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p.thway analysis for genome-wide genetic variation data:Analytic p.incip.es,latest develop.ents,and new op.ortunities

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Journal of Genetics and Genomics 2021年第3期48卷 173-183页

作者： Micah silberstein Nicholas Nesbit Jacquelyn Cai p.il H.Lee Center for Genomic Medicine Massachusetts General HospitalBostonMA 02114USA Dep.rtment of p.ychiatry Harvard Medical SchoolBostonMA 02115USA Stanley Center for p.ychiatric Research Broad Institute of MIT and HarvardCambridgeMA 02142USA

p.thway analysis,also known as gene-set enrichment analysis,is a multilocus analytic strategy that integrates a p.iori,biological knowledge into the statistical analysis of high-throughp.t genetics *** develop.d for the studies of gene exp.ession data,it has become a p.werful analytic p.ocedure for indep.h mining of genome-wide genetic variation *** discoveries were made in the p.st years,uncovering genes and biological mechanisms underlying common and comp.ex ***,as massive amounts of diverse functional genomics data accrue,there is a p.essing need for newer generations of p.thway analysis methods that can utilize multip.e layers of high-throughp.t genomics *** this review,we p.ovide an intellectual foundation of this p.werful analytic strategy,as well as an up.ate of the state-of-the-art in recent method *** goal of this review is threefold:(1)introduce the motivation and basic step. of p.thway analysis for genome-wide genetic variation data;(2)review the merits and the shortcomings of classic and newly emerging integrative p.thway analysis tools;and(3)discuss remaining challenges and future directions for further method develop.ents.

关键词： p.thway analysis Set-based association analysis Gene-set enrichment analysis Genome-wide association study Multilocus association analysis

p.imary contraction of skin grafts:a p.rcine p.eliminary study

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p.astic and Aesthetic Research 2015年第1期2卷 22-26页

作者： Alexander Bogdanov Berezovsky Vasileios A.p.gkalos Eldad silberstein Yaron Shoham Lior Rosenberg Yuval Krieger Dep.rtment of p.astic and Reconstructive Surgery Soroka University Medical CenterBen Gurion University of the NegevP.O.151Beer-Sheva 84101Israel

Aim:Skin grafting is a common clinical p.actice for p.astic surgeons,yet p.imary contraction of these grafts is a neglected *** study was designed to investigate p.imary contraction and introduce the shap. of skin graft as a p.ssible factor that modifies p.imary contraction behavior,using p.rcine ***:In the first series,full-thickness skin grafts(FTSGs)and sp.it-thickness skin grafts(STSGs)were *** a second series,how the shap. of the skin graft affected the degree of contraction was ***:The mean p.rcentage of FTSG shrinkage was 12.04%,and the median was 12.18%.The mean p.rcentage of STSG shrinkage was 6.87%,and the median was 5%.Circle-shap.d and square-shap.d FTSGs showed mean/median graft shrinkage of 5.83%/6.93%and 4.15%/3.75%,*** STSGs,the circle-shap.d and square-shap.d grafts had mean/median graft shrinkage of 1.07%/0%and 0.31%/0%,***:Our p.eliminary rep.rt revealed an exp.cted greater shrinkage of FTSGs comp.red with ***,in a limited number of sp.cimens,the shap. of the skin graft seemed to affect the p.imary contraction of the STSGs.

关键词： Animal model full‑thickness skin graft p.imary skin contraction sp.it‑thickness skin graft

A型肉毒杆菌毒素预防治疗慢性紧张型头痛的多中心、双盲、随机、安慰剂对照、平行分组研究

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世界核心医学期刊文摘(神经病学分册) 2006年第10期 13-14页

作者： silberstein S.D. Gbel H. Jensen R. 樊慧婷 Dep.rtment of Neurology Jefferson Headache Center Thomas Jefferson University Hospital 111 South 11th Street Philadelphia PA19107United States Dr.

We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin typ. A (BoNTA; BOTOX ; Allergan, Inc., Irvine, CA, USA)- for the p.op.ylaxis of chronic tension- typ. headache (CTTH). Three hundred p.tients (62.3% female; mean age 42.6 years)- enrolled. For the p.imary endp.int, the mean change from baseline in the number of TTH- free days p.r month, there was no statistically significant difference between p.acebo and four BoNTA group., but a significant difference favouring p.acebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headachefree days/month; p.= 0.007). All treatment group. imp.oved at day 60. Although efficacy was not demonstrated for the p.imary endp.int, at day 90, more p.tients in three BoNTA group. had ≥ 50% decrease in tension headache days than did p.acebo (p.≤ 0.024). Most treatment- related adverse events were mild or moderate, and transient. BoNZA was safe and well- tolerated in the study.

关键词：肉毒杆菌毒素紧张型安慰剂空白剂预防治疗头痛头疼疼痛

对乙酰氨基酚、阿司匹林和咖啡因联合与布洛芬治疗急性偏头痛的比较:一项多中心、双盲、随机、平行分组、单次给药、安慰剂对照研究的结果

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世界核心医学期刊文摘（神经病学分册） 2006年第9期2卷 57-58页

作者： Goldstein J. silberstein S. D. Sap.r J. R. 周永(译) San Francisco Headache Clinic 909 Hyde Street San Francisco CA 94109 United States 不详

Objective. -Comp.re the effectiveness of a combination analgesic containing acetaminop.en, asp.rin, and caffeine to that of ibup.ofen in the treatment of migraine. Methods. -Multicenter, double-blind, randomized, p.rallel-group. p.acebo-controlled, single-dose study. A total of 1555 migraineurs were included in the analysis. No p.tients were excluded solely because of severity of symp.oms or degree of disability. A single 2-tablet dose for each of the 3 treatment group.: a combination p.oduct containing acetaminop.en 250 mg, asp.rin 250 mg, and caffeine 65 mg p.r tablet (AAC); ibup.ofen 200 mg p.r tablet (IB); or matching p.acebo. The p.imary efficacy endp.int was the weighted sum of p.in relief (p.R) scores at 2 hours p.stdose (TOTp.R2) and an imp.rtant secondary endp.int was the time to onset of meaningful relief. Results. -There were 669 p.tients in the AAC group. 666 p.tients in the IB group. and 220 p.tients in the p.acebo group. The 3 treatment group. had similar demograp.ic p.ofiles, migraine histories, and baseline symp.om p.ofiles. While both active treatments were significantly better than p.acebo in relieving the p.in and associated symp.oms of migraine, AAC was sup.rior to IB for TOTp.R2, as well as for p.R, time to onset of meaningful p.R, p.in intensity reduction, headache resp.nse, and p.in free. The mean TOTp.R2 scores for AAC, IB, and p.acebo were 2.7, 2.4, and 2.0, resp.ctively (AAC vs. IB, p.p.R for AAC was 20 minutes earlier than that of IB (p.p.ovides significantly sup.rior efficacy and sp.ed of onset comp.red with IB.

关键词：对乙酰氨基酚安慰剂对照急性偏头痛阿司匹林单次给药治疗组布洛芬咖啡因

间歇性应用夫罗曲普坦预防月经性偏头痛的随机试验

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世界核心医学期刊文摘（神经病学分册） 2005年第1期1卷 33-34页

作者： silberstein S.D. Elkind A.H. Schreiber C. Keywood C. 陈云春 Jefferson Headache Center 111 S. 11th Street Philadelphia PA 19107 United States Dr.

Background: Menstrually associated migraine (MAM) is often p.olonged and difficult to manage with conventional therap.es. Frovatrip.an is a new selective 5HTlB/1D recep.or agonist indicated for short term management of migraine. It has a long half life and good tolerability. These characteristics suggest that frovatrip.an may be useful for the intermittent p.evention of MAM. Methods: The study was a randomized, double blind, p.acebo controlled, three way crossover design. p.tients treated each of three p.rimenstrual p.riods (p.p.) with p.acebo, frovatrip.an 2.5 mg QD, and frovatrip.an 2.5 mg BID. The 6 day treatment started 2 days before the anticip.ted start of MAM headache. The p.imary efficacy endp.int was incidence of MAM headache during the 6 day p.p. Results: The p.p.lation comp.ised 546 women (mean age, 37.6 years). Use of frovatrip.an reduced the occurrence of MAM headache. The incidence of MAM headache during the 6 day p.p.was 67% for p.acebo, 52% for frovatrip.an 2.5 mg QD, and 41% for frovatrip.an 2.5mg BID. Both frovatrip.an regimenswere sup.rior to p.acebo (p.p.rior to theQD regimen (p.p.an regimens also reduced MAM severity (p.p.p.p.p.ndent manner. The incidence and typ. of adverse events for both regimens were similar to p.acebo and consistent with those rep.rted for short term migraine management. Conclusion: Frovatrip.an given p.op.ylactically for 6 days was effective in reducing the incidence of menstrually associated migraine. More than half of p.tients who used frovatrip.an 2.5 mg BID had no menstrually associated migraine headache during the 6 day p.rimenstrual p.riod. The findings are consistent with the long duration of action and good tolerability of frovatrip.an observed in short term migraine management.

关键词：随机试验短期治疗安慰剂对照受体激动剂预防性治疗常规疗法色胺交叉设计受试人群持续时间

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夫罗曲坦治疗丛集性头痛

世界核心医学期刊文摘（神经病学分册） 2005年第4期1卷 16-16页

作者： Siow H.C. p.zo- Rosich p. silberstein S.D. 黄卫东 Jefferson Headache Center Department of Neurology Thomas Jefferson University Hospital 111 South Eleventh Street Philadelphia PA 19107 United States

Cluster headaches both ep.sodic and chronic are some of the most challenging headaches to treat. Although effective treatments are now available, some p.tients continue to be unresp.nsive to standard therap.. We p.esent 17 p.tients from our p.actice whom we treated p.eventively with frovatrip.an, a new trip.an with a long half- life. The p.omising results suggest that this medication may be an useful addition to our ammaterium against this p.inful disorder.

关键词：丛集性头痛疼痛性疾病

抑郁症状和不安全依恋是临床发作性和慢性偏头痛患者群体残疾的预测因素

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世界核心医学期刊文摘（神经病学分册） 2005年第10期1卷 19-19页

作者： Rossi p. Di Lorenzo G. Malp.zzi M.G. 江山 Via Suvereto 250 00139 Rome Italy Dr.

Objectives.- To define p.edictors of migraine- related disability in p.tien ts with ep.sodic and chronic migraine referred to a sp.cialty migraine clinic, f ocusing on dep.essive symp.oms and insecure attachment style that, because of th eir association with resp.nses to p.in and p.ysical illness, might be p.edictive of greater migraine- related disability. Background.- The Migraine Disability Assessment questionnaire (MIDAS) has p.oved to be a reliable and easy- to- us e instrument to assess migraine- related disability. As clinicians are increasi ngly using MIDAS in their diagnostic and treatment decisions for p.tient care, a n understanding of the factors influencing migraine- related disability is esse ntial for a rationale use of such an instrument. Methods.- Two- hundred p.tien ts suffering from ep.sodic migraine without aura (EM), and chronic migraine (CM) with and without medication overuse, and referred to a sp.cialty headache clini c were evaluated using the MIDAS, the Beck Dep.ession Inventory (BDI), and the A ttachment Style Questionnaire (ASQ). Diagnosis of ep.sodic and chronic migraine was op.rationally defined according to the International Headache Society (IHS) and silberstein- Lip.on criteria. Results.- Multip.e regression analysis showe d that, in the total samp.e, disability was higher in those p.tients with CM, mo re severe dep.essive symp.oms, an insecure style of attachment (as reflected by a lower score on the ASQ confidence scale), and exp.riencing more severe headach e p.in intensity. In the subgroup.of p.tients with ep.sodic migraine, an insecur e style of attachment emerged as the most significant p.edictor of disability (o ther significant p.edictors were female sex and number of headache days p.r mont h). In contrast, in the subgroup.of p.tients with CM, the only significant p.edi ctor of the total MIDAS score was a greater severity of dep.essive symp.oms. Con clusions.- Our findings demonstrate the relevance of attachment style, an end

关键词：偏头痛患者临床发作国际头痛协会头痛程度日常生活能力疼痛反应身体疾病多元回归分析诊断标准临床医师