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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 | Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology显示文摘笨重脱氧核糖核酸的修理由小径是的核苷酸切除修理(NER ) 使内收更万用的脱氧核糖核酸之一为脱氧核糖核酸损害的移动修理小径。有 NER 小径,全球 genomic-NER (GG-NER ) 和联合抄写的 NER (TC-NER ) 的二个子集,它仅仅在包含脱氧核糖核酸损害的识别的步不同。损坏的后面的识别,亚小径然后为充满的切口 / 切除步骤和结扎步骤收敛。这评论将集中于 NER 的 GGR 亚小径,当 TCR 亚小径将在这个问题在另一篇文章被盖住时。到修理的 NER 小径的能力一个宽数组使内收部分地,茎在影响人的生理的回答和事件的一个同等地宽的数组的 NER 损坏脱氧核糖核酸和结果从涉及起始的识别的机制走。在这评论, carcinogenesis 上的 NER 的影响,神经病学的功能,到环境因素的敏感和到癌症的敏感,治疗学将被讨论。在过去的 40 年在我们 NER 小径的理解产生的知识从进展,以及从体质研究和参予这条小径的蛋白质和酶的结构的分析导致了动物模型系统,哺乳动物的遗传和试管内生物化学的领域。每研究的这些大街显著地作出贡献到我们 NER 小径怎么并且怎么工作的理解在 NER 活动的改变,积极、否定,影响人生物学。 | Sarah C Shuck Emily A Short John J Turchi | 2008 | Cell Research2008，18，1： | 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 | Liver Transplantation for Neuroendocrine Tumors in Europe—Results and Trends in Patient Selection: A 213-Case European Liver Transplant Registry Study显示文摘 | Yves Patrice Le Treut Emilie Grégoire Jürgen Klempnauer Jacques Belghiti Elisabeth Jouve Jan Lerut Denis Castaing Olivier Soubrane Olivier Boillot Georges Mantion Kia Homayounfar Manuel Bustamante Daniel Azoulay Philippe Wolf Marek Krawczyk Andreas Pasche | 2013 | Annals of Surgery2013，，5： | 3 |
| 5 | Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice显示文摘Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress(PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead(Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling. Bone parameters were evaluated using microCT, histomorphometry, and strength determination in 8-month-old male mouse offspring subjected to PS on gestational days 16 and 17, lifetime Pb exposure(100 p.p.m. Pb in drinking water), or to both. Pb reduced trabecular bone mass and, when combined with PS, Pb unmasked an exaggerated decrement in bone mass and tensile strength. Next, to characterize a mechanism of glucocorticoid effect on bone, prednisolone was implanted subcutaneously(controlled-release pellet, 5 mg·kg^(-1) per day) in 5-month-old mice that decreased osteoblastic activity and increased sclerostin and leptin levels. Furthermore, the synthetic glucocorticoid dexamethasone alters the anabolic Wnt signaling pathway. The Wnt pathway inhibitor sclerostin has several glucocorticoid response elements, and dexamethasone administration to osteoblastic cells induces sclerostin expression. Dexamethasone treatment of isolated bone marrow cells decreased bone nodule formation, whereas removal of sclerostin protected against this decrement in mineralization.Collectively, these findings suggest that bone loss associated with steroid-induced osteoporosis is a consequence of sclerostin-mediated restriction of Wnt signaling, which may mechanistically facilitate glucocorticoid toxicity in bone. | Eric E Beier Tzong-Jen Sheu Emily A Resseguie Masahiko Takahata Hani A Awad Deborah A Cory-Slechta J Edward Puzas | 2017 | Bone Research2017，5，2： | 3 |
| 6 | Portal vein thrombosis after splenectomy显示文摘 | Emily R Winslow L.Michael Brunt Jeffery A Drebin Nathaniel J Soper Mary E Klingensmith | 2002 | The American Journal of Surgery2002，，6： | 3 |
| 7 | 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 |
| 8 | 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 |
| 9 | Endogenous testosterone and mortality risk显示文摘在人,肥胖和新陈代谢的复杂并发症与更低的浆液睾丸激素被联系(T) 和 dihydrotestosterone 和增加的风险,和死亡从(DHT ) ,除了心血管的疾病(CVD ) 的多重长期的疾病。在这些因素之间的原因的相互关系仍然是争论的一件事。在有 hypogonadotropic 性腺机能减退的未经治疗的先天、终生的形式的人,看起来不是增加的风险。有 Klinefelters 症候群的人有癌症,以及 CVD 的各种各样的类型的增加的风险,尽管有 T,它坚持治疗。当 hypothalamic-pituitary-gonadal 轴的病理不在时,在在使人变老的浆液 T 的谦虚减小的效果是不清楚的。低浆液 T 集中的流行在有癌症,肾的疾病,和呼吸疾病的人高并且是可能的是全身的疾病,不是性腺机能减退的严厉的指示物。一些基于人口的研究发现了低浆液 T 与归因于癌症,肾的疾病,和呼吸疾病的死亡的更高的风险被联系,当其它没有时。尽管纵的研究的元分析显示出在低浆液 T 和所有原因死亡之间的一个协会,在研究之间的显著异质限制了一个坚挺的结论。因此,当在以后特别地发生在生活的 T 的减少可以与人的所有原因和死亡的特定的类型的增加被联系时,如果有的话,微分效果作为与健康和生活方式因素相比 T 和另外的性别类固醇是未知的在当前的时间。 | Emily J Meye Gary Wittert | 2018 | Asian Journal of Andrology2018，20，2： | 2 |
| 10 | Weather from the stratosphere? 显示文摘 | MARK P B DAVIDW J T EMILY FS | 2003 | Science2003，301，： | 1 |
| 11 | Induction of tolerance by Por- phyromonas gingivalis on APCs:a mechanism implicated in peri- odontal infection 显示文摘 | Cohen N Morisset J Emilie D | 2004 | J Dent Res2004，83，5： | 1 |
| 12 | Self-eare and qual- ity of life of heart failure patients at a multidisciplinary heart function clinic显示文摘 | Emily S Kevin J L Joseph A C | 2011 | J Cardiovase Nuts2011，26，5： | 1 |
| 13 | 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 |
| 14 | Microsatellite instability in aberrant crypt foci from patients without concurrent colon cancer显示文摘 | Greenspan Emily J Cyr Jennifer L Pleau Devon C | 2007 | Carcinogenesis2007，28，4： | 1 |
| 15 | 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 |
| 16 | Using biological net- works to search for interacting loci in genome-wide associa- tion studies显示文摘 | Emily M Mailund T Hein J | 2009 | Eur J Hum Genet2009，17，10： | 1 |
| 17 | Vascular calcification does not predict anastomotic leak or conduit necrosis following oesophagectomy显示文摘BACKGROUND Anastomotic leaks(AL)and gastric conduit necrosis(CN)are serious complications following oesophagectomy.Some studies have suggested that vascular calcification may be associated with an increased AL rate,but this has not been validated in a United Kingdom population.AIM To investigate whether vascular calcification identified on the pre-operative computed tomography(CT)scan is predictive of AL or CN.METHODS Routine pre-operative CT scans of 414 patients who underwent oesophagectomy for malignancy with oesophagogastric anastomosis at the Queen Elizabeth Hospital Birmingham between 2006 and 2018 were retrospectively analysed.Calcification of the proximal aorta,distal aorta,coeliac trunk and branches of the coeliac trunk was scored by two reviewers.The relationship between these calcification scores and occurrence of AL and CN was then analysed.The Esophagectomy Complications Consensus Group definition of AL and CN was used.RESULTS Complication data were available in n=411 patients,of whom 16.7%developed either AL(15.8%)or CN(3.4%).Rates of AL were significantly higher in female patients,at 23.0%,compared to 13.9%in males(P=0.047).CN was significantly more common in females,(8.0%vs 2.2%,P=0.014),patients with diabetes(10.6%vs 2.5%,P=0.014),a history of smoking(10.3%vs 2.3%,P=0.008),and a higher American Society of Anaesthesiologists grade(P=0.024).Out of the 14 conduit necroses,only 4 occurred without a concomitant AL.No statistically significant association was found between calcification of any of the vessels studied and either of these outcomes.Multivariable analyses were then performed to identify whether a combination of the calcification scores could be identified that would be significantly predictive of any of the outcomes.However,the stepwise approach did not select any factors for inclusion in the final models.The analysis was repeated for composite outcomes of those patients with either AL or CN(n=69,16.7%)and for those with both AL and CN(n=10,2.4%)and again,no significant associations were detected.In the subset of patients that developed these outcomes,no significant associations were detected between calcification and the severity of the complication.CONCLUSION Calcification scoring was not significantly associated with Anastomotic Leak or CN in our study,therefore should not be used to identify patients who are high risk for these complications. | Benjamin J Jefferies Emily Evans James Bundred James Hodson John L Whiting Colm Forde Ewen A Griffiths | 2019 | World Journal of Gastrointestinal Surgery2019，11，7： | 1 |
| 18 | Combustion synthesis of metallic foams from nanocomposite reactants 显示文摘 | Emily M H Michelle L P Jouet R J | 2006 | Intermetallics2006，14，6： | 1 |
| 19 | Management of multidrug-resistant organisms in healthcare settings,2006显示文摘 | Jane D S Emily R Marguerite J | 2007 | Am J Infect Control2007，35，102： | 1 |
| 20 | Wind resource estimates with an analog ensemble approach显示文摘 | Vanvyve Emilie Delle Monache Luca Monaghan Andrew J | 2015 | Renewable Energy2015，74，： | 1 |
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