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| 1 | Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy显示文摘AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob/ob chow),respectively.Furthermore,fibrosis stage was significantly elevated for DIO-NASH mice(0 vs 1.2±0.2,P<0.05 compared to lean chow)and ob/ob NASH(0.1±0.1 vs 3.0±0.2,P<0.001compared to ob/ob chow).Notably,fibrosis stage was significantly(P<0.001)increased in ob/ob-NASH mice,when compared to DIO-NASH mice.CONCLUSION:These data introduce the obese dietinduced DIO-NASH and ob/ob-NASH mouse models with biopsy-confirmed individual disease staging as a preclinical platform for evaluation of novel NASH therapeutics. | Maria Nicoline Baandrup Kristiansen Sanne Skovgard Veidal Kristoffer Tobias Gustav Rigbolt Kirstine Sloth Tolbol Jonathan David Roth Jacob Jelsing Niels Vrang Michael Feigh | 2016 | World Journal of Hepatology2016，8，16： | 10 |
| 2 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 3 | Pushing the boundaries of diode-pumped solid-state lasers for high-energy applications显示文摘We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled,diode-pumped multi-slab Yb:YAG laser operating at 1 Hz.To the best of our knowledge,this is the highest energy ever recorded for a diodepumped laser system. | Saumyabrata Banerjee Paul Mason Jonathan Phillips Jodie Smith Thomas Butcher Jacob Spear Mariastefania De Vido Gary Quinn Danielle Clarke Klaus Ertel Cristina Hernez-Gomez Chris Edwards John Collier | 2020 | High Power Laser Science and Engineering2020，8，2： | 4 |
| 4 | Power Output and Electromyography Activity of the Back Squat Exercise with Cluster Sets显示文摘 | Jordan M. Joy Jonathan M. Oliver Sean A. McCleary Ryan P. Lowery Jacob M. Wilson | 2013 | Journal of Sports Science2013，1，1： | 2 |
| 5 | Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort显示文摘 | Ian Jacobs Aleksandra Gentry-Maharaj Matthew Burnell Ranjit Manchanda Naveena Singh Aarti Sharma Andy Ryan Mourad W Seif Nazar N Amso Gillian Turner Carol Brunell Gwendolen Fletcher Rani Rangar Kathy Ford Keith Godfrey Alberto Lopes David Oram Jonathan He | 2011 | Lancet Oncology2011，，1： | 2 |
| 6 | United States-based practice patterns and resource utilization in advanced neuroendocrine tumor treatment显示文摘AIM: To assess advanced neuroendocrine tumor (NET) treatment patterns and resource utilization by tumor progression stage and tumor site in the United States. METHODS: United States Physicians meeting eligibility criteria were provided with online data extraction forms to collect patient chart data on recent NET patients. Resource utilization and treatment pattern data were collected over a baseline period (after diagnosis and before tumor progression), as well as initial and secondary progression periods, with progression defined according to measureable radiographic evidence of tumor progression. Resource categories used in the analysis include: Treatments (e.g. , surgery, chemotherapy, radiotherapy, targeted therapies), hospitalizations and physician visits, diagnostic tests (biomarkers, imaging, laboratory tests). Comparisons between categories of resource utilization and tumor progression status were examined using univariate (by tumor site) and multivariate analyses (across all tumor sites). RESULTS: Fifty-five physicians were included in the study and completed online data extraction forms using the charts of 110 patients. The physician sample showed a relatively even distribution for those affiliated with academic versus community hospitals (46% vs 55%). Forty (36.3%) patients were reported to have pancreatic NET (pNET), while 70 (63.6%) patients had gastrointestinal tract (GI)/Lung as the primary NET site. Univariate analysis showed the proportion of patients hospitalized increased from 32.7% during baseline to 42.1% in the progression stages. While surgeries were performed at similar proportions overall at baseline and progression, pNET patients, were more likely than GI/Lung NET patients to have undergone surgery during the baseline (33.3% vs 25.0%) and any progression periods (26.7% vs 23.4%). While peptide-receptor radionuclide and targeted therapy utilization was low across NET types and tumor stages, GI/Lung types exhibited greater utilization of these technologies compared to pNET. Chemotherapy utilization was also greater among GI/Lung types. Multivariate analysis results demonstrated that patients in first progression period were over 3 times more likely to receive chemotherapy when compared to baseline (odds ratio: 3.31; 95%CI: 1.46-7.48, P=0.0041). Further, progression was associated with a greater likelihood of having a study physician visit [relative risk (RR): 1.54; 95%CI: 1.10-2.17, P=0.0117], and an increased frequency of other physician visits (RR: 1.84; 95%CI: 1.10-3.10, P=0.0211). CONCLUSION: Resource utilization in advanced NET in the United States is significant overall and data suggests progression has an impact on resource utilization regardless of NET tumor site. | Jonathan Strosberg Roman Casciano Lee Stern Rohan Parikh Maruit Chulikavit Jacob Willet Zhimei Liu Xufang Wang Krzysztof J Grzegorzewski | 2013 | World Journal of Gastroenterology2013，19，15： | 1 |
| 7 | Lymphocyte levels of GRK2 (ARK1) mirror changes in the LVAD-supported failing human heart: lower GRK2 associated with improved -adrenergic signaling after mechanical unloading显示文摘 | Jonathan AH Matthew LW Jacob NS | 2006 | Cardiac Fail2006，12，5： | 1 |
| 8 | Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells显示文摘 | Ayelet Itzhaki-Alfia Jonathan Leor Ehud Raanani Leonid Sternik Dan Spiegelstein Shiri Netser Radka Holbova Meirav Pevsner-Fischer Jacob Lavee Israel M. Barbash | 2009 | Circulation2009，，25： | 1 |
| 9 | Fine-scale habitats influence tree species assemblage in a miombo forest显示文摘Aims Relationships between local habitat heterogeneity and tree commu-nities in miombo woodlands have been very little studied.While some studies have addressed this topic at broad scales and based on few environmental parameters,this study aims at(i)detecting fine-scale habitats(≤10 ha)on the basis of a detailed characterisation of soil explicitly considering past anthropogenic disturbances,and an exhaustive census of the tree community,and at(ii)searching for indicator tree species corresponding to the resulting habitats.Methods The study was carried out in the miombo woodland of Mikembo Forest Reserve,Upper Katanga,The Democratic Republic of the congo.A complete census of the tree community was conducted in a 10-ha forest dynamics plot comprising 160 adjacent quadrats of 25×25 m,with a total of 4604 trees(diameter at breast height>10 cm).Thirty-six physicochemical soil parameters were measured.Studying the frequency distribution of soil charcoal content allowed identifying local signature of past human agriculture in the soil.Two strategies were used to define habitats:(i)a combination of principal component analysis(PcA)on soil variables and Ward clustering and(ii)multivariate regression trees(MRT)to search for key soil parameters allowing the best prediction of species composition.Tree-habitat associations were tested by means of a robust statistical framework combining the IndVal index and torus randomisations.Important Findings The forest contained 82 tree species and a significant proportion of wet miombo species(e.g.Marquesia macroura).We detected a strong east-west edaphic gradient driven by soil texture;most chemical soil parameters followed this pattern.Five habitats were identified based on soil factors and floristic composition.Nine indicator species of these habitats were found.The key soil fac-tors discriminating habitats were total calcium,available forms of phosphorus and clay content.Even though past agricultural practices were successfully detected in soils,they did not display any significant influence neither on habitat differentiation nor on the associated tree communities.Based on an unprecedented large number of soil parameters,fine-scale soil heterogeneity and niche partitioning were shown to contribute to the variabil-ity of the floristic composition in this forest.Our results indicated that considering the most variable environmental parameters,as in PcA,is a poor manner for defining habitats.In contrast,combining MRT with the IndVal index and torus randomisation has proved to be a much more robust and sensitive approach to highlight tree-habitat associations at this scale.The common dichotomous viewpoint of considering deterministic and neutral effects as acting at broad and fine scales,respectively,is not confirmed when measuring suitable environmental variables,even in a case where the physical environment does not exhibit strong heterogeneity. | Jonathan Ilunga Muledi David Bauman Thomas Drouet Jason Vleminckx Arnaud Jacobs Jean Lejoly Pierre Meerts Mylor Ngoy Shutcha | 2017 | Journal of Plant Ecology2017，10，6： | 1 |
| 10 | Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells显示文摘 | Ayelet Itzhaki-Alfia Jonathan Leor Ehud Raanani Leonid Sternik Dan Spiegelstein Shiri Netser Radka Holbova Meirav Pevsner-Fischer Jacob Lavee Israel M. Barbash | 2009 | Circulation2009，，25： | 1 |
| 11 | Acute Neurocardiogenic Injury After Subarachnoid Hemorrhage显示文摘 | Nader M. Banki Alexander Kopelnik Michael W. Dae Jacob Miss Poyee Tung Michael T. Lawton Barbara J. Drew Elyse Foster Wade Smith William W. Parmley Jonathan G. Zaroff | 2005 | Circulation2005，，21： | 1 |
| 12 | Vital Signs: Carbapenem-Resistant Enterobacteriaceae显示文摘 | Jacob Jesse T Klein Eili Laxminarayan Ramanan Beldavs Zintars Lynfield Ruth Kallen Alexander J Ricks Philip Edwards Jonathan Srinivasan Arjun Fridkin Scott Rasheed J Kamile Lonsway David Bulens Sandie Herrera Rosa McDonald L Clifford Patel | 2013 | MMWR Morbidity and Mortality Weekly Report2013，，9： | 1 |
| 13 | Multi-Detector Row CT of Relevant Vascular Anatomy of the Surgical Plane in Split-Liver Transplantation显示文摘 | Michael JG Jonathan BK Jacob S | 2003 | Radiology2003，229，2： | 1 |
| 14 | Novel APC- like properties of human NK cells directly regulate T cell activation显示文摘 | JACOB H TSUFIT G G JONATHAN F | 2004 | J Clin Invest2004，114，11： | 1 |
| 15 | Intraoper- ative sonography for neurosurgery显示文摘 | Jacob Sosna Mara M Barth Jonathan B Kruskal | 2005 | Ultrasound Med2005，24，： | 1 |
| 16 | Artificial power markets and unintended consequences显示文摘 | JONATHAN M JACOBS | 1997 | IEEE Transactions on Power Systems1997，12，2： | 1 |
| 17 | On discretetime linear systems with almost-periodic kernels显示文摘 | Birgit Jacob Jonathan Partington R | 2000 | Journal of Mathematical Analysis and Application2000，252，： | 1 |
| 18 | Gut microbiome and pancreatic cancer cachexia:An evolving relationship显示文摘Nearly 80% of patients with pancreatic ductal adenocarcinoma(PDAC)develop cachexia along their disease course.Cachexia is characterized by progressive weight loss,muscle wasting,and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life.Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support,pancreatic enzyme replacement therapy,and/or pharmacologic interventions.Despite current interventions to mitigate PDAC cachexia,a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome.We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC.Additionally,we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia.Novel insights into the relationship between enteral nutritional support,cachexia,and the gut microbiome are presented.These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia. | Andrew Hendifar Rasaq Akinsola Hayato Muranaka Arsen Osipov Shant Thomassian Natalie Moshayedi Julianne Yang Jonathan Jacobs Suzanne Devkota Neil Bhowmick Jun Gong | 2022 | World Journal of Gastrointestinal Oncology2022，14，7： | 1 |
| 19 | Identification of Genetic Variants That Affect Histone Modifications in Human Cells显示文摘 | Graham McVicker Bryce van de Geijn Jacob F. Degner Carolyn E. Cain Nicholas E. Banovich Anil Raj Noah Lewellen Marsha Myrthil Yoav Gilad Jonathan K. Pritchard | 2013 | Science2013，，6159： | 1 |
| 20 | Neuroprotection of Host Cells by Human Central Nervous System Stem Cells in a Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis显示文摘 | Stanley J. Tamaki Yakop Jacobs Monika Dohse Alexandra Capela Jonathan D. Cooper Michael Reitsma Dongping He Robert Tushinski Pavel V. Belichenko Ahmad Salehi William Mobley Fred H. Gage Stephen Huhn Ann S. Tsukamoto Irving L. Weissman Nobuko Uchida | 2009 | Cell Stem Cell2009，，3： | 1 |
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