tbuckley/cabot-search huggingface dataset:
Risk Factors for 12-Month Comorbidity of Mood, Anxiety, and Substance Use Disorders: Findings From the Netherlands Mental Health Survey and Incidence Study
Authors: Ron de Graaf, Rob V. Bijl, Filip Smit, Wilma A.M. Vollebergh, J. Spijker
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study examined risk factor profiles of pure and comorbid 12-month mood, anxiety, and substance use disorder in the general population. METHOD: Data were derived from the Netherlands Mental Health Survey and Incidence Study, a prospective epidemiologic study in which a representative sample of 7,076 adults age 18–64 years were interviewed with the Composite International Diagnostic Interview. Logistic regression was used to compare subjects with a diagnosis of pure and comorbid disorders with nonpsychopathological comparison subjects and to compare subjects with comorbid disorders with those with pure disorder on sociodemographic characteristics, chronic somatic conditions, parental psychiatric history, and childhood traumas and adversities. RESULTS: Only 39.5% of the subjects with a 12-month mood disorder, 59.3% of those with an anxiety disorder, and 75.4% of those with a substance use disorder exhibited the disorder in the pure form. Comorbid anxiety and mood disorders, the most prevalent comorbid condition, showed associations with eight of the nine sociodemographic and long-term vulnerability factors investigated; pure mood disorder and pure anxiety disorder were each linked to only about half of the factors. Female gender, younger age, lower educational level, and unemployment were associated with comorbid anxiety and mood disorders but not with pure mood disorders. The risk profiles of pure anxiety disorder and pure substance use disorder similarly diverged from those of the comorbid conditions. CONCLUSIONS: High levels of psychiatric comorbidity exist in the general population. The risk factor profiles for comorbid disorders differ considerably from those for pure disorders. Primary prevention of secondary disorders in populations with a history of a primary disorder are important for reducing psychiatric burden.
VEGF Inhibits Tumor Cell Invasion and Mesenchymal Transition through a MET/VEGFR2 Complex
Authors: Kan V. Lu, Jeffrey P. Chang, Christine A. Parachoniak, Melissa M. Pandika, Manish K. Aghi, David Meyronet, Nadezda Isachenko, Shaun D. Fouse, Joanna J. Phillips, David A. Cheresh, Morag Park, Gabriele Bergers
Journal: Cancer Cell (2012)
Treating nerves: from anecdote to systematic review
Authors: R. A C Hughes
Journal: Journal of the Royal Society of Medicine (2003)

The principle that systematic reviews are the best evidence on which to base clinical practice seems so obvious that it is surprising that their methodology is so recent.It was only in 1979 that Archie Cochrane berated the medical profession for not constructing such reviews.In 1991 the UK Cochrane Centre was founded to respond to this challenge. 1n 1998 we founded the Cochrane Neuromuscular Disease Review Group to apply the principles and methods of the Cochrane Collaboration to peripheral nerve and muscle disease.In this article, examples principally from peripheral nerve diseases illustrate how our knowledge of the effectiveness of treatments has progressed from anecdotes or observational studies through randomized controlled trials to systematic reviews.
A prospective phase II study of L-asparaginase- CHOP plus radiation in newly diagnosed extranodal NK/T-cell lymphoma, nasal type
Authors: Ningjing Lin, Yuqin Song, Wen Zheng, Meifeng Tu, Yan Xie, Xiaopei Wang, Lingyan Ping, Zhitao Ying, Chen Zhang, Lijuan Deng, Weiping Liu, Jun Zhu
Journal: Journal of Hematology & Oncology (2013)

To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T -cell lymphoma (ENKTL), we conducted a prospective phase II study of L-asparaginase, cyclophosphamide, vincristine, doxorubicin and dexamethasone (CHOP-L) regimen in combination with radiotherapy.Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included 6-8 cycles of CHOP-L (cyclophosphamide, 750 mg/m(2) day 1; vincristine, 1.4 mg/m(2) day 1 (maximal dose 2 mg), doxorubicin 50 mg/m(2) day 1; dexamethasone 10 mg days 1-8; L-asparaginase 6000 u/m(2) days 2-8). Radiotherapy was scheduled after 4-6 cycles of CHOP-L regimen, depending on stage and primary anatomic site. The primary endpoint was complete response (CR) rate.A total of 38 eligible patients were enrolled. The median age was 40.5 years (range, 15 to 71 years). Their clinical characteristics were male to female ratio, 24:14; Ann Arbor stage I, 20; II, 11; III, 3; IV, 4. CR and overall response rates were 81.6% (95% CI, 69.3% to 93.9%) and 84.2%, respectively. With a median follow-up of 25 months, the 2-year overall survival, progression-free survival and disease-free survival rates were 80.1% (95%CI, 73.3% to 86.9%), 81% (95%CI, 74.5% to 87.5%) and 93.6% (95%CI, 89.3% to 97.9%), respectively. The major adverse events were myelosuppression, liver dysfunction, and digestive tract toxicities. Grade 3 to 4 leukopenia and neutropenia were 76.3% and 84.2%, respectively. No treatment-related death was observed.CHOP-L chemotherapy in combination with radiotherapy is a safe and highly effective treatment for newly diagnosed ENKTL.
Oral ulceration and Behcet's syndrome.
Authors: T Lehner
Journal: Gut (1977)

Progress reportOral ulceration and Behget's syndrome Ulcers in the mouth are common manifestations of many local or general disorders.Inadequate attention has been paid to the differential diagnosis of recurrent oral ulcers, perhaps because some of these ulcers may be trivial and they do not carry a threat of serious complications, as do ulcers in the gastrointestinal tract.However, a small but important proportion of patients suffer from frequent or continuous ulceration which causes severe pain, with associated difficulties in speaking and eating and loss of weight.Stomatology has been developing rapidly in this country, as a specialty concerned with the aetiology, differential diagnosis, pathogenesis, investigation, and management or oral disease.Ulceration is the most common lesion of the oral mucosa and the differential diagnosis can be complex.The frequent label of 'aphtha' to any oral ulcer is meaningless and can be harmful, as it may delay the diagnosis, at times, of a life-threatening disease.Recurrent oral ulcers are the most common lesions and they will be con- sidered with Beheet's syndrome, as there is no obvious line of division between focal oral ulcers and the multifocal involvement of different tissues.This syndrome is more common than was previously thought, if one allows for the definition of two or more major sites of involvement', especially with regard to oral and genital ulcers.The gastroenterological and haematological disorders will also be discussed, as considerable interest has been generated in the relationship between aphthous ulcers and those associated with ana- emia and malabsorption. Recurrent aphthous and herpetiform ulcersThere are three types of recurrent oral ulcers (ROU); the terms minor aph- thous ulcers (MiAU)2 was applied to 'aphthae'3 and major aphthous ulcers (MjAU) to the misleadingly named periadenitis mucosa necrotica recurrens lesion4.A third type have been termed herpetiform ulcers (HU)5.The differ- ential diagnosis of minor and major aphthous and herpetiform ulcers, based on a series of 210 patients, is presented in Table 16. EPIDEMIOLOGYThe prevalence ofROU varies with the population studied, but the most reliable data show that 20 1 % of a large hospital outpatient population and 10-6 % of patients in general practice have ROU7.Although a very high prevalence of 55 % was recorded in a student population8, if those with a doubtful history of ulcers were excluded8'9 the prevalence was 33'6 %.ROU is more often found in females than males, but the ratio varies from 2:1: to 1: 13 5-7,1.The ulcers may appear at any age; the highest frequency of onset of ROU is during the second decade and 67 % to 85 % of patients develop ROU in the first three decades5-7'O.It is noteworthy that ROU is common in children and the youngest child with MiAU observed by the author was 2 years of age.
Effect of pelvic floor muscle training during pregnancy and after childbirth on prevention and treatment of urinary incontinence: a systematic review
Authors: Siv Mørkved, Kari Bø
Journal: British Journal of Sports Medicine (2013)

Background Urinary incontinence (UI) is a common condition in women causing reduced quality of life and withdrawal from fitness and exercise activities. Pregnancy and childbirth are established risk factors. Current guidelines for exercise during pregnancy have no or limited focus on the evidence for the effect of pelvic floor muscle training (PFMT) in the prevention and treatment of UI. Aims Systematic review to address the effect of PFMT during pregnancy and after delivery in the prevention and treatment of UI. Data sources PubMed, CENTRAL, Cochrane Library, EMBASE and PEDro databases and hand search of available reference lists and conference abstracts (June 2012). Methods Study eligibility criteria: Randomised controlled trials (RCTs) and quasiexperimental trials published in the English language. Participants: Primiparous or multiparous pregnant or postpartum women. Interventions: PFMT with or without biofeedback, vaginal cones or electrical stimulation. Study appraisal and synthesis methods: Both authors independently reviewed, grouped and qualitatively synthesised the trials. Results 22 randomised or quasiexperimental trials were found. There is a very large heterogeneity in the populations studied, inclusion and exclusion criteria, outcome measures and content of PFMT interventions. Based on the studies with relevant sample size, high adherence to a strength-training protocol and close follow-up, we found that PFMT during pregnancy and after delivery can prevent and treat UI. A supervised training protocol following strength-training principles, emphasising close to maximum contractions and lasting at least 8 weeks is recommended. Conclusions PFMT is effective when supervised training is conducted. Further high-quality RCTs are needed especially after delivery. Given the prevalence of female UI and its impact on exercise participation, PFMT should be incorporated as a routine part of women's exercise programmes in general.
Chemotherapy for advanced lung cancer: is the glass half full or half empty?
Authors: G Silvestri
Journal: Thorax (2004)

Patients with advanced lung cancer should share in the decision whether or not to undergo chemotherapy

Pulmonologists have generally taken a nihilistic view of chemotherapy for the treatment of advanced lung cancer. In a study of beliefs among pulmonologists in the therapeutic treatment of lung cancer, Schroen and colleagues found that only one third of those surveyed believed that chemotherapy conferred a survival benefit for patients with stage IV non-small cell lung cancer and 35% said they would refer patients with metastatic cancer directly to a hospice without referral to medical oncology.1 A survey of British physicians also found that beliefs about the benefits of chemotherapy did not correspond with current medical knowledge and portrayed a more negative impression than the literature would indicate.2 There may be legitimate explanations for this difference in perception about outcomes for this patient population. As a group, respiratory physicians may not believe that the small survival benefit achieved with chemotherapy is enough to offset the toxicity associated with treatment. Perhaps we are biased against chemotherapy because we have seen the …
Tumor Suppressor Ras-Association Domain Family 1 Isoform A Is a Novel Regulator of Cardiac Hypertrophy
Authors: Delvac Oceandy, Adam Pickard, Sukhpal Prehar, Min Zi, Tamer M.A. Mohamed, Peter J. Stanley, Florence Baudoin-Stanley, Raja Nadif, Stella Tommasi, Gerd P. Pfeifer, Angel L. Armesilla, Elizabeth J. Cartwright, Ludwig Neyses
Journal: Circulation (2009)

Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy.A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A(-)(/)(-)) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A(-)(/)(-) mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras.Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway.
The Molecular Adapter Carma1 Controls Entry of IκB Kinase into the Central Immune Synapse
Authors: Hiromitsu Hara, Christopher Bakal, Teiji Wada, Denis Bouchard, Robert Rottapel, Takashi Saito, Josef M. Penninger
Journal: The Journal of Experimental Medicine (2004)

Carma1 (also known as caspase recruitment domain [CARD]11, Bimp3) is a CARD-containing membrane-associated guanylate kinase family protein that plays an essential role in antigen receptor–induced nuclear factor κB activation. We investigated the role of Carma1 in the assembly of signaling molecules at the immune synapse using a peptide-specific system. We report that Carma1 is essential for peptide-induced interleukin 2 and interferon γ production, but dispensable for proliferation in T cells. Recruitment and distribution of T cell receptor, lymphocyte function associated 1, lipid rafts, and protein kinase C (PKC)θ to central and peripheral immune synapse regions occur normally in Carma1−/− T cells. Carma1 controls entry of IκB kinase (IKK) into lipid raft aggregates and the central region of the immune synapse, as well as activation of IKK downstream of PKC. Our data provide the first genetic evidence on a new class of molecular scaffold that controls entry of defined signaling components, IKK, into the central supramolecular activation cluster at T cell–antigen-presenting cell interfaces without having any apparent effect on the overall organization and formation of immune synapses.
Glomerular Hyperfiltration and Renal Disease Progression in Type 2 Diabetes
Authors: Piero Ruggenenti, Esteban L. Porrini, Flavio Gaspari, Nicola Motterlini, Antonio Cannata, Fabiola Carrara, Claudia Cella, Silvia Ferrari, Nadia Stucchi, Aneliya Parvanova, Ilian Iliev, Alessandro Roberto Dodesini, Roberto Trevisan, Antonio Bossi, Jelka Zaletel, Giuseppe Remuzzi
Journal: Diabetes Care (2012)

To describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] ≥120 mL/min/1.73 m(2)), GFR decline, and nephropathy onset or progression in type 2 diabetic patients with normo- or microalbuminuria.We longitudinally studied 600 hypertensive type 2 diabetic patients with albuminuria <200 μg/min and who were retrieved from two randomized trials testing the renal effect of trandolapril and delapril. Target blood pressure (BP) was <120/80 mmHg, and HbA(1c) was <7%. GFR, albuminuria, and glucose disposal rate (GDR) were centrally measured by iohexol plasma clearance, nephelometry in three consecutive overnight urine collections, and hyperinsulinemic euglycemic clamp, respectively.Over a median (range) follow-up of 4.0 (1.7-8.1) years, GFR declined by 3.37 (5.71-1.31) mL/min/1.73 m(2) per year. GFR change was bimodal over time: a larger reduction at 6 months significantly predicted slower subsequent decline (coefficient: -0.0054; SE: 0.0009), particularly among hyperfiltering patients. A total of 90 subjects (15%) were hyperfiltering at inclusion, and 11 of 47 (23.4%) patients with persistent hyperfiltration progressed to micro- or macroalbuminuria versus 53 (10.6%) of the 502 who had their hyperfiltration ameliorated at 6 months or were nonhyperfiltering since inclusion (hazard ratio 2.16 [95% CI 1.13-4.14]). Amelioration of hyperfiltration was independent of baseline characteristics or ACE inhibition. It was significantly associated with improved BP and metabolic control, amelioration of GDR, and slower long-term GFR decline on follow-up.Despite intensified treatment, patients with type 2 diabetes have a fast GFR decline. Hyperfiltration affects a subgroup of patients and may contribute to renal function loss and nephropathy onset or progression. Whether amelioration of hyperfiltration is renoprotective is worth investigating.
Effects of Heat Stress on Thermoregulatory Responses in Congestive Heart Failure Patients
Authors: Jian Cui, Armin Arbab-Zadeh, Anand Prasad, Sylvain Durand, Benjamin D. Levine, Craig G. Crandall
Journal: Circulation (2005)

Background— Clinical observations suggest that tolerance to heat stress may be impaired in patients with cardiovascular diseases, particularly those associated with impaired ventricular function and congestive heart failure (CHF). However, thermoregulatory function during a controlled heat stress challenge in patients with CHF has not been studied. Methods and Results— To test the hypothesis that thermoregulatory responses are attenuated in such patients, we assessed cutaneous vasodilation and sweat rate in patients with stable class II–III CHF and in matched healthy subjects during passive whole-body heating. Whole-body heating induced a similar increase in internal temperature (≈0.85°C) in both groups. The sweating responses in patients with CHF were not significantly different from that in control subjects. In contrast, the elevation in forearm cutaneous vascular conductance in patients with CHF was reduced by nearly 50% relative to the control subjects (3.8±0.8 versus 6.9±1.0 mL/100 mL tissue per minute per 100 mm Hg, P =0.04). Moreover, maximal cutaneous vasodilator capacity to direct local heating in patients with CHF was also significantly lower than in control subjects, suggesting that vascular remodeling may be limiting cutaneous vasodilation during hyperthermia. Conclusions— These observations suggest that patients with CHF exhibit attenuated cutaneous vasodilator responses to both whole-body and local heating, whereas sweating responses are preserved. Attenuated cutaneous vasodilation may be a potential mechanism for heat intolerance in patients with CHF.
Cardiovascular RNA Interference Therapy
Authors: Wolfgang Poller, Juliane Tank, Carsten Skurk, Martina Gast
Journal: Circulation Research (2013)

Understanding of the roles of noncoding RNAs (ncRNAs) within complex organisms has fundamentally changed. It is increasingly possible to use ncRNAs as diagnostic and therapeutic tools in medicine. Regarding disease pathogenesis, it has become evident that confinement to the analysis of protein-coding regions of the human genome is insufficient because ncRNA variants have been associated with important human diseases. Thus, inclusion of noncoding genomic elements in pathogenetic studies and their consideration as therapeutic targets is warranted. We consider aspects of the evolutionary and discovery history of ncRNAs, as far as they are relevant for the identification and selection of ncRNAs with likely therapeutic potential. Novel therapeutic strategies are based on ncRNAs, and we discuss here RNA interference as a highly versatile tool for gene silencing. RNA interference-mediating RNAs are small, but only parts of a far larger spectrum encompassing ncRNAs up to many kilobasepairs in size. We discuss therapeutic options in cardiovascular medicine offered by ncRNAs and key issues to be solved before clinical translation. Convergence of multiple technical advances is highlighted as a prerequisite for the translational progress achieved in recent years. Regarding safety, we review properties of RNA therapeutics, which may immunologically distinguish them from their endogenous counterparts, all of which underwent sophisticated evolutionary adaptation to specific biological contexts. Although our understanding of the noncoding human genome is only fragmentary to date, it is already feasible to develop RNA interference against a rapidly broadening spectrum of therapeutic targets and to translate this to the clinical setting under certain restrictions.
[18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study
Authors: R.E. Ferner, J.F. Golding, M. Smith, E. Calonje, W. Jan, V. Sanjayanathan, M. O’Doherty
Journal: Annals of Oncology (2007)
Estimating Absolute Rates of Synonymous and Nonsynonymous Nucleotide Substitution in Order to Characterize Natural Selection and Date Species Divergences
Authors: T.-K. Seo
Journal: Molecular Biology and Evolution (2004)

The rate of molecular evolution can vary among lineages. Sources of this variation have differential effects on synonymous and nonsynonymous substitution rates. Changes in effective population size or patterns of natural selection will mainly alter nonsynonymous substitution rates. Changes in generation length or mutation rates are likely to have an impact on both synonymous and nonsynonymous substitution rates. By comparing changes in synonymous and nonsynonymous rates, the relative contributions of the driving forces of evolution can be better characterized. Here, we introduce a procedure for estimating the chronological rates of synonymous and nonsynonymous substitutions on the branches of an evolutionary tree. Because the widely used ratio of nonsynonymous and synonymous rates is not designed to detect simultaneous increases or simultaneous decreases in synonymous and nonsynonymous rates, the estimation of these rates rather than their ratio can improve characterization of the evolutionary process. With our Bayesian approach, we analyze cytochrome oxidase subunit I evolution in primates and infer that nonsynonymous rates have a greater tendency to change over time than do synonymous rates. Our analysis of these data also suggests that rates have been positively correlated.