tbuckley/cabot-search huggingface dataset:
Proposed 7.4% cut in public health budget threatens antismoking and antiobesity initiatives, leader says
Authors: M. Limb
Journal: BMJ (2015)

Public health leaders have warned that the UK Treasury risks causing a “disaster” to people’s health in England if it implements cuts of £200m (€280m; $320m) to local authorities’ public health budgets by March 2016.

The Faculty of Public Health said that services covering children’s health, obesity, drug treatment, and sexual health could be badly affected. It said that an estimated “flat rate” cut of around 7.4% applied to public health budgets across the country would worsen existing health inequalities.

The faculty’s president, John Ashton, said on 22 June, “No matter where people live in England these cuts are a potential disaster for their health and healthcare.” He warned that there could be increases in unplanned pregnancies and drug related crime if people could not access sexual health or drug treatment services. “Even people …
Use of a US population-based survey to describe the relationship of COPD and co-morbidities
Authors: Roy Pleasants, Harry Herrick, Winston Liao, Janet Croft, Jill Ohar
Journal: European Respiratory Journal (2011)

The Behavioral Risk Factor Surveillance System (BRFSS) is a US state-based survey that includes 90+ questions on health issues primarily related to chronic diseases. In 2007 and 2009, 6 questions were added to the North Carolina (NC) BRFSS to describe the prevalence and impact of COPD. In the 2009 NC BRFSS, there were 12,337 adults who completed the survey and 993 reported they had been diagnosed with COPD. The age-adjusted prevalence of COPD was > 5%. The age-adjusted relative risk (RR, 95% CI) for 7 chronic diseases were compared between COPD and non-COPD: arthritis (1.64, 1.46-1.84); diabetes mellitus (1.76,1.39-2.24); myocardial infarction (2.58, 2.0-3.33); coronary artery disease (CAD) (3.49, 2.5-4.9); stroke (2.04, 1.53-2.74); kidney disease (2.85, 1.89-4.3); current asthma (7.5, 6.24-9.0); 3+ of these co-morbidities (4.95, 3.93-6.3). About 1 in 5 persons with COPD had 3 or more of these co-morbidities compared to 1 in 40 persons without COPD. One of the 6 BRFSS questions in 2009 addressed the use of prednisone in the prior year in persons with COPD. The RR of prednisone use in COPD patients with any of the co-morbidities were: arthritis 1.15 (0.89-1.48); diabetes mellitus 0.73 (0.47-1.11); myocardial infarction 1.0 (0.6-1.68); CAD 1.86 (1.02-3.38); stroke 1.28 (0.67-2.43); kidney disease 1.77 (0.77-4.07); current asthma 1.48 (1.08-2.03); 3+ of these co-morbidities 1.44 (0.95-2.2). Increased prednisone use in concurrent asthma and COPD is expected whereas increased likelihood of receiving prednisone in patients with concurrent COPD and CAD is an unexpected finding, possibly related to severity of disease in these patients.
The Structural Characterization and Antigenicity of the S Protein of SARS-CoV
Authors: Jingxiang Li, Chunqing Luo, Yajun Deng, Yujun Han, Lin Tang, Jing Wang, Jia Ji, Jia Ye, Fanbo Jiang, Zhao Xu, Wei Tong, Wei Wei, Qingrun Zhang, Shengbin Li, Wei Li, Hongyan Li, Yudong Li, Wei Dong, Jian Wang, Shengli Bi, Huanming Yang
Journal: Genomics Proteomics & Bioinformatics (2003)

Abstract The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets.
Accelerated lung function decline increases the risk of lung cancer
Authors: Pablo Sanchez, Juan P. de-Torres, Juan Bertó, Pilar Rivera, Arantzazu Campo, Jorge Zagaceta, Ana B. Alcaide, Javier Zulueta
Journal: European Respiratory Journal (2013)

Impaired lung function (LF) has been described as an important risk factor for lung cancer (LC). However, most studies assess LC risk based on LF status at baseline rather than on its change over time. Data on the relationship between LF progression and LC risk is limited.  The cohort is from an ongoing LC screening program using low-dose chest CT scans held at our institution. Between 2000 and 2012, active and former smokers ≥40 years of age, with at least 10 pack-years of smoking, and with a baseline and at least 2 additional annual pulmonary function tests were selected. Individual mean annual changes in FEV1 (in ml and % predicted) and in FEV1/FVC were calculated using linear regression. Cox proportional hazards method was used to assess the association between LC and different rates of LF decline.  A total of 362 subjects met the inclusion criteria (Table 1). Mean annual declines were 37±66 ml, 0.2±2 units and 0.5±1, for FEV1 (ml), FEV1% predicted and FEV1/FVC, respectively. Thirteen cancer diagnoses were made. The Cox analysis showed significant hazard ratios (HR) at higher rates of decline (Table 2). Significant HR were observed for declines >80 ml/year, >2 units of FEV1% predicted and >1 unit of FEV1/FVC (p  Accelerated LF decline appears to be an important risk factor for LC and could be useful when selecting high risk subjects suitable for LC screening.
Profibrotic cytokine TGF-β1 increases endothelial progenitor cell angiogenic properties
Authors: Solene Evrard, Clement d'Audigier, Laetitia Mauge, Dominique Israel-Biet, Anne-Marie Fischer, Pascale Gaussem, David Smadja
Journal: European Respiratory Journal (2012)

Background: TGF-β1 is a profibrotic cytokine that plays a major role in vascular biology, and is known to regulate the phenotype and activity of various vascular cell populations. Because most fibrotic diseases, such as Idiopathic Pulmonary Fibrosis (IPF), are associated with vascular remodeling and since endothelial progenitor cells may be involved in this process, we investigated the impact of TGF-β1 modulation of endothelial progenitor cell angiogenic properties.  Patients/ methods: TGF-β1 plasma levels were determined in 64 patients with IPF and compared to controls. The effect of TGF-β1 on angiogenesis was studied in vivo in a Matrigel plug model and in vitro on Endothelial Colony Forming Cells (ECFCs). We studied the effects of inhibiting the expression of the three main receptors of TGF-β1 in ECFCs using siRNA.  Results: Total TGF-β1 plasma levels were significantly increased in patients with IPF compared to controls (P   Conclusions: TGF-β1 is pro-angiogenic in vivo and induces ECFC angiogenic properties in vitro, suggesting that TGF-β1 may play a role during vascular remodeling in fibrotic disease states via endothelial progenitor cells.
Folate Deficiency Due to Giardiasis
Authors: N S Ambrose, S Hutchison, J Tejan
Journal: Journal of the Royal Society of Medicine (1989)

Giardiasis is an unusual cause of symptoms in this country in anyone who has not travelled abroad. Symptoms may be vague and the diagnosis unclear until the protozoan is discovered. We report an unusual case of anaemia with an unusual history and a satisfactory outcome following intensive investigation.
How do patterns of wheeze change over the first 14 years of life
Authors: Anina Pescatore, Marie-Pierre Strippoli, Ben Spycher, Caroline Beardsmore, Erol Gaillard, Claudia Kuehni
Journal: European Respiratory Journal (2012)

Aim: 

Only few studies described changes in clinical patterns of wheeze in children over a wide age range. This study aimed to describe reported symptom patterns in children with wheeze from age 1 to 14 yrs, focusing on indicators of wheeze severity and triggers of attacks.

Methods: 

In a population-based cohort study in Leicestershire, UK, we assessed prevalence of parent-reported wheeze and associated symptoms at ages 1, 2, 4, 6, 9 and 14 yrs. We analyzed variables related to severity (frequency of wheezing attacks, shortness of breath, sleep disturbance and activity disturbance due to wheeze) and triggers of wheeze (colds, exercise, food, contact with aeroallergens) in the past 12 months.

Results: 

The prevalence of wheeze decreased from 36% (1446/4035) at age 1 to 16% (471/3003) at age 6 years and remained stable thereafter. Among children with wheeze the proportion with frequent attacks (≥4) changed little from age 1 (35%) to 14 years (32%) and so did prevalence of activity disturbance, sleep disturbance, wheeze associated with colds and food-induced attacks. In contrast, the following symptoms became more frequent with increasing age: shortness of breath (increasing from 54% at age 1 to 85% at age 14), wheeze apart from colds (32% to 61%), exercise-induced attacks (26% to 71%) and aeroallergen-induced wheeze (6% to 50%).

Conclusion: 

We found significant age-related changes in wheezing patterns from infancy to adolescence. When designing questionnaires and planning studies, such differences in patterns of wheezing illness by age should to be taken into account.

Funding: SNF PDFMP3-123162, SNF 3200B0-122341, Asthma UK 07/048.
More reasons why private practice is unethical
Authors: D. Oliver
Journal: BMJ (2015)

Dean should be commended for rethinking his personal priorities and realising that private practice doesn’t chime with his values.1 Most of those who have responded are doctors who do private work. Those who don’t do any have nothing to justify. This article was written in the context of the UK health system—where less than 10% of healthcare is private; which has universal coverage; and which is high on access, value …
Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα
Authors: C Bueno, J L Sardina, B Di Stefano, D Romero-Moya, A Muñoz-López, L Ariza, M C Chillón, A Balanzategui, J Castaño, A Herreros, M F Fraga, A Fernández, I Granada, O Quintana-Bustamante, J C Segovia, K Nishimura, M Ohtaka, M Nakanishi, T Graf, P Menendez
Journal: Leukemia (2015)
CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
Authors: F Cichocki, S Cooley, Z Davis, T E DeFor, H Schlums, B Zhang, C G Brunstein, B R Blazar, J Wagner, D J Diamond, M R Verneris, Y T Bryceson, D J Weisdorf, J S Miller
Journal: Leukemia (2015)
Pseudotumoral lung tuberculuosis – A controversed clinical and imagistic entity
Authors: Ovidiu Burlacu, Voicu Voiculescu, Gabriel Cozma, Iris Miron, Calin Tunea, Ioan Petrache, Dorin Vancea, Voicu Tudorache, Alexandru Nicodin
Journal: European Respiratory Journal (2011)

Objectives: Our aim is to signal the frequent existence of a clinical and imagistic entity inside the thoracic surgical pathology, easily mistaken preop. for lung cancer – the pseudotumoral lung TB.

Method: Our clinic's experience in the surgery of tuberculosis is limited by the existence of an outside compartment, specialized in these types of surgeries. Between 2001–2010 we had 196 cases with postoperative diagnosis of TB. From these 196 cases we selected only 64 cases of tuberculomas, that had imagistic and clinical aspect of a lung malignant tumor.

All of these patients were admitted with a symptomatology unlike lung TB – weight loss, fatigue, hemoptysis, no fever, no previous infections or contact with TB patients, negative bronchoscopy, sputum cultures and Quantiferon test (3 patients). The CT images showed round tumoral formations, with poor limits and pathological mediastinal lymph nodes.

![Figure][1] 



Results: From the 64 cases we had 9 lobectomies, 1 bilobectomy and 54 wedge resections. We had complications in 5 cases, one postoperative clot, 4 cases with prolonged air leaks that were treated by connecting to a water seal. The mortality was 0.

Conclusions: Lung TB resembles more frequently to lung cancer, both by localization in the lung and by clinical and imagistic aspect of the lesions, making a preoperative diagnosis extremely difficult. Wedge resections are very efficient in the surgical treatment of lung TB.

 [1]: pending:yes
Abstract IA10: Kinase-impaired BRAF mutations as predictors of resistance and sensitivity
Authors: Faye Johnson, Banibrata Sen, Tuhina Mazumdar, Shaohua Peng, Humam Kadara, Lixia Diao, Lauren Byers
Journal: Clinical Cancer Research (2015)

Abstract Non-small cell lung cancer (NSCLC) is a common and rapidly fatal cancer for which targeted therapies have been markedly effective in only about 15% of patients - specifically those with EGFR mutations or EML4-ALK translocations. During a clinical trial of the multi-targeted tyrosine kinase inhibitor dasatinib we identified a patient with stage IV NSCLC who harbored a novel BRAF mutation (Y472C), had a near complete radiographic response to the multitargeted kinase inhibitor dasatinib as sole therapy and remained without active cancer 7 years following treatment. We discovered that Y472CBRAF is a kinase-inactivating BRAF mutation (KIBRAF). BRAF mutations can result in increased or decreased BRAF kinase activity, as well as kinase-neutral mutations, and occur in 8% of NSCLC and many other tumor types. We found that NSCLC cells that harbor KIBRAF undergo senescence when exposed to the dasatinib whereas NSCLC patients and cell lines with wild type BRAF are resistant to dasatinib. Transfection of other NSCLC cells with KIBRAF mutations also increased their dasatinib sensitivity, whereas transfection with an activating BRAF mutation led to their increased dasatinib resistance. NSCLC cells transfected with Y472CBRAF exhibited CRAF, MEK, and ERK activation. Currently there are no well-defined, canonical pathways that explain the observed dasatinib-induced senescence in NSCLC cells with KIBRAF. Dasatinib inhibits the activity of 40 distinct kinase targets and can induce BRAF-CRAF dimerization and CRAF activation in cells with activated RAS or KIBRAF mutations. To investigate the mechanism leading to senescence we performed reverse phase protein arrays to simultaneously examine the expression of 137 proteins and phosphoproteins and gene expression arrays. This approach was limited by the existence of only two NSCLC cell lines with KIBRAF but nonetheless we determined that dasatinib induced DNA damage and subsequently activated DNA repair pathways and the HIPPO signaling pathway only in NSCLC cells with KIBRAF. We are currently conducting a clinical trial for NSCLC patients with KIBRAF mutations to determine the efficacy of dasatinib in these patients prospectively. Citation Format: Faye Johnson, Banibrata Sen, Tuhina Mazumdar, Shaohua Peng, Humam Kadara, Lixia Diao, Lauren Byers. Kinase-impaired BRAF mutations as predictors of resistance and sensitivity. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr IA10.
Ultrasonic Nebulization for Efficient Delivery of Surfactant in a Model of Acute Lung Injury
Authors: R. SCHERMULY, T. SCHMEHL, A. GÜNTHER, F. GRIMMINGER, W. SEEGER, D. WALMRATH
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We investigated the effect of ultrasonic nebulization versus instillation of exogenous surfactant on gas exchange abnormalities provoked by detergent inhalation in perfused rabbit lungs. Ventilation-perfusion (VA/Q) distribution was assessed by the multiple inert gas elimination technique. For nebulization of natural bovine surfactant (Alveofact), an ultrasonic device was placed in line with the inspiratory gas flow tubing, manufacturing particles with a mass median aerodynamic diameter of approximately 4.5 microM and high aerosol concentration. In vitro studies demonstrated biochemical and biophysical integrity of postnebulization surfactant. Lung aerosol deposition was monitored by a laser-photometric technique. In lungs with sham inhalation of saline, tracheal instillation of surfactant (approximately 11 mg/kg body weight, infused over 50 min) provoked substantial VA/Q mismatch and limited shunt flow, whereas lung surfactant deposition by ultrasonic nebulization (approximately 7 to 9 mg/kg body weight; nebulization time, 50 min) did not interfere with physiologic gas exchange. Tween 20 inhalation provoked severe VA/Q mismatch with predominant shunt-flow (approximately 21%). This was not reversed by "rescue" application of instilled surfactant, but largely reversed by nebulized surfactant (shunt reduced to 5.5%; p < 0.01). Analysis of postaerosol lavage fluid demonstrated partial reconstitution of surface activity by nebulized surfactant. We conclude that ultrasonic nebulization may be employed for efficient delivery of functionally intact natural surfactant to the distal bronchoalveolar space. This approach effects rapid improvement of gas exchange in a model of acute homogeneous lung injury.
Rhinosinusitis in children: Seasonality and etiology
Authors: Elena Radtsig, Evgeniya Selkova, Anastasiya Lapitskaya, Lubov Malygina
Journal: European Respiratory Journal (2014)

Introduction. It9s believed that rhinosinusitis (RS) is one of the most desease that has viral etiology. Even though there is a lack of statistical data about what percentage of cases and what kind of virus causes the development of RS.  Aims. The purpose of our research was determining the frequency of RS throw out a calendar year and identifying the leading etiological factor and comparing it with the data of circulating of respiratory viruses in the given region.  Methods. 316 RS patients were analyzed from January to December 2013 in ENT-department children clinic. For identifying the etiology of RS the aspirate taken from paranasal sinuses was sent for microbiological tests.  Results. Patients with RS were 15,6% out of hospitalized. The frequency of RS coinsided with the amount of patients with common cold: maximum in February-March (31%-30,7%), recession in June-August (12,5%- 13,4%-14,4%) and average (16,5% - 23,4%) in other months. Out of 252 punctured sinuses only 141 aspirates were suitable for virological and bacteriological tests. Currently we have received the results of 92 aspirate tests, the other ones are currently being analyzed. In most cases (19,6%) there is a rhinovirus, no tests identified metapneumo- and coronaviruses. Comparing the results of viral and bacteriological research showed the viral RS was determined in 14,1%, bacterial – 33,7%, mixt- 28,3% and undetermined – 23,9%. The most common bacterial agents were Streptococcus pneumonia (29,3%) and Hemophilis influenza (14,1%).  Conclusions. The received data of viruses taken from paranasal sinuses coincide with the data of circulation of respiratory viruses in the given region in a certain time period.
Effect of infliximab on lung function and well-being in patients with refractory sarcoidosis
Authors: H.N.A.J. van Rijswijk, A.D.M. Vorselaars, I.H.E. Korenromp, H.J.T. Ruven, R.G.M. Keijsers, J.C. Grutters
Journal: European Respiratory Journal (2011)

Rationale:  Infliximab improves lung function in refractory sarcoidosis. Changes in other clinical parameters are still unclear.   Objectives:  To assess the effect of treatment with infliximab on change in lung function tests, fatigue severity and physical functioning, serum parameters and uptake on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with refractory sarcoidosis.   Methods:  Retrospectively, 45 patients with refractory sarcoidosis were evaluated. All patients received 6 infusions of infliximab (5mg/kg).  Main endpoints were the change in percentage of predicted vital capacity (VC), forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide corrected for haemoglobin concentration (DLCOc) from baseline till after dose 6. Other endpoints were the changes in fatigue (Checklist Individual Strength) and physical functioning (Medical Outcome Score-short form), serum soluble interleukin-2 receptor (sIL-2R), angiotensin converting enzyme (ACE) and change on FDG-PET, expressed as maximum standardized uptake value (SUVmax).   Results:  VC showed an increase of 5,4% (p   In the total group fatigue severity and physical functioning significantly changed over time, indicating clinically relevant improvement.  Additionally, a significant decrease in ACE, sIL-2R and SUVmax was observed.   Conclusions:  Infliximab improves lung function, well-being and serum and PET-parameters in patients with refractory sarcoidosis.
Identification of type 2 diabetes subgroups through topological analysis of patient similarity
Authors: Li Li, Wei-Yi Cheng, Benjamin S. Glicksberg, Omri Gottesman, Ronald Tamler, Rong Chen, Erwin P. Bottinger, Joel T. Dudley
Journal: Science Translational Medicine (2015)

Patient networks constructed from genotype data and electronic medical records pinpointed three type 2 diabetes subtypes.
Effect of 4-Hydroxyphenylretinamide and Retinoic Acid on Proliferation and Cell Cycle of Cultured Human Breast Cancer Cells
Authors: Christian Marth, Günther Böck, Günter Daxenbichler
Journal: JNCI Journal of the National Cancer Institute (1985)

The synthetic retinoid 4-hydroxyphenylretinamide (HPR) showed antiproliferative effect on cultured human breast cancer cells, which were sensitive to retinoic acid (RA) too. Investigation of the cell cycle by flow cytophotometry showed a significant increase of cells in the S-phase of the cell cycle after 24 hours of RA treatment, whereas HPR did not show this effect. After 4-7 days of retinoid treatment, the percentage of resting cells increased. The influence on the cell cycle and the antiproliferative effect were more pronounced for RA than for HPR treatment in both cell lines investigated (ZR-75.1 and 734 B).
The role of eucapnic voluntary hyperpnea in the diagnosis of exercise-induced vocal cord dysfunction in athletes: A pilot study
Authors: Julie Turmel, Simon Gagnon, Mélanie Bernier, Louis-Philippe Boulet
Journal: European Respiratory Journal (2014)

Introduction: Exercise-induced bronchoconstriction (EIB) is a common condition. Exercise-induced vocal cords dysfunction (EIVCD) is a frequent confounder of EIB and is the most common cause of upper airway obstruction during exercise.The diagnosis of EIVCD is not obvious and can be missed as the problem is often intermittent and may only occur during intense exercise. EVH is considered one of the best tests to detect EIB. This pilot study aims to assess if EVH can be helpful in the diagnosis of EIVCD associated or not to EIB in athletes. Methods: A nasolaryngoscopy was done during a 6-minute EVH test by an otorhinolaryngologist (ENT), in 13 female athletes suspected to have EIVCD, aged 21 ± 6 years.Image analysis was conducted by 2 ENT in random order. Results: During the EVH, 3 athletes showed incomplete paradoxical vocal cordsmovement, without inspiratory stridor. However, 12 athletes showed supraglottic movement without inspiratory stridor. In 2 athletes, this supraglottic movement was severe, one showing a marked epiglottis collapse with an almost complete obstruction of the larynx by the arytenoid cartilage mucosa. In three of the 12 athletes with supraglottic movement, severe vibration of the arytenoid cartilage mucosa was also observed. Conclusion: EVH challenge in athletes although it can provide information on various types of laryngeal dysfunction in reproducing laryngeal movement during hyperventilation. Exercise-induced inspiratory stridor may be associated with a paradoxical movement of the vocal cords or to a supraglottic movement of various magnitudes.