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Immune checkpoint inhibitor-induced colitis:A comprehensive review

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World journal of Clinical Cases 2019年第4期7卷 405-418页

作者： Aniruddh Som Rohan Mandaliya Dana Alsaadi Maham Farshidpour aline charabaty Nidhi Malhotra Mark C Mattar Department of Internal Medicine Medstar Washington Hospital Center Department of Gastroenterology MedStar Georgetown University Hospital Department of Internal Medicine MedStar Georgetown University Hospital Department of Internal Medicine MedStar Union Memorial Hospital and Good Samaritan Hospital Department of Gastroenterology Sibley Memorial Hospital Department of Gastroenterology MedStar Washington Hospital Center

Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand *** have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.

关键词： Immune checkpoint inhibitors Immune-related adverse events Cytotoxic Tlymphocyte-associated antigen 4 Programmed cell death protein 1 Programmed deathligand 1 Immune-mediated colitis

Monitoring inflammatory bowel disease during pregnancy:Current literature and future challenges

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World journal of Gastrointestinal Pharmacology and Therapeutics 2018年第1期9卷 1-7页

作者： Tenzin Choden Rohan Mandaliya aline charabaty Mark C Mattar Department of Internal Medicine MedStar Georgetown University HospitalWashingtonDC 20007United States Division of Gastroenterology MedStar Georgetown University HospitalWashingtonDC 20007United States

Inflammatory bowel disease has a high prevalence in women of childbearing age and can have a significant impact on pregnancy, from conceiving to carrying the pregnancy. Active disease during pregnancy is known to have negative effects on pregnancy outcomes; therefore, careful monitoring during this period is an important but challenging aspect of care and is crucial as it affects important management decisions. Recent data seems to suggest that endoscopy is a relatively safe procedure during all trimesters of pregnancy. Serum biomarkers such as C-reactive protein and fecal calprotectin are helpful non-invasive markers, but have shown conflicting results for correlation with disease activity in some initial studies. Further work is necessary to establish standard of care monitoring during pregnancy.

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Pregnancy Fecal calprotectin

Role of colonoscopy in diagnosis of capecitabine associated ileitis:Two case reports

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World journal of Gastrointestinal Endoscopy 2019年第5期11卷 383-388页

作者： Alexander E Dao Angela Hsu Ahmad Nakshabandi Rohan Mandaliya Sandeep Nadella Anita Sivaraman Mark Mattar aline charabaty Department of Gastroenterology Medstar Georgetown University Hospital Department of Gastroenterology Johns Hopkins University at Sibley Memorial Hospital

BACKGROUND Capecitabine is considered a first line agent in adjuvant therapy for breast and colorectal cancer. However,cases of severe diarrhea have been reported with increasing frequency in recent years. When diarrhea is severe and prolonged,capecitabine associated ileitis should be considered as a possible *** SUMMARY Herein,we present two cases of capecitabine ileitis,specifically involving the terminal ileum and ascending colon. We will demonstrate the disease course and treatment modalities applied to alleviate this condition,as well as discuss the merits of using colonoscopy to aid in *** Ultimately our cases demonstrate that symptomatic management with traditional anti-diarrheal medications is largely ineffective. Prompt recognition and discontinuation of capecitabine is an imperative step in proper management of this condition and colonoscopy with biopsy can be helpful when the diagnosis is unclear.

关键词： Capecitabine Xeloda 5-Fluorouracil Ileitis Ileocolitis Colonoscopy Case report

Pigs receiving daily tailored diets using precision-feeding techniques have different threonine requirements than pigs fed in conventional phase-feeding systems

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journal of Animal Science and Biotechnology 2019年第3期10卷 719-735页

作者： aline Remus Luciano Hauschild Etienne Corrent Marie-Pierre Letourneau-Montminy Candido Pomar Sherbrooke Research and Development Centre Agriculture and Agri-Food CanadaSherbrookeQuebec J1M 0C8Canada Departement des sciences animales Universite LavalQuebec CityQuebec G1V 0A6Canada School of Agricultural and Veterinary Studies(FCAV) Department of Animal ScienceUniversity of Sao Paulo State (UNESP)JaboticabalSao Paulo 14883-108Brazil Ajinomoto Animal Nutrition Europe Paris Cedex 17 F-75817France

Background: There is large variation in amino acids requirements among pigs,hence feeding pigs individually with daily tailored diets or in groups with a single feed may require different levels of ***,the response to different threonine levels(70%,85%,100%,115%,and 130% of the ideal threonine:lysine protein ratio of 0.65) was studied in growing pigs raised in a conventional group phase-feeding(GPF) system or fed individually using individual precision-feeding(IPF) *** a 21-day trial,110 barrows(25 ± 0.80 kg body weight) were housed in the same room and fed using electronic *** pigs per treatment were slaughtered at the end of the ***: Threonine intake increased linearly for the IPF and GPF pigs(P < 0.05).Lysine intake was similar across the *** daily gain,gain:feed ratio,and protein deposition were affected linearly by threonine level(P < 0.05)in both feeding *** deposition in the GPF pigs was maximized at 150 g/d and a 0.65 threonine:lysine ratio,whereas protein deposition increased linearly in the IPF *** Met and serine levels were 11 and 7% higher,respectively,in the IPF pigs than in the GPF pigs(P < 0.05).Dietary threonine increased(P < 0.05)threonine concentration in the longissimus dorsi in a quadratic manner in the IPF pigs,whereas there was no effect in the GPF *** dorsi collagen decreased as dietary threonine increased in the IPF and GPF pigs(P < 0.10).Carcass muscle crude protein was 2% higher in the GPF pigs than in the IPF pigs(P < 0.05).Conclusions: Individual pigs are able to modulate growth and the composition of growth according to threonine *** average amino acid ratio value that is currently used for GPF cannot be used for IPF.

关键词： Amino acid body composition Dose-response Ideal protein profile Lysine Threonine

Wilson's disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance

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World journal of Gastroenterology 2017年第36期23卷 6715-6725页

作者： Kassem Barada aline El Haddad Meghri Katerji Mustapha jomaa julnar Usta Department of Internal Medicine American University of Beirut Medical Center Department of Biochemistry and Molecular Genetics Faculty of Medicine American University of Beirut

AIM To determine the phenotypes and predominant diseasecausing mutations in Lebanese patients with Wilson's disease,as compared to regional non-European *** The clinical profile of 36 patients diagnosed in Lebanon was studied and their mutations were determined by molecular *** patients underwent full physical exam,including ophthalmologic slit-lamp examination ultrasound imaging of the liver,as well as measurement of serum ceruloplasmin and 24-h urinaryCu *** addition,genetic screening using PCR followed by sequencing to determine disease-causing mutations and polymorphisms in the ATP7B gene was carried on extracted DNA from patients and immediate family *** phenotypic-genotypic findings were then compared to reported mutations in Wilson's disease patients from regional Arab and non-European countries. RESULTS Patients belonged to extended consanguineous *** majority were homozygous for the disease-causing mutation,with no predominant mutation identified. The most common mutation,detected in 4 out of 13families,involved the ATP hinge region and was present in patients from Lebanon,Egypt,Iran and ***,mutations in Lebanese patients and those of the region were scattered over 17 exons of *** the homozygous exon 12 mutation Trp939Cys was only detected in patients from Lebanon but none from the regional countries,the worldwide common mutation H1069Q was not present in the Lebanese and was rare in the *** hepatic phenotype was predominant in patients from both Lebanon and the region(25%-65%).Furthermore,the majority of patients,including those who were asymptomatic,had evidence of some hepatic *** neurologic phenotype was rare. CONCLUSION Findings do not support presence of a founder *** and genetic screening is recommended for family members with index patients and unexplained hepatic dysfunction.

关键词： Wilson Disease Cu-metabolism Phenotype Genotype ATP7B Hepatic manifestations

Gene capture by transposable elements leads to epigenetic conflict in maize

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Molecular Plant 2021年第2期14卷 237-252页

作者： aline Muyle Danelle Seymour Nikos Darzentas Elias Primetis Brandon S.Gaut Alexandros Bousios Department of Ecology and Evolutionary Biology UC IrvineIrvineCA 92697USA Department of Botany and Plant Sciences UC RiversideRiversideCA 92521USA Central European Institute of Technology Masaryk UniversityBrnoCzech Republic School of Life Sciences University of SussexBrightonUK

Transposable elements(TEs)regularly capture fragments of *** the host silences these TEs,siRNAs homologous to the captured regions may also target the *** epigenetic crosstalk establishes an intragenomic conflict:silencing the TEs has the cost of silencing the *** genes are important,however,natural selection may maintain function by moderating the silencing response,which may also advantage the *** this study,we examined this model by focusing on Helitrons,Pack-MULEs,and Sirevirus LTR retrotransposons in the maize *** documented 1263 TEs containing exon fragments from 1629 donor *** with epigenetic conflict,donor genes mapped more siRNAs and were more methylated than genes with no evidence of ***,these patterns differed between syntelog versus translocated donor *** appeared to maintain function,as measured by gene expression,consistent with moderation of silencing for functionally important *** marks did not spread beyond their captured regions and 24nt crosstalk siRNAs were linked with CHH *** genes,in contrast,bore the signature of *** were highly methylated and less expressed,but also overrepresented among donor genes and located away from chromosomal arms,which suggests a link between capture and gene *** genes into potential functional categories based on evolutionary constraint supported the synteny-based *** families captured genes in different ways,but the evidence for their advantage was generally less obvious;nevertheless,TEs with captured fragments were older,mapped fewer siRNAs,and were slightly less methylated than TEs without captured ***,our results argue that TE capture triggers an intragenomic conflict that may not affect the function of important genes but may lead to the pseudogenization of less-constrained genes.

关键词： transposable elements intragenomic conflict gene capture epigenetic silencing methylation synteny

Fine mapping of genomic regions associated with female fertility in Nellore beef cattle based on sequence variants from segregating sires

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journal of Animal Science and Biotechnology 2020年第2期11卷 303-315页

作者： Gerson A.Oliveira júnior Daniel j.A.Santos aline S.M.Cesar Solomon A.Boison Ricardo V.Ventura Bruno C.Perez joséF.Garcia joséBento S.Ferraz Dorian j.Garrick Department of Veterinary Medicine University of São Paulo(USP)Faculty of Animal Science and Food EngineerPirassunungaSPBrazil Department of Animal Bioscience Center for Genetic Improvement of LivestockUniversity of GuelphGuelphONCanada Department of Animal and Avian Sciences University of MarylandCollege ParkMarylandUSA Department of Animal Science University of São Paulo(USP)PiracicabaSPBrazil Department of Sustainable Agricultural Systems University of Natural Resources and Life SciencesViennaAustria Department of Animal Nutrition and Production School of Veterinary Medicine and Animal ScienceUniversity of São Paulo(USP)PirassunungaBrazil Department of Support Production and Animal HealthSchool of Veterinary MedicineSão Paulo State University(Unesp)AraçatubaSPBrazil School of Agriculture Massey UniversityRuakura Ag CentreHamiltonNew Zealand

Background:Impaired fertility in cattle limits the efficiency of livestock production *** the genetic architecture of fertility traits would facilitate their improvement by *** this study,we characterized SNP chip haplotypes at QTL blocks then used whole-genome sequencing to fine map genomic regions associated with reproduction in a population of Nellore(Bos indicus)***:The dataset comprised of 1337 heifers genotyped using a GeneSeek®Genomic Profiler panel(74677 SNPs),representing the daughters from 78 *** performing marker quality control,64800 SNPs were *** carried by each sire at six previously identified QTL on BTAs 5,14 and 18 for heifer pregnancy and BTAs 8,11 and 22 for antral follicle count were constructed using findhap *** significance of the contrasts between the effects of every two paternally-inherited haplotype alleles were used to identify sires that were heterozygous at each ***-genome sequencing data localized to the haplotypes from six sires and 20 other ancestors were used to identify sequence variants that were concordant with the haplotype *** analyses were applied to these variants using KEGG and MeSH ***:A total of six(BTA 5),six(BTA 14)and five(BTA 18)sires were heterozygous for heifer pregnancy QTL whereas six(BTA 8),fourteen(BTA 11),and five(BTA 22)sires were heterozygous for number of antral follicles’*** to inadequate representation of many haplotype alleles in the sequenced animals,fine mapping analysis could only be reliably performed for the QTL on BTA 5 and 14,which had 641 and 3733 concordant candidate sequence variants,*** KEGG“Circadian rhythm”and“Neurotrophin signaling pathway”were significantly associated with the genes in the QTL on BTA 5 whereas 32 MeSH terms were associated with the QTL on BTA *** the concordant sequence variants,0.2%and 0.3%were classified as missense variants for BTAs 5 and 14,respe

关键词： Antral follicles Causal variants Haplotype Heifer pregnancy WGS

Electrochemical ageing study of mixed lanthanum/praseodymium nickelates La2-xPrxNiO4+δ as oxygen electrodes for solid oxide fuel or electrolysis cells

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journal of Energy Chemistry 2020年第7期29卷 62-70,I0003页

作者： Vaibhav Vibhu Aurélien Flura aline Rougier Clément Nicollet Sébastien Fourcade Teresa Hungria jean-Claude Grenier jean-Marc Bassat CNRS Univ.BordeauxBordeaux INPICMCBUMR 5026F-33600 PessacFrance Centre de Microcaractérisation Raimond CASTAING Universitéde ToulouseCNRSUT3–Paul SabatierINPINSAEspace Clément Ader3 rue Caroline AigleToulouse 31400France

The chemical and electrochemical stability of lanthanide nickelates La2 NiO4+δ(LNO),Pr2 NiO4+δ(PNO)and their mixed compounds La(2-x)PrxNiO4+δ(LPNOs)with x=0.5,1 or 1.5 is *** aim is to promote these materials as efficient electrodes for solid oxide fuel cell(SOFC)and/or solid oxide electrolysis cell(SOEC).La2 NiO4+δand La1.5Pr0.5NiO4+δcompounds are chemically very stable as powders over one month in the temperature range 600-800℃,while the other materials rich in praseodymium progressively decompose into various perovskite-deriving components with additional Pr6 *** their uneven properties,all these materials are quite efficient and sustainable as electrodes on top of gadolinium doped ceria(GDCBL)//yttrium doped zirconia(8 YSZ)electrolyte,for one month at 700℃without *** polarization(300 mA·cm-2),the electrochemical performances of LNO,PNO and La1.5Pr0.5NiO4+δ(LP5 NO)quickly degrade in SOFC mode,*** the oxygen reduction reaction,while they show durability in SOEC mode,*** the oxide oxidation reaction.

关键词： Lanthanide nickelates SOFC cathode SOEC anode Stability Inductive loop Degradation

Growth and differentiation of human induced pluripotent stem cell(hiPSC)-derived kidney organoids using fully synthetic peptide hydrogels

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Bioactive Materials 2023年第3期21卷 142-156页

作者： Niall j.Treacy Shane Clerkin jessica L.Davis Ciar´an Kennedy aline F.Miller Alberto Saiani jacek K.Wychowaniec Dermot F.Brougham john Crean Diabetes Complications Research Centre University College Dublin(UCD)Conway Institute of Biomolecular and Biomedical Research and BelfieldDublin 4Ireland UCD School of Biomolecular and Biomedical Science BelfieldDublin 4Ireland Department of Materials&Manchester Institute of Biotechnology(MIB) School of Natural SciencesFaculty of Science and EngineeringThe University of ManchesterUK UCD School of Chemistry University College DublinBelfieldDublin 4Ireland

Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised ***,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid *** within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and ***,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,***-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct *** compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell ***,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression ***-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid *** work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.

关键词： Human kidney organoids Fully synthetic matrices Self-assembling peptide hydrogels Single-cell RNA sequencing