bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Recombinant Gonadotropin on Testicular Function and Testicular Sperm Extraction in Five Cases of NR0B1 (DAX1) Pathogenic Variants
Authors: Teoli Jordan , Mezzarobba Vincent , Renault Lucie , Mallet Delphine , Lejeune Hervé , Chatelain Pierre , Tixier Frédérique , Nicolino Marc , Peretti Noël , Giscard D’estaing Sandrine , Cuzin Béatrice , Dijoud Frédérique , Roucher-Boulez Florence , Plotton Ingrid 
Published: March 2022

BackgroundNR0B1 pathogenic variants can cause congenital adrenal hypoplasia or primary adrenal insufficiency in early childhood usually associated with hypogonadotropic hypogonadism. NR0B1 is necessary for organogenesis of the adrenal cortex and to maintain normal spermatogenesis. In humans, restoration of fertility in patients carrying NR0B1 pathogenic variants is challenging.ObjectiveThe aim of the study was to investigate the clinical, hormonal, histological, spermiological, and molecular genetic characteristics of a cohort of patients with NR0B1 pathogenic variants, monitored for fertility preservation.PatientsWe included five patients, including four teenagers, with NR0B1 pathogenic or likely pathogenic variants. They all had primary adrenal insufficiency and were receiving replacement therapy with glucocorticoids and mineralocorticoids. Patients received recombinant follicle-stimulating hormone and recombinant human chorionic gonadotropin in order to induce spermatogenesis. Combined gonadotropin treatment was initiated between 13 years and 15 years and 6 months for the four teenagers and at 31 years and 2 months for the only adult. Physical and hormonal assessments were performed just before starting gonadotropin treatment. After 12 months of gonadotropin treatment, physical examination and hormonal assessments were repeated, and semen analyses were performed. If no sperm cells were observed in at least 2 semen collections at 3-month interval, testicular biopsy for testicular sperm extraction was proposed.ResultsBilateral testicular volume increased from 8 ml (interquartile range, 6–9) to 12 ml (10–16) after gonadotropin treatment. Inhibin B levels were relatively stable: 110 ng/L (46–139) before and 91 ng/L (20–120) at the end of gonadotropin treatment. Azoospermia was observed in all semen analyses for all cases during gonadotropin treatment. Three patients agreed to testicular biopsy; no mature sperm cells could be retrieved in any.ConclusionWe characterized a cohort of patients with NR0B1 pathogenic or likely pathogenic variants for fertility preservation by recombinant gonadotropin treatment, which began either at puberty or in adulthood. No sperm cells could be retrieved in semen samples or testicular biopsy even after gonadotropin treatment, indicating that gonadotropin treatment, even when started at puberty, is ineffective for restoring fertility.
Conservation Agriculture With Optimum Fertilizer Nitrogen Rate Reduces GWP for Rice Cultivation in Floodplain Soils
Authors: Jahangir M. M. R. , Bell R. W. , Uddin S. , Ferdous J. , Nasreen S. S. , Haque M. E. , Satter M. A. , Zaman M. , Ding W. , Jahiruddin M. , Müller C. 
Published: March 2022

Wetland rice cultivation contributes significantly to global warming potential (GWP), an effect which is largely attributed to emissions of methane (CH4). Emerging technologies for wetland rice production such as conservation agriculture (CA) may mitigate greenhouse gas (GHG) emissions, but the effects are not well defined. Investigations were carried out in an irrigated rice (Boro rice) field in the fifth crop after conversion of conventional tillage (CT) to strip tillage (ST). Two crop residue levels (low versus high, LR versus HR) and three nitrogen (N) application rates (N1 = 108, N2 = 144, and N3 = 180 kg N ha−1) were laid out in a split-plot experiment with three replicates. Yield-scaled GHG emissions and GWP were estimated to evaluate the impacts of CA on mitigating CH4 and N2O emissions in the rice paddy field. There was a 55% higher N2O emission in ST with HR coupled with N3 than that in CT with LR coupled with N1. The N2O emission factors ranged from 0.43 to 0.75% in ST and 0.45 to 0.59% in CT, irrespective of the residue level and N rate. By contrast, CH4 emissions were significantly lower in CA than in the conventional practices (CT plus LR). The ST with LR in N2 reduced the GWP by 39% over the GWP in CT with HR in N1 and 16% over the conventional practices. Based on our investigation of the combination of tillage, residue, and N rate treatments, the adoption of CA with high and low residue levels reduced the GWP by 10 and 16%, respectively, because of lower CH4 and N2O emissions than the current management practices. The relatively high N2O emission factors suggest that mitigation of this GHG in wetland rice systems needs greater attention.
Genomic Resources for Salminus brasiliensis
Authors: Graciano Raissa Cristina Dias , Oliveira Rafael Sachetto , Santos Isllas Miguel , Yazbeck Gabriel M. 
Published: March 2022

The Neotropical region bears the most diverse freshwater fish fauna on the planet and is the stage for dramatic conservation struggles. Initiatives aiming for conservation of a single emblematic fish, a flagship species, to which different onlookers relate on a cultural/personal level, holds promise towards engagement and conservation actions benefiting whole biological communities and ecosystems. Here, we present the first comprehensive genomic resources for Salminus brasiliensis, a potential flagship Neotropical species. This fish faces pressing conservation issues, as well as taxonomic uncertainty, being a main species relevant to angling and commercial fisheries. We make available 178 million Illumina paired-end reads, 90 bases long, comprising 16 Gb (≈15X coverage) of filtered data, obtained from a primary genomic library of 500-bp fragments. We present the first de novo genomic assembly for S. brasiliensis, with ∼1 Gb (N50 = 10,889), as well as the coding genome annotation of 12,962 putative genes from assembled genomic fragments over 10 kb, most of which could be identified from the Ostariophysi GenBank database. We also provide a genome-wide panel for more than 80,000 predicted microsatellite loci for low-cost, fast and abundant DNA marker development for this species. A total of 47, among 52 candidates, empirically assayed microsatellites were confirmed as polymorphic in this fish. All genomic data produced for S. brasiliensis is hereby made publicly accessible. With the disclosure of these results, we intend to foster general biology studies and to provide tools to be applied immediately in conservation and aquaculture in this candidate flagship Neotropical species.
Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis
Authors: Bonami Rachel H. , Thurman Christina E. , Verma Sonam , Westlake Camille S. , Nyhoff Lindsay E. , Barron Bridgette B. , Reboldi Andrea , Kendall Peggy L. 
Published: March 2022

Bruton’s tyrosine kinase (Btk) deficiency preferentially eliminates autoreactive B cells while sparing normal humoral responses, but has not been studied in mucosal immunity. Commensal microbes and intact BTK signaling have been independently shown to be essential for arthritis development in K/BxN mice. Here, we examine how BTK-mediated signaling interfaces with the gut microbiome.Btk-deficient K/BxN mice were found to have small Peyer’s Patches with reduced germinal center and IgA class-switched B cells. IgA-switched plasma cells in small intestines were reduced, especially in villi ofBtk-deficient mice. IgH CDR3 sequencing showed similar V gene diversity and somatic hypermutation frequency despiteBtkdeficiency but showed reduced CDR3 amino acid polarity, suggesting potential qualitative differences in the gut plasma cell repertoire. Small intestinal IgA was low and IgA coating of commensal bacteria was reduced. IgA-seq showed a shift in small intestinal microbes that are normally IgA-coated into the uncoated fraction inBtk-deficient mice. Overall, this study shows that BTK supports normal intestinal IgA development in response to commensals.This manuscript was previously published as a preprint at:https://www.biorxiv.org/content/10.1101/2021.03.10.434762v2.
A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity
Authors: Shang Shunlai , Zhou Yena , Chen Keng , Chen Lang , Li Ping , Li Diangeng , Cui Shaoyuan , Zhang Mei-Jun , Chen Xiangmei , Li Qinggang 
Published: March 2022

BackgroundAs genetic genetic factors are important in SLE, so screening causative genes is of great significance for the prediction and early prevention in people who may develop SLE. At present, it is very difficult to screen causative genes through pedigrees. The analytical method described herein can be used to screen causative genes for SLE and other complex diseases through pedigrees.MethodsFor the first time, 24 lupus pedigrees were analyzed by combining whole exon sequencing and a variety of biological information tools including common-specific analysis, pVAAST (pedigree variant annotation, analysis and search tool), Exomiser (Combining phenotype and PPI associated analysis), and FARVAT (family based gene burden), and the causative genes of these families with lupus identified. Selected causative genes in peripheral-blood mononuclear cells (PBMCs) were evaluated by quantitative polymerase chain reaction (qPCR).ResultsCell division cycle 27 (CDC27) was screened out by common-specific analysis and Exomiser causative gene screening. FARVAT analysis on these families detected only CDC27 at the extremely significant level (false discovery rate &lt;0.05) by three family-based burden analyses (BURDEN, CALPHA, and SKATO). QPCR was performed to detect for CDC27 in the PBMCs of the SLE family patients, sporadic lupus patients, and healthy people. Compared with the healthy control group, CDC27 expression was low in lupus patients (familial and sporadic patients) (P&lt;0.05) and correlated with lupus activity indicators: negatively with C-reactive protein (CRP) (P&lt;0.05) and erythrocyte sedimentation rate (P&lt;0.05) and positively with complement C3 and C4 (P&lt;0.05). The CDC27 expression was upregulated in PBMCs from SLE patients with reduced lupus activity after immunotherapy (P&lt;0.05). Based on Receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity of CDC27 in diagnosing SLE were 82.30% and 94.40%.ConclusionThe CDC27 gene, as found through WES combined with multiple analytical method may be a causative gene of lupus. CDC27 may serve as a marker for the diagnosis of SLE and is closely related to the lupus activity. We hope that the analytical method in this study will be used to screen causative genes for other diseases through small pedigrees, especially among non-close relatives.
The Efficacy and Safety of Adalimumab in Treating Pediatric Noninfectious Chronic Anterior Uveitis With Peripheral Retinal Vascular Leakage: A Pilot Study
Authors: Song Hang , Zhao Chan , Xiao Junyan , Gao Fei , Li Donghui , Zhang Meifen 
Published: March 2022

PurposeThis study is aimed to assess the efficacy of adalimumab in alleviating peripheral vascular leakage in pediatric chronic anterior uveitis patients, along with its ability to improve best-corrected visual acuity (BCVA) and inflammation parameters, its efficacy in reducing topical glucocorticosteroids (GCs) and systemic immunomodulatory therapy (IMT), and its safety profile.MethodsA self-controlled study of pediatric chronic anterior uveitis patients who presented with peripheral retinal vascular leakage on ultra-widefield fluorescein fundus angiography and underwent adalimumab treatment was conducted. The primary outcome was the extent of retinal vascular leakage at the 3- and 6-month follow-up visits. Secondary outcomes included BCVA, inflammation parameters (fresh keratic precipitates, anterior chamber cell, and vitreous cell grades), frequency of topical glucocorticosteroid eye drops, IMT load, and adverse effects at the 3- and 6-month follow-up visits.ResultsTwenty patients with a mean age of 9.30 ± 3.26 years old were included. The mean follow-up period was 9.0 ± 3.0 months, with all patients followed up for at least 6 months. At the 3- and 6-month follow-ups, the peripheral vascular leakage score decreased significantly (2.87, 95% CI (2.14, 3.60), p &lt; 0.001 for 3 months, 2.75, 95% CI (1.76, 3.73), p &lt; 0.001 for 6 months). Alongside BCVA (p = 0.013 for 3 months, p = 0.005 for 6 months) was improved significantly, inflammatory parameters represented by fresh keratic precipitates, anterior chamber cell, and vitreous cell grades were improved significantly (p &lt; 0.001, p &lt; 0.001, for all parameters) and topical GC usage was significantly reduced (p &lt; 0.001, p &lt; 0.001) at 3 and 6 months. There was also a statistically significant reduction in systemic IMT load at 6 months (p &lt; 0.001). Adverse events in the observation period included local redness around the injection site and mild upper respiratory symptoms.ConclusionAdalimumab could effectively alleviate peripheral vascular leakage in pediatric patients with chronic anterior uveitis. It could also be helpful in improving BCVA and inflammation parameters and decreasing topical glucocorticosteroid eye drops and systemic IMT. Adalimumab is generally safe for pediatric uveitis.
The Benefits, Challenges and Impacts of Telehealth Student Clinical Placements for Accredited Health Programs During the COVID-19 Pandemic
Authors: Bacon Rachel , Hopkins Sian , Kellett Jane , Millar CaraJane , Smillie Linda , Sutherland Rebecca 
Published: March 2022

IntroductionDespite the advantages of telehealth, there has been a reluctance in its widespread adoption. During the COVID-19 pandemic, telehealth services and related placements increased internationally. Yet, there is currently limited research on the use of telehealth for student clinical placements.AimTo explore the perceived benefits, challenges, and impacts of telehealth placements for key stakeholders (clients, students, clinical educators, and placement co-ordinators) in allied health courses.MethodsStakeholder experiences with telehealth placements, undertaken within an Australian Allied Health University Clinic, were explored in virtual focus groups held between November 2020 and March 2021. These discussions used semi-structured interview questions, were audiotaped and transcribed verbatim. They were then thematically analyzed independently by two researchers, then cross-checked for consistency, using a qualitative descriptive approach, with reflexivity applied.ResultsTwenty-six stakeholders from six allied health disciplines participated in seven homogeneous focus groups. Three themes were identified: (1) telehealth placements support competency development and graduate employability; (2) telehealth placements enable students to provide person centered-care; and (3) telehealth placements enabled innovation.ConclusionTelehealth placements can make a valuable contribution as part of an overall placement program within accredited health courses and offer distinct advantages to student learning outcomes.
Increasing of Blood Brain Barrier Permeability and the Association With Depression and Anxiety in Systemic Lupus Erythematosus Patients
Authors: Wang Xiangyu , Ma Lihua , Luo Yuli , Yang Yifan , Upreti Bibhuti , Cheng Yuqi , Cui Ruomei , Liu Shuang , Xu Jian 
Published: March 2022

ObjectiveTo study changes in blood brain barrier (BBB) permeability in systemic lupus erythematosus (SLE) patients, and explore the association between the alterations in BBB permeability and depression/anxiety in SLE.MethodsBrain dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) images were collected from 42 SLE patients and 23 healthy controls (HCs). Based on the Patlak pharmacokinetic model, the Ktrans value of each voxel in the whole brain of each subject was calculated. BBB permeability indicator (the Ktrans value) between SLE patients and healthy control group was compared. Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to assess the mental health of SLE patients. The difference in BBB permeability was compared on SLE patients with depression/anxiety, SLE patients without depression/anxiety and HCs by ANOVA analysis.ResultsThe Ktrans value of the right insular region of the SLE group was significantly higher than that of the healthy control group. And the Ktrans value of the right insular region in SLE patients with depression/anxiety was significantly increased compared with SLE patients without depression/anxiety and HCs.ConclusionsSLE patients have increased BBB permeability, mainly in the right insular area. The increased BBB permeability in the right insular region is associated with the depression/anxiety in SLE patients.
Translation, Cultural Adaptation, Reliability, and Validity Testing of a Chinese Version of the Self-Administered Mediterranean Diet Scale
Authors: Li Jiajia , Ding Huirong , Wang Zheng , El-Ansary Doa , Adams Roger , Han Jia , Meng Shu 
Published: March 2022

Mediterranean Diet management for people with cardiovascular disease (CVD) or CVD risk is supported by evidence. However, there is no valid Chinese language instrument for the measurement of adherence to this diet. The objective of this study was to generate a Chinese version of the Mediterranean Diet Scale (MDS-Chinese) and to validate a self-administered version with Chinese participants with CVD or CVD risk. The MDS-Chinese was created by translation and cultural adaptation and tested for psychometric properties. A panel of 10 experts in the field, who evaluated the MDS-Chinese content, showed that the content validity index ranged from 0.88 to 1.00. Sixteen native Chinese speakers with CVD or CVD risk evaluated the clarity of the MDS-Chinese, and the resulting instruction and items clarity scores ranged from 9.2 to 10.0. A total of 326 participants completed the MDS-Chinese and a Chinese version of the Coronary Artery Disease Education Questionnaire–Short Version (CADE-Q SV). Analysis indicated that the MDS-Chinese has 4 factors, and the Pearson's correlation between the MDS-Chinese and CADE-Q SV was 0.73. Fifty randomly selected participants completed the MDS-Chinese again with a 1-week interval to assess reliability. Internal consistency was acceptable (Cronbach's α was 0.62) and the inter-class correlation reliability coefficients (ICC) for each item ranged from 0.73 to 0.88. This study showed that the MDS-Chinese has acceptable reliability and validity for use among those in the Chinese population with CVD or CVD risk. Given that diet is one of the key secondary prevention strategies for management in cardiac rehabilitation, the MDS-Chinese instrument may be a useful and convenient tool for use with those in the Chinese population with CVD or with high risk of CVD, to monitor the level of Mediterranean diet (MD) adherence, information which is important for clinical practice. In addition, the establishment of the MDS-Chinese gives a fundamental tool for diet-related CVD research in the Chinese population. Moreover, employment of the MDS-Chinese in the Chinese community may improve awareness of the importance of a healthy diet in CVD prevention and management.Clinical Trial Registration:http://www.chictr.org.cn/enIndex.aspx, identifier: ChiCTR2000032810.
Up-Regulated MISP Is Associated With Poor Prognosis and Immune Infiltration in Pancreatic Ductal Adenocarcinoma
Authors: Huang Xinyang , Zhao Liangchao , Jin Yixun , Wang Zhuoxin , Li Tong , Xu Hui , Wang Qi , Wang Lifu 
Published: March 2022

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis. More effective biomarkers and treatment options remain to be discovered. Mitotic Spindle Positioning (MISP), also called C19orf21, has been reported to be upregulated in several malignancies. However, the effects of MISP on PDAC have yet to be investigated.Materials and MethodsThe differential expression of MISP at the mRNA and protein levels were evaluated using Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) databases, and was further verified by quantitative real-time PCR and western blotting in PDAC cell lines. Correlations between MISP expression and clinical characteristics were explored using Kaplan-Meier Plotter Database and clinical data from The Cancer Genome Atlas (TCGA). CCK-8 assays, Transwell assays, and immunoblotting were used to determine the role of MISP in PDAC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were executed by the R package ‘clusterProfiler’. Correlations between MISP expression and immune cell infiltration, immune checkpoints, immunophenoscore (IPS) and the tumor mutational burden (TMB) in PDAC were explored using the R package ‘CIBERSORT’, the Tumor Immune Estimation Resource 2.0 (TIMER2.0), and The Cancer Immunome Atlas (TCIA) database based on TCGA data.ResultMISP expression was significantly higher in pancreatic cancer tissues compared to normal pancreas tissues, which was associated with a poor prognosis. Increased expression of MISP was related to the proliferation, migration and invasion of PDAC cell lines. GO and KEGG pathway analyses determined that MISP is involved in the Ras signaling pathway and immune regulation. Higher expression of MISP was associated with decreased infiltration levels of activated CD4+ memory T cells, CD8+ T cells, M2 macrophages and neutrophils. Furthermore, increased MISP was associated with lower expression of immune checkpoint molecules, higher gene mutation burden and IPS.ConclusionsThis study reveals that MISP, which is associated with the progression and prognosis of PDAC, may exert a potential regulatory effect on immune infiltration and predict the response to immunotherapy in PDAC.