tbuckley/cabot-search huggingface dataset:
Does selection bias explain increases in pneumoconiosis observed in United States coal miners
Authors: Edward Petsonk, Eva Suarthana, Anthony Laney, Anita Wolfe, Janet Hale, Nicole Edwards, Michael Attfield
Journal: European Respiratory Journal (2011)

Background:  Radiographic surveillance among U.S. coal miners showed declining tenure-specific disease prevalence until 2000, when abnormalities consistent with coal workers9 pneumoconiosis (CWP) and progressive massive fibrosis (PMF) began to increase. Some have suggested the increase may be due to selection bias in the surveillance programs.   Methods:  For the period 2006-2009, results from the routine health surveillance program (in which costs of radiographs are paid by industry) were compared with results of a government-funded enhanced surveillance program utilizing a mobile examination unit stationed in mining regions. Observed disease prevalence was stratified by region and by mining tenure, and compared between participants in the two programs.   Results:  Overall, participants in the routine and enhanced surveillance programs were similar for participation rate, mining location (surface/underground), gender, and race/ethnicity. Participants in the enhanced program were older (47.1 vs 36.4 yr), had longer tenure (21.8 vs 11.4 yr), and higher prevalence of abnormal radiographs (3.9% vs 1.9%) compared to the routine program. However, among miners with at least 20 years of mining, rates of both CWP (6.1% vs 7.0%) and PMF (1.1% vs 0.9%) were similar for participants in the enhanced and routine surveillance programs, respectively.   Conclusions:  Tenure-specific prevalences in the routine and enhanced surveillance programs were similar, indicating that selection bias does not explain the recent increases in CWP and PMF among U.S. miners. Previous reports have implicated increased lung deposition of respirable dust and silica as explanations for the ongoing pneumoconiosis problem.
Nasal Hypersensitivity in Wood Furniture Workers
Authors: B. Wilhelmsson, Y. Jernudd, E. Ripe, K. Holmberg
Journal: Allergy (1984)

Occupational nasal allergies caused by moulds and wood dust were extensively studied in six wood furniture factories. The concentration of moulds, wood dust and endotoxins was registered and occasionally high values were found. Paccilomyces spec, was the most common mould. Answers to a special questionnaire showed that 16% (42/268) of the wood workers with a mean exposure time of 12 years had a history compatible with hypersensitivity in the upper airways associated with their work. Calculations based on skin prick tests and provocation tests with relevant allergens showed that the wood furniture workers had an incidence of allergy to moulds in 3% and to wood dust in 2%. Most of the workers (5/7) sensitive to moulds and/or woods were also skin prick sensitive to other allergens. No statistical difference concerning the presence of precipitating antibodies against mould and wood antigens could be registered between workers with discomfort and workers without symptoms.
Ninety-six-hour paclitaxel infusion after progression during short taxane exposure: a phase II pharmacokinetic and pharmacodynamic study in metastatic breast cancer.
Authors: A D Seidman, D Hochhauser, M Gollub, B Edelman, T J Yao, C A Hudis, P Francis, D Fennelly, T A Gilewski, M E Moynahan, V Currie, J Baselga, W Tong, M O'Donaghue, R Salvaggio, L Auguste, D Spriggs, L Norton
Journal: Journal of Clinical Oncology (1996)

PURPOSE A phase II trial of paclitaxel infused over 96 hours in patients with metastatic breast cancer with demonstrated disease progression (PD) during short-infusion taxane treatment was performed to evaluate schedule-dependent activity with prolonged drug exposure. The tolerability of this strategy and its pharmacokinetic profile and pharmacodynamic correlates were also investigated. PATIENTS AND METHODS Paclitaxel was administered to 26 patients with metastatic breast cancer at 120 to 140 mg/m2 intravenously over 96 hours. Twenty-three patients had demonstrated PD while receiving prior 3-hour paclitaxel, two during 1-hour docetaxel, and one during infusions of docetaxel and then paclitaxel. Twenty-one patients (81%) had no prior response to the short taxane infusion (primary resistance) and five (19%) had prior partial responses (PRs) of brief duration before PD (secondary resistance). Plasma paclitaxel concentrations were assessed at 24, 48, 72, and 96 hours. RESULTS After delivery of 195 cycles, seven of 26 assessable patients (26.9%; 95% confidence interval, 11.6% to 47.8%) had major objective responses, with a median response duration of 6 months (range, 1 to 13). The predominant toxicities were neutropenia (76% grade &gt; or = 3) and stomatitis (15% grade &gt; or = 3). Despite omission of premedications, no significant hypersensitivity reactions occurred. The median steady-state paclitaxel concentration (Css) in 23 assessable patients was 0.047 mumol/L (range, .023 to .176). Patients who experienced grade 4 neutropenia had significantly decreased paclitaxel clearance and higher Css than those with grade 1 to 3 neutropenia (P &lt; .05). Pretreatment elevation of hepatic transaminases was associated with delayed clearance (P &lt; .01) and increased myelo-suppression and mucosal toxicity. CONCLUSION Paclitaxel demonstrates activity against metastatic breast cancer when administered over 96 hours to patients with disease that recently had progressed during short taxane exposure. Delayed paclitaxel clearance and consequent increased toxicity occurred in patients with hepatic dysfunction. The activity observed supports preclinical data that suggest variability in efficacy and resistance patterns to paclitaxel based on duration of exposure.
OC-071 Facilitation of human cortical swallowing pathways by stimulation of the cerebellum
Authors: V Jayasekeran, J Rothwell, S Hamdy
Journal: Gut (2010)

<h3>Introduction</h3> Animal studies1 have suggested that the cerebellum plays an important role in the control of swallowing. Moreover human brain imaging studies have reported the activation of the cerebellum in the process of swallowing.2 In this study, we probed the interaction between cerebellum and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can be excited to induce pharyngeal activity, and also to elucidate if stimulation of the cerebellum can modulate cortical swallowing circuitry in the motor system. <h3>Methods</h3> Healthy volunteers (n=16, 8 males, mean age=32) underwent TMS measurements of pharyngeal EMG recorded from a swallowed intra luminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm where active or sham TMS conditioning pulses over the cerebellum were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at interstimulus intervals (ISIs) of 3, 5, 9, 20, 50, 100 and 200 ms allocated randomly, and the cortical responses were then assessed (compared to baseline and sham) for change in amplitude using T-tests. <h3>Results</h3> Stimulation of the cerebellum over the midline or either hemisphere evoked distinct EMG responses in the pharynx. There was a trend towards cerebellar hemispheric stimulation eliciting greater pharyngeal responses (mean amplitude 55.5±6.9 mV) than cerebellar midline stimulation (42.8±5.9 mV); p=0.08. Following active preconditioning cerebellar stimulation, the cortically evoked responses were facilitated with maximal effects at ISIs of 50–200 ms (p&lt; 0.05); in Abstract 019 figure, an effect was not seen with sham preconditioning. <h3>Conclusion</h3> This novel study demonstrates that cerebellar stimulation can evoke direct motor responses within the pharynx, and when excited with TMS, can modulate cortical swallowing motor pathways. These findings are in keeping with the animal literature suggesting a facilitatory role for the cerebellum in regulating swallowing and raises the possibility that excitatory neurostimulation of the cerebellum may be therapeutically useful in promoting recovery of dysphagia after brain damage.
The Parker B. Francis Fellowship Program
Authors: Thomas R. Martin, Deborah L. Snapp, Diane M. Tomita
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The Parker B. Francis (PBF) Fellowship Program has supported more than 750 M.D., M.D./Ph.D., and Ph.D. fellows since 1976, but there is little information about the effectiveness of the program in fostering successful careers and producing important research.Objectives: To survey all past PBF Fellows to obtain information about their productivity and career pathways.Methods: We obtained e-mail addresses for 526 (74%) of the 712 PBF awardees from 1976 to 2006, then sent an e-mail survey to the 526 past fellows and received 365 replies (69% response rate, 49% overall). Survey questions addressed time in research, areas of research, current position and responsibilities, and research funding.Measurements and Main Results: Seventy percent of the 365 respondents spend 25% or greater effort in research and 56% report 50% or more effort in research. Respondents have published an average of 2.7 peer-reviewed publications per year, totaling more than 15,678 peer-reviewed publications, of which 1,875 appeared in high-impact journals. Respondents have received more than $1.8 billion in direct research funding since their PBF Fellowships began. Ph.D. awardees spend more time in research than M.D. awardees, and current research effort did not differ by gender. PBF awardees have become prominent leaders in universities, the National Institutes of Health, health care, and industry.Conclusions: The PBF Program has been highly successful in producing a large number of scientific and clinical leaders in pulmonary and critical care medicine. The results provide comprehensive data about the success of this career development program and provide a model for programs designed to build the workforce in pulmonary and critical care medicine.
Correlation between single items in COPD assessment test (CAT) and outcome parameters of pulmonary rehabilitation (PR)
Authors: Rainer Gloeckl, Inga Heinzelmann, Katrin Beutel, Andreas Jerrentrup, Klaus Kenn
Journal: European Respiratory Journal (2013)

Background  The COPD Assessment Test (CAT) is a short, validated and simple to use quality of life questionnaire that assesses the impact of COPD on health status. The CAT sum score is well validated. Correlations between single items have not been investigated yet.  Objective  Aim of this prospective study was to identify correlations between single items of the CAT and standard outcome parameters of PR like exercise capacity, physical activity and health related quality of life.  Methods  50 COPD-patients (60±8 ys, FEV1: 32±9%pred., DLCO: 36±18%pred.) performed a 6-minute walking test, activity monitoring (72 hours) and completed the CAT, SGRQ and HADS.  Results  Prior to PR, CAT item “cough” correlated best with SGRQ category “symptoms” (r=0.42, p=0.004; post PR: r=0.49, p=0.001), item “breathless when walking” with SGRQ “symptoms” (r=0.37, p=0.01; post PR best correlation with 6MWD: r=-0.35, p=0.01), item “limitations doing activities at home” with SGRQ “activity” (r=0.52, p 0.0001). Weak but significant correlations were found post PR between steps per day and item “limitations doing activities at home” (r=-0.38, p=0.01) and “confident leaving my home” (r=-0.32, p=0.03).  Conclusion  Categories of SGRQ and HADS showed the best accordance to single items of the CAT score. It was possible to allocate some of the CAT questions to the measured outcome parameters.
Addressing the Complexity of Chronic Obstructive Pulmonary Disease
Authors: Alvar Agusti, Patricia Sobradillo, Bartolomé Celli
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Chronic obstructive pulmonary disease (COPD) is a complex disease at the clinical, cellular, and molecular levels. However, its diagnosis, assessment, and therapeutic management are based almost exclusively on the severity of airflow limitation. A better understanding of the multiple dimensions of COPD and its relationship to other diseases is very relevant and of high current interest. Recent theoretical (scale-free networks), technological (high-throughput technology, biocomputing), and analytical improvements (systems biology) provide tools capable of addressing the complexity of COPD. The information obtained from the integrated use of those techniques will be eventually incorporated into routine clinical practice. This review summarizes our current knowledge in this area and offers an insight into the elements needed to progress toward an integrated, multilevel view of COPD based on the novel scientific strategy of systems biology and its potential clinical derivative, P4 medicine (Personalized, Predictive, Preventive, and Participatory).
Calculated prostate cancer volume greater than 4.0 cm3 identifies patients with localized prostate cancer who have a poor prognosis following radical prostatectomy or external-beam radiation therapy.
Authors: A V D'Amico, R Whittington, S B Malkowicz, D Schultz, I Kaplan, C J Beard, J E Tomaszewski, A A Renshaw, K R Loughlin, J P Richie, A Wein
Journal: Journal of Clinical Oncology (1998)

PURPOSE Patients with palpable extraprostatic disease (T3) have a poor prostate-specific antigen (PSA) failure-free (bNED) survival rate after radical prostatectomy (RP) or external-beam radiation therapy (RT). This study was performed to validate or refute the prognostic value of the previously defined calculated prostate cancer volume (cV(Ca)). PATIENTS AND METHODS For patients with clinically localized disease (T1c,2), a Cox regression multivariable analysis was used to assess the ability of the cV(Ca) value to predict time to posttherapy PSA failure following RP or RT. RESULTS The cV(Ca) value was a significant predictor (P &lt; or = .0005) of time to posttherapy PSA failure in both an RP and RT data set independent of the one used to derive the cV(Ca)-based clinical staging system. In both RP- and RT-managed patients, estimates of 3-year bNED survival were not statistically different for patients with either T1c,2 disease and a cV(Ca) greater than 4.0 cm3 (RP, 27%; RT, 18%) or T3 disease (RP, 37%; RT, 34%). Despite pathologic T2 disease, the 3-year estimate of bNED survival was at most 51% in RP-managed patients with T1c,2 disease and cV(Ca) greater than 4.0 cm3. CONCLUSION A cV(Ca) greater than 4.0 cm3 identified patients with T1c.2 disease whose bNED survival was poor after RT or RP despite pathologic T2 disease that suggests the presence of occult micrometastatic disease in many of these patients. Prospective randomized trials to evaluate the impact on survival of adjuvant systemic therapy in these high-risk patients are justified.
Phase III Trial of Interferon Alfa-2a With or Without 13-cis-Retinoic Acid for Patients With Advanced Renal Cell Carcinoma
Authors: Robert J. Motzer, Barbara A. Murphy, Jennifer Bacik, Lawrence H. Schwartz, David M. Nanus, Tania Mariani, Patrick Loehrer, George Wilding, Diane L. Fairclough, David Cella, Madhu Mazumdar
Journal: Journal of Clinical Oncology (2000)

PURPOSE: A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNα2a) is superior to IFNα2a alone in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Two hundred eighty-four patients were randomized to treatment with IFNα2a plus 13-CRA or treatment with IFNα2a alone. IFNα2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless ≥ grade 2 toxicity occurred, in which case dose escalation was stopped. Patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFNα2a. Quality of life (QOL) was assessed. RESULTS: Complete or partial responses were achieved by 12% of patients treated with IFNα2a plus 13-CRA and 6% of patients treated with IFNα2a (P = .14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P = .03). Nineteen percent of patients treated with IFNα2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFNα2a alone (P = .05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P = .26). QOL decreased during the first 8 weeks of treatment, and a partial recovery followed. Lower scores were associated with the combination therapy. CONCLUSION: Response proportion and survival did not improve significantly with the addition of 13-CRA to IFNα2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFNα2a therapy in patients with IFNα2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.
Mycosis fungoides and the Sézary syndrome: a review of pathogenesis, diagnosis, and therapy.
Authors: T M Kuzel, H H Roenigk, S T Rosen
Journal: Journal of Clinical Oncology (1991)

Mycosis fungoides (MF) and the Sézary syndrome (SS) are non-Hodgkin's lymphomas with a T-cell phenotype, which have cutaneous involvement as their predominant feature. These disorders are becoming more common, and the patients are frequently being referred to medical oncologists for assistance in management. The development of advanced laboratory techniques, such as molecular genetics and cell-surface phenotyping, has greatly enhanced our understanding of their pathogenesis and may lead to identification of responsible etiologic factors. A myriad of treatment options have been investigated including topical approaches, systemic chemotherapy, and external radiation. Currently, extensive trials are underway examining the potential benefits of agents such as the interferons, interleukin-2, monoclonal antibodies, the retinoids, 2-chlorodeoxyadenosine, and other novel biologic response modifiers or chemotherapeutics. Although all these therapies have benefit in phase II trials, few randomized comparative trials have been performed to identify optimal therapies. Performance of such trials should now become a priority.
Small-interfering RNA targeted at antiapoptotic mRNA increases keratinocyte sensitivity to apoptosis
Authors: G. Lerman, E. Volman, Y. Sidi, D. Avni
Journal: British Journal of Dermatology (2010)

Gene silencing RNA interference technology concentrates on downregulation of gene expression using specific double-stranded RNA molecules (small-interfering RNA, siRNA), which induce the degradation of complementary mRNA. SiRNA therapeutics is currently being tested in several clinical trials. Skin disorders are an attractive target for siRNA-based technology because effective agents can be delivered by topical application. In several inflammatory skin disorders, the barrier function of the skin is markedly impaired and this may increase the delivery efficiency. Psoriasis is a very common skin disorder. The characteristics of this disorder are abnormal keratinocyte proliferation and inflammation. Keratinocytes from psoriatic epidermis express much higher levels of the antiapoptotic protein, Bcl-xL, compared with normal keratinocytes. Insulin-like growth factor 1 receptor (IGF-1R) plays a major role in cell growth, differentiation and apoptosis in many cell types, including keratinocytes and IGF-1R activation plays an important role in the pathogenesis of psoriasis. Keratinocytes from patients with psoriasis are more susceptible to IGF-1-stimulated proliferation compared with normal keratinocytes. IGF-1R is expressed by proliferating basal and suprabasal keratinocytes and is more abundant in psoriatic lesions.To prove the validity of IGF-1R and Bcl-xL as useful targets for siRNA-based therapeutics and to deliver siRNA selectively and efficiently to primary human keratinocytes; this is a primary essential step in the development of siRNA.Primary normal human keratinocytes were transfected with various siRNA molecules, and transfection efficiency was monitored by fluorescent labelling. Cell growth and apoptosis induction were evaluated in the transfected cells.We were able to deliver efficiently siRNA targeting Bcl-xL or IGF-1R to primary human keratinocyte cultures. We also showed that siRNAs targeting Bcl-xL and IGF-1R induce growth inhibition, apoptosis and increased sensitivity to ultraviolet B in keratinocytes.The present findings demonstrate that Bcl-xL and IGF-1R are valid, important targets for siRNA-based technology directed at the suppression of keratinocyte hyperproliferation.
New cases of HIV in India could fall by 38% with early ART and better retention, finds study
Authors: Cheryl Travasso
Journal: BMJ (2015)

Starting antiretroviral therapy (ART) early in India could reduce new infections by 18% and AIDS mortality by 9%, a study has found. Better retention in care could reduce new cases by 38% over the next 20 years.

The study used dynamic compartmental modelling to compare early ART initiation (at CD4 counts of ≤500 cells/mm3) with delayed ART initiation (CD4 count ≤350 cells/mm3), under both ideal and realistic conditions of care.1

In 2011 over two million Indian people were estimated to have HIV/AIDS.2 Current practice in India is to initiate ART when CD4 counts drop to …
Resolvin D1 attenuates lung inflammation in LPS induced-ALI partly through PPARγ/NF-κB pathway
Authors: Zenglin Liao, Jiajia Dong, Tao Wang, Fuqiang Wen
Journal: European Respiratory Journal (2011)

Objective:  Acute Lung Injury (ALI) is characterized by tissue damage and respiratory failure with uncontrolled inflammation. Since docosahexaenoic acid (DHA) and DHA-derived lipid mediators have recently been shown to possess anti-inflammatory and pro-resolving properties, we sought to investigate the effect of a novel DHA-derived mediator termed resolvin D1 (RvD1) on LPS-induced ALI.   Methods:  BALB/c mice were randomly divided into seven groups: saline group; RvD1 (600ng) group; LPS group; LPS+RvD1 (300ng) group; LPS+RvD1 (600ng) group; GW9662 (a PPARγ antagonist) group; LPS+RvD1 (600ng) + GW9662 group. LPS (50ug/mouse in 100ul saline) or saline was instilled intratracheally. RvD1 was injected intravenously 24h and 30min before LPS instillation. GW9662 was injected intravenously 30min before RvD1 injection. Mice were killed at 6, 12, and 24h. BALF samples were collected for cell counts and cytokine analysis. Lung tissues were collected for histological analysis and western blot analysis.   Results:  RvD1 significantly decreased total leukocyte counts by 44±7%, and also reduced TNF-α, IL-6 expression levels in BALF in comparison to the LPS group (p   Conclusions:  These results suggest that RvD1 may attenuate lung inflammation of LPS-induced ALI through suppressing NF-κB activation, which is partly dependent on PPARγ activation.