bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTOR controls endoplasmic reticulum–Golgi apparatus trafficking of VSVg in specific cell types
Authors: Koscielny Alicja , Liszewska Ewa , Machnicka Katarzyna , Wezyk Michalina , Kotulska Katarzyna , Jaworski Jacek 
Published: May 2021

Abstract
Background
Mammalian/mechanistic target of rapamycin (mTOR) complexes are essential for cell proliferation, growth, differentiation, and survival. mTORC1 hyperactivation occurs in the tuberous sclerosis complex (TSC). mTORC1 localizes to the surface of lysosomes, where Rheb activates it. However, mTOR was also found on the endoplasmic reticulum (ER) and Golgi apparatus (GA). Recent studies showed that the same inputs regulate ER-to-GA cargo transport and mTORC1 (e.g., the level of amino acids or energy status of the cell). Nonetheless, it remains unknown whether mTOR contributes to the regulation of cargo passage through the secretory pathway.

Methods
The retention using selective hooks (RUSH) approach was used to image movement of model cargo (VSVg) between the ER and GA in various cell lines in which mTOR complexes were inhibited. We also investigated VSVg trafficking in TSC patient fibroblasts.

Results
We found that mTOR inhibition led to the overall enhancement of VSVg transport through the secretory pathway in PC12 cells and primary human fibroblasts. Also, in TSC1-deficient cells, VSVg transport was enhanced.

Conclusions
Altogether, these data indicate the involvement of mTOR in the regulation of ER-to-GA cargo transport and suggest that impairments in exocytosis may be an additional cellular process that is disturbed in TSC.
Soluble cytotoxic T-lymphocyte–associated antigen 4 (sCTLA-4) as a potential biomarker for diagnosis and evaluation of the prognosis in Glioma
Authors: Liu Jiajia , Tian Xiaoyi , Wang Yan , Kang Xixiong , Song Wenqi 
Published: May 2021

Abstract
Background
The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients.

Methods
In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4.

Results
Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor.

Conclusion
These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.
Predictive factors of viral load high-risk events for virological failure in HIV/AIDS patients receiving long-term antiviral therapy
Authors: Qin Shanfang , Lai Jingzhen , Zhang Hong , Wei Di , Lv Qing , Pan Xue , Huang Lihua , Lan Ke , Meng Zhihao , Liang Hao , Ning Chuanyi 
Published: May 2021

Abstract
Background
In the era of anti-retroviral therapy (ART), the plasma HIV viral load (VL) is an important primary indicator for monitoring the HIV treatment response. To optimize the clinical management of HIV/AIDS patients, we investigated VL high-risk events related to virological failure (VF) and further explored the preventive factors of VL high-risk events.

Methods
The data were derived from China’s HIV/AIDS Comprehensive Response Information Management System. HIV infected patients who initiated or received ART in Guangxi between 2003 and 2019 were included. The contributions of VL after 6 months of ART to VF and AIDS-related death were analysed by Kaplan-Meier curves, log-rank tests and Cox regression analyses. Both descriptive analyses and bivariate logistic regression were employed to further explore the preventive factors related to VL high-risk events of VF.

Results
The cumulative rates of VF in the high low-level viremia group (high LLV) (χ2 = 18.45; P <  0.001) and non-suppressed group (χ2 = 82.99; P <  0.001) were significantly higher than those in the viral suppression (VS) group. Therefore, the VL high-risk events of VF was defined as highest VL > 200 copies/ml after 6 months of ART. Compared with the VS group, the adjusted hazard risk was 7.221 (95% CI: 2.668; 19.547) in the high LLV group and 8.351 (95% CI: 4.253; 16.398) in the non-suppressed group. Compared with single patients, married or cohabiting (AOR = 0.591; 95% CI: 0.408, 0.856) and divorced or separated (AOR = 0.425, 95% CI: 0.207, 0.873) patients were negatively associated with VL high-risk events. So were patients acquired HIV homosexually (AOR = 0.572; 95% CI: 0.335, 0.978). However, patients who had ART modification were 1.728 times (95% CI: 1.093, 2.732) more likely to have VL high-risk events, and patients who used cotrimoxazole during ART were 1.843 times (95% CI: 1.271, 2.672) more likely to have VL high-risk events.

Conclusions
A VL greater than 200 copies/ml is a VL high-risk event for VF. Intervention measurements should be adopted to optimize the surveillance of ART in patients who are single or widowed, who have ART modification, and who use cotrimoxazole during ART.
Pregnancy outcomes in women with infertility and coexisting endometriosis and adenomyosis after laparoscopic surgery: a long-term retrospective follow-up study
Authors: Shi Jinghua , Dai Yi , Zhang Junji , Li Xiaoyan , Jia Shuangzheng , Leng Jinhua 
Published: May 2021

Abstract
Background
Adenomyosis (AM) and endometriosis (EM) often coexist. Laparoscopic surgery is one of the main methods for diagnosing and treating these conditions. This study aims to investigate the pregnancy outcomes of women with infertility with both AM and EM after laparoscopic surgery and to identify the relevant associated factors.

Methods
This is a retrospective study involving women with infertility diagnosed with EM and AM. All patients had undergone laparoscopic surgery and were divided into two groups according to their pregnancy outcomes. Demographic data, operation records, and pregnancy outcomes were collected.

Results
A total of 226 female patients with infertility diagnosed with both AM and EM underwent laparoscopic surgery. Of these, a total of 176 patients completed follow-up. Ninety-seven patients had live births, including 81 full-term and 16 preterm deliveries. The clinical pregnancy and live birth rates were 67.4 and 55.11%, respectively. One hundred thirty-five patients received in vitro fertilization (IVF), with 70 (51.85%) of these patients having live births. Age, endometrioma size, and uterus size were significantly lower in those who had a successful delivery. There was no statistically significant difference in symptoms, except that those who achieved live birth had a lower rate of anaemia (13.40% vs. 25.32%, p = 0.044). The group that did not proceed to have a live birth had a higher percentage of ovarian and peritoneal endometriosis (p < 0.05), while the distribution of deep infiltrating endometriosis and adenomyosis types were similar. Mean uterus diameter (OR: 0.636, 95% CI: 0.434–0.932, p = 0.020) and endometriosis fertility index (EFI) (OR: 1.299, 95% CI: 1.101–1.531, p = 0.002) were significantly correlated with live birth in the multivariable analysis.

Conclusions
Endometriosis and adenomyosis appear to have an adverse effect on pregnancy outcome. These might be related to the size of the uterus and EFI. Obstetricians and gynaecologists should be alert to this potential adverse effect and manage these patients accordingly.
Neonatal intrahepatic cholestasis caused by citrin deficiency with no hepatic steatosis: a case report
Authors: Miyamoto Ryosuke , Sada Jun , Ota Koki , Kaneko Kenitiro , Kusano Hironori , Azuma Yoshiteru , Okumura Akihisa 
Published: May 2021

Abstract
Background
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a common form of neonatal jaundice. Histopathological examination of the liver in patients with NICCD typically shows fatty liver, steatohepatitis, and liver fibrosis. Jaundice and fatty liver often improve by 1 year of age. We herein describe a girl who was diagnosed with NICCD based on an SLC25A13 mutation, although no fatty deposits were found on pathologic examination of the liver.

Case presentation
The patient in this case was a 3-month-old girl. At 2 months of age, she presented with jaundice, discolored stools, and poor weight gain and was found to have hyperbilirubinemia. Cholangiography revealed that she did not have biliary atresia. A laparoscopic liver biopsy was performed, and liver histopathology showed no fatty deposits. Genetic analysis revealed a compound heterozygous mutation in SLC25A13, and she was diagnosed with NICCD. She was given medium-chain triglyceride milk and gained weight. She resumed consumption of normal milk and breast milk, and her stool color improved. She was discharged at 4 months of age with adequate weight gain and a lower total bilirubin concentration. She was in good condition after discharge and showed normal development at the time of outpatient follow-up.

Conclusions
We experienced a case of NICCD in a patient without fatty liver. This case illustrates that the absence of hepatic steatosis in neonatal cholestasis does not rule out NICCD.
Rescue radiofrequency ablation or percutaneous ethanol injection: a strategy for failed RALPPS stage-1 in patients with cirrhosis-related hepatocellular carcinoma
Authors: Wang Qiang , Chen Shu , Yan Jun , Brismar Torkel , Sparrelid Ernesto , Qu Chengming , Ji Yujun , Chen Shihan , Ma Kuansheng 
Published: May 2021

Abstract
Background
The future liver remnant (FLR) faces a risk of poor growth in patients with cirrhosis-related hepatocellular carcinoma (HCC) after stage-1 radiofrequency-assisted ALPPS (RALPPS). The present study presents a strategy to trigger further FLR growth using supplementary radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI).

Methods
At RALPPS stage-1 the portal vein branch was ligated, followed by intraoperative RFA creating a coagulated avascular area between the FLR and the deportalized lobes. During the interstage period, patients not achieving sufficient liver size (≥ 40%) within 2–3 weeks underwent additional percutaneous RFA/PEI of the deportalized lobes (rescue RFA/PEI) in an attempt to further stimulate FLR growth.

Results
Seven patients underwent rescue RFA/PEI after RALPPS stage-1. In total five RFAs and eight PEIs were applied in these patients. The kinetic growth rate (KGR) was highest the first week after RALPPS stage-1 (10%, range − 1% to 15%), and then dropped to 1.5% (0–9%) in the second week (p < 0.05). With rescue RFA/PEI applied, KGR increased significantly to 4% (2–5%) compared with that before the rescue procedures (p < 0.05). Five patients proceeded to RALPPS stage-2. Two patients failed: In one patient the FLR remained at a constant level even after four rescue PEIs. The other patient developed metastasis. Except one patient died after RALPPS stage-2, no severe complications (Clavien-Dindo ≥ IIIb) occurred among remaining six patients.

Conclusions
Rescue RFA/PEI may provide an alternative to trigger further growth of the FLR in patients with cirrhosis-related HCC showing insufficient FLR after RALPPS stage-1.
Trial registration Retrospectively registered.
The role of mpMRI in qualification of patients with ISUP 1 prostate cancer on biopsy to radical prostatectomy
Authors: Nyk Łukasz , Tayara Omar , Ząbkowski Tomasz , Kryst Piotr , Andrychowicz Aneta , Malewski Wojciech 
Published: May 2021

AbstractBackgroundTo investigate the role of mpMRI and high PIRADS score as independent triggers in the qualification of patients with ISUP 1 prostate cancer on biopsy to radical prostatectomy.MethodsBetween January 2017 and June 2019, 494 laparoscopic radical prostatectomies were performed in our institution, including 203 patients (41.1%) with ISUP 1 cT1c-2c PCa on biopsy. Data regarding biopsy results, digital rectal examination, PSA, mpMRI and postoperative pathological report have been retrospectively analysed.ResultsIn 183 cases (90.1%) mpMRI has been performed at least 6 weeks after biopsy. Final pathology revealed ISUP Gleason Grade Group upgrade in 62.6% of cases. PIRADS 5, PIRADS 4 and PIRADS 3 were associated with Gleason Grade Group upgrade in 70.5%, 62.8%, 48.3% of patients on final pathology, respectively. Within PIRADS 5 group, the number of upgraded cases was statistically significant.ConclusionsPIRADS score correlates with an upgrade on final pathology and may justify shared decision of radical treatment in patients unwilling to repeated biopsies. However, the use of PIRADS 5 score as a sole indicator for prostatectomy may result in nonnegligible overtreatment rate.
Evaluation and pilot implementation of essential interventions for the management of hypertension and prevention of cardiovascular diseases in primary health care in the Republic of Tajikistan
Authors: Collins Dylan , Inglin Laura , Laatikainen Tiina , Shoismatuloeva Mekhri , Sultonova Dilorom , Jonova Bunafsha , Faromuzova Katoyon , Abdullaeva Marifat , Otambekova Maisara , Farrington Jill L. 
Published: May 2021

Abstract
Background
The aim of this study was to determine the feasibility of implementing and evaluating essential interventions for the management of hypertension and prevention of cardiovascular disease in primary healthcare in Tajikistan.

Methods
The study protocol was published a priori. A pragmatic, sequential, mixed methods explanatory design was piloted. The quantitative strand is reported here. All primary health care facilities that met inclusion criteria in Shahrinav district were included and computer randomized to either usual care or intervention. The intervention consisted of: adaptation of WHO PEN/HEARTS clinical algorithms for hypertension and diabetes, a two-day training of doctors and nurses, supportive supervision visits, clinical decision support tools, and quality improvement support. Data were collected from paper-based clinical records at baseline and 12 months follow-up. The primary outcome was blood pressure control among patients with hypertension, in addition to several secondary process indicators along the care pathway. Age and sex adjusted logistic regression models were used for intervention and control clinics to determine changes between baseline and follow-up and to assess interactions between allocation group and time. For continuous variables, multivariate linear regression models were used.

Results
19 primary health care centres were included of which ten were randomized to intervention and nine to control. 120 clinicians received training. The records of all registered hypertensive patients were reviewed at baseline and follow-up for a total of 1,085 patient records. Blood pressure control significantly improved in the intervention clinics (OR 3.556, 95 % CI 2.219, 5.696) but not the control clinics (OR 0.644, 95 % CI 0.370, 1.121) (p < 0.001 for interaction). Smoking assessment, statin prescribing, triple therapy prescribing, and blood pressure measurement significantly improved in intervention clinics relative to control, whereas cholesterol and glucose testing, and aspirin prescribing did not.

Conclusions
It is feasible to use routine, paper-based, clinical records to evaluate essential CVD interventions in primary health care in Tajikistan. Adapted WHO PEN/HEARTS guidelines in the context of a complex intervention significantly improved blood pressure control after 12 months.
The expression of the GATA6 gene in oral carcinoma cell lines
Authors: Xu Cheng-Lin , Guan Wei-Qun , Wang Xue-Ying 
Published: May 2021

Abstract
Background
This study aimed to investigate the expression level of the GATA6 gene in different oral cancer cells.

Methods
In this study, we sub-cultured normal oral epithelial cell lines HOK, human tongue squamous cell carcinoma cell lines CAL-27 and SCC-4, and human salivary gland adenoid cystic carcinoma cell lines SACC-LM and SACC-83. Subsequently, we used reverse transcription-polymerase chain reaction RT-PCR and Western blot methods to detect the mRNA and the protein expressions of GATA6 in normal oral epithelial cells, human tongue squamous cell carcinoma cells, and human salivary gland adenoid cystic carcinoma cells.

Results
The results of this study showed that the mRNA expression levels of GATA6 in CAL-27, SCC-4, and SACC-LM cells were significantly increased when compared with the HOK cells. However, the mRNA expression level of GATA6 in the SACC-83 cells had no significant difference compared with the HOK cells. The protein expression levels of GATA6 in the SCC-4 and SACC-LM cells were, however, significantly increased whereas the protein expression levels of GATA6 in the CAL-27 and SACC-83 cells had no significant difference when compared with the HOK cells.

Conclusion
The GATA6 gene may be related to the occurrence and progression of certain oral cancers.
Development of a triple antibody sandwich enzyme-linked immunosorbent assay for cassava mosaic disease detection using a monoclonal antibody to Sri Lankan cassava mosaic virus
Authors: Charoenvilaisiri Saengsoon , Seepiban Channarong , Kumpoosiri Mallika , Rukpratanporn Sombat , Warin Nuchnard , Phuangrat Bencharong , Chitchuea Phakamat , Siripaitoon Sirima , Chatchawankanphanich Orawan , Gajanandana Oraprapai 
Published: May 2021

Abstract
Background
Cassava mosaic disease (CMD) is one of the most devastating viral diseases for cassava production in Africa and Asia. Accurate yet affordable diagnostics are one of the fundamental tools supporting successful CMD management, especially in developing countries. This study aimed to develop an antibody-based immunoassay for the detection of Sri Lankan cassava mosaic virus (SLCMV), the only cassava mosaic begomovirus currently causing CMD outbreaks in Southeast Asia (SEA).

Methods
Monoclonal antibodies (MAbs) against the recombinant coat protein of SLCMV were generated using hybridoma technology. MAbs were characterized and used to develop a triple antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA) for SLCMV detection in cassava leaves and stems. Assay specificity, sensitivity and efficiency for SLCMV detection was investigated and compared to those of a commercial ELISA test kit and PCR, the gold standard.

Results
A TAS-ELISA for SLCMV detection was successfully developed using the newly established MAb 29B3 and an in-house polyclonal antibody (PAb) against begomoviruses, PAb PK. The assay was able to detect SLCMV in leaves, green bark from cassava stem tips, and young leaf sprouts from stem cuttings of SLCMV-infected cassava plants without cross-reactivity to those derived from healthy cassava controls. Sensitivity comparison using serial dilutions of SLCMV-infected cassava sap extracts revealed that the assay was 256-fold more sensitive than a commercial TAS-ELISA kit and 64-fold less sensitive than PCR using previously published SLCMV-specific primers. In terms of DNA content, our assay demonstrated a limit of detection of 2.21 to 4.08 × 106 virus copies as determined by quantitative real-time PCR (qPCR). When applied to field samples (n = 490), the TAS-ELISA showed high accuracy (99.6%), specificity (100%), and sensitivity (98.2%) relative to the results obtained by the reference PCR. SLCMV infecting chaya (Cnidoscolus aconitifolius) and coral plant (Jatropha multifida) was also reported for the first time in SEA.

Conclusions
Our findings suggest that the TAS-ELISA for SLCMV detection developed in this study can serve as an attractive tool for efficient, inexpensive and high-throughput detection of SLCMV and can be applied to CMD screening of cassava stem cuttings, large-scale surveillance, and screening for resistance.
The effect of SOX4 gene 3′UTR polymorphisms on osteoporosis
Authors: Li Guo , Gu Zuchao , He Yue , Wang Chongwen , Duan JiQiang 
Published: May 2021

Abstract
Objective
This study aimed to explore the correlation between the SRY-related high-mobility-group box gene 4 (SOX4) 3′ untranslated region (UTR) single nucleotide polymorphism (SNP) and osteoporosis susceptibility.

Methods
The study recruited 330 osteoporosis patients (the case group) and 330 non-osteoporosis patients (the control group) in Sichuan Chengdu First People’s Hospital and Zibo Central Hospital from August 2016 to August 2019. Sanger sequencing was used to analyze the genotypes of SOX4 gene rs79958549, rs139085828, and rs201335371 loci. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction between the SOX4 gene rs79958549, rs139085828, and rs201335371 loci and the clinical characteristics of the subjects.

Results
The risk of osteoporosis in the carriers of A allele at SOX4 rs79958549 was 5.40 times that in the carriers of the G allele (95% CI 3.25–8.96, P < 0.01). The risk of osteoporosis in the carriers of the A allele at SOX4 rs139085828 was 1.68 times that in the carriers of the G allele (95% CI 1.45–1.85, P < 0.01). The risk of osteoporosis in the carriers of the T allele at SOX4 rs201335371 was 0.54 times that in the carriers of the C allele (95% CI 0.43–0.69, P < 0.01). The SOX4 gene rs79958549, rs139085828, and rs201335371 A-A-C haplotype (OR = 5.14, 95% CI 2.45–10.57, P < 0.01) were associated with increased risk of osteoporosis and G-G-T haplotype was significantly associated with decreased risk of osteoporosis (OR = 0.48, 95% CI 0.38–0.62, P < 0.01). The interaction among the factors of sex, smoking, drinking, rs79958549, rs201335371 was the best model for osteoporosis prediction, and the risk for osteoporosis in ‘high-risk combination’ was 2.74 times that of ‘low-risk combination’ (95% CI 1.01–7.43, P = 0.04). Multiple logistic regression analysis revealed that the risk factors for osteoporosis were BMD (OR = 5.85, 95% CI 2.88–8.94, P < 0.01), T score (OR = 8.54, 95% CI 5.66–10.49, P < 0.01), Z score (OR = 3.77, 95% CI 2.15–8.50, P < 0.01), rs79958549 SNP (OR = 6.92, 95% CI 3.58–8.93, P < 0.01), and rs139085828 SNP (OR = 2.36, 95% CI 1.85–4.27, P < 0.01). The protective factor for osteoporosis was rs201335371SNP (OR = 0.48, 95% CI 0.32–0.75, P < 0.01).

Conclusion
The SOX4 gene SNPs rs79958549, rs139085828, and rs201335371 loci were significantly associated with osteoporosis risk.