bluuebunny/crossref_metadata_2025 huggingface dataset:
In-Vivo Generation of Antigen-Specific Tregs with AAV8 Suppresses Collagen-Induced Arthritis in DBA1 Mice through IL-10 Production
Authors: Wade Matthew , Fausther-Bovendo Hugues , Vega Marc-Antoine De La , Kobinger Gary
Published: June 2021

Available therapeutics for autoimmune disorders focused on mitigating symptoms, rather than treating the cause of the disorder. A novel approach using adeno-associated virus (AAV) could restore tolerance to the autoimmune targets and provide a permanent treatment for autoimmune diseases. Here, we evaluated the ability of collagen II T-cell epitopes packaged in adeno-associated virus serotype 8 (AAV-8) vectors to reduce pathogenic cellular and humoral responses against collagen and to mitigate the disease in the collagen-induced arthritis mouse model. The cytokines and immune cells involved in the immune suppression were also investigated. Mice treated with AAV-8 containing collagen II T-cell epitopes demonstrated a significant reduction in the arthritis symptoms, pathogenic collagen specific antibody and T cell responses. The AAV-8 mediated immune suppression was mediated by increased interleukin-10 expression and regulatory T cells expansion. Altogether, this study strengthens the notion that AAV vectors are promising candidates for the treatment of autoimmune diseases.
Low-specific Symbiotic Germination of Dendrobium Huoshanense in Vitro, an Endangered Epiphytic Orchid Endemic From South China
Authors: Tang Yan-Jing , Dai Jun , Li Yang , Zhou Dong-Yu , Xing Yong-Mei , Guo Shun-Xing , Chen Juan
Published: June 2021

Background: Dendrobium huoshanense is an endangered epiphytic orchid and is endemic to Anhui province of China with a narrow distribution. In nature, orchid seed germination depends on specific mycorrhizal fungi and it is generally assumed that there is a high specific symbiotic germination in narrow distribution orchid. To evaluate the mycorrhizal compatibility and germination-promoting activity of mycorrhizal fungi of D. huoshanense in vitro, we isolated and identified cultured mycorrhizal fungi from the roots of D. huoshanense and D. officinale. A total of 20 mycorrhizal fungal strains (D. huoshanense (n = 6), D. officinale (n = 12), D. nobile (n = 1), D. moniliforme (n = 1)) were used to test the germination-promoting activity of D. huoshanense. Results: In symbiotic germination tests, the mycorrhizal fungi displayed different efficiency in stimulating D. huoshanense seed germination, nine strains stimulated seed development to an advanced seedling stage, while the rest promoted only initial seed germination to stage 2 or stage 3, and the most effective in promoting rapid seed germination was strain 12825(seb) isolated from D. moniliforme, besides, the second most effective fungus was strain WX-7(seb) isolated from D. officinale, both of them belong to Sebacina isolated from non-D. huoshanense. In this study, all twenty fungal strains formed pelotons inside seeds of D. huoshanense based on the trypan blue staining results. Conclusions: Despite its narrow specific habitat preference, D. huoshanense was found to be a mycorrhizal generalist during symbiotic seed germination in vitro. The study is the first to demonstrate the different abilities of orchid mycorrhizal fungi to promote seed germination, protocorm formation and seedling development of D. huoshanense in vitro, providing important microbiological resources for its conservation and reintroduction in nature.
Paradox of Nonpathogenicity and Cytopathic Effects：Characterization of Regulator Tas in Foamy Virus Evolution and De-Ubiquitylation of Tas in Virus Duplication
Authors: Jie Wei , Fen Zhang Rui , Jing Song , Yan Wu , Ping Ma Yong , Zhi Li , Hong Liu Wan , Hua He Xiao , Yan Sun
Published: June 2021

Background: Foamy virus, which belong to the Spumaretrovirinae subfamily of Retroviridae, bridge the gap between Orthoretrovirinae and Hepadnaviridae, and display a long co-evolution with their hosts. Like other retroviruses, FVs encode a transactivator, Tas, which governs the levels of viral transcripts initiated through binding to the conserved promoters in 5’ long terminal repeat (LTR) and a unique internal promoter (IP). Unlike the other retrovirus, HIV, foamy viruses induced significant cytopathic effects in vitro, but has no significant disease association at the infection level in vivo. The characterization of regulator Tas in the Paradox of nonpathogenicity and cytopathic effects was still unknown.Results: Foamy virus separated from different hosts could form three groups which paralleled with the worldwide distribution of hosts due to geographical isolation. Although the physicochemical properties of different Tas were mainly in line with each other, the conserved motifs analyses still suggested divergences in protein functions. The proteins identified to interact with Tas of PFV, SFVora and SFVagm displayed that the three kinds of foamy viruses regulated different signal pathways and impacted virus-host immune interaction. Interestingly, predictions of interactional factors based on protein sequence showed USP7, a kind of deubiquitinating enzyme, could binding directly to Tas which led to its ubiquitin-dependent proteasome degradation. And this results also implyed that fomay virus could hijacked cytokine USP7 to stabilize the transcriptional activator Tas by de-ubiquitylation and thereby regulate the viral life cycle.Conclusion: Our experiments help to understand the survival strategy of foamy viruses in their hosts.
Association between Climate Parameters and COVID-19 Pandemic in Jordan
Authors: Dabbour Loai , Abdelhafez Eman , Hamdan Mohammad
Published: June 2021

This research aims to study the association between the daily confirmed COVID − 19 cases in the three major cities of Jordan; Amman, Zarqa, and Irbid and climate indicators to include the average daily temperature (0C), wind speed (m/s), relative humidity (%), pressure (kPa), and the concertation of the four pollutants (CO, NO2, PM10 and SO2). The data were obtained from both the World Air Quality Project website and the Jordanian Ministry of Environment. In this work, the multiple linear regression and feedforward artificial neural network were used for data analysis. It was concluded that the multiple linear regression and feedforward artificial neural network had the capability to forecast the COVID-19 confirmed cases in the case studies; Amman, Irbid and Zarqa. Finally, global sensitivity analysis using Sobol analysis indicated that pressure in Amman and Zarqa and the concentration of NO2 in Irbid has a high rate of positive cases that supports the virus's spread.
Vitrectomy and External Drainage of Subretinal Fluid Containing High Concentration of Vascular Endothelial Growth Factor for Advanced Coats Disease
Authors: Mano Fukutaro , Matsushita Itsuka , Kondo Hiroyuki , Utamura Shoko , Kondo Chiori , Kusaka Shunji
Published: June 2021

This study investigated the surgical outcomes of Coats disease and the role of external drainage (XD) of subretinal fluid (SRF). The study is a multicenter retrospective interventional case series of 26 consecutive eyes of 26 patients who underwent surgeries for advanced Coats disease with retinal detachment. Main outcomes measured were: 1) comparison of complete SRF resolution with or without XD, and 2) variables that were associated with functional postoperative best-corrected visual acuity (BCVA) defined as BCVA of 0.1 or better, 3) intraocular vascular endothelial growth factor (VEGF) levels. Complete SRF resolution was achieved in all 14 eyes in which XD had been performed and in 75% of 12 eyes in which XD had not been performed (P =.03). Multivariable logistic regression analysis revealed that initial BCVA was the only variable associated with functional postoperative BCVA (odds ratio 3.24, 95% CI 0.93–11.33; P =.04). Markedly elevated VEGF levels were noted in the SRF compared with those in the vitreous humor (49,760 ± 52,990 vs. 707 ± 611 pg/mL, P =.03). XD seems to provide better anatomical success than without XD in the treatment of advanced Coats disease as XD could effectively eliminate substantial amount of VEGF in the SRF.
Caffeic Acid Phenethyl Ester Attenuates Gingival Tissue Inflammation in Experimental Periodontitis
Authors: DEMİR Esra , ÖZDEN Feyza Otan , AVCI Bahattin
Published: June 2021

The authors have requested that this preprint be removed from Research Square.
The Study of Soft Soil Seismic Subsidence Based On 3D Model
Authors: li Ping , Gu Junru , Liu Yingci , Li Yuying
Published: June 2021

Soft soils are characterized by high sensitivity, low strength, and susceptibility to seismic subsidence. In this study, nonlinear dynamic finite element analysis was performed by OpenSees numerical simulation method to evaluate seismic subsidence response of soft soil site to input ground motions. Higher peak acceleration of ground motion enhanced degree of uneven seismic subsidence, depth of seismic depression, and damage to horizontal surface. Frequency characteristics of a ground motion are another factor influencing seismic subsidence of soft soil. Similar predominant frequency of a ground motion to natural frequency of soil site, high number of low frequency contents, and high amplitude of a ground motion promoted a more severe seismic subsidence of soft soil. The findings of this study expand current understanding on seismic subsidence of soft soil.
Racial Disparities in the Incidence, Breast Conserving Rate and Survival of Breast Cancer Patients Who Underwent Breast Conserving Surgery
Authors: Han Shu , Liu Jianjun , Tang Weifang , Wang Shengying , Hong Shikai
Published: June 2021

Objective: In the current study, we aimed to provide a clear insight on the racial disparity of breast conserving rate (BCR) and survival in breast cancer after breast conserving surgery (BCS). Materials and Methods: Using data from the Surveillance, Epidemiology, and End Results program (SEER), we estimated breast cancer incidence rates and the rate of BCS by race in two periods (2000-2004 and 2013-2017). Relative survival analysis was based on patient-level data from 1998 to 2017. To be adjusted for baseline differences for different races, inverse probability weighting (IPW) models were stepwise performed.Results: From 2000-2004 to 2013-2017, both the breast cancer incidence (from 4.18 to 5.05 per 1000 white women) and the proportion of patients after BCS (from 55.5% to 59.9) were highest in whites than that of other races. Black individuals’ incidence (1.20 per 1000 black women or relatives 43.6% increased) and the BCR were increased most rapidly (6%) than other races. Asian or Pacific Islanders (APIs) were less likely to be diagnosed at a later stage and had the best prognosis than those of other races. After baselines fully adjusted, whites had the better Breast Cancer Specific Survival (BCSS) and Overall Survival (OS) than that of minorities (all p< 0.001).Conclusions: We identified the racial disparities of breast cancer incidence, BCR, and survival differences. We found increase trends of breast cancer incidence and BCR in minorities; however, we also identified the worse survival of minorities than that of whites, regardless of age, tumor stage, grade, and Luminal subtype.
Visualizing designer quantum states in stable macrocycle quantum corrals
Authors: Lu Jiong , Peng Xinnan , Mahalingam Harshitra , Dong Shaoqiang , Mutombo Pingo , Su Jie , Telychko Mykola , Song Shaotang , Ng Pei Wen , Wu Jishan , Jelinek Pavel , Chi Chunyan , Rodin Aleksandr , Lyu Pin
Published: June 2021

Creating atomically-precise quantum architectures with high digital fidelity and desired quantum states is an important goal in a new era of quantum technology. The strategy of creating these quantum nanostructures mainly relies on atom-by-atom, molecule-by-molecule manipulation or molecular assembly through non-covalent interactions, which thus lack sufficient chemical robustness required for on-chip quantum device operation at elevated temperature. Here, we report a bottom-up synthesis of covalently linked organic quantum corrals (OQCs) with atomic precision to induce the formation of topology-controlled quantum resonance states, arising from a collective interference of scattered electron waves inside the quantum nanocavities. Individual OQCs host a series of atomic orbital-like resonance states whose orbital hybridization into artificial homo-diatomic and hetero-diatomic molecular-like resonance states can be constructed in Cassini oval-shaped OQCs with desired topologies corroborated by joint and analytic calculations. Our studies open up a new avenue to fabricate covalently linked large-sized OQCs with atomic precision to engineer desired quantum states with high chemical robustness and digital fidelity for new-generation quantum technology.
Condensation Product of 5-Bromosalicylaldehyde and Amino Phenol: Fluorescence Sensor for Ascorbic Acid and AND Logic Gate
Authors: Bharali Bidisha , Das Diganta Kumar
Published: June 2021

Condensation product of 5-bromosalicylaldehyde and aminophenol (L) has been synthesised and characterised. Fluorescence of L enhances by 23 times on interaction with Ce3+ while it is quenched completely by Ce4+. Ascorbic acid (AA) is a well known strong reducing agent and this property has been used to act L:Ce4+ adduct as a fluorescence “on” sensor for AA. AA reduces Ce4+ into Ce3+ and thereby increasing fluorescence of L due to the formation of L:Ce3+ adduct. Molecules which generally coexist with AA viz. Cholesterol, Glucose, Sucrose and Dopamine found not to interfere. The interaction of L with Ce3+, Ce4+ and subsequently with AA has been verified with cyclic voltammetry.
Spatio-Temporal Classification and Prediction of Land Use and Land Cover Change for the Vembanad Lake System, Kerala – a Machine Learning Approach
Authors: Sundar Parthasarathy Kulithalai Shiyam , Deka Paresh Chandra
Published: June 2021

Land use and land cover (LULC) change has become a critical issue for decision planners and conservationists due to inappropriate growth and its effect on natural ecosystems. As a result, the goal of this study is to identify the LULC for the Vembanad Lake System (VLS), Kerala in the short term, i.e., within a decade, utilizing two standard machine learning approaches, Random Forest (RF) and Support Vector Machines (SVM), on the Google Earth Engine (GEE) platform. When comparing the two techniques, SVM is classified at an average accuracy of around 84.5%, while RF is classified at 89%. The RF outperformed the SVM in almost identical spectral classes such as barren land and built-up areas. As a result, RF classified LULC is considered to predict the Spatio-temporal distribution of LULC transition analysis for 2035 and 2050. The study was conducted in Idrisi TerrSet software using the Cellular Automata (CA)-Markov chain analysis. The model's efficiency is evaluated by comparing the projected 2019 image to the actual 2019 classified image. The efficiency was good with more than 94% accuracy for the classes except for barren land, which might have resulted from the recent natural calamities and the accelerated anthropogenic activity in the area.
Development and Validation of a Risk Prediction Model of Linezolid-induced Thrombocytopenia in Elderly Patients
Authors: Qin Yan , Chen Zhe , Gao Shuai , Pan Ming Kun , Li Yu Xiao , Lv Zhou Qian , Shen Yun , Ye Yanrong
Published: June 2021

Background Linezolid is an oxazolidinone antimicrobial agent developed for treating multi-drug-resistant gram-positive bacterial infections. Objective This study aimed at investigating risk factors of linezolid (LI)-induced thrombocytopenia (LI-TP) and establishing a risk predictive model for LI-TP.Setting ZhongShan Hospital, FuDan University, China. Method A retrospective study was performed in patients aged ≥ 65 years receiving linezolid therapy from January 2015 to April 2021. Clinical characteristics and demographic data were collected and compared between patients with LI-TP and those without.Main outcome measures Incidence and risk factors of LI-TP in elderly patients.Results A total of 343 inpatients were included as the train set from January 2015 to August 2020. Among them, 67 (19.5%) developed LI-TP. Multivariate logistic regression analysis revealed that baseline platelet counts < 150×109·L-1 (OR=3.576; P< 0.001), age ≥ 75 years (OR=2.258; P=0.009), eGFR< 60 mL·(min·1.73m2)-1 (OR=2.553; P=0.002), duration of linezolid therapy ≥ 10 d (OR=3.218; P<0.001), ICU admittance (OR=2.682; P=0.004), and concomitant with piperacillin-tazobactam (PTZ) (OR=3.863; P=0.006) were independent risk factors for LI-TP. The risk predictive model was established and exhibited a moderate discriminative power, with an AUC of 0.795 [95%CI 0.740-0.851] and 0.849 [95%CI 0.760-0.939] in train set (n=343) and validation set (n=90), respectively.Conclusion The risk factors of LI-TP in elderly patients were duration of linezolid therapy, age, eGFR, ICU admittance, baseline platelet counts, and concomitant with PTZ. A risk predictive model based on these risk factors may be useful to identify patients with high risk of LI-TP.
Prognostic Value of Long Non-Coding RNAs MALAT1 in Colorectal Cancer Patients: A Pooled Analysis of Two Cohorts.
Authors: Li Heng , Zhang YuXue , Liu YanLong , Qu ZhangYi , Liu YuPeng , Qi JiPing
Published: June 2021

Background: Previous researches have shown that the aberrant expression of Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in tumour tissues may serve as a biomarker for colorectal cancer (CRC) prognosis. However, these previous studies have small sample sizes and lacked validation from independently external populations. We therefore aimed to clarify the prognostic value of MALAT1 expression status in CRC patients using a large cohort and validate the findings with another large external cohort. Methods: The prognostic association between MALAT1 expression status and CRC outcomes was evaluated initially in a prospective cohort in China (n=164) and then validated in an external TCGA population (n=596). In the initial cohort, MALAT1 expression levels were quantified by quantitative reverse transcriptase polymerase chain reaction. Propensity score (PS) adjustment method was used to control potential confounding biases. The prognostic significance was reported as PS-adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI). Results: There was no statistically significant association between MALAT1 expression status and CRC patient overall survival (OS) or disease free survival (DFS) in both initial cohort and external validation cohort populations. When combining these populations together, the results did not change materially. The summarized HRPS-adjusted were 1.010 (95%CI, 0.752-1.355, P=0.950) and 1.170 (95%CI, 0.910-1.502, P=0.220) for OS and DFS, respectively. We performed extensive sensitivity analyses, and demonstrated a very robustness of these results. Conclusions: The MALAT1 expression status was not associated with prognostic outcomes in CRC patients. Our findings did not support a prognostic association of MALAT1 expression with CRC outcomes.
Activated mTORC1-SIRT6 Mediates Myofibroblast Differentiation and Idiopathic Pulmonary Fibrosis
Authors: Zhang Ji , Hu Yi , Huang Huiping , Liu Qun , Du Yang , Wang Guangdong , Gao Dehong , Guo Weixi , Wang Zhanxiang , Ma Aiping
Published: June 2021

BackgroundIdiopathic pulmonary fibrosis (IPF) is characterised by accumulation of myofibroblasts and deposition of extracellular matrix proteins. Fibroblast-to-myofibroblast transdifferentiation and myofibroblast hyperproliferation plays a major role in pulmonary fibrosis. Moreover, mTOR signaling pathway and SIRT6 play a critical role in pulmonary fibrosis. However, the mechanisms whether SIRT6 affect the myofibroblasts differentiation during IPF remain unclear.MethodWe investigated myofibroblast differentiation using a bleomycin-induced mouse pulmonary fibrosis model and TGF-b1 induced human fetal lung fibroblasts (MRC5) in vitro. We used both SIRT6 siRNA and rapamycin to study the role of SIRT6 and mTOR signaling pathway in the normal human lung fibroblasts and the myofibroblasts from human IPF lungs.ResultsOur data show that high level of SIRT6 was detected in IPF samples, and SIRT6 was signiﬁcantly upregulated by TGF-β1 in a time and concentration-dependent manner. SIRT6 expression and activation of mTORC1 signalling pathway were upregulated in fibrotic lung tissues and primary lung fibroblasts isolated from patients with IPF and bleomycin-challenged mice. Furthermore, rapamycin treatment inhibited mTORC1 pathway activity and SIRT6 protein expression. SIRT6 SiRNA failed to mediate the activity of mTORC1 pathway and autophagy induction. However, SIRT6 knockdown could promote TGF-b1 induced pro-fibrotic cytokines.ConclusionActivated mTORC1 signalling pathway regulated SIRT6 overexpression. Deficiency of SIRT6 mediated myofibroblasts differentiation through induced pro-fibrotic cytokines production in the present of TGF-β1. The study indicated that manipulations of SIRT6 expression may provide a new therapeutic strategy to prevent and reverse the progression of pulmonary fibrosis.
Management of a Pipkin Type III Femoral Head Fracture Via Ganz Approach with a Cannulated Lag Screw & Herbert Screw
Authors: Hu Liangcong , Xie Xudong , Mi Bobin , Michael. Le Grange Jehane , Wang Tiantian , Xue Hang , Lin Ze , Xiong Yuan , Hu Yiqiang , Yan Chengcheng , Chen Lang , Zhou Wu , Liu Mengfei , Liu Guohui
Published: June 2021

Objective: To evaluate the medium - to long-term efficacy of a Ganz approach and cannulated lag screw combined with Herbert screw, in the management of a Pipkin type III femoral head fracture.Methods:Retrospective analysis was performed on 11 patients (6 males, 5 females) who sustained Pipkin type III femoral head fractures and were managed with a cannulated lag screw, combined with Herbert screw, inserted using the Ganz approach and who were admitted to our department between June 2018 to June 2020. Perioperative indicators, postoperative function and follow-up complications at 9 months after surgery, Harris score at 6 and 9 months after surgery, Thompson-Epstein score, hip femoral head necrosis and incidence of post traumatic hip arthritis were analysis.Results:10 patients completed follow-up, with an average follow-up time of (13.7 ± 2.1) months. The mean operative time was (100.3 ± 23.67) minutes, intraoperative blood loss was (138.6 ± 50.18) ml, peripheral blood hemoglobin (Hb) was (105.6 ± 18.94) g/L 24 hours after surgery, and the complication rate was 1/10 2 weeks after surgery. The Harris Hip Scores for joint function at 6 and 9 months after the operation were (68.6 ± 5.49) points and (88.8 ± 5.77) points respectively. The excellent and good rate in the last follow-up was 80% (Thompson-Epstein score). The complication rate was 10%.Conclusion:A cannulated lag screw combined with a Herbert screw and inserted via the Ganz approach, is an effective method for the treatment of Pipkin type III fractures.
Risk Factors for Maternal and Fetal Mortality in Acute Fatty Liver of Pregnancy and New Predictive Models
Authors: Meng Zhaoli , Fang Wei , Zhang Jicheng , Meng Mei , Wang Qizhi , Qie Guoqiang , Chen Man , Wang Chunting
Published: June 2021

Background: Acute fatty liver of pregnancy (AFLP) is a rare but potentially life-threatening hepatic disorder that leads to considerable maternal and fetal mortality. A better understanding of the risk factors of AFLP is required.Methods: We analyzed demographic characteristics, clinical symptoms, and laboratory findings of 106 patients with acute fatty liver of pregnancy. Risk factors for maternal and fetal mortality were analyzed by univariate and multivariate logistic regression analysis. The new models based on the multivariate logistic regression analysis and model for end-stage liver disease were tested for all patients with acute fatty liver of pregnancy. The receiver operating characteristic curve was applied to compare the prediction efficiency, sensitivity, and specificity of the two models.Results: Prenatal nausea (p = 0.037), prolonged prothrombin time (p = 0.003), and elevated serum creatinine (p = 0.003) were independent risk factors for maternal mortality in patients with acute fatty liver of pregnancy. The receiver operating characteristic curve showed that the area under the curve of the model for end-stage liver disease was 0.948, with a sensitivity of 100% and a specificity of 83.3%. The area under the curve of new model was 0.926, with a sensitivity of 90% and a specificity of 94.8%. Hepatic encephalopathy (p = 0.016) and thrombocytopenia (p = 0.001) were independent risk factors for fetal mortality. Using receiver operating characteristic curve, the area under the curve of the model for end-stage liver disease was 0.694, yielding a sensitivity of 68.8% and a specificity of 64.4%. The area under the curve of the new model was 0.893, yielding a sensitivity of 100% and a specificity of 73.3%. Conclusion: Both the new predictive model for maternal mortality and the model for end-stage liver disease showed good predictive efficacy for maternal mortality in patients with acute fatty liver of pregnancy (the area under the curve = 0.948 and 0.926, respectively), and the new predictive model for fetal mortality was superior to the model for end-stage liver disease in predicting fetal mortality (the area under the curve = 0.893 and 0.694, respectively) with better sensitivity and specificity.
ERBB2 S310F Mutation Independently activates PI3K/AKT And MAPK Pathways through Homo-Dimerization to Contribute Gallbladder Carcinoma Growth
Authors: Fan Kun , Wang Jiwen , Shen Sheng , Ni Xiaojian , Gong Zijun , Zheng Bohao , Sun Wentao , Suo Tao , Liu Han , Ni Xiaoling , Liu Houbao
Published: June 2021

Genomic instability and mutability are a prominent character of tumor. The whole-exosome sequence reveals that ERBB2 mutations are the representative mutations of gallbladder carcinoma, which takes potential targets for gallbladder carcinoma therapy. However, the roles of ERBB2 mutations are unclear in gallbladder carcinoma. We identified S310F mutation is the hottest mutation of ERBB2 mutations from TCGA PanCancer Altas data with 10967samples and our previous study with 157 gallbladder carcinoma samples. S310F mutation located in ERBB2 extracellular domain, promoted ERBB2 homodimerization and consequent auto-phosphorylation to activate the downstream PI3K/AKT and MAPK pathways, which was independent on ERBB1、ERBB3 and ERBB4. ERBB2 S310F mutation up-regulated aerobic glycolysis and promoted gallbladder carcinoma growth. Our study reveals the roles of ERBB2 S310F mutation, which is beneficial to ERBB2 S310F mutant gallbladder carcinoma therapy.
Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next-generation sequencing in Ramathibodi Hospital, Mahidol University
Authors: Oranratnachai Songporn , Yamkaew Watchalawalee , Tunteeratum Atchara , Sukarayothin Thongchai , Iemwimangsa Nareenart , Panvichian Ravat
Published: June 2021

Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (HBOC) syndrome. A few studies have reported the prevalence of germline BRCA mutations in Asian patients with breast cancer. Here, we aimed to explore the prevalence and characteristics of breast cancers in Thai patients with germline BRCA1/2 mutations. We retrospectively reviewed breast cancer patients tested for germline BRCA1/2 mutations in our institute during 2014–2018. BRCA mutations were detected using next-generation sequencing and confirmed using Sanger sequencing. We analyzed the characteristics of patients with or without BRCA mutations, disease-free survival (DFS), and associated factors. Among the 67 included patients, 12 (18%) were BRCA1/2 carriers (6 each), 4 (6%) harbored variants of uncertain significance, and 51 (76%) were non-carriers. We discovered two novel frameshift mutations in BRCA2 (c.2380delA and c.8855dupT). Mean ages at breast cancer diagnosis in BRCA1 carriers, BRCA2 carriers, and non-carriers were 39.8, 46.2, and 42.0 years, respectively. The 12 tumors of BRCA carriers were mostly the luminal-B subtypes. Two of these tumors were HER2-positive luminal-B; however, the triple-negative subtype was not observed. After adjusting for stages and luminal subtypes, BRCA carriers experienced worse 3-year DFS than non-carriers (81.5% vs. 90.3%, HR 2.04 (0.64–6.49), P = 0.229). The stage at diagnosis was the sole factor significantly associated with 3-year DFS (100%, 84.8%, and 72.7%; stages I, II, and III, respectively). In summary, breast cancers in Thai patients with germline BRCA1/2 mutations were mostly the luminal-B subtypes and experienced a worse prognosis than those without mutations.
Novel Cattail Fiber Composites - Converting Waste Biomass into Reinforcement for Composites
Authors: Shadhin Md , Rahman Mashiur , Jayaraman Raghavan , Mann Danny
Published: June 2021

Vacuum Assisted Resin Transfer Molding (VARTM), used to manufacture medium to large sized composites for transportation industries, require non-woven mats. While non-woven glass mats used in these applications are optimized for resin impregnation and properties, such optimized mats for natural fibers are not available. In the current research, cattail fibers were extracted from plants (18–30% yield) using alkali retting and nonwoven cattail fiber mat was manufactured. The extracted fibers exhibited a normal distribution in diameter (davg. = 32.1 µm) and the modulus and strength decreased with increase in diameter with average values of 19.1 GPa and 172.3 MPa, respectively. The cattail fiber composites were manufactured using non-woven mats, Stypol polyester resin, and VARTM (101 kPa) and compression molding pressures (260 and 560 kPa) and tested. Out-of-plane permeability changed with Vf of mats, which was influenced by areal density, thickness, and fiber packing in the mat. The cattail fibers reinforced the stypol resin significantly. The modulus and the strength increased with consolidation pressures due to increase in fiber volume fraction (Vf), with maximum values of 7.4 GPa and 48 MPa, demonstrating the utility of Cattail fibers from waste biomass as reinforcements.
Trefoil Factors as Screening Biomarkers for Gastric Cancer and Premalignant Lesions: A Cross-Sectional Population-Based Cohort Study
Authors: Zan Xiangyi , Chen Zhaofeng , Guo Qinghong , Wang Yuping , Zhang Zhiyi , Ji Rui , Zheng Ya , Zhang Jinhua , Wu Zhengqi , Li Min , Wang Xiang , Ye Yuwei , Li Xiaohua , An Feng , Xu Chuanggui , Lu Linzhi , Fan Ping , Zhang Jun , Guan Quanlin , Li Qiang , Liu Min , Ren Qian , Hu Xiaobin , Lu Hong , Wang Yuling , Zhang Hongling , Zhao Yue , Gou Xi , Shu Xiaochuang , Wang Jun , Hu Zenan , Liu Rong , Yuan Hao , Liu Jiankang , Qiao Liang , Zhou Yongning
Published: June 2021

Background:

The lack of effective biomarkers for screening gastric cancer (GC) and premalignant lesions (PMLs) is a significant roadblock in the prevention and early intervention of GC. We aimed to identify noninvasive biomarkers to improve the screening of high-risk populations.
Methods:

We evaluated 25,000 adults residing in Wuwei. We collected baseline characteristics, GC risk indicators, including trefoil factors (TFF1–3), endoscopy diagnosis, and pathological information. We analyzed the data to determine the association of risk biomarkers with the progression of GC and the prediction capacities of these biomarkers using odds ratio (OR)-adjusted models and receiver operating characteristic (ROC) curve analyses.
Results:

TFF1 and TFF2 serum levels showed incremental changes from the PMLs to the GC group, with the highest serum TFF3 levels reported in the intestinal metaplasia group. TFF1 and TFF2 had significant predictive values in the PMLs and GC in the three OR-adjusted models but not in the non-atrophic gastritis group. Similar results were obtained after adjusting for all biomarkers and risk factors wherein the ORs (95 % confidence intervals) of TFF1 and TFF2 in the GC group were 2.71 (1.57–4.67) and 2.87 (1.75–4.71), respectively (P < 0.001). The combination of TFF1–3 showed the largest area under the curve across all four groups (chronic atrophic gastritis [0.74], intestinal metaplasia [0.79], low-grade intraepithelial neoplasia/dysplasia [0.79], and GC [0.84]), making it the best-fit ROC.
Conclusions:

TFF1, TFF2, and the combination of TFF1–3 can serve as sensitive, specific, and noninvasive biomarkers for detecting GC and PMLs, facilitating the early identification of these lesions.
Antioxidant Systems Response, Mineral Element Uptake and Safe Utilization of Polygonatum Sibiricum in Cadmium-Contaminated Soil
Authors: Kang Yuchen , Yang Li , Dai Haibo , Xie Mengdi , Wang Yuhao , Peng Jie , Sun Hui , Ao Tianqi , Chen Wenqing
Published: June 2021

Chinese herbal medicine is widely cultivated in southwest China where the soil cadmium (Cd) contamination of farmland is more serious than that in the whole of China. In this study, Polygonatum sibiricum were exposed to Cd at the concentrations of e− 1, e0, e2, and e4 mg·kg− 1 for up to 30,60, and 90 days and their physiological stress responses, Cd and mineral element uptake, antioxidant enzyme activities, and content changes of pharmaceutical ingredients (polysaccharides) were analyzed to decipher the feasibility of safety use in Cd contaminated soil. Results showed that the activity of antioxidant enzymes (SOD, POD, and CAT) of the aboveground part was enhanced in response to Cd stress after 90 d. Compared with the control, the underground part mobilizes non-enzymatic systems to facilitate the synthesis of polysaccharides (PCP1, PCP2) with antioxidant properties to cope with Cd stress. Mineral elements (P, K, Ca, Mg, Fe, Cu, and Zn) were significantly changed after 90 d of cultivation. In particular, the changes in iron and zinc contents were significantly correlated with the activities of SOD and POD. The soil Cd safety thresholds value for Polygonatum sibiricum is e0 mg·kg− 1, under which concentration the stimulation of Cd promotes polysaccharides synthesis and biomass growth.
TNFR1 is Upregulated and Mediates Apoptosis in Cumulus Cells of Women With Polycystic Ovarian Syndrome
Authors: Jiang Yaping , Jiang Rui , Zhang Peng , Yu qiong , Ba Hongping , Jin Lei
Published: June 2021

Purpose

To investigate the changes of human granulosa cell, TNFR1, TNFR2 and their downstream molecules in patients with polycystic ovary syndrome (PCOS) and the control group.
Methods

We recruited infertile women with polycystic ovary syndrome (n = 30) and compared them with infertility due to fallopian tube obstruction(n = 30, control group). The ovaries were stimulated with GnRH agonists and gonadotropins. Follicular fluid from large follicles ([14 mm]) was pooled and granulosa cells (GCs) were separated by a cellular filter. The TNF-α level of follicular fluid was measured by ELISA. TUNEL assay were used to detect the apoptosis of purified GCs. Real-time PCR and Western blotting were used to detect the expression of TNF-related signaling molecules in GCs.
Results

The rate of high quality embryos in the PCOS group was lower than that in the control group. There were higher percentages of apoptosis in GCs of PCOS patients than in the control group. TNF-α is upregulated in follicular fluid of PCOS patients. TNFR1 and caspase-3 mRNA level were signifificantly higher in PCOS group than in the control group. TNF-α-mediated apoptosis of PCOS granulosa cells was mainly dependent on TNFR1.The TNF-α/TNFR1 signaling pathway mediates apoptosis rather than survival in cumulus cells of PCOS patients.
Conclusions

TNF-α expression was upregulated in follicular fluid of PCOS patients, and TNFR1 overexpression in female granulosa cells of PCOS was associated with higher levels of apoptosis in these cells, suggesting that the TNF-α/TNFR1 signaling pathway may be a candidate for higher apoptosis in female granulosa cells of PCOS.
Cytomegalovirus Retinitis in Patients of Non-Hodgkin’s Lymphoma: Clinical Presentations and Outcomes
Authors: Reddy Subhakar , Tyagi Mudit , Behera Shaswat , Pappuru Rajeev R , Dave Vivek P , Basu Soumyava , Agrawal Hitesh
Published: June 2021

BackgroundCytomegalovirus (CMV) retinitis in patients with Non-Hodgkin’s Lymphoma (NHL) can occur even in presence of high CD 4 counts and can behave differently when compared to CMV retinitis in human immunodeficiency (HIV) patients. It, therefore, becomes important to understand its varied presentations and challenges in the management of these cases. The aim of this study was to analyse the various patterns of presentations and outcomes of CMV Retinitis in patients with NHLStudy designA retrospective chart review of seven eyes of four patients of NHL presenting with CMV retinitis between June 2017 and May 2020 was done. MethodsClinical patterns of CMV Retinitis, the CD4 counts at the time of presentation and the duration of treatment along with recurrences and time for recurrence of retinitis were assessed.ResultsGranular or indolent retinitis (6 out of 7 eyes) was the commonest form of CMV retinitis in patients of NHL. Three patients had a presenting CD4 count above 150 cells/mm3 and none of them were below 50 cells/mm3. Floaters were the commonest presenting complaint. All patients had vitritis and majority of the patients (3 out of 4) had anterior chamber (AC) inflammation. Two out of the 4 patients had a recurrence (mean time 33.8 days) after stopping the maintenance phase of ganciclovir and one patient had significant myelosuppression related to oral valganciclovir which required discontinuation of the drug. ConclusionCMV retinitis in NHL patients is usually of an indolent or granular type and can occur even in the presence of high CD4 counts as compared to patients with HIV. These patients may require a long term maintenance in view of frequent recurrences after discontinuation of treatment
A Pilot Study on Home Range and Habitat Use of Chinese Goral (Naemorhedus Griseus): Exploring GPS Tracking Data in Cliff Landscape by Three Estimation Methods
Authors: teng yang , TANG Shupei , meng lai heda , Wu Liji , HAN Zhiqing , HAN Yingying , BAO Weidong
Published: June 2021

Home range size estimation is a crucial basis for developing effective conservation strategies and provides important insights into animal behavior and ecology. This study aimed at analyzing the home range variations, the influence of altitude in habitat selection, and comparing three methods in home range estimation of Chinese gorals (Naemorhedus griseus) living at a cliff landscape. The results indicated that there were significant differences between the annual home range sizes of individual animals but there was no difference in their seasonal home range sizes based on GPS tracking data of five female Chinese gorals from February 2015 to September 2018. The monthly home ranges decreased dramatically in May, June and July due to birth-giving. Notable seasonal variations were found in the micro-habitats of the Chinese gorals, as reflected by the altitude they inhabit, with higher altitude habitats used in spring and lower altitude habitats used in winter. Additionally, the altitude of monthly habitats was lowest in January, which may indicate an adaptation to low air temperature. We also found differences between estimation methods, namely minimum convex polygon (MCP), kernel density estimation (KDE) and α-local convex hull (α-LoCoH), with seasonal home range sizes derived from α-LoCoH being substantially smaller than those derived from MCP and KDE. In conclusion, our findings filled the gaps in home range study for this endangered species and contributed to effective conservation strategies. Considerations shall have to be given to the variations in home range estimation caused by different methods when dealing with rugged habitats, so as to make sure that any interpretation concerning the habitat use of the targeted species made on basis of such results would be meaningful and valid.
Explicating Sediment Sources of the Catchment Upstream of the Miyun Reservoir in Beijing, China
Authors: Fang Haiyan
Published: June 2021

As the only water drinking resource in Beijing, the Miyun Reservoir is still suffered over ten thousand tons of sediment input from its upper catchment. Explicating sediment sources of the catchment upstream of the reservoir is urgently required to further implement soil conservation measures. In this paper, the Revised Universal Soil Loss Equation (RUSLE) and Sediment Delivery (SEDD) models were combined to explicate the major sediment source of the catchment through exploring the spatial distributions of soil erosion and sediment delivery as well as their relations with land use and topography, and sediment source areas were then identified. The catchment average soil erosion intensity (SEI) of 4.08 t ha− 1 yr− 1 was two times the soil loss tolerance (T = 2.00 t ha− 1 yr− 1) of the study region. The values of cell sediment delivery ratio (SDR) showed a network distribution pattern, ranging from zero to unit, with an average of 1.65%. Cell specific sediment yield (SSY) presented a similar spatial pattern to SDR, ranging from 0 to 902 t ha− 1 yr− 1, with an average of 0.04 t ha− 1 yr− 1. Bare land suffered the highest SEI of 39.01 t ha− 1 yr− 1, followed by shrub land and orchard field. Nearly 70% of the sediment came from grass land. Farmland was the second sediment contributor. Grass land and farmland are the two major sediment source areas. Soil conservation practices should be further implemented on these lands, especially on the 3–5°slopes with elevations less than 500 m a.s.l.
Identification of the Ferroptosis-Related Long Non-Coding RNAs Signature to Improve the Prognosis Prediction in patients with NSCLC
Authors: Li Meng , Zhang Yanpeng , Fan Meng , Ren Hui , Chen Mingwei , Shi Puyu
Published: June 2021

Background: Non-small cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with an unfavorable prognosis. Ferroptosis, a novel iron-dependent programmed cell death, is involved in the development of multiple cancers. Of note, the prognostic value of ferroptosis-related lncRNAs in NSCLC remains uncertain. Methods: Gene expression profiles and clinical information of NSCLC were retrieved from the TCGA database. Ferroptosis-related genes (FRGs) were explored in the FerrDb database and ferroptosis-related lncRNAs (FRGs-lncRNAs) were identified by the correlation analysis and the LncTarD database. Next, The differentially expressed FRGs-lncRNAs were screened and FRGs-lncRNAs associated with the prognosis were explored by univariate Cox regression analysis and Kaplan-Meier survival analysis. Then, an FRGs-lncRNAs signature was constructed by the Lasso-penalized Cox model in the training cohort and verified by internal and external validation. Finally, the potential correlation between risk score, immune response, and chemotherapeutic sensitivity was further investigated.Results: 129 lncRNAs with a potential regulatory relationship with 59 differentially expressed FRGs were found in NSCLC and 10 FRGs-lncRNAs associated with the prognosis of NSCLC were identified (P<0.05). 9 prognostic-related FRGs-lncRNAs (AQP4-AS1, DANCR, LINC00460, LINC00892, LINC00996, MED4-AS1, SNHG7, UCA1, and WWC2-AS2) were used to construct the prognostic model and stratify patients with NSCLC into high- and low-risk groups. Kaplan-Meier analysis demonstrated a worse outcome in patients with high risk (P<0.05). Moreover, a good predictive capacity of this signature in predicting NSCLC prognosis was confirmed by the ROC curve analysis. Additionally, 45 immune checkpoint genes and 8 m6A-related genes were found differentially expressed in the two risk groups, and the sensitivity of 28 chemotherapeutics were identified to be correlated with the risk score. Conclusion: A novel FRGs-lncRNAs signature was successfully constructed, which may contribute to improving the management strategies of NSCLC.
A Perg Adaptation Paradigm for Detection of Retinal Ganglion Cell Dysfunction in Glaucoma Patients.
Authors: Salgarello Tommaso , Cozzupoli Grazia Maria , Giudiceandrea Andrea , Antonello Fadda , Placidi Giorgio , De Siena Elisa , Amore Filippo , Rizzo Stanislao , Falsini Benedetto
Published: June 2021

Purpose: It has been previously demonstrated that the adaptive phase changes of steady-state pattern electroretinogram (SS-PERG), recorded during 4-minute presentation of patterned stimuli, are reduced in glaucoma suspects and patients compared to normal subjects. Our study aims at testing the hypothesis that adaptive changes of SS-PERG, recorded using the novel optimized Next Generation PERG (PERGx) protocol, differ between glaucoma patients and controls.Methods: In this pilot cross-sectional study, we included 28 glaucoma patients and 17 age-matched normal subjects. Both patients and controls underwent a full ophthalmologic examination, visual field testing, OCT and PERGx. The PERGx signal was sampled over 2 minutes (providing 1 noise and 9 signal packets) in response to alternating gratings generated on an OLED display. PERGx amplitude and phase were analyzed to quantify adaptive changes over recording time. Receiver operating characteristic (ROC) curves were used to study the diagnostic accuracy of PERGx parameters in distinguishing glaucoma patients from normal subjects.Results: PERGx amplitude and phase data showed declining trends in both groups. PERGx amplitude slope and grand-average vector amplitude were significantly lower in patients compared to controls (p < 0.01). The area under the ROC curves of PERGx amplitude slope and grand-average vector amplitude were 0.87 and 0.76, respectively.Conclusion: The PERGx paradigm resulted highly accurate in detecting the reduction of amplitude adaptive changes in glaucoma patients, presumably due to the loss of functional RGC autoregulation. Thus, PERG adaptation, recorded by this new protocol, might be helpful in the identification and diagnosis of early glaucomatous dysfunction.
A Single-cell Interactome of Human Tooth Germ Elucidates Signaling Networks Regulating Dental Development
Authors: Shi Yueqi , Yu Yejia , Zhang Wenjie , Zou Duohong , Wang Jiajia , Zhou Yuqiong , Li Mengyu , Son Geehun , Song Weichen , Wang Shaoyi
Published: June 2021

Background: Development of dental tissue is regulated by extensive cell crosstalk based on various signaling molecules, such as BMP, FGF and SHH pathways. However, an intact network of the intercellular regulation is still lacking.Result: To gain an unbiased and comprehensive view of this dental cell interactome, we applied single-cell RNA-seq on immature human tooth germ of the third molar, discovered refined cell subtypes, and applied multiple network analysis to identify the central signaling pathways. We found that immune cells made up over 80% of all tooth germ cells, which exhibited profound regulation on dental cells via TGF-β, TNF and IL-1. During osteoblast differentiation, expression of genes related to extracellular matrix and mineralization was continuously elevated by signals from BMP and FGF family. As for the self-renewal of apical papilla stem cell, BMP-FGFR1-MSX1 pathway directly regulated the G0-to-S cell cycle transition. We also confirmed that CSF1 secreted from pericyte and TNFSF11 secreted from osteoblast regulated a large proportion of genes related to osteoclast transformation from macrophage and monocyte. Conclusion: We constructed the intercellular signaling networks that regulated the essential developmental process of human tooth, which served as a foundation for future dental regeneration engineering and the understanding of oral pathology.