bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel circ_0018289/miR-183-5p/TMED5 regulatory network in cervical cancer development
Authors: Zou Heng , Chen Huijia , Liu Shuaibin , Gan Xiaoling 
Published: August 2021

Abstract
Background
Circular RNAs (circRNAs) are increasingly implicated in regulating human carcinogenesis. Previous work showed the oncogenic activity of circ_0018289 in cervical cancer. However, the molecular basis underlying the modulation of circ_0018289 in cervical carcinogenesis is still not fully understood.

Methods
The levels of circ_0018289, microRNA (miR)-183-5p, and transmembrane p24 trafficking protein 5 (TMED5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Ribonuclease (RNase) R and subcellular localization assays were used to characterize circ_0018289. Cell proliferation was detected by the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (Edu) assays. Cell apoptosis and tube formation were assessed by flow cytometry and tube formation assays, respectively. A dual-luciferase reporter assay was performed to confirm the direct relationship between miR-183-5p and circ_0018289 or TMED5. The role of circ_0018289 in tumor growth was gauged by mouse xenograft experiments.

Results
Circ_0018289 was overexpressed in cervical cancer tissues and cells. Circ_0018289 silencing impeded cell proliferation, enhanced cell apoptosis, and suppressed angiogenesis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0018289 targeted and regulated miR-183-5p by binding to miR-183-5p, and circ_0018289 regulated cervical cancer development and angiogenesis partially through miR-183-5p. Moreover, TMED5 was directly targeted and inhibited by miR-183-5p through the perfect complementary sites in TMED5 3′UTR, and TMED5 knockdown phenocopied miR-183-5p overexpression in suppressing cervical cancer development and angiogenesis. Furthermore, circ_0018289 induced TMED5 expression by competitively binding to shared miR-183-5p.

Conclusion
Our observations identified the circ_0018289/miR-183-5p/TMED5 regulatory network as a novel molecular basis underlying the modulation of cervical carcinogenesis.
Gastric cancer with positive peritoneal cytology: survival benefit after induction chemotherapy and conversion to negative peritoneal cytology
Authors: Valletti Massimiliano , Eshmuminov Dilmurodjon , Gnecco Nicola , Gutschow Christian Alexander , Schneider Paul Magnus , Lehmann Kuno 
Published: August 2021

Abstract
Background
The optimal treatment in patients with gastric cancer and peritoneal disease remains controversial. Some guidelines indicate palliative treatment only, while others consider surgical treatment in case of positive lavage cytology (CY+) or limited peritoneal disease. Here, we analyzed the role of peritoneal disease in patients with gastric cancer, and the prognostic relevance of response to neoadjuvant therapy.

Methods
In this retrospective cohort analysis, we analyzed patients with adenocarcinoma of the stomach or esophago-gastric junction from a single center operated between 2011 and 2019. According to histology and lavage cytology, patients were classified into four risk groups: (A) no peritoneal disease, (B) CY+ who converted to negative lavage cytology (CY−) after neoadjuvant chemotherapy, (C) CY+ without conversion after chemotherapy, and (D) patients with visible peritoneal metastasis.

Results
Overall, n = 172 patients were included. At initial presentation, n = 125 (73%) had no peritoneal disease, and about a third of patients (n = 47, 27%) had microscopic or macroscopic peritoneal disease. Among them, n = 14 (8%) were CY+ without visible peritoneal metastasis, n = 9 converted to CY− after chemotherapy, and in n = 5 no conversion was observed. Median overall survival was not reached in patients who had initially no peritoneal disease and in patients who converted after chemotherapy, resulting in 3-year survival rates of 65% and 53%. In contrast, median overall survival was reduced to 13 months (95% CI 8.7–16.7) in patients without conversion and was 16 months (95% CI 12–20.5) in patients with peritoneal metastasis without difference between the two groups (p = .364). The conversion rate from CY+ to CY− was significantly higher after neoadjuvant treatment with FLOT (5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel) compared to ECF (epirubicin, cisplatin, and 5-fluorouracil) (p = 0.027).

Conclusion
Conversion of CY+ to CY− after neoadjuvant chemotherapy with FLOT is a significant prognostic factor for a better overall survival. Surgical treatment in well-selected patients should therefore be considered. However, peritoneal recurrence remains frequent despite conversion, urging for a better local control.
Maternal and infant outcomes during the COVID-19 pandemic: a retrospective study in Guangzhou, China
Authors: Wang Jingyun , Wang Yun , He Mei-yao , Li Yi-xiao , Cheng Xin , Yang Xuesong , Li Rui-man , Wang Guang 
Published: August 2021

AbstractIn late December 2019, the COVID-19 pandemic caused a great threat to people’s lives worldwide. As a special category of the population, pregnant women are vulnerable during emergencies. This study was designed to explore whether or not the COVID-19 pandemic has influenced maternal and infant outcomes. We collected maternal characteristics, laboratory results, condition in the third trimester, maternal outcome, fetal or neonatal outcomes, and characteristics of amniotic fluid, umbilical cord and placenta from pregnant women and fetals or newborns in the first affiliated hospital of Jinan university from 24 January to 31 March 2020 (peak period), chose the same types of data at the hospital during the same period in 2019 and 1 January—23 January 2020 (prior to the outbreak of COVID-19 in 2020) as a control. Our study focused on uncomplicated singleton pregnancies among women not infected by COVID-19. The results demonstrated that there was not an increase in adverse outcomes of pregnant women and newborns during the COVID-19 pandemic; This might be associated with the updated design of major epidemic prevention and control systems in Guangzhou, and the extension of pregnant women’s rest time during the third trimester of pregnancy. Nevertheless, the survey showed an increased incidence rate of 25-hydroxyvitamin D and zinc deficiency in newborns during the epidemic, implying that pregnant women should participate in appropriate physical exercise, increase their exposure to outdoor sunlight and improve nutrition intake to ensure healthy newborns during the quarantine period. Our study has provided some guidance for maternal management during the COVID-19 pandemic.
Retention of visa-trainee post-graduate residents in Canada: a retrospective cohort study
Authors: Mathews Maria , Koudieh Dania , Yi Yanqing , Hedden Lindsay , Marshall Emily Gard , Samarasena Asoka , Barnum Geoff , Bourgeault Ivy 
Published: August 2021

Abstract
Background
Visa trainees (international medical graduates [IMG] who train in Canada under a student or employment visa) are expected to return home after completing their training. We examine the retention patterns of visa trainee residents funded by Canadian (regular ministry and other), foreign, or mixed sources.

Methods
We linked data from the Canadian Post-MD Medical Education Registry with Scott’s Medical Database for a retrospective cohort study. Eligible trainees were IMG visa trainees as of their first year of training, started their residency program no earlier than 2000, and exited training between 2006 and 2016. We used Cox regression to compare the retention of visa trainees by funding source.

Results
Of 1,913 visa trainees, 431(22.5%), 1353 (70.7%) and 129 (6.8%) had Canadian, foreign, or mixed funding, respectively. The proportion of trainees remaining in Canada decreased over time, with 35.5% (679/1913); 17.7% (186/1052); 10.8% (11/102) in Canada one, five, and ten years, respectively after their exit from PGME training. Trainees who remained on visas (HR: 1.91; [95% CI 1.59, 2.30]), were funded exclusively by foreign sources (HR: 1.46; [95% CI 1.25, 1.69]), and who had graduated from ‘Western’ countries (HR: 1.39; [95% CI 1.06, 1.84]) were more likely to leave Canada compared to trainees who became citizens/permanent residents, were funded by Canadian sources, or were visa graduates of Canadian medical schools, respectively.

Conclusions
Most visa trainees leave Canada following their training. Trainees with Canadian connections (funding and/or change in legal status) were more likely to remain in Canada.
Different modulation effects of 1 Hz and 20 Hz transcutaneous auricular vagus nerve stimulation on the functional connectivity of the periaqueductal gray in patients with migraine
Authors: Cao Jin , Zhang Yue , Li Hui , Yan Zhaoxian , Liu Xian , Hou Xiaoyan , Chen Weicui , Hodges Sierra , Kong Jian , Liu Bo 
Published: August 2021

Abstract
Background
A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. Frequency is one of the key stimulation parameters. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine.

Methods
Twenty-four episodic migraineurs without aura (21 females) were recruited for the single-blind, crossover, functional magnetic resonance imaging (fMRI) study. Each participant attended two separate fMRI scan sessions, one for 1 Hz and another for 20 Hz taVNS, in a random order. Seed-based functional connectivity analysis was applied using the ventrolateral periaqueductal gray (PAG) as the region of interest.

Results
Compared with the pre-taVNS resting state, continuous 1 Hz taVNS (during) produced a significant increase in functional connectivity between the PAG and the bilateral middle cingulate cortex (MCC), right precuneus, left middle frontal gyrus (MFG), and left cuneus. Compared with 20 Hz taVNS, 1 Hz taVNS produced greater PAG connectivity increases with the MCC, right precuneus/posterior cingulate cortex, left insula, and anterior cingulate cortex (ACC). A significant negative correlation was observed between the number of migraine attacks in the previous 4 weeks and the PAG-MCC functional connectivity in the pre-taVNS resting-state before 1 Hz taVNS.

Conclusions
Our findings suggest that taVNS with different frequencies may produce different modulation effects on the descending pain modulation system, demonstrating the important role of stimulation frequency in taVNS treatment.
Urinary small extracellular vesicles derived CCL21 mRNA as biomarker linked with pathogenesis for diabetic nephropathy
Authors: Feng Ye , Zhong Xin , Ni Hai-Feng , Wang Cui , Tang Tao-Tao , Wang Li-Ting , Song Kai-Yun , Tang Ri-Ning , Liu Hong , Liu Bi-Cheng , Lv Lin-Li 
Published: August 2021

Abstract
Background
Diabetic nephropathy (DN) is a leading cause of renal failure, whereas the effective and early diagnostic biomarkers are still lacking.

Methods
Fourteen cytokines and chemokines mRNA were detected in urinary extracellular vesicles (EVs) from the screening cohort including 4 healthy controls (HC), 4 diabetes mellitus (DM) and 4 biopsy-proven DN patients, and was validated in another 16 HC and 15 DM and 28 DN patients. Correlation analysis was performed between the candidate biomarkers and clinic parameters as well as kidney histological changes. The findings were also confirmed in DN rat model with single injection of STZ.

Results
The number of small EVs secreted in urine was increased in DN patients compared to DM patients and healthy controls, with expression of AQP1 (a marker of proximal tubules) and AQP2 (a marker of distal/collecting tubules). Small EVs derived CCL21 mRNA increased significantly in DN patients and correlated with level of proteinuria and eGFR. Interestingly, elevated CCL21 mRNA from urine small EVs was observed in DN patients with normal renal function and could discriminate early DN patients from DM more efficiently compared to eGFR and proteinuria. CCL21 also showed an accurate diagnostic ability in distinguishing incipient from overt DN. Histologically, CCL21 mRNA expression increased progressively with the deterioration of tubulointerstitial inflammation and showed the highest level in nodular sclerosis group (class III) in DN patients. Remarkable infiltration of CD3 positive T cells including both CD4 and CD8 positive T cell population were observed in DN patients with high-CCL21 expression. Besides, accumulation of CD3 positive T cells correlated with level of urinary small EVs derived CCL21 and co-localized with CCL21 in the tubulointerstitium in DN patients. Finally, the correlation of CCL21 expression in renal cortex and urinary small EVs was confirmed in STZ-induced DN rat model.

Conclusions
Urinary small EVs derived CCL21 mRNA may serve as early biomarker for identifying DN linked with pathogenesis. CCL21 mRNA mediated T cell infiltration may constitute the key mechanism of chronic inflammation in DN.
Comparison of minimally invasive percutaneous fixation and open reduction internal fixation for patella fractures: a meta-analysis
Authors: Lo Chun-Hong , Chen Chih-Hwa 
Published: August 2021

Abstract
Background
Open reduction internal fixation (ORIF) has long been the conventional procedure for managing displaced patella fracture. This surgical approach has certain drawbacks, which might affect clinical outcomes and patient prognosis. Minimally invasive percutaneous fixation (MIPF) was proposed to overcome these disadvantages. Few in-depth investigations have been performed to determine the superiority of MIPF over ORIF. The aim of this study was to compare the efficacies of MIPF and ORIF for patella fractures.

Methods
The PubMed, Cochrane Library, Embase, and Scopus databases were searched for relevant studies from November 26 to December 17, 2020. Non-English publications and pediatric orthopedic articles were excluded. Statistical analysis was performed using Review Manager, version 5.4, with mean differences (MDs), standardized mean differences (SMDs), odds ratios (ORs), and respective 95% confidence intervals (CIs) calculated using a random effects model. The primary outcomes were the pain score, knee range of motion, and joint functionality. The secondary outcomes were the surgical time, complications, and implant removal rate.

Results
Six articles with a total of 304 patients were included in the meta-analysis. Pooled analysis revealed that patients with MIPF had a significantly reduced pain score (MD = − 1.30, 95% CI = − 1.77 to −0.82; p < 0.00001) and increased knee extension angles (MD = 0.72, 95% CI = 0.18 to 1.25; p = 0.009) at 3-month follow-up. Furthermore, knee flexion angles (MD = 8.96, 95% CI = 5.81 to 12.1; p < 0.00001) and joint functionality (SMD = 0.54, 95% CI = 0.21 to 0.86; p = 0.001) had statistically improved at 2 years. However, no difference was observed between MIPF and ORIF with regard to the surgical time. The risk of complications (OR = 0.10, 95% CI = 0.05 to 0.18; p < 0.00001) and implant removal rate (OR = 0.20, 95% CI = 0.07 to 0.57; p = 0.003) were significantly lower with MIPF than with ORIF.

Conclusions
MIPF is more favorable than ORIF in terms of the pain score, knee range of motion, joint functionality, complications, and implant removal rate. Thus, it can be adopted as an alternative to ORIF.
Clinicopathological and prognostic features of hepatitis B virus-associated diffuse large B-cell lymphoma: a single-center retrospective study in China
Authors: Chen Dao-guang , Chen Gang , Wang Chang , Ke Long-feng , Wu Hui , He Hong-ming , Yang Yu , Chen Yan-ping 
Published: August 2021

Abstract
Background
While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known about the pathological characteristics and outcome of DLBCL arising in patients with HBV infection.

Methods
We retrospectively studied a cohort of 420 patients with DLBCL for the incidence of HBV infection, and the clinicopathologic features and prognostic factors in HBsAg-positive DLBCL patients in China, a hepatitis B endemic area.

Results
In our study, 127 (30.2%) patients were HBsAg-positive. HBsAg-positive DLBCL displayed a younger median onset age (50 vs. 54 years, P = 0.002), more frequent involvement of the spleen (19.7% vs. 6.1%, P < 0.001), less frequent involvement of the small and large intestine (2.3% vs. 11.2%, P = 0.003), more advanced disease (stage III/IV: 56.7% vs. 45.1%, P = 0.028), and lower expression rate of MYC (49.1% vs. 66.7%, P = 0.026). The median follow-up time was 61.9 months. Univariate analysis showed that there was no significant difference in overall survival (OS) between HBsAg-negative and -positive DLBCL (P = 0.577). In the HBsAg-positive DLBCL subgroup, age older than 60 years, advanced disease, elevated lactate dehydrogenase (LDH), spleen involvement, B symptoms (fever, night sweats, weight loss), and double expressers of MYC and BCL2 had a significantly worse outcome, and patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) had a better prognosis. Multivariate analysis further confirmed that spleen involvement and rituximab use were independent prognostic factors in HBsAg-positive DLBCL patients.

Conclusions
Our study indicates that HBsAg-positive DLBCL has unique clinicopathological features and independent prognostic factors. Moreover, under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients, and the use of rituximab significantly improved OS in HBsAg-positive DLBCL patients.
Complement inhibitor CSMD1 modulates epidermal growth factor receptor oncogenic signaling and sensitizes breast cancer cells to chemotherapy
Authors: Gialeli Chrysostomi , Tuysuz Emre Can , Staaf Johan , Guleed Safia , Paciorek Veronika , Mörgelin Matthias , Papadakos Konstantinos S. , Blom Anna M. 
Published: August 2021

Abstract
Background
Human CUB and Sushi multiple domains 1 (CSMD1) is a large membrane-bound tumor suppressor in breast cancer. The current study aimed to elucidate the molecular mechanism underlying the effect of CSMD1 in highly invasive triple negative breast cancer (TNBC).

Methods
We examined the antitumor action of CSMD1 in three TNBC cell lines overexpressing CSMD1, MDA-MB-231, BT-20 and MDA-MB-486, in vitro using scanning electron microscopy, proteome array, qRT-PCR, immunoblotting, proximity ligation assay, ELISA, co-immunoprecipitation, immunofluorescence, tumorsphere formation assays and flow cytometric analysis. The mRNA expression pattern and clinical relevance of CSMD1 were evaluated in 3520 breast cancers from a modern population-based cohort.

Results
CSMD1-expressing cells had distinct morphology, with reduced deposition of extracellular matrix components. We found altered expression of several cancer-related molecules, as well as diminished expression of signaling receptors including Epidermal Growth Factor Receptor (EGFR), in CSMD1-expressing cells compared to control cells. A direct interaction of CSMD1 and EGFR was identified, with the EGF-EGFR induced signaling cascade impeded in the presence of CSMD1. Accordingly, we detected increased ubiquitination levels of EGFR upon activation in CSMD1-expressing cells, as well as increased degradation kinetics and chemosensitivity. Accordingly, CSMD1 expression rendered tumorspheres pretreated with gefitinib more sensitive to chemotherapy. In addition, higher mRNA levels of CSMD1 tend to be associated with better outcome of triple negative breast cancer patients treated with chemotherapy.

Conclusions
Our results indicate that CSMD1 cross-talks with the EGFR endosomal trafficking cascade in a way that renders highly invasive breast cancer cells sensitive to chemotherapy. Our study unravels one possible underlying molecular mechanism of CSMD1 tumor suppressor function and may provide novel avenues for design of better treatment.
Clinical significance for combined coagulation indexes in epithelial ovarian cancer prognosis
Authors: Yang Jiani , Jin Yue , Cheng Shanshan , Wang Chao , Zhang Nan , Huang Shan , Zhao Yaqian , Wang Yu 
Published: August 2021

AbstractBackgroundIncreasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC).MethodsA retrospective study was conducted on patients who underwent optimal tumor debulking followed by platinum-based chemotherapy at our institution. The predictive value of coagulation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for recurrence-free survival (RFS) and overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis.ResultsWe involved 482 EOC patients and followed up for 64 (range, 36–87) months. According to ROC curves, D-dimer and International normalized ratio (INR) had superior predictive value than other coagulation indexes, with area under curve (AUC) of 0.758 and 0.742. Patients were then stratified into three combined D-dimer and INR (DD-INR) groups based on the cut-off value of 0.97 mg/L and 0.86, respectively. Through regression analysis, we demonstrated that age (HR 1.273; 95%CI 1.048–2.047;p = 0.045), pathological grade (HR 1.419; 95% CI 1.102–2.491;p = 0.032), clinical stage (HR 2.038; 95%CI 1.284–3.768;p = 0.008), CA-125 (HR 1.426; 95%CI 1.103–1.894;p = 0.038) and DD-INR (HR 2.412; 95%CI 1.683–3.241;p = 0.009) were independent prognostic factors. Survival analysis showed that patients with higher DD-INR experienced poor survival (p = 0.0013 for RFS andp = 0.0068 for OS). Further subgroup analysis revealed that evaluated DD-INR was significantly associated with poor survival among patients with advanced stage (p = 0.0028 for RFS andp = 0.0180 for OS).ConclusionOur findings suggested that coagulation indexes, especially the combined DD-INR were promising biomarkers for prognosis stratification in EOC patients, especially those with advanced clinical stages.
Chlorhexidine–alcohol versus povidone–iodine as preoperative skin antisepsis for prevention of surgical site infection in cesarean delivery—a pilot randomized control trial
Authors: Luwang Athokpam Lenin , Saha Pradip Kumar , Rohilla Minakshi , Sikka Pooja , Saha Lekha , Gautam Vikas 
Published: August 2021

Abstract
Objectives
To compare the efficacy of chlorhexidine–alcohol and povidone–iodine as preoperative antiseptic skin preparation for prevention of surgical site infection (SSI) after cesarean delivery (CD).

Materials and methods
A total of 311 eligible women who underwent CS were recruited in the study after fulfilling all the eligibility and exclusion criteria. Patients were randomized into two groups (153 in chlorhexidine–alcohol group and 158 in povidone–iodine group) by a computer-generated randomization table. Patients were followed for a period of 30 days in postoperative period to monitor for SSI.

Results
The rate of SSI in the chlorhexidine–alcohol group is 5.4% and that of the povidone–iodine group is 8.6%. E. coli, K. pneumoniae, and Acinetobacter baumannii were the most common organisms isolated. E. coli was found in 9.5% of the total SSI cases.

Conclusions
The study found that the patients who received chlorhexidine–alcohol as skin antiseptic had less chance of developing SSI than those who received povidone–iodine; however, it did not reach a statistical significance.

Trial registration
Clinical Trials Registry of India CTRI/2018/05/014294. Registered on May 31, 2018