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Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome

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World Journal of Hepatology 2021年第11期13卷 1494-1511页

作者： Carolina Castillo-Castro Alexandro JoséMartagón-Rosado Rocio Ortiz-Lopez Luis Felipe Garrido-Treviño Melissa Villegas-Albo francisco javier bosques-padilla Tecnológico de Monterrey Escuela de Medicina y Ciencias de la SaludMonterrey 64710Mexico Unidad de Investigación de Enfermedades Metabólicas Instituto Nacional de Ciencias Médicas y NutriciónCiudad de México 14080Mexico Centro Regional para el Estudio de las Enfermedades Digestivas Servicio de GastroenterologíaFacultad de Medicina y Hospital Universitario Dr.JoséEleuterio GonzálezUniversidad Autónoma de Nuevo LeónMonterrey 64460Mexico

Fatty liver has been present in the lives of patients and physicians for almost two centuries.Vast knowledge has been generated regarding its etiology and consequences,although a long path seeking novel and innovative diagnostic biomarkers for nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)is still envisioned.On the one hand,proteomics and lipidomics have emerged as potential noninvasive resources for NAFLD diagnosis.In contrast,metabolomics has been able to distinguish between NAFLD and NASH,even detecting degrees of fibrosis.On the other hand,genetic and epigenetic markers have been useful in monitoring disease progression,eventually functioning as target therapies.Other markers involved in immune dysregulation,oxidative stress,and inflammation are involved in the instauration and evolution of the disease.Finally,the fascinating gut microbiome is significantly involved in NAFLD and NASH.This review presents state-of-the-art biomarkers related to NAFLD and NASH and new promises that could eventually be positioned as diagnostic resources for this disease.As is evident,despite great advances in studying these biomarkers,there is still a long path before they translate into clinical benefits.

关键词： Fatty liver Biomarkers Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis

A Tutorial on Federated Learning from Theory to Practice:Foundations,Software Frameworks,Exemplary Use Cases,and Selected Trends

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 824-850页

作者： M.Victoria Luzón Nuria Rodríguez-Barroso Alberto Argente-Garrido Daniel Jiménez-López Jose M.Moyano javier Del Ser Weiping Ding francisco Herrera Department of Software Engineering Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Computer Science and Artificial Intelligence Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Communications Engineering University of the Basque Country(UPV/EHU)and also with TECNALIABasque Research&Technology Alliance(BRTA)Spain School of Information Science and Technology Nantong UniversityNantong 226019China

When data privacy is imposed as a necessity,Federated learning(FL)emerges as a relevant artificial intelligence field for developing machine learning(ML)models in a distributed and decentralized environment.FL allows ML models to be trained on local devices without any need for centralized data transfer,thereby reducing both the exposure of sensitive data and the possibility of data interception by malicious third parties.This paradigm has gained momentum in the last few years,spurred by the plethora of real-world applications that have leveraged its ability to improve the efficiency of distributed learning and to accommodate numerous participants with their data sources.By virtue of FL,models can be learned from all such distributed data sources while preserving data privacy.The aim of this paper is to provide a practical tutorial on FL,including a short methodology and a systematic analysis of existing software frameworks.Furthermore,our tutorial provides exemplary cases of study from three complementary perspectives:i)Foundations of FL,describing the main components of FL,from key elements to FL categories;ii)Implementation guidelines and exemplary cases of study,by systematically examining the functionalities provided by existing software frameworks for FL deployment,devising a methodology to design a FL scenario,and providing exemplary cases of study with source code for different ML approaches;and iii)Trends,shortly reviewing a non-exhaustive list of research directions that are under active investigation in the current FL landscape.The ultimate purpose of this work is to establish itself as a referential work for researchers,developers,and data scientists willing to explore the capabilities of FL in practical applications.

关键词： Data privacy distributed machine learning federated learning software frameworks

Microfluidic bubble-generator enables digital light processing 3D printing of porous structures

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Aggregate 2024年第1期5卷 280-291页

作者： Philipp Weber Ling Cai francisco javier Aguilar Rojas Carlos Ezio Garciamendez-Mijares Maria Celeste Tirelli Francesco Nalin Jakub Jaroszewicz Wojciech Swi eszkowski Marco Costantini Yu Shrike Zhang Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMassachusettsUSA Institute of Physical Chemistry—Polish Academy of Sciences KasprzakaPoland Biomaterials Group Materials Design DivisionFaculty of Materials Science and EngineeringWarsaw University of TechnologyWoloskaPoland

Three-dimensional(3D)printing is an emerging technique that has shown promising success in engineering human tissues in recent years.Further development of vatphotopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and components.Similarly,the development of microfluidic chip systems is an emerging research sector with promising medical applications.This work demonstrates the coupling of a digital light processing(DLP)printing procedure with a microfluidic chip system to produce size-tunable,3D-printable porosities with narrow pore size distributions within a gelatin methacryloyl(GelMA)hydrogel matrix.It is found that the generation of size-tunable gas bubbles trapped within an aqueous GelMA hydrogel-precursor can be controlled with high precision.Furthermore,the porosities are printed in two-dimensional(2D)as well as in 3D using the DLP printer.In addition,the cytocompatibility of the printed porous scaffolds is investigated using fibroblasts,where high cell viabilities as well as cell proliferation,spreading,and migration are confirmed.It is anticipated that the strategy is widely applicable in a range of application areas such as tissue engineering and regenerative medicine,among others.

关键词： 3D printing biofabrication bubble digital light processing microfluidics porous

mRNA levels of TLR4 and TLR5 are independent of H pylori

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World Journal of Gastroenterology 2008年第34期14卷 5306-5310页

作者： Elvira Garza-González Virgilio Bocanegra-García francisco javier bosques-padilla Juan Pablo Flores-Gutiérrez francisco Moreno Guillermo Ignacio Perez-Perez Departmento de Microbiología Facultad de MedicinaUniversidad Autónoma de Nuevo León Departmento de Biología Molecular y Bioingeniería UAM Reynosa Aztlán Universidad Autónoma de Tamaulipas Hospital Universitario "Dr. José Eleuterio González" Universidad Autónoma de Nuevo León Department of Medicine and Microbiology New York University School of Medicine

AIM:To determine if the presence H pylori or its viru- lence affect toll-like receptor 4 (TLR4) and TLR5 mRNA expression levels. METHODS:For the in vivo assays, gastric biopsies were obtained from 40 patients and H pylori status was determined. For the in vitro assays, human gastric adenocarcinoma mucosal cells (AGS) were cultured in the presence or absence of twelve selected H pylori strains. H pylori strains isolated from culture-positive patients and selected strains were genotyped for cagA and vacA. The cDNA was obtained from mRNA extracted from biopsies and from infected AGS cells. TLR4 and TLR5 mRNA levels were examined by real-time PCR. RESULTS: The presence of H pylori did not affect the mRNA levels of TLR4 or TLR5 in gastric biopsies. The mRNA levels of both receptors were not influenced by the vacA status (P > 0.05 for both receptors) andthere were no differences in TLR4 or TLR5 mRNA levels among the different clinical presentations/histological fi ndings (P > 0.05). In the in vitro assay, the mRNA levels of TLR4 or TLR5 in AGS cells were not influenced by the vacAs1 status or the clinical condition as-sociated with the strains (P > 0.05 for both TLR4 and TLR5). CONCLUSION: The results of this study show that the mRNA levels of TLR4 and TLR5 in gastric cells, both in vivo and in vitro, are independent of H pylori colonization and suggest that vacA may not be a significant player in the first step of innate immune recognition mediated by TLR4 or TLR5.

关键词：幽门杆菌 TLR4 TLR5 胃腺癌黏膜细胞 mRNA

A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication

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World Journal of Gastroenterology 2014年第6期20卷 1438-1449页

作者： Elvira Garza-González Guillermo Ignacio Perez-Perez Héctor Jesús Maldonado-Garza francisco javier bosques-padilla Servicio de Gastroenterología y Departamento de Patología Clínica Hospital Universitario "Dr. José Eleuterio González" Universidad Autónoma de Nuevo León Departments of Medicine and Microbiology New York University School of Medicine

Helicobacter pylori(H. pylori) affects nearly half of the world's population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patient's clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.

关键词： Diagnosis Helicobacter pylori Treatment Hybrid the

Sex and habitat differences in size and coloration of an amphibian’s poison glands match differential predator pressures

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Integrative Zoology 2022年第5期17卷 764-776页

作者： francisco javier ZAMORA-CAMACHO Department of Phisical Chemical and Natural SystemsPablo de Olavide UniversitySevilleSpain Department of Biodiversity Ecology and EvolutionComplutense University of MadridMadridSpain

Chemical defenses are frequently accompanied by salient color patterns actively avoided by predators,a phe-nomenon referred to as aposematism.However,the production of both chemical defenses and pigments is costly,and is thus expected to be reduced under mild predator pressure.In this work,I compared the size and coloration of parotoid glands(2 dorsal,external swollen structures that secrete toxins in toads)of male and female Epidalea calamita toads from agrosystems and from pine groves.I also quantiﬁed the predator attacks received by plas-ticine toad models,whose“parotoid glands”differed in size and color conspicuousness,exposed in each habitat.Predators avoided models with large and conspicuous parotoid glands,but models in agrosystems were more of-ten attacked.Concerning actual toads,agrosystem and male individuals had larger parotoid glands,presumably implying greater production of chemical defenses than in pine grove and female conspeciﬁcs.Theseﬁndings are aligned with previous research suggesting that both agrosystem toads and males in this system are subjected to a more intense predator pressure.Difference between parotoid gland and dorsum coloration was greater in agrosys-tem toads.A marked internal pattern could function as an aposematic signal,which could counteract increased predator pressure.

关键词： anuran agrosystem aposematism Epidalea calamita plasticine model

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 386-397页

作者： Vilma Pacheco-Barcia Sara Custodio-Cabello Fatima Carrasco-Valero Magda Palka-Kotlowska Axel Mariño-Mendez Alberto Carmona-Bayonas javier Gallego A J Muñoz Martín Paula Jimenez-Fonseca Luis Cabezon-Gutierrez Department of Medical Oncology Hospital Universitario de TorrejonMadrid 28850Spain Department of Internal Medicine Hospital Universitario de TorrejonMadrid 28850Spain Department of Medical Oncology Hospital Universitario Central de AsturiasOviedo 33011Spain Department of Medical Oncology Hospital Universitario Morales MeseguerUniversity of MurciaMurcia 30001Spain Department of Medical Oncology Hospital General Universitario de ElcheElche 03202Spain Department of Medical Oncology Hospital General Universitario Gregorio MarañónUniversidad Complutense MadridMadrid 28007Spain Universidad francisco de Vitoria Madrid 28223Spain

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not

关键词： Pancreatic cancer Nutrition Prognostic factor Inflammation Advanced cancer Systemic inflammatory response index Weight loss

Feeding on clean food?Potential effects of electric organ discharges by Torpedo spp.(Torpediniformes:Torpedinidae)on their trophically transmitted parasites

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Integrative Zoology 2022年第2期17卷 234-245页

作者： Jaime PENADÉS-SUAY Tania REGACHO francisco javier AZNAR Marine Zoology Unit Cavanilles Institute of Biodiversity and Evolutionary BiologyUniversity of ValenciaValènciaSpain LAMNA Association for the study of elasmobranchs from the Valencian Community ValènciaSpain

Members of the Torpedinidae(torpedoes)and Hypnidae(coffin ray)use electric organ discharges(EOD)to stun or kill their prey before consumption.We investigated whether EOD could also negatively affect the helminth larvae infecting these preys through a surrogate model:we applied electric discharges to individuals of blue whiting,Micromesistius poutassou,that harbored live larvae of Anisakis.Larval mortality throughout a 6-h period was significantly higher in the treatment group,suggesting that EODs could significantly hamper helminth recruitment.We then tested whether torpedinids and hypnids(“strong-EOD”families)harbored species-poor helminth(cestode)assemblages compared with“weak-EOD”Torpediniformes(Narcidae and Narkidae)and other Batoidea.Based on comparisons on estimated species diversity and mean species richness of tapeworms at host individual level we found that(i)Torpediniformes had the lowest tapeworm diversity of all Batoidea orders;(ii)Torpedo spp.consistently had the lowest mean cestode richness at host individual level,and this could not be related to other host factors influencing cestode diversity in chondrichthyans,that is body size,trophic level or dietary breath.However,a preliminary comparison between“strong-EOD”and“weak-EOD”Torpediniformes did not detect clear differences of cestode richness.Thus,evidence supporting an unambiguous contribution of EODs to depauperate cestode assemblages requires further research.

关键词： Anisakis Batoidea cestode EOD behavior Torpediniform Torpedo

Diffusion dynamics and characterization of attogram masses in optically trapped single nanoparticles using laser-induced plasma imaging

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Nano Research 2023年第5期16卷 7470-7480页

作者： Pablo Purohit francisco J.Fortes javier Laserna UMALASERLAB Departamento de Química AnalíticaUniversidad de MálagaC/Jiménez Fraud 4Malaga 29010Spain Niels Bohr Institute University of CopenhagenBlegdamsvej 172100 CopenhagenDenmark

In the present work,a wavelength-selected plasma imaging analysis system is presented and used to track photons emitted from single-trapped nanoparticles in air at atmospheric pressure.The isolated nanoentities were atomized and excited into plasma state using single nanosecond laser pulses.The use of appropriate wavelength filters alongside time-optimized acquisition settings enabled the detection of molecular and atomic emissions in the plasma.The photon detection efficiency of the imaging line resulted in a signal>400 times larger than the simultaneously-acquired dispersive spectroscopy data.The increase in sensitivity outlined the evolution of diverse physicochemical processes at the single particle scale which included heat and momentum transfer from the plasma into the particle as wells as chemical reactions.The imaging detection of excited fragments evidenced different diffusion kinetics and time frames for atoms and molecules and their influence upon both the spectroscopic emission readout and fabrication processes using the plasma as a reactor.Moreover,the origin of molecular species,whether naturally-occurring or derived from a chemical reaction in the plasma,could also be studied on the basis of compositional gradients found on the images.Limits of detection for the inspected species ranged from tens to hundreds attograms,thus leading to an exceptional sensing principle for single nanoentities that may impact several areas of science and technology.

关键词： single nanoparticle inspection wavelength-selected laser-induced plasma imaging laser fabrication attogram characterization atomic/molecular diffusion