tbuckley/cabot-search huggingface dataset:
Abstract 4277: Alternative splicing in cancer transcriptomes
Authors: Shihao Shen, Ying Nian Wu, Yi Xing
Journal: Cancer Research (2014)

Abstract Alternative splicing of precursor mRNA is a key mechanism of eukaryotic gene regulation. Cancer-associated changes in alternative splicing can modulate gene function or activity, and consequently affect downstream molecular pathways critical for tumorigenesis or metastasis. RNA-Seq has become a powerful technology for genome-wide analysis of alternative splicing. We have developed sensitive and robust computational methods for quantitative analysis of alternative splicing using RNA-Seq data. Using these methods, we have analyzed the alternative splicing profiles of &amp;gt;4000 cancer samples across multiple types of cancer. Our analysis has identified important alternative splicing events that may contribute to the development and progression of cancer. Note: This abstract was not presented at the meeting. Citation Format: Shihao Shen, Ying Nian Wu, Yi Xing. Alternative splicing in cancer transcriptomes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4277. doi:10.1158/1538-7445.AM2014-4277
Evolution of an interstitial lung disease MDT: 5.5 years of data
Authors: Nazia Chaudhuri, Lisa Spencer, Colm Leonard
Journal: European Respiratory Journal (2014)

Introduction  Interstitial Lung Diseases (ILD) is a group of heterogeneous diseases. Accurate and early diagnosis is paramount as it improves diagnostic confidence [1], and allows accurate targeting of treatment modalities. An integrated approach involving a multidisciplinary team (MDT) of physicians, radiologists and pathologists is considered gold standard treatment and is strongly advised in ATS/ERS guidelines [2].  Aims.  To retrospectively review over time the accuracy of ILD diagnosis after a single center MDT discussion of clinical cases, how these diagnosis are achieved and the influence of MDT discussion on subsequent management.  Methods  A retrospective review of electronic patient notes and MDT records for 2005-08 and 2010-13.  Results  318 patients were referred for MDT review (n=167 2005-08 and n=159 2010-13). The proportion of discussions based on biopsies increased from 8 to 40% from 2005-08 to 2010-13. Usual Interstitial Pneumonia (UIP) was the pre-MDT diagnosis in 107 (34%) cases (n=74(45%) in 2005-08 and n=33(22%) in 2010-13). Post MDT 57 (54%) individuals had their diagnosis altered, leading to a change of treatment in 53 (51%) cases.  Of the 75 (24%) cases referred with no diagnosis MDT consensus was reached in 61 (81%) cases, leading to a change of treatment in 30 (40%) cases.  Consensus diagnosis was primarily made using CT data alone however a greater proportion of patients were deemed too unfit or that biopsy would not change management in the earlier 2005-08 time period.  Conclusion  Our findings support the need for specialist ILD MDT review of clinical cases to enhance diagnostic accuracy and improve patient care and management.
The use of telehealth system in improving adherence to nebulised treatment in children with cystic fibrosis: Benefits and pitfalls
Authors: Catherine Thornton, Omar Lamptey, Elaine Chan
Journal: European Respiratory Journal (2014)

Background : Adherence to treatment among Cystic Fibrosis (CF) patients is variable. Strategies to improve adherence via feedback to patients in home setting are being developed.  Aim : To determine whether telehealth system (I-neb Insight Online), ± prompts/feedback from physiotherapists, improves adherence to nebulised treatment  Method :Consenting CF patients (aged 6 -17 years) were set up to use Insight Online for self-monitoring adherence from home. Patients9 baseline adherence data was recorded. Patients were asked to upload data from their I-neb 2-weekly. Over a 2-month(m) period, if uploads were not done, patients/parents were prompted by physiotherapists at regular intervals, who reviewed uploaded data and fedback to patients.  Results : 28 CF patients recruited are divided into 3 groups, those who (1) independently uploaded(n=3); (2) uploaded with prompts(n=10); (3) failed to upload despite prompts(n=15). With baseline adherence ≥85%(median100%), Group 1 maintained their adherence over 2m period. The median [IQR] baseline adherence of Group 2 and Group 3 were 38% [18-51%] and 71% [54-72.5%] respectively(p=0.03). Over a 2m period, Group 2 increased their adherence by median [IQR] of 111% [33-181%] while Group 3 showed median [IQR] change 7%[-3-16%] on I-neb downloads (p=0.025).  Conclusion : Using Insight Online is effective in improving adherence in patients, who engaged with regular uploads. Feedback from physiotherapists may also have a role in improving adherence. However >50% of patients failed to upload regularly. Identifying practical barriers and characterising patients who would benefit from telehealth system, helps to best direct resources.
Brigid (Breda) T McCoy
Authors: R. Clyde
Journal: BMJ (2015)

Brigid Teresa McCoy (“Breda”) came from a farming family in west County Tyrone in Northern Ireland. An aspiring linguist, she taught Gaelic in summer schools in Donegal while an A level student. She was a keen debater at school, but an interest in science took her in the direction of medicine.

She loved the Guardian crossword and competed with other students to finish it first during the more tedious undergraduate lectures. She shared the prize for dermatology in final year in 1975 at Queen’s University Belfast

Her interests were dermatology and paediatrics. She loved neonatal paediatrics …
Safety and Efficacy of Eplerenone in Patients at High Risk for Hyperkalemia and/or Worsening Renal Function
Authors: Romain Eschalier, John J.V. McMurray, Karl Swedberg, Dirk J. van Veldhuisen, Henry Krum, Stuart J. Pocock, Harry Shi, John Vincent, Patrick Rossignol, Faiez Zannad, Bertram Pitt
Journal: Journal of the American College of Cardiology (2013)
Randomized Comparison of Oral and Intravenous Fluid Regimens after Gallbladder Surgery
Authors: O C S Cassell, N Oakley, A R W Forrest, W E G Thomas, A R Dennison
Journal: Journal of the Royal Society of Medicine (1996)

Numerous studies of post-operative fluid status have utilized sophisticated measurements of electrolyte distribution and fluid shift without relating results to clinical practice. The aim of this prospective randomized study was to investigate the response of patients undergoing abdominal surgery of moderate severity to conservative postoperative fluid administration. Forty-five patients undergoing open cholecystectomy were randomized to receive 2.51 of fluid (11 normal saline and 1.51 5% dextrose), 11 of normal saline, or free oral fluids (groups 1, 2, 3, respectively). Serum and urine osmolality and electrolytes were measured pre-operatively and at 24 and 48h post-operatively. Patients remained in the study irrespective of the urine output. Plasma electrolytes and osmolality remained within normal limits in all three groups despite significant changes in urine electrolyte and osmolality in groups 2 and 3. This confirms that a conservative approach to fluid administration has no detrimental effect on hydration in fit patients with uncomplicated surgery.
Prevalence of COPD in Algerian military
Authors: Kherbi Salah
Journal: European Respiratory Journal (2012)

The Survey is about one of the determinants of the chronic obstructive pulmonary disease (COPD), tobacco and the military environment. The objective is to measure the prevalence of this pathology and to make a first assessment of it in order to elaborate an efficient anti-tobacco policy and to associate a better handling of this pathology within our institutions.  It is about a transversal survey that uses the questionnaire and the spirometry on a population of soldiers and civilian staff working for the army aged of 40 years and more, current smokers or former smokers having accumulated 10 P/Y and more, belonging to 10 randomly chosen military camps belonging to the fifth military region. So 720 men have been included in the investigation and have been questioned during the period of November 01/2008 to October 31/2009.  The prevalence of the chronic obstructive pulmonary disease (COPD) is of 5.35 % for the whole population, of 6.37 % for current smokers and 3.75 % among the former smokers, the prevalence of the different stages of severity is of 2.67 % for the two stages I and II. The active tobacco addiction or weaned was the only factor of risk found with a percentage of 43.15 % and 36.06 % respectively, associated with the passive tobacco addiction.  The chronic obstructive pulmonary disease (COPD) in the military institution is a real problem that challenges medical community and decision–makers on the emergency of the elaboration of a health policy based on the prevention through strict measures of struggle against the tobacco addiction and the early detection of patients in a precocious stage by the practice of the minimal advice and the popularization of the breath measure.
Small airways function in allogeneic hematopoietic stem cell transplant recipients worsens over time and is correlated with change in chronic GVHD grade
Authors: Samir Lahzami, Robin E. Schoeffel, Victoria Pechey, Cassandra Reid, Matthew Greenwood, Cheryl M. Salome, Norbert Berend, Gregory King
Journal: European Respiratory Journal (2011)

Bronchiolitis obliterans (BO) following allogeneic hematopoietic stem cell transplantation (HSCT) is believed to be related to chronic graft-versus-host disease (cGVHD). Detection of BO is presently delayed by the low sensitivity of spirometry.  We examined the changes in small airways function and spirometry during 2 separate visits following allogeneic HSCT in 22 clinically stable recipients. Measurements of lung function, exhaled NO, forced oscillatory respiratory system resistance and reactance, acinar (Sacin) and conductive airways (Scond) ventilation heterogeneiy and lung clearance index (LCI) measured by multiple breath nitrogen washout were performed. These functional measurements were then compared with changes in cGVHD grade and respiratory quality of life (RQOL).  Patients were tested 12±9 months after HSCT and repeat visits were performed 10±6 months later. Sacin and LCI were the only measures to change significantly between 2 visits, with both worsening. Changes in Sacin and LCI were not correlated with change in FEV1%predicted, change in RV/TLC% predicted, nor with change in any other measured parameters. Change in Sacin was the only parameter to correlate with change in cGVHD grade (r=0.63, p=0.003). Change in RQOL was not correlated with change in any physiological measurement.  This study shows that change in small airways function in HSCT recipients can be detected without change in spirometry or in RQOL. The correlation between change in Sacin and change in cGVHD grade suggests that Sacin may be more sensitive than spirometry in detecting BO at an early stage, which needs confirmation in a prospective study.
Wide variation in price paid for basic supplies means NHS wastes millions
Authors: C. White
Journal: BMJ (2015)

The price the NHS in England pays for basic supplies such as syringes and toilet rolls varies widely among hospital trusts and adds up to significant sums that could instead be used for frontline care.

Reiterating the need for the NHS to make £22bn (€30bn; $34bn) of savings by 2020, which he acknowledged would be no easy task, the health secretary, Jeremy Hunt, outlined to the NHS Confederation’s annual conference in Liverpool this week how the government would try to help the NHS steer a course through the challenges of the next …
HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia.
Authors: M R Schwenn, S R Blattner, E Lynch, H J Weinstein
Journal: Journal of Clinical Oncology (1991)

We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.
Hypogammaglobulinemia, reduced B cell count and recurrent sinopulmonary infections: Good's syndrome
Authors: Murat Türk, Nurdan Köktürk, Numan Ekim
Journal: European Respiratory Journal (2012)

A 62-year-old woman with a history of thymectomy for capsule-invasion-free, type AB thymoma, presented with cough, dyspnea and fever. She had frequent respiratory tract infections for 9 months. Her initial physical examination was normal. Abnormal laboratory studies on admission were anemia,leukocytosis, proteinuria, elevated erithrocyte sedimentation rate, C-reactive protein and procalcitonin levels. On chest tomography, multiple mediastinal and hiler lymph nodes, bilateral traction bronchiectasis and milimetric nodules were seen. E.Coli was isolated in bronchoalveolar lavage. TBNA and TBB were negative for probable thymoma metastasis.  For the probability of Good9s Syndrome, serum immunoglobulin levels were measured and found normal for IgA, low for IgG and high for IgM. Flow cytometry demonstrated 8% of CD19+, 12% of CD56+, 14% of CD57+, 30% of CD4+, 37% of CD8+ cells in total lymphocytes; consistent with B-cell immunodeficiency. With the diagnosis of Good9s Syndrome, intravenous immunoglobulin treatment was started. During her follow-up,she was hospitalized twice for respiratory tract infections. Now she is on ciprofloxacin profilaxis.  Good9s syndrome is a rare cause of combined B or T cell deficiency. Its main characteristics are hypogammaglobulinemia, reduced or absent B cells, reduced serum levels of IgG, IgA and IgM,recurrent sinopulmonary infections caused by encapsulated microorganisms. Management of syndrome includes surgical resection of thymoma, treatment of infections and immunoglobulin replacement therapy.  Good Syndrome is a rare but treatable condition and it should be considered in patients with the diagnosis of thymoma and frequent respiratory tract infections.
Changes in brain volume after hypoxic exposure and exercise investigated by magnetic resonance imaging
Authors: Samuel Verges, Thomas Rupp, Marc Jubeau, Laurent Lamalle, Jan Warnking, Guillaume Millet, François Esteve, Alexandre Krainik, Patrick Levy
Journal: European Respiratory Journal (2014)

Recent data suggest that hypoxia can increase brain volume by inducing cerebral oedema. Exercise is thought to exacerbate acute mountain sickness (AMS) and possibly to enhance cerebral suboedema. The present study investigated the effect of hypoxic exposure and exercise on cerebral volume and oedema by magnetic resonance imaging. Twelve healthy males performed 3 semi-randomized 11-h sessions with i) an inspiratory O 2  fraction (FiO 2 ) of 11% and 4-h cycling, ii) FiO 2 =21% and 4-h cycling and iii) FiO 2 =8.5-11% (adjusted to match arterial O 2  saturation measured during session 1) at rest. Volumetric, apparent diffusion coefficient and arterial spin labelling 3T sequences performed after 30 min and 10 h in each session assessed changes in brain volume, cerebral oedema and cerebral blood flow, respectively. 30 min of hypoxia at rest induced a significant increase in white matter volume (+0.8 ± 1.0% compared to normoxia) that was even larger after 10 h in hypoxia at rest (+1.5 ± 1.1%) or with 4-h cycling (+1.6 ± 1.1%). Total brain parenchyma volume increased significantly after 10 h in hypoxia and 4-h cycling only (+1.3 ± 1.1%). Apparent diffusion coefficient was significantly reduced after 10 h in hypoxia at rest (-2.1 ± 3.5%) or with 4-h cycling (-2.4 ± 1.9%). No significant change in cerebral blood flow was observed. Symptoms of AMS did not correlate with changes in cerebral volume. These results demonstrate early change in white matter volume as soon as after 30 min of hypoxia that worsens after 10 h of exposure, probably due to cytotoxic oedema. Exercise accentuates the effect of hypoxia by increasing total brain volume. These changes may not however underlie AMS symptoms.
Endovascular Treatment of Common Femoral Artery Disease
Authors: Robert F. Bonvini, Aljoscha Rastan, Sebastian Sixt, Elias Noory, Thomas Schwarz, Ulrich Frank, Marco Roffi, Pierre André Dorsaz, Uwe Schwarzwälder, Karlheinz Bürgelin, Roland Macharzina, Thomas Zeller
Journal: Journal of the American College of Cardiology (2011)
Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia
Authors: Yusuke Shimakawa, Maud Lemoine, Harr Freeya Njai, Christian Bottomley, Gibril Ndow, Robert D Goldin, Abdoulie Jatta, Adam Jeng-Barry, Rita Wegmuller, Sophie E Moore, Ignatius Baldeh, Makie Taal, Umberto D'Alessandro, Hilton Whittle, Ramou Njie, Mark Thursz, Maimuna Mendy
Journal: Gut (2015)

<h3>Background</h3> The natural history of chronic HBV infection in sub-Saharan Africa is unknown. Data are required to inform WHO guidelines that are currently based on studies in Europe and Asia. <h3>Methods</h3> Between 1974 and 2008, serosurveys were repeated in two Gambian villages, and an open cohort of treatment-naive chronic HBV carriers was recruited. Participants were followed to estimate the rates of hepatitis B e (HBeAg) and surface antigen (HBsAg) clearance and incidence of hepatocellular carcinoma (HCC). In 2012–2013, a comprehensive liver assessment was conducted to estimate the prevalence of severe liver disease. <h3>Results</h3> 405 chronic carriers (95% genotype E), recruited at a median age of 10.8 years, were followed for a median length of 28.4 years. Annually, 7.4% (95% CI 6.3% to 8.8%) cleared HBeAg and 1.0% (0.8% to 1.2%) cleared HBsAg. The incidence of HCC was 55.5/100 000 carrier-years (95% CI 24.9 to 123.5). In the 2012–2013 survey (n=301), 5.5% (95% CI 3.4% to 9.0%) had significant liver fibrosis. HBV genotype A (versus E), chronic aflatoxin B1 exposure and an HBsAg-positive mother, a proxy for mother-to-infant transmission, were risk factors for liver fibrosis. A small proportion (16.0%) of chronic carriers were infected via mother-to-infant transmission; however, this population represented a large proportion (63.0%) of the cases requiring antiviral therapy. <h3>Conclusions</h3> The incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa.
Mechanism of Induction of Ovarian Tumors in the Mouse by 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene. III. Tumor Induction in Organ Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. W. Jull, A. Hawryluk, A. Russell
Journal: JNCI Journal of the National Cancer Institute (1968)

Ovaries were removed from immature mice, maintained in organ culture for periods ranging from 4 hours to 4 days, and then reimplanted subcutaneously into the same mice from which they were obtained. A granulosa-cell tumor arose in only 1 of 87 mice whose ovaries had been exposed to the culture medium only. Addition of 7,12-dimethylbenz[a]anthracene (DMBA) to the organ culture medium in concentrations varying between 0.5 and 4 μg/ml resulted in incidences of granulosa-cell tumors ranging from 7–60% in (BALB/cJ ♀ × A/J♂)F1 (CAF1/J) mice and 44% in one experiment at a concentration of 4 μg/ml of DMBA in hybrids of C3H and NZY mice. The incidence of granulosa-cell tumors reached a significantly greater level than the controls with 1.0 or 4.0 μg/ml of DMBA but not with 0.5 μg/ml. Adding 10 μg/ml of various steroids to the medium did not result in any significant incidence of granulosa-cell tumors. In experiments in which steroids at 10 μg/ml were added to medium containing 4 μg/ml of DMBA, the incidence of tumors was lower in 3 groups than with DMBA alone, i.e., 17-hydroxyprogesterone 0/9, deoxycorticosterone 2/25, and 4-pregnen-3β,20β-diol 1/14, but 5 other steroids did not affect tumor induction. Luteomas were equally common in both control and carcinogen-treated ovaries, but were less frequent in ovaries exposed to steroids alone. Injecting chorionic gonadotropin after reimplantation did not influence the yield of ovarian tumors. Hyperplasia of type-B cells of the adrenal cortex, together with vaginal mucification, was associated with the complete absence of ovarian tissue or the presence of ovaries that had been treated with DMBA.
How Inhibitory Circuits in the Thalamus Serve Vision
Authors: Judith A. Hirsch, Xin Wang, Friedrich T. Sommer, Luis M. Martinez
Journal: Annual Review of Neuroscience (2015)

Inhibitory neurons dominate the intrinsic circuits in the visual thalamus. Interneurons in the lateral geniculate nucleus innervate relay cells and each other densely to provide powerful inhibition. The visual sector of the overlying thalamic reticular nucleus receives input from relay cells and supplies feedback inhibition to them in return. Together, these two inhibitory circuits influence all information transmitted from the retina to the primary visual cortex. By contrast, relay cells make few local connections. This review explores the role of thalamic inhibition from the dual perspectives of feature detection and information theory. For example, we describe how inhibition sharpens tuning for spatial and temporal features of the stimulus and how it might enhance image perception. We also discuss how inhibitory circuits help to reduce redundancy in signals sent downstream and, at the same time, are adapted to maximize the amount of information conveyed to the cortex.