tbuckley/cabot-search huggingface dataset:
General practitioners' beliefs and attitudes about how to respond to death and bereavement: qualitative study Commentary: Use of personal experience should be legitimised
Authors: E. M Saunderson, L. Ridsdale, D. Jewell
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To investigate the perceptions of general practitioners when they are notified or hear of a death or bereavement in their practice; to explore doctors9 accounts of their relationships with their patients in the context of bereavement; and to explore the concerns of general practitioners in managing themselves and bereaved patients. <b>Design:</b> Semistructured interviews followed by qualitative content analysis. <b>Setting:</b> London borough of Redbridge <b>Participants:</b> 25 general practitioners <b>Results:</b> Almost all the doctors had felt guilty about issues relating to the death of patients. These feelings were based on their expectations of not making mistakes and diagnostic precision. They described a culture gap existing between hospital and general practice and a need to develop new models and methods to explain and manage the causes of illness presented to them. In the absence of useful teaching on bereavement, many devised strategies which relied more on their personal experiences. General practitioners used various methods to contact bereaved patients, especially if they had been involved in the terminal care or if the death was particularly shocking. The doctor was also bereaved by the death of well known patients and sometimes needed to grieve and express emotion. <b>Conclusion:</b> General practitioners may need support and learning methods to manage their own and their patients9 bereavement. <h3>Key messages</h3> Most general practitioners fear making mistakes because they have a model of diagnostic precision based on their initial professional medical socialisation Doctors differ in their approaches to bereavement management The techniques developed by doctors to manage the immediate phase of bereavement stem from personal experience rather than medical training General practitioners may need to express their own grief at the loss of a patient and a relationship General practice needs to develop its own models to reduce the stress felt by practitioners
Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese
Authors: Yukinori Okada, Yukihide Momozawa, Kyota Ashikawa, Masahiro Kanai, Koichi Matsuda, Yoichiro Kamatani, Atsushi Takahashi, Michiaki Kubo
Journal: Nature Genetics (2015)
Editor's Note: p38 Mitogen-activated Protein Kinase Pathway Suppresses Cell Survival by Inducing Dephosphorylation of Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase1,2
Authors: Song-Ping Li, Melissa R. Junttila, Jiahuai Han, Veli-Matti Kähäri, Jukka Westermarck
Journal: Cancer Research (2020)

Raf/mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)1,2/extracellular signal-regulated kinase1,2 and MKK3,6/p38 mitogen-activated protein kinase pathways play an important role in cellular survival and apoptosis. The results of this study identify novel mechanisms to explain the opposing effects of these pathways in the regulation of apoptosis induction. Our results show that activation of p38 by adenoviral expression of MKK3b or arsenite treatment was followed by rapid dephosphorylation of MEK1,2 and subsequent apoptosis in human skin fibroblasts. Inhibition of p38 activity by SB203580 and adenoviral expression of dominant-negative forms of p38 potently inhibited MEK1,2 dephosphorylation and apoptosis. Strikingly, p38-mediated dephosphorylation of MEK1,2, was not detected in a series of transformed human cell lines. Taken together, we provide evidence for mechanisms unidentified previously that negatively regulates survival signaling during apoptosis induction. In addition, we show that in all transformed cell lines we have studied thus far, the function of this pathway is impaired.
Cecil Review of General Internal Medicine
Authors: [edited by] J. Allen D. Cooper, Peter G. Pappas
Journal: Annals of Internal Medicine (1989)

Cardiovascular Disease. Pulmonary Disease. Critical Care. Renal Disease. Oncology. Hematology. Gastrointestinal Disease. Infectious Diseases. Rheumatology and Clinical Immunology. Diabetes Mellitus and Metabolism. Neurology. Dermatology.
Abstract 98: Spontaneous Refibrillation Following External Defibrillation of Long Duration Ventricular Fibrillation in Swine
Authors: James D Allred, Cheryl R Killingsworth, Scott Allison, Derek J Dosdall, Sharon B Melnick, William M Smith, Raymond E Ideker, Gregory P Walcott
Journal: Circulation (2007)

Background: Following successful defibrillation of the long duration ventricular fibrillation (LDVF) associated with sudden cardiac arrest (SCA), refibrillation occurs in over half of resuscitation attempts. In experimental animals with normal hearts, refibrillation almost never occurs following short duration VF lasting &lt; 1 min (SDVF). It is not known if refibrillation following LDVF is due to the cardiac disease that caused the initial LDVF of SCA or if the LDVF itself causes abnormalities that can initiate VF. Further, the mechanism of refibrillation initiation is unknown. We tested the hypothesis that refibrillation occurs frequently following LDVF in previously normal hearts and propagates from a common area within the heart. Methods : In 6 pigs, 115–120 plunge needles containing 3– 6 electrodes each were inserted throughout the heart. With the chest closed, external defibrillation pads were placed in a left lateral to right lateral configuration. Following successful defibrillation of 20 s of SDVF, the animal was observed for spontaneous VF for at least 4 min. After termination of 7 min of LDVF, the animal was placed on cardiopulmonary bypass and observed for 15 min for spontaneous VF. Results: Following LDVF, 1.33 ±0.8 episodes of spontaneous VF occurred in each animal. The mean time to VF was 71 s (range 5 – 139 s) following defibrillation of LDVF. Three animals had a second episode of VF within 3 min of termination of LDVF. Earliest sites of origin of spontaneous VF occurred equally in the LV (3), RV (3), and septum (2) and arose equally from the endocardium (3), epicardium (2), and myocardium (3). Refibrillation originated in the posterior half of the ventricles 75% of the time. The first refibrillation cycle appeared focal in 75% of cases and reentrant in 25%. Premature ventricular beats arising out of the posterior RV base immediately preceded 75% of VF episodes. Conclusions: Spontaneous VF is common after defibrillation of LDVF but not SDVF in previously health swine, indicating that refibrillation does not require preexisting cardiac disease but can be caused by the detrimental effects of LDVF. Most episodes of refibrillation begin as focal activity within the posterior half of the ventricles.
Effectiveness and Cost-Effectiveness of Vaccination against Pandemic (H1N1) 2009
Authors: Nayer Khazeni, David W Hutton, Alan M Garber, Nathaniel Hupert, Douglas K Owens
Journal: Annals of Internal Medicine (2009)

Background
A matched vaccine for the Pandemic (H1N1) 2009 virus will not be ready until autumn, 2009; decisions regarding timing of vaccination and percentage of population to vaccinate are complex.
Are at Least 12 Months of Dual Antiplatelet Therapy Needed for All Patients With Drug-Eluting Stents?
Authors: Sorin J. Brener
Journal: Circulation (2015)

C oronary artery disease (CAD) remains a principal source of morbidity and mortality among adults in both the developed world and the developing world. 1 Despite important advances in medical therapy for CAD, revascularization is frequently necessary.Currently, nearly 2 million percutaneous coronary interventions (PCIs) are performed in the United States and Europe, and >90% of them entail the deployment of at least 1 coronary stent. 2 The introduction of metallic coronary stents (bare metal stents [BMS]) 2 decades ago resulted in a significant reduction in the immediate and long-term complications of PCI, particularly dissections, abrupt vessel closure, and need for repeat target lesion or target vessel revascularization.Abrupt vessel closure was essentially eliminated by stents. 3The incidence of target lesion and target vessel revascularization was halved from ≈20% to 25% at 1 year to 10% to 15%.5][6] This innovation further reduced the need for target vessel or target lesion revascularization to the single-digit range.
Cognitive dysfunction after concussion
Authors: M. W J Strachan, B. M Frier, I. J Deary, T. W Teasdale, A. Engberg
Journal: BMJ (1998)

Editor—Teasdale and Engberg examined the duration of cognitive dysfunction after concussive head injury in young men.1 We are concerned about their interpretation of some of the data presented. The observation that cognitive function was impaired up to one week after head injury was based on examination of only eight subjects, four of whom showed impaired performance. The authors placed considerable weight on this result even though the relative risk of cognitive impairment in the subjects with head injury was not significant by conventional criteria. It was additionally perplexing, given this non-significant result, that the 95% confidence interval did not pass through unity. Perhaps most surprising of all was that the authors failed to comment on the one truly significant result in that section of the paper—that impaired cognitive performance was shown in those subjects tested more than 200 days after the head injury. 

The other main finding, that the risk of concussion was greater in subjects with premorbid cognitive dysfunction, is readily understandable. It is disconcerting, however, that a similar degree of cognitive dysfunction was not apparent in subjects tested after head injury. The authors suggested that this may have been due to differences in the mean age of men tested before and after head injury (20.6 years and 18.0 years, respectively). There was indeed a greater frequency of dysfunctional scores in men injured at age ⩽18 than in those injured at age ⩾19. These data, however, were derived from the combined test results of men examined both before and after head injury. The authors’ argument would be strengthened if a similar age difference were to be shown individually in both groups.
Abstract MP21: Circulating Biomarkers of Dairy Fat and Incident Type 2 Diabetes in Two US Prospective Cohorts
Authors: Mohammad Y Yakoob, Peilin Shi, Frank B Hu, Hannia Campos, Kathryn M Rexrode, John E Orav, Walter C Willett, Dariush Mozaffarian
Journal: Circulation (2014)

Background: Prior observational studies suggest that self-reported consumption of dairy foods is associated with lower risk of type 2 diabetes (DM). Few studies have used circulating biomarkers that provide objective measures of dairy fat consumption. Aim: To test the hypothesis that plasma fatty acid biomarkers of dairy fat, 15:0, 17:0, 16:1 n-7t and 14:0, are associated with lower incidence of DM. Methods: We used gas-liquid chromatography to measure plasma 15:0, 17:0, 16:1 n-7t and 14:0 biomarkers in 3,347 adults aged 30-75 years and free of prevalent DM at baseline in two separate U.S. prospective cohorts, Nurses’ Health Study (NHS) and Health Professionals’ Follow Up Study (HPFS). Incident DM was identified through 2008 and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Cox proportional hazards regression was used and cohort findings pooled by fixed-effects meta-analysis. Results: During mean ± SD follow-up of 14.0 ± 4.9 years, 254 new cases of DM were diagnosed. Correlations with self-reported dairy fat consumption were modest for 17:0 (r=0.19), 16:1 n-7t (r=0.21) and 15:0 (r=0.27), and weaker for 14:0 (r=0.12). In pooled multivariate analyses, comparing highest to lowest quartiles, lower risk of DM was seen for 17:0 [HR=0.57 (95% CI: 0.39 - 0.82), P-trend=0.001] and 16:1 n-7t [HR=0.60 (0.42 - 0.87), P-trend=0.007], while 14:0 was positively associated [HR=1.98 (1.35 - 2.91), P-trend &lt;0.0001] and 15:0 was not associated [HR=1.11 (0.75 - 1.63), P-trend=0.80] ( Table ). Conclusion: In separate prospective cohorts, two biomarkers of dairy fat (17:0 and 16:1 n-7t) were associated with lower incidence of DM. 14:0, which is also obtained from beef, and is a marker of de novo lipogenesis, was associated with increased risk. Further research is needed on plausible biological and mechanistic pathways.
Radioepidemiological tables. Council on Scientific Affairs
Authors: J.R. Beljan, G.M. Bohigian, E.H. Estes, I.R. Friedlander, W.R. Kennedy, J.H. Moxley, P. Salva, W.C. Scott, J.H. Skom, R.M. Steinhilber, J.P. Strong
Journal: JAMA (1987)

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Abstract 11254: Association of Sleep Disordered Breathing and Sleep Architecture With Atrial Fibrillation: The MESA Study
Authors: Younghoon Kwon, Sina A Gharib, Mary Lou Biggs, David R Jacobs, Alvaro Alonso, Daniel Duprez, Joao Lima, Gen-Min Lin, Elsayed Z Soliman, Reena Mehra, Susan Redline, Susan Heckbert
Journal: Circulation (2014)

Background: Sleep disordered breathing (SDB) has been associated with nocturnal atrial fibrillation (AF). However, the association of SDB and other important sleep characteristics with prevalent AF (beyond nocturnal AF) is unclear. We explored the cross-sectional association of SDB and other objectively measured sleep characteristics with AF. Methods: Prevalence of AF was examined among MESA (Multi-Ethnic Study of Atherosclerosis) study participants who underwent polysomnography (PSG) (n=2048) (MESA Sleep Study). Presence or a history of AF was determined if AF or atrial flutter was identified by at least one of the following measures: (i) 12-lead ECG during study examination; (ii) PSG; (iii) ICD-9 codes from hospital discharge diagnosis; (IV) inpatient and outpatient Medicare claims data. Results: Overall prevalence of AF was 4.9 % (n=100). Prevalence of AF was significantly higher at 6.7% in subjects with moderate to severe SDB (n = 691, apnea hypopnea index (AHI) ≥15/h) compared with a prevalence of 4.0% in participants without SDB (n = 707, AHI &lt; 5/h) (p=0.02). After accounting for demographics, body habitus, cardiovascular disease (CVD) risk factors and prevalent CVD, participants with higher values of AHI were more likely to have AF, although the result was not statistically significant (OR: 1.22 [0.99-1.49] per SD [17/hr], p = 0.06). Exploratory analyses of the association of sleep architecture with AF using the same model found significantly lower odds of AF associated with longer duration of slow wave sleep (SWS) (OR: 0.66 [0.5-0.89] per SD [34 min], p = 0.01). Results from a multivariable model that included 3 key sleep characteristics (AHI, SWS time and arousal index (AI)) suggested that all were independently associated with AF (AHI: OR 1.45 [1.13-1.87] per SD, p = 0.004; SWS time: OR 0.65 [0.49-0.87] per SD, p = 0.004; AI: OR 0.65 [0.50-0.86] per SD (12/hr), p = 0.002). Conclusion: In a cross-sectional study of a large multi-ethnic population, the prevalence of AF was associated with more severe SDB, shorter SWS time, and lower AI. This finding highlights sleep architecture’s implication, potentially via autonomic balance, in the association between sleep and AF.
Soluble suppression of tumorigenicity 2 (s<scp>ST</scp>2), but not galactin‐3, adds to prognostication in patients with systemic <scp>AL</scp> amyloidosis independent of <scp>NT</scp>‐pro<scp>BNP</scp> and troponin <scp>T</scp>
Authors: Angela Dispenzieri, Morie A. Gertz, Amy Saenger, Shaji K. Kumar, Martha Q. Lacy, Francis K. Buadi, David Dingli, Nelson Leung, Steven Zeldenrust, Suzanne R. Hayman, Prashant Kapoor, Martha Grogan, Lisa Hwa, Stephen J. Russell, Ronald S. Go, S. Vincent Rajkumar, Robert A. Kyle, Allan Jaffe
Journal: American Journal of Hematology (2015)

The use of soluble cardiac biomarkers such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and troponin has revolutionized prognostication for patients with AL amyloidosis. Soluble ST2 (sST2) and galectin‐3 have also been reported to have prognostic value in other cardiac patient populations. We identified 502 patients with AL amyloidosis, who provided a research sample and consent to review their medical records between 1/1/2006‐12/31/2010 within 90 days of their diagnosis. Samples were assayed for sST2 and galectin‐3. Within this AL amyloidosis population, overall survival (OS) was 25.5 months (95% CI 18, 35.7 months). Receiver operating curve analyses were done to detect the best cut‐points for sST2 and galectin‐3 to predict both 1‐ and 5‐year OS. The respective cut points for sST2 were 30 and 29.7 ng/mL, while the median sST2 for the entire population was 31 ng/mL (IQR 19.8, 53.6). The respective cut points for galectin‐3 were 11 and 10.4 ng/mL while the median for the entire population was 16.6 ng/mL (IQR 11.5, 24.0). Although on univariate analysis, both sST2 and galectin‐3 were prognostic, upon multivariate analysis, only sST2 was independent of troponin, NT‐proBNP, serum immunoglobulin free light chain, and blood pressure. Not only did sST2 add to previously reported prognostication systems, but a novel prognostication 5‐point system including sST2 was possible. The addition of sST2 – but not galectin‐3 – to existing prognostication systems for patients with AL amyloidosis strengthens the ability to predict for death. Am. J. Hematol. 90:524–528, 2015. © 2015 Wiley Periodicals, Inc.
Abstract #5565: The therapeutic effects against refractory and multiple drug resistant xenograft tumors by the third generation microtubule targeting epothilone: Iso-oxazole-fludelone
Authors: Ting-Chao Chou, Xiu-Guo Zhang, Huajin Dong, Samuel Danishefsky
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Epothilones, 16-member ring macrolides, originally isolated from myxobacterium Sorangium cellulosum in soil were shown to exert potent cytotoxicity via stabilization of microtubule polymerization, like Taxol®. They are not cross-resistant to multi-drug resistance drugs. At MSKCC, we have synthesized over 100 epothilones through pharmacology directed de novo total synthesis via molecular design of new pharmacophores. The third generation epothilone, iso-oxazole-fludelone (17-iso-oxazole-26-F3-9,10-deH-12,13-desoxy-epothilone B)(Iso-flu) is 20- and 1,000-fold more potent than Taxol against CCRF-CEM and CCRF-CEM/Taxol cell growth, respectively. It is not only with enhanced potency and solubility, but also with markedly improved metabolic stability and tumor penetrating capabilities. It has been shown that it achieved \#8220;Therapeutic cure\#8221; (> 10-log cell kill or no relapse from complete remission (CR) for over 10% of life-span) against human mammary MX-1, ovarian SK-OV-3, colon HCT-116, and leukemic CCRF-CEM xenograft tumors [Chou et al, PNAS USA 105: 13157-13162, 2008 (9/2/08 issue)]. We hereby report the therapeutic results against refractory or drug-resistant human tumor xenografts in nude mice, as specified by [Dose (mg/kg), schedule, results from 6-hr-i.v. infusion via tail vein, or otherwise specified], comparing with the widely used cancer chemotherapeutic agents, such as Taxol® or Temodar®. For lung A549/Taxol, Iso-flu [15, Q7Dx4, 80% suppression (supp.)] and Taxol [25, Q3Dx9, 42% supp.]; For mammary MCF-7/Adriamycin, Iso-flu [15, Q7Dx2, 100% supp.] and Taxol [25, Q2Dx4, 3.7% supp.]; For neuroblastoma SK-NAS, s.c., Iso-flu [45, Q12Dx4, cure, 120-Day, No Relapse 4/4] and Taxol [30, Q2Dx4, 74.4% supp.]; For SK-NAS-i.c. [30, Q10Dx2, median survival time 26.3±1.3 days] and Temodar [200, Q2Dx3, oral, median survival time 19.2±1.3 days]; For pancreatic adenoca BX-PC-3, Iso-flu [25, Q12Dx3, 100% supp.] and Taxol [20, Q2Dx8, 95% supp.]; For prostate adenoca PC-3, Iso-flu [25, Q12Dx4, 5/5CR] and Taxol [25, Q2Dx8, 5/5CR]; and for CCRF-CEM/Taxol, Iso-flu [30, Q12Dx, 4/4CR] and Taxol [25, Q2Dx6, 3% supp.]. Thus, Iso-flu is not only curative against MX-1, SK-OV-3, HCT-116, and CCRF-CEM human tumor xenografts but also has superior therapeutic effects against refractory or drug resistant human xenograft tumors than the major cancer chemotherapeutic agents, such as Taxol or Temodar, with the exception of two cases, where they were equal to Iso-flu. Therefore, Iso-flu is an extraordinarily promising candidate that warrants anticancer clinical developments.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5565.