tbuckley/cabot-search huggingface dataset:
The impact of signaling pathways stimulated by HER2 receptor on prediction of clinical outcome in metastatic breast cancer patients treated with trastuzumab
Authors: P. Grell, M. Svoboda, P. Fabian, L. Radova, M. Dziechciarkova, M. Palacova, R. Nenutil, M. Hajduch, R. Vyzula
Journal: Journal of Clinical Oncology (2008)

1048 Background: The overexpression of HER-2 (c-erbB2/Neu) in breast cancer is associated with poor prognosis, tumor recurrence and shortened survival. The administration of the trastuzumab significantly improves patients prognosis. However, in spite of these successful results, trastuzumab is effective only in 20–40% of cases. PI3K/Akt and Ras/MAPK signaling pathways are activated through HER-2 receptor and both play important role in tumor behavior. Methods: The study included 76 women with verified Her-2+ metastatic breast cancer (MBC) who were treated with trastuzumab based palliative chemotherapy. Immunohistochemistry was performed on formalin fixed, paraffin embedded tissue sections with antibodies against Akt-1, Akt-2, phospho(p)-Akt-Ser-473 and p-Akt-Thr-308, PTEN, S6K, p-S6K- Ser235/236, MAPK, p-MAPK-Thr202/Tyr204. Except PTEN, the cytoplasmatic and nuclear fractions were assessed separately. Results: Patients whose tumors showed high Akt-2 expression (≥ 80% positive cells) accompanied with nuclear and cytoplasmatic (n+c) positivity of a) p-Akt-473, b) p-Akt-308, c) or both p-Akts (p-Akt-473/308) exhibited improved TTP compared to those with any Akt-2 expression, but negative for nuclear staining of any p-Akt: a) TTP (13.1 vs 7.6 months; P<0.018, Hazard Ratio 2.09, CI95% 1.13- 3.5; b) TTP (17.1 vs 7.6 months; P<0.007, Hazard Ratio 2.41, CI95% 1.25–4.0; c) TTP (13.1 vs 7.6 months; P<0.028, Hazard Ratio 1.9, CI95% 1.12–3.49. Of the remaining results, only S6K kinase had significant impact on TTP. Activation of S6K was associated with shorter TTP. Median follow-up was 9.2 months. Conclusions: This study was the first to prove that prediction of the response to trastuzumab treatment depends on the Akt kinase iso-form, activity and compartmentalization. Patients, whose tumors had high level of Akt-2 and concurrent nuclear and cytoplasmatic presence of the activated forms of Akt kinase, had greater benefit from trastuzumab based therapy. In contrast, activation of S6K was associated with worse prognosis. Supported by the Internal Grant Agency of Ministry of Health, Czech Republic, No.NR/8335–3. No significant financial relationships to disclose.
The effects of physical fitness on lung function from childhood to adulthood - The Odense schoolchild study
Authors: Finn Rasmussen, Bob Hancox
Journal: European Respiratory Journal (2013)

The potential beneficial role of physical activity on the development of lung function is not well known. The present study is aimed to investigate the longitudinal association between physical fitness level and the development of lung function. 1369 children from the Odense schoolchild study (Denmark) were assessed from age 9 to 29 years. Physical fitness and lung function was tested at all occasions. In longitudinal analysis high physical fitness at age 9 years was associated a higher percent predicted FEV1, a higher ratio of FEV1/FVC from 9 to 29 years. Physical fitness at age 9 was associated with an absolute increase FVC up to age 21 adjusted for asthma, sex and smoking status and height increase from age 9. At age 29 years the associated between absolute increase FVC an fitness at age 9 did not reach statistically significance (p=0.1) when the increase in height from age 9 was taken into account.  In conclusion, high physical fitness levels at age 9 years predict a higher FEV1 and a higher FEV1/FVC ratio in young adulthood: An absolute increase in FVC was seen at age 15 and 29. This brings further evidence for a weak but beneficial effect of high physical activity in childhood on lung function in adulthood.
Lesson of the Week: Consultants' workload in outpatient clinics
Authors: D. Armstrong, M. Nicoll
Journal: BMJ (1995)

The impact on hospital resources of variability in referral rates among general practitioners was of concern throughout the 1980s. The overall number of patients referred to outpatient clinics, however, has increased only slowly since the NHS began; in contrast, the number of new outpatients seen by each hospital consultant has declined appreciably. Ironically, despite this decline, further increasing the number of consultants in now being presented as a solution to the demand for outreach clinics in general practice.
Response to: ‘The effects of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions were overestimated or not?’ by Zeng<i>et al</i>
Authors: Michael Callaghan, Matthew Parkes, David T Felson
Journal: Annals of the Rheumatic Diseases (2015)

As we noted in our paper reporting results of the BRACE trial,1 a trial of patellar bracing in patellofemoral osteoarthritis (OA), we did not use a placebo control because all such feasible controls recapitulated at least one mechanism of action of the patellar brace, and we were interested in examining whether any action of the brace might be therapeutic. Our means of demonstrating the effect of the brace was to examine compartment-specific bone marrow lesion (BML) change on MRI in addition …
Paired exome analysis of Barrett's esophagus and adenocarcinoma
Authors: Matthew D Stachler, Amaro Taylor-Weiner, Shouyong Peng, Aaron McKenna, Agoston T Agoston, Robert D Odze, Jon M Davison, Katie S Nason, Massimo Loda, Ignaty Leshchiner, Chip Stewart, Petar Stojanov, Sara Seepo, Michael S Lawrence, Daysha Ferrer-Torres, Jules Lin, Andrew C Chang, Stacey B Gabriel, Eric S Lander, David G Beer, Gad Getz, Scott L Carter, Adam J Bass
Journal: Nature Genetics (2015)
Changing trends in domiciliary non-invasive ventilation (NIV) set-up
Authors: Jumaa Bwika, Asad Ali, Olliver O'Sullivan, Ben Beauchamp, Rebecca D'Cruz, Kirstie Morley, Miriam Vaughan, Rahul Mukherjee
Journal: European Respiratory Journal (2013)

Introduction: Domiciliary NIV is being increasingly used to treat chronic ventilatory failure, particularly due to obesity and neuromuscular conditions. At the start of an NIV unit, most domiciliary NIVs are set up at the end of an acute admission with hypercapnic acidotic respiratory failure to start with, but over time, as more at-risk patients come under surveillance for respiratory failure, we hypothesized that a unit supervising domiciliary NIV/Home Mechanical Ventilation is expected to do more elective set-ups which are associated with better quality of life.  Methods: Comparison of the volume of new domiciliary NIV set-ups and the elective NIV set-up rate over two 12-month periods: Apr 2005-Mar 2006 (period 1) and Apr 2011-Mar 2012 (period 2) in a dedicated 11-bedded ward-based NIV unit (established: Aug 2004) in a 1000-bedded central England teaching hospital, providing domiciliary NIV support to >200 patients with >350 under surveillance for respiratory failure.  Results: The volume doubled from 19 new domiciliary NIV set-ups in period 1 to 39 new domiciliary NIV set-ups in period 2; the elective domiciliary NIV set-up rate increased from 7/19 (36.8%) to 19/39 (48.7%) between periods 1 and 2.  Discussion: Over time, both volume and elective set-up rate for new domiciliary NIV have gone up. This is due to that a larger proportion of people at risk of respiratory failure treatable with NIV are coming under the unit9s surveillance and has clearly been associated with the expansion and maturation of the NIV service. The 9elective domiciliary NIV set-up rate9 can therefore be tested as a metric for comparison of centres supervising domiciliary NIV/Home Mechanical Ventilation in this rapidly evolving field.
Poor association of allergen‐specific antibody, T‐ and B‐cell responses revealed with recombinant allergens and a <scp>CFSE</scp> dilution‐based assay
Authors: J. Eckl‐Dorna, R. Campana, R. Valenta, V. Niederberger
Journal: Allergy (2015)

The adaptive immunity underlying allergy comprises two components, the allergen-specific antibody (i.e. IgE, IgG) and the T-cell response. These two components are responsible for different disease manifestations and can be targeted by different therapeutic approaches. Here, we investigated the association of allergen-specific antibody and T- as well as B-cell responses in pollen-allergic patients using recombinant (r) major birch pollen allergen rBet v 1 and major timothy grass pollen allergen rPhl p 5 as defined antigens.Allergen-specific IgE and IgG antibody responses were determined by ELISA, and allergen-specific T- and B-cell responses were measured in peripheral blood mononuclear cells using a carboxyfluorescein-diacetate-succinimidylester (CFSE) dilution assay.CFSE staining in combination with T-cell- and B-cell-specific gating allowed discriminating between allergen-specific T-cell and B-cell responses. Interestingly, we identified patients where mainly T cells and others where mainly B cells proliferated in response to allergen stimulation. No association between the level of allergen-specific Ig responses and B- or T-cell proliferation was observed.Purified recombinant allergens in conjunction with CFSE staining allow the dissection of allergen-specific B- and T-cell responses. The dissociation of allergen-specific antibody, and B- and T-cell responses may explain the occurrence of selective IgE- and T-cell-mediated manifestations of allergic inflammation and may be important for the development of diagnostic and therapeutic strategies selectively targeting B cells and T cells.
Sorting by Reversals: Genome Rearrangements in Plant Organelles and Evolutionary History of X Chromosome
Authors: V Bafna, PA Pevzner
Journal: Molecular Biology and Evolution (1995)

Sequence comparison in computational molecular biology is a powerful tool for deriving evolutionary and functional relationships between genes. However, classical alignment algorithms handle only local mutations (i.e., insertions, deletions, and substitutions of nucleotides) and ignore global rearrangements (i.e., inversions and transpositions of long fragments). As a result, applications of sequence alignment in analyzing highly rearranged genomes (i.e., herpes viruses or plant mitochondrial DNA) are very limited and may lead to contradictions in molecular phylogeny studies since different genes give rise to different evolutionary trees. The paper addresses the problem of genome comparison versus classical gene comparison and presents algorithms to analyze rearrangements in genomes evolving by inversions. In the simplest form the problem corresponds to sorting by reversals, that is, sorting of an array using reversals of arbitrary fragments. We describe algorithms to analyze genomes evolving by inversions and discuss applications of these algorithms in molecular evolution.
Changes in inspiratory capacity and respiratory muscle strength after maximal exercise in pulmonary hypertension
Authors: Camila Oliveira, Marcelo Gazzana, Igor Benedetto, Marli Knorst, Danilo Berton
Journal: European Respiratory Journal (2014)

Background: Inspiratory capacity (IC) reduction indicates exercise dynamic hyperinflation (DH) in COPD patients, since inspiratory muscle pressure did not change during IC maneuvers. A proportion of patients with pulmonary hypertension (PH) exhibit IC decrement with exercise, suggesting DH. However, respiratory muscle strength is reduced in these patients, which could affect IC measurements.  Aims: Evaluate the behavior of respiratory muscle pressures and IC after exercise in PH.  Methods: Incremental cardiopulmonary exercise testing with serial measurements of IC was performed. Mouth occlusion maximal inspiratory (PImax) and expiratory (PEmax) pressures were measured before and after peak exercise.  Results: We evaluated 20 patients (15 with arterial PH and 5 with chronic thromboembolic PH; 85% females). They were 47.1±13.7 yrs old, presenting a mean pulmonary arterial pressure and pulmonary vascular resistance by right heart catheterization of 49.9±17.3mmHg and 7.8±5.2 Woods, respectively. PImax was 64.7±23.5 before and 61.9±23.7 cmH2O after exercise (p=0.20). Otherwise, PEmax decreased significantly after exercise (94.8±29.9 vs 80.6±25,4cmH2O; p  Conclusions: PImax did not significantly decrease after exercise and was not related to IC reduction. This data support a real DH in PH patients that show reduction in IC.
Re: Cancer Chemoprevention: Progress and Promise RESPONSE
Authors: F. L. Meyskens,, S. M. Lippman, J. J. Lee, A. L. Sabichi
Journal: JNCI Journal of the National Cancer Institute (1999)

Re: Cancer Chemoprevention: Progress and Promise The commentary by Lippman et al. (1) provides a useful review of the topic by organizing a massive amount of in- formation in an organized way. How- ever, because this review will be widely read and referenced, there are two gen- eral points made by the authors that could be challenged. The authors define two of the four criteria for identifying a “definitive” chemoprevention trial as “primary end point of cancer incidence” and “large scale (n 艌 1000) with the Journal of the National Cancer Institute, Vol. 91, No. 6, March 17, 1999 definitive sample size and duration based on anticipated event rates in the intervention arm (treatment effect) and placebo arm.” One major goal of chemoprevention research is to determine the protective effect of an agent while placing as few participants as possible at risk. One straightforward way to accomplish this goal is to understand the process of the disease (carcinogenesis) sufficiently to conduct trials with markers that predis- pose to or predict the final end point of cancer. In general, most histologically identifiable precancers (e.g., cervical in- traepithelial neoplasia, Barrett’s esopha- gus, adenoma polyps, actinic kerotoses, and dysplastic nevi) evolve to cancer with a sufficiently predictable frequency to conclude that their reversal or sup- pression can be used to predict cancer development and to assess the value of a chemoprevention agent. There are, in fact, as the authors note, several studies (2–6) that have addressed the effective- ness of chemoprevention in this manner. The medical community accepts hyper- tension and cholesterol as surrogate “preneoplasias” of cardiovascular dis- ease risk and their modulation as indica- tive of a favorable or unfavorable drug effect. Modulation of the pathobiology of precancers is as valid a marker of carcinogenesis as is the end point of can- cer. Undoubtedly, advances in our un- derstanding of carcinogenesis will allow us to identify and develop new agents by the modulation of a biochemical event earlier in the carcinogenic process and this should be a major goal of chemo- prevention research. Large numbers may provide comfort to the investigator that a definitive result has been obtained. However, there are many instances in medicine when large numbers were not required to make the point, i.e., where the underlying cause CORRESPONDENCE 563
Long term reduction of blood pressure in young and elderly hypertensive patients with sleep apnea syndrome treated with CPAP
Authors: Andra Elena Malaut, Oana Claudia Deleanu, Anca Donoaica, Ruxandra Ulmeanu, Florin Dumitru Mihaltan
Journal: European Respiratory Journal (2013)

INTRODUCTION: Guidelines added obstructive sleep apnea(OSA) as important cause of hypertension(HT) but the reduction of blood pressure(BP) values under CPAP treatment is controversial,without long term follow up.  AIM: We studied difference between young(  METHOD: We applied exclusion criteria(hypoventilation syndromes, respiratory dysfunctions, other secondary HT, modifying treatment during study, noncompliant patients) to 96 patients(Chi test,T-test).  RESULTS: We studied remaining 30 patients:14 young ,16 elderly, without significant differences regarding AHI and somnolence. Diastolic BP(DBP) measured by sphygmomanometer was significantly lower after CPAP treatment in young (from 85.0±12.5 to 71.4±6.9mmHg,p=0.028 after 3 months, to 70.0±7.0mmHg,p=0.038 after 6 months),without differences regarding systolic blood pressure(SBP). Elderly had a reduction in SBP (knowing to be connected with age) and DBP after 3 months(from 141.2±8.3 to 123.6±15.9mmHg,p=0.019, respectively from 80.0±9.2 to 66.2±7.4mmHg, p=0.006),without any differences after 6 months of CPAP. Measured by ABPM elderly patients had a significant decrease only of minimum nocturnal values of DBP from 55.3±6.3 to 47.5±5.7mmHg after 3 months, p=0.021. There was no modification regarding the dipper pattern at 3 or 6 months.  CONCLUSION: There is a significant reduction in DBP in both young and elderly OSA patients under CPAP treatment measured by sphygmomanometer only, more pronounced in the first 3 months.
Faecal calprotectin levels and colorectal neoplasia Reply
Authors: W G BRYDON
Journal: Gut (2001)

Editor,—We read with interest the paper by Kronborg and colleagues ( Gut 2000: 46 :795–800)—a large multicentre study measuring faecal calprotectin levels in high risk populations for colorectal neoplasia.

The authors did not discuss their results in comparison with those of Roseth and colleagues1 or Kristinsson and colleagues2 who did the ground breaking work in this area and where calprotectin levels were shown to be far higher in patients with colonic polyps and cancer compared with normal controls (table 1).

View this table:

Table 1 
Median and range calprotectin levels …
Tracking the naturally occurring mutations across the full-length genome of hepatitis B virus of genotype D in different phases of chronic e-antigen-negative infection
Authors: S. Ghosh, R.K. Mondal, P. Banerjee, M. Nandi, S. Sarkar, K. Das, A. Santra, S. Banerjee, A. Chowdhury, S. Datta
Journal: Clinical Microbiology and Infection (2012)
High prevalence of respiratory symptoms and obstructive airways diseases among employees of the 9sanitation department9 in an Indian city
Authors: Monica Barne, Renuka Gaikwad, Komalkirti Apte, Sunayana Shinde, Jyoti Londhe, Priyanka Choudhary, Yogesh Thorat, Sapna Madas, Archana Rao, Sundeep Salvi
Journal: European Respiratory Journal (2014)

Introduction : An estimated 1.2 million people in India are employed in sanitation departments as street sweepers, garbage collectors, garbage transporters and sewer cleaners who are exposed to several organic and inorganic air pollutants. There is little knowledge about the lung health of this population. Aim:  To study the respiratory health of employees of the 9Sanitation Department9 from Pune city in India. Methods:  All employees who came for the health check-up were administered a respiratory health questionnaire, examined by a medical doctor and underwent Spirometry according to ATS/ERS 2005 guidelines. Results:  Of the 166 (M=72, F=94) employees examined, 127 were street sweepers and 39 were others (garbage, sewers and administration). 38.6% of employees had some respiratory symptom (Runny/blocked nose=17.5%, cough 15%, Chest pain/tightness=15%, shortness of breath=14.5%, Headache=14.5%, wheezing/whistling from chest=13.85%, Sinusitis=2.4%). Compared to street sweepers, employees in other occupations had a significantly higher prevalence of cough [11.02% Vs 28.21% (p= 0.02)] and wheeze [7.9% Vs 23.08% (p= 0.02)]. Prevalence of obstructive airways diseases (OADs) (FEV1/FVC 25-75%  Conclusion:  Employees of the sanitation department had a high prevalence of respiratory symptoms, OADs and SAOs. Although prevalence of respiratory symptoms was higher in other occupations; street sweepers were at a higher risk of having SAOs.
Immunity, inflammation, and cancer: an eternal fight between good and evil
Authors: Shabnam Shalapour, Michael Karin
Journal: Journal of Clinical Investigation (2015)

Cancer development and its response to therapy are strongly influenced by innate and adaptive immunity, which either promote or attenuate tumorigenesis and can have opposing effects on therapeutic outcome. Chronic inflammation promotes tumor development, progression, and metastatic dissemination, as well as treatment resistance. However, cancer development and malignant progression are also associated with accumulation of genetic alterations and loss of normal regulatory processes, which cause expression of tumor-specific antigens and tumor-associated antigens (TAAs) that can activate antitumor immune responses. Although signals that trigger acute inflammatory reactions often stimulate dendritic cell maturation and antigen presentation, chronic inflammation can be immunosuppressive. This antagonism between inflammation and immunity also affects the outcome of cancer treatment and needs to be considered when designing new therapeutic approaches.
Vitamin D3 associated to lactobacillus reuteri improves effects of allergen immunotherapy in asthmatic children
Authors: Vincenzo Patella, Giovanni Florio, Mario Palmieri
Journal: European Respiratory Journal (2013)

BACKGROUND: The possibility of additional strategies to enhance the effectiveness of specific immunotherapy (SIT) is highly attractive. The aim of our study was to assess the influence vitamin D(3) associated or not to Lactobacillus Reuteri in asthmatic children on the SIT efficacy.  METHODS: It was a randomized, double-blind, placebo-controlled trial conducted in 112 asthmatic children allergic to house dust mites. Intervention was based on receiving a dose/weight of vitamin D (3) associated to Lactobacillus Reuteri (VD3R+) or no Lactobacillus Reuteri (VDR3R-) or placebo during SIT. We compared in these 3 arms: eosinophil cationic protein (ECP), fractionated exhaled nitric oxide (FeNO), asthma symptoms and medication scores.  RESULTS: After 12 months of SIT, in the group treated with VD3R+ a control of asthma9s symptoms was observed of 24% better than VD3R- group. However, a 50% reduction was observed in the control group. Serum ECP levels decreased significantly in the SIT group with VD3R+ (P = .01 and P = .018) compared to baseline, whereas VD3R- group vs control group values remained similar. We found a statistically significant difference in two group between median pre- and post treatment FeNO levels but better in VD3R+ treated group [22.5 ppb (16.0-29.0 ppb) vs 15.6 ppb (11.8-26.4 ppb), p=0.008], as well as in asthma symptoms (P=0 .001) and medication scores (P=0.001).  CONCLUSIONS: SIT with D. pteronyssinus improves immunological and clinical parameters in mite-allergic asthmatic children after 1 year of treatment. Vitamin D(3) associated to Lactobacillus Reuteri increases clinical effects of SIT on asthma better than without Lactobacilli Reuteri.
Early routine follow-up chest radiographs for pneumonia are not useful
Authors: J Sembatya
Journal: Thorax (2008)

This study investigated the clinical value of chest radiographs during the 4-week period after diagnosis of severe community acquired pneumonia (CAP) in immune competent hospitalised patients. The time to resolution of pulmonary infiltrates and other radiographic abnormalities caused by infection was compared with resolution of clinical parameters, and factors associated with …