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In Silico Pipeline to Identify Tumor‑Specific Antigens for Cancer Immunotherapy Using Exome Sequencing Data

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Phenomics 2023年第2期3卷 130-137页

作者： Diego Morazán‑Fernández javier Mora Jose Arturo Molina‑Mora Caja Costarricense de Seguro Social San José10104Costa Rica Centro de Investigación de Enfermedades Tropicales Centro de Investigación en Cirugía y Cáncerand Facultad de MicrobiologíaUniversidad de Costa RicaSan José2060Costa Rica

Tumor-specific antigens or neoantigens are peptides that are expressed only in cancer cells and not in healthy cells.Some of these molecules can induce an immune response,and therefore,their use in immunotherapeutic strategies based on cancer vaccines has been extensively explored.Studies based on these approaches have been triggered by the current high-throughput DNA sequencing technologies.However,there is no universal nor straightforward bioinformatic protocol to discover neoan-tigens using DNA sequencing data.Thus,we propose a bioinformatic protocol to detect tumor-specific antigens associated with single nucleotide variants(SNVs)or“mutations”in tumoral tissues.For this purpose,we used publicly available data to build our model,including exome sequencing data from colorectal cancer and healthy cells obtained from a single case,as well as frequent human leukocyte antigen(HLA)class I alleles in a specific population.HLA data from Costa Rican Central Valley population was selected as an example.The strategy included three main steps:(1)pre-processing of sequencing data;(2)variant calling analysis to detect tumor-specific SNVs in comparison with healthy tissue;and(3)prediction and characterization of peptides(protein fragments,the tumor-specific antigens)derived from the variants,in the context of their affinity with frequent alleles of the selected population.In our model data,we found 28 non-silent SNVs,present in 17 genes in chromosome one.The protocol yielded 23 strong binders peptides derived from the SNVs for frequent HLA class I alleles for the Costa Rican population.Although the analyses were performed as an example to implement the pipeline,to our knowledge,this is the first study of an in silico cancer vaccine using DNA sequencing data in the context of the HLA alleles.It is concluded that the standardized protocol was not only able to identify neoantigens in a specific but also provides a complete pipeline for the eventual design of cancer vaccines using the best bioinformatic practices.

关键词： Neopeptide Colorectal cancer Cancer vaccine Neoantigens Human leukocyte antigen Costa Rica

Viability,behavior,and color expression in the offspring of matings between common wall lizard Podarcis muralis color morphs

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Current Zoology 2022年第1期68卷 41-55页

作者： javier ABALOS Guillem PEREZ I DE LANUZA Alicia BARTOLOME Fabien AUBRET Tobias ULLER Enrique FONT Ethology Lab Instituto Cavanilles de Biodiversidad y Biologı´a EvolutivaUniversitat de ValenciaValenciaSpain CIBIO/InBIO Centro de Investigacao em Biodiversidade e Recursos Geneticos da Universidade do PortoPortoPortugal SETE Station d’Ecologie Theorique et ExperimentaleUPR2001Centre National de la Recherche ScientifiqueParisFrance Department of Biology Lund UniversityLundSweden

Color polymorphisms are widely studied to identify the mechanisms responsible for the origin and maintenance of phenotypic variability in nature.Two of the mechanisms of balancing selection currently thought to explain the long-term persistence of polymorphisms are the evolution of alternative phenotypic optima through correlational selection on suites of traits including color and heterosis.Both of these mechanisms can generate differences in offspring viability and fitness arising from different morph combinations.Here,we examined the effect of parental morph combination on fertilization success,embryonic viability,newborn quality,antipredator,and foraging behavior,as well as inter-annual survival by conducting controlled matings in a polymorphic lacertid Podarcis muralis,where color morphs are frequently assumed to reflect alternative phenotypic optima(e.g.,alternative reproductive strategies).Juveniles were kept in outdoor tubs for a year in order to study inter-annual growth,survival,and morph inheritance.In agreement with a previous genome-wide association analysis,morph frequencies in the year-old juveniles matched the frequencies expected if orange and yellow expressions depended on recessive homozygosity at 2 separate loci.Our findings also agree with previous literature reporting higher reproductive output of heavy females and the higher overall viability of heavy newborn lizards,but we found no evidence for the existence of alternative breeding investment strategies in female morphs,or morphcombination effects on offspring viability and behavior.We conclude that inter-morph breeding remains entirely viable and genetic incompatibilities are of little significance for the maintenance of discrete color morphs in P.muralis from the Pyrenees.

关键词： alternative breeding strategies color polymorphism controlled matings lizard behavior morph ontogeny newborn viability

Are we ready for telemonitoring inflammatory bowel disease?A review of advances,enablers,and barriers

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World Journal of Gastroenterology 2023年第7期29卷 1139-1156页

作者： javier Del Hoyo Mónica Millán Alejandro Garrido-Marín Mariam Aguas Department of Gastroenterology La Fe University and Polytechnic HospitalValencia 46026Spain Department of Surgery La Fe University and Polytechnic HospitalValencia 46026Spain Health Research Institute La Fe La Fe University and Polytechnic HospitalValencia 46026Spain

This review summarizes the evidence about telemonitoring in patients with inflammatory bowel disease(IBD). To give an overview of the advances performed, as well as the enablers and barriers which favoured/hindered telemonitoring implementation. We performed a literature search in Pub Med, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts published up to September 2022 were screened for a set of inclusion criteria: telemonitoring intervention, IBD as the main disease, and a primary study performed. Ninety-seven reports were selected for full review. Finally, 20 were included for data extraction and critical appraisal. Most studies used telemonitoring combined with tele-education, and programs evolved from home telemanagement systems towards web portals through m Health applications. Web systems demonstrated patients’ acceptance, improvement in quality of life, disease activity and knowledge, with a good cost-effectiveness profile in the short-term. Initially, telemonitoring was almost restricted to ulcerative colitis, but new patient reported outcome measures, home-based tests and mobile devices favoured its expansion to different patients’ categories. However, technological and knowledge advances led to legal, ethical, economical and logistic issues. Standardization of remote healthcare is necessary, to improve the interoperability of systems as well as to address liability concerns and users’ preferences. Telemonitoring IBD is well accepted and improves clinical outcomes at a lower cost in the short-term. Funders, policymakers, providers, and patients need to align their interests to overcome the emerging barriers for its full implementation.

关键词： Inflammatory bowel disease Telemedicine Telemonitoring Information and communication technology Crohn´s disease Ulcerative colitis

Enduring association between irritable bowel syndrome and war trauma during the Nicaragua civil war period:A population-based study

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World Journal of Gastroenterology 2023年第45期29卷 5953-5961页

作者： Edgar M Peña-Galo Daniel Wurzelmann javier Alcedo Rodolfo Peña Loreto Cortes Douglas Morgan Department of Digestive Diseases Miguel Servet University HospitalZaragoza 50009AragonSpain javier Alcedo Aragon Health Research InstituteIIS AragonZaragoza 50009AragonSpain Department of Mental Health Carolina PartnersDurhamNC 27707United States Department of Data Analysis CIDE(ResearchDevelopment and Epidemiology Center)Tegucigalpa 11101Francisco MorazánHonduras School of Medicine National Autonomous University of NicaraguaLeon 21000LeonNicaragua Department of Gastroenterology and Hepatology UAB University of Alabama BirminghamBirminghamAL 35233United States School of Medcine The University of North CarolinaChapel HillNC 9500United States

BACKGROUND Psychosocial and physical trauma are known risk factors for irritable bowel syndrome(IBS),including in war veterans,whereas war exposure in civilians is unclear.Nicaragua experienced two wars,1970-1990:The Sandinistas Revolution(1970s)and The Contra War(1980s).Our aim was to investigate the role of exposure to war trauma in the subsequent development of IBS in the context of an established health surveillance system(11000 households).AIM To investigate in a civilian population the relationship between exposure to war trauma and events and the subsequent development of IBS in the context of an established public health and demographic surveillance system in western Nicaragua.METHODS We conducted a nested population-based,cross-sectional study focused on functional gastrointestinal disorders based on Rome II criteria.1617 adults were randomly selected.The Spanish Rome II Modular Questionnaire and Harvard Trauma Questionnaire were validated in Nicaragua.War exposure was assessed with 10 measures of direct and indirect war trauma and post-war effects.Multiple exposures were defined by≥3 measures.RESULTS The prevalence of IBS was 15.2%[Female(F)17.1%,Male(M)12.0%],war exposure 19.3%(F 9.3%,M 36.7%),and post-traumatic stress disorder(PTSD)5.6%(F 6.4%,M 4.3%).Significant associations with IBS in the civilian population were observed(adjusted by gender,age,socioeconomic status,education):physical and psychological abuse[adjusted odds ratio(aOR):2.25;95%confidence interval:1.1-4.5],witnessed execution(aOR:2.4;1.1-5.2),family member death(aOR:2.2;1.2-4.2),and multiple exposures(aOR:2.7;1.4-5.1).PTSD was independently associated with IBS(aOR:2.6;1.2-5.7).CONCLUSION An enduring association was observed in the Nicaragua civilian population between specific civil war-related events and subsequent IBS.Civilian populations in regions with extended armed conflict may warrant provider education and targeted interventions for patients.

关键词： Irritable bowel syndrome Functional gastrointestinal disorders War trauma Civil war Post-traumatic stress disorder Central America

Classification of Plant Endogenous States Using Machine Learning-Derived Agricultural Indices

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Plant Phenomics 2023年第3期5卷 474-483页

作者： Sally Shuxian Koh Kapil Dev javier Jingheng Tan Valerie Xinhui Teo Shuyan Zhang Dinish U.S. Malini Olivo Daisuke Urano Temasek Life Sciences Laboratory National University of SingaporeSingaporeSingapore Department of Biological Sciences National University of SingaporeSingaporeSingapore Translational Biophotonics Laboratory Institute of Bioengineering and BioimagingAgency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Institute of Materials Research and Engineering(IMRE) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore

Leaf color patterns vary depending on leaf age,pathogen infection,and environmental and nutritional stresses;thus,they are widely used to diagnose plant health statuses in agricultural fields.The visible-near infrared-shortwave infrared(VIS-NIR-SWIR)sensor measures the leaf color pattern from a wide spectral range with high spectral resolution.However,spectral information has only been employed to understand general plant health statuses(e.g.,vegetation index)or phytopigment contents,rather than pinpointing defects of specific metabolic or signaling pathways in plants.Here,we report feature engineering and machine learning methods that utilize VIS-NIR-SWIR leaf reflectance for robust plant health diagnostics,pinpointing physiological alterations associated with the stress hormone,abscisic acid(ABA).Leaf reflectance spectra of wild-type,ABA2-overexpression,and deficient plants were collected under watered and drought conditions.Drought-and ABA-associated normalized reflectance indices(NRIs)were screened from all possible pairs of wavelength bands.Drought associated NRIs showed only a partial overlap with those related to ABA deficiency,but more NRIs were associated with drought due to additional spectral changes within the NIR wavelength range.Interpretable support vector machine classifiers built with 20 NRIs predicted treatment or genotype groups with an accuracy greater than those with conventional vegetation indices.Major selected NRIs were independent from leaf water content and chlorophyll content,2 well-characterized physiological changes under drought.The screening of NRIs,streamlined with the development of simple classifiers,serves as the most efficient means of detecting reflectance bands that are highly relevant to characteristics of interest.

关键词： drought reflectance indices

Taxonomy-based differences in feeding guilds of fish

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Current Zoology 2020年第1期66卷 51-56页

作者： javier SANCHEZ-HERNANDEZ Departamento de Zooloxla Xenetica e Antropoloxfa FlsicaFacultade de BioloxfaUniversidade de Santiago de CompostelaCampus Vida s/nSantiago de CompostelaEspana

It has been taken for granted that feeding guilds and behavior in animals are linked to the taxonomic relatedness of species,but empirical evidence supporting such relationship is virtually missing.To examine the importance of taxonomy on trophic ecology,I here present the first well-resolved dietary taxonomy analysis based on feeding guilds(predation,herbivory,and filtering)among families and genera within the fish order Perciformes.Taxonomic relatedness in feeding did not vary with ecosystem dimension(marine vs.freshwater).Although predation dominates among Perciformes fishes,this study shows that in most cases taxonomic units(family or genus)are composed by species with several feeding guilds.Related species are more similar in feeding compared with species that are taxonomically more distant demonstrating that there is a greater variation of feeding guilds within families than genera.Thus,there is no consistency in feeding guilds between family-and genus-level taxonomy.This study provides empirical support for the notion that genera are more informative than families,underlining that family-level taxonomy should be avoided to infer feeding habits of fish species at finer taxonomic resolution.Thus,the choice of taxonomic resolution(family or genus level)in ecological studies is key to avoid information loss and misleading results.I conclude that high-rank taxonomic units(i.e.,above the generic level)are not appropriate to test research hypotheses about the feeding of fish.

关键词： aquatic systems clades FishBase global datasets taxonomic sufficiency trophic ecology

Insights into the role of major bioactive dietary nutrients in lamb meat quality:a review

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Journal of Animal Science and Biotechnology 2022年第4期13卷 951-966页

作者： javierÁlvarez-Rodríguez Olaia Urrutia Sandra Lobón Guillermo Ripoll Juan Ramón Bertolín Margalida Joy Departament de Ciència Animal Universitat de Lleida25198 LleidaSpain Departamento de Agronomía Biotecnología y AlimentaciónIS-FOOD InstituteEscuela Técnica Superior de Ingeniería Agronómica y BiocienciasUniversidad Pública de NavarraPamplonaSpain Centro de Investigación y Tecnología Agroalimentaria de Aragón(CITA) Avda.Montañana 93050059 ZaragozaSpain Instituto Agroalimentario de Aragón–IA2(CITA-Universidad de Zaragoza) Avda.Miguel Servet17750013 ZaragozaSpain.

Feed supplementation withα-linolenic acid(ALA)and linoleic acid(LA)increases their content in muscle,ALA increases n-3 polyunsaturated fatty acids and decrease n-6/n-3 ratio in muscle,and LA increases rumenic acid.However,high LA supplementation may have negative effects on lambs’lipid oxidative stability of meat.When the sources of ALA and LA are fed as fresh forage,the negative effects are counterbalanced by the presence of other bioactive compounds,as vitamin E(mainlyα-tocopherol)and polyphenols,which delay the lipid oxidation in meat.There is a wide consensus on the capability of vitamin E delaying lipid oxidation on lamb meat,and its feed content should be adjusted to the length of supplementation.A high dietary inclusion of proanthocyanidins,phenolic compounds and terpenes reduce the lipid oxidation in muscle and may improve the shelf life of meat,probably as a result of a combined effect with dietary vitamin E.However,the recommended dietary inclusion levels depend on the polyphenol type and concentration and antioxidant capacity of the feedstuffs,which cannot be compared easily because no routine analytical grading methods are yet available.Unless phenolic compounds content in dietary ingredients/supplements for lambs are reported,no specific association with animal physiology responses may be established.

关键词： Fatty acid Forage Oilseed Polyphenol Vitamin E

Wing morphology covaries with migration distance in a highly aerial insectivorous songbird

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Current Zoology 2023年第3期69卷 255-263页

作者： Piotr Matyjasiak Cosme Lopez-Calderon Roberto Ambrosini javier Balbontin Alessandra Costanzo Yosef Kiat Andrea Romano Diego Rubolini Museum and Institute of Zoology Polish Academy of Sciences Wilcza 64PL-00-679 WarsawPoland Departamento de Zoologia Facultad de BiologiaEdificio VerdeAvda.de Reina Mercedes s/nE-41012 SevillaSpain Dipartimento di Scienze e Politiche Ambientali Universita degli Studi di Milanovia Celoria 26I-20133 MilanItaly Israeli Bird Ringing Center(IBRC) Israel Ornithological CenterSociety for the Protection of Nature in IsraelHanegev 2Tel-AvivIsrael Istituto di Ricerca sulle Acque IRSA-CNRVia del Mulino 19I-20861 Brugherio(MB)Italy Institute of Biological Sciences Cardinal Stefan Wyszynski University in WarsawWoycickiego 1/3PL-01-815 Warsaw Department of Wetland Ecology Estacion Biologica de Donana CsiCAmerico Vespucio s/nE-41092 SevilleSpain

According to classical prediction of aerodynamic theory,birds and other powered fliers that migrate over long distances should have longer and more pointed wings than those that migrate less.However,the association between wing morphology and migratory behavior can be masked by contrasting selective pressures related to foraging behavior,habitat selection and predator avoidance,possibly at the cost of lower flight energetic efficiency.We studied the handwing morphology of Eurasian barn swallows Hirundo rustica from four populations representing a migration distance gradient.This species is an aerial insectivore,so it flies extensively while foraging,and may migrate during the day using a‘fly-and-forage’migration strategy.Prolonged foraging flights may reinforce the effects of migration distance on flight morphology.We found that two wings’aerodynamic properties—isometric handwing length and pointedness,both favoring energetically efficient flight,were more pronounced in barn swallows from populations undertaking longer seasonal migrations compared to less migratory populations.Our result contrast with two recent interspecific comparative studies that either reported no relationship or reported a negative relationship between pointedness and the degree of migratory behavior in hirundines.Our results may thus contribute to confirming the universality of the rule that longer migrations are associated with more pointed wings.

关键词： flight morphology geographical differences Hirundo rustica migration syndrome population wing shape

Auricular embryonal rhabdomyosarcoma

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World Journal of Pediatrics 2022年第5期18卷 358-360页

作者： javier Arredondo Montero Monica Bronte Anaut Sara Hernandez-Martin Juan Carlos Lopez-Gutierrez Pediatric Surgery Department Complejo Hospitalario de NavarraCalle Irunlarrea 331008 PamplonaNavarraSpain Pathology Department Complejo Hospitalario de NavarraPamplonaSpain Pediatric Surgery Department Hospital Universitario La PazMadridSpain

A 13-month-old girl presented with a red-violaceous tumor of 13 mm in diameter on the inner side of the root of the right helix,with increased temperature and cystic consistency(Fig.1).No pulse was palpable in the lesion.An ultrasonography was performed,showing a 1.6 cm rounded lesion with well-defined margins,hypoechogenic and homogeneous,compatible with hemangioma.Empirical treatment with oral propranolol was started without improve-ment.

关键词： sarcoma ultrasonography showing