bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function
Authors: Cho Youngkyung , Kim Sang Bum , Kim Jiyoon , Pham An Vuong Quynh , Yoon Min Ji , Park Jeong Hwan , Hwang Ki-Tae , Park Dongeun , Cho Yongcheol , Kim Moon Gyo , Kim Chungho 
Published: June 2020

Abstract
Background
Epithin/PRSS14, a type II transmembrane serine protease, is an emerging target of cancer therapy because of its critical roles in tumor progression and metastasis. In many circumstances, the protease, through its ectodomain shedding, exists as a soluble form and performs its proteolytic functions in extracellular environments increasing cellular invasiveness. The seemingly functional integrity of the soluble form raises the question of why the protease is initially made as a membrane-associated protein.

Results
In this report, we show that the epithin/PRSS14 intracellular domain (EICD) can be released from the membrane by the action of signal peptide peptidase-like 2b (SPPL2b) after ectodomain shedding. The EICD preferentially localizes in the nucleus and can enhance migration, invasion, and metastasis of epithelial cancer when heterologously expressed. Unbiased RNA-seq analysis and subsequent antibody arrays showed that EICD could control the gene expression of chemokines involved in cell motility, by increasing their promoter activities. Finally, bioinformatics analysis provided evidence for the clinical significance of the intramembrane proteolysis of epithin/PRSS14 by revealing that the poor survival of estrogen receptor (ER)-negative breast cancer patients with high epithin/PRSS14 expression is further worsened by high levels of SPPL2b.

Conclusions
These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment.
Routine data for malaria morbidity estimation in Africa: challenges and prospects
Authors: Alegana Victor A. , Okiro Emelda A. , Snow Robert W. 
Published: June 2020

Abstract
Background
The burden of malaria in sub-Saharan Africa remains challenging to measure relying on epidemiological modelling to evaluate the impact of investments and providing an in-depth analysis of progress and trends in malaria response globally.
In malaria-endemic countries of Africa, there is increasing use of routine surveillance data to define national strategic targets, estimate malaria case burdens and measure control progress to identify financing priorities. Existing research focuses mainly on the strengths of these data with less emphasis on existing challenges and opportunities presented.

Conclusion
Here we define the current imperfections common to routine malaria morbidity data at national levels and offer prospects into their future use to reflect changing disease burdens.
Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020
Authors: Tariq Amna , Lee Yiseul , Roosa Kimberlyn , Blumberg Seth , Yan Ping , Ma Stefan , Chowell Gerardo 
Published: June 2020

AbstractBackgroundAs of March 31, 2020, the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued.MethodsHere we estimate the effective reproduction number,Rt, of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts.ResultsThe local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI 0.3, 1.0) during the first transmission wave by February 14, 2020, while the overall R based on the cluster size distribution as of March 17, 2020, was estimated at 0.6 (95% CI 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test,p < 0.001).ConclusionThe trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.
Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicenter nested case-control study
Authors: Shi Jichan , Li Yang , Zhou Xian , Zhang Qiran , Ye Xinchun , Wu Zhengxing , Jiang Xiangao , Yu Hongying , Shao Lingyun , Ai Jing-Wen , Zhang Haocheng , Xu Bin , Sun Feng , Zhang Wenhong 
Published: June 2020

Abstract
Background
Coronavirus disease 2019 (COVID-19) has infected more than 4 million people within 4 months. There is an urgent need to properly identify high-risk cases that are more likely to deteriorate even if they present mild diseases on admission.

Methods
A multicenter nested case-control study was conducted in four designated hospitals in China enrolling confirmed COVID-19 patients who were mild on admission. Baseline clinical characteristics were compared between patients with stable mild illness (stable mild group) and those who deteriorated from mild to severe illness (progression group).

Results
From Jan 17, 2020, to Feb 1, 2020, 85 confirmed COVID-19 patients were enrolled, including 16 in the progression group and 69 in the stable mild group. Compared to stable mild group (n = 69), patients in the progression group (n = 16) were more likely to be older, male, presented with dyspnea, with hypertension, and with higher levels of lactase dehydrogenase and c-reactive protein. In multivariate logistic regression analysis, advanced age (odds ratio [OR], 1.012; 95% confidence interval [CI], 1.020–1.166; P = 0.011) and the higher level of lactase dehydrogenase (OR, 1.012; 95% CI, 1.001–1.024; P = 0.038) were independently associated with exacerbation in mild COVID-19 patients.

Conclusion
Advanced age and high LDH level are independent risk factors for exacerbation in mild COVID-19 patients. Among the mild patients, clinicians should pay more attention to the elderly patients or those with high LDH levels.
Exploiting bacterial outer membrane vesicles as a cross-protective vaccine candidate against avian pathogenic Escherichia coli (APEC)
Authors: Hu Rujiu , Li Jing , Zhao Yuezhen , Lin Hua , Liang Liu , Wang Mimi , Liu Haojing , Min Yuna , Gao Yupeng , Yang Mingming 
Published: June 2020

Abstract
Background
The well-known fact that avian pathogenic Escherichia coli (APEC) is harder to prevent due to its numerous serogroups has promoted the development of biological immunostimulatory materials as new vaccine candidates in poultry farms. Bacterial outer membrane vesicles (OMVs), known as spherical nanovesicles enriched with various immunostimulants, are naturally secreted by Gram-negative bacteria, and have gained much attention for developing effective vaccine candidates. Recent report has demonstrated that OMVs of APEC O78 can induce protective immunity in chickens. Here, a novel multi-serogroup OMVs (MOMVs) vaccine was developed to achieve cross-protection against APEC infection in broiler chickens.

Results
In this study, OMVs produced by three APEC strains were isolated, purified and prepared into MOMVs by mixing these three OMVs. By using SDS-PAGE and LC–MS/MS, 159 proteins were identified in MOMVs and the subcellular location and biological functions of 20 most abundant proteins were analyzed. The immunogenicity of MOMVs was evaluated, and the results showed that MOMVs could elicit innate immune responses, including internalization by chicken macrophage and production of immunomodulatory cytokines. Vaccination with MOMVs induced specific broad-spectrum antibodies as well as Th1 and Th17 immune responses. The animal experiment has confirmed that immunization with an appropriate dose of MOMVs could not cause any adverse effect and was able to reduce bacteria loads and pro-inflammatory cytokines production, thus providing effective cross-protection against lethal infections induced by multi-serogroup APEC strains in chickens. Further experiments indicated that, although vesicular proteins were able to induce stronger protective efficiency than lipopolysaccharide, both vesicular proteins and lipopolysaccharide are crucial in MOMVs-mediated protection.

Conclusions
The multi-serogroup nanovesicles produced by APEC strains will open up a new way for the development of next generation vaccines with low toxicity and broad protection in the treatment and control of APEC infection.
DSG2 expression is correlated with poor prognosis and promotes early-stage cervical cancer
Authors: Qin Shuhang , Liao Yuandong , Du Qiqiao , Wang Wei , Huang Jiaming , Liu Pan , Shang Chunliang , Liu Tianyu , Xia Meng , Yao Shuzhong 
Published: June 2020

Abstract
Background
The pathogenesis and developmental mechanism of early-stage (FIGO 2009 IA2-IIA2) cervical cancer (CC) remain unclear. Seeking novel molecular biomarkers based on The Cancer Genome Atlas (TCGA) will facilitate the understanding of CC pathogenesis and help evaluate early-stage CC prognosis.

Methods
To identify prognosis-related genes in early-stage CC, we analyzed TCGA mRNA-seq data and clinical data by univariate Cox and Kaplan–Meier plotter analyses. Differential expression analysis identified upregulated genes in early-stage CC. Combined with the genes correlated with unfavorable prognosis, we selected desmoglein-2 (DSG2) for further investigation. To detect DSG2 expression in early-stage CC, we used immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and western blotting. The relationship between the expression of DSG2 and clinical features was analyzed by the Chi square test. Cox analysis was applied to assess the relationship between CC overall survival (OS) and risk factors. The correlations between DSG2 expression and CC cell line proliferation and migration were investigated with Cell Counting Kit-8 (CCK-8) and migration assays.

Results
There were 416 prognosis-related genes in early-stage CC. DSG2, matrix metallopeptidase 1 (MMP1), carbonic anhydrase IX (CA9), homeobox A1 (HOXA1), and serine protease inhibitor B3 (SERPINB3) were upregulated in early-stage CC compared with adjacent noncancerous tissue (ANT) and correlated with unfavorable prognosis. Among them, DSG2 was most significantly correlated with patient survival. Coexpression analysis indicated that DSG2 was probably involved in cell division, positive regulation of transferase activity, positive regulation of cell migration, EGFR upregulation pathway and regulation of lymphangiogenesis. IHC, qRT-PCR and western blotting showed that DSG2 expression was higher in CC than in normal tissue. Significant correlations were identified between DSG2 expression and several aggressive clinical features, including pelvic lymph node metastasis (PLNM). Multivariate Cox analysis showed that DSG2 and PLNM were independent prognostic factors for OS. DSG2 knockdown inhibited CC cell proliferation and migration.

Conclusions
DSG2 is a biomarker that promotes tumor proliferation and metastasis and is correlated with poor prognosis in early-stage CC.
Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma
Authors: Lv Lei , Zhao Yujia , Wei Qinqin , Zhao Ye , Yi Qiyi 
Published: June 2020

AbstractBackgroundHydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6), a key protein involved in synthetizing dihydrotestosterone, is abundant in the liver. Previous studies have suggested a role for dihydrotestosterone in modulating progress of various malignancies, and HSD17B6 dysfunction was associated with lung cancer and prostate cancer. However, little is known about the detailed role of HSD17B6 in hepatocellular carcinoma (HCC).MethodsClinical implication and survival data related to HSD17B6 expression in patients with HCC were obtained through TCGA, ICGC, ONCOMINE, GEO and HPA databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The ChIP-seq data were obtained from Cistrome DB. Protein–Protein Interaction and gene functional enrichment analyses were performed in STRING database. The correlations between HSD17B6 and tumor immune infiltrates was investigated via TIMER and xCell. The proliferation, migration and invasion of liver cancer cells transfected with HSD17B6 were evaluated by the CCK8 assay, wound healing test and transwell assay respectively. Expression of HSD17B6, TGFB1 and PD-L1 were assessed by quantitative RT-PCR.ResultsHSD17B6 expression was lower in HCC compared to normal liver and correlated with tumor stage and grade. Lower expression of HSD17B6 was associated with worse OS, PFS, RFS and DSS in HCC patients. HNF4A bound to enhancer and promoter regions of HSD17B6 gene, activating its transcription, and DNA methylation of HSD17B6 promoter negatively controlled the expression. HSD17B6 and its interaction partners were involved in androgen metabolism and biosynthesis in liver. HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infiltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1.ConclusionsThis study indicate that HSD17B6 could be a new biomarker for the prognosis of HCC and an important negative regulator of immune responses in HCC.
Circular RNA and tumor microenvironment
Authors: Song Huixin , Liu Qiaofei , Liao Quan 
Published: June 2020

AbstractCircular RNAs (circRNAs) are small non-coding RNAs with a unique ring structure and play important roles as gene regulators. Disturbed expressions of circRNAs is closely related to varieties of pathological processes. The roles of circRNAs in cancers have gained increasing concerns. The communications between the cancer cells and tumor microenvironment (TME) play complicated roles to affect the malignant behaviors of cancers, which potentially present new therapeutic targets. Herein, we reviewed the roles of circRNAs in the TME.
The fiber metabolite butyrate reduces gp130 by targeting TRAF5 in colorectal cancer cells
Authors: Yuan Yin , Li Bo , Kuang Yanbin , Ni Shuo , Zhuge Aoxiang , Yang Jing , Lv Longxian , Gu Silan , Yan Ren , Li Yating , Wang Kaicen , Yang Liya , Zhu Xueling , Wu Jingjing , Bian Xiaoyuan , Li Lanjuan 
Published: June 2020

Abstract
Background
Dietary fiber is effective for colorectal cancer (CRC) treatment. Interleukin-6 (IL-6) and its adaptors are potential targets for CRC therapy. Butyrate, a metabolite of dietary fiber, is a new, highly safe type of targeted drug.

Methods
In this study, Cell Counting Kit-8 cell viability and wound healing assays, western blot analysis, immunofluorescence staining, and xenograft tumor mouse models were used to evaluate the anticancer effect of butyrate and its possible mechanism in vivo and in vitro.

Results
Dietary fiber and sodium butyrate (NaB) decreased CRC burden by decreasing IL-6 receptor gp130 and blocking IL-6/JAK2/STAT3 axis activation in vitro and in vivo. Furthermore, NaB reduced the gp130 protein level by regulating its degradation rate via targeting TRAF5.

Conclusions
The fiber metabolite butyrate inhibits CRC development by reducing gp130 via TRAF5.
Impacts of skull stripping on construction of three-dimensional T1-weighted imaging-based brain structural network in full-term neonates
Authors: Wang Geliang , Hu Yajie , Li Xianjun , Wang Miaomiao , Liu Congcong , Yang Jian , Jin Chao 
Published: June 2020

AbstractBackgroundSkull stripping remains a challenge for neonatal brain MR image analysis. However, little is known about the accuracy of how skull stripping affects the neonatal brain tissue segmentation and subsequent network construction. This paper therefore aimed to clarify this issue by comparing two automatic (FMRIB Software Library’s Brain Extraction Tool, BET; Infant Brain Extraction and Analysis Toolbox, iBEAT) and a semiautomatic (iBEAT with manual correction) processes in constructing 3D T1-weighted imaging (T1WI)-based brain structural network.MethodsTwenty-two full-term neonates (gestational age, 37–42 weeks; boys/girls, 13/9) without abnormalities on MRI who underwent brain 3D T1WI were retrospectively recruited. Two automatic (BET and iBEAT) and a semiautomatic preprocessing (iBEAT with manual correction) workflows were separately used to perform the skull stripping. Brain tissue segmentation and volume calculation were performed by a Johns Hopkins atlas-based method. Sixty-four gray matter regions were selected as nodes; volume covariance network and its properties (clustering coefficient,Cp; characteristic path length,Lp; local efficiency,Elocal; global efficiency,Eglobal) were calculated by GRETNA. Analysis of variance (ANOVA) was used to compare the differences in the calculated volume between three workflows.ResultsThere were significant differences in volumes of 50 brain regions between the three workflows (P < 0.05). Three neonatal brain structural networks presented small-world topology. The semiautomatic workflow showed remarkably decreased Cp, increased Lp, decreasedElocal, and decreasedEglobal, in contrast to the two automatic ones.ConclusionsImperfect skull stripping indeed affected the accuracy of brain structural network in full-term neonates.
Automatic group-wise whole-brain short association fiber bundle labeling based on clustering and cortical surface information
Authors: Vázquez Andrea , López-López Narciso , Houenou Josselin , Poupon Cyril , Mangin Jean-François , Ladra Susana , Guevara Pamela 
Published: June 2020

Abstract
Background
Diffusion MRI is the preferred non-invasive in vivo modality for the study of brain white matter connections. Tractography datasets contain 3D streamlines that can be analyzed to study the main brain white matter tracts. Fiber clustering methods have been used to automatically group similar fibers into clusters. However, due to inter-subject variability and artifacts, the resulting clusters are difficult to process for finding common connections across subjects, specially for superficial white matter.

Methods
We present an automatic method for labeling of short association bundles on a group of subjects. The method is based on an intra-subject fiber clustering that generates compact fiber clusters. Posteriorly, the clusters are labeled based on the cortical connectivity of the fibers, taking as reference the Desikan–Killiany atlas, and named according to their relative position along one axis. Finally, two different strategies were applied and compared for the labeling of inter-subject bundles: a matching with the Hungarian algorithm, and a well-known fiber clustering algorithm, called QuickBundles.

Results
Individual labeling was executed over four subjects, with an execution time of 3.6 min. An inspection of individual labeling based on a distance measure showed good correspondence among the four tested subjects. Two inter-subject labeling were successfully implemented and applied to 20 subjects and compared using a set of distance thresholds, ranging from a conservative value of 10 mm to a moderate value of 21 mm. Hungarian algorithm led to a high correspondence, but low reproducibility for all the thresholds, with 96 s of execution time. QuickBundles led to better correspondence, reproducibility and short execution time of 9 s. Hence, the whole processing for the inter-subject labeling over 20 subjects takes 1.17 h.

Conclusion
We implemented a method for the automatic labeling of short bundles in individuals, based on an intra-subject clustering and the connectivity of the clusters with the cortex. The labels provide useful information for the visualization and analysis of individual connections, which is very difficult without any additional information. Furthermore, we provide two fast inter-subject bundle labeling methods. The obtained clusters could be used for performing manual or automatic connectivity analysis in individuals or across subjects.
Salutogenic model of health to identify turning points and coping styles for eating practices in type 2 diabetes mellitus
Authors: Polhuis C. M. M. , Vaandrager L. , Soedamah-Muthu S. S. , Koelen M. A. 
Published: June 2020

Abstract
Background
It is important for people with Type 2 Diabetes Mellitus (T2DM) to eat healthily. However, implementing dietary advice in everyday life is difficult, because eating is not a distinguishable action, but a chain of activities, embedded in social practices and influenced by previous life experiences. This research aims to understand why and how eating practices are developed over the life-course by investigating influential life experiences – turning points – and coping strategies for eating practices of people with T2DM.

Methods
The Salutogenic Model of Health guided the study’s objective, study design and analysis. Seventeen interviews were performed and analysed based on the principles of interpretative phenomenological analysis. Narrative inquiry and the creation of timelines and food boxes were used as tools to facilitate reflection on turning points and eating practices.

Results
Turning points for unhealthier eating were experiences that strongly disturbed the participants’ emotional stability. These experiences included psychosocial trauma, physical health disorders, job loss, and smoking cessation. Turning points for healthier eating were experiences that significantly changed participants views on life and made participants reflective about the effects of current eating practices on future health and life goals. These turning points included confrontation with ill-health, becoming a parent, psychosocial therapy, and getting married. Notably, turning points for healthier eating seemed only to happen when life was relatively stress-free. All participants experienced turning points for healthier eating, yet, not all participants succeeded in improving their diets. Two coping styles were distinguished: active and passive coping. Active coping individuals were able to act in line with their personal intentions, whereas passive coping individuals could not. Differences between active and passive coping styles seemed to be explained by differences in available resources important for adapting and maintaining a healthy diet.

Conclusion
Disadvantaged childhood and later life adversities together with the inability to manage the mental stress explained the development unhealthier eating practices. All participants experienced turning points for healthier eating that caused eating to become a priority in their life. Yet, the fact that not all were able to eat as they intended, advocates for nutritional guidance for people with T2DM, with a greater emphasis on reflexivity, psycho-social well-being and social support.