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| 1 | Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond显示文摘Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer. | Emily M Lin Jun Gong Samuel J Klempner Joseph Chao | 2018 | World Journal of Gastroenterology2018，24，25： | 10 |
| 2 | Helical tomotherapy and volumetric modulated arc therapy:New therapeutic arms in the breast cancer radiotherapy显示文摘AIM To analyse clinical and dosimetric results of helical tomotherapy(HT) and volumetric modulated arc therapy(VMAT) in complex adjuvant breast and nodes irradiation.METHODS Seventy-three patients were included(31 HT and 42 VMAT). Dose were 63.8 Gy(HT) and 63.2 Gy(VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes(SCN) and internal mammary chain(IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort(7 mm vs 5 mm).RESULTS For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC:96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5%(HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2%(VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1%(HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9%(VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy(HT) and 4.6 ± 0.9 Gy(VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts.CONCLUSION HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues. | Olivier Lauche Youlia M Kirova Pascal Fenoglietto Emilie Costa Claire Lemanski Celine Bourgier Olivier Riou David Tiberi Francois Campana Alain Fourquet David Azria | 2016 | World Journal of Radiology2016，8，8： | 7 |
| 3 | Dementia and osteoporosis in a geriatric population: Is there a common link?显示文摘AIM To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base. METHODS This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MEDLINE(1950 to June 2016) was conducted. The keywords 'osteoporosis', 'osteoporotic fracture', 'dementia' and 'Alzheimer's disease'(AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia(predominantly Alzheimer's type) and osteoporosis.RESULTS Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies. CONCLUSION Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed. | Candice L Downey Adam Young Emily F Burton Simon M Graham Robert J Macfarlane Eva-Maria Tsapakis Eleftherios Tsiridis | 2017 | World Journal of Orthopedics2017，8，5： | 6 |
| 4 | Predictors of spine deformity progression in adolescent idiopathic scoliosis: A systematic review with meta-analysis显示文摘AIM: To evaluate published data on the predictors of progressive adolescent idiopathic scoliosis(AIS) in order to evaluate their efficacy and level of evidence. METHODS: Selection criteria:(1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies;(2) participants: adolescents with AIS aged from 10 to 20 years; and(3) treatment: observation, bracing, and other. Search method: Ovid MEDLINE, Embase, the Cochrane Library, Pub Medand patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio(OR), sensitivity, specificity, positive and negative predictive values were also collected. A metaanalysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence.RESULTS: The review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics:(1) An increase of the Cobb angle or axial rotation during brace treatment;(2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment;(3) initial Cobb angle severity(> 25o);(4) osteopenia;(5) patient age < 13 years at diagnosis;(6) premenarche status;(7) skeletal immaturity;(8) thoracic deformity;(9) brain stem vestibular dysfunction; and(10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes:(1) calmodulin 1;(2) estrogen receptor 1;(3) tryptophan hydroxylase 1;(3) insulin-like growth factor 1;(5) neurotrophin 3;(6) interleukin-17 receptor C;(7) melatonin receptor 1B, and(8) Scoli Score test. Other predictors included:(1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells(PBMC);(2) G-protein signaling dysfunction in PBMC; and(3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies.CONCLUSION: This review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria. | Andriy Noshchenko Lilian Hoffecker Emily M Lindley Evalina L Burger Christopher MJ Cain Vikas V Patel Andrew P Bradford | 2015 | World Journal of Orthopedics2015，6，7： | 4 |
| 5 | A striking local esophageal cytokine expression profile in eosinophilic esophagitis显示文摘 | Carine Blanchard Emily M. Stucke Beatriz Rodriguez-Jimenez Karen Burwinkel Margaret H. Collins Annette Ahrens Eileen S. Alexander Bridget K. Buckmeier Butz Sean C. Jameson Ajay Kaul James P. Franciosi Jonathan P. Kushner Philip E. Putnam J. Pablo Abonia M | 2010 | The Journal of Allergy and Clinical Immunology2010，，1： | 3 |
| 6 | Hospital readmissions in decompensated cirrhotics: Factors pointing toward a prevention strategy显示文摘AIM To reduce readmissions and improve patient outcomes in cirrhotic patients through better understanding of readmission predictors.METHODS We performed a single-center retrospective study of patients admitted with decompensated cirrhosis from January 1, 2011 to December 31, 2013(n = 222). Primary outcomes were time to first readmission and 30-d readmission rate due to complications of cirrhosis. Clinical and demographic data were collected to help describe predictors of readmission, along with care coordination measures such as post-discharge status and outpatient follow-up. Univariate and multivariateanalyses were performed to describe variables associated with readmission.RESULTS One hundred thirty-two patients(59.4%) were readmitted at least once during the study period. Median time to first and second readmissions were 54 and 93 d, respectively. Thirty and 90-d readmission rates were 20.7 and 30.1 percent, respectively. Predictors of 30-d readmission included education level, hepatic encephalopathy at index, ALT more than upper normal limit and Medicare coverage. There were no statistically significant differences in readmission rates when stratified by discharge disposition, outpatient follow-up provider or time to first outpatient visit.CONCLUSION Readmissions are challenging aspect of care for cirrhotic patients and risk continues beyond 30 d. More initiatives are needed to develop enhanced, longitudinal post-discharge systems. | Siamak M Seraj Emily J Campbell Sarah K Argyropoulos Kara Wegermann Raymond T Chung James M Richter | 2017 | World Journal of Gastroenterology2017，23，37： | 3 |
| 7 | National Forest Inventories capture the multifunctionality of managed forests in Germany显示文摘Background:Forests perform various important ecosystem functions that contribute to ecosystem services.In many parts of the world,forest management has shifted from a focus on timber production to multi-purpose forestry,combining timber production with the supply of other forest ecosystem services.However,it is unclear which forest types provide which ecosystem services and to what extent forests primarily managed for timber already supply multiple ecosystem services.Based on a comprehensive dataset collected across 150 forest plots in three regions differing in management intensity and species composition,we develop models to predict the potential supply of 13 ecosystem services.We use those models to assess the level of multifunctionality of managed forests at the national level using national forest inventory data.Results:Looking at the potential supply of ecosystem services,we found trade-offs(e.g.between both bark beetle control or dung decomposition and both productivity or soil carbon stocks)as well as synergies(e.g.for temperature regulation,carbon storage and culturally interesting plants)across the 53 most dominant forest types in Germany.No single forest type provided all ecosystem services equally.Some ecosystem services showed comparable levels across forest types(e.g.decomposition or richness of saprotrophs),while others varied strongly,depending on forest structural attributes(e.g.phosphorous availability or cover of edible plants)or tree species composition(e.g.potential nitrification activity).Variability in potential supply of ecosystem services was only to a lesser extent driven by environmental conditions.However,the geographic variation in ecosystem function supply across Germany was closely linked with the distribution of main tree species.Conclusions:Our results show that forest multifunctionality is limited to subsets of ecosystem services.The importance of tree species composition highlights that a lack of multifunctionality at the stand level can be compensated by managing forests at the landscape level,when stands of complementary forest types are combined.These results imply that multi-purpose forestry should be based on a variety of forest types requiring coordinated planning across larger spatial scales. | Nadja K.Simons María R.Felipe-Lucia Peter Schall Christian Ammer Jürgen Bauhus Nico Blüthgen Steffen Boch François Buscot Markus Fischer Kezia Goldmann Martin M.Gossner Falk Hänsel Kirsten Jung Peter Manning Thomas Nauss Yvonne Oelmann Rodica Pena Andrea Polle Swen C.Renner Michael Schloter Ingo Schöning Ernst-Detlef Schulze Emily F.Solly Elisabeth Sorkau Barbara Stempfhuber Tesfaye Wubet Jörg Müller Sebastian Seibold Wolfgang W.Weisser | 2021 | Forest Ecosystems2021，8，1： | 2 |
| 8 | Effect of alcohol exposure on hepatic superoxide generation and hepcidin expression显示文摘AIM: To understand the role of mitochondrial-produced superoxide(O 2 ?) in the regulation of iron-regulatory hormone, hepcidin by alcohol in the liver. METHODS: For alcohol experiments, manganese superoxide dismutase knockout mice heterozygous for Sod2 gene expression(Sod2 +/) and age-matched littermate control mice(LMC), expressing Sod2 gene on both alleles, were exposed to either 10%(w/v) ethanol in the drinking water or plain water(control) for 7 d. Total cellular O 2 ? levels in hepatocytes isolated from the livers of mice were measured by electron paramagnetic resonance spectroscopy. The mitochondrial-targeted, O 2 ?-sensitive fluorogenic probe, MitoSOX Red and flow cytometry were utilized to measure O 2 ? in mitochondria. Gene and protein expression were determined by Taqman Real-time quantitative PCR and Western blotting, respectively. RESULTS: Sod2 +/- mice expressed 40% less MnSOD protein(SOD2) in hepatocytes compared to LMC mice. The deletion of Sod2 allele did not alter the basal expression level of hepcidin in the liver. 10% ethanol exposure for 1 wk inhibited hepatic hepcidin mRNA expression three-fold both in Sod2 +/ and LMC mice. O 2 ? levels in hepatocytes of untreated Sod2 +/ mice were three-fold higher than in untreated LMC mice, as observed by electron paramagnetic resonance spectroscopy. O 2 ? levels in mitochondria of Sod2 +/ mice were four-fold higher than in mitochondria of untreated LMC mice, as measured by MitoSOX Red fluorescence and flow cytometry. Alcohol induced a two-fold higher increase in O 2 ? levels in hepatocytes of LMC mice than in Sod2 +/ mice compared to respective untreated counterparts. In contrast, 1 wk alcohol exposure did not alter mitochondrial O 2 ? levels in both Sod2 +/- and control mice. CONCLUSION: Mitochondrial O2 ? is not involved in the inhibition of liver hepcidin transcription and thereby regulation of iron metabolism by alcohol. These findings also suggest that short-term alcohol consumption significantly elevates O 2 ? levels in hepatocytes, which appears not to originate from mitochondria. | Duygu Dee Harrison-Findik Sizhao Lu Emily M Zmijewski Jocelyn Jones Matthew C Zimmerman | 2013 | World Journal of Biological Chemistry2013，4，4： | 2 |
| 9 | Aberrant Th2 inflammation drives dysfunction of alveolar macrophages and susceptibility to bacterial pneumonia显示文摘The ubiquitin ligase,Itch,is required to prevent autoinflammatory disease in mice and humans.Itch-deficient mice develop lethal pulmonary inflammation characterized by the production of Th2 cytokines(for example,interleukin-4(IL-4));however,the contribution of Itch to immune defense against respiratory pathogens has not been determined.We found that Itch-deficient mice were highly susceptible to intranasal infection with the respiratory pathogen Klebsiella pneumoniae.Infected Itch-deficient mice exhibited increased immune cell infiltration,cytokine levels and bacterial burden in the respiratory tract compared with control mice.However,numbers of resident alveolar macrophages were reduced in the lungs from Itch-deficient mice both before and after infection.High levels of Th2 cytokines in the respiratory tract correlated with deceased alveolar macrophages,and genetic ablation of IL-4 restored alveolar macrophages and host defense to K.pneumoniae in Itch-deficient mice,suggesting that loss of alveolar macrophages occurred as a consequence of Th2 inflammation.Adoptive transfer of Itch−/−CD4+T cells into Rag−/−mice was sufficient to drive reduction in numbers of Itch-replete alveolar macrophages.Finally,we found that Stat6 signaling downstream of the IL-4 receptor directly reduced fitness of alveolar macrophages when these cells were exposed to the Itch−/−inflamed respiratory tract.These data suggest that Th2 inflammation directly impairs alveolar macrophage fitness in Itch−/−mice,and elucidate a previously unappreciated link between Th2 cells,alveolar macrophages and susceptibility to bacterial infection. | Emily K Moser Natania S Field Paula M Oliver | 2018 | Cellular & Molecular Immunology2018，15，5： | 2 |
| 10 | Impacts and challenges of United States medical students during the COVID-19 pandemic显示文摘The delivery of medical student education has changed rapidly during the coronavirus disease 2019(COVID-19)pandemic.Students in their pre-clinical years have transitioned to online courses and examinations.Students in their clinical years are not permitted on clinical rotations,and face uncertainties in career exploration and the residency application process.Medical students in all stages of training are volunteering and helping their communities.The future presence of COVID-19 throughout the United States is unknown,and medical students are eager to return to their training.This paper outlines current challenges in medical student education and the various responses that have been adopted.We also discuss possible future directions for students through involvement in telemedicine,outpatient clinic visits,and non-respiratory inpatient care tasks as adequate personal protective equipment,COVID-19 testing,and resources become more widely available. | Stacey Rolak Alexis M Keefe Emily L Davidson Prabesh Aryal Sandesh Parajuli | 2020 | World Journal of Clinical Cases2020，8，15： | 2 |
| 11 | Hannon, role for a bidentate ribonuclease in the initiation step of RNA interference显示文摘 | EMILY BERNSTEIN AMY A CAUDY SCOTT M | 2001 | Nature2001，411，： | 1 |
| 12 | The cytoplasmic tails of infectious bronchitis virus E and M proteins mediate their interaction显示文摘 | EMILY C CAROLYN E M | 2003 | Virology2003，312，： | 1 |
| 13 | Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a T H 2-skewed immune response显示文摘 | Stephanie T. Yerkovich Marjut Roponen Miranda E. Smith Kathy McKenna Anthony Bosco Lily S. Subrata Emilie Mamessier Matthew E. Wikstr?m Peter Le Souef Peter D. Sly Patrick G. Holt John W. Upham | 2009 | The Journal of Allergy and Clinical Immunology2009，，1： | 1 |
| 14 | Spread thin in the Arctic显示文摘 | Emily M Klein | 2003 | Nature2003，423，： | 1 |
| 15 | Gas filter correlation technique applied to in-situ monitoring of nitrogen monoxide (NO) in industrial exhaust 显示文摘 | Shu Emily Y Cueman M K Fortin Gabriel | 2000 | SPIE2000，2834，： | 1 |
| 16 | Septal to posterior wall motion delay fails to predict reverse remodeling or clinical improvement in patients undergoing cardiac resynchronization therapy显示文摘 | Gregory M Marcus MD Emily Rose | 2005 | J Am Coll Cardiol2005，46，12： | 1 |
| 17 | Chemokine macrophage inflammatory protein-lalpha mRNA expression in lung biopsy specimens of primary pulmonary hypertension显示文摘 | Fartoukh M Emilie D Le Gall C | 1998 | Chest1998，114，： | 1 |
| 18 | Hepatic Lesions Observed in Hepatitis C Virus Transgenic Mice Infected by H elicobacter hepaticus显示文摘 | Emilie Roux‐Goglin Pierre Dubus Corinne Asencio Marthe‐Aline Jutand Jean Rosenbaum Francis Mégraud | 2012 | Helicobacter2012，，1： | 1 |
| 19 | Multipotential marrow stromal cells transduced to produce L-DOPA: Engraftment in a rat model of Parkinson disease 显示文摘 | Emily J Schwarz Guillermon M | 1999 | Human Gene Therapy1999，10，： | 1 |
| 20 | Dynamic Interaction of DNA Damage Checkpoint Protein Rad53 with Chromatin Assembly Factor Asf1显示文摘 | Emili A Schieltz D M Yates J R | 2001 | Mol Cell2001，7，1： | 1 |
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