tbuckley/cabot-search huggingface dataset:
In vitro stimulation of lymphocytes by neutral proteinases from human polymorphonuclear leukocyte granules.
Authors: T L Vischer, U Bretz, M Baggiolini
Journal: The Journal of Experimental Medicine (1976)

Two neutral proteinases from human polymorphonuclear leukocytes (PMN), an elastase and the chymotrypsin-like cathepsin G, were purified, and their actions on lymphocytes in culture were studied. Both PMN proteinases stimulate lymphocytes from human peripheral blood and from mouse spleen in vitro, but do not affect thymic cells from either normal or hydrocortisone-treated mice. In stimulated mouse spleen cell cultures, most of the developing blast cells bear surface immunoglobulins, and subsequently appear to engage in antibody synthesis. In their stimulatory action, the two PMN proteinases thus resemble the classic B-cell mitogen LPS and neutral pancreatic proteinases such as trypsin, chymotrypsin, and elastase. The effects of proteinase inhibitors indicate that lymphocyte stimulation is dependent on the proteolytic activity of the enzymes. This work suggests that PMN proteinases, which are released at sites of inflammation, may modulate the function of lymphocytes.
Trainee concerns regarding the Specialty Certificate Examination: results of a British Thoracic Society national survey
Authors: Caroline Marie Patterson, Richard Ian Carter, James William Dodd, Andrea Collins
Journal: Thorax (2013)

As aspiring respiratory physicians are aware, The Federation of Royal Colleges of Physicians of the UK (FRCPUK) has introduced Specialty Certificate Examinations (SCEs) to complement workplace-based assessments. Successful completion of the SCE in Respiratory Medicine is a prerequisite for Certificate of Completion of Training for all UK respiratory trainees whose specialist training began during or after August 2007.

The SCE comprises two papers, each lasting 3 h and containing 100 questions in a ‘best of five’ format. Delivery and marking of the examination is computer-based. The FRCPUK has worked in partnership with specialist societies, including the British Thoracic Society (BTS), to optimise examination validity and reliability.

Analyses of SCE performance have been reported by the …
Peripheral changes in endometriosis-associated pain
Authors: Matteo Morotti, Katy Vincent, Jennifer Brawn, Krina T. Zondervan, Christian M. Becker
Journal: Human Reproduction Update (2014)

BACKGROUNDPain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis.
P53/microRNA-34-induced metabolic regulation: new opportunities in anticancer therapy
Authors: Ding-Guo Zhang, Jun-Nian Zheng, Dong-Sheng Pei
Journal: Molecular Cancer (2014)

MicroRNA-34 (miR-34) is directly regulated by p53, and its potential tumor suppressive roles have been studied extensively. As a p53-induced microRNA, miR-34 functions as a tumor suppressor by playing a role in cell cycle arrest, apoptosis and metabolic regulation. Among these p53/miR-34 associated processes, apoptosis and cell cycle arrest are known as essential for p53/miR-34-mediated tumor suppression. P53-mediated metabolic processes have been shown to play pivotal roles in cancer cell biology. Recent studies have also identified several miR-34 targets involved in p53/miR-34-induced metabolic regulation. However, correlations among these metabolic targets remain to be fully elucidated. In this review, we summarize the current progress in the field of metabolic regulation by the p53/miR-34 axis and propose future directions for the development of metabolic approaches in anticancer therapy.
Cumulative exposure to ionising radiation in adults with interstitial lung disease (ILD)
Authors: Lamis Taha, Dilip Nazareth, Syed Kazmi, Martin Walshaw
Journal: European Respiratory Journal (2012)

Background: The cumulative exposure to potentially carcinogenic ionising radiation is important in patients with ILD as they are exposed to multiple radiological investigations. We looked at the amount of ionising radiation given to adults with ILD (n=41) attending our Respiratory clinic over a 12-month period.

Method: All ionising radiation studies were reviewed for their impact on management. Radiation was calculated using standard reference doses and expressed as milliSievert [mSv].

Results: See Table. The average radiation dose was 12.33 mSv with 56% of investigations impacting care. Those with UIP pattern of fibrosis had a greater cumulative dose of radiation.

Conclusion: Patients with ILD receive significant medical radiation each year, but most impacts on their management. Those with NSIP had a greater number of investigations impacting care as compared to those with UIP, in keeping with the wider spectrum of disease and more treatment options being available in this sub-group of patients. Care should be taken when ordering investigations associated with ionising radiation, to reduce the long term effects of potentially harmful investigations.

View this table:

Radiation doses and % impacting care
Interventions for Intimate Partner Violence Against Women
Authors: Karin V. Rhodes, Wendy Levinson
Journal: JAMA (2003)

Sufficient evidence regarding the effectiveness of physician screening, counseling, and referral for intimate partner violence is lacking. However, even in the absence of sufficient evidence, many medical organizations recommend that physicians make efforts to identify and refer patients who have experienced abuse. This article presents 3 cases that illustrate the interaction between patients experiencing violence in intimate relationships and physicians and other members of the health care team. Suggestions for care are based on guidelines and evidence where available. Resources to assist physicians with referral to appropriate services also are provided.
Evolutionary Dynamics of Satellite DNA Family PIM357 in Species of the Genus Pimelia (Tenebrionidae, Coleoptera)
Authors: Joan Pons, Eduard Petitpierre, Carlos Juan
Journal: Molecular Biology and Evolution (2002)

A large number of repeats of a satellite DNA (stDNA) family have been cloned and sequenced from species and populations of the genus Pimelia (Tenebrionidae, Coleoptera). The beetles were collected in the Canary Islands, Morocco, the Iberian Peninsula, and the Balearic Islands in order to analyze the evolutionary forces and processes acting on abundant stDNAs conserved at the genus level. This repetitive family is composed of an abundant A-T-rich stDNA, with basic units of 357 bp. All the sequences obtained showed similarity to the 22 repeat units of the PIM357 stDNA family described previously for six Iberian Pimelia species (Pons et al. 1997 ). An analysis based on similarity shows the presence of three different groups of sequences clearly in accordance with their geographical origin. One is composed of satellite sequences from Iberian and Balearic species, a second group from the Moroccan taxa, whereas the third one is from the Pimelia species endemic to the Canary Islands. The latter group shows higher nucleotide diversities for their stDNA sequences and a lack of relationship between transition stages to fixation and sequence divergence. Phylogeographic data of Canarian Pimelia show that the PIM357 stDNA family has persisted for more than 8 Myr and could probably be traced to the origin of the lineage. The data suggest that distinct demographic and phylogenetic patterns related to the colonization of the volcanic Canarian island chain account for particular evolutionary dynamics of the repeat DNA family in this group.
Impact of Antidepressant Discontinuation After Acute Bipolar Depression Remission on Rates of Depressive Relapse at 1-Year Follow-Up
Authors: Lori Altshuler, Trisha Suppes, David Black, Willem A. Nolen, Paul E. Keck, Mark A. Frye, Susan McElroy, Ralph Kupka, Heinz Grunze, Jörg Walden, Gabrielle Leverich, Kirk Denicoff, David Luckenbaugh, Robert Post
Journal: American Journal of Psychiatry (2003)

While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode.Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group").A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse.The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.
Association between genetic factors, naevus count and dermoscopic pattern
Authors: C. Longo, G. Pellacani
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 1081 It is well known that naevogenesis is a complex process that has its critical periods in childhood and adolescence.1 Moreover, the development of naevi is influenced not only by age but also by factors such as sex, sun exposure, skin type and freckling, to name just a few.2 A growing body of evidence has suggested that naevi have a strong heritable component in which gene variants implicated in naevus development include those involved in pigmentation, cell cycle regulation, telomere function and senescence. A deep understanding of the dynamic process of naevogenesis has been offered by dermoscopy and in vivo confocal microscopy. These methods have provided new insights into the growing pattern of some naevi (lesions with peripheral globules) and the stability of other naevi typified by a reticular pattern, suggesting that dermoscopically defined subsets of acquired naevi are biologically distinct.1 3 The study by Orlow et al.4, in this issue of the BJD, evaluates the potential associations between genetics and both melanocytic naevus count and dermoscopic naevus patterns in early life.
Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma
Authors: Richard I. Fisher, Steven H. Bernstein, Brad S. Kahl, Benjamin Djulbegovic, Michael J. Robertson, Sven de Vos, Elliot Epner, Amrita Krishnan, John P. Leonard, Sagar Lonial, Edward A. Stadtmauer, Owen A. O'Connor, Hongliang Shi, Anthony L. Boral, André Goy
Journal: Journal of Clinical Oncology (2006)

Purpose Evaluate response rate, duration of response (DOR), time-to-progression (TTP), overall survival (OS), and safety of bortezomib treatment in patients with relapsed or refractory mantle cell lymphoma (MCL). Patients and Methods Bortezomib 1.3 mg/m 2 was administered on days 1, 4, 8, and 11 of a 21-day cycle, for up to 17 cycles. Response and progression were determined using International Workshop Response Criteria, both using data from independent radiology review and by the investigators. Primary efficacy analyses were based on data from independent radiology review. Results In total, 155 patients were treated. Median number of prior therapies was one (range, one to three). Response rate in 141 assessable patients was 33% including 8% complete response (CR)/unconfirmed CR. Median DOR was 9.2 months. Median TTP was 6.2 months. Results by investigator assessments were similar. Median OS has not been reached after a median follow-up of 13.4 months. The safety profile of bortezomib was similar to previous experience in relapsed multiple myeloma. The most common adverse events grade 3 or higher were peripheral neuropathy (13%), fatigue (12%), and thrombocytopenia (11%). Death from causes that were considered to be treatment related was reported for 3% of patients. Conclusion These results confirm the activity of bortezomib in relapsed or refractory MCL, with predictable and manageable toxicities. Bortezomib provides significant clinical activity in terms of durable and complete responses, and may therefore represent a new treatment option for this population with usually very poor outcome. Studies of bortezomib-based combinations in MCL are ongoing.
Qa-2, H-2K, and H-2D alloantigens evolved from a common ancestral gene.
Authors: M J Soloski, J W Uhr, L Flaherty, E S Vitetta
Journal: The Journal of Experimental Medicine (1981)

The Tla region located on the murine 17th chromosome controls several serologically defined cell surface antigens. These antigens, referred to as Qa-1-5 and TL, are expressed on a variety of hematopoeitic cell populations. In the present studies we have immunoprecipitated isotopically labeled Qa-2 and H-2 molecules from mitogen-stimulated B6 spleen cells. Sequential immunoprecipitation experiments have shown that the determinants recognized by alpha Qa-2, alpha H-2Kb, and alpha H-2Db alloantisera reside on separate molecular species. Comparative mapping of the arginine-labeled tryptic peptides from Qa-2, H-2Kb, and H-2Db molecules indicate that Qa-2 is structurally distinct but that there is considerable structural homology; 21-43% of the Qa-2 peptides co-chromatograph with peptides derived from H-2Db and H-2Kb, respectively. Similar levels of homology are observed when Qa-2 is compared with H-2Kk or H-2Dd. The results show that the Qa-2 alloantigen is encoded by a locus separate from the loci encoding H-2K or H-2D alloantigens, but that the Qa-2, H-2K, and H-2D alloantigens are sufficiently related at the primary structural level to indicate that they evolved from a common primordial gene.
Resting Heart Rate in Middle Age and Diabetes Development in Older Age
Authors: Mercedes R. Carnethon, Lijing Yan, Philip Greenland, Daniel B. Garside, Alan R. Dyer, Boyd Metzger, Martha L. Daviglus
Journal: Diabetes Care (2008)

OBJECTIVE—Based on prior research showing inverse associations between heart rate and life expectancy, we tested the hypothesis that adults with higher resting heart rate in middle age were more likely to have diagnosed diabetes or to experience diabetes mortality in older age (&amp;gt;65 years). RESEARCH DESIGN AND METHODS—Resting heart rate was measured at baseline (1967–1973) in the Chicago Heart Association Detection Project in Industry. We used Medicare billing records to identify diabetes-related hospital claims and non–hospital-based diabetes expenses from 1992 to 2002 in 14,992 participants aged 35–64 years who were free from diabetes at baseline. Diabetes-related mortality was determined from 1984 to 2002 using National Death Index codes 250.XX (ICD-8 and -9) and E10–E14 (ICD-10). RESULTS—After age 65, 1,877 participants had diabetes-related hospital claims and 410 participants had any mention of diabetes on their death certificate. The adjusted (demographic characteristics, cigarette smoking, and years of Medicare eligibility) odds of having a diabetes-related claim was ∼10% higher (odds ratio [OR] 1.10 [95% CI 1.05–1.16]) per 12 bpm higher baseline heart rate. Following adjustment for BMI and postload glucose at baseline, the association attenuated to nonsignificance. Higher heart rate was associated with diabetes mortality in adults aged 35–49 years at baseline following adjustment for postload glucose and BMI (1.21 [1.03–1.41]). CONCLUSIONS—Higher resting heart rate is associated with diabetes claims and mortality in older age and is only due in part to BMI and concurrently measured glucose.
Care for chronic diseases
Authors: E. H Wagner
Journal: BMJ (2002)

See pp 954, 914, 925, 961 

This is the third in the BMJ 's series of theme issues on managing chronic diseases. This focus reflects the increasing demands on practitioners and health systems around the globe posed by mounting numbers of chronically ill patients.1 The term “chronic disease” usually connotes the prevalent chronic degenerative diseases such as diabetes, coronary artery disease, hypertension, and chronic obstructive pulmonary disease. But papers in the three theme issues argue that a much broader array of health problems generate similar needs for patients and similar challenges for health services—these include diseases such as chronic uveitis, gastro-oesophageal reflux disease, multiple sclerosis, depression, and osteoporosis.

Despite the clinical differences across these chronic conditions, each illness confronts patients and their families with the same spectrum of needs: to alter their behaviour; to deal with the social and emotional impacts of symptoms, disabilities, and approaching death; to take medicines; and to interact with medical care over time. In return, healthcare must …
Risk of subarachnoid haemorrhage in first degree relatives of patients with subarachnoid haemorrhage: follow up study based on national registries in Denmark
Authors: D. Gaist
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To estimate the risk of occurrence of subarachnoid haemorrhage in first degree relatives (parents, siblings, children) of patients with subarachnoid haemorrhage. <b>Design:</b> Population based cohort study using data from the Danish National Discharge Registry and the Central Person Registry. <b>Subjects:</b> Incident cases of subarachnoid haemorrhage admitted to hospital from 1977 to 1995 (9367 patients) and their first degree relatives (14 781). <b>Main outcome measures:</b> The incidence rate of subarachnoid haemorrhage was determined for the relatives and compared with that of the entire population, standardised for age, sex, and calendar period. This process was repeated for patients discharged from neurosurgery units, as diagnoses from these wards had high validity (93%). <b>Results:</b> 18 patients had a total of 19 first degree relatives with subarachnoid haemorrhage during the study period, corresponding to a standardised incidence ratio of 2.9 (95% confidence interval 1.9 to 4.6). Patients discharged from neurosurgery wards had a higher standardised incidence ratio (4.5, 2.7 to 7.3). <b>Conclusions:</b> First degree relatives of patients with subarachnoid haemorrhage have a threefold to fivefold increased risk of subarachnoid haemorrhage compared with the general population.
The Transcriptional Regulatory Network of Proneural Glioma Determines the Genetic Alterations Selected during Tumor Progression
Authors: Adam M. Sonabend, Mukesh Bansal, Paolo Guarnieri, Liang Lei, Benjamin Amendolara, Craig Soderquist, Richard Leung, Jonathan Yun, Benjamin Kennedy, Julia Sisti, Samuel Bruce, Rachel Bruce, Reena Shakya, Thomas Ludwig, Steven Rosenfeld, Peter A. Sims, Jeffrey N. Bruce, Andrea Califano, Peter Canoll
Journal: Cancer Research (2014)

Abstract Proneural glioblastoma is defined by an expression pattern resembling that of oligodendrocyte progenitor cells and carries a distinctive set of genetic alterations. Whether there is a functional relationship between the proneural phenotype and the associated genetic alterations is unknown. To evaluate this possible relationship, we performed a longitudinal molecular characterization of tumor progression in a mouse model of proneural glioma. In this setting, the tumors acquired remarkably consistent genetic deletions at late stages of progression, similar to those deleted in human proneural glioblastoma. Further investigations revealed that p53 is a master regulator of the transcriptional network underlying the proneural phenotype. This p53-centric transcriptional network and its associated phenotype were observed at both the early and late stages of progression, and preceded the proneural-specific deletions. Remarkably, deletion of p53 at the time of tumor initiation obviated the acquisition of later deletions, establishing a link between the proneural transcriptional network and the subtype-specific deletions selected during glioma progression. Cancer Res; 74(5); 1440–51. ©2014 AACR.
Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors
Authors: M.A. Dickson, S.H. Okuno, M.L. Keohan, R.G. Maki, D.R. D'Adamo, T.J. Akhurst, C.R. Antonescu, G.K. Schwartz
Journal: Annals of Oncology (2012)
Correlation and Regression
Authors: Sybil L. Crawford
Journal: Circulation (2006)

I n many health-related studies, investigators wish to assess the strength of an association between 2 measured (continuous) variables.For example, the relation between highsensitivity C-reactive protein (hs-CRP) and body mass index (BMI) may be of interest.Although BMI is often treated as a categorical variable, eg, underweight, normal, overweight, and obese, a noncategorized version is more detailed and thus may be more informative in terms of detecting associations.Correlation and regression are 2 relevant (and related) widely used approaches for determining the strength of an association between 2 variables.Correlation provides a unitless measure of association (usually linear), whereas regression provides a means of predicting one variable (dependent variable) from the other (predictor variable).This report summarizes correlation coefficients and least-squares regression, including intercept and slope coefficients. CorrelationCorrelation provides a "unitless" measure of association between 2 variables, ranging from Ϫ1 (indicating perfect negative association) to 0 (no association) to ϩ1 (perfect positive association).Both variables are treated equally in that neither is considered to be a predictor or an outcome. Pearson Product-Moment Coefficient of CorrelationThe most commonly used version is the Pearson productmoment coefficient of correlation, r.Suppose one wants to estimate the correlation between XϭBMI, denoted for the i th subject as X i , and Yϭhs-CRP, denoted for the i th subject as Y i .This is estimated for a sample of size n (iϭ1, . . ., n) using the following formula 1 :andHere, X indicates the sample mean of X (ϭBMI), and Y the sample mean of Y (ϭhs-CRP).The numerator of r reflects how BMI and hs-CRP co-vary, and the denominator reflects the variability of both BMI and hs-CRP about their respective sample means.