tbuckley/cabot-search huggingface dataset:
Response and oligoclonal resistance to pembrolizumab in uterine leiomyosarcoma: Genomic, neoantigen, and immunohistochemical evaluation.
Authors: Diana Miao, Dennis Adeegbe, Scott J. Rodig, Sachet Shukla, Ali Amin-Mansour, Scott L. Carter, Catherine Wu, Kwok-Kin Wong, Chandrajit P. Raut, Patrick Alexander Ott, Eliezer Mendel Van Allen, George D. Demetri, Suzanne George
Journal: Journal of Clinical Oncology (2016)

11043 Background: Predictive biomarkers for response and resistance to immune checkpoint blockade targeting programmed death 1 (PD-1) are incompletely characterized, and the utility of anti-PD-1 therapy for uterine leiomyosarcoma (ULMS) is unknown. Methods: A 49 yo woman with ULMS developed rapidly progressive metastatic disease 4 months after R1-resection of the primary tumor and was enrolled on a phase 1b study of pembrolizumab (10 mg/kg every 2 wks) (KEYNOTE-028). Tumor regression at multiple metastatic sites occurred within 2 months. A single pre-existing metastasis increased in size and was resected at 9 months. IHC, whole exome/transcriptome sequencing, and neoantigen analysis was performed on primary pretreatment (preRx) and treatment-resistant tumors (postRx). Results: Responsive tumor sites revealed complete pathologic response at time of surgery. Progressive tumor demonstrated viable ULMS. IHC showed tumor cells negative for PD-L1 and positive for PD-L2 both preRx and postRx. Degree of PD-1+ lymphocyte infiltration decreased significantly postRx compared to preRx. PreRx harbored exomic focal MYC amplification, TP53 nonsense mutation, and heterozygous PTEN deletion. PostRx maintained these genomic alterations and acquired a loss-of-function mutation in PTEN that resulted in biallelic PTEN inactivation. PreRx tumor expressed tumor-specific neoantigens (TSNs) that were immunogenic to patient-derived peripheral blood mononuclear cells; expression of TSNs decreased postRx. Conclusions: This patient exhibited complete pathologic response to pembrolizumab at all but one metastatic ULMS site. Genomic analysis of the resistant tumor revealed acquired bialllelic PTEN loss - recently implicated in resistance to PD-1 inhibition in melanoma and glioblastoma – reduced infiltration of PD-1+ lymphocytes, and diminished expression of neoantigens. To our knowledge, this is the first report of exceptional response to PD-1 inhibition in ULMS, and highlights biallelic PTEN loss and neoantigen downregulation as potential mechanisms of acquired resistance to immune checkpoint blockade across cancer types.
Autologous HER2 CMV bispecific CAR T cells for progressive glioblastoma: Results from a phase I clinical trial.
Authors: Nabil M. Ahmed, Vita S Brawley, Oumar Diouf, Alexia Ghazi, Joanna Yi, Hao Liu, Cliona M. Rooney, Gianpietro Dotti, Adrian P. Gee, Robert Grossman, Yvonne Kew, David S. Baskin, Aidin Ashoori, Jonathan Zhang, John Hicks, Suzanne Powell, Winfried Wels, Malcolm K. Brenner, Helen E. Heslop, Stephen M Gottschalk
Journal: Journal of Clinical Oncology (2015)

3008 Background: Glioblastoma (GBM) remains virtually incurable. T-cell therapy holds the promise to improve outcomes for GBM patients since it does not rely on the cytotoxic mechanisms of conventional therapies. We have shown in preclinical studies that HER2 and CMV are potential T-cell therapy targets for GBM. Methods: We report the initial results of the phase I clinical study, NCT01109095, administering autologous CMV.pp65 T cells grafted with a second generation HER2 chimeric antigen receptor (CAR; with a CD28.zeta signaling domain) to patients with progressive GBM. Results: Sixteen CMV-seropositive patients with HER2-positive GBM and radiological evidence of progression aged 11-70 (median age 49) were enrolled. Autologous HER2-CAR CMV T cells were successfully generated for all patients from a peripheral blood draw (maximum 90mL). T-cell products contained HER2-CAR expressing T cells as judged by FACS analysis (median: 67% (range: 46-82) %), and CMV.pp65-specific T cells as judged by IFN-gamma Elispot assays (median 985.5 (range 390 to 1292) SFC/105 T cells). Infusions of 1x106/m2, 3x106/m2, 1x107/m2, 3x107/m2 or 1x108/m2HER2-CAR.CMV-T cells were well tolerated without systemic side effects and no dose limiting toxicity was observed. HER2-CAR CMV T cells were detected in the peripheral blood for up to 12 weeks post infusion as judged by real-time PCR of a CAR-specific amplicon. Out of fifteen evaluable patients, 10 had progressive disease. Five out of fifteen patients had objective responses: 1 patient had a partial response with a ~62% reduction in tumor volume lasting 8 months, 1 patient had stable disease lasting 4 months and 3 patients have stable disease and are currently alive with a follow up of 18 to >24 months, after T cell infusion. Conclusions: This initial evaluation of the safety and efficacy of autologous HER2-CAR CMV bispecific T cells in patients with progressive GBM shows that infusions are safe and that cells could persist for up to 12 weeks in the peripheral blood. Clinical benefit was observed in 33% of patients setting the stage for studies that combine HER2-CAR CMV T cells with other immunomodulatory approaches to enhance their expansion and anti-GBM activity. Clinical trial information: NCT01109095.
Is Oxygen Therapy Beneficial in Acute Myocardial Infarction? Simple Question, Complicated Mechanism, Simple Answer
Authors: Joseph Loscalzo
Journal: New England Journal of Medicine (2017)

Joseph Priestley first reported his discovery of oxygen in 1775 through observations of a candle burning in "dephlogisticated air." He remarked that the candle burned with great "strength and vivacity" and speculated that this oxygen-enriched air could be used as a medicine; he also expressed concern for its toxic potential, since the candle burned out much faster in it than in "common air."1 In many respects, these inferences on the potential for benefits and harms of supplemental oxygen have been borne out by experience over the subsequent two centuries. Blodgett first reported the beneficial effect of supplemental oxygen continuously administered . . .
Abstract 320: Roles of Estrogen, AMPK and Micro RNAs in the Progression of Cardiac Hypertrophy
Authors: Yulia Lipovka, John P Konhilas
Journal: Circulation Research (2013)

In industrialized countries, the prevalence of congestive heart failure (CHF) is increasing steadily and has become one of the leading causes of hospitalization. In addition, the risk of cardiovascular disease increases in post-menopausal women. Yet, the association between estrogen and the risk of CHF has not been adequately studied. Recently, MicroRNAs (miR) and AMP-kinase (AMPK) have emerged as prominent players in the development of cardiac hypertrophy and heart failure. Our on-going studies indicate differential AMPK regulation through two miR species (miR195 and miR451) in a mouse model harboring a missense mutation (R403Q) in alpha-myosin heavy chain (αMHC) causing hypertrophic cardiomyopathy (HCM). Using bioinformatic algorithms (TargetScanMouse, 5.2), we were able to predict miR candidates that potentially target the AMPK axis. In addition, Altered expression of miRs that target AMPK axis was found in phenylephrine induced hypertrophic neonatal rat cardiomyocytes (NRCM). However, Estradiol treatment of NRCM blocked the hypertrophic changes induced by phenylephrine treatment. It was known that the activation of AMPK pathway inhibits cardiomyocyte hypertrophy. Our data showed that AMPK pathway was activated by Estradiol treatment, which can be blocked by estrogen receptor (ER) β antagonist. Therefore, estradiol increase AMPK pathway activation which in turn attenuate phenylephrine induced increase in cardiomyocyte cell size. Further studies are need to further explore the role of estrogen in the regulation of miR expression in hypertrophic cardiomyocytes, and the role of the expression changes of miRs regulated by estrogen in the development of hypertrophic phenotype.
Episode Payment Model for Coronary Artery Bypass Grafting—Opportunities and Challenges
Authors: Faisal G. Bakaeen, Jeffrey B. Rich, Lars G. Svensson
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
in vivoにおける再内皮化のための生体模倣心臓血管ステント【Powered by NICT】
Authors: Liang Chunyong, Hu Yuecheng, Wang Hongshui, Xia Dan, Li Qiang, Zhang Jiao, Yang Jianjun, Li Baoe, Li Haipeng, Han Dong, Dong Mingdong
Journal: Biomaterials (2016)
What is the evidence for different management options for difficult to treat severe asthma?
Journal: BMJ (2017)

#### What you need to know

The management of adults with asthma that remains uncontrolled despite treatment with high dose therapies poses a challenge to clinicians and patients. National and international guidelines recommend intensification of treatment that typically involves the use of oral corticosteroids.12 The risks associated with long term systemic corticosteroid treatment are well documented and have led to the search for alternatives. Recent advances in the understanding of the pathology of asthma have prompted the development of other treatment options. Here, we consider the options available for people who require continuous or frequent use of oral corticosteroids and review the safety and efficacy of such treatments.

In the UK, over four million adults are being treated for asthma, and it remains responsible for more than 1000 deaths a year.34 Asthma exacerbations resulted in over 60 000 hospital admissions in 2013-14, with an estimated annual cost of £1bn to the NHS.34

The goals of asthma management are good symptom control with minimal exacerbations (see box 1).12

#### Box 1: Definition of complete control of asthma1

The goals of treatment …
Influences of Breakfast on Clock Gene Expression and Postprandial Glycemia in Healthy Individuals and Individuals With Diabetes: A Randomized Clinical Trial
Authors: Daniela Jakubowicz, Julio Wainstein, Zohar Landau, Itamar Raz, Bo Ahren, Nava Chapnik, Tali Ganz, Miriam Menaged, Maayan Barnea, Yosefa Bar-Dayan, Oren Froy
Journal: Diabetes Care (2017)

The circadian clock regulates glucose metabolism by mediating the activity of metabolic enzymes, hormones, and transport systems. Breakfast skipping and night eating have been associated with high HbA1c and postprandial hyperglycemia after lunch and dinner. Our aim was to explore the acute effect of breakfast consumption or omission on glucose homeostasis and clock gene expression in healthy individuals and individuals with type 2 diabetes.In a crossover design, 18 healthy volunteers and 18 volunteers with 14.5 ± 1.5 years diabetes, BMI 30.7 ± 1.1 kg/m2, and HbA1c 7.6 ± 0.1% (59.6 ± 0.8 mmol/mol) were randomly assigned to a test day with breakfast and lunch (YesB) and a test day with only lunch (NoB). Postprandial clock and clock-controlled gene expression, plasma glucose, insulin, intact glucagon-like peptide 1 (iGLP-1), and dipeptidyl peptidase IV (DPP-IV) plasma activity were assessed after breakfast and lunch.In healthy individuals, the expression level of Per1, Cry1, Rorα, and Sirt1 was lower (P < 0.05) but Clock was higher (P < 0.05) after breakfast. In contrast, in individuals with type 2 diabetes, Per1, Per2, and Sirt1 only slightly, but significantly, decreased and Rorα increased (P < 0.05) after breakfast. In healthy individuals, the expression level of Bmal1, Rorα, and Sirt1 was higher (P < 0.05) after lunch on YesB day, whereas the other clock genes remained unchanged. In individuals with type 2 diabetes, Bmal1, Per1, Per2, Rev-erbα, and Ampk increased (P < 0.05) after lunch on the YesB day. Omission of breakfast altered clock and metabolic gene expression in both healthy and individuals with type 2 diabetes.Breakfast consumption acutely affects clock and clock-controlled gene expression leading to normal oscillation. Breakfast skipping adversely affects clock and clock-controlled gene expression and is correlated with increased postprandial glycemic response in both healthy individuals and individuals with diabetes.
Macrophages, Smooth Muscle Cells, and Tissue Factor in Unstable Angina
Authors: Pedro R. Moreno, Vi´ctor H. Bernardi, Julio Lo´pez-Cue´llar, Alvaro M. Murcia, Igor F. Palacios, Herman K. Gold, Roxana Mehran, Samin K. Sharma, Yale Nemerson, Valenti´n Fuster, John T. Fallon
Journal: Circulation (1996)

Background Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. Methods and Results Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42±3%) than in stable angina (18±4%) ( P =.0001). Macrophage content was also larger in unstable angina (16±2%) than in stable angina (5±2%) ( P =.002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67±8%) than in samples from patients with stable angina (40±5%) ( P =.00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly ( r =.83, P &lt;.0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel ( r =.98, P &lt;.0001). Conclusions Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.
Effect of long-term treatment with tumour necrosis factor-α inhibitors on single-dose ultraviolet-induced changes in human skin
Authors: H.J. Kim, J.L. Langenhan, E.S. Robinson, E. Privette, J.C. Achtman, R.A. Mitrani, M. Zeidi, M.R. Sharma, R. Feng, J.L. Nevas, C. Calianno, J. Okawa, L. Taylor, L. Pappas-Taffer, V.P. Werth
Journal: British Journal of Dermatology (2017)

Tumour necrosis factor (TNF)-α is induced by ultraviolet (UV) light and is important in photoinflammation. 1 Although TNF-α inhibitors are commonly used for various inflammatory disorders like psoriasis, sometimes in combination with phototherapy, the effect of long-term TNF-α inhibitor treatment with UV exposure on skin is unclear.This study was undertaken to see if chronic TNF-α inhibition affects epidermal responses to UV, inflammatory infiltrate and collagen composition in vivo.Among 20 included patients, 10 were on long-term TNF-α inhibitors (mean duration 32•5 months; etanercept, n = 6; adalimumab, n = 3; infliximab, n = 1).The other 10 subjects were not on TNF-α inhibitors and were receiving only topical steroids and calcipotriene.All were white, nonsmoking men, and TNF-α inhibitor-untreated and inhibitor-treated patients had similar distribution of age (65•32 ± 5•66 vs. 62•48 ± 13•18 years), Fitzpatrick skin type and median minimal erythema dose (MED; 7•36 vs. 8•15).Following individual MED measurement, nonlesional inner arm skin was irradiated with 1× MED, followed by biopsy before (baseline) and after (24 h and 48 h).The light source emits UVA1, UVA2 and UVB in a ratio similar to sunlight.
植物ホスホリパーゼストレス応答におけるDおよびCとその多様な機能【Powered by NICT】
Authors: Hong Yueyun, Zhao Jian, Guo Liang, Kim Sang-Chul, Deng Xianjun, Wang Geliang, Zhang Gaoyang, Li Maoyin, Wang Xuemin
Journal: Progress in Lipid Research (2016)
複雑な微細構造を有する構築血管予形成組織の直接3Dバイオプリンティング【Powered by NICT】
Authors: Zhu Wei, Qu Xin, Zhu Jie, Ma Xuanyi, Patel Sherrina, Liu Justin, Wang Pengrui, Lai Cheuk Sun Edwin, Gou Maling, Xu Yang, Zhang Kang, Chen Shaochen
Journal: Biomaterials (2017)
Noninvasive Testing for Nonalcoholic Steatohepatitis and Hepatic Fibrosis in Patients With Psoriasis Receiving Long-term Methotrexate Sodium Therapy
Authors: Bruce Bauer, Po-Huang Chyou, Erik J. Stratman, Clayton Green
Journal: JAMA Dermatology (2017)

The long-term implications of hepatotoxic effects in patients with psoriasis remains uncharacterized, and a method is needed for the noninvasive monitoring of the development and progression of hepatic fibrosis in patients with psoriasis receiving long-term methotrexate therapy.To evaluate if NASH FibroSure, a noninvasive test for nonalcoholic steatohepatitis (NASH) and hepatic fibrosis, can be used for patients with psoriasis to aid in determining eligibility for methotrexate sodium (MTX) therapy, monitor for the development of MTX-induced hepatotoxic effects, and monitor for worsening of hepatic fibrosis scores during MTX therapy.A retrospective descriptive analysis was conducted among a cohort of patients with psoriasis treated with MTX who underwent NASH FibroSure testing between January 1, 2007, and December 31, 2013, at a dermatology referral center at a single institution. Data analysis was performed from January 1 to December 31, 2014.NASH FibroSure risk scores suggesting the development and progression of hepatic fibrosis in patients with psoriasis receiving long-term MTX therapy.Included in the institutional experience portion of the study were 129 patients with psoriasis undergoing treatment with MTX, while 107 patients (57 women and 50 men; mean [SD] age, 83.3 [13.5] years) underwent NASH FibroSure testing during MTX therapy and were eligible for correlation analysis. Of the 129 patients with psoriasis undergoing treatment with MTX, 69 (53.5%) underwent NASH FibroSure testing prior to starting MTX; 19 of those patients (27.5%) had elevated fibrosis scores, and 54 (78.3%) had elevated steatosis scores. Among the 107 patients who underwent NASH FibroSure testing during MTX therapy, the cumulative MTX dose corresponded to a statistically significant association of a higher NASH FibroSure hepatic fibrosis score in women (Spearman ρ = 0.21; P = .02) but not in men (Spearman ρ = 0.17; P = .11). All patients in the cohort except 1 were managed without a liver biopsy.The patients with psoriasis in this study had a high prevalence of elevated hepatic steatosis scores. The NASH FibroSure test can be used to monitor changes in fibrosis score in patients with psoriasis receiving MTX. In a single-institution cohort, these results suggest that NASH FibroSure may be used, especially among female patients, to help monitor for risk of worsening fibrosis during MTX therapy.
The effects of structural damage on functional disability in psoriatic arthritis
Authors: Andreas Kerschbaumer, Daniel Baker, Josef S Smolen, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2017)

Background Functional outcomes are central in patients with chronic inflammatory musculoskeletal diseases. In a secondary data analysis of the GO-REVEAL trial ( NCT00265096 ), we investigated wether structural damage is linked to functional impairment in patients with psoriatic arthritis (PsA), a link that is still elusive in this disease. Methods We analysed 363 patients enrolled in the GO-REVEAL study and obtained modified Sharp/van der Heijde Scores (mSvdHS) from X-rays performed at baseline, after 24, 52 and 104 weeks. Using longitudinal analyses, we assessed the effect of total mSvdHS (and its subscores, joint space narrowing (JSN) and erosions (ERO)) on functional status (measured by the Health Assessment Questionnaire) in all patients and in those attaining remission (n=117). Furthermore, we analysed wether structural damage reduces the responsiveness of functional limitations to treatment in a subgroup of responders who had functional impairment at baseline (n=67). Additionally, internal and external validation analyses were performed. Results The effect of damage on function was seen in the disease activity-adjusted models using total mSvdHS (p=0.005), JSN (p=0.019) and ERO (p=0.001) as well as in the remission analyses for mSvdHS (p=0.029) and JSN (p=0.010), respectively. Functional responsiveness was limited by increasing total mSvdHS (p=0.010), JSN (p=0.002) and ERO (p=0.040). The results were validated using other functional outcomes and in an independent clinical cohort. Conclusions In PsA, structural damage, particularly JSN, has implications for physical function. Functional outcomes have an irreversible component that is strongly related to the extent of joint destruction. This needs to be considered when targeting functional outcomes in clinical practice.
Dietary fiber intake and risks of proximal and distal colon cancers: A systematic review and meta-analysis.
Authors: Yu Ma, Peilin Huang, Mingyue Hu, Sunkai Ling, Yuan Li, Baoan Chen, Yueshuang Xu
Journal: Journal of Clinical Oncology (2017)

e15080 Background: Epidemiological studies have suggested that intake of dietary fiber is associated with decreased risk of colon cancer, however, these findings are inconsistent in that dietary fiber intake is differentially associated with risks of proximal colon and distal colon cancers. To address this, we conducted a systematic review and meta-analysis. Methods: Pubmed database were searched to identify relevant cohort studies up to December 2016 to examine the association between dietary fiber and risks of proximal colon and distal colon cancers, respectively. A random-effects model was used to compute summary risk estimates. Results: 11 prospective cohort studies were identified and included in the analysis. We observed that the risk of proximal colon cancer was 14% lower among the highest dietary fiber intake compared with the lowest intake (RR = 0.86, 95% confidence interval [CI] = 0.78 to 0.95). A similar result was also found for distal colon cancer (RR = 0.79, 95% CI = 0.71 to 0.87). Conclusions: In current analysis, we show that dietary fiber intake is associated inversely with risks of both proximal and distal colon cancers.
in vitro3次元PDAC間質に富む回転楕円体モデルの生成【Powered by NICT】
Authors: J Ware Matthew, Keshishian Vazrik, J Law Justin, C Ho Jason, A Favela Carlos, Rees Paul, Smith Billie, Mohammad Sayeeduddin, F Hwang Rosa, Rajapakshe Kimal, Coarfa Cristian, Huang Shixia, P Edwards Dean, J Corr Stuart, Godin Biana, A Curley Steven
Journal: Biomaterials (2016)
Experimental Roentgen Injury. IV. Effects of Repeated Small Doses of X-Rays on Blood Picture, Tissue Morphology, and Life Span in Mice
Authors: Paul S. Henshaw
Journal: JNCI Journal of the National Cancer Institute (1944)

Experimental Roentgen Injury. IV. Effects of Repeated Small Doses of X-Rays on Blood Picture, Tissue Morphology, and Life Span in Mice Paul S. Henshaw Paul S. Henshaw senior radiobiologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 5, April 1944, Pages 513–522, https://doi.org/10.1093/jnci/4.5.513 Published: 01 April 1944