bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma
Authors: Kong Wen , Yang Tongtong , Wen Xiaodong , Mu Zhongyi , Zhao Cheng , Han Sujun , Tian Jing , Zhang Xinhao , Zhou Tao , Zhang Yanrui , Lou Feng , Cao Shanbo , Wang Huina , Zhang Jin 
Published: December 2021

BackgroundRenal cell carcinoma (RCC) is a disease of genomic alterations, of which the complete panorama helps in facilitating molecular-guided therapy. Germline mutation profiles and associated somatic and clinical characteristics remains unexplored in Chinese RCC patients.MethodsWe retrospectively profiled the germline and somatic mutations of 322 unselected RCC patients using a panel consisting of 808 cancer-related genes. We categorized patients into three groups based on germline mutation status and compared the somatic mutation spectrum among different groups.ResultsApproximately one out of ten (9.9%) RCC patients were identified to carry pathogenic/likely pathogenic (P/LP) germline variants (PGVs), of which 3.7% were variants in syndromic RCC-associated genes and 6.2% were other cancer-predisposition genes. The most common PGV was found in VHL (2.2%), followed by FH, TSC2, ATM, BRCA1, NBN, and BLM (0.6% each). Young patients (≤46 years) were more likely to harbor PGVs. Variants in syndromic RCC-associated genes were predominant identified in young patients, while variants in other cancer-predisposition genes were found in patients &gt;46 years more frequently. Furthermore, 39.3% (11/28) of patients carrying PGVs were detected to have somatic “second hit” events. Germline and somatic sequencing, including microsatellite instability (MSI) status analysis, provided potentially actionable therapeutic targets in 17.1% of patients in the whole cohort.ConclusionsOur results revealed that approximately 10% of RCC patients carried clinically significant germline mutations. Current guidelines recommendation for genetic testing seemed not sensitive enough to identify patients with hereditary RCC susceptibility. It is rational to promote genetic testing in RCC population.
Tumor Stage-Based Gross Tumor Volume of Resectable Esophageal Squamous Cell Carcinoma Measured on CT: Association With Early Recurrence After Esophagectomy
Authors: Wu Yu-ping , Tang Sun , Tan Bang-guo , Yang Li-qin , Lu Fu-lin , Chen Tian-wu , Ou Jing , Zhang Xiao-ming , Gao Dan , Li Ke-ying , Yu Zi-yi , Tang Zhao 
Published: December 2021

ObjectiveTo investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy.Materials and MethodsTwo hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen’s Kappa tests were used to evaluate the performances of the previous ROC predictive models.ResultsER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values &lt; 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533–7.459] and 1.222 (95% CI: 1.125–1.327), respectively (all P-values &lt; 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values &lt; 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498–0.894), 0.733 (95% CI, 0.386–1.080), and 0.862 (95% CI, 0.603–1.121), respectively.ConclusionGTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.
Study on Motion Management of Pancreatic Cancer Treated by CyberKnife
Authors: Jing Shenghua , Jiang Changchen , Ji Xiaoqin , Qiu Xiangnan , Li Jing , Sun Xiangdong , Zhu Xixu 
Published: December 2021

PurposeWe investigated the movement characteristics of pancreas and the clinical accuracy of tracking pancreas with the Synchrony Respiratory Tracking System (SRTS) during the CyberKnife treatment. These data provide a clinical data basis for the expansion margins of pancreatic tumor target.Methods and MaterialsForty-two patients with pancreatic cancer treated by CyberKnife were retrospectively studied. The pancreatic displacement calculated from the x-ray images collected during the time interval between two consecutive movements constituted a data set.ResultsThe total mean motion amplitudes and standard deviations of pancreatic tumors in SI, LR, AP, and radial directions were 3.66 ± 1.71 mm, 0.97 ± 0.62 mm, 1.52 ± 1.02 mm, and 1.36 ± 0.49 mm, respectively. The overall mean correlation errors and standard deviations were 0.82 ± 0.46 mm, 0.47 ± 0.33 mm, 0.41 ± 0.24 mm, and 0.98 ± 0.37 mm, respectively. The overall mean prediction errors and standard deviations were 0.57 ± 0.14 mm, 0.62 ± 0.28 mm, 0.39 ± 0.17 mm, and 1.58 ± 0.36 mm, respectively. The correlation errors and prediction errors of pancreatic tumors at different anatomical positions in SI, LR, and AP directions were statistically significant (p &lt; 0.05).ConclusionsThe tumor motion amplitude, the tumor location, and the treatment time are the main factors affecting the tracking accuracy. The pancreatic tumors at different anatomical locations should be treated differently to ensure sufficient dose coverage of the pancreatic target area.
Two Novel Mutations in the SI Gene Associated With Congenital Sucrase-Isomaltase Deficiency: A Case Report in China
Authors: Zhou Jianli , Zhao Yuzhen , Qian Xia , Cheng Yongwei , Cai Huabo , Chen Moxian , Zhou Shaoming 
Published: December 2021

Background: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive inherited disease that leads to the maldigestion of disaccharides and is associated with mutation of the sucrase-isomaltase (SI) gene. Cases of CSID are not very prevalent in China or worldwide but are gradually being identified and reported.Case Presentation: We report a case involving a 14-month-old male who presented with failure to thrive that had begun after food diversification and was admitted for chronic diarrhea. We used a whole-exome sequencing (WES) approach to identify mutations in this patient's genome. WES revealed two novel heterozygous mutations in the SI gene, c.2626C &gt; T (p.Q876*) and c.2872C &gt; T (p.R958C), which were confirmed by Sanger DNA sequencing. With a strict sucrose- and starch-restricted diet, the patient's diarrhea was resolved, and he began to gain weight.Conclusions: We report a case of novel variants in the SI gene that caused CSID. This report provides valuable information for the clinical field, especially in China.
Developing a Reference Database for Typical Body and Organ Growth of the Artificially Reared Pig as a Biomedical Research Model
Authors: Vu Vinh H. , Donovan Sharon M. , Brink Lauren R. , Li Qian , Gross Gabriele , Dilger Ryan N. , Fleming Stephen A. 
Published: December 2021

Objectives: The pig is a common model utilized to support substantiation of novel bioactive components in infant formula. However, reference ranges for outcomes to determine safety are unclear. Our objective was to use historical data to objectively define typical body and organ growth metrics of the domesticated pig in research.Methods: Twenty-two studies were compiled to assess typical growth of body and organ weights in young pigs. Metadata were organized to include milk replacer sources, bioactive components, sex, breed, source of herd, feeding regimen, and rearing environment. A combination of statistical models including simple linear regression and linear mixed effect models were used to assess typical growth patterns.Results: Over 18,000 data points from 786 animals were available. In general, minimal differences in the growth of pigs who were male and female, artificially- or sow-reared, or fed ad libitum- or by scheduled-feeding, were observed in the first 30 days of life (P &gt; 0.05). A weight-for-age chart from reference pigs was developed to compare body weights of pigs demonstrating growth characterized as accelerated, typical, reduced, and failure to thrive to illustrate effects of dietary interventions. Distributions of relative brain, liver, and intestine weights (as % of total body weight) were similar between rearing environments and sexes. An alternative bivariate level approach was utilized for the analysis of organ weights. This approach revealed significant biologically-relevant insights into how deficient diets can affect organ weight that a univariate level assessment of weight distribution was unable to detect.Conclusions: Ultimately, these data can be used to better interpret whether bioactive ingredients tested in the pig model affect growth and development within typical reference values for pigs in the first 30 days of life.
Heparin-Binding Protein in Critically Ill Children With Severe Community-Acquired Pneumonia
Authors: Huang Caizhi , Zhang Cong , Zhang Jie , Zhang Lin , Mo Yi , Mo Liya 
Published: December 2021

Objective: The aim of this study was to investigate possible associations between Heparin-binding protein (HBP) and the development of respiratory failure (RF) and sepsis in critically ill children with severe community-acquired pneumonia (CAP).Methods: This study enrolled 157 children with severe CAP admitted to Intensive Care Unit (ICU). At ICU admission, the levels of HBP and other biomarkers, including C-reactive protein, interleukin-6 (IL-6), procalcitonin, white blood cells, neutrophil percentage, and D-dimer, were determined.Results: Of the enrolled patients, 106 developed RF (35 with RF at enrollment and 71 with RF after enrollment), while 51 did not developed RF. The number of patients progressing to sepsis in those with or without RF were 34 (21 with severe sepsis) and 14, respectively. The plasma level of HBP at admission was more than eightfold higher than the upper normal value. HBP, IL-6, and D-dimer could significantly predict the development of RF, and a high level of HBP (odds ratio = 1.008, 95% confidence interval: 1.003–1.013) was independently associated with the development of RF in this population. Compared with other biomarkers, HBP was the best indicator of progression to severe sepsis, with an area under the receiver operating characteristic curve of 0.85, the best specificity at 96.30%, and a positive predictive value of 92.86% at the optimal cut-off value of 340.29 ng/mL. The HBP level was also positively correlated with other conventional biomarkers.Conclusion: HBP might represent a better predictor of disease progression in children with severe CAP than currently used biomarkers.
Impact of SARS-CoV-2 Infection During Pregnancy on Infant Neurobehavioral Development: A Case-Control Study
Authors: Cheng Yao , Teng Haoyue , Xiao Yue , Yao Mengxin , Yin Jieyun , Sun Guoqiang 
Published: December 2021

Background: Previous studies on the pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on the general population and pregnant women, while little is known about the effects of SARS-CoV-2 on retardation during and after pregnancy. The purpose of this study was to evaluate the potential influence of SARS-CoV-2 on infant neurobehavioral development.Methods: A case-control study was conducted in Maternal and Child Health Hospital of Hubei Province. Nine pregnant women with SARS-CoV-2 infection and 9 controls matched by maternal age, parity, and status of chronic disease were included. Infantile neurobehavioral development was assessed through the Ages and Stages Questionnaires Edition 3 (ASQ-3).Results: The majority of pregnant women with SARS-CoV-2 experienced cesarean section (7 of 9), which was higher than the control group (5 of 9). The throat swabs of all newborn were negative. We found that compared with the control group, neonates of mothers with SARS-CoV-2 infection during pregnancy had lower scores in communication, gross movement, fine movement, problem solving, and personal-social domains; but only fine movement domain yielded statistical significance (P = 0.031).Conclusion: Infection with SARS-CoV-2 during pregnancy may have a certain impact on infant neurobehavioral development. Further studies with larger sample size are warranted for validation.
An Integration of Network Pharmacology and Experimental Verification to Investigate the Mechanism of Guizhi to Treat Nephrotic Syndrome
Authors: He Dan , Li Qiang , Du Guangli , Meng Guofeng , Sun Jijia , Chen Shaoli 
Published: December 2021

Background: Guizhi has the pharmacological activity of anti-inflammatory. However, the effect mechanism of Guizhi against nephrotic syndrome (NS) remains unclear. A network pharmacological approach with experimental verification in vitro and in vivo was performed to investigate the potential mechanisms of Guizhi to treat NS.Methods: Active compounds and potential targets of Guizhi, as well as the related targets of NS were obtained from the public databases. The intersecting targets of Guizhi and NS were obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI), genes ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. And the overall network was constructed with Cytoscape. Molecular docking verification was carried out by AutoDock Vina. Finally, in vitro and in vivo experiments were performed to verify the mechanism of Guizhi to treat NS.Results: 63 intersecting targets were obtained, and the top five key targets mainly involed in NF- Kappa B and MAPK signaling pathway. In the overall network, cinnamaldehyde (CA) was the top one active compound with the highest degree value. The molecular docking showed that the top five key targets were of good binding activity with the active components of Guizhi. To in vitro experiment, CA, the main active component of Guizhi, inhibited the secretion of IL-1β, IL-6, TNF-α in LPS challenged RAW264.7 cells, and down regulated the protein expression of p-NF-κB p65 and p-p38 MAPK in LPS challenged RAW264.7 cells. In vitro experiment showed that, 24 urinary protein and renal function were increased in ADR group. To western blot, CA down regulated the protein expression of p-p38 MAPK in rats of adriamycin-induced nephropathy.Conclusion: CA might be the main active component of Guizhi to treat NS, and the underlying mechanism might mainly be achieved by inhibiting MAPK signaling pathway.
Fourier-Domain Optical Coherence Tomographic Assessment of Changes in the Schlemm’s Canal of Nonglaucomatous Subjects After Keratoplasty
Authors: Zhao Yujin , Li Yue , Hong Jiaxu , Le Qihua , Xu Jianjiang 
Published: December 2021

Purpose: This study aimed to evaluate the impact of keratoplasty on the in vivo anatomical structures in the Schlemm’s canal (SC) of nonglaucomatous subjects using Fourier-domain optical coherence tomography (FD-OCT).Methods: Sixty-six nonglaucomatous eyes that underwent penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), or triple surgery were enrolled in this prospective, comparative, observational study. The SC imaging was performed using FD-OCT before and after surgery in both the nasal and temporal quadrants. Patient demographics, SC parameters [e.g., cross-sectional area (CSA), meridional diameter of SC (MSC), sagittal diameter of SC (SSC), and circumference (CCF)], and the correlations between the variation of SC parameters and intraocular pressure (IOP) were analyzed.Results: The mean age of all subjects was 40.27 ± 18.97 years. Among all cases, the nasal, temporal, and mean MSC significantly decreased on the first day after surgery and then increased at 1 week (p = 0.04, 0.017, and 0.01, respectively). Temporal CSA (tCSA), temporal MSC (tMSC), and temporal circumference (tCCF) after PK (p = 0.017, 0.020, and 0.018, respectively) and nasal MSC (nMSC) after DALK (p = 0.025) decreased significantly on the first day after surgery. The shift in mean IOP was significantly correlated with the changes in tMSC (r = 0.341, p = 0.003) and CCF (r = 0.207, p = 0.048).Conclusion: SC had significant in vivo morphological changes in the early period after keratoplasty in nonglaucomatous eyes, accompanied with elevation of IOP. Early intervention might be necessary to prevent secondary glaucoma early after keratoplasty.
Human Bone Marrow Mesenchymal Stromal Cell-Derived Extracellular Vesicles Promote Proliferation of Degenerated Nucleus Pulposus Cells and the Synthesis of Extracellular Matrix Through the SOX4/Wnt/β-Catenin Axis
Authors: Wang Haoyu , Li Fei , Ban Wenrui , Zhang Jing , Zhang Guiqi 
Published: December 2021

Objective: Intervertebral disk degeneration (IDD) is a major cause of pain in the back, neck, and radiculus. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) are therapeutic in musculoskeletal degenerative diseases such as IDD. This study explored the effect and functional mechanism of human bone MSCs (hBMSCs)-derived EVs in proliferation and apoptosis of degenerated nucleus pulposus cells (DNPCs) and extracellular matrix (ECM) synthesis.Methods: Extracellular vesicles were isolated from hBMSCs and identified. DNPCs were induced by TNF-α. EVs were incubated with DNPCs for 24h. Internalization of EVs by DNPCs, DNPCs proliferation, apoptosis, and expressions of ECM synthetic genes, degrading genes and miR-129-5p were assessed. Downstream target genes of miR-129-5p were predicted. Target relation between miR-129-5p and SRY-box transcription factor 4 (SOX4) was verified. DNPCs proliferation, apoptosis, and ECM synthesis were measured after treatment with EVs and miR-129-5p inhibitor or SOX4 overexpression. Expressions of SOX4 and Wnt/β-catenin pathway-related proteins were determined.Results: hBMSC-EVs promoted DNPCs proliferation, inhibited apoptosis, increased expressions of ECM synthetic genes, and reduced expressions of ECM degrading genes. hBMSC-EVs carried miR-129-5p into DNPCs. Silencing miR-129-5p in EVs partially inverted the effect of EVs on DNPCs proliferation and ECM synthesis. miR-129-5p targeted SOX4. SOX4 overexpression annulled the effect of EVs on DNPCs proliferation and ECM synthesis. Expressions of Wnt1 and β-catenin were decreased in EVs-treated DNPCs, while silencing miR-129-5p in EVs promoted expressions of Wnt1 and β-catenin.Conclusion: hBMSC-EVs promoted DNPCs proliferation and ECM synthesis by carrying miR-129-5p into DNPCs to target SOX4 and deactivating the Wnt/β-catenin axis.
Shifting Positionalities in a Time of COVID-19: The Transnational Public Health Doctor and Ethnographer
Authors: Saleh Sepeedeh 
Published: December 2021

Ethnographic research is characterised by in-person engagement with individuals and groups within a social setting, usually over an extended timeframe. These elements provide valuable insights which cannot be gained through other forms of research. In addition, such levels of involvement in “the field” create complex, shifting researcher-participant relationships which themselves shape the course of the project and its findings. The COVID-19 pandemic disrupted many research projects, but impacts on ethnographic research, with its emphasis on physical presence in the field and interpersonal relationships, reveals much about these key elements of our praxis.I discuss how the pandemic influenced the progress of an ethnographic research project, based in Malawi, including consideration of how, as lead for the project, my clinical/“public health” positionalities interacted with relationships in the village and the arrival of COVID-19 in Malawi. This account reveals shifting intersubjectivities of researchers and participants as the pandemic brought changes in the nature of the engagement, from ethnographic explorations into the roles of smoke in everyday life, through fieldwork suspension, and contextualised COVID-19 response. These experiences demonstrate how a basis of reflexive ethnographic engagement with communities can underpin thoughtful responses to upcoming challenges, with implications for future “global health” work, both within and beyond the pandemic context.
Perfil clínico-epidemiológico e fatores de risco associados ao desenvolvimento de depressão perinatal em gestantes de risco acompanhadas nos anos de 2017-2018 em Hospital Materno-Infantil no Distrito Federal / Clinical-epidemiological profile and risk factors associated with the development of perinatal depression in high-risk pregnant women followed in 2017-2018 at the Hospital Materno-Infantil in the Federal District
Authors: Suarte Antonio Pedro de Melo Moreira , Barbosa Júlia Visconti Segovia , Feire Maria Marta Neves de Oliveira , Arrais Alessandra da Rocha 
Published: December 2021

A prevalência de Depressão Perinatal (DP) em gestantes vai de 10-15%, podendo chegar a 44,2% em gestações de alto risco. Objetivo: avaliar a prevalência da DP em gestações de alto risco, descrever o perfil clínico e epidemiológico e destacar os principais fatores de risco associados à DP. Método: estudo retrospectivo, amostra por conveniência, analisou-se os prontuários de 282 usuárias do Ambulatório de Psiquiatria Perinatal do HMIB (234 grupo experimental e 48 grupo controle). Para a análise das variáveis qualitativas utilizou-se o teste Qui-quadrado de Pearson ou teste exato de Fisher quando mais adequado, e para as variáveis quantitativas, utilizou-se o teste de Kolmogorov Smirnov, e/ou o teste U de Mann-Whitney. Resultados: 52,56% (n=123) das gestantes desenvolveram DP. Histórico de transtorno mental antenatal, ideação suicida, falta de suporte social, história de tentativa ou abuso sexual na infância foram apontados como fatores de risco para DP. Conclusões: Mesmo com a crescente da importância de uma abordagem interdisciplinar no pré-natal há tendência de foco apenas no aspecto biológico materno-fetal. A falta de políticas públicas, a ausência de triagem psíquica no pré-natal e poucas intervenções dirigidas a promover prevenção de saúde mental materna e prevenir o adoecimento em mulheres em idade reprodutiva, reforça a necessidade de pré-natal psicológico na rede de atenção pública.