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PD-1 inhibitors monotherapy in hepatocellular carcinoma: Meta-analysis and systematic review

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Hepatobiliary & Pancreatic Diseases International 2019年第6期18卷 505-510页

作者： ioannis A.Voutsadakis Algoma District Cancer Program Sault Area Hospital Section of Internal Medicine Division of Clinical Sciences Northern Ontario School of Medicine

Background:Immunity plays a major role in carcinogenesis and this is the case also for hepatocellular carcinomas(HCC).Checkpoint inhibitors,novel drugs that enhance the immune system’s ability to attack cancers,have been successfully introduced for the therapy of various malignancies including *** important target of these drugs is the PD-L1/PD-1 ligand/receptor pair and several clinically available inhibitors of this pair *** sources:A search of the literature until April 20,2019 was performed in the MEDLINE/PubMed database,the Embase database and the Cochrane Central Register of Controlled *** clinical studies describing treatment with PD-L1/PD-1 inhibitors as monotherapy in HCC patients were *** characteristics with relevance for treatment efficacy,such as liver function,disease extend and previous treatment,were extracted from identified *** and survival outcomes were the primary focus of the *** estimates of response rates and survival were calculated using a random or fixed effect model,depending on *** common adverse effects were also recorded and ***:Three studies(two on nivolumab and one on pembrolizumab)with a total of 400 patients were included in the *** summary response rate(RR)was 17.3%[95%confidence interval(CI):13.2%–21.4%].The summary disease control rate(DCR)was 56.6%(95%CI:44.7%–68.5%).Summary progression free survival(PFS)was 3.5 months(95%CI:2.8–4.2 months).Summary overall survival(OS)was 10.4 months(95%CI:3.5–17.2 months).Adverse effect rate was low and also consistent with the adverse effect profile of PD-L1/PD-1 inhibitors in other disease ***:Pembrolizumab and nivolumab are the only checkpoint inhibitors with data in *** of their effectiveness discloses rates not dissimilar to other systemic therapies available for this *** interest also are the observed long responses in a sub-set of ***

关键词： Hepatocellular carcinoma Immune checkpoint inhibitors Nivolumab Pembrolizumab Meta-analysis

Thrombocytosis as a prognostic marker in gastrointestinal cancers

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World Journal of Gastrointestinal Oncology 2014年第2期6卷 34-40页

作者： ioannis A Voutsadakis Division of Medical Oncology Sault Area Hospital

Thrombocytosis is an adverse prognostic factor in many types of cancer. These include breast cancer, ovarian and other gynecologic cancers, renal cell carcinoma and lung cancers. In gastrointestinal cancers of various locations and histologic types, thrombocytosis has been reported in general to be associated with adverse clinical outcomes. Platelet count measurement is well standardized and available in every clinical laboratory, making its use as a prognostic marker practical. This paper will discuss the data on the prognostic value of thrombocytosis in gastrointestinal cancers as well as pathogenic aspects of the association that strengthen the case for its use in clinical prognostication.

关键词： Thrombocytosis Platelets Cancer Gastroin-testinal Prognosis

Landscape of BRIP1 molecular lesions in gastrointestinal cancers from published genomic studies

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World Journal of Gastroenterology 2020年第11期26卷 1197-1207页

作者： ioannis A Voutsadakis Algoma District Cancer Program Sault Area HospitalSault Ste MarieON P6B 0A8Canada Section of Internal Medicine Division of Clinical SciencesNorthern Ontario School of MedicineSudburyON P0M 2Z0Canada

BACKGROUND BRIP1 is a helicase that partners with BRCA1 in the homologous recombination(HR) step in the repair of DNA inter-strand cross-link lesions. It is a rare cause of hereditary ovarian cancer in patients with no mutations of BRCA1 or BRCA2. The role of the protein in other cancers such as gastrointestinal(GI) carcinomas is less well characterized but given its role in DNA repair it could be a candidate tumor suppressor similarly to the two BRCA *** To analyze the role of helicase BRIP1(FANCJ) in GI cancers *** Publicly available data from genomic studies of esophageal, gastric, pancreatic,cholangiocarcinomas and colorectal cancers were interrogated to unveil the role of BRIP1 in these carcinomas and to discover associations of lesions in BRIP1 with other more common molecular defects in these *** Molecular lesions in BRIP1 were rare(3.6% of all samples) in GI cancers and consisted almost exclusively of mutations and amplifications. Among mutations,40% were possibly pathogenic according to the Onco KB database. A majority of BRIP1 mutated GI cancers were hyper-mutated due to concomitant mutations in mismatch repair or polymerase ε and δ1 genes. No associations were discovered between amplifications of BRIP1 and any mutated genes. In gastroesophageal cancers BRIP1 amplification commonly co-occurs with ERBB2 *** Overall BRIP1 molecular defects do not seem to play a major role in GI cancers whereas mutations frequently occur in hypermutated carcinomas and co-occur with other HR genes mutations. Despite their rarity, BRIP1 defects may present an opportunity for therapeutic interventions similar to other HR defects.

关键词： BRIP1 FANCJ BACH1 Gastrointestinal cancers Mutations Copy number alterations

Striatum-specific mechanisms regulate neuronal cell cycle re-entry:the choice between life and death

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Neural Regeneration Research 2023年第3期18卷 523-524页

作者： Paula Dietrich ioannis Dragatsis Department of Physiology The University of TennesseeHealth Science CenterMemphisTNUSA

Mitochondria dysfunction occurs in the aging brain as well as in several neurodegenerative disorders and predisposes neuronal cells to enhanced sensitivity to *** particular,defects in any of the mitochondria respiratory chain complexes lead to impaired adenosine triphosphate production resulting in diseases that often affect the central nervous *** instance,innate deficits in succinate dehydrogenase(SDH)mitochondria respiratory chain complex II activity caused by genetic mutations in SDH subunits lead to early-onset neurodegeneration(Jain-Ghai et al.,2013),while several adult-onset genetic neurodegenerative disorders are associated with variable levels of complex II deficiency in the central nervous system(Túnez et al.,2010).Also,chemically induced complex II deficiency leads to neurodegeneration.

关键词： SDH impaired cycle

A historical evaluation of Chinese tongue diagnosis in the treatment of septicemic plague in the pre-antibiotic era, and as a new direction for revolutionary clinical research applications

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Journal of Integrative Medicine 2018年第3期16卷 141-146页

作者： ioannis Solos Yuan Liang Department of Orthopedics and Traumatology Guangzhou Zhongxing Sports Trauma Hospital Institute of Basic Theory in Chinese Medicine China Academy of Chinese Medical Sciences

Chinese tongue diagnosis was initially developed to quickly and efficiently diagnose and prescribe medicine, while at the same time allowing the doctor to have minimal contact with the patient. At the time of its compiling, the spread of Yersinia pestis, often causing septicaemia and gangrene of the extremities,may have discouraged doctors to come in direct contact with their patients and take the ***, in recent decades, modern developments in the field of traditional Chinese medicine, as well as the spread of antibiotics in conjunction with the advancements of microbiology, have overshadowed the original purpose of this methodology. Nevertheless, the fast approaching post-antibiotic era and the development of artificial intelligence may hold new applications for tongue diagnosis. This article focuses on the historical development of what is the world＇s earliest tongue diagnosis monograph, and discusses the directions that such knowledge may be used in future clinical research.

关键词： Tongue diagnosis Chinese medicine Yersinia pestis Literature research

On the Convergence of Broyden-Like Methods

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Acta Mathematica Sinica,English Series 2007年第11期23卷 2087-2096页

作者： ioannis K.ARGYROS Department of Mathematical Sciences Cameron UniversityLawtonOK 73505USA

The author provides a finer local as well as semilocM convergence analysis of a certain class of Broyden-like methods for solving equations containing a nondifferentiable term on the m-dimensional Euclidean space （m ... 详细信息

关键词： Broyden-like methods l2 norm Fréchet derivative radius of convergence local/semilocal convergence analysis

Hesitant steps from the artificial skin to organ regeneration

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Regenerative Biomaterials 2018年第4期5卷 189-195页

作者： ioannis V.Yannas Department of Mechanical Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA

This is a historical account of the steps,both serendipitous and rational,that led my group of students and colleagues at MIT and Harvard Medical School to discover induced organ *** research led to methods for growing back in adult mammals three heavily injured organs,skin,peripheral nerves and the *** conclude that regeneration in adults is induced by a modification of normal wound healing.

关键词： skin regeneration peripheral nerve regeneration contraction blocking dermis regeneration template

Impact of earthquake-induced bridge damage and time evolving traffic demand on the road network resilience

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Journal of Traffic and Transportation Engineering(English Edition) 2019年第1期6卷 35-48页

作者： ioannis Kilanitis Anastasios Sextos Department of Civil Engineering Aristotle University of Thessaloniki Department of Civil Engineering University of Bristol

Damage from recent earthquakes has shown that substandard bridges are particularly vulnerable to strong ground motions being the weakest components of a road *** and foundation damages in bridges lead to a significant loss related to both repair process and a prolonged traffic disruption, which in turn results in large indirect loss in the affected area. Along these lines, the estimation of the overall loss related to earthquake-induced damage in highway bridges and overpasses must be based on a wider network analysis rather than on a single structural assessment. Key concept in such a comprehensive loss estimation procedure is the network resilience, expressing the extent of both direct and indirect loss, as well as the system's ability to quickly recover its preearthquake state. In this paper, a recently developed framework for assessing the loss and resilience associated with seismic impact on the structural and geotechnical components of a road network, as well as the relevant software developed are extended to further consider the implications of post-earthquake traffic demand variation. Moreover, a sensitivity analysis is conducted for a case study network to investigate the impact of traffic demand variation after a major earthquake event and the subsequent trip cancelations on the time-variant, cumulative cost at a network level. The results clearly highlight that not only the seismic resilience of a highway network should be assessed in a holistic manner coupling seismic hazard, structural and traffic analysis, but the latter shall include realistic scenarios with respect to the potential variation of origin-destination demand after the earthquake and during the recovery period.

关键词： Seismic resilience Road networks Traffic analysis Bridges Earthquake damage

Fundamental problems in hydrodynamics of ellipsoidal forms

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Journal of Hydrodynamics 2018年第3期30卷 403-410页

作者： Touvia Miloh ioannis K.Chatjigeorgiou Faculty of Engineering Tel Aviv University School of Naval Architecture and Marine Engineering National Technical University of Athens

In this study, we tackle with one single effort, three fundamental problems in ship hydrodynamics, namely the attraction force exerted on a single ship moving rectilinearly close and parallel to a rigid wall（berthing）, the determination of the associated added-mass coefficients（maneuvering） and finally evaluating the forces exerted on a ship in a two-ship crossing scenarios. The novelty of the present approach relies on using Weinblum’s proposition to assimilate the ship’s hull by an ＂equivalent＂ tri-axial ellipsoid, as well as the employment of ellipsoidal harmonics expansion techniques.

关键词： Ellipsoidal forms ellipsoidal harmonics Lamé functions ship hydrodynamics ultimate image singularities