bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microsecond Pulse Electrical Stimulation Inhibit the Proliferation of Cervical Cancer Cells through the Ras-Raf-MAPK Pathway
Authors: Xu Xiaoyue , Wang Shiyan , Cao Tingting , Xie Bing , Sun Xiuli , Wang Jianliu 
Published: December 2020

Abstract
Objective: Using microsecond pulsed electrical stimulation (μsPES) applied to treat pelvic floor dysfunctions(PFDs) to stimulate the cervical cancer cells. To explore the effects and mechanisms of different μsPES on the proliferation of cervical cancer cells. Methods: Scheme #1 (1/4/1 Hz, 270/230/270 μs, 30min), scheme #2 (30 Hz, 500 μs, 20min), and scheme #3 (50 Hz, 250 μs, 20min) were selected from a pelvic floor rehabilitation therapy instrument. Three μsPES-based schemes each at 20, 40, 60, 80, and 100 mA current values were used to stimulate SiHa cells and HeLa cells. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Scheme #2 at 100 mA current was employed to stimulate SiHa cells and HeLa cells and then western blotting was applied to detect the expressions of the Ras-Raf-MAPK pathway. Results: Current with higer frequency and current intensity tended to have a more proliferation inhibition on cervical cancer cells. μsPES had a stronger proliferation inhibition in SiHa cells than HeLa cells. The expressions of MAPK, MEK1/2 and p-MEK1/2, Raf and p-Raf, Ras protein were significantly decreased in SiHa cells and HeLa cells compared with the control. The p-MAPK was up-regulated in HeLa cells while down-regulated in SiHa cells. Conclusions: μsPES could inhibit the proliferation of cervical cancer cells by suppressing the Ras-Raf-MAPK pathway. The μsPES applied for functional rehabilitation of pelvic floor nerves and muscles is safe for cervical cancer patients at the cellular level
KLF5 Inhibition Overcomes Oxaliplatin Resistance In Patient-Derived Colorectal Cancer Organoids by Restoring Apoptotic Response
Authors: Shen Xiaohui , Gao Han , Zhang Yuchen , Xu Zhuoqing , Feng Wenqing , Li Wenchang , Miao Yiming , Xu Zifeng , Zong Yaping , Zhao Jingkun , Lu Aiguo 
Published: December 2020

Abstract
Background: Oxaliplatin resistance is a major challenge for treatment of metastatic colorectal cancer (mCRC). Many molecular targeted drugs for refractory CRC have been developed to solve colorectal cancer drug resistance, but their effectiveness and roles in the progression of CRC and oxaliplatin- resistance still not clear.Methods: PDOs derived from CRC patients were constructed to conduct the sensitivity assays of oxaliplatin in vitro. Oxaliplatin resistant PDOs were selected and treated under the combined treatment of ML264(a KLF5 inhibitor) and oxaliplatin to determine the effects of KLF5 inhibition on apoptosis. Using CRC cell lines to investigate downstream mechanisms and xenograft models to confirm whether ML264 can restore oxaliplatin sensitivity of CRC cells in vivo.Results: We successfully constructed CRC PDOs and conducted the sensitivity test of oxaliplatin in PDOs from different patients. We found that ML264 restores oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response, and this effect was achieved by inhibiting the KLF5/Bcl-2/caspase3 signal pathway. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay verified that KLF5 promoted the transcription of Bcl-2 in CRC cells. KLF5 inhibition also overcomed oxaliplatin resistance in xenograft tumors.Conclusions: Our study demonstrated that ML264 can restores oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response. KLF5 might be a potential therapeutic target for CRC resistant to oxaliplatin. PDOs have strong potential in evaluating inhibitors and drug combinations therapy in a preclinical environment.
The Ideal Approach for Treatment of cT1N+ and cT2Nany Esophageal Cancer.: A NCDB Analysis
Authors: Huang Binhao , Chan Ernest G. , Pennathur Arjun , Luketich James D. , Zhang Jie 
Published: December 2020

Abstract
BackgroundNeoadjuvant therapy followed by surgery is recommended for locally advanced esophageal cancer. With the inaccuracies of clinical staging particularly for cT1N+ and cT2Nany tumors, some have proposed consideration of surgery followed by adjuvant treatment. Our objective is to evaluate the efficacy of neoadjuvant therapy vs surgery followed by adjuvant therapy, and to identify the ideal sequence of treatment in patients with cT1N+ and cT2Nany tumors.MethodsWe performed an analysis utilizing the National Cancer Database (2006-2015) identifying all patients with cT1N+ and cT2Nany esophageal cancer undergoing esophagectomy and additional chemotherapy or radiotherapy. The treatment was stratified as: neoadjuvant therapy (NT), adjuvant therapy (AT) and combination therapy of neoadjuvant and adjuvant (CT) groups and outcomes were analyzed.ResultsWe identified 2795 patients with 81.9% (n=2289) receiving NT, 10.2% (n=285) AT, and 7.9% (n=221) CT. There were no significant differences noted in survival among AT, NT, and CT group in cT1N+(P=0.376), cT2N-(P=0.436), cT2N+(P=0.261) esophageal cancer by multivariate analysis using Cox regression model. This relationship held true in both squamous cell carcinoma and adenocarcinoma. ConclusionIn clinical T1N+, T2Nany patients, there was no evident superiority of NT over AT. Surgery followed by adjuvant therapy can be considered to be an alternative option in these patients. Further prospective studies are needed to validate these findings.
Baseline Malaria Prevalence at the Targeted Pre-elimination Districts in Ethiopia
Authors: Nega Desalegn , Abera Adugna , Gidey Bokretsion , Mekasha Sindew , Abebe Abnet , Dillu Dereje , Mehari Degu , Assefa Gudissa , Hailu Samuel , Haile Mebrahatom , Etana Kebede , Solomon Hiwot , Tesfaye Gezahagn , Nigatu Daniel , Destaw Zelalem , Tesfaye Berhane , Serda Belendia , Yeshiwondim Asnakew , Yeshiwondim Assefaw , Teka Hiwot , Nahusenay Honelegn , Abdulmenan Semira , Reda Hailemariam , Bekele Worku , Zewdie Ayele , Tollera Getachew , Assefa Ashenafi , Tasew Geremew , Woyessa Adugna , Abate Ebba 
Published: December 2020

Abstract
Background: Encouraged by the success in malaria control and prevention strategies, several malaria endemic countries have adopted elimination strategies worldwide. Accordingly, Ethiopian ministry of health launched malaria elimination with a stepwise approach by primarily targeting the low-transmission districts and their adjacent areas/zones in order to shrink the country’s malaria map progressively. Hence, this community survey was conducted to establish baseline malaria information at the preliminary phase of elimination for measuring future intervention success in elimination goal. Methods: Community based cross-sectional survey was conducted at twenty malaria elimination targeted districts selected from five regional states and one city administration in Ethiopia. The GPS enabled smart phones programmed with Open Data Kit were used to enumerate 9326 study households and collect data from 29,993 residents. Care Start™ Malaria HRP-2/PLDH Rapid Diagnostic Tests (RDTs) were used for blood testing at field level. Armpit digital thermometers were used to measure axillary temperature.Result: Overall malaria prevalence by RDTs was 1.17% (339/28973). The prevalence at district levels ranged from 0.0% to 4.7%. The total prevalence of febrile cases (axillary temperature >37.5oc) in the survey was 9.2% (2760/29993). Among the 2,510 febrile individuals tested with RDTs, only 3.35% (84/2510) were malaria positive. Among all study participants, 0.88% (255/28973) malaria positives were afebrile and 0.29% (84/28973) were febrile individuals. The 75.2% (255/339) of all malaria positives were afebrile. Of the total afebrile malaria cases, 10.2% (26/255) were under-five children and 89.8% (229/255) were above 5 years of age. Conclusion: The 1.17% malaria prevalence that ranges 0 to 4% in some districts by rapid diagnostic tests should be given due consideration by the elimination program. Especially the higher prevalence of afebrile individuals (0.88%) in these transmission settings indicates there may be sustaining hidden transmission. Therefore, active case detection with more sensitive diagnostic techniques than this conventional method is suggested to know more real magnitude of residual malaria in the elimination targeted low transmission areas and break the chain of transmission.
ITGA3 Is a Reliable Biomarker and Putative Therapeutic Target for Glioma
Authors: Zhang Qing , Zhu Chen , Guan Gefei , Shen Shuai , Han Yunhe , Yang Lianhe , Cheng Wen , Wu Anhua 
Published: December 2020

Abstract
Background: Glioma is the most prevalent and malignant primary central nervous system tumor in adults. As a member of the integrin alpha chain family of proteins, integrin subunit alpha 3 (ITGA3) has been found to play a critical role in the occurrence and progression of several cancers, including lung, ovarian, and pancreatic cancers. However, the role of ITGA3 in glioma remains unclear.Methods: The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), REMBRANDT, GSE16011, GSE59612, and GSE4290 datasets were used to analyze relevant characteristics of ITGA3 in glioma. R language and GraphPad Prism 7.00 were employed as major tools for statistical analysis and graph manipulation.Results: We identified that ITGA3 expression was upregulated in glioma and related to unfavorable outcomes of glioma patients. Expression of ITGA3 also tended to be enriched in aggressive subtypes of glioma. We demonstrated that expression of ITGA3 was negatively correlated with glioma purity. In gliomas with high ITGA3 expression, the anti-glioma immune response was inhibited. ITGA3 also regulated angiogenesis within the glioma microenvironment and promoted the epithelial–mesenchymal transition (EMT) and autophagy of glioma cells. GSEA analysis revealed that ITGA3 could activate ERK1/2 and PI3K/AKT/mTOR pathways.Conclusion: Our data suggested that ITGA3 promoted the malignant progression of glioma by regulating the immunity of glioma as well as the EMT and autophagy of glioma cells, which could act as a therapeutic target for glioma.
Long non-coding RNA SREBF2-AS1 promotes cell progression by increasing SREBF2 expression in Hepatocellular carcinoma
Authors: Qu Lili , Cai Xiaoxiao , Gong Lailing , Shen Peng , Zhu Yefei , Jiao Mei , su chuan 
Published: December 2020

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Long non-coding RNAs (lncRNAs) are emerging as one of important regulators that may be involved in the progression of cancers in humans.
Methods
Comprehensive analysis of the lncRNA expression profile of HCC was performed by using TCGA and Gene Expression Omnibus (GEO) database to screen the target lncRNA(s). LncRNA of SREBF2-AS1 was selected and its expression level in a cohort of 15 pairs of HCC tissues was verified by quantitative real-time PCR (qRT-PCR). Loss-of-function and gain-of-function assays were carried out to investigate the role of SREBF2-AS1 in HCC progression in vitro. Tumor formation assay was performed to verity the role of SREBF2-AS1 in HCC progression in vivo.
Results
Database analysis showed that the expression of SREBF2-AS1 was upregulated in HCC, which was correlated with neoplasm grade and over survival time. The expression of SREBF2-AS1 was verified in a cohort of 15 pairs of HCC tissues. SREBF2-AS1 knockdown mitigated HCC cell growth and promoted apoptosis in vitro and in vivo. Whereas, SREBF2-AS1 overexpression promoted tumor cell growth. Furthermore, our investigation demonstrated that the oncogenic activity of SREBF2-AS1 is partially attributable to the regulation of sterol regulatory element-binding protein 2 (SREBF2) expression.
Conclusions
Our study highlights the regulatory role of SREBF2-AS1 in promoting HCC progression, suggesting that SREBF2-AS1 might be a potent therapeutic target by regulating the expression of SREBF2 for patients with HCC.
Unexplained infertility and expectant management in women aged 39 or above: is it acceptable to ask couples to wait one year before receiving IVF? A retrospective cohort study
Authors: Carosso Andrea Roberto , EEKELEN Rik van , Revelli Alberto , CANOSA Stefano , MERCALDO Noemi , STURA Ilaria , COSMA Stefano , SCARAFIA Carlotta , SESTERO Marta , BENEDETTO Chiara , GENNARELLI Gianluca 
Published: December 2020

Abstract
Background: in older women, it is difficult to distinguish between ‘true’ unexplained infertility and age-related infertility. Unexplained infertile couples can have further expectant management before starting assisted reproductive treatments to avoid unnecessary, invasive and expensive treatment. However, ovarian reserve rapidly declines after 39 years or more, as the live birth rate after in vitro fertilization. It is thus uncertain if such a waiting policy, is also appropriate for women of advanced age.Methods: couples who had access to a waiting list for approximately one year before receiving reimbursed public IVF were compared with those paying for access to immediate private treatment at the IVF unit of S. Anna academic hospital and its private appendix. To allow for comparisons between these two strategies, we followed up couples who opted to pay for one year after the last embryo transfer from their first cycle. Clinical procedures regarding diagnosis and treatment were the same for both groups. We calculated the proportion of live births in both groups and compared these using a two-sample Z test for equality of proportions. The imbalance between these groups in terms of prognosis was accounted for using inverse probability weighting.Results: 635 couples were evaluated. Out of 359 couples in the immediate group, 70 (19.5%) had a live birth of which 11 after natural conception and 59 after IVF. Out of 276 couples in the waiting group, 57 (20.7%) had a live birth of which 37 after natural conception and 20 after IVF. There was no statistically significant difference between the two strategies in terms of the cLBR (19.5% immediate versus 20.7% waiting, 95% CI for difference: -0.07to 0.05), also after weighting (16.8% immediate versus 26.6% waiting, bootstrap 95%, CI for difference: -0.20 to 0.01).Conclusion(s): the cLBR for the ‘waiting before in vitro fertilization’ and the ‘immediate’ strategies were similar. Further studies are necessary to validate these findings and to better characterize these patients in order to individualize treatment and optimize economic resources, particularly in a setting of publicly-funded IVF.Trial registration: retrospectively registered
The architecture of the SARS-CoV-2 RNA genome
Authors: Cao Changchang , Cai Zhaokui , Xiao Xia , Rao Jian , Hu Naijing , Yang Minnan , Xing Xiaorui , Zhou Bing , Wang Xiangxi , Wang Jianwei , Xue Yuanchao 
Published: December 2020

Abstract
SARS-CoV-2 carries the largest single-stranded RNA genome and is the causal pathogen of the ongoing COVID-19 pandemic. How the SARS-CoV-2 RNA genome is folded in the virion remains unknown. To fill the knowledge gap and facilitate structure-based drug development, we developed a virion RNA in situ conformation sequencing technology, named vRIC-seq, for probing viral RNA genome structure unbiasedly. Using vRIC-seq data, we reconstructed the tertiary structure of the SARS-CoV-2 genome and revealed a surprisingly "unentangled globule" conformation. We uncovered many long-range duplexes and higher-order junctions, both of them were under purifying selections and contributed to the sequential package of the SARS-CoV-2 genome. Unexpectedly, the D614G and two accompanying mutations might remodel duplexes into more stable forms. Lastly, the structure-guided design of potent small interfering RNAs could obliterate the SARS-CoV-2 in Vero cells. Overall, our work provides a framework for studying the genome structure, function, and dynamics of emerging deadly RNA viruses.
Dynamic accuracy analysis of a 5PSS/UPU parallel mechanism based on rigid-flexible coupled modeling
Authors: Li Yanbiao , Wang Zesheng , Chen Chaoqun , Xu Taotao , Chen Bo 
Published: December 2020

Abstract
In order to improve the low output accuracy caused by the elastic deformations of the branch chains, a finite element-based dynamic accuracy analysis method for parallel mechanisms is proposed in this paper. First, taking a 5–prismatic–spherical–spherical (PSS)/universal–prismatic–universal (UPU) parallel mechanism as an example, the error model is established by a closed vector chain method while its influence on the dynamic accuracy of the parallel mechanism is analyzed through numerical calculation and simulation. According to the structural and error characteristics of the parallel mechanism, a vector calibration algorithm is proposed to reduce the position and pose errors along the whole motion trajectory. Then, considering the elastic deformation of the rod, the rigid-flexible coupling dynamic equations of the mechanism are established by combining the finite element method with the Lagrange method, and the equations are vectorially superimposed by means of internal force cancellation to synthesize the elastic dynamics equation of the connecting rod. Based on the constraint condition of each moving part, the elastodynamic model of the whole machine is obtained. Furthermore, the effect of component flexibility on the dimensionless root mean square error of the displacement, velocity and acceleration of the moving platform is investigated by using a Newmark method, and the dynamic accuracy influenced by these dimensionless root mean square errors is further studied. The research work establishes an important theoretical foundation for the development of the prototype.
Demographic Features of Identified PLWHA Infected through Commercial and Nonmarital Noncommercial Heterosexual Contact in China from 2015 – 2018: A Retrospective Cross-Sectional Study
Authors: Dong Zhilong , Ma Liying , Cai Chang , Gao George Fu , Lyu Fan 
Published: December 2020

Abstract
Background:Understanding the demographic characteristics of people living with HIV/AIDS (PLWHA) infected through commercial heterosexual contact (CHC) or nonmarital noncommercial heterosexual contact (NMNCHC) is important for HIV/AIDS prevention and control.Methods:Cases reported through the Chinese HIV/AIDS Case Reporting System (CRS) from 2015 to 2018 were analyzed. A descriptive and preliminary inferential analysis were performed for those demographic characteristics deemed of interest.Results:Overall, 523,121 identified PLWHA between 2015 and 2018 in the CRS were analyzed. The constituent ratio of heterosexual transmission increased from 66.25% in 2015 to 71.48% in 2018. The proportion of CHC heterosexual transmission decreased from 40.18% in 2015 to 37.99% in 2018, while that of NMNCHC increased from 46.33% in 2015 to 49.02% in 2018. PLWHA infected through NMNCHC were significantly younger than those who were infected through CHC (Student’s t test, P<0.0001), with an average age gap ranging from 5.63 (2015) to 7.46 (2018) years, and the average age of both groups increased annually. The frequency of newly identified PLWHA who were infected through CHC had a remarkable increase among the ages of 65 and above. Gender distribution was significantly different between CHC and NMNCHC (χ2 = 8909.00(2015), 9941.90(2016), 11004.00 (2017), 12836.00(2018), all P < 0.0001), and the ratio of men to women in the NMCHC group was 1.50:1 (2015), 1.51:1 (2016), 1.54:1 (2017), and 1.52:1 (2018), while in the commercial heterosexual contact (CHC) group, these ratios were 11.45:1 (2015), 12.08:1 (2016), 12.53:1 (2017), and 13.28:1 (2018). Marital status was significantly different between CHC and NMNCHC (χ2 = 94.67 (2015), 109.88(2016), 58.18(2017), 152.38(2018), all P < 0.0001). As the educational level improved, the proportion of NMNCHC also increased (Cochran - Armitage test, P<0.0001).Conclusions:We found that heterosexual transmission was the primary mode of HIV transmission in China from 2015 to 2018. PLWHA infected through CHC and NMNCHC had different characteristics in age, gender, marital status, and educational level. The frequency of PLWHA infected through CHC increased substantially in the age group of 65 and above. This study provides useful baseline data for future studies on the heterosexual transmission of HIV in China.
Clinical effect of minimally invasive surgery for inguinal cryptorchidism
Authors: Wang Yunjin , Chen Liu , Cui Xu , Zhou Chaoming , Zhou Qing , Zhang Zhengmian 
Published: December 2020

Abstract
Background: The purpose of this study was to investigate the clinical effect of minimally invasive surgery for inguinal cryptorchidism. Methods: The patients were divided into the minimally invasive surgery group (n=100) and the traditional surgery group (n=58). In the minimally invasive surgery group, patients with low inguinal cryptorchidism (n=54) underwent surgery with a transscrotal incision, and patients with high inguinal cryptorchidism (n=46) underwent laparoscopic surgery. Results: There was no difference in the hospital stay duration or cost between the minimally invasive surgery group and the traditional surgery group (P>0.05). As for the operative time, minimally invasive surgery of low inguinal cryptorchidism was shorter than traditional surgery (P=0.033), while minimally invasive surgery of high inguinal cryptorchidism was comparable to traditional surgery (P=0.658). Additionally, there were no cases of testicular atrophy, testicular retraction, inguinal hernia or hydrocele in either group. There was no significant difference in the incidence of poor wound healing between the two groups (P>0.05). Although there was no significant difference in the incidence of scrotal hematoma between the two groups (P>0.05), the incidence in the minimally invasive surgery group was higher than that in the traditional surgery group. Conclusions: Minimally invasive surgery including a transscrotal incision for low inguinal cryptorchidism and laparoscopic surgery for high inguinal cryptorchidism is as safe and effective as traditional surgery, and could also provide a good cosmetic effect for children.
Microbial fuel cell assisted utilization of glycerol for succinate production by mutant of Actinobacillus succinogenes
Authors: Zheng Tianwen , Xu Bin , Ji Yaliang , Zhang Wenming , Xin Fengxue , Dong Weiliang , Wei Ping , Ma Jiangfeng , Jiang Min 
Published: December 2020

Abstract
Background: The global production of glycerol is increasing year by year since the demands of biodiesel is rising. It is benefit for high-yield succinate synthesis due to its high reducing property. A. succinogenes, a succinate-producing candidate, cannot grow on glycerol anaerobically, as it needs a terminal electron acceptor to maintain the balance of intracellular NADH and NAD+. Microbial fuel cell (MFC) has been widely used to release extra intracellular electrons. However, A. succinogenes is a non-electroactive strain which need the support of electron shuttle in MFC, and pervious research showed that acid tolerant A. succinogenes has higher content of unsaturated fatty acids, which may be beneficial for the transmembrane transport of lipophilic electron shuttle.Results: MFC assisted succinate production was evaluated using neutral red as an electron shuttle to recover the glycerol utilization. Firstly, an acid tolerant mutant JF1315 was selected by atmospheric and room temperature plasma (ARTP) mutagenesis aiming to improve transmembrane transport of neutral red (NR). Additionally, MFC was established to increase the ratio of oxidized NR to reduced NR. By combining these two strategies, ability of JF1315 for glycerol utilization was significantly enhanced, and 23.92 g/L succinate was accumulated with a yield of 0.88 g/g from around 30 g/L initial glycerol, along with an output voltage above 300 mV.Conclusions: A novel MFC-assisted system was established to improve glycerol utilization by A. succinogenes for succinate and electricity production, making this system as a platform for chemicals production and electrical supply simultaneously.