tbuckley/cabot-search huggingface dataset:
Involvement of Human Herpesvirus-6 Variant B in Classic Hodgkin's Lymphoma via DR7 Oncoprotein
Authors: Aurélie Lacroix, Sophie Collot-Teixeira, Laurent Mardivirin, Arnaud Jaccard, Barbara Petit, Christophe Piguet, Franck Sturtz, Pierre-Marie Preux, Dominique Bordessoule, Sylvie Ranger-Rogez
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Hodgkin's lymphoma (HL) is associated with the presence of EBV in Reed-Sternberg (RS) cells in ∼40% of cases. Here, we studied the presence of human herpesvirus type 6 (HHV-6) variant B in RS cells of HL patients and correlated results with clinical parameters. We then examined the implication of HHV-6 DR7B protein in cell deregulation. Experimental Design: HHV-6 DR7B protein was produced in a Semliki Forest virus system. Polyclonal antibodies were then generated and used for immunochemical HHV-6 localization in HL biopsies. Binding between DR7B and p53 was studied using a double-hybrid system. Transactivation of NFκB was observed after transient transfection using reporter gene assays. We looked for Id2 factor expression after stable transfection of the BJAB cell line by reverse transcription-PCR and Western blot analysis. Results: HHV-6 was more common in nodular sclerosis subtype HL, and DR7B oncoprotein was detected in RS cells for 73.7% of EBV-negative patients. Colocalization of EBV and HHV-6 was observed in RS cells of doubly infected patients. DR7B protein bound to human p53 protein. p105-p50/p65 mRNA expression and activation of the NFκB complex were increased when DR7B was expressed. Stable expression of DR7B exhibited a strong and uniform expression of Id2. A slightly higher percentage of remission was observed in patients with RS cells testing positive for DR7B than in those testing negative. Conclusions: Collectively, these data provide evidence for the implication of a novel agent, HHV-6, in cases of nodular sclerosis HL. Clin Cancer Res; 16(19); 4711–21. ©2010 AACR.
Statins for people at low risk
Authors: Emma Parish, Theodora Bloom, Fiona Godlee
Journal: BMJ (2015)

Independent review of the trial data is an essential next step

Statins are the UK’s most commonly prescribed drugs and are among the most widely prescribed drugs globally.1 Though their use in people at high risk of stroke and heart disease is uncontroversial, recent recommendations to treat much larger numbers of people at low risk2 3 have caused a storm of controversy.4 Most hotly debated are the nature and frequency of side effects of statins and whether arguably small gains in life expectancy are worth the risk.5 6

In August 2014 an expert panel convened by The BMJ called for the anonymised individual patient data from the statins trials to be made available for independent scrutiny.7 Our subsequent inquiries, guided by an expert advisory group (www.bmj.com/campaign/statins-open-data) have revealed the worrying extent to which these data remain hidden.

In reply to a letter from The BMJ , Rory Collins and colleagues of the Cholesterol Treatment Trialists (CTT) collaboration in Oxford confirmed that their meta-analyses have so far been limited to patient level data on cause specific mortality, major vascular events, and site specific cancers. They had not analysed data on other adverse events as these were not part of the original CTT agreement. Collins and colleagues explained, however, that the trialists agreed in 2013 to pool and analyse data on all adverse events. …
Relationship between trace elements, sugar consumption, and taste in Crohn's disease.
Authors: W J Penny, J F Mayberry, P J Aggett, J O Gilbert, R G Newcombe, J Rhodes
Journal: Gut (1983)

Seventy patients with Crohn's disease, 50 with ulcerative colitis, and 58 control subjects were questioned about their sugar consumption, measurements were made of their taste acuity, and blood levels of various trace elements including zinc and selenium were estimated. Sugar consumption was significantly increased in Crohn's disease (p less than 0.01). There was only a minor reduction in taste acuity for acid taste in Crohn's disease. Plasma zinc and whole blood selenium were reduced in Crohn's disease. No relationship was found between sugar consumption, plasma zinc, and taste acuity in Crohn's disease.
Intermittent Hypoxia Induces Proteasome-Dependent Down-Regulation of Estrogen Receptor α in Human Breast Carcinoma
Authors: Charlton Cooper, Guang-Yu Liu, Yu-Lian Niu, Sylvia Santos, Leigh C. Murphy, Peter H. Watson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Hypoxia may influence gene expression to promote malignancy, and acute hypoxia has been shown to transiently repress estrogen receptor (ER)-α expression in breast cell lines. However, the effect of intermittent hypoxia, which is likely more prevalent in breast cancers, remains to be determined. Experimental Design: ER-α expression was assessed by Western blot and immunohistochemistry in a selected cohort of 51 ER-α–positive breast carcinomas, in relation to markers of hypoxia. The effect of acute and intermittent hypoxia on ER-α expression was also determined in MCF7 and ZR-75 breast cell lines, together with the role of proteasome function with the proteasome inhibitor bortezomib. Results: Regional loss of ER-α expression occurs in breast tumors and is consistently present in hypoxic regions defined by the proximity of necrosis and induction of hypoxia-induced genes carbonic anhydrase IX (CA-IX) and glucose transporter 1 (Glut-1), in both in situ (n = 29; P &amp;lt; 0.0001) and invasive (n = 20; P = 0.0001) carcinomas. In MCF7 and ZR-75 cells, ER-α is transiently down-regulated by acute hypoxia and rapidly restored by reoxygenation. However, intermittent, acute hypoxia can cause a similar down-regulation of ER-α that is not attributable to decreased mRNA and persists in MCF7 cells despite reoxygenation for up to 14 days. This effect occurs with no change in cell viability but a corresponding reduction in growth response to estradiol. However, ER-α expression can be restored by bortezomib. Conclusions: Intermittent hypoxia can cause persistent changes in proteasome function that may contribute to reduced ER-α expression in breast tumors and consequently to diminished response and development of resistance to endocrine therapy.
Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial
Authors: M.A. Gordon, H.M. Gundacker, J. Benedetti, J.S. Macdonald, J.C. Baranda, W.J. Levin, C.D. Blanke, W. Elatre, P. Weng, J.Y. Zhou, H.J. Lenz, M.F. Press
Journal: Annals of Oncology (2013)
Incidence and risk of hemorrhagic events with vascular endothelial growth factor receptor tyrosine-kinase inhibitors: an up-to-date meta-analysis of 27 randomized controlled trials
Authors: W.-X. Qi, L.-N. Tang, Y.-J. Sun, A.-N. He, F. Lin, Z. Shen, Y. Yao
Journal: Annals of Oncology (2013)
Subacute Effusive-Constrictive Pericarditis
Authors: E. W. HANCOCK
Journal: Circulation (1971)

Clinical and hemodynamic observations are reported in 13 patients who demonstrated a distinct pathophysiologic form of compressive pericardial disease characterized by effusion into a free pericardial space associated with constriction of the heart by the visceral pericardium. The pericardial disease was idiopathic (nine patients) or subsequent to radiotherapy (four patients), with a maximal duration of symptoms of 16 months. Enlarged heart shadow, prominent paradoxical pulse, predominant systolic dip in the venous pressure pulse, and absence of atrial fibrillation were features that tended to distinguish the effusive-constrictive cases from those with noneffusive chronic constrictive pericarditis. The value of pressure measurements during combined cardiac catheterization and pericardiocentesis is emphasized in the differentiation of effusive-constrictive pericarditis from cardiac tamponade without constriction. Four patients were observed to progress through an effusive-constrictive phase to noneffusive constrictive pericarditis. Corticosteroids, pericardiocentesis, and other medical therapy produced some benefit but did not relieve constriction. The results of surgery were generally satisfactory.
Neuropsychological Deficits in Psychotic Versus Nonpsychotic Major Depression and No Mental Illness
Authors: A F Schatzberg, J A Posener, C DeBattista, B M Kalehzan, A J Rothschild, P K Shear
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: At least three studies have indicated that patients with psychotic major depression studied under non-drug-free conditions differ from patients with nonpsychotic major depression and healthy comparison subjects on several measures of neuropsychological performance. The current study explored specific impairments in cognitive function in subjects with psychotic major depression, subjects with nonpsychotic major depression, and healthy comparison subjects studied under drug-free conditions.METHOD: A battery of neuropsychological tests was administered to 11 patients with psychotic major depression, 32 patients with nonpsychotic major depression, and 23 normal comparison subjects under drug-free conditions. The three groups did not differ statistically in age, sex, or level of education. To ensure that participants had minimal levels of severity and endogenicity, all patients were required to have a score of at least 20 on the 21-item Hamilton Depression Rating Scale and a score of at least 7 on the Core Endogenomorphic Scale, which uses eight items from the Hamilton depression scale.RESULTS: Patients with psychotic major depression demonstrated significantly greater impairment than patients with nonpsychotic major depression and/or comparison subjects in attention and response inhibition (as measured by the Stroop color-word subscale score) as well as in verbal declarative memory (as measured by the Paragraph Recall Test).CONCLUSIONS: These data indicate that patients with psychotic major depression demonstrate impairment in functions thought to be mediated by the frontal cortex and mediotemporal lobes.
Peripheral joint inflammation in early onset spondyloarthritis is not specifically related to enthesitis
Authors: Jacqueline E Paramarta, Christiaan van der Leij, Ioana Gofita, Nataliya Yeremenko, Marleen G van de Sande, Maria J de Hair, Paul P Tak, Mario Maas, Dominique Baeten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> A pivotal MRI study of knee arthritis indicated that enthesitis was more frequently observed in established spondyloartritis (SpA) than rheumatoid arthritis (RA). Subsequent MRI and ultrasound studies, however, failed to consistently demonstrate primary synovitis in RA versus primary enthesitis in SpA. Therefore, the current study aimed to reassess enthesitis versus synovitis in peripheral arthritis by a combined imaging and histopathological study in early untreated disease. <h3>Methods</h3> MRI and mini-arthroscopic synovial biopsy sampling were performed in 41 patients with early untreated knee or ankle arthritis, who were diagnosed with SpA (n=13), RA (n=20) or crystal arthropathy (n=8) at follow-up. MRI evaluation of enthesitis and synovitis, and immunohistochemical characterisation of synovitis were performed by two observers blinded to diagnosis. <h3>Results</h3> MRI showed similar prevalence of perientheseal fluid/oedema (67% vs 75%), perientheseal bone marrow oedema (0% vs 10%) and entheseal enhancement (46% vs 47%) in SpA versus RA, respectively. The number and distribution of affected entheseal sites were not different between both diseases. The MRI synovitis score was significantly higher in SpA (median 1.4; IQR 1.1–1.5) compared with RA (median 0.5; IQR 0.0–1.3) (p=0.028). Synovial histopathology showed a numerical increase in infiltrating cells in SpA versus RA synovitis which reached significance for CD163 macrophages in the synovial sublining (p=0.030). There were no differences compared with the crystal arthropathy control group. <h3>Conclusions</h3> Enthesitis on MRI is not a specific feature of peripheral arthritis in recent onset SpA versus RA. Synovitis is prominent in both diseases as evaluated by MRI and immunohistochemistry.
Retransplantation After Failure of First Renal Homografts
Authors: Ray W. Gifford
Journal: JAMA (1967)

Nineteen patients whose first renal homografts failed have undergone retransplantation; one patient has received a third homograft after the first two failed to function. As of July 1, 1966, eight of these patients are living, five with life-sustaining homografts that have been functioning for periods from 11 to 21 months. Three patients are being maintained with periodic hemodialyses. Second renal homografts functioned in six of seven patients who lost their first homografts because of technical problems and four of these patients are alive with functioning homografts. Second renal homografts were rejected by five of 10 patients who lost their first homografts because of rejection or thrombosis of the renal artery; only one of these patients is alive with a functioning homograft. We are reluctant to recommend retransplantation in patients who have rejected their first homograft, while we unhesitatingly recommend retransplantation in patients whose first homograft, though functioning, had to be removed because of technical problems.
Burnout and Suicidal Ideation among U.S. Medical Students
Authors: Liselotte N. Dyrbye, Matthew R. Thomas, F. Stanford Massie, David V Power, Anne Eacker, William Harper, Steven Durning, Christine Moutier, Daniel W. Szydlo, Paul J. Novotny, Jeff A. Sloan, Tait D. Shanafelt
Journal: Annals of Internal Medicine (2008)

Background: Little is known about the prevalence of suicidal ideation among U.S. medical students or how it relates to burnout. Objective: To assess the frequency of suicidal ideation among medical students and explore its relationship with burnout. Design: Cross-sectional 2007 and longitudinal 2006 to 2007 cohort study. Setting: 7 medical schools in the United States. Participants: 4287 medical students at 7 medical schools, with students at 5 institutions studied longitudinally. Measurements: Prevalence of suicidal ideation in the past year and its relationship to burnout, demographic characteristics, and quality of life. Results: Burnout was reported by 49.6% (95% CI, 47.5% to 51.8%) of students, and 11.2% (CI, 9.9% to 12.6%) reported suicidal ideation within the past year. In a sensitivity analysis that assumed all nonresponders did not have suicidal ideation, the prevalence of suicidal ideation in the past 12 months would be 5.8%. In the longitudinal cohort, burnout (P < 0.001 for all domains), quality of life (P < 0.002 for each domain), and depressive symptoms (P < 0.001) at baseline predicted suicidal ideation over the following year. In multivariable analysis, burnout and low mental quality of life at baseline were independent predictors of suicidal ideation over the following year. Of the 370 students who met criteria for burnout in 2006, 99 (26.8%) recovered. Recovery from burnout was associated with markedly less suicidal ideation, which suggests that recovery from burnout decreased suicide risk. Limitation: Although response rates (52% for the cross-sectional study and 65% for the longitudinal cohort study) are typical of physician surveys, nonresponse by some students reduces the precision of the estimated frequency of suicidal ideation and burnout. Conclusion: Approximately 50% of students experience burnout and 10% experience suicidal ideation during medical school. Burnout seems to be associated with increased likelihood of subsequent suicidal ideation, whereas recovery from burnout is associated with less suicidal ideation.
Nonaddictive instrumental drug use: Theoretical strengths and weaknesses
Authors: Andrew J. Goudie, Matthew J. Gullo, Abigail K. Rose, Paul Christiansen, Jonathan C. Cole, Matt Field, Harry Sumnall
Journal: Behavioral and Brain Sciences (2011)

Abstract The potential to instrumentalize drug use based upon the detection of very many different drug states undoubtedly exists, and such states may play a role in psychiatric and many other drug uses. Nevertheless, nonaddictive drug use is potentially more parsimoniously explained in terms of sensation seeking/impulsivity and drug expectations. Cultural factors also play a major role in nonaddictive drug use.
miR-363-5p regulates endothelial cell properties and their communication with hematopoietic precursor cells
Authors: Ana Costa, Joana Afonso, Catarina Osório, Ana L Gomes, Francisco Caiado, Joana Valente, Sandra I Aguiar, Francisco Pinto, Mário Ramirez, Sérgio Dias
Journal: Journal of Hematology & Oncology (2013)

Recent findings have shown that the blood vessels of different organs exert an active role in regulating organ function. In detail, the endothelium that aligns the vasculature of most organs is fundamental in maintaining organ homeostasis and in promoting organ recovery following injury. Mechanistically, endothelial cells (EC) of tissues such as the liver, lungs or the bone marrow (BM) have been shown to produce "angiocrine" factors that promote organ recovery and restore normal organ function. Controlled production of angiocrine factors following organ injury is therefore essential to promote organ regeneration and to restore organ function. However, the molecular mechanisms underlying the coordinated production and function of such "angiocrine" factors are largely undisclosed and were the subject of the present study. In detail, we identified for the first time a microRNA (miRNA) expressed by BM EC that regulates the expression of angiocrine genes involved in BM recovery following irradiation. Using a microarray-based approach, we identified several miRNA expressed by irradiated BMEC. After validating the variations in miRNA expression by semi-quantitative PCR, we chose to study further the ones showing consistent variations between experiments, and those predicted to regulate (directly or indirectly) angiogenic and angiocrine factors. Of the mi-RNA that were chosen, miR-363-5p (previously termed miR-363*) was subsequently shown to modulate the expression of numerous EC-specific genes including some angiocrine factors. By luciferase reporter assays, miR-363-5p is shown to regulate the expression of angiocrine factors tissue inhibitor of metalloproteinases-1 (Timp-1) and thrombospondin 3 (THBS3) at post-transcriptional level. Moreover, miR-363-5p reduction using anti-miR is shown to affect EC angiogenic properties (such as the response to angiogenic factors stimulation) and the interaction between EC and hematopoietic precursors (particularly relevant in a BM setting). miR-363-5p reduction resulted in a significant decrease in EC tube formation on matrigel, but increased hematopoietic precursor cells adhesion onto EC, a mechanism that is shown to involve kit ligand-mediated cell adhesion. Taken together, we have identified a miRNA induced by irradiation that regulates angiocrine factors expression on EC and as such modulates EC properties. Further studies on the importance of miR-363-5p on normal BM function and in disease are warranted.
The toll of road traffic accidents
Authors: I. Hindmarch
Journal: Journal of the Royal Society of Medicine (2003)

While I wholeheartedly support the conclusion of the editorial by Rodger Charlton and Gary Smith (October 2003 JRSM1) I am surprised that the authors make no mention of the reduction in road traffic accidents (RTAs) that the appropriate prescription of certain medications to car driving patients would produce. I realize there are few data investigating the role of prescription medicines in RTAs, but those that exist (e.g. Barbone et al., Association of road traffic accidents with benzodiazepine use, Lancet 1998, 352, 1331–6, or Currie et al., The use of antidepressants and benzodiazepines in the perpetrators and victims of accidents, Occup Med 1995, 45, 323–5) clearly indicate that certain prescription-only medications are implicated as causative agents in RTAs.

An easy way to help reduce the toll of such drugs is that they be clearly labelled as incompatible with vehicle operating and should therefore be avoided by road users. Such a mechanism, an unambiguous red warning triangle on the dispensing pack, is employed in several European countries. The UK use of a label on the lines of ‘if you feel affected, do not drive’ is not a straightforward indication to that patient not to operate a motor vehicle. The ‘red triangle’ alerts physicians, pharmacists and patient, and the good news is that for every red-triangle medicine there exist several clinically equipotent compounds with no measurable effect on car driving skills.
Hepatocellular carcinoma associated with recreational anabolic steroid use: Figure 1
Authors: P Gorayski, C H Thompson, H S Subhash, A C Thomas
Journal: British Journal of Sports Medicine (2008)

A 35-year-old male bodybuilder was found to have a hepatocellular carcinoma (HCC) arising in a pre-existing hepatic adenoma following recreational anabolic steroid use. Given the widespread use of recreational anabolic steroids, another potentially life-threatening complication is highlighted in addition to the more commonly recognised hepatic adenoma. Malignant transformation to HCC from a pre-existing hepatic adenoma confirmed by immunohistochemical study has previously not been reported in athletes taking anabolic steroids. Further studies using screening programmes to identify high-risk individuals are recommended.
Microsatellite Instability Status Is Critical to Analysis of Survival in Stage II Colon Cancer
Authors: Susie Bae, Jeanne Tie, Jayesh Desai, Peter Gibbs
Journal: Journal of Clinical Oncology (2012)

with radiotherapy intended as a preoperative procedure before abdominoperineal resection, were not included in our patient cohort.Therefore, excluding the patients with pretreatment colostomies, as suggested by Ozsahin et al, 1 would cause us to underestimate the actual number of patients needing a colostomy despite intended sphincter-sparing treatment.Finally, we observed in patients with local excision preceding radiotherapy a substantially higher risk of therapy-related colostomy despite slightly lower radiotherapy doses (mean dose, 61.6 v 63.1 Gy; P ϭ .007).However, our speculation that local excision should not be the primary therapeutic option was also based on other studies, which reported higher frequency of colostomy 14 or severe anorectal injury, 15 but no decrease in local failure in patients with local excision before radiotherapy or chemoradiotherapy. 15
The influence of adenovirus fiber structure and function on vector development for gene therapy
Authors: Stuart A. Nicklin, Eugene Wu, Glen R. Nemerow, Andrew H. Baker
Journal: Molecular Therapy (2005)

The collective attributes of adenoviruses (Ads), including ease of accomplishing replication deficiency, readily achievable high titers, encoding of large expression cassettes, efficiency of gene delivery to most cell types, and well-characterized biology, have made Ads, particularly Ad serotype 5 (Ad 5), some of the most utilized vectors for gene delivery. In recent years, however, it has become apparent that additional aspects of basic Ad virology must be uncovered for this vector system to succeed in the clinic. While local gene delivery is generally efficient, the broad tropism of Ad 5 and its tendency to home to the liver after systemic administration have proved to be limitations for other therapeutic applications, such as the treatment of disseminated cancers and cardiovascular disease. This has refocused research into the biology of Ad capsid components, particularly the main tropism determinant, the fiber/penton base complex, and their influence on transduction of selected cell types in vivo.