tbuckley/cabot-search huggingface dataset:
Altered gut microbiota composition in immune-impaired<i>Nod2</i><sup>−/−</sup>mice
Authors: Stanislas Mondot, Frédérick Barreau, Ziad Al Nabhani, Monique Dussaillant, Karine Le Roux, Joël Doré, Marion Leclerc, Jean-Pierre Hugot, Patricia Lepage
Journal: Gut (2011)

We read with great interest the recently published study by Rehman and colleagues.1 Investigating microbial diversity on faecal and ileal samples from 48 mice using Sanger and 454 techniques, Rehman et al detected increased percentages of Bacteroidetes in the faeces of adult Nod2 −/− mice, whereas Firmicutes levels were significantly higher only in the ileum of Nod2 −/− mice.

Since we demonstrated that antibiotic …
Clostridium difficile PCR ribotype 027: assessing the risks of further worldwide spread
Authors: Archie CA Clements, Ricardo J Soares Magalhães, Andrew J Tatem, David L Paterson, Thomas V Riley
Journal: The Lancet Infectious Diseases (2010)

Highly virulent strains of Clostridium difficile have emerged since 2003, causing large outbreaks of severe, often fatal, colitis in North America and Europe. In 2008-10, virulent strains spread between continents, with the first reported cases of fluoroquinolone-resistant C difficile PCR ribotype 027 in three Asia-Pacific countries and Central America. We present a risk assessment framework for assessing risks of further worldwide spread of this pathogen. This framework first requires identification of potential vehicles of introduction, including international transfers of hospital patients, international tourism and migration, and trade in livestock, associated commodities, and foodstuffs. It then calls for assessment of the risks of pathogen release, of exposure of individuals if release happens, and of resulting outbreaks. Health departments in countries unaffected by outbreaks should assess the risk of introduction or reintroduction of C difficile PCR ribotype 027 using a structured risk-assessment approach.
Loss of β2-spectrin prevents cardiomyocyte differentiation and heart development
Authors: Jeong A. Lim, Hye Jung Baek, Moon Sun Jang, Eun Kyoung Choi, Yong Min Lee, Sang Jin Lee, Sung Chul Lim, Joo Young Kim, Tae Hyun Kim, Hye Sun Kim, Lopa Mishra, Sang Soo Kim
Journal: Cardiovascular Research (2013)

Aimsβ2-Spectrin is an actin-binding protein that plays an important role in membrane integrity and the transforming growth factor (TGF)-β signalling pathway as an adaptor for Smads. Loss of β2-spectrin in mice (Spnb2−/−) results in embryonic lethality with gastrointestinal, liver, neural, and heart abnormalities that are similar to those in Smad2+/−Smad3+/− mice. However, to date, the role of β2-spectrin in embryogenesis, particularly in heart development, has been poorly delineated. Here, we demonstrated that β2-spectrin is required for the survival and differentiation of cardiomyocytes, and its loss resulted in defects in heart development with failure of ventricular wall thickening.
MORPHOLOGICAL AND BIOLOGICAL STUDIES ON A VIRUS IN CULTURED LYMPHOBLASTS FROM BURKITT'S LYMPHOMA
Authors: M. A. Epstein, G. Henle, B. G. Achong, Y. M. Barr
Journal: The Journal of Experimental Medicine (1965)

Lymphoblasts of two tissue culture strains (EB1 and EB2) from different biopsy specimens of Burkitt's lymphoma have been examined in thin sections by electron microscopy, and have each been found to carry a morphologically identical virus. The virus was observed in samples taken over many months, being present in about 1 to 2 per cent of the cells in two forms: Immature particles about 75 mmicro in diameter which were seen in both the nucleus and cytoplasm; and larger mature particles with a diameter of 110 to 115 mmicro, which were either within membrane-bounded cytoplasmic spaces or at the cell surface. There was some indication that the particles matured by budding through the cytoplasmic membranes. Both types of particle occurred in dead degenerating cells or, less frequently, in intact altered cells. The characteristic alterations of the latter included margination of the chromatin, fragmentation of the nuclear envelope, beaded opaque material in the mitochondria, and, with one of the cell strains (EB1), sheaves of altered spindle tubules. All attempts to isolate and identify the virus carried by the two strains of lymphoblasts failed. No pathological effects were caused in 8-day chick embryos inoculated either with whole lymphoblasts or extracts of disrupted lymphoblasts, using the intraallantoic, amniotic, and chorioallantoic routes, and the extraembryonic fluids of such chicks were without haemagglutinating activity for human, chicken, guinea pig, or monkey erythrocytes. Whole lymphoblasts or lymphoblast extracts were likewise without effect when inoculated intraperitoneally into newborn hamsters or two strains of newborn mice. Similar lymphoblast inocula did not cause detectable changes in 9 different test tissue culture systems even after 8 blind passages. The nature of the unknown, unidentified virus in the cultured lymphoblasts from Burkitt's lymphomas is considered and its possible relationship to the cells discussed.
Searching for differentially expressed gene combinations.
Authors: Marcel Dettling, Edward Gabrielson, Giovanni Parmigiani
Journal: Genome biology (2005)

We propose 'CorScor', a novel approach for identifying gene pairs with joint differential expression. This is defined as a situation with good phenotype discrimination in the bivariate, but not in the two marginal distributions. CorScor can be used to detect phenotype-related dependencies and interactions among genes. Our easily interpretable approach is scalable to current microarray dimensions and yields promising results on several cancer-gene-expression datasets.
Current advances in using neurotrophic factors to treat neurodegenerative disorders
Authors: April M Weissmiller, Chengbiao Wu
Journal: Translational Neurodegeneration (2012)

Neurotrophic factors are best known for their roles in both development and continued maintenance of the nervous system. Their strong potential to elicit pro-survival and pro-functional responses in neurons of the peripheral and central nervous system make them good drug candidates for treatment of a multitude of neurodegenerative disorders. However, significant obstacles remain and need to be overcome before translating the potential of neurotrophins into the therapeutic arena. This article addresses current efforts and advances in resolving these challenges and provides an overview of roadmaps for future translational research and neurotrophin-based drug developments.
Selection criteria for genetic assessment of patients with familial melanoma
Authors: Sancy A. Leachman, John Carucci, Wendy Kohlmann, Kimberly C. Banks, Maryam M. Asgari, Wilma Bergman, Giovanna Bianchi-Scarrà, Teresa Brentnall, Brigitte Bressac-de Paillerets, William Bruno, Clara Curiel-Lewandrowski, Femke A. de Snoo, Tadeusz Debniak, Marie-France Demierre, David Elder, Alisa M. Goldstein, Jane Grant-Kels, Allan C. Halpern, Christian Ingvar, Richard F. Kefford, Julie Lang, Rona M. MacKie, Graham J. Mann, Kurt Mueller, Julia Newton-Bishop, Håkan Olsson, Gloria M. Petersen, Susana Puig, Darrell Rigel, Susan M. Swetter, Margaret A. Tucker, Emanuel Yakobson, John A. Zitelli, Hensin Tsao
Journal: Journal of the American Academy of Dermatology (2009)
Follow up of people fitted with hearing aids after adult hearing screening: the need for support after fitting
Authors: I. Gianopoulos
Journal: BMJ (2002)

In the British population only 20-25% of people who report hearing difficulties possess a hearing aid.1 – 2 We have proposed that adult hearing screening would increase the use of hearing aids.1 – 3 In three studies conducted in Wales between 1982 and 1992 all people aged 50-65 in four general practices were sent a screening questionnaire on hearing difficulties. Those who reported hearing problems were tested audiometrically and were offered a hearing aid if the average hearing level in their worse ear was worse than 30 dB. Two of these studies showed that this intervention increased by threefold the possession of hearing aids in the target populations.2 – 3 Screening was thus effective in the short term; in this …
Normalization of a NAFLD gene expression signature
Authors: Manlio Vinciguerra
Journal: Hepatology (2014)

We read with great interest the article by Moylan et al.1 in which the authors demonstrate that a 64-gene profile reproducibly differentiated severe nonalcoholic fatty liver disease (NAFLD) from mild NAFLD, and that a 20-gene subset within this profile correlated with NAFLD severity, independent of other known factors impinging on NAFLD progression. The need for accurate risk stratification for NAFLD is urgent because the disease is epidemic, imposing a public health burden, and cirrhosis and/or hepatocellular carcinoma (HCC) may develop on an NAFLD background. The authors unraveled, using microarrays and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in the livers of patients, a novel gene expression signature that independently correlated with NAFLD severity.1 Although these findings might help develop novel diagnostic tests and treatments that target NAFLD patients at greatest risk, there are some important aspects that need to be stressed. The choice of housekeeping (control) genes, whose expression is not susceptible to nutrients, is crucial to normalize results in gene expression studies involving liver tissue. Moylan et al. used ribosomal protein L35 (RPL35) as the only control gene for all analyses. Studies on the translatome (total proteins formed by mRNA translation) show tremendous fluctuations in polysome-associated RPL35 levels in the livers of obese versus chow-fed mice, and also between fasted and fed states.2 Gene expression of RPL35 is increased in HCC cell lines and tissues.3 Moylan et al. relied most likely on the fact that RPL35 levels did not vary significantly in the clinical samples analyzed. However, if the expression of a control gene is potentially heavily influenced by nutritional and proliferative status in the liver, that could pose a problem when defining a gene expression signature with clinical applications. There is now a strong consensus in the community on the validity of the "GeNorm" method, employing the geometric mean of multiple carefully selected housekeeping genes to achieve robust normalization of gene expression data.4, 5 It would be interesting to reassess the data obtained by Moylan et al. using three or more housekeeping genes for normalization. Without robust normalization strategies it will be hard to assess the prognostic power of gene expression signatures. Manlio Vinciguerra, Ph.D. University College London (UCL) Institute for Liver and Digestive Health UCL Medical School Royal Free Campus London, UK
Endobronchial ultrasound-guided cryobiopsies in peripheral pulmonary lesions: a feasibility study
Authors: Maren Schuhmann, Korkut Bostanci, António Bugalho, Arne Warth, Philipp A. Schnabel, Felix J.F. Herth, Ralf Eberhardt
Journal: European Respiratory Journal (2013)

Peripheral lung lesions are sometimes difficult to reach even with endobronchial ultrasound (EBUS) and insufficient material is often obtained by transbronchial forceps biopsy. Cryoprobes can be used for performing tissue biopsies. We evaluated the safety and feasibility of the cryoprobe in combination with EBUS for the diagnosis of peripheral lung lesion. Patients with peripheral lung lesions of up to 4 cm were enrolled. After identifying the lung lesion by radial EBUS, forceps biopsies and cryobiopsies were performed in a randomised order. We evaluated safety and feasibility, and compared diagnostic yield and sample size. 39 patients were randomised and the peripheral lung lesion was reached in 31. The overall diagnostic yield was 60.5% and, in the lesions reached by EBUS, it was 74.2%. In 19 cases, the diagnosis was made with forceps as well as cryobiopsy and, in four cases, only with cryobiopsy. Cryobiopsies were significantly larger than forceps biopsies (11.17 mm(2) versus 4.69 mm(2), p<0.001). We observed one case of moderate bleeding. Transbronchial cryobiopsy with EBUS guidance is safe and useful to obtain histological samples. Larger tissue samples can be obtained by cryoprobe.
The relationship between sarcoidosis and lymphoma
Authors: I.C. Papanikolaou, O.P. Sharma
Journal: European Respiratory Journal (2010)

To the Editors:

Lymphocyte activation in sarcoidosis and the involvement of the reticuloendothelial system (liver, spleen, lymph nodes) make differential diagnosis between sarcoidosis and lymphoma a difficult task. In an earlier epidemiological study, an 11-fold increase in lymphoma cases among patients with sarcoidosis was observed; however, the methodology of this study has been questioned 1–3. In order to elucidate the clinical characteristics of sarcoidosis and lymphoma, we conducted this retrospective review of cases of patients in which sarcoidosis and lymphoma coexisted in the same patient. These cases have been retrieved from our institution (University of Southern California, Los Angeles, CA, USA) and from an extensive Medline review.

Our inclusion criteria were: 1) biopsy-proven sarcoidosis, based on American Thoracic Society (ATS)/European Respiratory Society (ERS)/World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) criteria 4 applied by the authors retrospectively; 2) biopsy-proven lymphoma classified as Hodgkin Lymphoma (HL) and non-HL (NHL) according to the World Health Organization (WHO) classification 5. Exclusion criteria were diagnosis of other malignancies and sarcoid-like reactions (SLR). These reactions, secondary to malignancies, are considered to occur either adjacent to the primary malignant site or to local drainage nodes. Group A consisted of cases in which sarcoidosis preceded lymphoma; group B consisted of cases in which the two diseases presented concurrently (in a period <1 month); and, in group C, lymphoma preceded sarcoidosis.

The primary end-point was to clarify the symptoms and signs 1) of lymphoma in a patient already diagnosed with sarcoidosis and 2) of sarcoidosis in a patient already diagnosed with lymphoma. We compared initial sarcoidosis presentation (group A) with initial lymphoma presentation (group C); then, sarcoidosis as the second disease (group C) with lymphoma as the second disease (group A). Our secondary end-point …
Membrane association of nitric oxide-sensitive guanylyl cyclase in cardiomyocytes
Authors: L AGULLO, D GARCIADORADO, N ESCALONA, M RUIZMEANA, M MIRABET, J INSERTE, J SOLERSOLER
Journal: Cardiovascular Research (2005)

Journal Article Membrane association of nitric oxide-sensitive guanylyl cyclase in cardiomyocytes Get access Luis Agulló, Luis Agulló Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 129, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar David Garcia-Dorado, David Garcia-Dorado * Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 129, 08035 Barcelona, Spain *Corresponding author. Tel.: +34 93 489 40 38; fax: +34 93 489 40 32. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Noelia Escalona, Noelia Escalona Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 129, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Marisol Ruiz-Meana, Marisol Ruiz-Meana Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 129, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Maribel Mirabet, Maribel Mirabet Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 129, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Javier Inserte, Javier Inserte Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 129, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Jordi Soler-Soler Jordi Soler-Soler Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Pg Vall d'Hebron 129, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 68, Issue 1, October 2005, Pages 65–74, https://doi.org/10.1016/j.cardiores.2005.05.021 Published: 01 October 2005 Article history Received: 07 September 2004 Revision received: 11 April 2005 Accepted: 18 May 2005 Published: 01 October 2005
A Randomized Trial of Sibutramine in the Management of Obese Type 2 Diabetic Patients Treated With Metformin
Authors: Steven J. McNulty, Ehud Ur, Gareth Williams
Journal: Diabetes Care (2003)

To evaluate the effects of sibutramine (15 and 20 mg/day) on weight, metabolic control, and blood pressure in metformin-treated obese subjects with type 2 diabetes.A 12-month randomized prospective placebo-controlled double-blind study was performed. It included 21 primary and secondary care centers in England, Canada, France, and Belgium. A total of 195 subjects (44% male) with type 2 diabetes and a BMI >27 kg/m(2) were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA(1c), fasting glucose, and lipids.Sibutramine induced significant weight loss (P < 0.001) with both 15 mg/day (5.5 +/- 0.6 kg at 12 months) and 20 mg/day (8.0 +/- 0.9 kg), whereas placebo did not (0.2 +/- 0.5 kg). Weight loss > or = 10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo. Glycemic control improved in parallel with weight loss, and subjects who lost > or = 10% weight showed significant decreases in both HbA(1c) (1.2 +/- 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of > or = 10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with placebo, P < 0.05), but this effect was less evident in subjects who had a weight loss of > or = 10% weight. Pulse rate increased significantly more with sibutramine, being > or = 10 bpm higher in 42% of treated patients versus 17% with placebo (P < 0.01).Sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight.
Making the unbearable bearable
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2012)

Compassion isn't even a dirty word in the National Health Service since it is a behaviour that, according to popular belief, isn't displayed by clinicians who are too preoccupied with targets, efficiency drives, and restructuring to care for their patients—in the Florence Nightingale sense. A spoonful of compassion helps the medicine go down but also helps nudge your institution's performance on patient satisfaction surveys in the right direction. These attacks on heartless unfeeling clinicians are a little unkind; plenty of compassion is displayed every minute of every day although admittedly not enough.

Ken Schwartz, an American lawyer who died in his 40s from lung cancer, wrote in the Boston Globe that ‘the smallest acts of kindness made the unbearable bearable.’ Schwartz was grateful for the care and compassion he received during his illness, a sentiment that perhaps too few patients are able to share. Clinicians are expected to control their emotions, a stiff upper lip preferable to a wobbly precursor to a tearful outburst.1

The debate on compassion in healthcare focuses rightly on patient experience, although the emotional needs of clinical staff are usually forgotten and addressing them may lead to benefits for patients. Illness or death can profoundly affect carers yet where is the debate on compassion towards staff? What of their emotional trauma? As our clinical lives become more disjointed and insecure, the wellbeing of staff will be increasingly difficult to maintain.2 Schwartz's family were so grateful for the care he received that they set up a legacy to support monthly meetings where staff freely, and confidentially, discuss their feelings about the care of a particular patient.

Known as Schwartz Rounds, these meetings have become established in the United States and are now being introduced in the United Kingdom. A pilot study in two trusts suggests that Schwartz Rounds are a source of support for participants, benefit patients and team working, and have potential to change hospital culture.3 These are bold claims for a fascinating initiative. Failing that, a social influence approach based on nudge theory and custard creams might be worth considering.4
Phase IB Study of Gene-Mediated Cytotoxic Immunotherapy Adjuvant to Up-Front Surgery and Intensive Timing Radiation for Malignant Glioma
Authors: E. Antonio Chiocca, Laura K. Aguilar, Susan D. Bell, Balveen Kaur, Jayson Hardcastle, Robert Cavaliere, John McGregor, Simon Lo, Abhik Ray-Chaudhuri, Arnab Chakravarti, John Grecula, Herbert Newton, Kimbra S. Harris, Robert G. Grossman, Todd W. Trask, David S. Baskin, Carissa Monterroso, Andrea G. Manzanera, Estuardo Aguilar-Cordova, Pamela Z. New
Journal: Journal of Clinical Oncology (2011)

Despite aggressive therapies, median survival for malignant gliomas is less than 15 months. Patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) fare worse, presumably because of temozolomide resistance. AdV-tk, an adenoviral vector containing the herpes simplex virus thymidine kinase gene, plus prodrug synergizes with surgery and chemoradiotherapy, kills tumor cells, has not shown MGMT dependency, and elicits an antitumor vaccine effect.Patients with newly diagnosed malignant glioma received AdV-tk at 3 × 10(10), 1 × 10(11), or 3 × 10(11) vector particles (vp) via tumor bed injection at time of surgery followed by 14 days of valacyclovir. Radiation was initiated within 9 days after AdV-tk injection to overlap with AdV-tk activity. Temozolomide was administered after completing valacyclovir treatment.Accrual began December 2005 and was completed in 13 months. Thirteen patients were enrolled and 12 completed therapy, three at dose levels 1 and 2 and six at dose level 3. There were no dose-limiting or significant added toxicities. One patient withdrew before completing prodrug because of an unrelated surgical complication. Survival at 2 years was 33% and at 3 years was 25%. Patient-reported quality of life assessed with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) was stable or improved after treatment. A significant CD3(+) T-cell infiltrate was found in four of four tumors analyzed after treatment. Three patients with MGMT unmethylated glioblastoma multiforme survived 6.5, 8.7, and 46.4 months.AdV-tk plus valacyclovir can be safely delivered with surgery and accelerated radiation in newly diagnosed malignant gliomas. Temozolomide did not prevent immune responses. Although not powered for efficacy, the survival and MGMT independence trends are encouraging. A phase II trial is ongoing.
Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial
Authors: Michiel L Bots, Frank L Visseren, Gregory W Evans, Ward A Riley, James H Revkin, Charles H Tegeler, Charles L Shear, William T Duggan, Ralph M Vicari, Diederick E Grobbee, John J Kastelein
Journal: The Lancet (2007)