tbuckley/cabot-search huggingface dataset:
Recent TB transmission, clustering and predictors of large clusters in London, 2010–2012: results from first 3 years of universal MIRU-VNTR strain typing
Authors: Esther L Hamblion, Arnaud Le Menach, Laura F Anderson, Maeve K Lalor, Tim Brown, Ibrahim Abubakar, Charlotte Anderson, Helen Maguire, Sarah R Anderson
Journal: Thorax (2016)

<h3>Background</h3> The incidence of TB has doubled in the last 20 years in London. A better understanding of risk groups for recent transmission is required to effectively target interventions. We investigated the molecular epidemiological characteristics of TB cases to estimate the proportion of cases due to recent transmission, and identify predictors for belonging to a cluster. <h3>Methods</h3> The study population included all culture-positive TB cases in London residents, notified between January 2010 and December 2012, strain typed using 24-loci multiple interspersed repetitive units-variable number tandem repeats. Multivariable logistic regression analysis was performed to assess the risk factors for clustering using sociodemographic and clinical characteristics of cases and for cluster size based on the characteristics of the first two cases. <h3>Results</h3> There were 10 147 cases of which 5728 (57%) were culture confirmed and 4790 isolates (84%) were typed. 2194 (46%) were clustered in 570 clusters, and the estimated proportion attributable to recent transmission was 34%. Clustered cases were more likely to be UK born, have pulmonary TB, a previous diagnosis, a history of substance abuse or alcohol abuse and imprisonment, be of white, Indian, black-African or Caribbean ethnicity. The time between notification of the first two cases was more likely to be &lt;90 days in large clusters. <h3>Conclusions</h3> Up to a third of TB cases in London may be due to recent transmission. Resources should be directed to the timely investigation of clusters involving cases with risk factors, particularly those with a short period between the first two cases, to interrupt onward transmission of TB.
Case 31-1975
Authors: David A. Rytand, Benjamin Castleman, Ronald F. Dorfman
Journal: New England Journal of Medicine (1975)

Presentation of Case*A 53-year-old man was admitted to the hospital† because of dyspnea.He was well until one year previously, when his exercise tolerance began to decrease, and he became progressively tired at his custodial job. Five months before admission he experienced the first of numerous episodes of hemoptysis; a dry cough developed and was occasionally productive of sputum that was streaked with bright-red blood. One month before entry an episode of hemoptysis was accompanied by sharp pain in the right side of the chest. The neck became stiff, and the temperature rose to 38.3° C. An x-ray film . . .
Mutational Landscape and Sensitivity to Immune Checkpoint Blockers
Authors: Roman M. Chabanon, Marion Pedrero, Céline Lefebvre, Aurélien Marabelle, Jean-Charles Soria, Sophie Postel-Vinay
Journal: Clinical Cancer Research (2016)

Immunotherapy is currently transforming cancer treatment. Notably, immune checkpoint blockers (ICB) have shown unprecedented therapeutic successes in numerous tumor types, including cancers that were traditionally considered as nonimmunogenic. However, a significant proportion of patients do not respond to these therapies. Thus, early selection of the most sensitive patients is key, and the development of predictive companion biomarkers constitutes one of the biggest challenges of ICB development. Recent publications have suggested that the tumor genomic landscape, mutational load, and tumor-specific neoantigens are potential determinants of the response to ICB and can influence patients' outcomes upon immunotherapy. Furthermore, defects in the DNA repair machinery have consistently been associated with improved survival and durable clinical benefit from ICB. Thus, closely reflecting the DNA damage repair capacity of tumor cells and their intrinsic genomic instability, the mutational load and its associated tumor-specific neoantigens appear as key predictive paths to anticipate potential clinical benefits of ICB. In the era of next-generation sequencing, while more and more patients are getting the full molecular portrait of their tumor, it is crucial to optimally exploit sequencing data for the benefit of patients. Therefore, sequencing technologies, analytic tools, and relevant criteria for mutational load and neoantigens prediction should be homogenized and combined in more integrative pipelines to fully optimize the measurement of such parameters, so that these biomarkers can ultimately reach the analytic validity and reproducibility required for a clinical implementation. Clin Cancer Res; 22(17); 4309-21. ©2016 AACR.
Safety and Efficacy Of Eltrombopag At Escalated Doses Up To 150mg In Patients With Persistent and Chronic Immune Thrombocytopenia (ITP) Not Responsive To 75 Mg
Authors: Catherine E. McGuinn, Allison Imahiyerobo, Micha Thompson, Naznin Haq, Claudia Tchatchouang, James B Bussel
Journal: Blood (2013)
Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR).
Authors: Tetsuya Mitsudomi, Satoshi Morita, Yasushi Yatabe, Shunichi Negoro, Isamu Okamoto, Takashi Seto, Miyako Satouchi, Hirohito Tada, Tomonori Hirashima, Kazuhiro Asami, Nobuyuki Katakami, Minoru Takada, Hiroshige Yoshioka, Kazuhiko Shibata, Shinzoh Kudoh, Eiji Shimizu, Hiroshi Saito, Shinichi Toyooka, Kazuhiko Nakagawa, Masahiro Fukuoka
Journal: Journal of Clinical Oncology (2012)

7521 Background: WJTOG3405 met its primary endpoint of progression free survival (PFS) (9.2 months (mo.) for G vs. 6.3 mo. for CD, hazard ratio (HR) 0.489, 95% confidence interval (CI): 0.336-0.710). (Mitsudomi et al., Lancet Oncol., 2010). However, the impact on overall survival (OS) was not clear then because of relatively short follow-up period. Methods: Overall survival (OS) was re-evaluated using updated data (data cutoff, 31 July, 2011, median follow-up, 34 months) for 172 patients. Results: Eighty-two events had occurred (48%). Median survival time (MST) for G arm was 36 mo. (95% CI: 26.3 -) which was not significantly different from 39 mo. (95% CI: 31.2 -) for CD arm (HR 1.185, 95% CI 0.767-1.829). Multivariate analysis using Cox proportional hazards model revealed that none of covariates (treatment arm, smoking status, sex, age, postoperative recurrence or IIIB/IV, and mutation type) significantly affected OS. In the G arm, MST of patients with exon 19 deletion (36 mo.) was comparable to that of patients with L858R (35 mo.). In the CD arm, 78 patients (91%) received EGFR-TKI as the 2 nd or later line treatment, whereas in the G arm, 52 patients (61%) received platinum doublet. Accordingly, 130 patients received both platinum doublet and EGFR-tyrosine kinase inhibitor (TKI) and 34 patients received EGFR-TKI without platinum doublet in their whole courses of therapy. MST for the former and the latter group were 36 months (95% CI: 31.2-45.7) and 45 months (95% CI: 25.6-), without significant difference. Conclusions: This update OS analysis revealed that G for advanced NSCLC with EGFR mutation offers distinct survival benefit of 3 years. There was no difference in OS whether the first-line treatment was G or CD, in accordance with the precedent studies. The reason why PFS difference was not translated into OS difference is probably due to high cross over rate to EGFR-TKI. However, it was noteworthy that 40% of patients in the G arm could be managed without platinum doublet and yet had similar outcome.
ON- VS OFF CABG: EFFECTS ON POSTOPERATIVE LACTATE, BASE EXCESS AND PH OVER THE FIRST 24 HOURS IN INTENSIVE CARE
Authors: F Chiarenza, C Cassisi, F Sanfilippo, C Santonocito, M Astuto, S George, M Trivella, D Altman, D Taggart
Journal: Intensive Care Medicine (2014)
Comprehensive Identification Of Germline Alterations In Telomerase Complex Genes By Whole Exome Sequencing Of MDS and Related Myeloid Neoplasms
Authors: Swapna Thota, Sarah McMahon, Bartlomiej Przychodzen, Thomas LaFramboise, Hideki Makishima, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2013)
THE PENSION PROBLEM.
Authors: K SCHANKE
Journal: JAMA (1898)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Multicohort phase II KEYNOTE-059 study of pembrolizumab (MK-3475) for recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Charles S. Fuchs, Andrew E. Denker, Josep Tabernero, Eric Van Cutsem, Atsushi Ohtsu, Baohoang Lam, Minori Koshiji, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2015)

TPS4135 Background: Many tumors suppress immune control via the programmed death receptor 1 (PD-1) pathway. Pembrolizumab is an anti–PD-1 monoclonal antibody designed to block the interaction of PD-1 with its ligands PD-L1 and PD-L2. In 39 patients (pts) with PD-L1–positive metastatic gastric cancer enrolled in the phase I KEYNOTE-012 trial, 67% of whom had ≥ 2 prior lines of therapy, pembrolizumab 10 mg/kg every 2 wk (Q2W) provided a 22% confirmed ORR (RECIST v1.1, central review) and an acceptable safety profile. KEYNOTE-59 (NCT02335411) is an ongoing, international, 3-cohort, phase II study designed to further assess pembrolizumab in pts with gastric cancer. Methods: All cohorts of KEYNOTE-059 will enroll pts with recurrent or metastatic gastric or GEJ adenocarcinoma, ≥ 1 measurable lesion, and ECOG PS 0 or 1. All pts must provide a newly collected (preferred) or archival tumor biopsy sample for immunohistochemical determination of PD-L1 expression at a central laboratory. In cohort 1, up to 180 pts with any PD-L1 status who progressed on ≥ 2 prior chemotherapy regimens that included a fluoropyrimidine and platinum doublet and, if HER2+, trastuzumab, will receive pembrolizumab 200 mg Q3W. In cohort 2, approximately 20 non-Asian and 20 Asian treatment-naive, HER2– pts with any PD-L1 status will receive pembrolizumab 200 mg Q3W plus infusional 5-FU or capecitabine and 6 cycles of cisplatin. In cohort 3, approximately 50 treatment-naive, HER2– pts with PD-L1–positive tumors will receive pembrolizumab 200 mg Q3W. In all cohorts, pembrolizumab will be given for 24 mo or until disease progression, intolerable toxicity, or investigator decision; treatment may be discontinued for complete response. Eligible pts may continue pembrolizumab beyond initial RECIST-defined progression. AEs will be monitored. Response will be assessed at wk 9 and every 6 wk thereafter per RECIST v1.1 and RECIST adapted to account for response patterns observed with immunotherapies. Primary end point is ORR per RECIST v1.1 by central review; secondary end points include PFS, OS, disease control rate, and duration of response. KEYNOTE-059 enrollment began in February 2015. Clinical trial information: NCT02335411.
Interrelationship Of c-Myc, Micro RNA 29 and 34 Families, DNA methyltransferases and Methylation In Acute Myeloid Leukemia
Authors: Ayaka Kaneko, Itsumi Suda, Yuta Masuda, Nami Goto, Master, Hikaru Hattori, Kenichi Tahara, Hiroaki Shimizu, Takuma Ishizaki, Takeki Mitsui, Akihiko Yokohama, Hiromi Koiso, Makiko Takizawa, Hirono Iriuchishima, Lobna A. Alkebsi, Naoko Hatsumi, Satoru Takada, Toru Sakura, Norifumi Tsukamoto, Takayuki Saitoh, Yoshihisa Nojima, Hirokazu Murakami
Journal: Blood (2013)
Targeting Programmed Cell Death Using Small‐Molecule Compounds to Improve Potential Cancer Therapy
Authors: Bowen Ke, Mao Tian, Jingjing Li, Bo Liu, Gu He
Journal: Medicinal Research Reviews (2016)

Evasion of cell death is one of the hallmarks of cancer cells, beginning with long-established apoptosis and extending to other new forms of cell death. An elaboration of cell death pathways thus will contribute to a better understanding of cancer pathogenesis and therapeutics. With the recent substantial biochemical and genetic explorations of cell death subroutines, their classification has switched from primarily morphological to more molecular definitions. According to their measurable biochemical features and intricate mechanisms, cell death subroutines can be divided into apoptosis, autophagic cell death, mitotic catastrophe, necroptosis, parthanatos, ferroptosis, pyroptosis, pyronecrosis, anoikis, cornification, entosis, and NETosis. Supportive evidence has gradually revealed the prime molecular mechanisms of each subroutine and thus providing series of possible targets in cancer therapy, while the intricate relationships between different cell death subroutines still remain to be clarified. Over the past decades, cancer drug discovery has significantly benefited from the use of small-molecule compounds to target classical modalities of cell death such as apoptosis, while newly identified cell death subroutines has also emerging their potential for cancer drug discovery in recent years. In this review, we comprehensively focus on summarizing 12 cell death subroutines and discussing their corresponding small-molecule compounds in potential cancer therapy. Together, these inspiring findings may provide more evidence to fill in the gaps between cell death subroutines and small-molecule compounds to better develop novel cancer therapeutic strategies.
Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume
Authors: Han Kyu Lee, Sehoon Keum, Huaxin Sheng, David S. Warner, Donald C. Lo, Douglas A. Marchuk
Journal: Journal of Clinical Investigation (2016)

Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in postischemic cerebral infarct volume observed between inbred strains. Here, we used ancestral haplotype analysis to fine-map this locus to 12 candidate genes. The gene encoding the IL-21 receptor (Il21r) showed a marked difference in strain-specific transcription levels and coding variants in neonatal and adult cortical tissue. Collateral vessel connections were moderately reduced in Il21r-deficient mice, and cerebral infarct volume increased 2.3-fold, suggesting that Il21r modulates both collateral vessel anatomy and innate neuroprotection. In brain slice explants, oxygen deprivation (OD) activated apoptotic pathways and increased neuronal cell death in IL-21 receptor-deficient (IL-21R-deficient) mice compared with control animals. We determined that the neuroprotective effects of IL-21R arose from signaling through JAK/STAT pathways and upregulation of caspase 3. Thus, natural genetic variation in murine Il21r influences neuronal cell viability after ischemia by modulating receptor function and downstream signal transduction. The identification of neuroprotective genes based on naturally occurring allelic variations has the potential to inform the development of drug targets for ischemic stroke treatment.
The Telomere Length In Peripheral Blood Lymphocytes Is a Useful Predictor of the Response to Immunosuppressive Therapy In Patients with Acquired Aplastic Anemia
Authors: Yoshiyuki Takahashi, Sayoko Doisaki, Nobuhiro Nishio, Hideki Muramatsu, Akira Shimada, Asahito Hama, Seiji Kojima
Journal: Blood (2010)
Economic analyses of new technologies: the case of stem-cell transplantation.
Authors: T M Waters, C L Bennett, J M Vose
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.1.2 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8996117 Economic analyses of new technologies: the case of stem-cell transplantation. T M WatersxT M WatersSearch for articles by this author , C L BennettxC L BennettSearch for articles by this author , J M VosexJ M VoseSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.1.2 First Page PDF © 1997 by American Society of Clinical Oncology
The organic-dynamic continuum in psychiatry: trends in attitudes among third-year residents
Authors: W Coryell
Journal: American Journal of Psychiatry (1982)

Identical surveys, designed to assess attitudes toward training and treatment in psychiatry, were distributed to the half of all third-year residents in 1976, 1978, and 1980. The 1976 survey results revealed considerable support for the medically oriented aspects of training and for organic approaches to treating endogenous depression and schizophrenia. Residents rated the treatment modalities for alcoholism differently than they did for schizophrenia and depression. Results from the 1978 and 1980 surveys replicated the 1976 findings, suggesting remarkable stability in attitudes. Changes in attitude over the three survey years may require a greater time span to manifest.
Patient and Physician Attitudes Toward Low-Value Diagnostic Tests
Authors: A. Sofia Warner, Neel Shah, Abraham Morse, Eliyahu Y. Lehmann, Rie Maurer, Zoe Moyer, Lisa Soleymani Lehmann
Journal: JAMA Internal Medicine (2016)

Many American physicians think unnecessary tests and procedures are a serious problem facing our health care system, but 53% order unnecessary tests if requested by patients. 1This discrepancy between appropriate and actual care suggests that patients' perceptions of good care are not aligned with physicians' commitment to care that optimizes quality while reducing unnecessary interventions.We assessed patients' and physicians' perceptions of high-value care.Methods | We conducted a cross-sectional survey of patients and physicians from 3 academic primary care clinics in the Northeastern United States.Eligible patients had a clinic appointment, could read English, and complete a survey independently.Patients received a self-administered paper survey and were given a $5 gift card or parking validation.Physicians completed an electronic survey and could enter a $50 gift card lottery.This study was
A single cognitive heuristic process meets the complexity of domain-specific moral heuristics
Authors: Veljko Dubljević, Eric Racine
Journal: Behavioral and Brain Sciences (2014)

Abstract The inherence heuristic (a) offers modest insights into the complex nature of both the is–ought tension in moral reasoning and moral reasoning per se, and (b) does not reflect the complexity of domain-specific moral heuristics. Formal and general in nature, we contextualize the process described as “inherence heuristic” in a web of domain-specific heuristics (e.g., agent specific; action specific; consequences specific).
Case 50-1963
Authors: Daniel D. Federman, Victor J. Rosen
Journal: New England Journal of Medicine (1963)

Presentation of Case First admission. A nineteen-year-old boy was referred to the hospital because of dyspnea and hemoptysis.Six weeks before entry the patient was struck on the left side of the head by a bowling ball, but did not lose consciousness. Two weeks later he experienced a diffuse headache and paroxysms of coughing productive of abundant blood-streaked sputum and was given expectorants, sedatives and demethylchlor-tetracycline (Declomycin). Dyspnea on exertion developed and progressed in severity. Two weeks before admission increased thirst and polyuria occurred. He became weak, had several episodes of vomiting and "blacked out" a few times. On admission . . .
Elderly (&gt;=75) small-cell lung cancer (SCLC) chemotherapy: A phase I study of carboplatin (CBDCA) and etoposide (vp-16)
Authors: M. Fukuda, M. Oka, Y. Soejima, M. Fukuda, A. Kinoshita, H. Takatani, T. Kasai, M. Kuba, H. Soda, S. Kohno
Journal: Journal of Clinical Oncology (2004)

7217 Background: Elderly patients (>=75 year-old) have a great risk for chemotherapy, however, appropriate chemotherapy has improved survival and QOL in patients (pts) with SCLC. The combination with cisplatin and VP-16 is an active regimen for SCLC, and CBDCA is an analogue of cisplatin with less nonhematological toxicity. Based on these findings, we conducted a phase I study of CBDCA and VP-16 for elderly pts with SCLC. This study aimed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Methods: Twenty-six pts fulfilling the eligibility criteria were enrolled; chemotherapy-naive, performance status (PS) 0–2, age>=75, and adequate hematological, hepatic and renal function. The pts received CBDCA with target AUC = 4–5 (Chatelut formula, Jaffe method) on day 1 and VP-16 80–120 mg/m2 i.v. on days 1, 2 and 3. Therapy was repeated 4 cycles in every 4 weeks and LD pts only received sequential thoracic radiotherapy. Results: Pts' characteristics: male/female = 21/5; PS 0/1/2 = 9/11/6; median age (range) = 77.5 (75–82); LD/ED = 16/10. The MTD dose of CBDCA/VP-16 were 5/80, 4/110 and 4/120. The DLT were thrombocytopenia, neutropenia, leukopenia and febrile neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (>=4 days), leukopenia (>=4 days) and febrile neutropenia occurred 27%, 20%, 7% and 13% in MTD levels, respectively, and no in other levels. Twenty of 26 pts showed objective responses (2CR,18PR; RR = 77%). The median survival time was 14.4 (LD15.7, ED 8.3) months. Conclusions: The dose of CBDCA AUC = 4 and VP-16 100 mg/m2 was recommended in this therapy. No significant financial relationships to disclose.