tbuckley/cabot-search huggingface dataset:
Escaping from placebo prison
Authors: J. Howick
Journal: BMJ (2009)

<h3>Abstract</h3> The evolution of SARS-CoV2 virus has led to the emergence of variants of concern (VOC). Children, particularly &lt;12 years old not yet eligible for vaccines, continue to be important reservoirs of SARS-CoV-2 yet VOC prevalence data in this population is lacking. We report data from a genomic surveillance program that includes 9 U.S. children’s hospitals. Analysis of SARS-CoV-2 genomes from 2119 patients &lt;19 years old between 03/20 to 04/21 identified 252 VOCs and 560 VOC signature mutations, most from 10/20 onwards. 75.00% of the VOC signature mutations detected were in children &lt;12 years old, including 32 cases of B.1.1.7 and 346 of B.1.419/B.1417. From 02/21 to 04/21, B.1.1.7 prevalence increased from 1.28% to 72.22% corresponding with the decline of B.1419/B.1417 from 52.57% to 5.56% at one institution. There continues to be a need for ongoing genomic surveillance, particularly among young children who will be the last groups to be vaccinated.
Academic performance of ethnic minorities in medical school
Authors: P. Carr, J. Woodson
Journal: BMJ (2008)

May be adversely affected by negative stereotyping

Increasing the number of doctors in the workforce who come from minority groups has been proposed as a way to tackle the health disparities of minority populations. Several themes have arisen regarding the education of such doctors, including low numbers of students from ethnic minorities applying for medical school, worse prior preparation in the sciences and humanities, and underachievement in their medical education.1

The qualitative study by Woolf and colleagues (doi: 10.1136/bmj.a1220) provides important insights into one aspect that affects clinical education in the United Kingdom—how ethnic stereotyping can add to a downward trend in performance.2 This reflects findings on how race affects the evaluation of African-American students in the United States, including the nature of the student-teacher interaction and the biases that may affect the evaluation of students and the educational process.1 Differences in the expectations and treatment of students that stem …
1234 Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy
Authors: B BRANDSAETER, H ISONIEMI, U BROOME, M OLAUSSON, L BACKMAN, B HANSEN, E SCHRUMPF, A OKSANEN, B ERICZON, K HOCKERSTEDT
Journal: Hepatology (2003)

The most widely used approach to cancer immunotherapy is vaccines. Unfortunately, the need for multiple administrations of antigens often limits the use of one of the most effective vaccine approaches, immunogene therapy using viral vectors, because neutralizing antibodies are rapidly produced. We hypothesized that after viral immunogene therapy “primed” an initial strong antitumor immune response, subsequent “boosts” could be provided by sequential courses of chemotherapy. Three adenoviral (Ad)-based immunogene therapy regimens were administered to animals with large malignant mesothelioma and lung cancer tumors followed by three weekly administrations of a drug regimen commonly used to treat these tumors (Cisplatin/Gemcitabine). Immunogene therapy followed by chemotherapy resulted in markedly increased antitumor efficacy associated with increased numbers of antigen-specific, activated CD8+ T-cells systemically and within the tumors. Possible mechanisms included: (i) decreases in immunosuppressive cells such as myeloid-derived suppressor cells (MDSC), T-regulatory cells (T-regs), and B-cells, (ii) stimulation of memory cells by intratumoral antigen release leading to efficient cross-priming, (iii) alteration of the tumor microenvironment with production of “danger signals” and immunostimulatory cytokines, and (iv) augmented trafficking of T-cells into the tumors. This approach is currently being tested in a clinical trial and could be applied to other trials of viral immunogene therapy.
BT-01 * TENASCIN-C: A NOVEL THERAPEUTIC TARGET IN PEDIATRIC BRAINSTEM GLIOMA
Authors: A. Saratsis, M. Kambhampati, J. Hall, M. Stampar, G. Xi, E. Raabe, R. Packer, J. Nazarian
Journal: Neuro-Oncology (2015)

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is the most deadly solid tumor of childhood. Histone 3 mutation occurs in 80% of DIPGs, causing global transcriptional changes. Tenascin-C (TNC) is an extracellular matrix protein expressed during normal brain development by oligodendroglial progenitor cells (OPCs), the purported DIPG cell of origin. TNC is highly expressed in adult glioma, contributing to local invasion and poor survival. We report increased TNC in tumor tissue and cerebrospinal fluid (CSF) from children with high-grade glioma, including DIPG, and characterize TNC expression in relation to H3K27M mutation and DNA methylation status. METHODS: Tumor tissue collected intraoperatively or post-mortem from children with brainstem (DIPG, n = 14), supratentorial (n = 7), and cerebellar astrocytoma (n = 2), and CSF from DIPG (n = 9) and supratentorial astrocytoma (n = 17) was subjected to MS/MS proteomic analysis. Tissue gene expression, DNA methylation, H3F3A and HIST1H3B sequencing was performed. TNC expression was validated via Western blot and immunohistochemistry. Data integration was performed with Genome Studio, Partek and Ingenuity Pathway Analysis. RESULTS: TNC expression was significantly increased in 75% of gliomas compared to normal tissue, including all DIPG specimens tested (fold change >2, p < 0.05). Secreted TNC was detected in 7/9 DIPG CSF specimens (77.8%). Tumor-specific TNC expression was confirmed with Western blot and tissue immunohistochemistry. TNC expression correlated with tumor grade and was associated with Notch pathway activation, H3K27M mutation, and TNC promoter hypomethylation. CONCLUSIONS: We report increased TNC expression in tissue and CSF of pediatric high-grade gliomas, including DIPGs, associated with promoter hypomethylation and H3K27M mutation. Given the effect of TNC on OPC proliferation, migration and differentiation, TNC could serve as a clinical biomarker of disease and rational therapeutic target for a substantial subgroup of DIPG patients. Studies exploring the mechanism of TNC overexpression and effects of targeting TNC expression in DIPG are currently underway.
Randomized, Double-Blind, Placebo-Controlled Trial of Vigabatrin for the Treatment of Cocaine Dependence in Mexican Parolees
Authors: Jonathan D. Brodie, Brady G. Case, Emilia Figueroa, Stephen L. Dewey, James A. Robinson, Joseph A. Wanderling, Eugene M. Laska
Journal: American Journal of Psychiatry (2009)

Cocaine dependence is associated with severe medical, psychiatric, and social morbidity, but no pharmacotherapy is approved for its treatment in the United States. The atypical antiepileptic vigabatrin (gamma-vinyl gamma-aminobutyric acid [GABA]) has shown promise in animal studies and open-label trials. The purpose of the present study was to assess the efficacy of vigabatrin for short-term cocaine abstinence in cocaine-dependent individuals.Participants were treatment seeking parolees who were actively using cocaine and had a history of cocaine dependence. Subjects were randomly assigned to a fixed titration of vigabatrin (N=50) or placebo (N=53) in a 9-week double-blind trial and 4-week follow-up assessment. Cocaine use was determined by directly observed urine toxicology testing twice weekly. The primary endpoint was full abstinence for the last 3 weeks of the trial.Full end-of-trial abstinence was achieved in 14 vigabatrin-treated subjects (28.0%) versus four subjects in the placebo arm (7.5%). Twelve subjects in the vigabatrin group and two subjects in the placebo group maintained abstinence through the follow-up period. The retention rate was 62.0% in the vigabatrin arm versus 41.5% in the placebo arm. Among subjects who reported prestudy alcohol use, vigabatrin, relative to placebo, was associated with superior self-reported full end-of-trial abstinence from alcohol (43.5% versus 6.3%). There were no differences between the two groups in drug craving, depressed mood, anxiety, or Clinical Global Impression scores, and no group differences in adverse effects emerged.This first randomized, double-blind, placebo-controlled trial supports the safety and efficacy of short-term vigabatrin treatment of cocaine dependence.
Sulfapyridine-Induced Serum-Sickness-Like Syndrome Associated with Plasmacytosis, Lymphocytosis and Multiclonal Gamma-Globulinopathy
Authors: Tin Han, Prem L. Chawla, Joseph E. Sokal
Journal: New England Journal of Medicine (1969)

W.B., a 38-year-old Negro, had previously been treated with sulfonamide ointment for dermatitis herpetiformis. On June 5, 1966, oral sulfapyridine, 2 gm daily, was started for a recurrence. Two weeks later, fever, abdominal pain, extreme weakness and generalized skin rash developed.On admission he was weak and lethargic, with hoarseness and somewhat labored respiration. The temperature was 102°F. The scleras were icteric. He had a generalized papular skin eruption, with exfoliation, moderate generalized lymphadenopathy, hepatomegaly and edema of the lips, tongue and fauces.The hemoglobin 1 week after onset of illness was 12.9 gm per 100 ml; subsequently, it fell . . .
Ventricular fibrillation sensing and detection with the jewel defibrillator: effect of programmed sensitivity threshold
Authors: P. Panotopoulos, K. Mughal, D. Krum, K. Axtell, M.R. Jazayeri, J. Sra, A. Dhala, Z. Blanck, M. Akhtar, S. Deshpande
Journal: Journal of the American College of Cardiology (1998)
L-Carnitine Supplementation for the Management of Fatigue in Patients With Cancer: An Eastern Cooperative Oncology Group Phase III, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Ricardo A. Cruciani, Jenny J. Zhang, Judith Manola, David Cella, Bilal Ansari, Michael J. Fisch
Journal: Journal of Clinical Oncology (2012)

Purpose L-carnitine, a popular complementary and alternative medicine product, is used by patients with cancer for the treatment of fatigue, the most commonly reported symptom in this patient population. The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer. Patients and Methods In this double-blind, placebo-controlled trial, patients with invasive malignancies and fatigue were randomly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo. The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory (BFI). Results Three hundred seventy-six patients were randomly assigned to treatment with L-carnitine supplementation or placebo. L-carnitine supplementation resulted in significant carnitine plasma level increase by week 4. The primary outcome, fatigue, measured using the BFI, improved in both arms compared with baseline (L-carnitine: −0.96, 95% CI, −1.32 to −0.60; placebo: −1.11, 95% CI −1.44 to −0.78). There were no statistically significant differences between arms (P = .57). Secondary outcomes, including fatigue measured by the Functional Assessment of Chronic Illness Therapy–Fatigue instrument, depression, and pain, did not show significant difference between arms. A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation. Conclusion Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status.
Inhibitors of 3-Hydroxy-3-Methylglutaryl–CoA Reductase Reduce Receptor-Mediated Endocytosis in Opossum Kidney Cells
Authors: James E. Sidaway, Robert G. Davidson, Fergus McTaggart, Terry C. Orton, Robert C. Scott, Graham J. Smith, Nigel J. Brunskill
Journal: Journal of the American Society of Nephrology (2004)

Renal proximal tubule cells are responsible for the reabsorption of proteins that are present in the tubular lumen. This occurs by receptor-mediated endocytosis, a process that has a requirement for some GTP-binding proteins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase used for the therapeutic reduction of cholesterol-containing plasma lipoproteins. However, they can also reduce intracellular levels of isoprenoid pyrophosphates that are derived from the product of the enzyme, mevalonate, and are required for the prenylation and normal function of GTP-binding proteins. The hypothesis that inhibition of HMG-CoA reductase in renal proximal tubule cells could reduce receptor mediated-endocytosis was therefore tested. Five different statins inhibited the uptake of FITC-labeled albumin by the proximal tubule-derived opossum kidney cell line in a dose-dependent manner and in the absence of cytotoxicity. The reduction in albumin uptake was related to the degree of inhibition of HMG-CoA reductase. Simvastatin (e.g., statin) inhibited receptor-mediated endocytosis of both FITC-albumin and FITC-beta(2)-microglobulin to similar extents but without altering the binding of albumin to the cell surface. The effect on albumin endocytosis was prevented by mevalonate and by the isoprenoid geranylgeranyl pyrophosphate but not by cholesterol. Finally, evidence that the inhibitory effect of statins on endocytosis of proteins may be caused by reduced prenylation and thereby decreased function of one or more GTP-binding proteins is provided. These data establish the possibility in principle that inhibition of HMG-CoA reductase by statins in proximal tubule cells may reduce tubular protein reabsorption.
Reduced surgical training hours harm patients and education, Canada study finds
Authors: M. McCarthy
Journal: BMJ (2014)

Reducing surgical trainees’ work hours has led to worse patient outcomes and poorer trainee performance on certification programmes without clearly improving the trainees’ sense of wellbeing, a new study claims.1

The systematic review was conducted as part of a project by the Royal College of Physicians and Surgeons of Canada to develop a consensus policy document on duty hour reductions for doctors in training.2

Najma Ahmed, of the University of Toronto in Ontario, was the lead author of the paper, which was published online by the journal Annals of Surgery .

In 2003 the Accreditation Council for Graduate Medical Education in the United States mandated an 80 hour duty limit for residents as an average …
Amiodarone hepatotoxicity: Prevalence and clinicopathologic correlations among 104 patients
Authors: James H. Lewis, Richard C. Ranard, Anthony Caruso, Lawrence K. Jackson, Florabel Mullick, Kamal G. Ishak, Leonard B. Seeff, Hyman J. Zimmerman
Journal: Hepatology (1989)

The prevalence of apparent amiodarone-related hepatic injury in 104 patients followed prospectively is compared to that reported in the literature. Asymptomatic elevation of serum aminotransferase levels was detected in approximately one-fourth of the patients, a figure similar to the average of reported cases. The frequency of extrahepatic organ toxicity was increased in patients with elevated levels. Symptomatic “hepatitis” developed in 3% of this series and in less than 1% of cases in the litérature. Evidence of hepatic phospholipidosis and the development of pseudoalcoholic liver injury is most likely due to the biochemical effects of the drug and to possible metabolic idiosyncrasy, respectively. Serial blood enzyme measurements, as recommended by the manufacturer, may offer some protection against the development of more serious liver injury. However, levels of amiodarone may persist in various tissues for weeks to months following withdrawal, and stopping the drug does not guarantee the prompt reversal of any organ toxicity. Accordingly, the risks posed and benefits offered by amiodarone should be carefully weighed prior to discontinuing the drug, as the risk of sudden cardiac death may outweigh the hazards of ongoing hepatic, pulmonary or other toxicity.
Effects of the Selective Estrogen Receptor Modulator Raloxifene on Coronary Outcomes in The Raloxifene Use for the Heart Trial
Authors: Peter Collins, Lori Mosca, Mary Jane Geiger, Deborah Grady, Marcel Kornitzer, Messan G. Amewou-Atisso, Mark B. Effron, Sherie A. Dowsett, Elizabeth Barrett-Connor, Nanette K. Wenger
Journal: Circulation (2009)

Background— The Raloxifene Use for The Heart (RUTH) trial showed that raloxifene, a selective estrogen receptor modulator, had no overall effect on the incidence of coronary events in women with established coronary heart disease or coronary heart disease risk factors. We provide detailed results of the effect of raloxifene on coronary outcomes over time and for 24 subgroups (17 predefined, 7 post hoc). Methods and Results— Postmenopausal women (n=10 101; mean age, 67 years) were randomized to raloxifene 60 mg/d or placebo for a median of 5.6 years. Coronary outcomes were assessed by treatment group in women with coronary heart disease risk factors and those with established coronary heart disease. Raloxifene had no effect on the incidence of coronary events in any subgroup except in the case of a post hoc age subgroup analysis using age categories defined in the Women’s Health Initiative randomized trials. The effect of raloxifene on the incidence of coronary events differed significantly by age (interaction P =0.0118). The incidence of coronary events in women &lt;60 years of age was significantly lower in those assigned raloxifene (50 events) compared with placebo (84 events; hazard ratio, 0.59; 95% confidence interval, 0.41 to 0.83; P =0.003; absolute risk reduction, 36 per 1000 women treated for 1 year). No difference was found between treatment groups in the incidence of coronary events in women ≥60 and &lt;70 or ≥70 years of age. Conclusions— In postmenopausal women at increased risk of coronary events, the overall lack of benefit of raloxifene was similar across the prespecified subgroups.
From identification to validation to gene count
Authors: Clara Amid, Adam Frankish, Bronwen Aken, Iakes Ezkurdia, Felix Kokocinsk, James Gilbert, Simon White, Piero Carninci, Thomas Gingeras, Roderic Guigo, Steve Searle, Michael L Tress, Jennifer Harrow, Tim Hubbard
Journal: Genome biology (2010)

The current GENCODE gene count of ~ 30,000, including 21,727 protein-coding and 8,483 RNA genes, is significantly lower than the 100,000 genes anticipated by early estimates. Accurate annotation of protein-coding and non-coding genes and pseudogenes is essential in calculating the true gene count and gaining insight into human evolution. 

As part of the GENCODE Consortium, the HAVANA team produces high quality manual gene annotation, which forms the basis for the reference gene set being used by the ENCODE project and provides a rich annotation of alternative splice variants and assignment of functional potential. However, the protein-coding potential of some splice variants is uncertain and valid splice variants can remain unannotated if they are absent from current cDNA libraries. Recent technological developments in sequencing and mass spectrometry have created a vast amount of new transcript and protein data that facilitate the identification and validation of new and existing transcripts, while harboring their own limitations and problems.
The Great East Japan Earthquake and Out-of-Hospital Cardiac Arrest
Authors: Tetsuhisa Kitamura, Kosuke Kiyohara, Taku Iwami
Journal: New England Journal of Medicine (2013)

On March 11, 2011, a magnitude 9.0 earthquake struck the northeast region of Japan. During the first 4 weeks after the earthquake, the numbers of out-of-hospital cardiac arrests were significantly increased as compared with the numbers during the same weeks from 2005 to 2010.
Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions
Authors: M Anlauf, A Perren, T Henopp, T Rudolf, N Garbrecht, A Schmitt, A Raffel, O Gimm, E Weihe, W T Knoefel, H Dralle, P. U Heitz, P Komminoth, G Kloppel
Journal: Gut (2006)

Patients with a multiple endocrine neoplasia type 1 (MEN1)-associated Zollinger-Ellison syndrome (ZES) show multifocal duodenal gastrinomas and precursor lesions.
Paresis and the Priest
Authors: BURTON A. WAISBREN
Journal: Annals of Internal Medicine (1974)

An analysis of two versions of Father Flynn's illness in "The Sisters," one of the stories in Dubliners, by James Joyce, suggests that in the second version of the story Joyce deliberately implied that Father Flynn had central nervous system syphilis. The evidence shows that Joyce was interested and qualified enough in medicine to be able to describe a syphilitic and that he had definite reasons for doing so. The syphilitic nature of Father Flynn's illness may not have been recognized in the past because many Joyce scholars apparently did not know that paralysis was often used synonymously with paresis (general paralysis of the insane) when Joyce began his revisions in 1905.
Irish judges rule that brain dead pregnant woman should be allowed to die
Authors: C. Dyer
Journal: BMJ (2014)

A brain dead pregnant woman has been taken off life support at a regional hospital in the Republic of Ireland after the country’s High Court ruled that her fetus had no chance of surviving until birth and that the woman should be allowed to die.

The case, which has made headlines around the world, sparked a nationwide debate about article 8 of the Irish constitution, which was passed in 1983 after pressure from antiabortion and religious groups in the overwhelmingly Catholic country. Some campaigners …
Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States
Authors: Thomas E. Delea, May Hagiwara, Simu K. Thomas, Jean‐Francois Baladi, Pradyumna D. Phatak, Thomas D. Coates
Journal: American Journal of Hematology (2007)

Abstract Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97–12/04 and representing 40 million members in &gt;70 health plans. Study subjects ( n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.