tbuckley/cabot-search huggingface dataset:
Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials
Authors: Saleh A. Alqahtani, Nezam Afdhal, Stefan Zeuzem, Stuart C. Gordon, Alessandra Mangia, Paul Kwo, Michael Fried, Jenny C. Yang, Xiao Ding, Phillip S. Pang, John G. McHutchison, David Pound, K. Rajender Reddy, Patrick Marcellin, Kris V. Kowdley, Mark Sulkowski
Journal: Hepatology (2015)

In phase III studies, treatment with the once‐daily fixed‐dose combination tablet of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV‐SOF with and without RBV. We analyzed treatment‐emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index ≥30 kg/m 2 , and 440 (23%) were treatment experienced. Treatment‐related AEs occurred in 71% and 45% of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving RBV with LDV/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV/SOF alone. Rates of treatment‐related serious AEs and discontinuations resulting from AEs were similarly low (&lt;1%) in both groups. The rate of SVR in those receiving RBV and those not receiving RBV was the same (97%). Conclusion : LDV/SOF plus RBV was associated with a greater incidence of AEs as well as concomitant medication use than LDV/SOF alone. Use of RBV did not impact the efficacy of LDV/SOF regimens in the ION phase III studies. (H epatology 2015;62:25‐30)
Abstract P33: Impact of Rapid Cooling, a Multidisciplinary Post Resuscitation Strategy, and Regionalization of Care Compared to Hypothermia Alone on Outcomes After Out of Hospital Cardiac Arrest
Authors: Mary Ann Peberdy, Joseph P Ornato, Michael C Kurz, Charlotte S Roberts, Michelle Gossip, Rene D Reid, Harinder S Dhindsa
Journal: Circulation (2009)

Background: Hypothermia (H) improves survival from VF OOH-CA. Addition of a standardized multidisciplinary post resuscitation strategy (SMPRS), faster time to target temperature, and higher patient...
Abstract 507: The Glycome Is Functionally Remodeled Throughout The Developing Myocardium
Authors: Marty L Montpetit, Patrick J Stocker, Stuart M Haslam, Steven R Head, Timothy Gilmartin, Lana Schaffer, Simon J North, Jihye Jang-Lee, Jamey D Marth, Eric S Bennett
Journal: Circulation (2007)

Cell surfaces are replete with complex, biologically important glycan structures responsible for multiple cellular functions including cell adhesion and cellular communication. Proper protein glycosylation is essential for normal development and physiology with the effects of improper glycosylation being severe and even lethal. Gene products involved in glycan formation (glycosylation-associated genes) comprise 1–2% of the genome, resulting in a glycome of thousands of structures; possibly more extensive than the proteome. Using GeneChip microarray analyses, we provide evidence that glycosylation-associated gene expression is highly regulated throughout the developing myocardium. Nearly one-third of the glycosylation-associated genes were significantly differentially expressed in neonatal atria versus neonatal ventricles while 46.8% of these same genes were differentially expressed in neonate versus adult ventricles. Quantitative-PCR of individual genes confirmed the microarray analyses. Such gross glycosylation-associated gene expression remodeling likely modifies the complexity and size of glycosylation structures attached to cell surface proteins. To confirm this, glycan structures were determined and compared among myocyte types using mass spectrometry. The data indicated that the observed regulation in gene expression translated into a change in glycan structure. Further, we report that remodeled glycans are likely responsible for alterations in voltage-gated sodium channel activity and action potential waveforms, suggesting a physiological role for regulation of glycosylation-associated genes in the heart. Specifically, differences in sodium channel gating in neonatal atria versus neonatal ventricles were abolished by knocking out a single polysialyltransferase expressed only in neonatal atria. Atrial action potential duration and the rate of depolarization were altered in the absence of this polysialyltransferase, while ventricle action potential waveforms were unaffected. Together, these data indicate that the glycome is tightly controlled in the heart, and proper glycosylation is apparently essential for normal myocyte functions.
Abstract 11839: Obesity Related Heart Rate Changes among Young Hispanic Women with Metabolic Syndrome
Authors: Mini M Jose
Journal: Circulation (2014)

Introduction: Visceral adiposity and metabolic syndrome have an earlier onset among Hispanic women due to genetic susceptibility. This study aimed to determine the association between changes in BMI, body weight and heart rate (HR) among Hispanic women aged 31-49years who met the ATP III criteria for metabolic syndrome and Obesity. Hypotheses: 1. There is a positive relationship between changes in BMI and Basal Heart rate 2. Patients with higher BMI will have a higher heart rate. Methods: In this retrospective study conducted in a community clinic, patient records meeting eligibility criteria were screened for three complete readings of anthropometric measurements and Vital signs. The readings taken when the patients had elevated temperature, respiratory rate, Blood pressure or when they were on Beta blockers were excluded. Final sample consisted of 61 records. Results: The sample BMI varied from 25 to 55 (Mean 34; SD 6) and the body weight ranged from 118lbs to 282lbs (Mean 188lbs; SD 35). The BMI change was between -4 to +4 (mean 1.15; SD 1.6), body weight change was from-30lbs to 22lbs (Mean 6.08 and SD 8.7) and the HR varied from -12 to 25 (mean 4.76; SD 8.38) Over 34 months. First hypothesis was accepted because Spearman Rho showed a significant positive correlation (r.298 p&lt;.05) between changes in BMI and HR and between changes in body weight and HR (r.304 p&lt;.05). A BMI change of one point raised the heart rate by 2beats/minute or 120beats/ hour accounting for 2,880 times/day. There was a no significant correlation between BMI and HR at all three data points leading reject the second hypothesis and conclude that the patients with highest BMI may not have the highest HR. Conclusions: The data showed that patients with metabolic syndrome and obesity suffer significant sympathetic stimulation raising basal HR, even when their blood pressure is controlled causing deleterious effect on already compromised heart with hypertension and atherosclerosis in metabolic syndrome. Patients with highest BMI may not have the highest HR due to failure to evoke an adequate sympathetic response and autonomic neuropathy signaling progressive chronic illnesses.
Abstract P3-05-10: Glucocorticoid and aldosterone mimic progestin-induction of a therapy-resistant cytokeratin-5 positive cell population in estrogen receptor-positive breast cancer through a Bcl6-dependent mechanism
Authors: Hallgeir Rui, Takahiro Sato, Amy Peck, Melanie A Girondo, Chengbao Liu, Albert J Kovatich, Jeffery A Hooke, Craig D Shriver, Edith Mitchell, Terry Hyslop, Chelain Goodman
Journal: Cancer Research (2015)

Abstract Resistance to anti-estrogen therapy remains a significant problem in patients diagnosed with estrogen receptor-α (ERα) positive breast cancer. Recent progress has defined a "lumino-basal" subclass of ERα-positive breast cancer characterized by mosaic presence of a minor population of ERα-negative cells expressing the basal cytokeratin-5 (CK5). The CK5-positive cells are therapy-resistant and have increased tumorigenic potential. Initial studies have suggested that progestins but not other steroids expand this CK5+ cell population. Unexpectedly, we discovered that at least two 3-ketosteroids other than progestins, glucocorticoids and mineralocorticoids, are capable of inducing the CK5+/ERα- cell population. CK5+ cells induced by glucocorticoid or aldosterone showed increased clonogenicity in soft agar, expressed the stem cell marker CD44, showed loss of ERα and PR expression, and demonstrated therapy-resistance with reduced apoptosis in response to chemotherapy, and were further enriched following adjuvant antiestrogen or chemotherapies. Induction of CK5+ cells by 3-ketosteroids was consistently preceded by induction of Bcl6, a transcriptional repressor implicated in breast cancer progression. Suppression of Bcl6 by shRNA or the Bcl6 suppressor, prolactin, abolished 3-ketosteroid-induction of CK5+ cells. Prolactin also blocked 3-ketosteroid-induced colony formation in vitro and suppressed progestin-induction of the CK5+ cell population in T47D xenograft tumors in vivo. Survival analyses with recursive partitioning revealed that CK5 and Bcl6 transcripts or protein levels in ERα+ breast cancer identify patients at high or low risk for tumor in two independent cohorts. The observations provide a mechanism by which stress-related or pharmacologic elevation of glucocorticoids may adversely affect patients with ERα+/CK5+ breast cancer, and may justify further exploring of inhibitors to 3-ketosteroid receptors or Bcl6 for therapeutic benefit. Citation Format: Hallgeir Rui, Takahiro Sato, Amy Peck, Melanie A Girondo, Chengbao Liu, Albert J Kovatich, Jeffery A Hooke, Craig D Shriver, Edith Mitchell, Terry Hyslop, Chelain Goodman. Glucocorticoid and aldosterone mimic progestin-induction of a therapy-resistant cytokeratin-5 positive cell population in estrogen receptor-positive breast cancer through a Bcl6-dependent mechanism [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-10.
Massachusetts Medical Society
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1974)

COMMITTEE ON MATERNAL WELFARE Paralytic IleusA 31-year-old single gravida 7 had easily borne six children (one later drowned), and now at eight weeks requested abortion. A variety of birth-control pills had been tried but could not be tolerated, and two intrauterine devices had been extruded. At the time of the present conception contraceptive foam was in use.The patient also complained of pain in the left leg and knee and, one week later, of pain in the right leg. Short, obese and known to have fibroids, she presented a uterus much too large for the dates, but her extremities . . .
Abstract OT2-2-02: Phase I/II clinical trial on the combination of carboplatin, eribulin and E7449
Authors: Virginia Kaklamani, Ruth o'Regan, Kari Wisinski, Kent Hoskins, James Wade, William Gradishar
Journal: Cancer Research (2015)

Abstract The combination of carboplatin and eribulin has been found to be effective in triple negative breast cancer patients. A recently conducted neoadjuvant clinical trial showed a pathologic complete response (pCR) of 45% with four cycle of carboplatin and eribulin. Recent preclinical data from EISAI suggest that there is synergy between carboplatin, eribulin and E7449 (an oral PARP inhibitor) in BRCA deficient and PTEN mutated xenograft models. Loss of Heterozygosity (LOH) is DNA alterations which develop through double strand DNA breaks. The homologous recombination (HRD) Score is calculated by the number of LOH regions greater 15Mb in length and less than an entire chromosome present in the genome. A high HRD score is present in BRCA deficient tumors and predicts for sensitivity to platinum-based chemotherapy. We propose a phase I/II clinical trial on the combination of carboplatin, eribulin and E7449. As part of the phase I clinical trial HRD will be performed and correlated to response to therapy. In the phase II clinical trial women with BRCA related breast or ovarian cancer, triple negative breast or ovarian cancer with high HRD score or PTEN deficient will be enrolled at a dose level found during the phase I clinical trial. Tissue will be requested to test for PARP inhibition. The primary endpoint of the phase II clinical trial is response rate. A total of 30 patients will be enrolled to the phase II clinical trial. Citation Format: Virginia Kaklamani, Ruth o'Regan, Kari Wisinski, Kent Hoskins, James Wade, William Gradishar. Phase I/II clinical trial on the combination of carboplatin, eribulin and E7449 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-2-02.
THE ASSOCIATION OF DISCHARGE ASPIRIN DOSE AND OUTCOMES IN ACUTE MYOCARDIAL INFARCTION: INSIGHTS FROM THE TRANSLATE-ACS STUDY
Authors: Ying Xian, Tracy Wang, Lisa Kaltenbach, Mark Effron, Timothy Henry, Richard Bach, Marjorie Zettler, Paul Vaitkus, Gregg Fonarow, Eric Peterson
Journal: Journal of the American College of Cardiology (2013)
Drug points: Alopecia and breast disease
Authors: C A Gateley, N J Bundred
Journal: BMJ (1997)

A 26 year old woman with refractory cyclical mastalgia was started on a regimen of 10 mg tamoxifen daily. She was otherwise well and not taking any other drugs. After three months she developed alopecia on her crown. Tamoxifen was stopped and her hair began to grow back. Because of continuing symptoms, she was given goserelin 3.6 mg monthly. After two injections the mastalgia resolved, but a …
Data from several sources are needed to show numbers taking drugs
Authors: D. A B St George
Journal: BMJ (1996)

EDITOR,—R Bracchi raises the point of how many patients are taking a drug.1 Pharmaceutical companies would very much like accurate data on this to help with calculations of the reported incidence of adverse drug reactions and with commercial monitoring. Several practical difficulties arise. The data cannot be obtained from the point at which prescriptions are measured since not all prescriptions written are dispensed and not all drugs prescibed are consumed.

For a product whose patent is protected—that is, no …
Abstract 11726: Novel Non-Invasive Method to Estimate Myocardial Mass at Risk Calculated From Cardiac Computed Tomography Data: Validation Study Using Angiographic Myocardial Jeopardy Scores in Patients With Single Vessel Disease
Authors: Seiko IDE, Satoru Sumitsuji, Kensuke Yokoi, Masatoki Yoshida, Isamu Mizote, Masaki Awata, Keita Yamasaki, Kouichi Tachibana, Shinsuke Nanto, Yasushi Sakata
Journal: Circulation (2014)

Background: The myocardial mass at risk (MMAR), representing volume of myocardium distal to culprit lesion, is one of important factors for predicting adverse cardiac event in ischemic heart disease. However, current non-invasive cardiac imaging fails to quantify MMAR in patients with stable coronary artery disease. We have developed a new software calculating MMAR of any designated coronary artery by reconstructing the 3-dimensional-volume-data of cardiac computed tomography (CCT). The novel index, ratio of MMAR to whole left ventricular volume (%LV-MMAR), calculated with this software would be appealing to obtain MMAR objectively. This study aims to compare the %LV-MMAR with Bypass Angioplasty Revascularization Investigation (BARI) and modified Albert Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores, both of which are invasive angiographic methods widely used to estimate MMAR, in patients with single-vessel disease. Methods: Between April 2008 and March 2014, patients suspected of effort angina pectoris without history of previous myocardial infarction were assessed with CCT and invasive coronary angiography. Of those, 48 patients who were revealed single-vessel disease (left anterior descending artery (LAD): n=22, left circumflex artery (LCX): n=11 and right coronary artery (RCA): n=15) were included in this study. %LV-MMAR was calculated on the software. BARI and modified APPROACH score were calculated and compared with %LV-MMAR. Results: Mean %LV-MMAR was 27.6 [18.2-37.1] %. BARI and APPROACH scores showed a significant correlation (r=0.92, p&lt;0.0001). Also, a significant correlation was observed between %LV-MMAR versus BARI and %LV-MMAR versus APPROACH (r=0.95, p&lt;0.0001 and r=0.9, p&lt;0.0001, respectively). %LV-MMAR showed significant correlation with BARI and APPROACH scores in all vessels; LAD (r=0.95, p&lt;0.0001 and r=0.91, p&lt;0.0001, respectively), LCX (r=0.91, p=0.0001 and r=0.83, p=0.0002, respectively) and RCA (r=0.92, p&lt;0.0001 and r=0.85, p&lt;0.0001, respectively). Conclusions: This study revealed %LV-MMAR, calculated from CCT data on novel software, to be a promising index for estimating perfusion territory noninvasively in good agreement with BARI and modified APPROACH score.
Abstract 3900: Pten deletion in SOX9+ cells leads to tumor initiating cell expansion and tumor development in mouse liver
Authors: Ni Zeng, Janel Kopp, Lina He, Maike Sander, Bangyan Stiles
Journal: Cancer Research (2014)

Abstract Liver cancer is one of the most aggressive malignancies with a five-year survival rate less than 10%. There is thus an urgent unmet need to understand the process of liver tumorigenesis in order to develop early diagnosis and effective therapeutic treatments. Clinical studies have suggested that tumor initiating cell (TIC) activation is observed in over 70% of liver cancer samples and is closely linked with poor survival outcome after treatment. Consistent with these observations, our previous studies utilizing a Pten (loxp/loxp); Albumin-Cre+ mouse liver cancer model also confirmed the expansion of TICs during liver tumorigenesis. However, how TICs are activated and what mechanisms contribute to liver tumor development remains unclear. Here, we studied the role of tumor suppressor PTEN in TICs using the Pten (loxp/loxp); SOX9-CreER+ mouse model. Lineage tracing results indicated that in the liver SOX9+ cells possess the progenitor cell characteristics and give rise to bile duct cells and peri-portal hepatocytes later on. Pten deletion in SOX9+ cells at 4 weeks of age leads to expansion of both CK+ duct cells and HNF4+ hepatocytes in the peri-portal areas. Interestingly, we also observed tumor development at 12 months old mutant mice and close examinations revealed that the tumors are heterogeneous, indicating the contribution of TICs during this process. Together, our study suggested that the PTEN signaling is critical for TICs regulation and that TICs activation plays a key role in liver tumorigenesis. Citation Format: Ni Zeng, Janel Kopp, Lina He, Maike Sander, Bangyan Stiles. Pten deletion in SOX9+ cells leads to tumor initiating cell expansion and tumor development in mouse liver. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3900. doi:10.1158/1538-7445.AM2014-3900
An open trial of L-tyrosine in the treatment of attention deficit disorder, residual type
Authors: Frederick W. Reimherr, Paul H. Wender, David R. Wood, Mark Ward
Journal: American Journal of Psychiatry (1987)

To elucidate the role of catecholamines in attention deficit disorder, the authors conducted an open 8-week trial of L-tyrosine in 12 adults with attention deficit disorder, residual type. Eight showed marked to moderate clinical response in 2 weeks; at 6 weeks these eight developed tolerance, suggesting that L-tyrosine is not useful in attention deficit disorder, residual type.
May be high risk, low benefit
Authors: John S Yudkin
Journal: BMJ (2008)

The problems with a glucocentric approach to managing patients with type 2 diabetes1 2 3 can be seen using data from the UKPDS.4 In the 10 years of follow-up of newly diagnosed patients with a mean age of 53, macrovascular events (myocardial infarction and stroke) were five times more common than serious microvascular events (blindness in one eye and renal failure) but, unlike these, were not significantly reduced by intensive glucose lowering. Moreover the observational data from …
An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
Authors: E Padron, G Garcia-Manero, M M Patnaik, R Itzykson, T Lasho, A Nazha, R K Rampal, M E Sanchez, E Jabbour, N H Al Ali, Z Thompson, S Colla, P Fenaux, H M Kantarjian, S Killick, M A Sekeres, A F List, F Onida, R S Komrokji, A Tefferi, E Solary
Journal: Blood Cancer Journal (2015)

Abstract Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication.
Abstract 13284: Identification of a Unique Proteolytic-Profibrotic Interaction Following Myocardial Infarction Which is Amplified Following a Second Episode of Ischemia-Reperfusion
Authors: Jennifer A Dixon, William F Gaillard, William T Rivers, Christine N Koval, Robert E Stroud, Rupak Mukherjee, Francis G Spinale
Journal: Circulation (2010)

Objectives: A recognized structural event following a myocardial infarction (MI) is extracellular matrix (ECM) remodeling which includes induction of proteolytic pathways such as matrix metalloprot...
The World Health Organisation: WHO in crisis
Authors: F. Godlee
Journal: BMJ (1994)

Media attention has been focused on the leadership of the World Health Organisation, rather than on the real factors that limit WHO's effectiveness. These factors relate to the organisation's structure and also to its current priorities, methods, and management. This article examines the objectives and strategy of WHO in view of financial constraints and donor countries' demands; WHO's stated goal of integrated primary health care; staff morale; and the growing dislocation between the regions and headquarters.