tbuckley/cabot-search huggingface dataset:
Candidate Genes and Adaptive Radiation: Insights from Transcriptional Adaptation to the Limnetic Niche among Coregonine Fishes (Coregonus spp., Salmonidae)
Authors: J. Jeukens, D. Bittner, R. Knudsen, L. Bernatchez
Journal: Molecular Biology and Evolution (2008)

In the past 40 years, there has been increasing acceptance that variation in levels of gene expression represents a major source of evolutionary novelty. Gene expression divergence is therefore likely to be involved in the emergence of incipient species, namely, in a context of adaptive radiation. In the lake whitefish species complex (Coregonus clupeaformis), previous microarray experiments have led to the identification of candidate genes potentially implicated in the parallel evolution of the limnetic dwarf lake whitefish, which is highly distinct from the benthic normal lake whitefish in life history, morphology, metabolism, and behavior, and yet diverged from it only ∼15,000 years before present. The aim of the present study was to address transcriptional divergence for six candidate genes among lake whitefish and European whitefish (Coregonus lavaretus) species pairs, as well as lake cisco (Coregonus artedi) and vendace (Coregonus albula). The main goal was to test the hypothesis that parallel phenotypic adaptation toward the use of the limnetic niche in coregonine fishes is accompanied by parallelism in candidate gene transcription as measured by quantitative real-time polymerase chain reaction. Results obtained for three candidate genes, whereby parallelism in expression was observed across all whitefish species pairs, provide strong support for the hypothesis that divergent natural selection plays an important role in the adaptive radiation of whitefish species. However, this parallelism in expression did not extend to cisco and vendace, thereby infirming transcriptional convergence between limnetic whitefish species and their limnetic congeners for these genes. As recently proposed (Lynch 2007a. The evolution of genetic networks by non-adaptive processes. Nat Rev Genet. 8:803–813), these results may suggest that convergent phenotypic evolution can result from nonadaptive shaping of genome architecture in independently evolved coregonine lineages.
The evolution of eccentric training as treatment for patellar tendinopathy (jumper’s knee): a critical review of exercise programmes
Authors: Håvard Visnes, Roald Bahr
Journal: British Journal of Sports Medicine (2007)

Eccentric training has become a popular treatment for patellar tendinopathy. Our purpose was to review the evolution of eccentric strength training programmes for patellar tendinopathy with a focus on the exercise prescriptions used, to help clinicians make appropriate choices and identify areas needing further research.A computerised search of the entire MEDLINE database was performed on 1 September 2006 to identify prospective and randomised clinical trials with a focus on clinical outcome of eccentric training for patellar tendinopathy.7 articles with a total of 162 patients and in which eccentric training was one of the interventions, all published after 2000, were included. The results were positive, but study quality was variable, with small numbers or short follow-up periods. The content of the different training programmes varied, but most were home-based programmes with twice daily training for 12 weeks. A number of potentially significant differences were identified in the eccentric programmes used: drop squats or slow eccentric movement, squatting on a decline board or level ground, exercising into tendon pain or short of pain, loading the eccentric phase only or both phases, and progressing with speed then loading or simply loading.Most studies suggest that eccentric training may have a positive effect, but our ability to recommend a specific protocol is limited. The studies available indicate that the treatment programme should include a decline board and should be performed with some level of discomfort, and that athletes should be removed from sports activity. However, these aspects need further study.
S164 Diminished left ventricular end-diastolic dimensions predict an amplified risk of death in chronic obstructive pulmonary disease
Authors: M. Mendonca, J. Brown, M. Rashid, H. Z. Ling, S. Kang, A. Cheng, E. Boston-griffiths, M. Okorie, M. Thomas, S. Woldman, H. Booth, None Do okonko
Journal: Thorax (2010)

<h3>Background</h3> Left ventricular (LV) dimensions are markedly attenuated in chronic obstructive pulmonary disease (COPD) possibly due to impairments in LV filling that result from increased pulmonary vascular resistance, ventricular interdependence, diastolic dysfunction or incessant tachycardia. Whether reductions in LV size carry adverse prognostic implications in this cohort is unclear. <h3>Methods</h3> We analysed the relation between echocardiographic indices and mortality in 147 COPD patients (mean [±SD] age 76±10 years, forced expiratory volume in 1 s [FEV1] 0.85±0.34 l, forced vital capacity [FVC] 1.44±0.60 l, FEV1/FVC 0.62±0.16, LV ejection fraction [LVEF] 56±12%) with homogenous right ventricular (42±14 mm Hg) and pulmonary arterial systolic (45±17 mm Hg) pressures. <h3>Results</h3> Decreased LV end-diastolic (LVEDD ≤37 mm) and end-systolic (LVESD ≤25 mm) diameters, ejection fraction (&lt;45%), and diastolic function (E/A ratio &lt;1 or &gt;2) were evident in 10%, 14%, 18% and 71% of patients, respectively. Lower LVEDDs correlated significantly to lower LVESDs (r=0.83), higher LVEFs (r=−0.54), lower FEV1s (r=0.29), and lower FVCs (r=0.20) but not to age, right ventricular systolic pressures or pulmonary arterial pressures. Over a mean follow-up of 26±18 months, 60 (41%) patients died. Only a lower LVEDD predicted increased mortality (c<sup>2</sup> 4.4, p=0.03) with each 1 mm decrement in LVEDD conferring a 3% escalated risk of death. An LVEDD ≤43 mm optimally predicted mortality and was associated with an 89% reduction in survival compared to an LVEDD &gt;43 mm (Abstract S164 Figure 1). No variable affected the prognostic impact of LVEDDs in adjusted analyses. <h3>Conclusions</h3> Attenuations in left ventricular end-diastolic diameter forecast an enhanced risk of death in patients with COPD, irrespective of lung function and pulmonary arterial pressures. Improving LV filing and dimensions in this cohort may augment survival.
Clinical Messages From the Treatment for Adolescents With Depression Study (TADS)
Authors: John S March, Benedetto Vitiello
Journal: American Journal of Psychiatry (2009)

Objective: The purpose of this report was to summarize the key clinical messages from the Treatment for Adolescents with Depression Study (TADS). Methods: TADS is a National Institute of Mental Health (NIMH)-funded randomized controlled trial designed to evaluate the relative effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and the combination of fluoxetine plus CBT across acute treatment, maintenance treatment, and naturalistic follow-up periods among adolescents with major depressive disorder. Results: Findings revealed that 6 to 9 months of combined fluoxetine plus CBT should be the modal treatment from a public health perspective as well as to maximize benefits and minimize harms for individual patients. Conclusion: The combination of fluoxetine and CBT appears to be superior to both CBT monotherapy and fluoxetine monotherapy as a treatment for moderate to severe major depressive disorder in adolescents.
Successful treatment of an aciclovir-resistant herpes simplex type 2 infection with cidofovir in an AIDS patient
Authors: T. Kopp, A. Geusau, A. Rieger, G. Stingl
Journal: British Journal of Dermatology (2002)

Journal Article Successful treatment of an aciclovir‐resistant herpes simplex type 2 infection with cidofovir in an AIDS patient Get access T. Kopp, T. Kopp Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Dr Tamara Kopp, MD. E‐mail: tamara.kopp@akh‐wien.ac.at Search for other works by this author on: Oxford Academic Google Scholar A. Geusau, A. Geusau Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar A. Rieger, A. Rieger Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar G. Stingl G. Stingl Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 1, 1 July 2002, Pages 134–138, https://doi.org/10.1046/j.1365-2133.2002.04747.x Published: 01 July 2002 Article history Accepted: 26 November 2001 Published: 01 July 2002
Integrated analyses of DNA methylation and hydroxymethylation reveal tumor suppressive roles of ECM1, ATF5, and EOMESin human hepatocellular carcinoma
Authors: Fei Gao, Yudong Xia, Junwen Wang, Zhilong Lin, Ying Ou, Xing Liu, Weilong Liu, Boping Zhou, Huijuan Luo, Baojin Zhou, Bo Wen, Xiuqing Zhang, Jian Huang
Journal: Genome biology (2014)

Abstract Background Differences in 5-hydroxymethylcytosine, 5hmC, distributions may complicate previous observations of abnormal cytosine methylation statuses that are used for the identification of new tumor suppressor gene candidates that are relevant to human hepatocarcinogenesis. The simultaneous detection of 5-methylcytosine and 5-hydroxymethylcytosine is likely to stimulate the discovery of aberrantly methylated genes with increased accuracy in human hepatocellular carcinoma. Results Here, we performed ultra-performance liquid chromatography/tandem mass spectrometry and single-base high-throughput sequencing, Hydroxymethylation and Methylation Sensitive Tag sequencing, HMST-seq, to synchronously measure these two modifications in human hepatocellular carcinoma samples. After identification of differentially methylated and hydroxymethylated genes in human hepatocellular carcinoma, we integrate DNA copy-number alterations, as determined using array-based comparative genomic hybridization data, with gene expression to identify genes that are potentially silenced by promoter hypermethylation. Conclusions We report a high enrichment of genes with epigenetic aberrations in cancer signaling pathways. Six genes were selected as tumor suppressor gene candidates, among which, ECM1 , ATF5 and EOMES are confirmed via siRNA experiments to have potential anti-cancer functions.
Topical capsaicin--a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study
Authors: J Lysy, M Sistiery-Ittah, Y Israelit, A Shmueli, N Strauss-Liviatan, V Mindrul, D Keret, E Goldin
Journal: Gut (2003)

<b>Purpose:</b> Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with capsaicin. <b>Methods:</b> Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with capsaicin treatment in an open labelled manner. <b>Results:</b> Thirty one of 44 patients experienced relief during capsaicin treatment periods and did not respond to menthol; all patients not responding to capsaicin also failed on menthol (p&lt;0.0001). In 13 patients, treatment with capsaicin was unsuccessful: eight patients did not respond to capsaicin treatment, one responded equally to capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 "responders" needed a mean application of capsaicin every day (1.6 (SD 1.2); range 0.5–7 days) to remain symptom free (or nearly symptom free). <b>Conclusion:</b> Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani.
Coeliac disease associated with systemic sclerosis
Authors: J A Gomez-Puerta
Journal: Annals of the Rheumatic Diseases (2003)

heumatoid arthritis (RA) is a chronic inflammatory disease which is characterised mainly by synovial inflammation and joint destruction, as well as extraarticular manifestations. 1 Cytokines have a central role in the pathogenesis of this synovial inflammation.Tumour necrosis factor a (TNFa) is one of the dominant cytokines.Many studies have shown that TNFa is present in biologically significant amounts in RA synovial tissue and fluids, and the amount seems to parallel the extent of inflammation and bone erosion. 2 3 Persistent inflamed monarthritis in patients with RA is difficult to treat.Usually it is treated with local patches, intraarticular injections of steroids, or even with chemical, radioactive, or surgical synovectomy. 4 The introduction of anti-TNFa treatments, especially the infusion of infliximab, 5 prompted us to investigate the effectiveness and safety of intra-articular injection of infliximab in patients with RA and resistant monarthritis.
Major histocompatibility complex class II and<i>BTNL2</i>associations in sarcoidosis: Table 1–
Authors: Annika Wennerström, Anne Pietinalho, Jagoda Lasota, Krista Salli, Ida Surakka, Mikko Seppänen, Olof Selroos, Marja-Liisa Lokki
Journal: European Respiratory Journal (2013)

To the Editor: 

Sarcoidosis is a multiple organ immune-mediated disease of unknown aetiology. Identified genetic risk factors within the major histocompatibility complex (MHC), such as butyrophilin-like ( BTNL)2 , human leukocyte antigen ( HLA)-DRB1*03 and HLA-DRB1*15 , and protective factors, such as HLA-DRB1*01 , are found in many populations [1, 2]. The vast majority of sarcoidosis patients have a favourable prognosis, but approximately 20% develop a chronic, disabling disease [3].

Chronic beryllium disease (CBD) and chronic sarcoidosis share similarities as granulomatous diseases and they are pathologically indistinguishable from each other. CBD has been associated with HLA-DPB1*02:01 , especially with a glutamic acid residue at position 69 (Glu69) [4]. A functional splice-site polymorphism rs2076530 within the BTNL2 gene has been suggested to predispose to sarcoidosis [5]. However, previous studies have shown conflicting results as to whether HLA-DPB1 also predisposes to sarcoidosis, and whether the BTNL2 association is a result of linkage disequilibrium with HLA-DRB1 [6, 7].

The main objective of this study was to evaluate the HLA-DPB1 polymorphisms and the BTNL2 splice-site variant in Finnish patients suffering from sarcoidosis followed-up for 5–15 years and clinically categorised into subgroups based on disease prognosis. In addition, we constructed haplotypes containing MHC class II genes ( HLA-DRB1 and - DPB1 ) and rs2076530, and studied the influence of MHC markers and their combinations on disease susceptibility.

We examined a total of 188 patients with verified pulmonary sarcoidosis. The patients were divided into those with a disease resolved within 2 years (n = 90) and those with persisting activity at …
A simple aid for the application of skin preparations
Authors: S.K. Goolamali
Journal: British Journal of Dermatology (1979)

Journal Article A simple aid for the application of skin preparations Get access S.K. Goolamali S.K. Goolamali Central Middlesex and Wembley Hospitals, London and Northwick Park Hospital, Harrow, Middlesex Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 101, Issue 6, 1 December 1979, Pages 723–724, https://doi.org/10.1111/j.1365-2133.1979.tb05654.x Published: 01 December 1979
The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial
Authors: W Cambach, RV Chadwick-Straver, RC Wagenaar, AR van Keimpema, HC Kemper
Journal: European Respiratory Journal (1997)

The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment, and a 3 month control period of drug treatment only, for asthmatic patients and patients with chronic obstructive pulmonary disease (COPD). The programme was run by physiotherapists in eight local practices, and included exercise training, patient education, breathing retraining, evacuation of mucus, relaxation techniques, and recreational activities. In a randomized controlled trial with a cross-over design, the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life (QOL). Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests. QOL was evaluated by means of the Chronic Respiratory Disease Questionnaire (CRDQ). After 3 months, the patients who started with rehabilitation showed significant improvements in endurance time (421 s) and cardiac frequency (6 beats.min-1) during cycling, walking distance (39 m), and total CRDQ score (17 points) compared to the control group. These improvements were still significant after 6 months. Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way, with the exception that there was a greater improvement in walking distance for asthmatics. Improvements in exercise tolerance were not significantly correlated with improvements in QOL. Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practices improves exercise tolerance and quality of life.
Effectiveness of Chloroquine and Inflammatory Cytokine Response in Patients With Early Persistent Musculoskeletal Pain and Arthritis Following Chikungunya Virus Infection
Authors: Arvind Chopra, Manjit Saluja, Anuradha Venugopalan
Journal: Arthritis & Rheumatology (2013)

To evaluate whether chloroquine (CQ) is more effective than meloxicam for treating early musculoskeletal pain and arthritis following acute chikungunya (CHIK) virus infection.During the 2006 CHIK epidemic, 509 rural community cases of acute CHIK virus infection were identified in the district of Sholapur in India. Seventy consenting adult patients (seropositive for IgM/IgG anti-CHIK antibody) with early persistent musculoskeletal pain and arthritis were randomized into a 24-week, 2-arm, parallel efficacy trial of CQ (250 mg/day) and meloxicam (7.5 mg/day). Assessors completed a rheumatology evaluation in a blinded manner and collected blood samples in the patients' homes, as per protocol. Laboratory parameters included serum cytokine assay (interleukin-6 [IL-6], interferon-γ [IFNγ], tumor necrosis factor α, CXCL10/IFNγ-inducible protein 10, and IL-13). Twenty-two patients who failed to meet the eligibility criteria (low pain cohort) were also followed up with similar evaluations. An intent-to-treat analysis was completed. At baseline, the 2 groups (38 patients randomized to receive CQ and 32 patients randomized to receive meloxicam) were well matched.There were no significant efficacy differences between the meloxicam group and the CQ group (mean changes in the visual analog scale score for pain -3.9 and -4.2, respectively). Patients improved significantly. Cytokine levels remained several-fold increased, were disproportionate to the clinical response, and were not different from those in the low pain cohort. Seven patients withdrew. Adverse events were mild and infrequent.This exploratory community intervention trial failed to identify an advantage of CQ over meloxicam to treat early musculoskeletal pain and arthritis following acute CHIK virus infection, but therapeutic efficacy of CQ was not ruled out. The inflammatory cytokine response was intense and was not consistent with clinical status.
The yin and the yang of p27Kip1 as a target for cancer therapy
Authors: B. Eymin, E. Brambilla
Journal: European Respiratory Journal (2004)

Schematically, human tumours arise because tumour cells escape from extracellular signals that physiologically monitor cellular proliferation, as well as cell death, and acquire the property to grow continuously. During tumourigenesis, many proteins that normally control the proper timing of cell growth, e.g. the cyclins, or prevent the occurrence of unappropriate apoptosis are abnormally expressed or activated, and act as typical oncogenes leading to hyperproliferation and/or protecting tumour cells from death. In contrast, proteins that normally prevent, for example, damaged cells to progress into the next phase of the cell cycle or act as apoptosis inducers, if the damage can not be repaired, are frequently inactivated in tumour cells and act as tumour suppressor genes. Therefore, loss of tumour suppressor genes associated with abnormal hyperactivity of oncogenes classically contribute to human carcinogenesis. However, affecting a clear-cut function of tumour suppressor or oncogene remains a subject of debate for certain proteins. The p27Kip1 is a member of the cyclin-dependent kinase inhibitory proteins, which also include: p21WAF1, the target gene of p53; p16INK4a, a member of the retinoblastoma (Rb) pathway; and p57Kip2. In combination with p16INK4a, it plays a major role in counteracting the activity of cyclins D1 and E on Rb phosphorylation and subsequent G1‐S transition. Therefore, it coordinates …
Cough frequency in health and disease
Authors: Nadia Yousaf, William Monteiro, Sergio Matos, Surinder S. Birring, Ian D. Pavord
Journal: European Respiratory Journal (2012)

To the Editor:

Chronic cough is a difficult clinical problem, partly because there is an absence of well-validated means to assess cough [1, 2]. We have previously reported that the semi-automated computerised Leicester Cough Monitor detects cough accurately over 6 h and that cough frequency is increased in patients with chronic cough compared to controls [3, 4]. There remains uncertainty on the performance of the system over 24 h and across the range of expected cough frequency in larger populations. We set out to address these questions in healthy adult volunteers and adult volunteers with respiratory disease.

44 healthy volunteers were recruited from those responding to a poster advertisement. All reported no current respiratory symptoms, were nonsmokers with a <5 pack-yr past smoking history and had normal spirometric values, methacholine airway responsiveness and induced sputum inflammatory cell counts. 78 patients with respiratory disease were recruited from respiratory clinics. The diagnostic criteria for the conditions have been described previously [5]. Six current smokers and four males taking angiotensin converting enzyme inhibitors (ACEi) were also recruited. The study was approved by the Leicestershire, Northampton and Rutland Research Ethics Committee.

All volunteers underwent spirometry and those with normal spirometry had a methacholine inhalation test using the tidal breathing method. The Leicester Cough Monitor (iRiver iFP-799 mp3 device; iRiver Europe GmbH, Eschborn, Germany and Sennheiser MKE 2–5 field microphone; Sennheiser electronic GmbH & Co. KG, Wedemark, Germany) was attached and recordings obtained and analysed as …