tbuckley/cabot-search huggingface dataset:
Frequent expression of PD-L1 in testicular germ cell tumors.
Authors: Christian Daniel Fankhauser, Alessandra Curioni Fontecedro, Joerg Beyer, Verena Tischler, Tullio Sulser, Holger Moch, Peter Karl Bode
Journal: Journal of Clinical Oncology (2015)

379 Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity . The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.
Re: Syed Johar Raza, Timothy Wilson, James O. Peabody, et al. Long-term Oncologic Outcomes Following Robot-assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium. Eur Urol 2015;68:721–8
Authors: Michael Froehner, Rainer Koch, Manfred P. Wirth
Journal: European Urology (2015)
An analysis of the dynamics of mammalian mitochondrial DNA sequence evolution.
Authors: C F Aquadro, N Kaplan, K J Risko
Journal: Molecular Biology and Evolution (1984)

The dynamics of the substitution process for mammalian mitochondrial DNA have been modeled. The temporal behavior of several quantities has been studied and the model's predictions have been compared with estimates obtained from recent mtDNA sequence data for an increasingly divergent series of primates, the mouse and the cow (Anderson et al. 1981, 1982; Bibb et al. 1981; Brown et al. 1982). The results are consistent with the hypothesis that the decrease in the proportion of transitions observed as divergence increases is a consequence of the highly biased substitution process. In addition, the results support the hypothesis that, although a portion of the mtDNA molecule evolves at an extremely rapid rate, a significant portion of the molecule is under strong selective constraints.
PD3-1-2: Phase I trial of vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with solid tumors
Authors: Yutaka Fujiwara, Noboru Yamamoto, Kazuhiko Yamada, Yasuhide Yamada, Fumiaki Koizumi, Tatsu Shimoyama, Kazuto Nishio, Tetsuya Otsuki, Stanley R. Frankel, Tomohide Tamura
Journal: Journal of Thoracic Oncology (2007)
Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction
Authors: Margaret M. Redfield, Kevin J. Anstrom, James A. Levine, Gabe A. Koepp, Barry A. Borlaug, Horng H. Chen, Martin M. LeWinter, Susan M. Joseph, Sanjiv J. Shah, Marc J. Semigran, G. Michael Felker, Robert T. Cole, Gordon R. Reeves, Ryan J. Tedford, W.H. Wilson Tang, Steven E. McNulty, Eric J. Velazquez, Monica R. Shah, Eugene Braunwald
Journal: New England Journal of Medicine (2015)

Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients.In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP).In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels.Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.).
Systemic Pharmacokinetics of Everolimus Eluted From the Absorb Bioresorbable Vascular Scaffold
Authors: David G. Rizik, Louis Cannon, Gregg W. Stone, Maureen Kennedy, Karine Piard-Ruster, Peter Staehr, Stephen G. Ellis, Dean J. Kereiakes
Journal: Journal of the American College of Cardiology (2015)
Response to Comment on Hempe et al. The Hemoglobin Glycation Index Identifies Subpopulations With Harms or Benefits From Intensive Treatment in the ACCORD Trial. Diabetes Care 2015;38:1067–1074
Authors: James M. Hempe, Shuqian Liu, Leann Myers, Robert J. McCarter, John B. Buse, Vivian Fonseca
Journal: Diabetes Care (2015)

Drs. Riddle and Gerstein (1) suggest renaming the hemoglobin glycation index (HGI) to reflect the possibility that interindividual variation in HGI in the ACCORD trial could be an artifact of how blood glucose was measured. HGI is the difference between an individual’s observed HbA1c and a predicted HbA1c derived by inserting a time-matched blood glucose measurement into a regression equation describing the linear population relationship between blood glucose and HbA1c. In our analysis of ACCORD (2), we used baseline HbA1c and fasting plasma glucose (FPG) to show that high HGI at baseline (i.e., HbA1c higher than predicted by FPG) was …
LP05 : Daclatasvir plus sofosbuvir with or without ribavirin in patients with HCV genotype 3 infection: Interim analysis of a french multicenter compassionate use program
Authors: C. Hezode, V. De Ledinghen, H. Fontaine, F. Zoulim, P. Lebray, N. Boyer, D. Larrey, C. Silvain, D. Botta-Fridlund, V. Leroy, M. Bourliere, L. D’Alteroche, I. Hubert-Fouchard, D. Guyader, I. Rosa, E. Nguyen-Khac, V. Di Martino, F. Carrat, L. Fedchuk, R. Akremi, Y. Bennai, J.-P. Bronowicki
Journal: Journal of Hepatology (2015)
Prognosis factors of pathological stage I non-small cell lung cancer
Authors: S. Lu
Journal: Journal of Clinical Oncology (2008)

22210 Background: The IASLC Lung Cancer Staging Project recommend changes in the T classification are to subclassify T1 into T1a and T1b, and T2 into T2a and T2b; and to reclassify T2c and additional nodule(s) in the same lobe as T3. But other well-known clinical and histopathological factors were also possible prognostic factors. Methods: We try to validate the new staging project in 325 patients who underwent complete surgical resection for stage I NSCLC in Single Institution of Shanghai Chest Hospital from 1998 to 2003. All the patients were followed up four years. Data were analyzed by SPSS 11.0 software. Results: The pT1NOR0 was divided into pT1a ≤2 cm (n=28) and pT1b>2 to 3 cm (n=15) and pT2NOR0 was divided into pT1a ≤2 cm (n=40), pT1b>2 to 3 cm (n=84),pT2a>3 to 5 cm (n=107), pT2b>5 to 7 cm (n=38), and pT2c >7 cm (n=13). The results validate the IASLC recommend changes(table 1). Table 1, Comparisons of Overall Survival between Tumor Size The 4-year survival rate for patients with systematic mediastinal lymphadenectomy (n=68) was 72.75% while patients with mediastinal lymph node sampling (n=257) was 49.63% (p=0.026). Female patients (n=116) was associated with a better survival than men's (n=209; 77.76% vs 68.13%, p=0.022). Patients without lymphovascular invasion (n=309) was associated with a better survival than patients with lymphovascular invasion (n=16; 72.75% vs 49.63%, p=0.025). Conclusions: We get the same results which shows the tumor diameter is significant independent prognostic factors in non-small cell lung cancer and lymphovascular invasion may add new information of the current TNM classification. Mediastinal lymphadenectomy is also a significant independent prognostic factor in resection non-small cell lung cancer. It needs further research. Stage T 4-year survival rate P value T1NOR0 pT1a ≤2 cm (n = 28) 78.42% 0.6488 pT1b >2 to 3 cm (n = 15) 74.33% T2NOR0 pT1a ≤2 cm (n = 40) 79.15% 0.027 pT1b >2 to 3 cm (n = 84) 79.28% pT2a >3 to 5 cm (n = 107) 66.41% pT2b >5 to 7 cm (n = 38) 61.07% pT2c >7 cm (n = 13) 46.15% T1NOR0 +T2NOR0 pT1a ≤2 cm (n = 68) 79.15% 0.026 pT1b >2 to 3 cm (n = 99) 79.28% pT2a >3 to 5 cm (n = 107) 66.41% pT2b >5 to 7 cm (n = 38) 61.07% pT2c >7 cm (n = 13) 46.15% No significant financial relationships to disclose.
Neurohumoral regulation of coronary flow: Role of the endothelium. (Developments in cardiovascular medicine, vol. 150): Edited by W.H. van Gilst, K.I. Lie, 145 pp., US$58.00 (hardback). Dordrecht: Kluwer Academic Publishers Group, 1993. ISBN 0-7923-2588-5
Authors: G. Billman
Journal: Cardiovascular Research (1995)
The influence of co-morbidity on the outcome of non-invasiveventilatory support in patients with acute respiratory failure(ARF) in chronic obstructive pulmonary disease (COPD)
Authors: Pavel Matuška, Olga Pilařová, Zdeněk Merta, Jana Skřičková, Ladislav Dušek
Journal: European Respiratory Journal (2002)

The outcome of non-invasive ventilatory support in acute
respiratory failure is dependent, among other things, on the
co-morbidity of the patient. The authors give a survey of the
influence of different diseases in such case.
Effect of experimental modulation of different mood states on dyspnea
Authors: Santosh Deo, BishnuHari Paudel, Rita Khadka, Nirmala Limbu
Journal: European Respiratory Journal (2014)

Dyspnea is the subjective experience of breathing discomfort, commonly reported during intense emotional states, heavy exercise and cardiorespiratory diseases.The objective of the study was to explore the effect of experimentally induced changes in mood on exertional dyspnea during standard exercise stress test.Standard emotional pictures were categorized into positive, negative and neutral picture series. Twenty five healthy male volunteers performed standard exercise stress test using cycle ergometer with simultaneously showing emotional pictures displayed on a monitor in front for 5 min with reporting of dyspnea and recording of respiratory rate and heart rate. In comparison to neutral mood state, there was significant increase in shortness of breathing [4.6(4.2-5.4) vs. 3.4(3.0-3.8)], botherness to shortness of breathing [4.6(4.0-5.8) vs. 3.6(2.8-4.2)], respiratory rate [32.2(29.7-35.3) vs. 28.4(26.6-31.2) cycles/min] and heart rate [116.4 (105.4-128.4) vs. 123(109.9-144.3) beats/min] in negative mood state whereas there was no significant difference in those variables in positive mood state. Likewise, in comparison to negative mood state, there was significant decrease in shortness of breathing [3.2(2.0-3.9) vs. 4.6(4.2-5.4)], botherness to shortness of breathing [3.2(2.2-3.8) vs. 4.6(4.0-5.8)], respiratory rate [29.0(26.3-31.6) vs. 32.2(29.7-35.3) cycles/min] and heart rate [114(102.7-138.7) vs. 123(109.9-144.3) beats/min] in positive mood state. The result suggests that negative mood state increases perceived dyspnea but positive mood state reduces it, indicating its potential psychotherapeutic use that can reduce troublesome dyspnea in patients of cardiorespiratory diseases.
Outcome in adolescent and young adult (AYA) patients compared with younger patients treated for high-risk B-precursor acute lymphoblastic leukemia (HR-ALL): A report from the Children’s Oncology Group study AALL0232.
Authors: Eric Larsen, Elizabeth A. Raetz, Naomi Joan Winick, Wanda L. Salzer, James B. Nachman, Meenakshi Devidas, Stephen Hunger, William L. Carroll
Journal: Journal of Clinical Oncology (2012)

CRA9508 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC)
Authors: V. Lorusso, M. Spada, M. Giampaglia, A. Misino, R. Calabrese, A. Latorre, G. Monticelli, M. Guida, D. Sambiasi
Journal: Journal of Clinical Oncology (2006)

10673 Background: Vinorelbine i.v. and capecitabine are two of the most effective single agents in previously treated advanced breast cancer (ABC). A number of studies have been reported with the combination of these agents. Actually, the availability of oral formulation for vinorelbine allows a full oral combination of the two agents. The aim of this study was to evaluate the activity and toxicity of this novel combination. Patients and Methods: Thirty-eight advanced breast cancer patients (pts) refractory to anthracyclines and taxanes were included in this study. Treatment consisted of vinorelbine 60 mg/m 2 (days 1 + 8), and capecitabine 2000 mg/m 2 (days 2–7 and 9–16) every 3 weeks. The pt characteristics were: median age 53 years (range 37–77 years); ECOG PS 0–1 in 35 pts (92.1%), and PS 2 in 3 pts (7.8%); ER+/PgR+ 20 pts (52.6%) and ER−/PgR− 11 pts (28.9%). Dominant sites of disease were visceral in 19 pts (50.0%), bone in 10 pts (26.3%), soft tissue in 9 pts (23.6%). Results: A total of 228 courses were given with a mean of three cycles/pt (range 1–12). Five pts (13.1%) had no toxicity at all. Hematologic side-effects were: neutropenia G2-G3 in 7 pts (18.9%), and G4 in 1 pt (2.7%), anemia G1 in 11 pts (29.7%), G2-G3 in 5 pts (13.5%), thrombocytopenia G1 in 6 pts (16.2%) and G3 in 1 pt (2.7%). Non-hematologic side-effects were: fatigue G1 in 5 pts (13.5%), hand-foot syndrome G1 in 2 pt (5.4%) and G2 in 2 pts (5.4%), nausea/vomiting G1 in 2 pts (5.4%), G2 in 3 pts (8.1%) and G3 in 1 pt (2.7%), constipation G1 in 2 pts (5.4%), peripheral neurotoxicity G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%), gastric pain G1 in 2 pts (5.4%), stomatitis G1 in 3 pts (8.1%) and G2 in 1 pt (2.7%). Out of 38 pts assessable, we observed 2 (5.4%) CR, 13 (34 %) PR, 14 (37.8%) SD, and 9 (26.3%) PD. The median time to progression was 4.5 months (range 1–18 months), the median response duration was 7 months (range 2–18 months), and the median survival duration was 10 months (range 2–26+). Conclusions: The oral vincap combination was well tolerated and effective in ABC. In fact, this regimen achieved results comparable to the previously reported combinations of capecitabine and i.v. vinorelbine. The oral vincap should be considered as an alternative to single agent capecitabine or vinorelbine in ABC refractory to antra-taxane combination. No significant financial relationships to disclose.
Obstructive sleep apnoea in the general population: highly prevalent but minimal symptoms
Authors: Erna S. Arnardottir, Erla Bjornsdottir, Kristin A. Olafsdottir, Bryndis Benediktsdottir, Thorarinn Gislason
Journal: European Respiratory Journal (2015)

The aim was to assess the prevalence of obstructive sleep apnoea (OSA) as defined by an apnoea–hypopnea index (AHI) ≥15 in the middle-aged general population, and the interrelationship between OSA, sleep-related symptoms, sleepiness and vigilance. A general population sample of 40–65-year-old Icelanders was invited to participate in a study protocol that included a type 3 sleep study, questionnaire and a psychomotor vigilance test (PVT). Among the 415 subjects included in the study, 56.9% had no OSA (AHI &lt;5), 24.1% had mild OSA (AHI 5–14.9), 12.5% had moderate OSA (AHI 15–29.9), 2.9% had severe OSA (AHI ≥30) and 3.6% were already diagnosed and receiving OSA treatment. However, no significant relationship was found between AHI and subjective sleepiness or clinical symptoms. A relationship with objective vigilance assessed by PVT was only found for those with AHI ≥30. Subjects already on OSA treatment and those accepting OSA treatment after participating in the study were more symptomatic and sleepier than others with similar OSA severity, as assessed by the AHI. In a middle-aged general population, approximately one in five subjects had moderate-to-severe OSA, but the majority of them were neither symptomatic nor sleepy and did not have impaired vigilance.
Cellular transporter pharmacogenetics in metastatic colorectal cancer: Initial analysis of C80203
Authors: H. L. McLeod, K. Owzar, D. Kroetz, F. Innocenti, S. Das, P. Friedman, K. Giacomini, R. M. Goldberg, A. P. Venook, M. J. Ratain
Journal: Journal of Clinical Oncology (2008)

3513 Background: Chemotherapy with 5-fluorouracil (FU) and irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) has become the mainstay of treatment for metastatic colorectal cancer (mCRC). Tools are needed to discern best patient therapy. Based on mechanistic studies, we hypothesized that germline genetic variation in cellular transporters is associated with response to chemotherapy for mCRC. Methods: Genomic DNA was prospectively collected after informed consent from 180 of 238 pts on C80203, a Phase III trial of FOLFIRI or FOLFOX ± cetuximab. Data on objective tumor response and systemic toxicities have been reported previously. Genotyping was performed for prespecified candidate genes, including the cellular transporters ABCC2, ABCC4, ABCG2, SLCO1B1, SLC22A1, and SLC22A2. Genotype by treatment interaction was tested in a multiplicative two-way logistic model, adjusted for treatment arm. Sensitivity analysis was also conducted. Given that this was considered a pilot study, no adjustments to account for multiple comparisons were applied. Results: ABCG2 34G>A was associated with relative susceptibility to FOLFOX and resistance to FOLFIRI (p<0.013, Caucasians only). Genetic variants in the other transporters were not associated with objective response. The low number of events for neutropenia and gastrointestinal toxicity precluded assessment of these parameters. Peripheral neuropathy was not associated with the evaluated genetic variants. Survival data has not yet been analyzed. Additional PG testing is ongoing and will be presented. Conclusions: A SNP in ABCG2 may be associated with treatment effect in mCRC pts. Genotype-related differences in common toxicities were not observed. The small sample size limits interpretation of these data, but these questions will be addressed with more precision in the analysis of C80405, the successor study to C80203. This study demonstrates the ability to conduct prospective pharmacogenetic studies across the NCI cooperative groups. ABCG2 34G/G ABCG2 34A/G FOLFOX 37/65 (57%) 5/5 (100%) FOLFIRI 32/73 (44%) 1/5 (20%) No significant financial relationships to disclose.
Immunologic determinants of head and neck cancer response to induction chemotherapy.
Authors: S P Schantz, H E Savage, T Racz, F J Liu, B W Brown, R D Rossen, W K Hong
Journal: Journal of Clinical Oncology (1989)

Various measures of immune response were assessed prior to induction chemotherapy (intravenous [IV] cisplatin, fluorouracil [5-FU], and bleomycin) in 43 previously untreated head and neck cancer patients to derive a clinical response prediction model. These were parameters of functional cellular immunity (natural killer [NK] cell activity, lymphocyte blastogenesis response to mitogens), total lymphocyte and lymphocyte subset numbers and percentages, and circulating humoral immunity (total immunoglobulin, immunoglobulin classes, and C1q binding activity [C1q BA]). The C1q BA may reflect levels of circulating immune complexes within peripheral blood. The objective primary tumor response rate was 65% (16 complete responses and 12 partial responses). Univariate logistic regression analysis showed that failure to respond to therapy was significantly related to higher value (vis-à-vis response) of humoral immune parameters total immunoglobulin (Ig), P less than .01; IgG, P less than .01; and C1q BA, P less than .001. No association between cellular immune response measurements and response to chemotherapy was identified. By multivariate logistic regression analysis, only C1q BA levels were predictive of drug therapy responsiveness (P less than .001). Results extend our previous investigations regarding C1q BA measurement in head and neck cancer patients, and show that C1q BA levels add accuracy of prediction of subsequent chemotherapy response to that based solely on standard staging criteria and other parameters of immune status.
Successful aging: Advancing the science of physical independence in older adults
Authors: Stephen D. Anton, Adam J. Woods, Tetso Ashizawa, Diana Barb, Thomas W. Buford, Christy S. Carter, David J. Clark, Ronald A. Cohen, Duane B. Corbett, Yenisel Cruz-Almeida, Vonetta Dotson, Natalie Ebner, Philip A. Efron, Roger B. Fillingim, Thomas C. Foster, David M. Gundermann, Anna-Maria Joseph, Christy Karabetian, Christiaan Leeuwenburgh, Todd M. Manini, Michael Marsiske, Robert T. Mankowski, Heather L. Mutchie, Michael G. Perri, Sanjay Ranka, Parisa Rashidi, Bhanuprasad Sandesara, Philip J. Scarpace, Kimberly T. Sibille, Laurence M. Solberg, Shinichi Someya, Connie Uphold, Stephanie Wohlgemuth, Samuel Shangwu Wu, Marco Pahor
Journal: Ageing Research Reviews (2015)
Localized Hair Repigmentation in a 91-Year-Old Woman
Authors: Valerie C. Amann, Reinhard Dummer
Journal: JAMA Dermatology (2015)

An elderly woman had a patch of black hair within otherwise gray hair, an irregularly pigmented, brownish patch on the underlying scalp skin, multiple seborrhoic keratoses, and a actinic keratosis. What is your diagnosis?