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Current and emerging therapies for alcohol-associated hepatitis

Liver Research 2023年第1期7卷 35-46页

作者： Francisco Idalsoaga Gustavo Ayares Luis antonio Díaz Jorge Arnold María Ayala-Valverde David Hudson Marco Arrese juan Pablo Arab Department of Gastroenterology School of MedicinePontificia Universidad Catolica de ChileSantiagoChile Internal Medicine Service Hospital El PinoCritical Patient UnitClinica DavilaSantiagoChile Division of Gastroenterology Department of MedicineSchulich School of MedicineWestern University&London Health Sciences CentreLondonOntarioCanada Department of Epidemiology and Biostatistics Schulich School of MedicineWestern UniversityLondonOntarioCanada Alimentiv LondonOntarioCanada

Alcohol-related liver disease(ALD)encompasses a spectrum of diseases caused by excessive alcohol consumption.ALD includes hepatic steatosis,steatohepatitis,variable degrees of fibrosis,cirrhosis,and alcohol-associated hepatitis(AH),the latter being the most severe acute form of the disease.Severe AH is associated with high mortality(reaching up to 30%e50%)at 90 days.The cornerstone of ALD,and particularly AH,treatment continues to be abstinence,accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome(AWS).In severe AH with model for end-stage liver disease(MELD)score21,corticosteroids can be used,especially MELD score between 25 and 39,where the highest benefit is achieved.Other key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver transplantation.The development of new therapies based on the pathophysiology and mechanisms of liver injury are underway.This includes the modulation and management of the innate immune response,gut dysbiosis,bacterial translocation,and bacteria-derived products from the intestine.These hold promise for the future of AH treatment.

关键词： Alcohol-associated hepatitis(AH) Alcohol-related liver disease(ALD) Alcohol use disorder(AUD) AUD treatment Nutritional therapy Steroids therapy Cirrhosis Fibrosis

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Risk Factors Associated with Unsuccessful Vaginal Birth after One Cesarean (VBAC-1) in Puerto Rico

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Open Journal of Obstetrics and Gynecology 2024年第6期14卷 888-902页

作者： Irazú Guinan Marjorie Suárez Fabiola Angulo Luis Mayol Paula Suárez Lisandris Dominicci Nathalie Chang Saribel Torres antonio Rodríguez Raymond L. Tremblay Maricarmen Colón-Díaz Department of Physiology and Pathology San Juan Bautista School of Medicine Caguas USA

Background: Cesarean section (CS) has increased steadily over the last decade, with an estimated one-third of women delivering by cesarean section worldwide. Objective: Our study aimed to investigate the demographic and associated factors influencing vaginal birth after one cesarean (VBAC-1) success focusing on variables like pre-pregnancy BMI, diabetes, hypertension, education, and smoking. Study Design and Methods: In this retrospective study, we analyzed 285 cases (81 unsuccessful VBAC-1, 204 successful VBAC-1) from San juan City Hospital (Puerto Rico) between January 1, 2019, and December 31, 2020. We used odds ratios and model selection comparison to assess the impact of variables on successful VBAC-1, using a significance threshold of 95% CI. Model selection assessed binomial model combinations using a generalized linear approach to identify key risk factors. Results: Unsuccessful VBAC-1 (a repeat cesarean), was associated with diabetes (OR: 0.376, p = 0.086), hypertension (OR: 0.23, p = 0.006), and university-educated women (OR: 1.372, p = 0.711). High school-educated women had an OR of 3.966 (p = 0.105), while overweight women were 0.481 times more likely to have unsuccessful VBAC-1 (p = 0.041). Significant associations were not found with obesity (OR: 0.574, p = 0.122), underweight/normal (OR: 1.01, p = 0.810), or smoking (OR: 1.227, p = 0.990). Conclusion: Results revealed women with higher education levels, hypertension, or diabetes are less likely to have a successful VBAC-1. Understanding the complex interactions affecting these outcomes is aimed at establishing guidelines for healthcare professionals to conduct systematic risk/benefit assessments. This study lays a foundation for evidence-based practices and policies, offering initial insights into VBAC-1 success factors in Puerto Rico.

关键词： Diabetes Hypertension Obesity Trial of Labor Vaginal Birth after Cesarean

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COMPLEX SYSTEMS IN SPORTS:INTRODUCTION TO THE SPECIAL ISSUE

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Journal of Systems Science & Complexity 2013年第1期26卷 1-3页

作者： MERELO juan Julin MORA antonio M COTTA Carlos Depto.ATC CITICUniversidad de Granada Depto.LCC Universidad de Malaga

1 Complex Systems in Sports Sport is one of the most important activities of humanity.Its relevance goes beyond the physical/psychological benefits that their practicing provides(an aspect that justifies in itself its importance in our current society).In fact,be it as actually playing some sport or just watching some games,it provides a huge means for socialization and education.Needless to say,the economical viewpoint is also enormously relevant:events such as the Olympic Games。

关键词：复杂系统运动教育手段社会化

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New perspectives in occult hepatitis C virus infection

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World Journal of Gastroenterology 2012年第23期18卷 2887-2894页

作者： Vicente Carreño Javier Bartolomé Inmaculada Castillo juan antonio Quiroga Foundation for the Study of Viral Hepatitis C/Guzmán el Bueno 7228015 MadridSpain

Occult hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays, can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology. Occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection. Occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV. This occult infection has been reported also in healthy populations without evidence of liver disease. Occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma. Thus, anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylated-interferon plus ribavirin. The persistence of very low levels of HCV RNA in serum and in PBMCs, along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C, indicate that occult HCV is a persistent infection that is not spontaneously eradicated. This is an updated report on diagnosis, epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases.

关键词：丙型肝炎病毒病毒感染隐匿性外周血单个核细胞肝脏疾病抗病毒治疗 T细胞反应抗原特异性

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COVID-19 and Indirect Liver Injury:A Narrative Synthesis of the Evidence

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Journal of Clinical and Translational Hepatology 2021年第5期9卷 760-768页

作者： Francisco Idalsoaga Gustavo Ayares juan Pablo Arab Luis antonio Díaz Departamento de Gastroenterología Escuela de MedicinaPontificia Universidad Católica de ChileSantiagoChile Centro de Envejecimiento y Regeneración(CARE) Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)infection.The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase,with a prevalence of 16-53%among patients.Cases with severe coronavirus disease 2019(COVID-19)seem to have higher rates of acute liver dysfunction,and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization.Patients with chronic liver diseases also have a higher risk of severe disease and mortality(mainly seen in patients with metabolic-associated fatty liver disease).Several pathways of damage have been proposed in the liver involvement of COVID-19 patients;although,the end-cause is most likely multifactorial.Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection.This enzyme is expressed widely in cholangiocytes and less in hepatocytes.Other factors attributed to liver damage include drug-induced liver injury,uncontrolled release of proinflammatory molecules(“cytokine storm”),pneumonia-associated hypoxia,and direct damage by the infection.Hepatic steatosis,vascular thrombosis,fibrosis,and inflammatory features(including Kupffer cell hyperplasia)are the most common liver histopathological findings in deceased COVID-19 patients,suggesting important indirect mechanisms of liver damage.In this translational medicinebased narrative review,we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19,the histopathological findings,and the impact of these mechanisms in patients with chronic liver disease.

关键词： COVID-19 SARS-CoV-2 Liver hepatitis Liver injury Novel coronavirus

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Reconstruction of debris-flow activity in a temperate mountain forest catchment of central Mexico

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Journal of Mountain Science 2019年第9期16卷 2096-2109页

作者： Osvaldo FRANCO-RAMOS Markus STOFFEL juan antonio BALLESTEROS-CANOVAS Instituto de Geografia. Universidad NacionalAutonoma de Mexico Ciudad Universitaria Coyoacan 04510 Mexico Dendrolab.ch Department of Earth Sciences University of Geneva 13 rue des Maraichers CH-1205 Geneva Switzerland Climate Change Impacts and Risks in the Anthropocene (C-CIA) Institute for Environmental Sciences University of Geneva 66 Boulevard Carl-Vogt CH-1205 Geneva Switzerland Department F.-A. Forelfor Environmental and Aquatic Sciences University of Geneva 66 Boulevard Carl-Vogt CH- 1205 Geneva Switzerland

The use of dendrochronology to study and date geomorphic processes in volcanic environments is still incipient, even more so on the volcanic slopes covered by temperate forests in central Mexico. Mass movements, such as debris flows, often impact forest stands where they cause damage to individual trees, thereby generating growth disturbances(GD) in the tree-ring records. The identification and dating of GD enables reconstruction of the age of trees colonizing bare surfaces after major events, but also allows the assessment of the frequency or spatial distribution of past geomorphic process activity. Here we used increment cores from 65 Pinus leiophylla, Abies religiosa, and Alnus jorullensis trees growing in the Axal gorge, on the southern slopes of La Malinche volcano, to unravel past debris-flow activity both temporally and spatially. Based on the combination of GD records, a weighted tree response index(Wit), field evidence and hydrometeorological records, we reconstructed 23 debris flows since 1933.Interestingly, almost two-thirds of the reconstructed years with debris-flow activity in Axal gorge match with events recorded in Axaltzintle gorge located on the NE slopes of La Malinche. These findings suggest a regional triggering mechanism, most likely related to the occurrence of hurricanes. This research could be useful for disaster risk management of the La Malinche National Park.

关键词： Debris flows La Malinche volcano Dendrogeomorphology Temperate forest Hydrometeorological phenomena

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CRISPR/Cas9 editing of the polygalacturonase FaPG1 gene improves strawberry fruit firmness

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Horticulture Research 2023年第3期10卷 201-210页

作者： Gloria López-Casado Cristina Sánchez-Raya Pablo D.Ric-Varas Candelas Paniagua Rosario Blanco-Portales juan Muñoz-Blanco Sara Pose antonio J.Matas Jose A.Mercado Departamento de Botánica y Fisiología Vegetal Instituto de Hortofruticultura Subtropical y Mediterránea‘La Mayora’(IHSM-UMA-CSIC)Universidad de Málaga29071 MálagaSpain Departamento de Bioquímica y Biología Molecular Universidad de Córdoba14071CórdobaSpain

Firmness is one of the most important fruit quality traits in strawberries.The postharvest shelf life of this soft fruit is highly limited by the loss of firmness,where cell wall disassembly plays an important role.Previous studies demonstrated that the polygalacturonase FaPG1 has a key role in remodelling pectins during strawberry softening.In this study,FaPG1 knockout strawberry plants have been generated using the CRISPR/Cas9 system delivered via Agrobacterium tumefaciens.Ten independent lines,cv.“Chandler”,were obtained,and all of them were successfully edited as determined by PCR amplification and T7 endonuclease assay.The targeted mutagenesis insertion and deletion rates were analyzed using targeted deep sequencing.The percentage of edited sequences varied from 47%up to almost 100%,being higher than 95%for seven of the selected lines.Phenotypic analyses showed that 7 out of the eight lines analyzed produced fruits significantly firmer than the control,ranging from 33 to 70%increase in firmness.There was a positive relationship between the degree of FaPG1 editing and the rise in fruit firmness.Minor changes were observed in other fruit quality traits,such as colour,soluble solids,titratable acidity or anthocyanin content.Edited fruits showed a reduced softening rate during postharvest,displayed a reduced transpirational water loss,and were less damaged by Botrytis cinerea inoculation.The analysis of four potential off-target sites revealed no mutation events.In conclusion,editing the FaPG1 gene using the CRISPR/Cas9 system is an efficient method for improving strawberry fruit firmness and shelf life.

关键词： fir straw PG1

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A NETWORK ANALYSIS OF THE 2010 FIFA WORLD CUP CHAMPION TEAM PLAY

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Journal of Systems Science & Complexity 2013年第1期26卷 21-42页

作者： COTTA Carlos MORA antonio M MERELO juan Julin MERELO-MOLINA Cecilia Department of Computer Science University of Mlaga Department of Architecture and Computer Technology University of Granada

This paper analyzes the network of passes among the players of the Spanish team during the last FIFA World Cup 2010,where they emerged as the champion,with the objective of explaining the results obtained from the behavior at the complex network level.The team is considered a network with players as nodes and passes as(directed) edges.A temporal analysis of the resulting passes network is also done,looking at the number of passes,length of the chain of passes,and to network measures such as player centrality and clustering coefficient.Results of the last three matches(the decisive ones) indicate that the clustering coefficient of the pass network remains high,indicating the elaborate style of the Spanish team.The effectiveness of the opposing team in negating the Spanish game is reflected in the change of several network measures over time,most importantly in drops of the clustering coefficient and passing length/speed,as well as in their being able in removing the most talented players from the central positions of the network.Spain's ability to restore their combinative game and move the focus of the game to offensive positions and talented players is shown to tilt the balance in favor of the Spanish team.

关键词：网络分析世界杯播放军队聚类系数移动游戏西班牙网络行为

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Myelin lipid deficiency:a new key driver of Alzheimer’s disease

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中国神经再生研究：英文版 2023年第1期18卷 121-122页

作者： Shulan Qiu juan Pablo Palavicini Xianlin Han Barshop Institute for Longevity and Aging Studies Division of DiabetesDepartment of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA

Lipids play essential biological functions that include acting as components of biological membranes,energy storage,signaling,nutrients,transporters,enzyme activators,among others.Compared with the multiple research methods to assess DNA,RNA,and protein content,location,and function in cells,there are relatively fewer methods to study lipids.Therefore,lipid-oriented mechanistic studies remain rare and challenging.

关键词： Alzheimer rare challenging

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Towards a Surreal Spin Theory: Surreal Superstrings?

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Journal of Applied Mathematics and Physics 2022年第12期10卷 3586-3600页

作者： juan antonio Nieto Jesús Adrián Félix-Algandar Facultad de Ciencias Fsico-Matemáticas de la Universidad Autónoma de Sinaloa Culiacán Sinaloa México

We propose a surreal spin theory. Our basic mathematical tools are the dyadic rational number which is one of the key mathematical notions in surreal number theory. We argue that from the perspective of such surreal numbers, bosons and fermions, and therefore supersymmetry, are mere particular cases of a very much larger dyadic spin structure which include -spin (semionics), -spin and in general -spin, with m odd integer and n a positive natural number. Finally, we conjecture that this development could imply the existence of a surreal superstring theory.

关键词： Higher Spin Theory Surreal Numbers Dyadic Rationals

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