. , Moraes Adriel S. , Stella Carla R. A. V. , Longhini Ana Leda F. , Santos Irene , Andrade Marília , Ferrari Breno , Damasceno Alfredo , Carneiro Rafael P. D. , Brandão Carlos Otávio , Farias Alessandro S. , Santos Leonilda M. B. 
Published: February 2022

BackgroundEmerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) pathogenesis.ObjectiveTo investigate whether CD19+ B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8+ T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients.MethodsIn this study, 104 RRMS patients during different treatments and 58 healthy donors were included. CD8, CD19, Runx3, and GzmB expression was assessed by flow cytometry analyses.ResultsRRMS patients during fingolimod (FTY) and natalizumab (NTZ) treatment showed increased percentage of circulating CD8+GzmB+ T lymphocytes when compared to healthy volunteers. An increase in circulating CD19+GzmB+ B cells was observed in RRMS patients during FTY and NTZ therapies when compared to glatiramer (GA), untreated RRMS patients, and healthy donors but not when compared to interferon-β (IFN). Moreover, regarding Runx3, the transcriptional factor classically associated with cytotoxicity in CD8+ T lymphocytes, the expression of GzmB was significantly higher in CD19+Runx3+-expressing B cells when compared to CD19+Runx3- counterparts in RRMS patients.ConclusionsCD19+ B cells may exhibit cytotoxic behavior resembling CD8+ T lymphocytes in MS patients during different treatments. In the future, monitoring “cytotoxic” subsets might become an accessible marker for investigating MS pathophysiology and even for the development of new therapeutic interventions.
The Influence of Temperature on the Antiviral Response of mIgM+ B Lymphocytes Against Hirame Novirhabdovirus in Flounder (Paralichthys olivaceus)
Authors: Tang Xiaoqian , Ma Xinbiao , Cao Jing , Sheng Xiuzhen , Xing Jing , Chi Heng , Zhan Wenbin 
Published: February 2022

Hirame novirhabdovirus (HIRRV) is an ongoing threat to the aquaculture industry. The water temperature for the onset of HIRRV is below 15°C, the peak is about 10°C, but no mortality is observed over 20°C. Previous studies found the positive signal of matrix protein of HIRRV (HIRRV-M) was detected in the peripheral blood leukocytes of viral-infected flounder. Flow cytometry and indirect immunofluorescence assay showed that HIRRV-M was detected in mIgM+ B lymphocytes in viral-infected flounder maintained at 10°C and 20°C, and 22% mIgM+ B lymphocytes are infected at 10°C while 13% are infected at 20°C, indicating that HIRRV could invade into mIgM+ B lymphocytes. Absolute quantitative RT-PCR showed that the viral copies in mIgM+ B lymphocytes were significantly increased at 24 h post infection (hpi) both at 10°C and 20°C, but the viral copies in 10°C infection group were significantly higher than that in 20°C infection group at 72 hpi and 96 hpi. Furthermore, the B lymphocytes were sorted from HIRRV-infected flounder maintained at 10°C and 20°C for RNA-seq. The results showed that the differentially expression genes in mIgM+ B lymphocyte of healthy flounder at 10°C and 20°C were mainly enriched in metabolic pathways. Lipid metabolism and Amino acid metabolism were enhanced at 10°C, while Glucose metabolism was enhanced at 20°C. In contrast, HIRRV infection at 10°C induced the up-regulation of the Complement and coagulation cascades, FcγR-mediated phagocytosis, Platelets activation, Leukocyte transendothelial migration and Natural killer cell mediated cytotoxicity pathways at 72 hpi. HIRRV infection at 20°C induced the up-regulation of the Antigen processing and presentation pathway at 72 hpi. Subsequently, the temporal expression patterns of 16 genes involved in Antigen processing and presentation pathway were investigated by qRT-PCR, and results showed that the pathway was significantly activated by HIRRV infection at 20°C but inhibited at 10°C. In conclusion, HIRRV could invade into mIgM+ B lymphocytes and elicit differential immune response under 10°C and 20°C, which provide a deep insight into the antiviral response in mIgM+ B lymphocytes.
Intermittent Theta Burst Stimulation Increases Natural Oscillatory Frequency in Ipsilesional Motor Cortex Post-Stroke: A Transcranial Magnetic Stimulation and Electroencephalography Study
Authors: Ding Qian , Chen Songbin , Chen Jixiang , Zhang Shunxi , Peng Yuan , Chen Yujie , Chen Junhui , Li Xiaotong , Chen Kang , Cai Guiyuan , Xu Guangqing , Lan Yue 
Published: February 2022

ObjectiveIntermittent theta burst stimulation (iTBS) has been widely used as a neural modulation approach in stroke rehabilitation. Concurrent use of transcranial magnetic stimulation and electroencephalography (TMS-EEG) offers a chance to directly measure cortical reactivity and oscillatory dynamics and allows for investigating neural effects induced by iTBS in all stroke survivors including individuals without recordable MEPs. Here, we used TMS-EEG to investigate aftereffects of iTBS following stroke.MethodsWe studied 22 stroke survivors (age: 65.2 ± 11.4 years; chronicity: 4.1 ± 3.5 months) with upper limb motor deficits. Upper-extremity component of Fugl-Meyer motor function assessment and action research arm test were used to measure motor function of stroke survivors. Stroke survivors were randomly divided into two groups receiving either Active or Sham iTBS applied over the ipsilesional primary motor cortex. TMS-EEG recordings were performed at baseline and immediately after Active or Sham iTBS. Time and time-frequency domain analyses were performed for quantifying TMS-evoked EEG responses.ResultsAt baseline, natural frequency was slower in the ipsilesional compared with the contralesional hemisphere (P= 0.006). Baseline natural frequency in the ipsilesional hemisphere was positively correlated with upper limb motor function following stroke (P= 0.007). After iTBS, natural frequency in the ipsilesional hemisphere was significantly increased (P&lt; 0.001).ConclusionsThis is the first study to investigate the acute neural adaptations after iTBS in stroke survivors using TMS-EEG. Our results revealed that natural frequency is altered following stroke which is related to motor impairments. iTBS increases natural frequency in the ipsilesional motor cortex in stroke survivors. Our findings implicate that iTBS holds the potential to normalize natural frequency in stroke survivors, which can be utilized in stroke rehabilitation.
Distinctive Temporal Trajectories of Alzheimer’s Disease Biomarkers According to Sex and APOE Genotype: Importance of Striatal Amyloid
Authors: Kim Jun Pyo , Chun Min Young , Kim Soo-Jong , Jang Hyemin , Kim Hee Jin , Jeong Jee Hyang , Na Duk L. , Seo Sang Won 
Published: February 2022

PurposePreviously, sex and apolipoprotein E (APOE) genotype had distinct effects on the cognitive trajectory across the Alzheimer’s disease (AD) continuum. We therefore aimed to investigate whether these trajectory curves including β-amyloid (Aβ) accumulation in the cortex and striatum, and tau accumulation would differ according to sex and APOE genotype.MethodsWe obtained 534 subjects for 18F-florbetapir (AV45) PET analysis and 163 subjects for 18F-flortaucipir (AV1451) PET analysis from the Alzheimer’s Disease Neuroimaging Initiative database. For cortical Aβ, striatal Aβ, and tau SUVR, we fitted penalized splines to model the slopes of SUVR value as a non-linear function of baseline SUVR value. By integrating the fitted splines, we obtained the predicted SUVR curves as a function of time.ResultsThe time from initial SUVR to the cutoff values were 14.9 years for cortical Aβ, 18.2 years for striatal Aβ, and 22.7 years for tau. Although there was no difference in cortical Aβ accumulation rate between women and men, striatal Aβ accumulation was found to be faster in women than in men, and this temporal difference according to sex was more pronounced in tau accumulation. However, APOE ε4 carriers showed faster progression than non-carriers regardless of kinds of AD biomarkers’ trajectories.ConclusionOur temporal trajectory models illustrate that there is a distinct progression pattern of AD biomarkers depending on sex and APOE genotype. In this regard, our models will be able to contribute to designing personalized treatment and prevention strategies for AD in clinical practice.
Neurofilament Light Chain as a Biomarker for Monitoring the Efficacy of Transcranial Magnetic Stimulation on Alcohol Use Disorder
Authors: Zhang Tian , Song Bin , Li Yanfei , Duan Ranran , Gong Zhe , Jing Lijun , Wang Kaixin , Ma Bingquan , Jia Yanjie 
Published: February 2022

ObjectiveThis study assessed the effects of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on serum neurofilament light chain (NfL) levels, alcohol consumption, craving, and psychological impairment in participants with alcohol use disorder (AUD).MethodsParticipants with AUD were randomly assigned to receive one of two treatments (active or sham rTMS). All participants received 10 daily active or sham rTMS sessions over the left DLPFC for 2 weeks, with follow-up visits at baseline and immediately after the completion of the treatments. Serum samples were obtained before and after the intervention. Days of heavy drinking, visual analog scale (VAS) scores, and mental health component scores (MCSs) of the Medical Outcomes Study 36-Item Short Form Health Survey were used to assess the effects of rTMS.ResultsActive rTMS had a significant effect on reducing days of heavy drinking, alcohol craving, and serum NfL levels, and improved social functioning and mental health. The improvement with active rTMS was significantly greater than that with sham rTMS. Correlation analysis revealed that the reduction in the baseline drinking level was positively correlated with declines in the VAS and NfL levels but not with psychological scores.ConclusionRepetitive transcranial magnetic stimulation of the left DLPFC was associated with reducing alcohol consumption and craving in patients with AUD and positively impacted neuropsychological and social function. Serum NfL levels may be useful as an early serological indicator of alcohol-induced brain injury.
Cancer Related Subarachnoid Hemorrhage: A Multicenter Retrospective Study Using Propensity Score Matching Analysis
Authors: Chen Shijian , Zhang Jian , Lu Xianfu , Cen Gengyu , Song Yiting , Deng Xuhui , Xie Yiju , Liu Liuyu , Liu Qianqian , Huang Junling , Li Jing , Yang Hong , Shi Shengliang , Pan Liya , Liang Zhijian 
Published: February 2022

ObjectiveTo investigate the clinical features, risk factors and underlying pathogenesis of cancer related subarachnoid hemorrhage (SAH).MethodsClinical data of SAH in patients with active cancer from January 2010 to December 2020 at four centers were retrospectively reviewed. Patients with active cancer without SAH were matched to SAH patients with active cancer group. Logistic regression was applied to investigate the independent risk factors of SAH in patients with active cancer, after a 1:1 propensity score matching (PSM). A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the joint predictive factor for cancer related SAH.ResultsA total of 82 SAH patients with active cancer and 309 patients with active cancer alone were included. Most SAH patients with cancer had poor outcomes, with 30-day mortality of 41.5%, and with 90-day mortality of 52.0%. The PSM yielded 75 pairs of study participants. Logistic regression revealed that a decrease in platelet and prolonged prothrombin time were the independent risk factors of cancer related SAH. In addition, receiver operator characteristic curve of the joint predictive factor showed the largest AUC of 0.8131, with cut-off value equaling to 11.719, with a sensitivity of 65.3% and specificity of 89.3%.ConclusionPatients with cancer related SAH often have poor outcomes. The decrease in platelet and prolonged prothrombin time are the independent risk factors of cancer related SAH, and the joint predictive factor with cutoff value equal to 11.719 should hence serve as a novel biomarker of cancer related SAH.
Ultrasound-Guided Nerve Hydrodissection With 5% Dextrose 4 Weeks After Steroid Injection in Treatment of Carpal Tunnel Syndrome: A Retrospective Study
Authors: He Juan-juan , Wei Xiao-mei , Dou Zu-lin , Zhang Jiang-shan , Wei Zhen-hai , Zhang Wei-xi , Jiang Li 
Published: February 2022

ObjectiveTo investigate the efficacy and safety of ultrasound-guided nerve hydrodissection (HD) with 5% dextrose (D5W) as add-on therapy after corticosteroid injection in carpal tunnel syndrome (CTS), and provide a novel strategy.MethodsIn this retrospective study, patients with CTS who received ultrasound-guided nerve HD with D5W as add-on therapy after corticosteroid injection (combination group) were enrolled. Patients who received corticosteroid injection without add-on therapy (steroid group) were recruited as the control group. Ultrasound-guided nerve HD with D5W was performed 4 weeks after corticosteroid injection. Treatment effectiveness were assessed by visual analog scale (VAS) and Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). The assessment was performed at baseline and 4, 8, and 12 weeks after corticosteroid injection. In addition, adverse events were recorded in this study.ResultsA total of 49 patients and 62 wrists meeting the criteria were included, with 24 patients and 31 wrists in the steroid group and 25 patients and 31 wrists in the combination group. Compared with baseline data, both groups showed greater improvement in VAS, BCTQs (BCTQ severity), and BCTQf (BCTQ function) at 4, 8, and 12 weeks follow-up. VAS, BCTQs, and BCTQf scores at baseline and week 4 were comparable between steroid group and combination group. Compared with steroid group, combination group exhibited a significant reduction in VAS, BCTQs, and BCTQf at 8- and 12-week follow-up (P ≤ 0.01). No adverse event occurred in any group.ConclusionsOur results showed that ultrasound-guided nerve HD with D5W as add-on therapy after corticosteroid injection was efficacious and safe in CTS, and combination therapy is more beneficial than corticosteroid monotherapy in the improvement of symptoms and function at 8- and 12-week follow-up.
Identification of Ferroptosis-Related Genes in Alzheimer’s Disease Based on Bioinformatic Analysis
Authors: Wang Ying , Chen Guohua , Shao Wei 
Published: February 2022

IntroductionAlzheimer’s disease (AD) is the most prevalent cause of dementia, and emerging evidence suggests that ferroptosis is involved in the pathological process of AD.Materials and MethodsThree microarray datasets (GSE122063, GSE37263, and GSE140829) about AD were collected from the GEO database. AD-related module genes were identified through a weighted gene co-expression network analysis (WGCNA). The ferroptosis-related genes were extracted from FerrDb. The apoptosis-related genes were downloaded from UniProt as a control to show the specificity of ferroptosis. The overlap was performed to obtain the module genes associated with ferroptosis and apoptosis. Then the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and the protein-protein interaction (PPI) were conducted. Cytoscape with CytoHubba was used to identify the hub genes, and the Logistic regression was performed to distinguish the AD patients from controls.Results53 ferroptosis-related module genes were obtained. The GO analysis revealed that response to oxidative stress and starvation, and multicellular organismal homeostasis were the most highly enriched terms. The KEGG analysis showed that these overlapped genes were enriched not only in renal cell carcinoma pathways and central carbon metabolism in cancer, but also in autophagy-related pathways and ferroptosis. Ferroptosis-related hub genes in AD (JUN, SLC2A1, TFRC, ALB, and NFE2L2) were finally identified, which could distinguish AD patients from controls (P &lt; 0.05). The area under the ROC curve (AUC) was 0.643. Apoptosis-related hub genes in AD (STAT1, MCL1, and BCL2L11) were also identified and also could distinguish AD patients from controls (P &lt; 0.05). The AUC was 0.608, which was less than the former AUC value, suggesting that ferroptosis was more special than apoptosis in AD.ConclusionWe identified five hub genes (JUN, SLC2A1, TFRC, ALB, and NFE2L2) that are closely associated with ferroptosis in AD and can differentiate AD patients from controls. Three hub genes of apoptosis-related genes in AD (STAT1, MCL1, and BCL2L11) were also identified as a control to show the specificity of ferroptosis. JUN, SLC2A1, TFRC, ALB, and NFE2L2 are thus potential ferroptosis-related biomarkers for disease diagnosis and therapeutic monitoring.
Brain and Spinal Cord Adaptations Associated With Patellofemoral Pain: A Systematic Review and Meta-Analysis
Authors: Ho Kai-Yu , Liang Jing Nong , Budge Savanna , Madriaga Austin , Meske Kara , Nguyenton Derrick 
Published: February 2022

ObjectiveTo evaluate the evidence for altered cortical and spinal cord functions in individuals with patellofemoral pain (PFP).MethodsWe conducted a comprehensive search of databases to appraise and analyze the studies published prior to December 10, 2021 that examined spinal reflex excitability measured using Hoffmann reflex (H-reflex) amplitudes, corticospinal excitability measured using transcranial magnetic stimulation (TMS)-elicited motor evoked potential (MEP) amplitudes, motor threshold (MT), or stimulus-response (SR) curves, cortical reorganization assessed using TMS cortical mapping or structural magnetic resonance imaging (MRI), or functional changes of the brain assessed using functional MRI (fMRI) in individuals with PFP.ResultsEight studies were eligible for analyses. While an earlier study showed that pain had no effect on the H-reflex amplitude of the quadriceps muscle, more recent evidence reported a decrease in vastus medialis (VM) H-reflex amplitude in participants with PFP. VM H-reflex amplitude was correlated with pain, chronicity, physical function, and isometric knee extensor torque production in participants with PFP. Altered corticospinal excitability was reported in participants with PFP, observed as increased MT in the VM and vastus lateralis (VL) muscles. In addition, cortical reorganization has been observed, where decreased number of cortical peaks, shifts and reduced volumes, and increased overlap of motor cortex representations for the VM, VL, and rectus femoris (RF) muscles were reported in participants with PFP.ConclusionThere is emerging evidence on altered cortical and spinal cord functions in individuals with PFP, however, solid conclusions cannot be drawn due to limited literature available. Further research is needed to better understand the adaptations of the brain and spinal cord in this population.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42020212128.
Prognostic Value of Radiomic Features of 18F-FDG PET/CT in Patients With B-Cell Lymphoma Treated With CD19/CD22 Dual-Targeted Chimeric Antigen Receptor T Cells
Authors: Zhou Yeye , Li Jihui , Zhang Xiaoyi , Jia Tongtong , Zhang Bin , Dai Na , Sang Shibiao , Deng Shengming 
Published: February 2022

ObjectiveIn the present study, we aimed to evaluate the prognostic value of PET/CT-derived radiomic features for patients with B-cell lymphoma (BCL), who were treated with CD19/CD22 dual-targeted chimeric antigen receptor (CAR) T cells. Moreover, we explored the relationship between baseline radiomic features and the occurrence probability of cytokine release syndrome (CRS).MethodsA total of 24 BCL patients who received 18F-FDG PET/CT before CAR T-cell infusion were enrolled in the present study. Radiomic features from PET and CT images were extracted using LIFEx software, and the least absolute shrinkage and selection operator (LASSO) regression was used to select the most useful predictive features of progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic curves, Cox proportional hazards model, and Kaplan-Meier curves were conducted to assess the potential prognostic value.ResultsContrast extracted from neighbourhood grey-level different matrix (NGLDM) was an independent predictor of PFS (HR = 15.16, p = 0.023). MYC and BCL2 double-expressor (DE) was of prognostic significance for PFS (HR = 7.02, p = 0.047) and OS (HR = 10.37, p = 0.041). The combination of NGLDM_ContrastPET and DE yielded three risk groups with zero (n = 7), one (n = 11), or two (n = 6) factors (p &lt; 0.0001 and p = 0.0004, for PFS and OS), respectively. The PFS was 85.7%, 63.6%, and 0%, respectively, and the OS was 100%, 90.9%, and 16.7%, respectively. Moreover, there was no significant association between PET/CT variables and CRS.ConclusionsIn conclusion, radiomic features extracted from baseline 18F-FDG PET/CT images in combination with genomic factors could predict the survival outcomes of BCL patients receiving CAR T-cell therapy.