tbuckley/cabot-search huggingface dataset:
Aerobic training decreases bronchial hyperresponsiveness and systemic inflammation in patients with moderate or severe asthma: a randomised controlled trial
Authors: Andrezza França-Pinto, Felipe A R Mendes, Regina Maria de Carvalho-Pinto, Rosana Câmara Agondi, Alberto Cukier, Rafael Stelmach, Beatriz M Saraiva-Romanholo, Jorge Kalil, Milton A Martins, Pedro Giavina-Bianchi, Celso R F Carvalho
Journal: Thorax (2015)

Background The benefits of aerobic training for the main features of asthma, such as bronchial hyperresponsiveness (BHR) and inflammation, are poorly understood. We investigated the effects of aerobic training on BHR (primary outcome), serum inflammatory cytokines (secondary outcome), clinical control and asthma quality of life (Asthma Quality of Life Questionnaire (AQLQ)) (tertiary outcomes). Methods Fifty-eight patients were randomly assigned to either the control group (CG) or the aerobic training group (TG). Patients in the CG (educational programme+breathing exercises ( sham )) and the TG (same as the CG+aerobic training) were followed for 3 months. BHR, serum cytokine, clinical control, AQLQ, induced sputum and fractional exhaled nitric oxide (FeNO) were evaluated before and after the intervention. Results After 12 weeks, 43 patients (21 CG/22 TG) completed the study and were analysed. The TG improved in BHR by 1 doubling dose (dd) (95% CI 0.3 to 1.7 dd), and they experienced reduced interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) and improved AQLQ and asthma exacerbation (p&lt;0.05). No effects were seen for IL-5, IL-8, IL-10, sputum cellularity, FeNO or Asthma Control Questionnaire 7 (ACQ-7; p&gt;0.05). A within-group difference was found in the ACQ-6 for patients with non-well-controlled asthma and in sputum eosinophil and FeNO in patients in the TG who had worse airway inflammation. Conclusions Aerobic training reduced BHR and serum proinflammatory cytokines and improved quality of life and asthma exacerbation in patients with moderate or severe asthma. These results suggest that adding exercise as an adjunct therapy to pharmacological treatment could improve the main features of asthma. Trial registration number NCT02033122.
Rheumatoid arthritis and herpes zoster: risk and prevention in those treated with anti-tumour necrosis factor therapy
Authors: K. L. Winthrop, D. E. Furst
Journal: Annals of the Rheumatic Diseases (2010)

In this issue of Annals of Rheumatic Diseases , Garcia-Doval and colleagues add to a flurry of recent studies examining the risk and outcomes of herpes zoster (HZ) among those patients who use anti-tumour necrosis factor (TNF) therapies. While the increased risk of infection due to granulomatous and select other intracellular pathogens has been clearly demonstrated in this setting,1,–,3 much less is clear with regard to viral pathogens.4 The reactivation of varicella zoster virus (HZ or shingles) is of public health concern given HZ's ability to cause substantial long-term pain, depression and disability due to postherpetic neuralgia (PHN).4 5 HZ is common; approximately one-third of the population will experience it during their lifetime, with 18% of cases resulting in PHN and 10% to 15% involving ocular tissues with potential for permanent visual loss. Rarely, HZ can disseminate and cause systemic complications and death, a risk heightened by HIV infection and other forms of severe immunosuppression.6 7 HZ rates increase substantially with age, as cell-mediated immunity to varicella virus wanes and as comorbidities associated with immunosuppression become more common. In the USA, HZ incidence rates range between 4 and 11/1000 patient-years in patients aged 50 and 80 years, respectively, with rates higher in women.6 7

Recently, a live-attenuated vaccine to prevent HZ (Zostavax, Merck, Whitehouse Station, New Jersey, USA) has been developed and approved for use in patients age 60 years or older, regardless of their HZ or varicella history.7 For rheumatologists, who frequently treat immunosuppresed individuals within this age group, the questions begin here: are my patients at increased risk for HZ due to their disease or their therapies? Should I avoid anti-TNF …
Satellite Cell Dysfunction and Impaired IGF-1 Signaling Cause CKD-Induced Muscle Atrophy
Authors: Liping Zhang, Xiaonan H. Wang, Huiling Wang, Jie Du, William E. Mitch
Journal: Journal of the American Society of Nephrology (2010)

Muscle wasting in chronic kidney disease (CKD) begins with impaired insulin/IGF-1 signaling, causing abnormal protein metabolism. In certain models of muscle atrophy, reduced satellite cell function contributes to atrophy, but how CKD affects satellite cell function is unknown. Here, we found that isolated satellite cells from mice with CKD had less MyoD, the master switch of satellite cell activation, and suppressed myotube formation compared with control mice. In vivo, CKD delayed the regeneration of injured muscle and decreased MyoD and myogenin expression, suggesting that CKD impairs proliferation and differentiation of satellite cells. In isolated satellite cells from control mice, IGF-1 increased the expression of myogenic genes through an Akt-dependent pathway. CKD impaired Akt phosphorylation in satellite cells after muscle injury. To test whether impaired IGF-1 signaling could be responsible for decreased satellite cell function in CKD, we created an inducible IGF-1 receptor knockout mouse and found impaired satellite cell function and muscle regeneration. In addition, both CKD and IGF-1 receptor knockout mice developed fibrosis in regenerating muscles. Taken together, impaired IGF-1 signaling in CKD not only leads to abnormal protein metabolism in muscle but also impairs satellite cell function and promotes fibrosis in regenerating muscle. These signaling pathways may hold potential therapeutic targets to reduce CKD-related muscle wasting.
Systematic qualitative review of randomised trials conducted in nonsmall cell lung cancer with a noninferiority or equivalence design
Authors: Marianne Paesmans, Bogdan Grigoriu, Sebahat Ocak, Martine Roelandts, Jean-Jacques Lafitte, Stéphane Holbrechts, Thierry Berghmans, Anne-Pascale Meert, Luigi Moretti, Sophie Danyi, Françoise Pasleau, Lieveke Ameye, Alain Van Meerhaeghe, Jean-Paul Sculier
Journal: European Respiratory Journal (2014)

The use of noninferiority randomised trials for patients with advanced non-small cell lung cancer has emerged during the past 10–15 years but has raised some issues related to their justification and methodology. The present systematic review aimed to assess trial characteristics and methodological aspects. All randomised clinical trials with a hypothesis of noninferiority/equivalence, published in English, were identified. Several readers extracted a priori defined methodological information. A qualitative analysis was then performed. We identified 20 randomised clinical trials (three phase II and 17 phase III), 11 of them being conducted in strong collaboration with industry. We highlighted some deficiencies in the reports like the lack of justification for both the noninferiority assumption and the definition of the noninferiority margin, as well as inconsistencies between the results and the authors' conclusions. CONSORT guidelines were better followed for general items than for specific items (p&lt;0.001). Improvement in the reporting of the meth"odology of noninferiority/equivalence trials is needed to avoid misleading interpretation and to allow readers to be fully aware of the assumptions underlying the trial designs. They should be restricted to limited specific situations with a strong justification why a noninferiority hypothesis is acceptable.
Effect of Race on the Outcome of Pediatric Patients With Hodgkin's Lymphoma
Authors: Monika L. Metzger, Sharon M. Castellino, Melissa M. Hudson, Shesh N. Rai, Sue C. Kaste, Matthew J. Krasin, Larry E. Kun, Ching-Hon Pui, Scott C. Howard
Journal: Journal of Clinical Oncology (2008)

Purpose Some cooperative groups have found a survival disadvantage in black children with various childhood cancers. We examine the effects of race on clinical outcomes among children with Hodgkin's lymphoma (HL) treated with contemporary therapy at a tertiary care children's hospital. Patients and Methods Retrospective analysis of 327 children and adolescents diagnosed with HL between 1990 and 2005. Patients were treated with risk-directed multimodal therapy regardless of race, ethnicity, or ability to pay. Event-free and overall survival rates were compared for black and white children. Clinical characteristics, socioeconomic factors, and biologic features were analyzed for prognosis of treatment failure. Results The 262 white and 65 black patients did not differ significantly in presenting features, clinical characteristics, or enrollment in a clinical trial. More black patients (71% v 45%) resided in poor counties (P &lt; .001). While black and white children were equally likely to have progressive disease or early relapse, black children were 3.7 times (95% CI, 1.7 to 8.0) more likely to relapse 12 months or more after diagnosis. The 5-year event-free survival was 71% ± 6.1% (SE) for black and 84% ± 2.4% for white children (P = .01). However, the 5-year survival rate did not differ between white and black children (94.4% v 94.7%). While black race and low hemoglobin concentration were independent predictors of treatment failure, only low hemoglobin concentration independently predicted poor survival. Conclusion Black children with Hodgkin's lymphoma have lower event-free survival than white children, but both populations have the same 5-year overall survival.
Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer
Authors: Jennifer S. Temel, Joseph A. Greer, Alona Muzikansky, Emily R. Gallagher, Sonal Admane, Vicki A. Jackson, Constance M. Dahlin, Craig D. Blinderman, Juliet Jacobsen, William F. Pirl, J. Andrew Billings, Thomas J. Lynch
Journal: New England Journal of Medicine (2010)

Patients with metastatic non-small-cell lung cancer have a substantial symptom burden and may receive aggressive care at the end of life. We examined the effect of introducing palliative care early after diagnosis on patient-reported outcomes and end-of-life care among ambulatory patients with newly diagnosed disease.We randomly assigned patients with newly diagnosed metastatic non-small-cell lung cancer to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Quality of life and mood were assessed at baseline and at 12 weeks with the use of the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively. The primary outcome was the change in the quality of life at 12 weeks. Data on end-of-life care were collected from electronic medical records.Of the 151 patients who underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better quality of life than did patients assigned to standard care (mean score on the FACT-L scale [in which scores range from 0 to 136, with higher scores indicating better quality of life], 98.0 vs. 91.5; P=0.03). In addition, fewer patients in the palliative care group than in the standard care group had depressive symptoms (16% vs. 38%, P=0.01). Despite the fact that fewer patients in the early palliative care group than in the standard care group received aggressive end-of-life care (33% vs. 54%, P=0.05), median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, P=0.02).Among patients with metastatic non-small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival. (Funded by an American Society of Clinical Oncology Career Development Award and philanthropic gifts; ClinicalTrials.gov number, NCT01038271.)
Genetic Association Analysis of Serotonin System Genes in Bipolar Affective Disorder
Authors: John B. Vincent, Mario Masellis, Jacob Lawrence, Victor Choi, Hugh M.D. Gurling, Sagar V. Parikh, James L. Kennedy
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: This study examined the putative role of serotonin genes in the etiology of bipolar affective disorder. METHOD: Genetic association analysis was performed for individuals with bipolar affective disorder and unaffected subjects closely matched in age, sex, and ethnic background (N=103 in each group). The allele and genotype frequencies of polymorphisms at the genes for serotonin receptors HTR1A, HTR1Dα, HTR1Dβ, HTR2A, HTR2C, HTR7, tryptophan hydroxylase (TPH), and the serotonin transporter (hSERT) were compared in the two groups of subjects. RESULTS: Statistically significant positive associations were found for HTR2A and hSERT polymorphisms. However, results from an independent replication group of over 100 patients with bipolar affective disorder and their matched comparison subjects failed to confirm these associations. CONCLUSIONS: These results suggest that the serotonin genes studied are not associated with bipolar affective disorder, although transmission disequilibrium studies are required in order to confirm this conclusion.
Skeletal Morbidity in Childhood Acute Lymphoblastic Leukemia
Authors: Karen Mandel, Stephanie Atkinson, Ronald D. Barr, Paul Pencharz
Journal: Journal of Clinical Oncology (2004)

Purpose Treatment for acute lymphoblastic leukemia (ALL) in childhood results in a reduction in bone mineral density (BMD). Whether there is a recovery of this lost bone mass in survivors of ALL is not known. We sought to determine if changes in BMD are common long-term sequelae in children with ALL. Methods Bone mineral densitometry of the lumbar spine and femoral neck was performed on 106 patients. The results were compared with those of age-matched normal controls. The effect of treatment was examined in those with low BMD compared with the remainder of the study group. Results When data were tested with respect to age, sex, and age and sex, no difference was observed in BMD between survivors of childhood ALL and controls. In the subgroup of patients with low BMD, the difference was not related to age, age at diagnosis, or years since diagnosis. Low BMD of the spine was not explained by radiotherapy (RT), methotrexate (MTX) dose, or corticosteroid dose. Low BMD of the femur was not explained by RT. However, those with low femoral BMD were more likely to have received high-dose MTX or higher-dose corticosteroids compared with the remainder of the group. Conclusion It appears that survivors of childhood ALL as a whole recover normal BMD. However, those patients who received a total MTX dose of greater than 40,000 mg/m 2 or a total corticosteroid dose of greater than 9,000 mg/m 2 may not recover normal BMD and therefore should be screened for decreased BMD of the femoral neck.
Physical examination of the adult patient with respiratory diseases: inspection and palpation
Authors: B Maitre, T Similowski, JP Derenne
Journal: European Respiratory Journal (1995)

Inspection of the thorax identifies the breathing position adopted by the patient, the shape of the thorax, the dynamics of respiration (breathing pattern, symmetry of expansion, mechanics and synchrony of rib cage and abdominal movements). Inspection of the neck adds useful information, particularly with respect to the dynamics of breathing. Palpation ascertains the signs suggested by inspection with respect to the mechanics of breathing. It also assesses the state of the pleura and pulmonary parenchyma by studying the tactile fremitus. It integrates extrarespiratory signs, such as enlarged lymph nodes or breast abnormalities. Extrathoracic respiratory signs should also be systematically looked for, including cyanosis, finger deformation, pulsus paradoxus, and pursed lips breathing. Interobserver agreement about respiratory signs has repeatedly been studied, and generally found to be low, as are clinical-functional correlations. However, some data on chronic obstructive pulmonary disease (COPD), asthma or pulmonary embolism are available. From the description of some signs and the current knowledge about their operative values, it appears that much clinical research remains necessary to better define the precise diagnostic value of a given sign. The impact of training on diagnostic performance also has to be defined. Both of these aspects should allow clinicians to optimize the way in which they use their hands and eyes to conduct respiratory diagnosis, as well as the way they teach respiratory symptomatology.
Acquired resistance of human T cells to sulfasalazine: stability of the resistant phenotype and sensitivity to non-related DMARDs
Authors: J van der Heijden
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> A recent study from our laboratory showed that induction of the multidrug resistance related drug efflux pump ABCG2 contributed to acquired resistance of human T cells to the disease modifying antirheumatic drug (DMARD) sulfasalazine (SSZ). <b>Objectives:</b> To investigate the duration of SSZ resistance and ABCG2 expression after withdrawal of SSZ and rechallenging with SSZ, and to assess the impact of SSZ resistance on responsiveness to other DMARDs. <b>Methods:</b> Human CEM cells (T cell origin) with acquired resistance to SSZ (CEM/SSZ) were characterised for (<i>a</i>) SSZ sensitivity and ABCG2 expression during withdrawal and rechallenge of SSZ, and (<i>b</i>) antiproliferative efficacy of other DMARDs. <b>Results:</b> ABCG2 protein expression was stable for at least 4 weeks when CEM/SSZ cells were grown in the absence of SSZ, but gradually declined, along with SSZ resistance levels, to non-detectable levels after withdrawal of SSZ for 6 months. Rechallenging with SSZ led to a rapid (&lt;2.5 weeks) resumption of SSZ resistance and ABCG2 expression as in the original CEM/SSZ cells. CEM/SSZ cells displayed diminished sensitivity to the DMARDs leflunomide (5.1-fold) and methotrexate (1.8-fold), were moderately more sensitive (1.6–2.0 fold) to cyclosporin A and chloroquine, and markedly more sensitive (13-fold) to the glucocorticoid dexamethasone as compared with parental CEM cells. <b>Conclusion:</b> The drug efflux pump ABCG2 has a major role in conferring resistance to SSZ. The collateral sensitivity of SSZ resistant cells for some other (non-related) DMARDs may provide a further rationale for sequential mono- or combination therapies with distinct DMARDs upon decreased efficacy of SSZ.
De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development
Authors: Juan R. Alvarez-Dominguez, Zhiqiang Bai, Dan Xu, Bingbing Yuan, Kinyui Alice Lo, Myeong Jin Yoon, Yen Ching Lim, Marko Knoll, Nikolai Slavov, Shuai Chen, Peng Chen, Harvey F. Lodish, Lei Sun
Journal: Cell Metabolism (2015)
Plasma immunoreactive beta-melanocyte-stimulating hormone and skin pigmentation in chronic renal failure.
Authors: A G Smith, S Shuster, J S Comaish, N A Plummer, A J Thody, F Alvarez-Ude, D N Kerr
Journal: BMJ (1975)

Plasma immunoreactive beta-melanocyte stimulating hormone (beta-MSH) concentrations were greatly increased in patients with chronic renal failure. There was no correlation between the severity of the renal failure or the degree of pigmentation and the plasma beta-MSH levels.
Mesenchymal gene program–expressing ovarian cancer spheroids exhibit enhanced mesothelial clearance
Authors: Rachel A. Davidowitz, Laura M. Selfors, Marcin P. Iwanicki, Kevin M. Elias, Alison Karst, Huiying Piao, Tan A. Ince, Michael G. Drage, Judy Dering, Gottfried E. Konecny, Ursula Matulonis, Gordon B. Mills, Dennis J. Slamon, Ronny Drapkin, Joan S. Brugge
Journal: Journal of Clinical Investigation (2014)

Metastatic dissemination of ovarian tumors involves the invasion of tumor cell clusters into the mesothelial cell lining of peritoneal cavity organs; however, the tumor-specific factors that allow ovarian cancer cells to spread are unclear. We used an in vitro assay that models the initial step of ovarian cancer metastasis, clearance of the mesothelial cell layer, to examine the clearance ability of a large panel of both established and primary ovarian tumor cells. Comparison of the gene and protein expression profiles of clearance-competent and clearance-incompetent cells revealed that mesenchymal genes are enriched in tumor populations that display strong clearance activity, while epithelial genes are enriched in those with weak or undetectable activity. Overexpression of transcription factors SNAI1, TWIST1, and ZEB1, which regulate the epithelial-to-mesenchymal transition (EMT), promoted mesothelial clearance in cell lines with weak activity, while knockdown of the EMT-regulatory transcription factors TWIST1 and ZEB1 attenuated mesothelial clearance in ovarian cancer cell lines with strong activity. These findings provide important insights into the mechanisms associated with metastatic progression of ovarian cancer and suggest that inhibiting pathways that drive mesenchymal programs may suppress tumor cell invasion of peritoneal tissues.
Worldwide Epidemiology of Atrial Fibrillation
Authors: Sumeet S. Chugh, Rasmus Havmoeller, Kumar Narayanan, David Singh, Michiel Rienstra, Emelia J. Benjamin, Richard F. Gillum, Young-Hoon Kim, John H. McAnulty, Zhi-Jie Zheng, Mohammad H. Forouzanfar, Mohsen Naghavi, George A. Mensah, Majid Ezzati, Christopher J.L. Murray
Journal: Circulation (2013)

Background— The global burden of atrial fibrillation (AF) is unknown. Methods and Results— We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5–22.2 million] and 12.6 million women [95% UI, 12.0–13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8–19.3) in men and 18.9% (95% UI, 15.8–23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8–612.7) and 359.9 in women (95% UI, 334.7–392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2–78.5) and 43.8 in women (95% UI, 35.9–55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4–636.7) in men and 373.1 (95% UI, 347.9–402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2–95.4) in men and 59.5 (95% UI, 49.9–74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0–2.2) and 1.9-fold (95% UI, 1.8–2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data. Conclusions— These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.