bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fault System-Based Probabilistic Seismic Hazard Assessment of a Moderate Seismicity Region: The Eastern Betics Shear Zone (SE Spain)
Authors: Gómez-Novell Octavi , García-Mayordomo Julián , Ortuño María , Masana Eulàlia , Chartier Thomas 
Published: December 2020

Including faults as seismogenic sources in probabilistic seismic hazard assessments (PSHA) has turned into a common practice as knowledge of active faults is improving. Moreover, the occurrence of earthquakes in multi-fault ruptures has evidenced the need to understand faults as interacting systems rather than independent sources. We present a PSHA for the Southeastern Spain obtained by including the faults of a moderate seismicity region, the Eastern Betics Shear Zone (EBSZ) in SE Spain, as the main seismogenic sources in two separate source models, one considering background seismicity. In contrast with previous studies in Spain, earthquake occurrence of the EBSZ system is modeled considering different hypotheses of multi-fault ruptures at the whole fault system scale and weighted in a logic tree. We compare the hazard levels with those from an area source PSHA and a previous fault-based approach. The results show a clear control of the EBSZ faults in the seismic hazard for all return periods, increasing drastically the hazard levels in the regions close to the fault traces and influencing up to 20 km farther with respect to the area source PSHA. The seismic hazard is dependent on the fault slip rates as peak ground accelerations and territorial extension of the fault influence appear higher around the Alhama de Murcia and Carboneras faults, while lower slip rate faults (Palomares Fault) show minor contribution to the hazard. For the return period of 475 years and near-fault locations, our models are more consistent with the ground motion values reached in the 2011 Mw 5.2 Lorca event than the building code or national seismic hazard map, which suggest that our fault system-based model performs more accurate estimations for this return period. Fault data, mainly slip rates, and its uncertainties have a clear impact on the seismic hazard and, for some faults, the lack of detailed paleoseismic studies can compromise the reliability of the hazard estimations. This, together with epistemic uncertainties concerning the background seismicity, are key discussion points in the present study, having an impact on further research and aiming to serve as a case example for other low-to-moderate seismicity regions worldwide.
Identification of Hub Prognosis-Associated Oxidative Stress Genes in Pancreatic Cancer Using Integrated Bioinformatics Analysis
Authors: Qiu Xin , Hou Qin-Han , Shi Qiu-Yue , Jiang Hai-Xing , Qin Shan-Yu 
Published: December 2020

BackgroundIntratumoral oxidative stress (OS) has been associated with the progression of various tumors. However, OS has not been considered a candidate therapeutic target for pancreatic cancer (PC) owing to the lack of validated biomarkers.MethodsWe compared gene expression profiles of PC samples and the transcriptome data of normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to identify differentially expressed OS genes in PC. PC patients’ gene profile from the Gene Expression Omnibus (GEO) database was used as a validation cohort.ResultsA total of 148 differentially expressed OS-related genes in PC were used to construct a protein-protein interaction network. Univariate Cox regression analysis, least absolute shrinkage, selection operator analysis revealed seven hub prognosis-associated OS genes that served to construct a prognostic risk model. Based on integrated bioinformatics analyses, our prognostic model, whose diagnostic accuracy was validated in both cohorts, reliably predicted the overall survival of patients with PC and cancer progression. Further analysis revealed significant associations between seven hub gene expression levels and patient outcomes, which were validated at the protein level using the Human Protein Atlas database. A nomogram based on the expression of these seven hub genes exhibited prognostic value in PC.ConclusionOur study provides novel insights into PC pathogenesis and provides new genetic markers for prognosis prediction and clinical treatment personalization for PC patients.
Four Immune-Related Long Non-coding RNAs for Prognosis Prediction in Patients With Hepatocellular Carcinoma
Authors: Li Muqi , Liang Minni , Lan Tian , Wu Xiwen , Xie Wenxuan , Wang Tielong , Chen Zhitao , Shen Shunli , Peng Baogang 
Published: December 2020

BackgroundLong non-coding RNA (LncRNA) plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). This study aims to establish an immune-related LncRNA model for risk assessment and prognosis prediction in HCC patients.MethodsHepatocellular carcinoma patient samples with complete clinical data and corresponding whole transcriptome expression were obtained from the Cancer Genome Atlas (TCGA). Immune-related genes were acquired from the Gene Set Enrichment Analysis (GSEA) website and matched with LncRNA in the TCGA to get immune-related LncRNA. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for screening the candidate LncRNAs and calculating the risk coefficient to establish the prognosis model. Patients were divided into a high-risk group and a low-risk group depending on the median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort. GSEA and principal component analysis were used for function evaluation.ResultsA total of 319 samples met the screening criteria and were randomly distributed across the training cohort and the validation cohort. After comparison with the IMMUNE_RESPONSE gene set and the IMMUNE_SYSTEM_PROCESS gene set, a total of 3094 immune-related LncRNAs were screened. Ultimately, four immune-related LncRNAs were used to construct a formula using LASSO regression. According to the formula, the low-risk group showed a higher survival rate than the high-risk group in the validation cohort and the whole cohort. The receiver operating characteristic curves data demonstrated that the risk score was more specific than other traditional clinical characteristics in predicting the 5-year survival rate for HCC.ConclusionThe four-immune-related-LncRNA model can be used for survival prediction in HCC and guide clinical therapy.
Have I Been Here? Sense of Location in People With Alzheimer's Disease
Authors: Pai Ming-Chyi , Jan Shau-Shiun 
Published: December 2020

Background: When navigating in a particular space, a sense of being at a current location is of great help for the navigators in reaching their destination or getting back to the start. To accomplish this work, interwoven neural structures and neurons are called into play. This system is called the heading direction cell-place cell-grid cell circuit. Evidence from various neuroscience studies has revealed that the regions responsible for this circuit are damaged in the early stages of Alzheimer's disease (AD). This may explain why wayfinding difficulty is one of the most frequent symptoms in persons with AD. The aim of this study was to examine the sense of location (SoL) in persons with mild AD, persons with prodromal AD (prAD), and those who were cognitively unimpaired (CU).Methods: We invited people with mild AD, prAD, and CU to participate in this study. The venue of the core experiment to assess SoL was a 660-m path located on the university campus. The participants were instructed to take a walk on the path and press a device to indicate their arrival at each of the five carefully chosen targets. The linear deviations from the target site were compared among the groups.Results: A total of 20 AD, 28 prAD, and 29 CU persons completed the study. Their Mini-Mental State Examination scores were on average 20 (SD 3), 24 (SD 3), and 28 (SD 2). The groups were well differentiated regarding several measurements for cognitive ability and spatial navigation. As for the SoL, the hit rates of exact location with linear deviation of 16 m or less were 0.05, 0.54, and 0.86 for AD, prAD, and CU persons, respectively. The hit rates were well correlated with the presence of getting lost. Also, SoL differentiated well among CU, PrAD, and AD in terms of average linear deviation.Conclusions: Our employing linear deviation by utilizing a grid-cell function device as an assessment for SoL showed distinct features among the three groups. This model can be used to develop more delicate devices or instruments to detect, monitor, and aid spatial navigation in persons with prAD and AD.
Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism
Authors: Lucchini Roberto G. , Guazzetti Stefano , Renzetti Stefano , Broberg Karin , Caci Margherita , Covolo Loredana , Crippa Patrizia , Gelatti Umberto , Hashim Dana , Oppini Manuela , Pepe Fulvio , Pilotto Andrea , Passeri Chiara , Placidi Donatella , Rizzetti Maira Cristina , Turla Marinella , Wahlberg Karin , Padovani Alessandro 
Published: December 2020

Objective: In the province of Brescia, Italy, historical neurotoxic metal exposure has occurred for several decades. This study aimed to explore the role of metal exposure and genetics on Parkinson's Disease (PD) and Parkinsonism.Methods: Cases were enrolled from four local clinics for movement disorders. Randomly selected controls non-affected by neurological or psychiatric conditions were enrolled from the same health centers keeping a similar gender ratio and age distribution as for cases. Data on sociodemographic variables, clinical onset and life habits were collected besides accurate occupational and residential history. Blood samples were collected from all participants for genotyping of target polymorphisms in genes linked to PD and/or metal transport.Results: A total number of 432 cases and 444 controls were enrolled in the study, with average age of 71 years (72.2 for cases and 70 for controls). The average age at diagnosis was 65.9 years (SD 9.9). Among the potential risk factors, family history of PD or Parkinsonism showed the strongest association with the diseases (OR = 4.2, 95% CI 2.3, 7.6 on PD; OR = 4.3, 95% CI 1.9, 9.5 for Parkinsonism), followed by polymorphism rs356219 in the alpha-synuclein (SNCA) gene (OR = 2.03, 95% CI 1.3, 3.3 for CC vs. TT on PD; OR = 2.5, 95% CI 1.1, 5.3 for CC vs. TT on Parkinsonism), exposure to metals (OR = 2.4;, 95% CI 1.3, 4.2 on PD), being born in a farm (OR = 1.8; 95% CI 1.1, 2.8 on PD; OR = 2.6; 95% CI 1.4, 4.9 on Parkinsonism) and being born in the province of Brescia (OR = 1.7; 95% CI 1.0, 2.9 on PD). Conditional OR of having PD depending by SNCA polymorphism and metal exposure highlights higher risk of PD among CC SNCA carriers and being exposed to metals. However, the interaction term was not statistically significant.Conclusions: Lifetime exposure to metals and genetic variation in SNCA gene are relevant determinants of PD and Parkinsonism in the highly industrialized area of Brescia, Italy. The lack of evidence of statistical interaction between environmental and genetic factors may be due to the low frequencies of subjects representing the exposure categories and the polymorphism variants and does not rule out the biological interaction.
Tissue-Type Plasminogen Activator and Tenecteplase-Mediated Increase in Blood Brain Barrier Permeability Involves Cell Intrinsic Complement
Authors: Keragala Charithani B. , Woodruff Trent M. , Liu Zikou , Niego Be'eri , Ho Heidi , McQuilten Zoe , Medcalf Robert L. 
Published: December 2020

Background: Tissue-type plasminogen activator (t-PA) has been the mainstay of therapeutic thrombolysis for patients with acute ischaemic stroke (AIS). However, t-PA can cause devastating intracerebral hemorrhage. t-PA can also influence the CNS in part by modulation of BBB permeability. Complement activation also occurs after AIS and has also been reported to increase BBB permeability. The complement components, C3 and C5, can also be activated by t-PA via plasmin formation and cell intrinsic complement may be involved in this process. Tenecteplase (TNK-tPA) is a t-PA variant with a longer plasma half-life, yet the ability of TNK-tPA to modulate the BBB and complement is less clear.Aim: To evaluate the effect of C5 and C5a-receptor 1 (C5aR1) inhibitors on t-PA- and TNK-tPA-mediated opening of the BBB.Methods: We used an in vitro model of the BBB where human brain endothelial cells and human astrocytes were co-cultured on the opposite sides of a porous membrane assembled in transwell inserts. The luminal (endothelial) compartment was stimulated with t-PA or TNK-tPA together with plasminogen, in the presence of PMX205 (a non-competitive C5aR1 antagonist), Avacopan (a competitive C5aR1 antagonist) or Eculizumab (a humanized monoclonal inhibitor of human C5). BBB permeability was assessed 5 and 24 h later. Immunofluorescence was also used to detect changes in C5 and C5aR1 expression in endothelial cells and astrocytes.Results: PMX205, but not Avacopan or Eculizumab, blocked t-PA-mediated increase in BBB permeability at both the 5 and 24 h time points. PMX205 also blocked TNK-tPA-mediated increase in BBB permeability. Immunofluorescence analysis revealed intracellular staining of C5 in both cell types. C5aR1 expression was also detected on the cell surfaces and also located intracellularly in both cell types.Conclusion: t-PA and TNK-tPA-mediated increase in BBB permeability involves C5aR1 receptor activation from cell-derived C5a. Selective inhibitors of C5aR1 may have therapeutic potential in AIS.
Reconstruction of Immune Microenvironment and Signaling Pathways in Endometrioid Endometrial Adenocarcinoma During Formation of Lymphovascular Space Involvement and Lymph Node Metastasis
Authors: Cheng Yuan , Zhang Xiaobo , Wang Zhiqi , Wang Jianliu 
Published: December 2020

BackgroundThe amplification or mutation of oncogenes and escape from immune surveillance systems promote tumor metastasis. However, subtle changes in the immune microenvironment and signaling pathways are poorly understood during the formation of lymphovascular space involvement (LVSI) and lymph node (LN) metastasis of endometrioid endometrial adenocarcinoma (EEA).Patients and methodsWe detected tumor immunology-related signaling pathways and immunocyte subtypes according to the mRNA levels of 750 oncogenes and genes relating to the tumor microenvironment and immune response using the Nanostring PanCancer IO 360 Panel in 24 paraffin-embedded tissues of EEAs and benign gynecological diseases. Internal reference genes were used for data normalization.ResultsAngiogenesis and immune cell adhesion signaling pathways were activated during LVSI formation of EEA progression. However, during the development of LVSI to LN metastasis, immune system signaling pathways were significantly inhibited, including antigen presentation, cytotoxicity, lymphoid compartment, interferon signaling, and costimulatory signaling pathways. Immune-related genes (CD69, HLA-DOA, ATF3, GBP1, AP2, DTX3L, EGR1, GBP4, TAP1, EIF2AK2, MX1, ISG15, STAT1, and HLA-DRA) were significantly downregulated in EEA with LN metastasis compared to those in EEA with LVSI. Instead, hypoxia, metabolic stress, epigenetic regulation, matrix remodeling, and metastasis signaling pathways were continuously activated in LN metastasis. We also found that neutrophils, macrophages, and mast cells might be involved in LVSI formation and LN metastasis in EEA.ConclusionsEEA with metastatic LNs showed significant immunosuppressive effects. Some oncogenes, matrix remodeling- and hypoxia-related genes, and neutrophil signatures showed higher expression, suggesting their potential as therapeutic targets and offering new immunotherapy strategies in EEA during LN metastasis.
Acquisition, Divergence, and Personalization of the Female Perineal Microbiomes Are Driven by Developmental Milestones and Disrupted by Urinary Tract Infection: A Pilot Study
Authors: Lucas Elizabeth J. , Ching Christina B. , Saraswat Shweta , Dabdoub Shareef M. , Kumar Purnima P. , Justice Sheryl S. 
Published: December 2020

Introduction:The pediatric perineal microbiomes inhabit a dynamic environment with changes related to diet, toileting habits, and hormonal development. We hypothesized that next-generation sequencing would reveal different perineal bacterial signatures associated with developmental milestones in premenstrual females. Furthermore, we predicted that these microbial changes would be disrupted in premenstrual females with a history of urinary tract infection (UTI).Study Design:Healthy females were recruited at well-child visits. Subjects were divided into 4 developmental groups: (1) 0–3 month old newborns; (2) 4–10 month old infants transitioning to solid foods; (3) 2–6 year old toddlers peri-toilet training; and (4) 7–12 year old premenstrual girls. A separate group of females with a history of culture proven UTI and off antibiotics &gt;1 month was also recruited. DNA was isolated from swabs of the perineum and subjected to 16S rRNA sequencing. The diversity and species changes between developmental cohorts and age matched children with history of UTI was determined.Results:A total of 75 subjects were recruited: 15 in each group. There was a clear evolution of the perineal microbiomes with development. There was a significant microbial disruption in girls with a history of UTI, irrespective of developmental milestone age group. The periurethral/perivaginal site displayed greater changes in microbiome structure than other sites in girls with a history of UTI.Discussion:This pilot study evaluates the normal microbiome of the premenstrual girl at specific developmental milestones. Although the number of children per cohort was limited to 15, we observed statistical significance corresponding with developmental milestones. This study provides the first, culture independent delineation of the development of the perineal microbiome in girls. Furthermore, the sites closest to the site of infection appear to be more sensitive to antibiotic remodeling than those more distant. The factors that remodel the perineal microbiomes and predispose females, particularly girls, to UTIs (e.g., increase in uropathogen presence, absence of protective organisms) are unclear. Identification of specific signatures that increase susceptibility to UTI and their sequelae will improve patient care and promote personalized medicine.
Risk Factors Related to Operative Duration and Their Relationship With Clinical Outcomes in Pediatric Patients Undergoing Roux-en-Y Hepaticojejunostomy
Authors: Zhou Yongjun , Zhang Yunfei , Guo Hongjie , Zheng Chao , Guo Chunbao 
Published: December 2020

Background: Operative duration might be important for perioperative morbidity, and its involvement has not been fully characterized in pediatric patients. We identified perioperative variables associated with operative duration and determined their influence on clinical outcomes in pediatric patients.Methods: We retrospectively reviewed 701 patients who underwent elective removal of choledochal cysts followed by Roux-en-Y hepaticojejunostomy. The patients were separated into the long operative time group (&gt;165 min) and short operative time group (&lt;165 min) based on the median operative time (165 min). Propensity score matching was performed to adjust for any potential selection bias. The independent risk factors for operative time were determined using multivariable logistic regression analyses.Results: The operative time was often increased by excision difficulty caused by a larger choledochal cyst size (OR = 1.56; 95% CI, 1.09–2.23; p &lt; 0.001), a greater BMI (OR = 1.02; 95% CI, 1.00–1.15; p = 0.018), and older age (OR = 1.17; 95% CI, 1.02–1.39; p = 0.012) in the multivariate analysis. A long surgical duration was associated with delayed gastrointestinal functional recovery, as measured using the time to first defecation (p = 0.027) and first bowel movement (p = 0.019). Significantly lower levels of serum albumin were found in the long operative time group than in the short operative time group (p = 0.0035). The total length of postoperative hospital stay was longer in patients in the long operative time group (7.51 ± 2.03 days) than in those in the short operative time group (6.72 ± 1.54 days, p = 0.006).Conclusions: Our data demonstrated that a short operative time was associated with favorable postoperative results. The influencing factors of operative time should be ameliorated to achieve better outcomes.
Appendicitis in Children in a Large Italian COVID-19 Pandemic Area
Authors: La Pergola Enrico , Sgrò Alberto , Rebosio Federico , Vavassori Daniele , Fava Giorgio , Codrich Daniela , Montanaro Beatrice , Leva Ernesto , Schleef Jurgen , Cheli M. , Pelizzo Gloria , Gamba Piergiorgio , Alberti Daniele , Betalli Pietro 
Published: December 2020

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed the routine activities of pediatric surgical centers, and it determined the reduction of admissions in the pediatric emergency departments (PED). We reviewed the records of patients affected by acute appendicitis (AA) during the COVID-19 pandemic period in a large Italian COVID-19 pandemic area.Methods: Data regarding demographics, age, macroscopic and microscopic findings, and time between symptom onset and PED admission of patients affected by confirmed AA in the period between March and April 2020 were considered. The data were compared with those obtained during the same period of 2019, 2018, and 2017 in the included centers. Data were quoted as median (range) or absolute number. Non-parametric statistical tests were used to compare groups. A p ≤ 0.05 was regarded as significant. Since only anonymous data have been used and the data storage meets current data protection regulations, ethical committee approval was not required for this study.Results: Eighty-six patients underwent surgical appendectomy for AA between February 20th, 2020 and April 20th, 2020; 32.5% were complicated appendicitis and 67.5% were uncomplicated. Fifty-three patients were males and 33 were females. Patients' age ranged from 3 to 17 years and the median age was 10 years. The median time between the onset of symptoms and the admission in PED was 1.85 days. The average time between the symptom onset and PED admission was 1.8 days.Conclusions: Although fear from the COVID-19 pandemic determined a delayed diagnosis of serious pediatric diseases, the increasing prevalence and severity of AA were not demonstrated in the most COVID-19-affected areas of Italy.
Heart Rate Turbulence Predicts Survival Independently From Severity of Liver Dysfunction in Patients With Cirrhosis
Authors: Oyelade Tope , Canciani Gabriele , Bottaro Matteo , Zaccaria Marta , Formentin Chiara , Moore Kevin , Montagnese Sara , Mani Ali R. 
Published: December 2020

BackgroundReduced heart rate variability (HRV) is an independent predictor of mortality in patients with cirrhosis. However, conventional HRV indices can only be interpreted in individuals with normal sinus rhythm. In patients with recurrent premature ventricular complexes (PVCs), the predictive capacity of conventional HRV indices is compromised. Heart Rate Turbulence (HRT) represents the biphasic change of the heart rate after PVCs. This study was aimed to define whether HRT parameters could predict mortality in cirrhotic patients.Materials and Methods24 h electrocardiogram recordings were collected from 40 cirrhotic patients. Turbulence Onset was calculated as HRT indices. The enrolled patients were followed up for 12 months after the recruitment in relation to survival and/or transplantation.ResultsDuring the follow-up period, 21 patients (52.5%) survived, 12 patients (30%) died and 7 patients (17.5%) had liver transplantation. Turbulence Onset was found to be strongly linked with mortality on Cox regression (Hazard ratio = 1.351, p &lt; 0.05). Moreover, Turbulence Onset predicted mortality independently of MELD and Child-Pugh’s Score.ConclusionThis study provides further evidence of autonomic dysfunction in cirrhosis and suggests that HRT is reliable alternative to HRV in patients with PVCs.