tbuckley/cabot-search huggingface dataset:
Associations between Blood and Urine Arsenic Concentrations and Global Levels of Post-Translational Histone Modifications in Bangladeshi Men and Women
Authors: Caitlin G. Howe, Xinhua Liu, Megan N. Hall, Vesna Slavkovich, Vesna Ilievski, Faruque Parvez, Abu B. Siddique, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, Max Costa, Mary V. Gamble
Journal: Environmental Health Perspectives (2016)

Background:Exposure to inorganic arsenic is associated with numerous adverse health outcomes, with susceptibility differing by sex. Although evidence from in vitro studies suggests that arsenic alters post-translational histone modifications (PTHMs), evidence in humans is limited.Objectives:The objectives were to determine: a) if arsenic exposure is associated with global (percent) levels of PTHMs H3K36me2, H3K36me3, and H3K79me2 in a sex-dependent manner, and b) if %PTHMs are stable when arsenic exposure is reduced.Methods:We examined associations between arsenic, measured in blood and urine, and %PTHMs in peripheral blood mononuclear cells from 317 participants enrolled in the Bangladesh Folic Acid and Creatine Trial (FACT). We also examined the stability of %PTHMs after the use of arsenic-removal water filters (n = 60).Results:Associations between natural log–transformed (ln) urinary arsenic, adjusted for creatinine (uAsCr), and %H3K36me2 differed significantly between men and women (p = 0.01). ln(uAsCr) was positively associated with %H3K36me2 in men [β = 0.12; 95% confidence interval (CI): 0.01, 0.23, p = 0.03] but was negatively associated with %H3K36me2 in women (β = –0.05; 95% CI: –0.12, 0.02, p = 0.19). The patterns of associations with blood arsenic were similar. On average, water filter use was also associated with reductions in %H3K36me2 (p < 0.01), but this did not differ significantly by sex. Arsenic was not significantly associated with %H3K36me3 or %H3K79me2 in men or women.Conclusions:Arsenic exposure was associated with %H3K36me2 in a sex-specific manner but was not associated with %H3K36me3 or %H3K79me2. Additional studies are needed to assess changes in %H3K36me2 after arsenic removal.Citation:Howe CG, Liu X, Hall MN, Slavkovich V, Ilievski V, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Costa M, Gamble MV. 2016. Associations between blood and urine arsenic concentrations and global levels of post-translational histone modifications in Bangladeshi men and women. Environ Health Perspect 124:1234–1240; http://dx.doi.org/10.1289/ehp.1510412
Regulation of Cholesterol Metabolism
Authors: John M. Dietschy, Jean D. Wilson
Journal: New England Journal of Medicine (1970)

Output from the System — Excretion and Degradation of CholesterolCholesterol excretion and degradation take place predominantly through the gastrointestinal tract by two mechanisms — excretion of cholesterol itself and catabolism of cholesterol to bile acids. Although these moieties and their bacterial transformation products are thought to account for the vast majority of cholesterol turnover in the normal state, the possibility has never been excluded that alternative mechanisms such as desquamation of skin and hair, conversion to steroid hormones and elimination in the urine and its sediment are important in some pathologic states.Neutral Sterol OutputThe mechanism (or mechanisms) . . .
Dalteparin Compared with an Oral Anticoagulant for Thromboprophylaxis in Patients with Cancer
Authors: François Nader
Journal: New England Journal of Medicine (2003)

1385 bronchiolitis. However, it does not seem justified to abandon treatment with either the use of epinephrine early in the course of the disease or the use of nose drops, a recommendation made with tongue in cheek at the end of our editorial. The main points of our editorial are that there are no indications for treatment with albuterol and that one might try either nose drops or nebulized epinephrine to relieve an infant’s distress. The site of the reduction in airway resistance may well be the nose, but we are not recommending a clinical trial of nose drops. On the basis of our experience, we do recommend that, before an infant requires intubation and intensive care, a course of nebulized epinephrine be given on a trial basis and that such therapy may be used in the emergency department, where there is clear evidence of its efficacy. 1 The study by Wainwright et al. also points out how important it is to use the appropriate outcome measure. Energy and attention to detail must go into the design of clinical trials; this energy should not be invested in trivial issues.
Reprogramming of Notch1-induced acute lymphoblastic leukemia cells into pluripotent stem cells in mice
Authors: H Zhang, H Cheng, Y Wang, Y Zheng, Y Liu, K Liu, J Xu, S Hao, W Yuan, T Zhao, T Cheng
Journal: Blood Cancer Journal (2016)

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells using the reprogramming factors (Oct4, Sox2, Klf4 and c-Myc, also called OSKM). 1 Cellular reprogramming and oncogenesis share many common features.The application of the iPS technology in cancers help us better understand the mechanism underlying the initiation and progression of cancer.Therefore, defining the reprogramming potential of cancer cells would provide unique opportunities to reveal epigenetic mechanisms and develop novel therapeutics for cancer.][5][6] However, whether the primary malignant leukemic T cells can be reprogrammed into the iPS cells is still a mystery.We first employed OSKM transgenic mice in which OSKM factors can be induced by doxycycline (Dox) and established the T-cell acute lymphoblastic leukemia (T-ALL) mouse model by transfecting the Lineage negative (Lin -) bone marrow cells from the OSKM mice with a Notch1-green fluorescent protein (GFP) retrovirus (Figure 1a).The mice developed leukemia within 2 months (Supplementary Figure S1A).The moribund mice exhibited a T-ALL phenotype (Supplementary Figures S1B-S1D).The flowchart shows the reprogramming scheme for the T-ALL cells (Figure 1b).GFP + leukemia cells were sorted and plated on mouse embryonic fibroblast feeder cells.After the formation of mouse embryonic stem (ES)-like colonies, a single colony was picked up and cultured on feeder cells to produce iPS cell lines (Figure 1c).Overall, the reprogramming efficiency was very low, only approximately 0.005 ± 0.0005% (Supplementary Figure S1E).Similarly to our previous study on acute myeloid leukemia cells. 4FP was not expressed in the established leukemia iPS (L-iPS) cells (Figure 1d), indicating that the retroviral vector was silenced in L-iPS cells.The expression of pluripotency markers Oct4, Nanog and SSEA-1 was confirmed by immunofluorescence staining (Figure 1e) and qRT-PCR analyses (Supplementary Figure S2A).Genomic PCR demonstrated the presence of ectopic Notch1 and immunoglobulin heavy chain rearrangement in all tested L-iPS cells, confirming that L-iPS cells were indeed derived from T-ALL cells (Supplementary
A comparative study of the correlations of the COPD assessment test (CAT) scores and high sensitive CRP levels to SPO2, FEV1, BODE index, and exacerbation rate
Authors: Hassan Ghobadi, Katrin Beukaghazadeh, Nasrin Fouladi
Journal: European Respiratory Journal (2011)

Background:  High sensitive CRP is used as a marker of systematic inflammation in COPD. Results have shown an inverse relation between serum hs-CRP and FEV 1 , except for small study which did not report any correlation between hs-CRP level and FEV 1 . However, we hypothesize that the raised hs-CRP is not closely related to the multiple consequences of COPD. CAT is a simple questionnaire for assessing and monitoring COPD. Thus, this study was undertaken to investigate the correlations between CAT score and SPO 2 , FEV 1 , BODE index, and exacerbation rate, and compare it with the correlations to the serum hs-CRP.   Method:  We studied 60 patients with stable COPD and 15 normal subjects as a control group. SPO 2 , BODE index, pulmonary function test and exacerbation rate were determined in COPD patients. Serum level of hs-CRP was measured in all patients and the control group. Then, the CAT questionnaire was completed by patients.   Results:  Hs-CRP level was significantly raised in patients (p=0.005). In these patients, correlations of hs-CRP level with BODE index appeared significant (p=0.008). However, the correlation between hs-CRP with SPO 2  and FEV 1  did not appear significant (p=0.47, p=0.17 respectively). Also, the CAT score correlations with SPO 2 , FEV 1 , BODE index, and exacerbation rate in the previous year were all found to be significant (p=0.000, p=0.000, p=0.000, p=0.017, respectively).   Conclusion:  We conclude that SPO 2 , FEV 1 , BODE index and exacerbation rate are more correlated with the CAT scores than with the serum level of hs-CRP in stable COPD patients. The findings of this study should be considered in management of stable COPD.
Case 26-1974
Authors: Richard C. Cabot, Robert E. Scully, Betty U. McNeely, George A. Jacoby, Max L. Goodman
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 27-year-old woman was admitted to the hospital because of hemoptysis.She was well until two and a half years previously, when she made a six-month voyage to the Orient with extended intervals in Nepal and India. Multiple episodes of bloody diarrhea occurred and were treated with diphenoxylate hydrochloride and iodochlorhydroxyquin. Two months after she returned to this country jaundice developed, and she was treated for infectious hepatitis at another hospital. An x-ray film of the chest revealed "a spot on the lung" that disappeared on follow-up films. Ten months before admission there was the onset of . . .
Expression levels of aldehyde dehydrogenase 1A1 (ALDH1A1) in circulating tumor and invasive cells (CTICs) as a biomarker for drug resistance and disulfiram in pancreatic adenocarcinoma (PDAC).
Authors: Mark Ricigliano, Brandon Cooper, Allyson J. Ocean, Herve Tiriac, David A. Tuveson, Kenneth H. Yu, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2016)

e15755 Background: We have previously demonstrated that gene expression profiling of CTICs can predict drug response in PDAC. ALDH1A1 has been proposed as a cancer stem cell marker in PDAC and other cancer types. ALDH1A1 controls the oxidation of aldehydes to corresponding acids, and has been proposed to confer drug resistance in ALDH1A1 overexpressing cancer cells. Disulfiram has been shown to inhibit ALDH1A1 activity. Methods: Expression data from 36 PDAC tumor biopsy samples was used to establish baseline ALDH1A1 and GAPDH levels in PDAC patients. A prospective MSKCC study was conducted, 29 treatment naïve patients with metastatic PDAC were accrued. Six mL of heparinized peripheral blood was collected prior to chemotherapy treatment. CTICs were isolated using a previously described cell adhesion assay. Total RNA and cDNA were isolated and qPCR was performed to establish ALDH1A1 levels. ALDH1A1 expression was normalized to levels obtained from tissue biopsy samples. ALDH1A1 levels obtained from CTICs were considered overexpressed at two standard deviations from the mean ALDH1A1 levels of the biopsy samples. ALDH1A1 expression was measured in 5 PDAC cell lines. IC50 to treatment with disulfiram was determined. Cells expressing ADH1A1 were counted by flow cytometry before and after disulfiram treatment. Results: In the 5 cell lines studied a strong negative correlation was observed between ALDH expression and disulfiram IC50 (p = 0.0167). Treatment of cell lines with disulfiram resulted in reduction in ALDH-high expressing cells. 11/29 (38%) patient-derived CTICs overexpressed ALDH1A1. Patients with high ALDH expressing CTICs experienced longer OS compared with low (11.9 v 3.7 mo). Conclusions: ALDH1A1 expression is a candidate biomarker for survival in PDAC. Preclinical studies suggest that disulfiram may be a promising therapy for treatment of ALDH-high expressing PDAC. Clinical trial information: NCT01474564.
Ublituximab (TG-1101), a Novel Glycoengineered Anti-CD20 Monoclonal Antibody, in Combination with Ibrutinib Is Highly Active in Patients with Relapsed and/or Refractory CLL and MCL; Results of a Phase II Trial
Authors: Jeff P. Sharman, Charles M. Farber, Daruka Mahadevan, Marshall T. Schreeder, Heather D. Brooks, Kathryn S. Kolibaba, Suzanne R. Fanning, Leonard M. Klein, Peter Sportelli, Hari P. Miskin, Michael S. Weiss, Daniel R. Greenwald
Journal: Blood (2014)
Abstract 6136: ECG Strain Pattern is Related to Endo/Epimyocardial Radial Strain Ratio aCoronary Flow Velocity Reserve in Hypertensive Patients
Authors: Yu Arita, Kumiko Hirata, Nobuo Nakamura, Kazushi Takemoto, Yuuichi Ozaki, Aiko Shimokado, Manabu Kashiwagi, Hiroki Matsumoto, Hideyuki Ikejima, Keishi Okouchi, Hiroto Tsujioka, Akio Kuroi, Kouhei Ishibashi, Hideaki Kataiwa, Kenichi Komukai, Takashi Tanimoto, Hironori Kitabata, Shigeho Takarada, Masato Mizukoshi, Atsushi Tanaka, Toshio Imanishi, Takashi Akasaka
Journal: Circulation (2008)

Background: Hypertensive patients with ECG strain pattern have been reported to have lower survival rate in comparison with those without strain pattern. It remains unclear whether endo/epimyocardi...
MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension
Authors: Georgina Carr, Vincenzo Barrese, Jennifer B. Stott, Oleksandr V. Povstyan, Thomas A. Jepps, Hericka B. Figueiredo, Dongling Zheng, Yalda Jamshidi, Iain A. Greenwood
Journal: Cardiovascular Research (2016)

Kv7.4, a voltage-dependent potassium channel expressed throughout the vasculature, controls arterial contraction and is compromised in hypertension by an unknown mechanism. MicroRNAs (miRs) are post-transcriptional regulators of protein production and are altered in disease states such as hypertension. We investigated whether miRs regulate Kv7.4 expression.In renal and mesenteric arteries (MAs) of the spontaneously hypertensive rat (SHR), Kv7.4 protein decreased compared with the normotensive (NT) rat without a decrease in KCNQ4 mRNA, inferring that Kv7.4 abundance was determined by post-transcriptional regulation. In silico analysis of the 3' UTR of KCNQ4 revealed seed sequences for miR26a, miR133a, miR200b, miR153, miR214, miR218, and let-7d with quantitative polymerase chain reaction showing miR153 increased in those arteries from SHRs that exhibited decreased Kv7.4 levels. Luciferase reporter assays indicated a direct targeting effect of miR153 on the 3' UTR of KCNQ4. Introduction of high levels of miR153 to MAs increased vascular wall thickening and reduced Kv7.4 expression/Kv7 channel function compared with vessels receiving a non-targeting miR, providing a proof of concept of Kv7.4 regulation by miR153.This study is the first to define a role for aberrant miR153 contributing to the hypertensive state through targeting of KCNQ4 in an animal model of hypertension, raising the possibility of the use of miR153-related therapies in vascular disease.
A Novel Method for Efficient Production of Multipotential Hematopoietic Progenitors from Human Embryonic Stem Cells by Co-Culture with Murine Fetal Liver-Derived Stromal Cells.
Authors: Feng Ma, Dan Wang, Sachiyo Hanada, Hirohide Kawasaki, Yuji Zaike, Toshio Heike, Toshio Kitamura, Tatsutoshi Nakahata, Kohichiro Tsuji
Journal: Blood (2005)
Phase III Trial Under Way For Melanoma Vaccine
Authors: M E Newman
Journal: JNCI Journal of the National Cancer Institute (1990)

Phase III Trial Under Way For Melanoma Vaccine Get access JNCI: Journal of the National Cancer Institute, Volume 82, Issue 4, 21 February 1990, Pages 253–254, https://doi.org/10.1093/jnci/82.4.253 Published: 21 February 1990
Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Authors: Scott Gettinger, Naiyer A. Rizvi, Laura Q. Chow, Hossein Borghaei, Julie Brahmer, Neal Ready, David E. Gerber, Frances A. Shepherd, Scott Antonia, Jonathan W. Goldman, Rosalyn A. Juergens, Scott A. Laurie, Faith E. Nathan, Yun Shen, Christopher T. Harbison, Matthew D. Hellmann
Journal: Journal of Clinical Oncology (2016)

Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial.Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point.Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively.First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC.
Beyond resilience: Positive mental health and the nature of cognitive processes involved in positive appraisals
Authors: Carmelo Vázquez
Journal: Behavioral and Brain Sciences (2015)

Abstract Although the PASTOR model provides a comprehensive framework to study resilience, it faces some challenges. First, some higher-order concepts (e.g., meaning) may be difficult to model in the laboratory. Second, defining resilience as an absence of pathology might be conceptually restrictive. Finally, the proposal that the severity of the event is associated to different appraisal mechanisms needs further evidence.
Efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation and heart failure: insights from <scp>ENGAGE AF‐TIMI</scp> 48
Authors: Giulia Magnani, Robert P. Giugliano, Christian T. Ruff, Sabina A. Murphy, Francesco Nordio, Marco Metra, Tiziano Moccetti, Veselin Mitrovic, Minggao Shi, Michele Mercuri, Elliott M. Antman, Eugene Braunwald
Journal: European Journal of Heart Failure (2016)
Some Observations on the Normal and Pathologic Anatomy of the Kidney of the Mouse
Authors: Thelma B. Dunn, M. D.
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article Some Observations on the Normal and Pathologic Anatomy of the Kidney of the Mouse Get access Thelma B. Dunn, M. D. Thelma B. Dunn, M. D. National Cancer Institute, National Institutes of Health, Public Health Service, Federal Security Agency Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 9, Issue 4, February 1949, Pages 285–301, https://doi.org/10.1093/jnci/9.4.285 Published: 01 February 1949 Article history Received: 31 August 1948 Published: 01 February 1949
Case 33-1969
Authors: Eugene A. Stead, Benjamin Castleman
Journal: New England Journal of Medicine (1969)

Presentation of Case First admission. A sixty-nine-year-old woman was admitted to the hospital because of dyspnea and abdominal pain.Fifty-one years previously dactylitis developed; amputation of the fingers was required, and pathological examination revealed sarcoidosis and acute and chronic osteomyelitis. Twenty-seven years before entry x-ray films of the chest showed hilar lymphadenopathy. The urine gave a + test for protein. The spleen was palpable. An old tuberculin skin test (1:10,000) and guinea-pig inoculation of sputum specimens were negative for tuberculosis. Nine years later eholecystectomy was performed; biopsy of lymph nodes around the cystic duct disclosed sarcoidosis; biopsy of the liver . . .
Survival and informed consent understanding of elderly advanced cancer patients enrolling in phase I trials
Authors: U. R. Teitelbaum, F. J. Hlubocky, C. K. Daugherty
Journal: Journal of Clinical Oncology (2005)

8109 Background: Demographic characteristics of geriatric advanced cancer patients in early phase trials have not been described, and little is specifically known about their understanding of the informed consent process for such trials. Methods: Subset analysis of an existing database of results from surveys and semi-structured face-to-face interviews of advanced cancer patients in Phase I trials regarding their informed consent and decisions to enroll in a clinical trial. Survival data was also collected. Results: Of 212 Phase I trial subjects, 36% were age 65 or older. The median age of this subgroup was 71 (range 65–82). Race distribution was comparable between the two age groups. Regarding informed consent understanding of the research purpose of a Phase I trial, younger patients were more likely to identify toxicity as the outcome measurement (80% vs 20%, p=0.06). Older Phase I subjects were more likely to answer “I don’t know” regarding trial purpose. Older Phase I subjects also reported not being given alternative care options, including palliative care (40% vs 11%, p=0.03). Older Phase I subjects reported being less worried about dying (28% vs 13%, p=0.01). There were significant differences in survival after enrollment. Median survival of older patients was 10.8 months (range 0.9 to 48.7 months), compared to younger patients at 6.4 months (range 0.2 to 35.9 months) (p=0.005). Conclusions: Older subjects in Phase I trials, while sharing many demographic characteristics with younger patients, survived significantly longer than younger subjects. Older subjects had poorer understanding of the trial purpose, and reported being offered fewer alternative treatment options. The survival advantage of the elderly patients in this highly selected population is an interesting and unexpected finding and suggests a significant selection bias of elderly advanced cancer patients entering early phase trials. This probable selection bias, and elderly subjects’ poor clinical trial consent understanding, deserve further study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vitas Hospice