bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irisin Serum Levels and Skeletal Muscle Assessment in a Cohort of Charcot-Marie-Tooth Patients
Authors: Colaianni Graziana , Oranger Angela , Dicarlo Manuela , Lovero Roberto , Storlino Giuseppina , Pignataro Patrizia , Fontana Antonietta , Di Serio Francesca , Ingravallo Angelica , Caputo Giuseppe , Di Leo Alfredo , Barone Michele , Grano Maria 
Published: May 2022

BackgroundCharcot-Marie-Tooth (CMT) indicates a group of inherited polyneuropathies whose clinical phenotypes primarily include progressive distal weakness and muscle atrophy. Compelling evidence showed that the exercise-mimetic myokine irisin protects against muscle wasting in an autocrine manner, thus possibly preventing the onset of musculoskeletal atrophy. Therefore, we sought to determine if irisin serum levels correlate with biochemical and muscle parameters in a cohort of CMT patients.MethodsThis cohort study included individuals (N=20) diagnosed with CMT disease. Irisin and biochemical markers were quantified in sera. Skeletal muscle mass (SMM) was evaluated by bioelectric impedance analysis, muscle strength by handgrip, and muscle quality was derived from muscle strength and muscle mass ratio.ResultsCMT patients (m/f, 12/8) had lower irisin levels than age and sex matched healthy subjects (N=20) (6.51 ± 2.26 vs 9.34 ± 3.23 μg/ml; p=0.003). SMM in CMT patients was always lower compared to SMM reference values reported in healthy Caucasian population matched for age and sex. Almost the totality of CMT patients (19/20) showed low muscle quality and therefore patients were evaluated on the basis of muscle strength. Irisin was lower in presence of pathological compared to normal muscle strength (5.56 ± 1.26 vs 7.67 ± 2.72 μg/ml; p=0.03), and directly correlated with the marker of bone formation P1PN (r= 0.669; 95%CI 0.295 to 0.865; p=0.002), but inversely correlated with Vitamin D (r=-0.526; 95%CI -0,791 to -0,095; p=0.017). Surprisingly, in women, irisin levels were higher than in men (7.31 ± 2.53 vs 5.31 ± 1.02 μg/ml, p=0.05), and correlated with both muscle strength (r=0.759; 95%CI 0.329 to 0.929; p=0.004) and muscle quality (r=0.797; 95%CI 0.337 to 0.950; p=0.006).ConclusionOur data demonstrate lower irisin levels in CMT patients compared to healthy subjects. Moreover, among patients, we observed, significantly higher irisin levels in women than in men, despite the higher SMM in the latter. Future studies are necessary to establish whether, in this clinical contest, irisin could represent a marker of the loss of muscle mass and strength and/or bone loss.
SLC44A2 Frequency, a New TaqMan Real-Time Polymerase Chain Reaction Method for HNA-3A/3B Genotyping, and a New Application of Droplet Digital PCR
Authors: Wang Yufeng , Chen Xihui , Chen Qi , Chen Tangdong , Chen Kun , Wu Yuanming , Wang Li 
Published: May 2022

Background: Human neutrophil antigen-3A (HNA-3A) and human neutrophil antigen-3B (HNA-3B) are generated by a single-nucleotide polymorphism (rs2288904, c.461G &gt; A) in exon 7 of the choline transporter-like protein-2 gene (CTL2, also known as SLC44A2). Antibodies to HNA-3 can be generated following blood transfusion or other factors resulting in exposure to HNA-3 antigens. These antibodies can cause transfusion-related acute lung injury (TRALI) or neonatal alloimmune neutropenia (NAIN). This study describes a sensitive and specific TaqMan real-time polymerase chain reaction (PCR) method to screen for the HNA-3 genotype using specific primers and probes designed to detect allelic polymorphisms. Considering the high sensitivity and accuracy of droplet digital PCR (ddPCR) in the identification of the rare SLC44A2*2 allele, we used this technique to identify blood donors with the rare HNA-3B antigen and calculate the allele frequency of SLC44A2 in mixed populations with different proportions.Methods: DNA samples purified from 208 donors in northwest China were subjected to TaqMan real-time PCR to detect allelic polymorphisms in SLC44A2. The results were confirmed by Sanger sequencing. The rare HNA-3B antigen was detected by ddPCR. SLC44A2 frequency was determined by two-channel ddPCR.Results: The genotypes of all DNA samples were detected by the TaqMan real-time PCR using specific probes for HNA-3, and the results were consistent with the Sanger sequencing results in respect to the HNA-3A and HNA-3B polymorphisms. The allele frequencies of SLC44A2*1 and SLC44A2*2 in the 208 donors in northwest China were 64.9% (95% confidence interval [CI], 59%–70.8%) and 35.1% (95% CI, 29.2%–41%), respectively. The ratio of SLC44A2*2 alleles was accurately detected in all blood pools by ddPCR but not by TaqMan real-time PCR. This allowed for the SLC44A2 frequency in the population to be accurately inferred.Conclusion: This new method of detecting SLC44A2 alleles was highly sensitive and specific, as confirmed by Sanger sequencing. ddPCR using the designed probes resulted in successful detection of the rare HNA-3B antigen. Furthermore, we successfully detected the rare HNA-3B antigen and inferred the SLC44A2 frequency by ddPCR using the probes that we designed.
The Mutation Analysis of the AMT Gene in a Chinese Family With Nonketotic Hyperglycinemia
Authors: Zhou Bing-bo , Hui Ling , Zhang Qing-hua , Chen Xue , Zhang Chuan , Zheng Lei , Feng Xuan , Wang Yu-pei , Ding Zhong-jun , Chen Rui-rong , Ma Pan-pan , Liu Fu-rong , Hao Sheng-ju 
Published: May 2022

Background: Nonketotic hyperglycinemia is a metabolic disease with autosomal recessive inheritance due to the glycine cleavage system (GCS) defect leading to the accumulation of glycine that causes severe and fatal neurological symptoms in the neonatal period.Methods: Genomic DNA was extracted from the peripheral blood of the female proband and her family members. The AMT variation was detected in the patient by whole-exome sequencing (WES), and the variant was validated by Sanger sequencing.Results: The WES showed that there were novel compound heterozygous frameshift variations c.977delA (p.Glu326Glyfs*12) and c.982_983insG (p.Ala328Glyfs*22) in exon eight of the AMT gene (NM_000481.4) in the proband. Genetic analysis showed that the former was inherited from the mother, and the latter was inherited from the father.Conclusion: We report the novel compound heterozygous variation of the AMT gene in a Chinese girl with NKH by WES, which has never been reported previously. Our case expanded the AMT gene mutation spectrum, further strengthened the understanding of NKH, and deepened the genetic and clinical heterogeneity of the disease. However, the study of treatment and prognosis is still our future challenge and focus.
Prenatal Diagnosis of Chromosomal Mosaicism in Over 18,000 Pregnancies: A Five-Year Single-Tertiary-Center Retrospective Analysis
Authors: Li Shuyuan , Shi Yiru , Han Xu , Chen Yiyao , Shen Yinghua , Hu Wenjing , Zhao Xinrong , Wang Yanlin 
Published: May 2022

Background: Chromosomal mosaicism (CM) is a common biological phenomenon observed in humans. It is one of the main challenges in prenatal diagnosis due to uncertain outcomes, especially when fetal ultrasonographic features appear normal. This study aimed to assess the phenotypic features of CM detected during prenatal diagnosis and the risk factors affecting parents’ pregnancy decisions.Materials and methods: A retrospective cohort study involving 18,374 consecutive pregnancies that underwent prenatal diagnosis by karyotyping, fluorescence in situ hybridization (FISH), or chromosome microarray analysis (CMA) was conducted. The association of risk factors with malformations detected by ultrasound and pregnancy outcomes was assessed using the chi-square test and binary logistic regression. Discordant results between the different methods were identified and further analyzed.Results: During this five-year period, 118 (0.6%) patients were diagnosed with CM. The incidences of CM in the chorionic villus, amniotic fluid, and umbilical cord blood were 3.2, 0.5, and 0.7%, respectively. The frequency of ultrasound malformations in individuals with a high fraction of autosomal CM was significantly higher than that in other groups (62.5% vs. 21.4–33.3%, all p &lt;0.05). Inconsistent results between karyotyping and CMA/FISH were observed in 23 cases (19.5%). The risk of pregnancy termination in cases with ultrasound malformations, consistent results, autosomal CM, or a high CM fraction increased with an odds ratio of 3.09, 8.35, 2.30, and 7.62 (all p &lt;0.05). Multiple regression analysis revealed that all four factors were independent risk factors for the termination of pregnancy.Conclusion: Patients with a high fraction of autosomal CM are more likely to have ultrasound malformations. Inconsistent results between different methods in CM are not rare. Ultrasound malformations, consistent results between different methods, autosomal CM, and a high CM fraction were independent risk factors for the choice to terminate pregnancies.
Multi-Size Deep Learning Based Preoperative Computed Tomography Signature for Prognosis Prediction of Colorectal Cancer
Authors: Li Cheng-Hang , Cai Du , Zhong Min-Er , Lv Min-Yi , Huang Ze-Ping , Zhu Qiqi , Hu Chuling , Qi Haoning , Wu Xiaojian , Gao Feng 
Published: May 2022

Background: Preoperative and postoperative evaluation of colorectal cancer (CRC) patients is crucial for subsequent treatment guidance. Our study aims to provide a timely and rapid assessment of the prognosis of CRC patients with deep learning according to non-invasive preoperative computed tomography (CT) and explore the underlying biological explanations.Methods: A total of 808 CRC patients with preoperative CT (development cohort: n = 426, validation cohort: n = 382) were enrolled in our study. We proposed a novel end-to-end Multi-Size Convolutional Neural Network (MSCNN) to predict the risk of CRC recurrence with CT images (CT signature). The prognostic performance of CT signature was evaluated by Kaplan-Meier curve. An integrated nomogram was constructed to improve the clinical utility of CT signature by combining with other clinicopathologic factors. Further visualization and correlation analysis for CT deep features with paired gene expression profiles were performed to reveal the molecular characteristics of CRC tumors learned by MSCNN in radiographic imaging.Results: The Kaplan-Meier analysis showed that CT signature was a significant prognostic factor for CRC disease-free survival (DFS) prediction [development cohort: hazard ratio (HR): 50.7, 95% CI: 28.4–90.6, p &lt; 0.001; validation cohort: HR: 2.04, 95% CI: 1.44–2.89, p &lt; 0.001]. Multivariable analysis confirmed the independence prognostic value of CT signature (development cohort: HR: 30.7, 95% CI: 19.8–69.3, p &lt; 0.001; validation cohort: HR: 1.83, 95% CI: 1.19–2.83, p = 0.006). Dimension reduction and visualization of CT deep features demonstrated a high correlation with the prognosis of CRC patients. Functional pathway analysis further indicated that CRC patients with high CT signature presented down-regulation of several immunology pathways. Correlation analysis found that CT deep features were mainly associated with activation of metabolic and proliferative pathways.Conclusions: Our deep learning based preoperative CT signature can effectively predict prognosis of CRC patients. Integration analysis of multi-omic data revealed that some molecular characteristics of CRC tumor can be captured by deep learning in CT images.
Identification of Two m6A Readers YTHDF1 and IGF2BP2 as Immune Biomarkers in Head and Neck Squamous Cell Carcinoma
Authors: Li Shaojie , Wu Qiuji , Liu Jia , Zhong Yahua 
Published: May 2022

Background: N6-methyladenosine (m6A) is the most abundant internal modification pattern in mammals that a plays critical role in tumorigenesis and immune regulations. However, the effect of m6A modification on head and neck squamous cell carcinoma (HNSCC) has not been clearly studied.Methods: We screened m6A regulators that were significantly correlated with tumor immune status indicated by ImmuneScore using The Cancer Genome Atlas (TCGA) dataset and obtained distinct patient clusters based on the expression of these m6A regulators with the R package “CensusClusterPlus.” We then performed gene set enrichment analysis (GSEA), CIBERSORT, and single-sample gene set enrichment analysis (ssGSEA) to assess the differences in gene function enrichment and tumor immune microenvironment (TIME) among these clusters. We further conducted differently expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) and constructed a protein–protein interaction (PPI) network to determine hub genes among these clusters. Finally, we used the GSE65858 dataset as an external validation cohort to confirm the immune profiles related to the expression of m6A regulators.Results: Two m6A readers, YTHDF1 and IGF2BP2, were found to be significantly associated with distinct immune status in HNSCC. Accordingly, patients were divided into two clusters with Cluster 1 showing high expression of YTHDF1 and IGF2BP2 and Cluster 2 showing low expression levels of both genes. Clinicopathologically, patients from Cluster 1 had more advanced T stage and pathological grades than those from Cluster 2. GSEA showed that Cluster 1 was closely related to the RNA modification process and Cluster 2 was significantly correlated with immune regulations. Cluster 2 had a more active TIME characterized by a more relative abundance of CD8+ T cells and CD4+ T cells and higher levels of MHC I and MHC II molecules. We constructed a PPI network composed of 16 hub genes between the two clusters, which participated in the T-cell receptor signaling pathway. These results were externally validated in the GSE65858 dataset.Conclusions: The m6A readers, YTHDF1 and IGF2BP2, were potential immune biomarkers in HNSCC and could be potential treatment targets for cancer immunotherapy.
Human Macrophages Exhibit GM-CSF Dependent Restriction of Mycobacterium tuberculosis Infection via Regulating Their Self-Survival, Differentiation and Metabolism
Authors: Mishra Abhishek , Singh Vipul K. , Jagannath Chinnaswamy , Subbian Selvakumar , Restrepo Blanca I. , Gauduin Marie-Claire , Khan Arshad 
Published: May 2022

GM-CSF is an important cytokine that regulates the proliferation of monocytes/macrophages and its various functions during health and disease. Although growing evidences support the notion that GM-CSF could play a major role in immunity against tuberculosis (TB) infection, the mechanism of GM-CSF mediated protective effect against TB remains largely unknown. Here in this study we examined the secreted levels of GM-CSF by human macrophages from different donors along with the GM-CSF dependent cellular processes that are critical for control ofM. tuberculosisinfection. While macrophage of different donors varied in their ability to produce GM-CSF, a significant correlation was observed between secreted levels of GM-CSF, survial of macrophages and intra-macrophage control ofMycobacterium tuberculosisbacilli. GM-CSF levels secreted by macrophages negatively correlated with the intra-macrophageM. tuberculosisburden, survival of infected host macrophages positively correlated with their GM-CSF levels. GM-CSF-dependent prolonged survival of human macrophages also correlated with significantly decreased bacterial burden and increased expression of self-renewal/cell-survival associated genes such asBCL-2andHSP27. Antibody-mediated depletion of GM-CSF in macrophages resulted in induction of significantly elevated levels of apoptotic/necrotic cell death and a simultaneous decrease in autophagic flux. Additionally, protective macrophages againstM. tuberculosisthat produced more GM-CSF, induced a stronger granulomatous response and produced significantly increased levels of IL-1β, IL-12 and IL-10 and decreased levels of TNF-α and IL-6. In parallel, macrophages isolated from the peripheral blood of active TB patients exhibited reduced capacity to control the intracellular growth ofM. tuberculosisand produced significantly lower levels of GM-CSF. Remarkably, as compared to healthy controls, macrophages of active TB patients exhibited significantly altered metabolic state correlating with their GM-CSF secretion levels. Altogether, these results suggest that relative levels of GM-CSF produced by human macrophages plays a critical role in preventing cell death and maintaining a protective differentiation and metabolic state of the host cell againstM. tuberculosisinfection.
SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease
Authors: Wagner Angelika , Garner-Spitzer Erika , Schötta Anna-Margarita , Orola Maria , Wessely Andrea , Zwazl Ines , Ohradanova-Repic Anna , Weseslindtner Lukas , Tajti Gabor , Gebetsberger Laura , Kratzer Bernhard , Tomosel Elena , Kutschera Maximilian , Tobudic Selma , Pickl Winfried F. , Kundi Michael , Stockinger Hannes , Novacek Gottfried , Reinisch Walter , Zielinski Christoph , Wiedermann Ursula 
Published: May 2022

BackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.MethodsIn a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.Results263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels &gt;8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.ConclusionImmunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.Trial registrationEudraCT Number: 2021-000291-11
Quantifying the Influence of Out-Time on Prepreg Material Properties and Out-Of-Plane Steering Defects During Automated Fiber Placement
Authors: Heller Klaus , Colin David , Drechsler Klaus 
Published: May 2022

In automated fiber placement (AFP), knowledge about the interaction between material properties and process parameters is essential to achieve cost-efficient manufacturing. Both, lay-up rate and defects are dependent on the properties of the uncured prepreg tapes which are out-time dependent. However, information thereof is not given in data sheets and there are no standardized test methods. To quantify the changes of the material properties, we conducted experiments on mechanical properties and tack with IM7/8552 up to 15 days out-time using previously evaluated test methods. Furthermore, we carried out AFP lay-up trials to quantify the effects on steering defects. The results for the mechanical properties reveal a non-linear increase of the shear modulus and the transverse tensile modulus and a strong correlation to the test temperature. Results from the probe tack tests show a strong dependence on out-time at 20°C and a weak dependence at 40°C. Results from a novel peel tack test method and the lay-up trials revealed a monotonous change as a function of out-time. In both cases, we identified the lay-up rate and the infrared (IR) emitter power as the process parameters with the largest influence. The obtained results present an overall view of the material behavior depending on different test and process parameters as a function of out-time. By this, they help optimize the AFP process parameters and serve as input for material models and AFP defect models.
A Multi-Center, Randomized, Blind, Controlled Clinical Trial of the Safety and Efficacy of Micro Radio Frequency Therapy System for the Treatment of Overactive Bladder
Authors: Xu Zhi-Hui , Zhang Peng-Fei , Wang Yu-Feng , Ma Ao , Bano Yasmeen , Ibrohimov Alisherjon , Zhang Chen , Jiang Hao-Fei , Zhang Yang , Yu Yan-Lan , Jiang Hai-Hong 
Published: May 2022

PurposeThe purpose of this study was to evaluate the efficacy and safety of low power micro radiofrequency (RF) therapy (μRFthera®) through urethra in the treatment of overactive bladders (OAB) through a prospective, single-blind, placebo-controlled, multi-center clinical protocol.Materials and MethodsOne hundred and fourteen patients with refractory OAB were randomized at 2:1 ratio, treatment to control undergoing same procedures except only the micro-RF treatment group at turned “on” setting in energy. Bladder diaries recorded during the screening period (3 days before enrollment) and during follow-up period on week 1, 3, and 7, respectively. The patients in control could choose receiving an energized treatment during extension stage.ResultsThe treatment efficacy was 76.1%. There was 49.80% rate improvement compared to control (95%CL 32.48%, 67.13%). The crude rate ration (RR) was 2.89, 95% CI (1.67–5.01) with p &lt; 0.001 in uni-variate analysis, while the RR became 2.94, 95% CI (1.67–5.16) with p &lt; 0.001 after adjusted potential confounding factors in multi-variate analysis. Statistically significant improvements have been demonstrated in the frequency of urination, urgency, nocturia, and quality of life (QoL) scores.ConclusionsMicro RF therapy is safe and effective for the treatment of OAB. The main treatment-related complications were catheterization related complications.Clinical Trial RegistrationZhejiang Device Registration Certificate No. 202090909, www.chictr.org.cn, Clinical Trial Accession Number: ChiCTR2100050096.