tbuckley/cabot-search huggingface dataset:
Abstract DDT01-02: AZD5991: A potent and selective macrocyclic inhibitor of Mcl-1 for treatment of hematologic cancers
Authors: Alexander W. Hird, J. Paul Secrist, Ammar Adam, Matthew A. Belmonte, Eric Gangl, Frank Gibbons, David Hargreaves, Jeffrey W. Johannes, Stephen L. Kazmirski, Jason G. Kettle, Stephen E. Kurtz, Michelle L. Lamb, Martin J. Packer, Bo Peng, Craig R. Stewart, Jeffrey W. Tyner, Wenzhan Yang, Qing Ye, XiaoLan Zheng, Edwin A. Clark
Journal: Cancer Research (2017)

Abstract Mcl-1, a member of the Bcl/Mcl family, is a key protein involved in evasion of apoptosis in a wide variety of tumors. Its amplification and overexpression have also been implicated in innate and acquired resistance to anticancer drugs. Mcl-1 is capable of preventing induction of apoptosis, both by binding and inactivating the pro-apoptotic executioner Bcl-2 protein, Bak, as well as by sequestering other pro-apoptotic BH3-only proteins such as Bim and Noxa. AZD5991 is a rationally designed macrocycle with sub-nanomolar affinity for Mcl-1. It demonstrates all the hallmarks of a true Mcl-1 inhibitor: 1. potent, selective, and rapid apoptosis in Mcl-1-dependent cell lines (e.g., GI50 as low as 10 nM in multiple myeloma cell lines); 2. loss of activity upon overexpression of Bcl-xL or siRNA-mediated knockout of Bak; 3. Mcl-1:Bak complex disruption as demonstrated by co-immunoprecipitation. AZD5991 is active in vivo, with complete (100%) tumor regression demonstrated in several mouse xenograft models after a single tolerated dose. We have also demonstrated synergistic in vivo efficacy in combination with standard-of-care agents. Analysis of ex vivo activity in primary samples from leukemia patients indicates that a high percentage of leukemia patients should respond to drug treatment, which supports our plan for a phase I trial of AZD5991 in patients with hematologic cancers. Citation Format: Alexander W. Hird, J. Paul Secrist, Ammar Adam, Matthew A. Belmonte, Eric Gangl, Frank Gibbons, David Hargreaves, Jeffrey W. Johannes, Stephen L. Kazmirski, Jason G. Kettle, Stephen E. Kurtz, Michelle L. Lamb, Martin J. Packer, Bo Peng, Craig R. Stewart, Jeffrey W. Tyner, Wenzhan Yang, Qing Ye, XiaoLan Zheng, Edwin A. Clark. AZD5991: A potent and selective macrocyclic inhibitor of Mcl-1 for treatment of hematologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr DDT01-02. doi:10.1158/1538-7445.AM2017-DDT01-02
Parent and teacher SNAP-IV ratings of attention deficit hyperactivity disorder symptoms: Psychometric properties and normative ratings from a school district sample
Authors: Regina Bussing, Melanie Fernandez, Michelle Harwood, Wei Hou, Cynthia Wilson Garvan, Sheila M. Eyberg, James M. Swanson
Journal: Circulation (2011)

To examine Swanson, Nolan, and Pelham-IV (SNAP-IV) psychometric properties, parent (N = 1,613) and teacher (N = 1,205) data were collected from a random elementary school student sample in a longitudinal attention deficit hyperactivity disorder (ADHD) detection study. SNAP-IV reliability was acceptable. Factor structure indicated two ADHD factors and an oppositional defiant disorder (ODD) factor. Parent and teacher scores varied by gender and poverty status (d = .49-.56) but not age; only teacher scores varied by race (d = .25-.55). Screening and diagnostic utility was evaluated with likelihood ratios (LRs) and posttest probabilities. Parent SNAP-IV scores above 1.2 increased probability of concern (LR > 10) and above 1.8, of ADHD diagnosis (LR > 3). Teacher hyperactivity/impulsivity scores above 1.2 and inattention scores above 1.8 increased probabilities of concern only (LR = 4.2 and >5, respectively). Higher teacher scores for African American children and race differences in measurement models require future study.
A multi-cohort phase 1 study of ramucirumab plus durvalumab: Preliminary safety and clinical activity in patients with locally advanced and unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma
Authors: Talia Golan, Chia-Chi Lin, Siqing Fu, Heather Wasserstrom, Gu Mi, Naomi Laing, Maria Karasarides, Yung-Jue Bang
Journal: Annals of Oncology (2017)
The aggressive peripheral <scp>T</scp>‐cell lymphomas: 2015
Authors: James O. Armitage
Journal: American Journal of Hematology (2015)

T-cell lymphomas make up approximately 10%-15% of lymphoid malignancies. The frequency of these lymphomas varies geographically, with the highest incidence in parts of Asia.The diagnosis of aggressive peripheral T-cell lymphoma (PTCL) is usually made using the World Health Organization classification. The ability of hematopathologists to reproducibly diagnosis aggressive PTCL is lower than that for aggressive B-cell lymphomas, with a range of 72%-97% for the aggressive PTCLs.Patients with aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat controversial, positron emission tomography scans seem to be useful as they are in aggressive B-cell lymphomas. The most commonly used prognostic index is the International Prognostic Index. The specific subtype of aggressive PTCL is an important risk factor, with the best survival seen in anaplastic large-cell lymphoma-particularly young patients with the anaplastic lymphoma kinase positive subtype.Anaplastic large-cell lymphoma is the only subgroup to have a good response to a CHOP-like regimen. Angioimmunoblastic T-cell lymphoma has a prolonged disease-free survival in only ~20% of patients, but younger patients who have an autotransplant in remission seem to do better. PTCL-not otherwise specified is not one disease. Anthracycline-containing regimens have disappointing results, and a new approach is needed. Natural killer/T-cell lymphoma localized to the nose and nasal sinuses seems to be best treated with radiotherapy-containing regimens. Enteropathy-associated PTCL and hepatosplenic PTCL are rare disorders with a generally poor response to therapy, although selected patients with enteropathy-associated PTCL seem to benefit from intensive therapy.
Neuroleptics for Delirium: More Research Is Needed
Authors: Alisha A. Morgan, Christian T. Sinclair
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Pembrolizumab versus investigator’s choice single-agent chemotherapy in patients with advanced/metastatic esophageal adenocarcinoma that progressed after first-line therapy: Phase 3 KEYNOTE-181 study
Authors: Toshihiko Doi, Jaafar Bennouna, Lin Shen, Peter Enzinger, Ruixue Wang, Rita Dalal, Minori Koshiji, Manish Shah
Journal: Annals of Oncology (2017)
Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non-inferiority, phase 2/3 trial
Journal: The Lancet HIV (2016)

For HIV-1-infected young people facing lifelong antiretroviral therapy (ART), short cycle therapy with long-acting drugs offers potential for drug-free weekends, less toxicity, and better quality-of-life. We aimed to compare short cycle therapy (5 days on, 2 days off ART) versus continuous therapy (continuous ART).
Role of ErbB/HER family of receptor tyrosine kinases in cholangiocyte biology
Authors: Anna Pellat, Javier Vaquero, Laura Fouassier
Journal: Hepatology (2017)

The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions, including differentiation, proliferation, survival, and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from complete. Current knowledge suggests a role for epidermal growth factor receptor (EGFR) in cholangiocyte specification and proliferation, and in hepatocyte transdifferentiation into cholangiocytes during liver regeneration to restore biliary epithelium integrity. High expression and activation of EGFR and/or ErbB2 were recently demonstrated in biliary lithiasis and primary sclerosing cholangitis, two cholangiopathies regarded as risk factors for CCA. In CCA, ErbB receptors are frequently overexpressed, leading to tumor progression and low prognosis. Anti-ErbB therapies were efficient only in preclinical trials and have suggested the existence of resistance mechanisms with the need to identify predictive factors of therapy response. This review aims to compile the current knowledge on the functions of ErbB receptors in physiology and physiopathology of the biliary epithelium. (Hepatology 2018;67:762-773).
Analysis of the acute radiation-induced toxicity in relation to the serum IL-8 level in postmenopausal women with receptor-positive breast cancer receiving adjuvant radiotherapy with concomitant or sequential anastrozole.
Authors: Qian Zhang, XiaoLi Yu, Chaosu Hu, XiaoMao Guo, Zhen Zhang, JiaYi Chen
Journal: Journal of Clinical Oncology (2014)

e11558 Background: To compare acute skin reaction occurrence rate and serum IL-8 level in postmenopausal hormone receptor-positive patients with concurrent or sequential anastrozole with radiotherapy. Compare the hematologic toxicity, radiation-induced lung injury and long-term outcome in these patients. Methods: From January 2, 2011 to June 20, 2012, 80 postmenopausal hormone receptor-positive breast cancer patients were enrolled in this prospective study. All patients received adjuvant radiotherapy in the Department of Radiation Oncology, Fudan University Shanghai Cancer Center and were randomly classified as concurrent group (n=40) in which hormonal therapy with anastrozole combined concurrently with radiotherapy, and sequential group (n=40) in which hormonal therapy with anastrozole were followed after completion of radiotherapy. Treatment complications, prognostic outcomes and serum IL-8 level (four weeks after the start of radiotherapy) were followed up and analyzed. Results: The median follow-up time was 24 months. 5 patients in the concurrent group and 7 patients in the sequential group had grade 2 or worse skin-related toxicity, the difference between two groups was not statistical significant (P>0.05). The incidence of hematologic adverse reactions of two group patients was no statistically significant difference (P>0.05). There was no radiation pneumonitis in two groups. The overall survival was 100% in both groups, the difference of metastasis-free survival between two groups was not statistically significant (P=0.653). Serum IL-8 between two groups was not statistically significant (P>0.05). In the whole group, the patients with grade 2 or worse skin-related toxicity had higher serum levels of IL-8 compared to those with grade 1 skin-related toxicity(P=0.008). Conclusions: Adjuvant anastrozole can be safely delivered in concurrent with radiotherapy in postmenopausal women with receptor positive breast cancer with comparable therapeutic outcome. The serum IL-8 level in the course of radiotherapy may predict the acute radiation-induced skin toxicity. Clinical trial information: NCT01402193.
Impact of primary tumour location on response and resection outcomes in patients with metastatic colorectal cancer (mCRC) undergoing first-line treatment
Authors: Marc Peeters, Timothy Price, Julien Taieb, Michael Geissler, Fernando Rivera, Jean-Luc Canon, Reija Koukakis, Peter Burdon, Salvatore Siena
Journal: Annals of Oncology (2017)
History of multiple sport-related concussions alters variability of heart rate response to activity
Authors: Alexander D Wright, Harjas S Grewal, Jonathan D Smirl, Kelsey Bryk, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective To examine the effect of multiple previous concussions on heart rate variability (HRV) in contact-sport athletes. Design Retrospective Cohort. Setting Laboratory. Participants 136 male elite contact-sport (hockey and football) athletes were recruited for this study. Forty-one had no previous concussion history (Hx-), while nineteen had a history of three or more concussions (Hx+). All testing was preformed prior to the start of the competitive season Interventions HRV was assessed during 5-minutes of quiet stance, and while actively squatting at 0.10 Hz via a 3-lead electrocardiogram, using Kubios software. Independent variables included condition (rest vs active) and group (Hx+ vs Hx-) Outcome measures Time-Domain: square root of mean squared differences of successive R-R intervals (RMSSD), percentage of successive R-R intervals that differ by more than 50 milliseconds (pNN50). Frequency-Domain: total power. Main results Mixed ANOVA revealed repeated squat-stand manoeuvres challenged the autonomic system, increasing total power by 2477 milliseconds 2 (95% CI: 1153–3801, p&lt;0.001). A significant interaction effect was observed for RMSSD (p=0.031) and pNN50 (p=0.012), characterised by a greater increase in HRV in the Hx+ group than in Hx- from rest to squatting (95%CIs for group differences, RMSSD: 13.2–26.3 ms, p=0.006; pNN50: 3.6–15.1%, p=0.002) Conclusions A history of multiple sport-related concussions impairs the ability of the autonomic system to respond to an everyday stressor applied to the cardiovascular system (squatting and standing). This is an important finding, as it reveals that cumulative concussions may impart long-term impairments in the ability to accurately regulate the autonomic system. Competing interests None.
An unusual case of impacted biliary stone
Authors: Massimiliano Mutignani, Lorenzo Dioscoridi, Edoardo Forti, Francesco Pugliese, Stephen Dokas, Alberto Tringali, Benedetto Mangiavillano
Journal: Endoscopy (2017)

The incidence of biliary stones is higher in the female sex [1] [2]. Common bile duct (CBD) stones are the most common cause of acute biliary pancreatitis (ABP) [3]. We report the case of a 39-year-old woman with ABP.
Evaluation of Chest Pain in the Emergency Department
Authors: Tsung O. Chen
Journal: Annals of Internal Medicine (1995)

Letters15 August 1995Evaluation of Chest Pain in the Emergency DepartmentTsung O. ChenTsung O. ChenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-4-199508150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the editorial by Kaul and Abbott [1] on evaluation of chest pain in the emergency department. Although the authors made several valuable recommendations on the assessment of acute chest pain in patients in the emergency department, they did not mention one simple and important aid in the decision-making process—the availability of a previously obtained electrocardiogram.If a patient with chest pain comes to the emergency department and has abnormal electrocardiographic findings (for example, Q waves, ST-segment changes, left bundle-branch block, premature ventricular contractions, or atrial fibrillation), no physician can determine from one isolated ...References1. Kaul S, Abbott RD. Evaluation of chest pain in the emergency department (Editorial). Ann Intern Med. 1994; 121:976-7. Google Scholar2. Cheng TO. Availability of a prior electrocardiogram. Mayo Clin Proc. 1992; 67:305-6. Google Scholar3. Cheng TO. An ECG credit card. Postgrad Med. 1992; 92:41. Google Scholar4. Lee TH, Cook EF, Weisberg MC, Rouan GW, Brand DA, Goldman L. Impact of the availability of a prior electrocardiogram on the triage of the patient with acute chest pain. J Gen Intern Med. 1990; 5:381-8. Google Scholar Author, Article, and Disclosure InformationAuthors: Tsung O. Chen PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1995Volume 123, Issue 4 Page: 314-318 Keywords Atrial fibrillation Cardiac care unit Electrocardiography Emergency department Infarction Ischemia Left bundle branch block Myocardial infarction Premature ventricular contraction ePublished: 15 August 2000 Issue Published: 15 August 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Incidence of second primary malignancies (SPM) in men with castration-resistant prostate cancer (CRPC) in SEER-Medicare database.
Authors: James A. Kaye, Catherine W Saltus, Brian Calingaert, David H Harris, Shannon Hunter, Jihong Zong, Gunnar Persson Brobert, Montse Soriano-Gabarro, Elizabeth B Andrews
Journal: Journal of Clinical Oncology (2017)

e13080 Background: A number of population-based epidemiological studies have been conducted to estimate incidence rates of SPM (newly detected malignancies) among cancer survivors, including those with prostate cancer. However, such data in patients with CRPC are limited. This study was conducted to estimate the incidence of SPM and overall survival (OS) in men with CRPC in the US. Methods: In the SEER-Medicare database, men aged &gt; 65 years with prostate cancer diagnosed in 2000 through 2011 were eligible for the study if they had no other prior malignancy, had surgical or medical castration, and met the protocol-defined criteria for ascertaining castration resistance based on subsequent treatment with any of these therapies: abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, or sipuleucel-T. First SPM were identified in Medicare data as 1 inpatient claim, 2 outpatient claims, or 2 physician claims; or in SEER data as 1 diagnosis. Follow-up data ended in 2013. We estimated incidence of SPM as events per 100 person-years (py) with 95% confidence intervals (CI) and survival by the Kaplan-Meier method. Results: Among 2,234 men with CRPC (83.6% white; mean age, 76.6 years; 80.4% with bone metastases), we identified 172 with SPM, of which 20 (11.6%) were in SEER data. The incidence of all first SPM was 5.9 per 100 py (95% CI, 5.0-6.8). The most common of these were lung (n = 29), bladder (n = 22), colorectal (n = 21), other genitourinary cancers (n = 18), and non-colorectal gastrointestinal cancers (n = 17). Mean (SD) time from CRPC ascertainment to SPM was 1.0 (1.1) year. Median OS for the entire study population was 1.2 years (95% CI, 1.1-1.3) after CRPC ascertainment; estimated survival probabilities (95% CI) at 1, 3, and 5 years were 56% (54%-58%), 17% (15%-18%), and 9% (7%-11%), respectively. Conclusions: Most CRPC patients had claims for a diagnosis of bone metastasis when CRPC was ascertained. SPM were common among the study population and occurred relatively soon after CRPC. Most SPM were identified in Medicare rather than SEER data. These results provided context for the incidence of SPM in men with CRPC up to 2013.
BMA annual meeting: Department of Health must stop sharing patient details with immigration enforcers, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

The BMA will call on the UK Department of Health to stop sharing patient details with the Home Office for immigration enforcement.

Delegates at the BMA’s annual representative meeting in Bournemouth on 28 June voted in favour of a motion opposing the practice of sharing patients’ administrative details, including their address, with the Home Office.

The motion said, “This meeting notes and deplores the recently signed memorandum of understanding between the UK Department of Health, NHS Digital and the Home Office, which agrees to the transfer of patient administrative details . . . without the consent of the patient and the knowledge of the GP.”

It said that this agreement was a …
ECCO2R for severe hypercapnic acidosis: analysis of CO2 removal on pulmonary hemodynamics and effects of regional citrate anticoagulation
Authors: Philippe Morimont, Simon Habran, Thomas Desaive, Francine Blaffart, Julien Guiot, Philippe Kolh, Pierre Dauby, Jean-Olivier Defraigne, Bernard Lambermont
Journal: European Journal of Heart Failure (2017)
Reverse-phase protein microarray (RPPA) analysis of PD-L1 and growth factor receptor signal transduction pathways in hormone receptor (HR)-positive primary breast cancer tissue and correlation with relapse.
Authors: Suhail M. Ali, Bing Han, Joseph J. Drabick, Meghan P. Riley, Kim Leitzel, Eric Marks, Luis Costa, Issam Makhoul, Harold A. Harvey, Cristina I. Truica, Leah Cream, J. Stanley Smith, Rena Kass, Kristine Widders, Monali K. Vasekar, Glenn D. Hoke, Nicholas N Hoke, Corinne Ramos, James Cooper, Allan Lipton
Journal: Journal of Clinical Oncology (2016)

558 Background: Despite considerabletreatment advances,resistance to hormone therapy remains a major clinical problem. We correlated the protein levels of multiple tyrosine kinase receptors, signal transduction pathway proteins, and PD-L1 with relapse in HR-positive, HER2-negative breast cancer. Methods: A case-control discovery Reverse-Phase Protein Array (RPPA) analysis of primary tumors from 40 HR-positive, HER2-negative breast cancer patients: 18 patients who had relapsed; and 22 patients who had not relapsed (with a minimum of 2.5 years follow-up) was conducted to evaluate the potential of a 24 analyte panel of total and phosphoproteins to predict for probability of relapse. Analytes evaluated include: PD-L1, total and phosphoproteins for EGFR, HER2, HER3, and AR; and phosphoproteins in the major downstream signaling pathways: Ras/MAPK, AKT/mTOR, and JAK/STAT. Rank sum, ROC, and multianalyte statistical analysis was conducted to correlate the FFPE analyte data with clinical outcome (relapse or not). Results: Rank sum analysis of the 24 individual analytes revealed that only PD-L1 was significantly predictive of relapse. Relapsed patients had a significantly higher PD-L1 level (median 679, range 434 to 2702 NFU-normalized flourescence intensity per unit protein) compared to the patients who did not relapse (median of 511, range 112 to 1877 NFU) (p = 0.0098). ROC curve analysis yielded an AUC of 0.74 at a cut point of 577.53 NFU for PD-L1, and revealed a sensitivity of 72.2% and specificity of 81.82% for prediction of relapse. Further analysis of doublet or triplet analyte combinations (including PD-L1) did not add any additional ability to predict for relapse. Conclusions: Quantitative analysis of PD-L1 (of 24 analytes tested) was significantly predictive of relapse; higher PD-L1 predicted for a higher relapse rate. These results suggest that PD-L1 quantitation in larger hormone receptor-positive primary breast cancer patient cohorts may show promise to identify and select patients more likely to benefit from immune checkpoint inhibitors.