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A novel stop codon mutation in exon 5 (c.639G>A) of the cadherin-1 gene in a Vietnamese man with hereditary diffuse gastric cancer: a case report

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JOURNAL OF MEDIcAL cASE REPORTS 2021年第1期15卷 263-263页

作者： Dzung Ngoc Thi Dang Huong Thanh Thi Nguyen Hoa Dieu Ngo Bac Manh Tran Anh Duc Vu Huy Quang Dang Van Thanh Ta Hanoi Med Univ Biochem Dept Hanoi Vietnam Natl Geriatr Hosp Dept Funct Explorat Hanoi Vietnam Hanoi Med Univ Fac Med Technol Dept Med Lab Sci Hanoi Vietnam

Background Germline pathogenic variants in the cadherin-1 (cDH1) gene cause a predisposition to hereditary diffuse gastric cancer (HDGc). We report an HDGc case in Vietnam and identify a novel mutation in the cDH1 gene. case presentation A 28-year-old Vietnamese man was diagnosed with HDGc and a novel mutation at c.639G>A. All exons of cDH1 were sequenced in his pedigree, which revealed the c.639G>A mutation in the proband, his father, and uncle. The patient refused treatment and died 4 months after diagnosis. Endoscopic surveillance of the father and the uncle showed structural abnormalities in the father. conclusion In cases of HDGc, identification of the cDH1 gene mutation is very important for better counseling and more effective strategies to prevent the development of diseases, such as prophylactic gastrectomy for family members with genetic mutations.

关键词： case report cadherin-1 Hereditary diffuse gastric cancer c 639G>A

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Effects of dual sofosbuvir/daclatasvir therapy on, chronic hepatitis c infected, survivors of childhood malignancy

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World Journal of clinical cases 2019年第16期7卷 2247-2255页

作者： Mortada HF El-Shabrawi Laila M Sherief Mostafa Yakoot Naglaa M Kamal Mohamed A Almalky Manal M AbdElgawad Aml A Mahfouz Sherine Helmy Enas M Kamal Dina Attia Hisham R El-Khayat Paediatric Hepatology Department Cairo Faculty of MedicineCairo 11559Egypt Paediatric Hematology-Oncology Department Zagazig Faculty of MedicineZagazig 21121Egypt Internal medicine Pediatrics and HepatologyGreen Clinic and Research CenterAlexandria UniversityAlexandria 21121Egypt Paediatric Hepatology Department Alexandria Faculty of medicineAlexandria 21121Egypt Innovations & Research Pharco CorporationAlexandria 21121Egypt Endemic medicine and Hepatology Department Minia UniversityMinia 22233Egypt Endemic medicine and Hepatology Department Beni-suef UniversityBeni-suef 62511Egypt Gastroenterology and Endemic Medicine Department Theodore Research InstituteCairo 23323Egypt

BAcKGROUND childhood cancer survivors are potentially at a higher risk of infection with hepatitis c virus (HcV).The effects of all-oral direct-acting antiviral therapy (DAA) on both the HcV infection as well as the state of cancer remission have not been well investigated in this *** To test the effects of dual sofosbuvir/daclatasvir (SOF/DcV) therapy in the treatment of chronic HcV in survivors of hematologic malignancy in pediatric age *** We conducted a prospective,uncontrolled,open-label multicenter study.A total of 20 eligible,chronic HcV,genotype-4,infected children who had been in continuous complete remission from hematologic cancer (leukemia/lymphoma) for at least one year were included in the *** patients were treated with combined SOF/DcV for 12 *** were monitored throughout the study till 12 wk after end of treatment for safety and efficacy outcomes including the sustained virologic response 12 (SVR12) rate,hematological indices,liver and kidney *** The intent-to-treat SVR12 rate was 20 of 20 (100%;95%cI: 84%-100%).All patients showed normalized liver enzymes from *** hematological indices,liver and kidney functions were kept normal throughout the *** fatalities or treatment-emergent serious or severe adverse events were reported throughout the *** SOF/DcV combined therapy could be used safely and effectively in the treatment of chronic HcV genotype-4 infection in leukemia/lymphoma treated *** relapses were detected during treatment and throughout the follow up period for either the original malignant disease or the HcV infection.

关键词： chronic hepatitis c Survivors of childhood cancer Sofosbuvir Daclatasvir Efficacy

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WormBot, an open-source robotics platform for survival and behavior analysis in c. elegans

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GEROScIENcE 2019年第6期41卷 961-973页

作者： Pitt, Jason N. Strait, Nolan L. Vayndorf, Elena M. Blue, Benjamin W. Tran, christina H. Davis, Brendon E. M. Huang, Karen Johnson, Brock J. Lim, Keong Mu Liu, Sophie Nikjoo, Arash Vaid, Anuj Wu, Judy Z. Kaeberlein, Matt Univ Washington Dept Pathol 1959 NE Pacific St Seattle WA 98195 USA

caenorhabditis elegans is a popular organism for aging research owing to its highly conserved molecular pathways, short lifespan, small size, and extensive genetic and reverse genetic resources. Here we describe the WormBot, an open-source robotic image capture platform capable of conducting 144 parallel c. elegans survival and behavioral phenotyping experiments. The WormBot uses standard 12-well tissue culture plates suitable for solid agar media and is built from commercially available robotics hardware. The WormBot is controlled by a web-based interface allowing control and monitoring of experiments from any internet connected device. The standard WormBot hardware features the ability to take both time-lapse bright field images and real-time video micrographs, allowing investigators to measure lifespan, as well as heathspan metrics as worms age. The open-source nature of the hardware and software will allow for users to extend the platform and implement new software and hardware features. This extensibility, coupled with the low cost and simplicity of the system, allows the automation of c. elegans survival analysis even in small laboratory settings with modest budgets.

关键词： c elegans Automated Survival Healthspan Open-source

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Prostate cancer induces c/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome

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PROSTATE 2019年第5期79卷 435-445页

作者： Adamo, Hanibal Hammarsten, Peter Hagglof, christina Scherdin, Tove Dahl Egevad, Lars Stattin, Paer Bergstrom, Sofia Halin Bergh, Anders Umea Univ Dept Med Biosci Pathol 6M Umea Sweden Karolinska Univ Hosp Dept Oncol Pathol Stockholm Sweden Uppsala Univ Dept Surg Sci Uppsala Sweden

BackgroundImplantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor ccAAT/enhancer-binding protein- (c/EBP). MethodsTo explore this further, we examined c/EBP expression by quantitative RT-PcR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting. ResultsIn rats, c/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, c/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial c/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of c/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of c/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome. conclusionsThis study suggest that the expression of c/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

关键词： biomarkers c EBP prostate cancer tumors instruct adjacent tissues

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Influence of mulch c/N ratio and decomposition stage on plant N uptake and N availability in soil with or without wheat straw

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JOURNAL OF PLANT NUTRITION AND SOIL ScIENcE 2019年第6期182卷 879-887页

作者： Thi Hoang Ha Truong Kristiansen, Paul Marschner, Petra Univ Adelaide Sch Agr Food & Wine Adelaide SA 5005 Australia Quang Binh Univ Dong Hoi City Quang Binh Prov Vietnam Univ New England Sch Environm & Rural Sci Armidale NSW 2351 Australia

Mulches can improve soil properties, but little is known about nutrient availability in mulched soil that contains plant residues and the effect of mulching with manures. The aim of this study was to determine the effects of mulching with high or low c/N organic materials, in which low c/N materials differed in decomposability, and the presence of wheat straw in the soil on plant growth and N uptake, soil N availability and microbial biomass N within about four months after mulching. Three organic materials were used: mature wheat straw (W, c/N 80), young faba bean shoots (FB, c/N 7), and sheep manure (SM, c/N 8). There were eight treatments differing in amendment methods (mulching or mixing with W or both) and mulching materials (W, FB or SM). Treatments that were only mulched with W, FB or SM are referred to as m-treatments. In m/s-treatments, after W was mixed into the soil, W, FB or SM were placed on the soil surface as mulch. Two other treatments included an unamended control and soil mixed with W. Wheat was planted 0, 35 or 70 days after mulching (referred to as 0, 35, and 70 DAM) and grown for 35 days. Faba bean mulch increased shoot dry weight, shoot N uptake and available N compared to wheat or sheep manure mulch, particularly in the m-treatments. Shoot dry weight was higher in m-treatments than corresponding m/s-treatments with the same mulch type. Shoot N uptake was higher in 70 DAM than in 0 DAM in all treatments and 0.3 to three-fold higher in m-treatments than the corresponding m/s-treatments. Microbial biomass N was higher in 0 DAM than in 35 and 70 DAM in most treatments and up to two-fold higher in m/s-treatments than the corresponding m-treatments. Available N in m/s-treatments was two to six-fold higher than m-treatments in 0 DAM, but differed little in older mulch ages of W and SM. It can be concluded that compared to soil with only mulch, mixing of wheat straw into soil reduced plant growth and N uptake, particularly in the early stages of mulch

关键词： c N ratio manure mulch microbial biomass N N availability shoot dry weight wheat straw

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[email protected] x /TiO 2 as a highly effective and stable recipe for c 3 H 8 and c 3 H 6 combustion

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Fuel 2023年 343卷

作者： Jiali Zhou Ge Li Hongfei Li Ziran Ma Shuang Liu Xiaolong Tang Department of Environmental Engineering University of Science and Technology Beijing Beijing 100083 China National Institute of Clean-and-Low-Carbon Energy Beijing 102211 China School of Materials Science and Engineering Ocean University of China Qingdao 266100 China

Sintering is among the most challenging obstacles preventing the development of platinum catalysts that highly effective for hydrocarbon combustion at low temperatures. To overcome this obstacle, a [email protected] 2 catalyst with platinum nanoparticles encapsulated by TiO x overlayers was synthesized in this article, via melamine-mediated calcinations at 800 °c in air. Being physically constrained (“protected”) and electronically buffered (“Pt x + /Pt 0 ↔ Ti 3+ /Ti 4+ ”) by the thermally stable TiO x , this catalyst preserved a large amount of reactive metallic Pt 0 sites, which therefore exhibited obviously higher activity for c 3 H 8 and c 3 H 6 combustion in comparison with conventional supported Pt/TiO 2 catalysts. Moreover, steam and SO 2 in the reaction atmospheres caused reversible influences on the catalytic performance of this sample, indicating the high practical potential of such a recipe for the design of platinum catalysts with superior activity and durability for hydrocarbon combustion.

关键词： Platinum catalysts TiO x overlayers Pt-TiO x interaction c 3 H 8 and c 3 H 6 combustion Thermal stability H 2 O and SO 2 resistance

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Management of betablocked patients after sustained virological response in hepatitis c cirrhosis

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World Journal of Gastroenterology 2019年第21期25卷 2665-2674页

作者： Marta Abadía María Luisa Montes Dolores Ponce consuelo Froilán Miriam Romero Joaquín Poza Teresa Hernández Rubén Fernández-Martos Antonio Olveira Antonio Olveira Servicio de Aparato DigestivoHospital Universitario La PazMadrid 28046Spain Unidad VIH Servicio de Medicina InternaHospital Universitario La PazMadrid 28046Spain Servicio de Radiología Hospital Universitario La PazMadrid 28046Spain CIBERehd IdiPAZ Madrid 28029Spain

BAcKGROUND current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis c virus (HcV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option. AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population. METHODS Inclusion criteria were age > 18 years, HcV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after directacting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician. RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, child-Pugh score A 77%, median platelets 77.000 × 103/μL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was

关键词： Hepatitis c virus Oesophageal varices Portal hypertension Betablocker Variceal bleeding

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Isolated c. elegans germ nuclei exhibit distinct genomic profiles of histone modification and gene expression

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BMc GENOMIcS 2019年第1期20卷 1-15页

作者： Han, Mei Wei, Guifeng McManus, catherine E. Hillier, LaDeana W. Reinke, Valerie Yale Univ Dept Genet New Haven CT 06520 USA Univ Oxford Dept Biochem Dev Epigenet Oxford OX1 3QU England Univ Washington Sch Med Dept Genome Sci Seattle WA 98195 USA

BackgroundThe wide variety of specialized permissive and repressive mechanisms by which germ cells regulate developmental gene expression are not well understood genome-wide. Isolation of germ cells with high integrity and purity from living animals is necessary to address these open questions, but no straightforward methods are currently *** we present an experimental paradigm that permits the isolation of nuclei from c. elegans germ cells at quantities sufficient for genomic analyses. We demonstrate that these nuclei represent a very pure population and are suitable for both transcriptome analysis (RNA-seq) and chromatin immunoprecipitation (chIP-seq) of histone modifications. From these data, we find unexpected germline- and soma-specific patterns of gene *** new capacity removes a major barrier in the field to dissect gene expression mechanisms in the germ line of c. elegans. consequent discoveries using this technology will be relevant to conserved regulatory mechanisms across species.

关键词： c elegans Germ cells Gene expression Genomics Method development

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Economic evaluation of the hepatitis c elimination strategy in Greece in the era of affordable direct-acting antivirals

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World Journal of Gastroenterology 2019年第11期25卷 1327-1340页

作者： Ilias Gountas Vana Sypsa George Papatheodoridis Kyriakos Souliotis Kostas Athanasakis Homie Razavi Angelos Hatzakis Department of Hygiene Epidemiology and Medical StatisticsMedical SchoolNational and Kapodistrian University of Athens Hellenic Scientific Society for the Study of AIDS and Sexually Transmitted Diseases Department of Gastroenterology Medical SchoolNational and Kapodistrian University of AthensLaiko General Hospital Faculty of Social and Political Sciences University of Peloponnese Department of Health Economics National School of Public Health Center for Disease Analysis

BAcKGROUND Hepatitis c virus(HcV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HcV-elimination by 2030. This study aims to estimate the required interventions to achieve elimination using updated information for direct-acting antiviral(DAA) treatment coverage, to compute the total costs(including indirect/societal costs) of the strategy and to identify whether the elimination strategy is cost-effective/cost-saving in *** To estimate the required interventions and subsequent costs to achieve HcV elimination in *** A previously validated mathematical model was adapted to the Greek HcVinfected population to compare the outcomes of DAA treatment without the additional implementation of awareness or screening campaigns versus an HcV elimination strategy, which includes a sufficient number of treated patients. We estimated the total costs(direct and indirect costs), the disability-adjusted life years and the incremental cost-effectiveness ratio using two different price *** Without the implementation of awareness or screening campaigns,approximately 20000 patients would be diagnosed and treated with DAAs by2030. This strategy would result in a 19.6% increase in HcV-related mortality in2030 compared to 2015. To achieve the elimination goal, 90000 patients need to be treated by 2030. Under the elimination scenario, viremic cases would decrease by78.8% in 2030 compared to 2015. The cumulative direct costs to eliminate the disease would range from 2.1-2.3 billion euros(€) by 2030, while the indirect costs would be €1.1 billion. The total elimination cost in Greece would range from €3.2-3.4 billion by 2030. The cost per averted disability-adjusted life year is estimated between €10100 and €13380, indicating that the elimination strategy is very costeffective. Furthermore, HcV elimination strategy would save €560-895 million *** Without

关键词： Hepatitis c elimination cost effectiveness cost of elimination Indirect costs Projections Mathematical modelling Awareness and screening programs World Health Organization targets

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Exploring c Semantics and Pointer Provenance

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PROcEEDINGS OF THE AcM ON PROGRAMMING LANGUAGES-PAcMPL 2019年第POPL期3卷 1-32页

作者： Memarian, Kayvan Gomes, Victor B. F. Davis, Brooks Kell, Stephen Richardson, Alexander Watson, Robert N. M. Sewell, Peter Univ Cambridge Cambridge England SRI Int 333 Ravenswood Ave Menlo Pk CA 94025 USA

The semantics of pointers and memory objects in c has been a vexed question for many years. c values cannot be treated as either purely abstract or purely concrete entities: the language exposes their representations, but compiler optimisations rely on analyses that reason about provenance and initialisation status, not just runtime representations. The ISO WG14 standard leaves much of this unclear, and in some respects differs with de facto standard usage D which itself is difficult to investigate. In this paper we explore the possible source-language semantics for memory objects and pointers, in ISO c and in c as it is used and implemented in practice, focussing especially on pointer provenance. We aim to, as far as possible, reconcile the ISO c standard, mainstream compiler behaviour, and the semantics relied on by the corpus of existing c code. We present two coherent proposals, tracking provenance via integers and not;both address many design questions. We highlight some pros and cons and open questions, and illustrate the discussion with a library of test cases. We make our semantics executable as a test oracle, integrating it with the cerberus semantics for much of the rest of c, which we have made substantially more complete and robust, and equipped with a web-interface GUI. This allows us to experimentally assess our proposals on those test cases. To assess their viability with respect to larger bodies of c code, we analyse the changes required and the resulting behaviour for a port of FreeBSD to cHERI, a research architecture supporting hardware capabilities, which (roughly speaking) traps on the memory safety violations which our proposals deem undefined behaviour. We also develop a new runtime instrumentation tool to detect possible provenance violations in normal c code, and apply it to some of the SPEc benchmarks. We compare our proposal with a source-language variant of the twin-allocation LLVM semantics proposal of Lee et al. Finally, we describe ong

关键词： c

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