tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Rivaroxaban Compared With Warfarin Among Elderly Patients With Nonvalvular Atrial Fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)
Authors: Jonathan L. Halperin, Graeme J. Hankey, Daniel M. Wojdyla, Jonathan P. Piccini, Yuliya Lokhnygina, Manesh R. Patel, Günter Breithardt, Daniel E. Singer, Richard C. Becker, Werner Hacke, John F. Paolini, Christopher C. Nessel, Kenneth W. Mahaffey, Robert M. Califf, Keith A.A. Fox
Journal: Circulation (2014)

Background— Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). This prespecified secondary analysis compares outcomes in older and younger patients. Methods and Results— There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0–3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance &lt;50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years; P =0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P &lt;0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63–1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76–1.19; interaction P =0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92–1.34; &lt;75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78–1.19; interaction P =0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response. Conclusions— Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly.
Accuracy of gated perfusion single-photon emission tomography for left ventricular ejection fraction assessment in the presence of large perfusion defects: correlation with cardiac magnetic resonance
Authors: Kevin Chen, Ru-San Tan, Felix Keng, Foong-Koon Cheah, Kim-Peng Tan, Bien-Soo Tan, Yean-Leng Lim, Terrance Chua
Journal: Journal of the American College of Cardiology (2002)
Autonomously Functioning Thyroid Rests Following Total Thyroidectomy for Graves?? Disease
Authors: PAULA TOULIOPOULOS, ELIZABETH OATES
Journal: Clinical Nuclear Medicine (1993)

Graves' disease may be managed medically, surgically, or with radioiodine. One of the least discussed surgical complications is incomplete resection and subsequent growth of residual thyroid tissue along the embryologic pathway of descent from the base of the tongue to the lower neck. Illustrated here is a woman who, 1 year following total thyroidectomy for Graves' disease, developed two palpable neck masses. Tc-99m pertechnetate imaging demonstrated two corresponding foci. The findings were most consistent with enlarging, autonomously functioning thyroid tissue rests. If the patient had received radioiodine, one can speculate that these foci might also have been ablated.
The Validity of the Polygraph with Hypnotically Induced Repression and Guilt
Authors: EDWIN WEINSTEIN, STANLEY ABRAMS, DONALD GIBBONS
Journal: American Journal of Psychiatry (1970)

The authors tested the polygraph's validity by hypnotically inducing repression and guilt in six subjects. They conclude that an individual who has committed a crime may repress this experience sufficiently to pass the polygraph test, while an anxious individual who has not committed a crime may render a falsely positive response on the machine. The authors discuss their conclusion that the polygraph is not foolproof in terms of implications for law enforcement agencies.
CESAREAN SECTION IN THE TREATMENT OF PLACENTA PRÆVIA.
Authors: W. A. BRIGGS
Journal: JAMA (1906)

Placenta prævia in its manifestations and in its combined mortality of mother and child is the most appalling complication of pregnancy. In its management the courage, judgment and knowledge of the obstetrician will be taxed to their uttermost. It behooves him, therefore, to be prepared for every contingency of this multifarious condition. To paraphrase a paraphrase of Addison, she who has a hesitating physician is lost. Within the brief period of three months I have seen four cases of total placenta prævia. <h3>CASE REPORTS.</h3><h3>Case 1.</h3> —This case occurred in the practice of Dr. S. E. Simmons and formed the basis of a paper read by him before the Sacramento Society for Medical Improvement. In this paper he laid particular emphasis on the importance of early diagnosis, insisting that every pregnant woman should be carefully examined with special reference to this condition as early as the sixth or seventh month.
Sexual and Temporal Dynamics of Molecular Evolution in C. elegans Development
Authors: Asher D. Cutter, Samuel Ward
Journal: Molecular Biology and Evolution (2004)

Dissection of the phenotypic and molecular details of development and differentiation is a centuries-old topic in evolutionary biology. However, an adequate understanding is missing for the molecular evolution of genes that are expressed differentially throughout development—across time, tissues, and the sexes. In this study, we investigate the dynamics of gene evolution across Caenorhabditis elegans ontogeny and among genes expressed differentially between each sex and gamete type. Using gene classes identified by genome-wide gene expression developmental time series and comparative sequence analysis with the congener C. briggsae, we demonstrate that genes expressed predominantly after reproductive maturity evolve more rapidly than genes expressed earlier in development and that genes expressed transiently during embryogenesis evolve faster than other embryonic transcripts. These results are indicative of relaxed selection on genes expressed after maturity, in accord with the mutation-accumulation model of aging. Furthermore, genes involved in spermatogenesis reveal more rapid evolution than other phenotypic classes of genes. Average rates of evolution among male soma-related genes indicates that selection acts to maintain males in these androdioecious species, despite their rarity, and the rapid evolution of sperm genes suggests that sexual selection acts on sperm development and function.
Accurate and quick assessment of left ventricular function in patients with ischemic heart disease using biplane advanced automated contour tracking method
Authors: Kenichi Sugioka, Takeshi Hozumi, Hiroyuki Watanabe, Yoshiki Matsumura, Yasuhiko Takemoto, Hiroyuki Yamagishi, Takashi Muro, Minoru Yoshiyama, Kazuhide Takeuchi, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2003)
Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource
Authors: Calliope A Dendrou, Vincent Plagnol, Erik Fung, Jennie H M Yang, Kate Downes, Jason D Cooper, Sarah Nutland, Gillian Coleman, Matthew Himsworth, Matthew Hardy, Oliver Burren, Barry Healy, Neil M Walker, Kerstin Koch, Willem H Ouwehand, John R Bradley, Nicholas J Wareham, John A Todd, Linda S Wicker
Journal: Nature Genetics (2009)
Myopia and Scleral Reinforcement: A Sensitive Nerve-Reply
Authors: Brian J. Curtin
Journal: JAMA (1985)

<h3>In Reply.—</h3> It appears that my negative comments on scleral reinforcement struck a sensitive nerve or two. Scleral reinforcement has proved to be an acute disappointment to me in its present form. My initial laboratory studies<sup>1</sup>and clinical trials<sup>2</sup>were both most encouraging. Long-term follow-up studies have indicated that these periscleral grafts do not effectively prevent axial elongation of the eye in my hands, however. I have stereophotographs of one youngster's fundus eight years postoperatively in which the cruciate-shaped reinforcement graft can be seen indenting the posterior pole. The posterior staphyloma, however, can be seen bulging outward in all areas around it. At our facility, A-mode ultrasonography also indicates that the great majority of eyes (85% ) elongate after scleral reinforcement surgery. This has also been observed in eyes in which the refractive myopia was stabilized or even showed regression. In my opinion, the reason that Drs Miller and
Abstract 5457: Contexts of vulnerability mediating TMZ response in metastatic melanoma
Authors: Holly Yin, Bradford Brooks, Donald Chow, Chris Sereduk, Aleksandar Sekulic, Kevin Brown, Jeff Trent
Journal: Cancer Research (2011)

Abstract Metastatic malignant melanoma is an incurable disease with average 5-year survival rates for patients with disseminated disease ranging from 5-18%. Despite the recent development of promising targeted and immunological approaches for treatment of melanoma patients, there remains an urgent need to improve the effectiveness of conventional chemotherapeutics such as TMZ treatment for those patients ineligible or unresponsive to these approaches. We hypothesized that genetic alterations or contexts of vulnerability (COVs) exist in melanoma cells that mediate sensitivity to TMZ, and thus developed RNA-interference-based (RNAi) TMZ chemosensitization assays in melanoma cell lines in order to better understand how to pharmacologically augment TMZ response. First, we extensively developed RNAi sensitization assay in 17 melanoma cell lines followed by screening siRNA kinome library in these cell lines. This screening result, combined with our previous melanoma genomic data (gene expression, aCGH, SNP, and gene mutations), would prioritize the critical essential genes in melanoma. In addition, we profiled 17 melanoma cell lines for TMZ sensitivity and subsequently optimized RNAi screening parameters for detection of TMZ sensitization in one sensitive (UACC903) and four resistant (UACC647, UACC1308, UACC91 and UACC1940) cell lines. We then performed high-throughput RNAi screens with a 7,000 gene siRNA library targeting the druggable genome in these five cell lines. The data from the screens were rigorously evaluated and top TMZ-sensitizing hits were identified and confirmed. Based on these data, we prioritized the ATR/ATM/Chk1 pathway for further evaluation. We tested two Chk1 inhibitors for synergistic effects when combined with TMZ. Notably, both Chk1 inhibitors demonstrated good synergistic effects in the TMZ-resistant cell lines, with moderate/marginal effects in the sensitive line UACC903. These data are consistent with previous reports that inhibition of Chk1 can sensitize TMZ-induced cytotoxicity in glioma cells, and suggest that targeting this pathway in melanoma may augment TMZ response in melanoma. We are presently following up these results across a larger panel of melanoma cell lines, as well as evaluating pharmacological inhibitors of additional TMZ-sensitizing siRNA hits and pathways with the hope that these results may serve as a starting point for the development of novel combination therapies for melanoma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5457. doi:10.1158/1538-7445.AM2011-5457
Appropriate chemotherapy for palliating advanced cancer.
Authors: M. S. Hamilton
Journal: BMJ (1992)

the final choice of treatment.In a recent survey on upwards, by Gleeson's chosen classification of deserved a mention in Rubens and colleagues' the mnageent flarngea caner inthe nite stag) ca be ured2 Not only is this clearly brief discussion of the treatment of myeloma, in Kingdom and Ontario, Canada, Gaze etal afound contrary to his statement that "Others present with preference to trials of high dose chemotherapy that 84% of otolaryngologists and 96% of clinical advanced disease, and for these unlucky patients with bone marrow transplantation, which are at oncologists would recommend primary radio-total laryngectomy provides the only hope of long present too small or in which long term follow up is therapy for T3,N0,M0 laryngeal cancer.'~termsurvival" but analysis of "salvage" surgeryinsufficient to determine outcome.MultipleThe recent advances in stomal valves and speech that is, total laryngectomy after failure of non-myeloma is perhaps an example of a cancer for buttons are excellent news for patients in whom surgical treatment -has confirmed that avoiding which achieving an accurate consensus view of laryngectomy is inevitable, but we should still early surgery does not seem to prejudice overall optimal management from published reports strive to allow as many patients as possible to retain survival (H R Grant et al, 5th European conference required more detailed and wider consultation their larynges with good speech function.on clinical oncology, London, September 1989).than was undertaken.
Results of the first planned analysis of the TEAM (tamoxifen exemestane adjuvant multinational) prospective randomized phase III trial in hormone sensitive postmenopausal early breast cancer.
Authors: SE Jones, C Seynaeve, A Hasenburg, D Rae, J Vannetzel, R Paridaens, C Markopoulos, Y Hozumi, H Putter, E Hille, D Kieback, L Asmar, J Smeets, R Urbanski, JM Bartlett, CJ van de Velde
Journal: Cancer Research (2009)

Abstract Abstract #15 Background: Exemestane (E) is a steroidal aromatase inactivator, which has been demonstrated to be more effective than tamoxifen (T) in metastatic breast cancer (BC). The role of E in adjuvant therapy has been established after 2 to 3 years of T compared to 5 years of T in the Intergroup Exemestane Study (Lancet 2007; 369: 599-70). One objective of the TEAM study was to evaluate E compared to T as initial adjuvant endocrine therapy.&amp;#x2028; Methods: Using common criteria, eligible postmenopausal patients in 9 countries with invasive ER+ and/or PR+ early BC, were prospectively randomized to either open-label E 25 mg/day or T 20 mg/day. All patients had completed primary therapy of surgery and chemotherapy if indicated. All data were collected and analyzed by the Central Data Center in Leiden, The Netherlands. The trial was initiated in 2001 with a primary endpoint of DFS between T and E. In 2004, based on results of the IES, TEAM was modified such that all patients on T were switched to E at 2.5-3 years. The modified design includes 2 primary endpoints: DFS of T versus E followed up to 2.75 years, and DFS of E for 5 years versus T switched to E treated for a total of 5 years. The present analysis focuses on the first primary endpoint: DFS for T compared to E at 2.75 years with censoring of events after 2.75 years. Log rank test with a 2-sided significance level of 2.98% stratified by country and factors nested in protocols will be utilized.&amp;#x2028; Results: Between January 2001 and January 2006, 9775 women were randomized to T or E of which 9300 will be followed for 2.75 years by October 2008: 99% were ER and/or /PgR+, 50% were node negative, 44% underwent mastectomy, 68% received radiotherapy, and 36% chemotherapy. There have been 693 DFS events (locoregional or distant recurrence, second breast cancers, or death without recurrence) by April 2008 within 2.75 years of randomization. In accordance with the statistical analysis plan, the first planned analysis will be based on 723 events or 9300 patients with at least 2.75 years follow-up. We will present a detailed analysis of the first primary endpoint of DFS between T and E at 2.75 years at the 2008 SABCS. The TEAM study represents the largest of the 3 major trials to compare efficacy of an aromatase inhibitor/inactivator versus tamoxifen as initial endocrine therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 15.
Mother Father Deaf: Living Between Sound and Silence
Authors: R. Greg Emerton
Journal: JAMA (1995)

What would you be like if you had been born and raised in a family disqualified from full membership in society? What would you be like if your grandparents saw your mother or father as their broken child? What would you be like if you learned when you grew up that you could never really belong to the social world in which you were raised? Is this the stuff of TV psychodrama? No, it is the social reality of a person caught on the margin between two cultures. It is the social reality of hearing children born to deaf parents. Paul Preston has written a scholarly and enjoyable ethnographic study based upon in-depth interviews with a broad, randomly selected cross-section of 150 hearing people with deaf parents in 24 states. Dr Preston is a medical anthropologist with appropriate concerns for research methods and a splendid command of the diverse applicable
Obstructive Lung Disease in Hereditary α1-Antitrypsin Deficiency
Authors: Robert G. Townley, Frank Ryning, Henry Lynch, Alfred W. Brody
Journal: JAMA (1970)

A genetically determined deficiency of α<sub>1</sub>-antitrypsin in 15 members of one family appeared with wheezing and progressive dyspnea in six. Because of the early age of onset of wheezing and dyspnea, it may be confused with bronchial asthma. Five of the 15 were found to have severe obstructive emphysema; one brother died at age 43 years of the disease, two have had severe hypoxia with oxygen tensions under 50 mm Hg and respiratory failure, and all five had a one-second-timed vital capacity of under 30% of predicted, residual volumes greater than 54% of total lung capacity, and marked uneveness of ventilation. Quantitation of α<sub>1</sub>-antitrypsin by radial immunoassay showed four of 13 studied to be homozygous and nine heterozygous. Total serum enzyme antitrypsin activity correlated highly with radial gel immunoassay. A hypothetical pathogenic mechanism is described.
Dorsal column stimulation in multiple sclerosis: effects on bladder and long term findings.
Authors: C H Hawkes, R Beard, D Fawcett, E A Paul, D G Thomas
Journal: BMJ (1983)

The effect of dorsal column stimulation on bladder function in 15 patients with established multiple sclerosis was analysed by urodynamic tests. Significant improvement in flow rate and urethral sphincter pressure was recorded in about two thirds. Of 31 patients examined over five years only 13 showed initial benefit from stimulation and were given permanent stimulators; of these, only three appeared to receive lasting benefit. Early complications occurred in nine patients and five had a relapse of their disease. These results suggest that at present stimulation of the dorsal column does not have a place in the routine management of multiple sclerosis.
The C104R mutant impairs the function of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) through haploinsufficiency
Authors: John J. Lee, Haifa H. Jabara, Lilit Garibyan, Ingrid Rauter, Tatyana Sannikova, Stacey R. Dillon, Richard Bram, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2010)
Abstract 4670: Characterization of Met signaling in urothelial cancer of the bladder
Authors: Young H. Lee, Andrea Apolo, Piyush K. Agarwal, Donald P. Bottaro
Journal: Cancer Research (2014)

Abstract Background: Mounting evidence supports Met as a target in urothelial cancer (UC). Activated Met can promote angiogenesis and tumor growth by upregulating VEGF and may play a role in UC pathogenesis. Cabozantinib inhibits both VEGFR2 and Met pathways. In this study, we assessed cabozantinib's effects on HGF-driven UC cell growth and invasion. Methods: sMet levels in serum and urine samples from 31 patients with UC (23 metastatic, 8 muscle-invasive) were correlated with stage, presence of visceral metastases and urinary source. The effects of cabozantinib on 6 human UC-derived cell lines were studied in vitro. Intact RT4, TCC-SUP, T24M2, T24M3, J82 and SW780 cells at 80% confluence were serum deprived 16 h, then left untreated or treated with hepatocyte growth factor (HGF) and/or cabozantinib prior to analysis of Met, phospho- (p)Met, pAkt, Akt, pErk and ErK by immunoassay or immunoblotting. Cabozantinib effects on basal and HGF-induced UC cell invasion, proliferation and soft agar growth were measured. Results: Median serum Met levels were modestly higher in patients with metastatic versus muscle-invasive disease. Urinary Met levels were clearly higher in patients with visceral metastasis (p=0.0111) and in urine from ileal conduits and neobladders compared to normally voided urine, regardless of stage (p=0.0489). Met content in UC cell lines was low in RT4 and higher in T24M2, T24M3, TCC-SUP, J82 and SW780. Basal pMet content was universally low, increased significantly by HGF and this was reversed by cabozantinib. HGF-driven increases in pAkt/Akt and pErK/ErK in all 6 cell lines were reversed by cabozantinib, as were HGF-enhanced UC cell invasion, proliferation and anchorage independent growth. Conclusions: Median urinary sMet is significantly higher in patients with visceral metastasis and in specimens from ileal conduits and neobladders relative to normally voided urine. UC cell Met content in culture increased with disease grade; HGF stimulated activation of Met and known effectors, and enhanced invasion, growth rate and anchorage-independent grow¬¬¬th; cabozantinib effectively reversed these HGF-driven effects. Citation Format: Young H. Lee, Andrea Apolo, Piyush K. Agarwal, Donald P. Bottaro. Characterization of Met signaling in urothelial cancer of the bladder. [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 4670. doi:10.1158/1538-7445.AM2014-4670
Should doctors go to patients' funerals?
Authors: Bruce Arroll, Karen Falloon
Journal: BMJ (2007)

Some years ago I (BA) decided to start attending the funerals of patients. This was in response to having had a positive experience of attending a funeral where the family was very appreciative of my presence. Recently I attended the funerals of two patients who died within a few weeks of each other. Again, both funerals afforded me the opportunity to meet the extended family of the deceased and again, in both cases the family appreciated my attendance.

What stood out with the two recent funerals was that in both cases a close relative came to visit me in the clinic within a week. It was obvious these were not visits for any particular pressing medical problem but more of a social nature. The talk revolved around the funeral and, having been a participant, I felt I could make a meaningful contribution to the conversation. I was left with the impression that my attendance at …
Fixed-dose combination pills reduced SBP and LDL-C in patients with, or at high risk for, cardiovascular disease
Authors: Paul Shekelle
Journal: Annals of Internal Medicine (2013)

Source Citation Thom S, Poulter N, Field J, et al; UMPIRE Collaborative Group. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA. 2013;310:918-29. 24002278