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Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

World Journal of Gastroenterology 2020年第33期26卷 4889-4899页

作者： ronald neil kostoff Michael Brandon Briggs Darla Roye Shores School of Public Policy Georgia Institute of TechnologyGainesvilleVA 20155United States Independent Consultant RoscommonMI 48653United States The Hopkins Resource for Intestinal Vitality and Enhancement the Johns Hopkins University School of MedicineBaltimoreMD 21287United States

Inflammatory bowel disease(IBD)incidence has been increasing steadily,most dramatically in the Western developed *** often includes lifelong immunosuppressive therapy and *** is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential *** of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug *** study used a treatment repurposing methodology,the literature-related discovery and innovation(LRDI)text mining system,to identify potential treatments(developed for non-IBD diseases)with sufficient promise for extrapolation to treatment of *** searching for desirable patterns of twenty key biomarkers relevant to IBD(e.g.,inflammation,reactive oxygen species,autophagy,barrier function),the LRDI-based query retrieved approximately 9500 records from *** most recent 350 records were further analyzed for *** 18%(64/350)met the criteria for discovery(not previously studied in IBD human or animal models)and relevance for application to IBD *** of the treatments were compounds derived from herbal remedies,and the majority of treatments were being studied in cancer,diabetes,and central nervous system disease,such as depression and *** further validation of the search strategy,the query identified ten treatments that have just recently begun testing in IBD models in the last three ***-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing.A more comprehensive query with additional key biomarkers would have retrieved many thousands more records,further increasing the yield of IBD treatment repurposing discovery.

关键词： Treatment repurposing Treatment repositioning Inflammatory bowel disease Literature-based discovery Text mining Crohn’s disease Ulcerative colitis Novel treatments

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The synthesis of polymers of intrinsic microporosity (PIMs)

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Science China Chemistry 2017年第8期60卷 1023-1032页

作者： neil B.McKeown School of Chemistry University of Edinburgh David Brewster Road Edinburgh EH9 3F J U

Polymers of intrinsic microporosity （PIMs） are a class of porous organic polymer （POP） that form microporous solids due to the inefficient packing of their rigid and contorted macromolecular chains. In contrast to other types of POP, PIMs are not comprised of a network of cross-linked covalent bonds so that they can be dissolved in organic solvents and processed into robust films, coatings or fibres. Here, over twelve years＇ accumulated research on the synthesis of PIMs is reviewed. To date, three types of polymerisation reaction have been used successfully to prepare PIMs of sufficient molecular mass to form robust self-standing films. These involve the formation of dibenzodioxin, Tr6ger＇s base and imide linkages between monomeric units. This rapid development of synthetic methods for preparing PIMs has been driven by their rich potential for numerous diverse applications and this synergistic relationship between synthesis and functionality is set to continue.

关键词： polymers of intrinsic microporosity synthesis porous organic polymers

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Gamma-ray bursts in the swift-Fermi era

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Frontiers of physics 2013年第6期8卷 661-678页

作者： neil Gehrels Soebur Razzaque Astrophysics Science Division NASA Goddard Space Flight Center Greenbelt MD 20771 USA George Mason University Fairfax VA 22030 USA Resident at Space Science Division Naval Research Laboratory Washington DC 20375 USA

Gamma-ray bursts （GRBs） are among the most violent occurrences in the universe. They are pow- erful explosions, visible to high redshift, and thought to be the signature of black hole birth. They are highly luminous events and provide excellent probes of the distant universe. GRB research has greatly advanced over the past 10 years with the results from Swift, Fermi and an active followup community. In this review we survey the interplay between these recent observations and the theoretical models of the prompt GRB emission and the subsequent afterglows.

关键词： gamma-ray bursts (GRBs) Swift Fermi

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Relative abundance of American badger (Taxidea taxus) and red fox (Vulpes vulpes) in landscapes with high and low rodenticide poisoning levels

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Integrative Zoology 2012年第1期7卷 41-47页

作者： Gilbert PROULX neil MacKENZIE Alpha Wildlife Research&Management Sherwood ParkAlbertaCanada

Over the past decade,extensive poisoning campaigns have been conducted in southern Saskatchewan to control Richardson’s ground squirrel Spermophilus richardsonii(Sabine,1822)*** campaigns might impact on predator abundance by decreasing prey levels,and also through secondary *** spotlighting,we investigated the relative abundance of American badgers Taxidea taxus(Schreber,1777)and red fox Vulpes vulpes(Linnaeus,1758)in 2 study areas with road access and crops,but with different levels of *** the study area with relatively low poisoning(19.6%of the area traversed by roads),there were 2.2 times more American badgers per km of road and 6.4 times more red foxes per km than in the study area with high poisoning(89.7%of the area).It is recommended that an Integrated Pest Management program be developed to conserve natural predators across landscapes.

关键词： ground squirrels poisoning populations predators

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Herb-Induced Liver Injury: A Global Concern

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Chinese Journal of Integrative Medicine 2018年第9期24卷 643-644页

作者： neil Kaplowitz USC Research Center for Liver Disease USC Keck School of Medicine

Chinese medicine and herb medicine though used to treat liver diseases are an important cause of liver injury. Many phytochemicals have the potential to injure the liver, some in a dose-related fashion and more often in an idiosyncratic fashion, meaning occurrence is uncommon to rare in the population using these treatments. As is the case with pharmaceuticals, the phytochemicals are usually tolerated despite either no or mild transient subclinical injury but rarely in some susceptible patients cause moderate to severe liver injury which is likely mediated by the adaptive immune system.

关键词： herb-induced liver injury diagnosis and management guideline Chinese medicine

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Multimodality treatment of potentially curative gastric cancer: Geographical variations and future prospects

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World Journal of Gastroenterology 2014年第36期20卷 12892-12899页

作者： neil D Merrett Discipline of Surgery School of Medicine University Of Western Sydney Penrith NSW 2751 Australia Department of Upper Gastrointestinal Surgery Sydney South West Local Health District Liverpool NSW 2170 Australia

After much controversy, multimodality therapy is now accepted worldwide as the gold standard for treatment of resectable bulky localized gastric cancer. There is significant regional variation in the style of multimodality treatment with adjuvant chemoradiation the North American standard, neoadjuvant chemotherapy preferred in Europe and Australasia, whilst adjuvant chemotherapy is preferred in Asia. With further standardization of surgery and D1+/D2 resections increasingly accepted world wide, and in particular in the West, as the surgical standard of care for potentially curable disease, it is timely to reassess the multimodality regimes being used. The challenge in the use of multimodality therapy is how current outcomes can be standardized and improved further. Recent studies indicate that mere intensification of the regime in time, dosage or addition of further agents does not improve localized gastric cancer outcomes. More novel strategies including early commencement of adjuvant therapies, intra-peritoneal chemotherapy or assessing neoadjuvant response with positron emission tomography scanning may give improvements in outcomes. The introduction of targeted therapies means that the adjuvant use of biological agents needs to be explored. By proper assessment of the patient’s co-morbidities, full tumour staging, and a better understanding of the tumour’s molecular pathology, multimodality therapy for gastric adenocarcinoma may be individualized to optimize the likelihood of cure.

关键词： Gastric cancer Gastrectomy Multimodality Adjuvant treatment Neoadjuvant Targeted therapy Human epidermal growth factor receptor

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The effects of acquired paternal obesity on the next generation

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Asian Journal of Andrology 2011年第2期13卷 195-196页

作者： neil A Youngson Emma Whitelaw Queensland Institute of Medical Research 300 HerstonRoad Herston Brisbane 4006 Australia

It is well established that the health of mothers can influence the health of theiroffspring, i ms can occur as a result or me transfer of viruses or toxins via the placenta or the milk, a compromised nutrient supply to the embryo or abnormal behavioural inter- actions between mother and offspring） However, examples of paternal health affecting the next generation are rare.

关键词： Neurophysiology Learning and memory

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Historical overview and review of current day treatment in the management of acute variceal haemorrhage

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World Journal of Gastroenterology 2014年第21期20卷 6481-6494页

作者： neil Rajoriya Dhiraj Tripathi Department of Hepatology The New Queen Elizabeth HospitalBirmingham B15 2THUnited Kingdom

Variceal haemorrhage is one of the most devastating consequences of portal hypertension, with a 1-year mortality of 40%. With the passage of time, acute management strategies have developed with improved survival. The major historical treatment landmarks in the management of variceal haemorrhage can be divided into surgical, medical, endoscopic and radiological breakthroughs. We sought to provide a historical overview of the management of variceal haemorrhage and how treatment modalities over time have impacted on clinical outcomes. A PubMed search of the following terms: portal hypertension, variceal haemorrhage, gastric varices, oesophageal varices, transjugular intrahepatic portosystemic shunt was performed. To complement this, Google™ was searched with the aforementioned terms. Other relevant references were identified after review of the reference lists of articles. The review of therapeutic advances was conducted divided into pre-1970s, 1970/80s, 1990s, 2000-2010 and post-2010. Also, a summary and review on the pathophysiology of portal hypertension and clinical outcomes in variceal haemorrhage was performed. Aided by the development of endoscopic therapies, medication and improved radiological interventions; the management of variceal haemorrhage has changed over recent decades with improved survival from an often-terminating event in recent past.

关键词： Variceal haemorrhage Oesophageal varices Gastric varices Portal hypertension

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Upper bounds of Schubert polynomials

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Science China Mathematics 2022年第6期65卷 1319-1330页

作者： neil Jiuyu Fan Peter Long Guo Department of Mathematics Sichuan UniversityChengdu 610064China Center for Combinatorics LPMCNankai UniversityTianjin 300071China

Let w be a permutation of{1,2,...,n},and let D(w)be the Rothe diagram of *** Schubert polynomial■w_(x)can be realized as the dual character of the flagged Weyl module associated with D(w).This implies the following coefficient-wise inequality:Min_(x)≤■_(w)(x)≤Max_(w)xwhere both Min_(w)(x)and Max_(w)(x)are polynomials determined by D(w).Fink et al.(2018)found that■w_(x)equals the lower bound Min_(w)(x)if and only if w avoids twelve permutation *** this paper,we show that■w_(x)reaches the upper bound Max_(w)(x)if and only if w avoids two permutation patterns 1432 and ***,for any given compositionα∈Z^(n)≥0,one can define a lower bound Min_(α)(x)and an upper bound Max_(α)(x)for the key polynomialκ_(α)(x).Hodges and Yong(2020)established thatκ_(α)(x)equals Min_(α)(x)if and only ifαavoids five composition *** show thatκ_(α)(x)equals Max_(α)(x)if and only ifαavoids a single composition pattern(0,2).As an application,we obtain that whenαavoids(0,2),the key polynomialκ_(α)(x)is Lorentzian,partially verifying a conjecture of Huh et al.(2019).

关键词： Schubert polynomial key polynomial flagged Weyl module upper bound Lorentzian polynomial

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Thermalization and relaxation mediated by phonon management in tin-lead perovskites

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Light(Science & Applications) 2023年第9期12卷 1971-1981页

作者： Linjie Dai Junzhi Ye neil C.Greenham Cavendish Laboratory University of Cambridge19 J.J.Thomson AvenueCambridge CB30HEUK

Understanding and control of ultrafast non-equilibrium processes in semiconductors is key to making use of the full photon energy before relaxation,leading to new ways to break efficiency limits for solar energy *** this work,we demonstrate the observation and modulation of slow relaxation in uniformly mixed tin-lead perovskites(MASn_(x)Pb_(1-x)I_(3)and CsSn_(x)Pb_(1-x)I_(3)nanocrystals).Transient absorption measurements reveal that slow cooling mediated by a hot phonon bottleneck effect appears at carrier densities above~10^(18)cm^(−3)for tin-lead alloy nanocrystals,and tin addition is found to give rise to suppressed *** the alloy nanoparticles,the combination of a newly introduced high-energy band,screened Fröhlich interaction,suppressed Klemens decay and reduced thermal conductivity(acoustic phonon transport)with increased tin content contributes to the slowed *** inorganic nanocrystals where defect states couple strongly with carriers,sodium doping has been confirmed to benefit in maintaining hot carriers by decoupling them from deep defects,leading to a decreased energy-loss rate during thermalization and an enhanced hot phonon bottleneck *** slow cooling we observe uncovers the intrinsic photophysics of perovskite nanocrystals,with implications for photovoltaic applications where suppressed cooling could lead to hot-carrier solar cells.

关键词： alloy relaxation phonon

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