bluuebunny/crossref_metadata_2025 huggingface dataset:
Sema4C induces the endothelial-mesenchymal transition of tumor-associated lymphatic endothelial cells in cervical cancer via the ERK pathway
Authors: Peng Jin , Liu Xijiang , Li Chengcheng , Gao Min , Wang Hongyan
Published: August 2020

Background: The endothelial-mesenchymal transition (EndMT) is a process that increases the promigratory abilities of endothelial cells (ECs). Although lymphatic endothelial cells (LECs) plays a positive role in tumor lymphatic metastasis, the regulation of LECs undergoing EndMT remains poorly understood. Previous study indicated that Semaphorin 4C (Sema4C) could be a marker of LECs in cervical cancer. Here, we try to understand the mechanism that Sema4C could promote LECs to get mesenchymal characters and enhance lymphatic metastasis in cervical cancer.
Methods: The co-location of Sema4C and lymphatic marker LYVE1 was verified by confocal laser scanning. Primary tumor-associated LECs (TLECs) were distinguished from cervical cancer by flow cytometry from a mouse xenograft cervical tumor model. The promigratory ability was assessed using the Transwell test. Lentivirus infection was used to alter the expression of Sema4C in TLECs and the infection efficiency was tested by confocal laser scanning. The phospho-extracellular signal-regulated kinase (p-ERK) signaling pathway was measured using the ERK inhibitor (PD98059) ,as well as quantitative PCR and Western blot analysis.
Results: Sema4C and LYVE1 co-located on TLECs. Primary TLECs were successfully separated and cultured. Overexpressing Sema4C by lentivirus infection stimulated the invasive capacity of TLECs and downregulated E-cadherin, whereas knocking down Sema4C had the opposite effects. TLECs pro-migratory ability was found to depend on the extracellular signal-regulated kinase (ERK) signaling pathway, as the ERK inhibitor (PD98059) reversed Sema4C-induced E-cadherin expression and migration ability.
Conclusion: The results of this study suggest that the Sema4C-ERK-E-cadherin pathway appears to be critical for the EndMT of TLECs, which might promote lymph node metastasis. Thus, Sema4C could be a promising target for the treatment of cervical cancer with lymphatic metastasis.
Machine Learning to Guide the use of Adjuvant Therapies for Breast Cancer
Authors: Alaa Ahmed , Gurdasani Deepti , Harris Adrian , Rashbass Jem , Schaar Mihaela van der
Published: August 2020

Accurate prediction of the individualized survival benefit of adjuvant therapy is key to making informed therapeutic decisions for patients with early invasive breast cancer. Here, we use a state-of the-art automated and interpretable machine learning algorithm to develop a breast cancer prognostication and treatment benefit prediction model — Adjutorium — using data from large-scale cohorts of nearly 1 million women captured in the national cancer registries of the United Kingdom and the United States. We trained and internally validated the Adjutorium model on 395,862 patients from the UK National Cancer Registration and Analysis Service (NCRAS); we then externally validated the model among 571,635 patients from the US Surveillance, Epidemiology, and End Results (SEER) Program. Adjutorium exhibited significantly improved accuracy compared to the major prognostic tool in current clinical use (PREDICT v2.1) in both internal and external validation (AUC-ROC for 5-year survival prediction in NCRAS was 0.835, 95% CI: 0.833–0.837 and 0.755, 95% CI: 0.753–0.757 for Adjutorium and PREDICT v2.1. In SEER, the AUC-ROC performance was 0.815, 95% CI: 0.813–0.817 and 0.775, 95% CI: 0.772–0.778 for Adjutorium and PREDICT v2.1, respectively). Importantly, our model substantially improved accuracy in specific subgroups known to be under-served by existing models. Adjutorium is currently implemented as a web-based decision support tool (vanderschaar-lab.com/adjutorium/) to aid decisions on adjuvant therapy in women with early breast cancer, and can be publicly accessed by patients and clinicians worldwide.
Association of The Cytotoxic T Lymphocyte Antigen-4 +49G/A Gene Polymorphism with Susceptibility to Malignant Bone Tumors
Authors: Guo Ningfeng , Wu Yaojun , Hu Yueming
Published: August 2020

Background Earlier research works have studied the part that cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays in the carcinogenesis of malignant bone tumors, nonetheless, findings had inconsistency. The current investigation aims at clarifying the association between CTLA-4 polymorphism and malignant bone tumor susceptibility through the meta-analysis.Methods We searched pertinent research works in not just PubMed, but also EMBASE, Cochrane library, and Chinese National Knowledge Infrastructure (CNKI) databases in humans published before October 2019. The use of the pooled odds ratio (OR) with its 95% confidence interval (95%CI) was made for estimating the strengths of the correlation existing between the CTLA-4 genetic polymorphism and malignant bone tumors susceptibility. An aggregate of six research works with 1191 malignant bone tumors patients and 1418 controls were selected eventually. The pooled results shed light on the fact that CTLA-4 +49G/A polymorphism had a significant correlation with an augmented vulnerability to the malignant bone tumors (A vs. G: OR=1.37, 95%CI=1.22-1.54; GA vs. GG: OR=1.20, 95%CI=1.01-1.42; AA vs. GG: OR=2.13, 95%CI=1.63-2.78; GA+AA vs. GG: OR=1.35, 95%CI=1.15-1.59; AA vs. GG+GA: OR=2.02, 95%CI=1.60-2.56). Subgroup analysis indicated that there exists a statistically significant correlation between CTLA-4 +49G/A polymorphism and augmented susceptibility to the malignant bone tumor in the population-based or hospital-based samples, and Ewing’s sarcoma or osteosarcoma. Moreover, there was also not observed any considerable heterogeneity across the research works. Results Our results suggest that the CTLA-4 +49G/A polymorphism may play a pivotal part in the carcinogenesis of malignant bone tumors. Conclusions More research works, on the basis of the large sample sizes as well as homogeneous specimens, are needed in order to verify these results.
Genomic and Histological Analysis of Helicobacter Himalayensis Sp. Nov. Isolated From Marmota Himalayana to Discovery the Potential Human Pathogen
Authors: Hu Shouhui , Niu Lina , Wu Lei , Zhu Xiaoxue , Cai Yu , Jin Dong , Yan Linlin , Zhao Fan
Published: August 2020

Background: Helicobacter himalayensis was isolated from Marmota himalayana in the Qinghai-Tibet Plateau, China, and is a new non-H. pylori species, with unclear taxonomy, phylogeny, and pathogenicity. Methods and results: A comparative genomic analysis was performed between the H. himalayensis type strain 80(YS1) and other the genomes of Helicobacter species present in the National Center for Biotechnology Information (NCBI) database to explore the molecular evolution and potential pathogenicity of H. himalayensis. We also compared the lesions of gastrointestinal tissue samples from H. himalayensis-positive Marmota himalayana with H. himalayensis-negative Marmota himalayana using histology. H. himalayensis 80(YS1)T formed a clade with H. cinaedi and H. hepaticus that was phylogenetically distant from H. pylori. The genome of 80(YS1)T comprised 1,829,936 bp, with a 39.9% GC content, a predicted genomic island, and 1,910 predicted proteins. Comparatively, H. himalayensis has more genes for functions in “cell wall/membrane/envelope biogenesis” and “nucleotide transport and metabolism” sub-branches than the other compared helicobacters, and its genome contained 42 virulence factors genes, including that encoding cytolethal distending toxin (CDT). Histologically, the gastrointestinal mucosa of H. himalayensis-infected Marmota himalayana showed obvious lesions, implying that H. himalayensis is pathogenic to its host. Conclusions: We characterized the H. himalayensis 80(YS1)T genome, its phylogenetic position, and its potential pathogenicity. 80(YS1)T may be pathogenic to animals or humans; however, further understanding of the pathogenesis of this potentially pathogenic bacterium is required, which might help to manage H. himalayensis-induced diseases.
Bioavailable iron produced through benthic cycling in glaciated Arctic fjords (Svalbard)
Authors: Laufer Katja , Michaud Alexander , Maisch Markus , Byrne James , Kappler Andreas , Patterson Molly , Røy Hans , Jørgensen Bo Barker
Published: August 2020

The Arctic has the highest warming rates world-wide. Glaciated fjord ecosystems, which are known hotspots of carbon cycling and burial, are predicted to be extremely sensitive to this warming. Glaciers are important sources of iron, an essential nutrient for phytoplankton, to high-latitude marine ecosystems. However, up to 95% of the glacially-sourced iron settles in sediments close to the glacial source. We found that only 0.6-12% of the total glacially-sourced iron is potentially bioavailable. Our results also show that biogeochemical cycling in fjord sediments converts the unreactive glacial iron into more reactive and bioavailable phases, leading to an up to 9-fold increase in the amount of potentially bioavailable iron. Arctic fjord sediments therefore likely are an important source of bioavailable iron. However, once glaciers retreat onto land, the flux of iron from sediments into the water column is reduced, such that glacial retreat could exacerbate iron limitation in polar oceans.
Rationing and triage of scarce, lifesaving therapy in the context of the COVID-19 pandemic - a cross-sectional, social media-driven, scenario-based online query of societal attitudes
Authors: Muensterer Oliver J. , Gianicolo Emilio A. , Paul Norbert W.
Published: August 2020

Background The recent COVID-19 pandemic made us aware that medical resources are limited. When demand for essential resources surpasses availability, difficult triaging decisions are necessary. While algorithms exist, almost nothing is known on societal attitudes regarding triage criteria.Methods A cross-sectional survey was conducted via social media channels to query a broad sample of society. Participants were asked to make triage decisions in case-based vignettes, exploring a variety of factors. They also were asked to assess how sure they were about their decisions, and how such decisions should be reached.Results The survey was completed in full by 1626 participants in April 2020. Median age was 39 years (range 12-80 years), 984 (61%) were female. Patient prognosis, responsibility towards others, the absence of behavior-induced co-morbidities, and younger age were rated the most important triage criteria, while participants found that insurance status, social status, and nationality should not play a substantial role. Ethics-committees and point systems were regarded potentially helpful for triage decision-making, while decisions based on order of presentation (first-come first-serve) or on a legal basis were viewed critically. Participants were least sure about their decision when dealing with age or behavior-induced co-morbidities. Overall, women were surer about their decisions than men, participants of Christian faith were also more secure about their decision than atheists-agnostics.Conclusions This study uses social media to generate insight into public opinion and attitudes regarding triage criteria and modalities. These findings may be helpful for the development of future medical triage algorithms.
Comparative transcriptome analysis to reveal putative genes responsible for high theacrine content in Kucha (Camellia kucha (Chang et Wang) Chang)
Authors: Li Hongjian , Fang Kaixing , Qin Dandan , Jiang Xiaohui , Wang Qiushuang , Pan Chendong , Li Bo , Wang Qing , Wu Hualing
Published: August 2020

Background: The purine alkaloid theacrine, synthesized in a high amount in Kucha (Camellia kucha (Chang et Wang) Chang), has shown multiple pharmacological effects such as anti-depression, dehydration and hypnotic activities. It is critical to better understand the theacrine metabolism at the molecular level for future breeding programs. Results: In this study, we carried out comparative transcriptome analysis of Kucha (Kucha-6 and Kucha-11) and conventional varieties (Yinghong 9 and Qingxin 1). HPLC showed that Kucha synthesized more than 27-fold theacrine in comparison to conventional varieties. A total of ~ 671.61 million high quality clean reads were yield, and 71.42 ~ 76.87% of these were aligned to the reference genome for each library. Among the 19,095 differentially expressed genes (DEGs) identified by a pairwise comparison approach, a pool of 1,142 common DEGs between Kucha and conventional varieties were screened. Functional annotation allowed the identified of 20 oxidoreductase (OR) genes and seven methyltransferase (MT) genes with enhanced expression in Kucha, which might be associated with theacrine diversity in the examined materials. Particularly, two N-methyltransferase-encoding genes (TEA010054 and TEA022559) may catalyze the final methylation step during theacrine synthesis in Kucha. Conclusion: The current study focused on screening genes of theacrine formation in tea plant, which contributes to the elucidation of candidate genes and breeding tea plant with high theacrine content.
The Mediating Role of Depressive Symptoms, Hopelessness, and Perceived Burden on the Association Between Pain Intensity and Late-Life Suicide in Rural China: A Case–Control Psychological Autopsy Study
Authors: Wang Jiali , Ma Zhenyu , Jia Cunxian , Wang Guojun , Zhou Liang
Published: August 2020

Background: Few studies have investigated the roles of psychosocial factors such as depressive symptoms and hopelessness on the relationship between pain and suicide with inconsistent results. The study aimed to analyze the impact of pain intensity on suicide death and to estimate the degree to which depressive symptoms, hopelessness, and perceived burden may explain the association in Chinese rural elderly. Methods: Using a 1: 1 matched case-control design, data were collected from 242 elderly suicide cases and 242 living community controls by psychological autopsy method in rural China, including demographic characteristics, pain intensity, depression, hopelessness, perceived burden, physical diseases, and social support. Conditional logistic regression was used to assess the association between pain intensity and completed suicide. Mediation analysis using the KHB method was applied to explore the mediation effects from depressive symptoms, hopelessness, and perceived burden. Results: The result of multivariable logistic regression showed that unemployment (odds ratio (OR) =5.06, 95% confidential interval (CI): 1.76- 14.49), higher levels of hopelessness (OR=7.72, 95% CI: 3.49- 17.10), depressive symptom (OR=15.82, 95% CI: 4.53- 55.25), and severe pain (OR=3.46, 95% CI: 1.31- 9.13) were significantly associated with elevated suicide risk in older people in rural China. Depressive symptoms, hopelessness, and perceived burden significantly mediated 43.71% of the pain-suicide association ( P = 0.020), with 17.39% due to depressive symptoms, 17.63% due to hopelessness, and 8.69% due to perceived burden. Conclusions: Regular screening of pain, depressive symptoms, hopelessness, and perceived burden using simple but sensitive questions or scales for older adults with pain are vital for the prevention and early detection of suicide risk in Chinese rural areas. Moreover, the importance of pain management and psychological interventions targeted on depressive symptoms and hopelessness should be emphasized.
Comparative transcriptomic analysis reveals the relationship between cold-acclimation and vernalization
Authors: Li Fei , Hu Qian , Chen Fadi , Jiang Jiafu
Published: August 2020

Background:

The relationship between cold acclimation and vernalization has been a hanging debate. Cold-acclimation is a cold-responding process that enable plants adapt to cold temperature in a rapid time. While vernalization is that plants flower by quantitative accumulation of cold exposure. 4℃ is both the acclimation temperature and vernalization temperature. We conducted transcriptomic analyses during 42 days 4℃ vernalization process to explore the whole process of transcriptional dynamics during vernalization and responding situation of short-term cold exposure in Arabidopsis
Results:

Brassinosteroid was found as the most sensitive hormone in response to cold shock. Phosphorylation played an important role in long-term temperature drop by time-course analysis. Independency between cold-acclimation and vernalization was confirmed based on time-lag initiation of these two pathways. Cold-acclimation suppress flowering after vernalization initiation by continuously blocking photoperiod and gibberellin (GA) pathway. FLM inhibited flowering in a FLM-β-upregulation and FLM-δ-independent way. Autonomous and aging pathway positively responded but did little contribution to flowering. Alternative splicing mechanism mediated cold responding through the whole vernalization process.
Conclusion

Transcriptomic analysis revealed that Cold-acclimation and vernalization are independent. Cold as winter signal either indirectly suppress flowering through cold-acclimation involved photoperiod and GA pathways or directly suppress flowering through thermosensory pathway. Additionally, alternative splicing mediation worked through the whole vernalization process.
Aberrant Methylation of the 16q22.1 Tumor Suppressor Gene CDH11 Promotes Tumorigenesis and Progression of Renal Cell Carcinoma through NF-kB Pathway
Authors: Xu Ben , Song Hai-feng , Luo Cheng , Liang Lei , Zhang Qian
Published: August 2020

The authors have requested that this preprint be removed from Research Square.
Comprehensive analysis of transcriptional regulation and functional genes induced by alkaline salt stress in roots of two switchgrass (Panicum virgatum L.) genotypes
Authors: Zhang Pan , Duo Tianqi , Wang Fengdan , Zhang Xunzhong , Yang Zouzhuan , Hu Guofu
Published: August 2020

Background: Soil salinization is a major limiting factor for crop cultivation. Switchgrass is a perennial rhizomatous bunchgrass that is considered an ideal plant for marginal lands, including sites with saline soil. Here, we investigated the physiological responses and transcriptome changes in the roots of two switchgrass genotypes under alkaline salt stress.Results: Alkaline salt stress significantly affected the membrane, osmotic adjustment and antioxidant systems in switchgrass roots, and the ASTTI values between Alamo and AM-314/MS-155 were divergent at different time points. A total of 108,319 unigenes were obtained after reassembly, including 73,636 unigenes in AM-314/MS-155 and 65,492 unigenes in Alamo. A total of 10,219 DEGs were identified, and the number of upregulated genes in Alamo was much greater than that in AM-314/MS-155 in both the early and late stages of alkaline salt stress. The DEGs in AM-314/MS-155 were mainly concentrated in the early stage, while Alamo showed greater advantages in the late stage. These DEGs were mainly enriched in plant-pathogen interactions, ubiquitin-mediated proteolysis and glycolysis/gluconeogenesis pathways. We characterized 1,480 TF genes into 64 TF families, and the most abundant TF family was the C2H2 family, followed by the bZIP and bHLH families. A total of 1,718 PKs were predicted, including CaMK, CDPK, MAPK and RLK. WGCNA revealed that the DEGs in the blue, brown, dark magenta and light steel blue 1 modules were associated with the physiological changes in roots of switchgrass under alkaline salt stress. The consistency between the qRT-PCR and RNA-Seq results confirmed the reliability of the RNA-seq sequencing data. A molecular regulatory network of the switchgrass response to alkaline salt stress was preliminarily constructed on the basis of transcriptional regulation and functional genes.Conclusions: The alkaline salt tolerance of switchgrass may be achieved by the regulation of ion homeostasis, transport proteins, detoxification, heat shock proteins, dehydration and sugar metabolism. These findings provide a comprehensive analysis of gene transcription and regulation induced by alkaline salt stress in two switchgrass genotypes and contribute to the understanding of the alkaline salt tolerance mechanism of switchgrass and the improvement of switchgrass germplasm.
Platinum-grade soybean reference genome facilitates characterization of genetic underpinnings of traits
Authors: Yi Xinxin , Liu Jing , Chen Shengcai , Wu Hao , Liu Min , Xu Qing , Lei Lingshan , Lee Seunghee , Zhang Bao , Kudrna Dave , Fan Wei , Wing Rod , Yang Chunyan , Zhang Mengchen , Zhang Jianwei , Wang Xuelu , Chen Nansheng
Published: August 2020

BackgroundCultivated soybean (Glycine max) is an important source for protein and oil. Each soybean strain has its own genetic diversity, and the availability of more soybean genomes may enhance comparative genomic analysis of soybean.ResultsIn this study, we constructed a high-quality de novo assembly of an elite soybean cultivar Jidou 17 (JD17) with high contiguity, completeness, and accuracy. We annotated 59,629 gene models and reconstructed 235,109 high-quality full-length transcripts. We have molecularly characterized the genotypes of some important agronomic traits of JD17 by taking advantage of these newly established genomic resources.ConclusionsWe reported a high-quality genome and annotations of a wide range of cultivars, and used them to analyze the genotypes of genes related to important agronomic traits of soybean in JD17. We have demonstrated that high-quality genome assembly can serve as a valuable reference for soybean genomics and breeding research community.
Telepsychiatry Adoption Across Hospitals in the United States: A Cross-Sectional Study
Authors: Li Zhong , Harrison Sayward E. , Li Xiaoming , Hung Peiyin
Published: August 2020

Background Access to psychiatric care is critical for patients discharged from hospital psychiatric units to ensure continuity of care. When face-to-face follow-up is unavailable or undesirable, telepsychiatry becomes a promising alternative. This study aimed to investigate hospital- and county-level characteristics associated with telepsychiatry adoption.Methods Cross-sectional national data of 3,475 acute care hospitals were derived from the 2017 American Hospital Association Annual Survey. Generalized linear regression models were used to identify characteristics associated with telepsychiatry adoption. Results About one-sixth (548 [15.8%]) reported having telepsychiatry. Rural noncore hospitals were less likely to adopt telepsychiatry (8.3%) than hospitals in rural micropolitan (13.6%) and urban counties (19.4%), with a wide variation across states. Hospitals with both outpatient and inpatient psychiatric care services (marginal difference [95% CI]: 16.0% [12.1% to 19.9%]) and hospitals only with outpatient psychiatric services (6.5% [3.7% to 9.4%]) were more likely to have telepsychiatry than hospitals with neither psychiatric services. Federal hospitals (48.9% [32.5% to 65.3%]), system-affiliated hospitals (3.9% [1.2% to 6.6%]), hospitals with larger bed size (Quartile IV vs. I: 6.2% [0.7% to 11.6%]), and hospitals with greater ratio of Medicaid inpatient days to total inpatient days (Quartile IV vs. I: 4.9% [0.3% to 9.4%]) were more likely to have telepsychiatry than their counterparts. Private non-profit hospitals (-6.9% [-11.7% to -2.0%]) and hospitals in counties designated as whole mental health professional shortage areas (-6.6% [-12.7% to -0.5%]) were less likely to have telepsychiatry. Conclusions Telepsychiatry adoption was low in US hospitals in 2017 with substantial variations by urban and rural status and by state. It raises concerns about access to psychiatric services and continuity of care for patients discharged from hospitals.
Patients Age is a Critical Factor in Determining the Severity of Osteoarthritis of the Shoulder
Authors: Märtens Nicole , Maerz Vincent , Bertrand Jessica , Lohmann Christoph H , Berth Alexander
Published: August 2020

Background: Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the aging population. The correlation of radiographic OA severity, disability and pain is variable and inconsistent for the different joints. This study aims to elucidate the relationship between histological and radiological signs of shoulder OA with pain sensation and functional impairment to potentially adapt the recommendation for surgical treatment for primary total shoulder arthroplasty (TSA). Methods: Forty-four patient with shoulder OA undergoing a TSA using an anatomic stemless implant were included in this study. The radiological OA severity was scored preoperatively on true ap X-rays according to the Kellgren-Lawrence-Score (KL-Score). The histological OA severity was determined according to the OARSI-Score using bone-cartilage sections from loaded areas of the humeral head. Pain was quantified with the Visual Analog Scale (VAS). The functional status was assessed by the items “mobility” and “strength” out of the Constant-Murley-Score (CS-Score). Results: There was no correlation between radiographic and histological severity in shoulder OA. However, a correlation between age and the severity of radiological changes was observed. Further, pain did not correlate with histological or radiological scores, whereas it correlated with age. The functional shoulder status (mobility, strength) correlated with the severity of radiological changes, but not with the histologic scoring. Conclusion: This study shows that increased age is the main determinant of radiological changes in shoulder OA, as well as pain. Therefore, age and pain sensation should be considered as important parameters for the recommendation for TSA.
Can Thoracolumbar Deformity Improve if Surgery Just for Lumbar Stenois Syndrome in Degenerative Thoracolumbar Kyphosis Patients ?
Authors: Meng Fanqi , Bao Xianguo , Xu Shuai , Liang Yan , Liu Haiying
Published: August 2020

Background: Fusion across thoracolumbar spine or not for degenerative thoracolumbar kyphosis (DTLK) in lumbar stenois syndrome (LSS) remains controversial. The influencing factors for postoperative TLK in this group have not been determined yet. So the study was to explore whether DTLK could improve with only surgery for lumbar stenois syndrome LSS and identify influencing factors on postoperative TLK.Methods: The study was performed from January 2016 to December 2018. 69 participants (25 male) diagnosed LSS with DTLK were enrolled and surgery was only for LSS. Radiological parameters included TLK, lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and osteoporosis. Clinical outcomes were visual analogue scale (VAS) and Oswestry disability index (ODI). According to lower instrumented vertebrae (LIV) on L5 or S1, inter-group comparisons were performed between LIV on L5 (L5 group) and S1 (S1 group).Results: Demographics was well-matched between L5 and S1 group with a mean follow-up of 24.3±12.1 (m). TLK improved with a mean of 16.2±7.6 (°) (P <0.001). It was insignificant on radiological and clinical parameters between L5 and S1 groups except a larger PT in S1 group (P=0.046). VAS (P=0.787) and ODI (P=0.530) were both indifference between normal TLK and DTLK at last (P˃0.05). Postoperative TLK was affected by osteoporosis and SS, the latter was determined by PI and PT. Osteoporosis was the risk factor for TLK correction (P=0.001, OR=9.58).Conclusions: DTLK get improved if suegery only performed for LSS. TLK and clinical outcomes are comparable between L5 and S1 groups. Severe osteoporosis can impede TLK correction.
A qualitative study on midwives’ identity and perspectives on the occurrence of disrespect and abuse in Maputo city
Authors: Galle Anna , Manaharlal Helma , Griffin Sally , Osman Nafissa , Roelens Kristien , Degomme Olivier
Published: August 2020

BACKGROUND
Midwifery care plays a vital role in the reduction of preventable maternal and newborn mortality and morbidity. There is a growing concern about the quality of care during facility based childbirth and the occurrence of disrespect and abuse (D&A) worldwide. While several studies have reported a high prevalence of D&A, evidence about the drivers of D&A is scarce.
AIM
This study aims to explore midwives’ professional identity and perspectives on the occurrence of D&A in urban Mozambique.
METHODS
A qualitative study took place in the central hospital of Maputo, Mozambique. Nine focus group discussions with midwives were conducted, interviewing 56 midwives. RQDA software was used for analyzing the data by open coding and thematic analysis.
RESULTS
Midwives felt proud of their profession but felt they were disrespected by the institution and wider society because of their inferior status compared to doctors. Furthermore, they felt being blamed for poor health outcomes. The occurrence of D&A seemed more likely in emergency situations but midwives tended to blame this on women being “uncooperative”. The involvement of birth companions was a protective factor against D&A together with supervision.
Conclusion
In order to improve quality of care and reduce the occurrence of D&A midwives will need to be treated with more respect within the health system. Furthermore, they should be trained in handling obstetric emergency situations with respect and dignity for the patient. Systematic and constructive supervision might be another promising strategy for preventing D&A.
The Relationship Between microRNA-195 and the Prognosis of Cervical Cancer
Authors: Cao Shuangqing , Zheng Lei
Published: August 2020

Background: MicroRNA-195 (miR-195), a tumor suppressor, had reported to be involved in carcinogenesis and the progression of some cancers. However, the prognostic value of miR-195 in cervical cancer remained unclear. The purpose of this study was to detect the expression of miR-195 in cervical cancer tissues and to investigate its correlation with tumor progression and prognosis.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of miR-195 in cervical cancer tissues and corresponding adjacent normal tissues. The relationship between miR-195 expression and clinical characteristics of patients was analyzed by chi-square test. Kaplan-Meier method was applied to compare the overall survival, and the prognostic value of miR-195 was estimated via cox regression analysis.Results: Compared with normal tissues, miR-195 expression was significantly down-regulated in cervical cancer tissues (P < 0.001). Importantly, decreased expression of miR-195 was closely associated with FIGO stage, lymph node metastasis and vascular invasion (P < 0.05). Additionally, Kaplan-Meier analysis indicated that patients with high miR-195 expression had obviously longer overall survival than those with low miR-195 expression (log rank test, P = 0.001). And miR-195 was an independent prognostic factor of cervical cancer patients via univariate and multivariate cox regression analyses.Conclusions: Decreased expression of miR-195 is associated with the progression of cervical cancer. And miR-195 may have potency to predict the prognosis of cervical cancer.
Aurora-B Knockdown Inhibits Osteosarcoma Metastasis by Inducing Autophagy via the mTOR/ULK1 Pathway
Authors: Wu Xin , Liu Jia-ming , Song Honghai , Yang Qikun , Ying Hui , Tong Weilai , Zhou Yang , Liu Zhi-li
Published: August 2020

Background
Autophagy plays an essential role in metastasis of malignancies. Although our studies showed that Aurora-B facilitate pulmonary metastasis in OS, the mechanism of Aurora-B kinase on autophagy and metastasis in OS has not been explored.
Methods
Clinical-pathological parameters and follow-up information was collected in OS patients. Immunohistochemical staining was performed to detect Aurora-B and LC3 protein in OS tissues. Short hairpin RNA transfection was used to silence Aurora-B in OS cells. Real-time quantitative PCR (RT-qPCR) was performed to detect Aurora-B mRNA expression in OS cells. Aurora-B and autophagy related protein were measured by Western blot. Transmission electron microscopy and laser scanning confocal microscopy were performed to observe the formation of autophagosomes and autolysosomes. Migratory and invasive ability of OS cells were measured by Wound healing and transwell assays. Orthotopic xenograft model was used to evaluate the effect of autophagy mediated by Aurora-B inhibition on pulmonary metastasis of OS.
Results
The elevated expression of Aurora-B protein in OS tissues negatively associated with the overall survival of OS patients. Further investigation has found that Aurora-B expression was negatively correlative with autophagy related protein LC3 in OS patient tissues. Knockdown Aurora-B stimulates autophagy and inhibits migratory and invasive ability of OS cells. Mechanistically, Aurora-B knockdown suppressed the mTOR/ULK1 signaling pathway and reactivation of the mTOR/ULK1 pathway decreased autophagy level. Furthermore, the inhibition effect of silencing Aurora-B on migration and invasion of OS was reversed by chloroquine and mTOR activator in vitro and vivo.
Conclusions
Our results suggest that silencing of Aurora-B stimulate autophagy via decreasing mTOR/ULK1 and result in inhibiting OS metastasis. Targeted Aurora-B/mTOR/ULK1 pathway may be a promising treatment strategy for OS patients.
Identification and Validation of a Predictive Immune-related Genes Signature for the Prognosis of Cholangiocarcinoma
Authors: Zhang Rui , Chen Chen , Li Qi , Fu Jialu , Zhang Dong , Li Wenzhi , Geng Zhimin
Published: August 2020

Background: Immune-related genes (IRGs) play a crucial role in the initiation and progression of cholangiocarcinoma (CCA). However, immune signatures have rarely been used to predict prognosis of CCA. The aim of this study was to construct a novel model for CCA to predict survival based on IRGs expression data.Methods: The gene expression profiles and clinical data of CCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were integrated to establish and validate prognostic IRG signatures. Differentially expressed immune-related genes were screened. Univariate and multivariate Cox analysis were performed to identify prognostic IRGs, and the risk model that predicts outcomes was constructed. Furthermore, receiver operating characteristic (ROC) and Kaplan-Meier curve were plotted to examine predictive accuracy of the model, and a nomogram was constructed based on IRGs signature, combining with other clinical characteristics. Finally, CIBERSORT was used to analyze the association of immune cells infiltration with risk score.Results: We identified that 223 IRGs were signiﬁcantly dysregulated in patients with CCA, among which five IRGs (AVPR1B, CST4, TDGF1, RAET1E and IL9R) were identified as robust indicators for overall survival (OS), and a prognostic model was built based on the IRGs signature. Meanwhile, patients with high risk had worse OS in training and validation cohort, and the area under the ROC was 0.898 and 0.846, respectively. Nomogram demonstrated that immune risk score contributed much more points than other clinicopathological variables, with a C-index of 0.819 (95% CI, 0.727-0.911). Finally, we found that IRGs signature was positively correlated with the proportion of CD8+ T cells, neurophils and T gamma delta, while negatively with that of CD4+ memory resting T cells.Conclusions: We established and validated an effective five IRGs-based prediction model for CCA, which could accurately classify patients into groups with low and high risk of poor prognosis.
Identification of Metabolism-associated Genes and Construction of a Prognostic Signature in Bladder Cancer
Authors: Shen Chengquan , Liu Jing , Wang Liping , Liang Zhijuan , Niu Haitao , Wang Yonghua
Published: August 2020

Background
Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs prognostic risk signature in BC by using The Cancer Genome Atlas (TCGA) database and proteomics data.
Methods
RNA-sequence data from the TCGA database and proteomics were used to identify differentially expressed MAGs and construct a prognostic MAGs signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs model in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) was further performed to investigate the expression levels of MAGs in BC cell lines and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted TGF-beta 1 in BC.
Results
A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that four MAGs were significantly elevated and the expression levels of three MAGs were positively correlated with M2 TAM secreted TGF-β1 in T24 cells.
Conclusions
Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent signature in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of three MAGs via TGF-β1 signaling pathway. Further clinical trials and experimental exploration are needed to validate our observations in BC.
CBX3 Regulated by miR-139 Promoted the Development of HCC by Regulating Cell Cycle Progression
Authors: Zhang Pan , Yang Xiaoyan , Zha Zhongming , Zhu Yumeng , Zhang Guoqiang , Li Guotao
Published: August 2020

Background Hepatocellular carcinoma (HCC), comprises of the major primary liver cancer, is one of the most lethal malignancies in the world [1]. Increasing evidence has demonstrated that chromobox protein homolog 3 (CBX3) functioned as an oncogene in different cancers. However, its expression profiles and biological functions in HCC remain exactly unknown. Methods Data of CBX3 expression in HCC acquired from TCGA and GEO databases were analyzed. The biological functions of CBX3 in HCC were examined by in vitro experiments. Bioinformatics analysis, qRT-PCR and western blot were performed to explpore the mechanism of CBX3 involved in HCC. Results CBX3 mRNA was upregulated in HCC tissues, and overexpression of CBX3 mRNA was negatively correlated with malignancies and poor prognosis in HCC patients. Knocking down of CBX3 induced slower growth, less migration and fewer invasions of the HCC cells in vitro. Moreover, bioinformatics analysis and experimental observation indicated that CBX3 expression was correlated with cell cycle regulation proteins of HCC cells. Finally, Starbase predicted that the miR-139 could directly target CBX3 in HCC; Confirmatory experiments verified that miR-139 overexpression attenuated the HCC cells proliferation and migration, which could be reversed by overexpressing CBX3 concurrently. Conclusion Our results concluded that miR-139/CBX3 axis may involve in the HCC development through regulating cell cycle progression and may be a promising target in the treatment of HCC.
Patients with Pretreatment Leukoencephalopathy and Older Patients have More Cognitive Decline after Whole Brain Radiotherapy
Authors: Chan Matthew , Ferguson David , Mhurchu Elaine Ni , Yuan Ren , Gondara Lovedeep , McKenzie Michael , Olson Robert , Thiessen Brian , Lalani Nafisha , Ma Roy , Nichol Alan
Published: August 2020

Purpose: To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases. Methods: A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1-10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every three months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline. Results: Forty-six patients survived ≥3 months after treatment. Age (OR 1.12 (1.04 – 1.21, p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06 – 1.52, p = 0.02) and baseline Fazekas score ≥ 3/6 (OR 6.4, 95% CI 1.7 – 24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pretreatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized. Conclusion: A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small, we propose that a Fazekas score of 6 should be a relative contraindication to WBRT. Trial Registration: clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010. https://clinicaltrials.gov/ct2/show/NCT01046123
Activation of the NF-κB Signaling Pathway Promotes Malignancy in Bladder Cancer Cells in a Positive Feedback Manner
Authors: guan Zhenfeng , Sun Yi , Jiang YaZhuo , Wang Xinyang , Fan Jinhai
Published: August 2020

Background: The main issue arising from bladder cancer (BCa) is the high relapse ratio and tumor progression, the mechanism of which remains to be elucidated. Interaction of tumor cells with the stroma of microenvironment promoting tumor progression warrants much attention from researchers. Among all stromal cells, endothelial cells (ECs) are exceptional. Numerous studies have investigated its role of angiogenesis, but have not studied immunocyte recruitment and chemokine secretion, the important significance of which in tumor progression has been proven. Meanwhile, to the best of our knowledge, few studies have focused on the direct interaction between tumor cells and ECs in BCa tissue, which was the aim of the present study. Methods: In the present study, immunohistochemical staining is used for detecting the distribution of ECs in BCa tissue, and we use SPSS 19 to analysis the relationship between ECs distribution and tumor grade/stage; inadition, co-curlturing of tumor cell with ECs is usd to mimicking the interaction of tumor cell with ECs, followed by Chamber Assay, BrdU incorporoartion, WB, Qt-PCR, ect, to investiatin the mechanism. Results: The distribution of ECs in BCa tissue is significantly increased according to BCa grade and negatively associated to the time from BCa diagnosis to progression, manifesting as an independent risk factor for BCa prognosis. The following in vitro experiment indicates that the conditional medium from co-culture of tumor cells (T24/J82) with ECs (human umbilical vein endothelial cells, which were used as ECs in the in vitro experiment) contributes to the activation of the NF-ĸB signaling pathway in tumor cells, leading to the upregulation of CXCL1/8. This further results in enhanced tumor cell malignancy and EC recruitment, manifested as a positive feedback loop. Conclusions: The present study provided a further understanding on the role of ECs in BCa progression—not only by angiogenesis but also by interacting with tumor cell dirctly.
Immune Gene Prognostic Signature for Disease Free Survival of Gastric Cancer: Translational Research of an Artificial Intelligence Survival Predictive System
Authors: Zhang Zhiqiao , He Tingshan , Huang Liwen , Li Jing , Wang Peng
Published: August 2020

Background: The progress of artificial intelligence algorithms and massive data provide new ideas and choices for individual mortality risk prediction for cancer patients. The current research focused on depict immune gene related regulatory network and develop an artificial intelligence survival predictive system for disease free survival of gastric cancer. Methods: Multi-task logistic regression algorithm, Cox survival regression algorithm, and Random survival forest algorithm were used to develop the artificial intelligence survival predictive system.Results: Nineteen transcription factors and seventy immune genes were identified to construct a transcription factor regulatory network of immune genes. Multivariate Cox regression identified fourteen immune genes as prognostic markers. These immune genes were used to construct a prognostic signature for gastric cancer. Concordance indexes were 0.800, 0.809, and 0.856 for 1-, 3- and 5- year survival. An interesting artificial intelligence survival predictive system was developed based on three artificial intelligence algorithms for gastric cancer. Gastric cancer patients with high risk score have poor survival than patients with low risk score.Conclusions: The current study constructed a transcription factor regulatory network and developed two artificial intelligence survival prediction tools for disease free survival of gastric cancer patients. These artificial intelligence survival prediction tools are helpful for individualized treatment decision.
Dual species dynamic transcripts reveal the interaction mechanisms between Chrysanthemum morifolium and Alternaria alternata
Authors: Liu Lina , Chen Fadi , Chen Sumei , Fang Weimin , Liu Ye , Guan Zhiyong
Published: August 2020

Background
Chrysanthemum (C. morifolium) black spot disease caused by Alternaria alternata is one of the plant’s most destructive diseases. Dual RNA-seq was performed to simultaneously assess their transcriptomes to analyze the potential interaction mechanism between the two species, i.e., host and pathogen.
Results
C. morifolium and A. alternata were subjected to dual RNA-seq at 1, 12, and 24 hours after inoculation, and differential expression genes (DEGs) in both species were identified. This analysis confirmed 153,532 DEGs in chrysanthemum and 14,932 DEGs in A. alternata, that were involved in plant-fungal interactions and phytohormone signaling. Fungal DEGs such as toxin synthesis related enzyme and cell wall degrading enzyme genes played important roles during chrysanthemum infecton. Moreover, a series of key genes highly correlated with the early, middle, or late infection stage was identified, together with the regulatory network of key genes annotated in PRG or PPI databases. Highly correlated genes were identified at the late infection stage, expanding our understanding of the interplay between C. morifolium and A. alternata. Additionally, six DEGs each from chrysanthemum and A. alternata were selected for qRT-PCR assays to validate the RNA-seq output.
Conclusions
Collectively, data obtained in this study enriches the resources available for research into the interactions that exist between chrysanthemum and A. alternata, thereby providing a theoretical basis for the development of new chrysanthemum varieties with resistance to pathogen.