tbuckley/cabot-search huggingface dataset:
Assessment of Protein Distance Measures and Tree-Building Methods for Phylogenetic Tree Reconstruction
Authors: Volker Hollich, Lena Milchert, Lars Arvestad, Erik L. L. Sonnhammer
Journal: Molecular Biology and Evolution (2005)

Distance-based methods are popular for reconstructing evolutionary trees of protein sequences, mainly because of their speed and generality. A number of variants of the classical neighbor-joining (NJ) algorithm have been proposed, as well as a number of methods to estimate protein distances. We here present a large-scale assessment of performance in reconstructing the correct tree topology for the most popular algorithms. The programs BIONJ, FastME, Weighbor, and standard NJ were run using 12 distance estimators, producing 48 tree-building/distance estimation method combinations. These were evaluated on a test set based on real trees taken from 100 Pfam families. Each tree was used to generate multiple sequence alignments with the ROSE program using three evolutionary models. The accuracy of each method was analyzed as a function of both sequence divergence and location in the tree. We found that BIONJ produced the overall best results, although the average accuracy differed little between the tree-building methods (normally less than 1%). A noticeable trend was that FastME performed poorer than the rest on long branches. Weighbor was several orders of magnitude slower than the other programs. Larger differences were observed when using different distance estimators. Protein-adapted Jukes-Cantor and Kimura distance correction produced clearly poorer results than the other methods, even worse than uncorrected distances. We also assessed the recently developed Scoredist measure, which performed equally well as more complex methods.
Molecular Mechanisms of Resistance to Therapies Targeting the Epidermal Growth Factor Receptor
Authors: E. Ramsay Camp, Justin Summy, Todd W. Bauer, Wenbiao Liu, Gary E. Gallick, Lee M. Ellis
Journal: Clinical Cancer Research (2005)

Abstract Targeted therapies that inhibit the activity of tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) have shown activity against solid malignancies when used as single agents or in combination with chemotherapy. Although anti-EGFR therapies are active in some patients, eventually disease in nearly all patients will become refractory to therapy. Therefore, a better understanding of the mechanisms of resistance to anti-EGFR therapies is critical to further improve the efficacy of this class of agents. Mechanisms that mediate resistance to anti-EGFR therapies include the presence of redundant tyrosine kinase receptors, increased angiogenesis, and the constitutive activation of downstream mediators. Two recent landmark publications have also shown that specific mutations in the kinase domain of EGFR in some lung carcinomas are associated with markedly improved response rates to an EGFR tyrosine kinase inhibitor. Mutations in the EGFR receptor seem to play a significant role in determining the sensitivity of tumor cells to EGFR inhibitor therapy by altering the conformation and activity of the receptor. As the field of molecular therapeutics continues to evolve, a comprehensive understanding of resistance mechanisms will ultimately lead to refinements in our regimens to provide better care for patients with cancer.
Quantitative longitudinal evaluations of hepatitis delta virus RNA and hepatitis B virus DNA shows a dynamic, complex replicative profile in chronic hepatitis B and D
Authors: Melanie Schaper, Francisco Rodriguez-Frias, Rosendo Jardi, David Tabernero, Maria Homs, Gerardo Ruiz, Josep Quer, Rafael Esteban, Maria Buti
Journal: Journal of Hepatology (2010)
Stem cell MicroRNAs in senescence and immortalization: novel players in cancer therapy
Authors: Jose A. Leal, Andrea Feliciano, Matilde E. LLeonart
Journal: Medicinal Research Reviews (2011)

The molecular etiology of malignancy remains one of the most challenging disease processes under scientific investigation; therefore, improved approaches for their treatment are urgently needed. MicroRNAs are highly conserved nonprotein‐coding RNAs that regulate gene expression. They are involved in important homeostatic processes, such as cellular proliferation, cell death and development, and affect many diseases, including cancer. High‐throughput screenings based on microRNAs related to senescence/immortalization are potential tools for identifying novel proliferative microRNAs that might be involved in carcinogenesis. Recently, a subgroup of highly proliferative microRNAs, which belong to a cluster expressed exclusively in embryonic stem cells and their malignant derivatives (embryonic carcinoma cells), was revealed to play a role in senescence bypass, thereby providing immortalization to human cells. This finding supports the cancer stem cell theory and the relevance of microRNAs in human tumors. This article recapitulates the role of microRNAs that are associated with stem cell properties and their possible link in common pathways related to immortalization and cancer. Ultimately, cancer therapy that is based on the induction of a senescence response is proposed to be highly associated with the loss of stemness properties. Thus, it would be possible to “kill two birds with one stone”: along with the inhibition of stemness properties in cancer stem cells, the senescence response could be induced to destroy the cancer stem cell population within a tumor. © 2011 Wiley Periodicals, Inc. Med Res Rev
Asthma in adolescent athletes
Authors: Kai-Håkon Carlsen, Erlend Hem, Trine Stensrud
Journal: British Journal of Sports Medicine (2011)

Athletes active in endurance sports are at an increased risk of acquiring asthma through their sports activities, especially so for cross-country skiers, biathlon skiers, swimmers and athletes of other endurance sports. Asthma may be present from early childhood or develop while in active sports. This article focuses on the physical activity and sports activities in children and adolescents. Exercise-induced asthma (EIA) is found in 8–10% of a normal child population of school age and in about 35% of children with current asthma. EIA is caused by the markedly increased ventilation during exercise, with increased heat and water loss through respiration, leading to bronchial constriction. The risk of developing asthma in the young athlete is related to the repeated daily training activity with increased epithelial damage of the airways, delayed repair due to the daily repetition of the training and increased airway mucosal inflammation. The increased environmental exposure through the sports activity to environmental agents, such as cold, dry air in skiers and chlorine compounds in swimmers, increases symptoms and signs of asthma and bronchial hyper-responsiveness, either worsening an existing asthma or leading to a novel disease in a previously healthy athlete. Several specific aspects of daily training life, environmental exposure, diagnostic procedures and aspects of treatment related to the regulations of medication use in sports need particular attention when addressing the adolescent athlete with respiratory symptoms.
Herpes simplex virus in the respiratory tract of critical care patients: a prospective study
Authors: Peggy Bruynseels, Philippe G Jorens, Hendrik E Demey, Herman Goossens, Stefaan R Pattyn, Monique M Elseviers, Joost Weyler, Leo L Bossaert, Yves Mentens, Margareta Ieven
Journal: The Lancet (2003)
Case of Ainhum
Authors: H. J. McC. Todd
Journal: BMJ (1891)

substances used in hiis anti-tuberculous treatment, it must not be concluded that our researches are necessarily upon exactly the same lines.Koch has stated that his liquid is a "gly- cerine extract of pure cultivations of the tuberele bacillus," and without further details it is impossible to interpret the exact meaning of this expression, and it does not necessarily follow, however probable it may be, that our extract of glycerine-broth cultivations, or the substances isolated tlhere- from, would produce exactly similar results to those produced by Koch's fluid.
Impotence as a Presenting Symptom of Presumed Prolactinoma in a Patient with Diabetes Mellitus
Authors: K M Mohamed Shakir
Journal: Diabetes Care (1983)

Impotence in diabetic men is usually considered to be due to neuropathic factors or vascular insufficiency. However, factors unrelated to diabetes may occasionally produce sexual dysfunction in these patients. Recently, a diabetic patient presented to our clinic with the complaint of impotence. In this patient, macroprolactinemia was discovered. With appropriate therapy, the sexual dysfunction improved and this case is reported here.
A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma
Authors: Laura Rosiñol, José Antonio Pérez-Simón, Anna Sureda, Javier de la Rubia, Felipe de Arriba, Juan José Lahuerta, José David González, Joaquín Díaz-Mediavilla, Belén Hernández, Javier García-Frade, Dolores Carrera, Angel León, Miguel Hernández, Pascual Fernández Abellán, Juan Miguel Bergua, Jesús San Miguel, Joan Bladé
Journal: Blood (2008)
Government’s public health responsibility deal is met with scepticism
Authors: Adrian O’Dowd
Journal: BMJ (2011)

A national agreement between the UK government and the food and drinks industry launched today has met with a sceptical reaction from health professionals and charities.

The “responsibility deal,” an agreement between the government, the industry, and health organisations, contains a series of voluntary pledges aimed at improving public health in England, but several health bodies and charities have refused to sign up to it.

In addition to the likes of the BMA and Alcohol Concern, which have already pulled out of the deal ( BMJ 2011;342:d1659, 14 Mar, doi:10.1136/bmj.d1659), Diabetes UK and the British Heart Foundation have now also withdrawn.

The health secretary, Andrew Lansley, launching the deal, said that joint working meant that the deal could deliver faster and better results …
Importance of Connexin-43 based gap junction in cirrhosis and acute-on-chronic liver failure
Authors: Vairappan Balasubramaniyan, Dipok Kumar Dhar, Anne E. Warner, Wai-Yin Vivien Li, Azin Farzan Amiri, Beverley Bright, Rajeshwar P. Mookerjee, Nathan A. Davies, David L. Becker, Rajiv Jalan
Journal: Journal of Hepatology (2013)
Inhibitory Effects of Glibenclamide on Cystic Fibrosis Transmembrane Regulator, Swelling-Activated, and Ca <sup>2+</sup> -Activated Cl <sup>−</sup> Channels in Mammalian Cardiac Myocytes
Authors: Jun Yamazaki, Joseph R. Hume
Journal: Circulation Research (1997)

Abstract Recent studies have provided evidence that sulfonylureas, in addition to blocking ATP-sensitive K + (K ATP ) channels, also inhibit cystic fibrosis transmembrane regulator (CFTR) Cl − channels in epithelial and cardiac cells. The purpose of this study was to test whether the sulfonylurea glibenclamide might also inhibit other types of cardiac Cl − channels. Whole-cell patch-clamp techniques were used to compare the effects of glibenclamide on CFTR Cl − currents in guinea pig ventricular myocytes, swelling-activated Cl − currents in guinea pig atrial myocytes, and Ca 2+ -activated Cl − currents in canine ventricular myocytes. Glibenclamide markedly inhibited CFTR Cl − currents in a voltage-independent manner at 22°C, with estimated IC 50 values of 12.5 and 11.0 μmol/L at +50 and −100 mV, respectively. The outwardly rectifying swelling-activated Cl − current in atrial cells was less sensitive to glibenclamide, and the block exhibited voltage dependence. At 22°C, the estimated IC 50 values were 193 and 470 μmol/L at +50 and −100 mV, respectively, and block was enhanced at 35°C. Macroscopic Cl − currents activated by a rise in intracellular Ca 2+ , induced by either Ca 2+ -induced Ca 2+ release or by external application of the Ca 2+ ionophore A23187, were also markedly inhibited at 22°C by glibenclamide in a voltage-independent manner. The estimated IC 50 values were 61.5 and 69.9 μmol/L at +50 and −100 mV, respectively. These results suggest that glibenclamide, an inhibitor of cardiac CFTR Cl − channels, also inhibits swelling-activated and Ca 2+ -activated Cl − channels at higher concentrations. The results also suggest that studies attributing the beneficial or deleterious effects of sulfonylurea compounds in the heart solely to blockade of K ATP channels should use submicromolar concentrations of these agents to minimize possible secondary interactions with cardiac Cl − channels.
Guidelines for the management of basal cell carcinoma
Authors: N R Telfer, G B Colver, C A Morton
Journal: British Journal of Dermatology (2008)

This article represents a planned regular updating of the previous British Association of Dermatologists guidelines for the management of basal cell carcinoma. These guidelines present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.
Long-term safety of rituximab in patients with rheumatic diseases and chronic or resolved hepatitis B virus infection
Authors: Ioannnis Mitroulis, Chrisoula Hatzara, Anna Kandili, Emilia Hadziyannis, Dimitrios Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2012)

Endometrioid carcinoma simultaneously involving ovaries as well as the uterine corpus may present a diagnostic dilemma because of the difficulty in determining whether the lesions are separate primary tumors or metastases. It has been reported that the detection of clonality using microsatellite markers may be useful in solving this dilemma. To determine the usefulness of this technique, we compared the genetic alterations in microsatellite markers present in matched pairs of ovarian tumors from 12 patients. The study includes four ovarian cancer FIGO stage I and eight stage III/IV patients, and four patients also with independent endometrial carcinoma of the uterus. DNA from paraffin-embedded tissue was extracted and amplified using a multiplex polymerase chain reaction, after which the status of microsatellite instability and loss of heterozygosity in four microsatellite loci (<i>BAT25</i>, <i>BAT26</i>, <i>D17S250</i>, and <i>D5S346</i>) were determined. In the four patients with stage I ovarian cancer, four microsatellite markers were identical in one patient and three were identical in the remaining three patients. In high-stage patients, three markers were identical in at least 4/8 cases. In three of four patients with uterine involvement, three of the four markers were identical in the uterine tumor and one of the corresponding ovarian tumors. These results suggest that genetic discordance does not indicate independent origin or metastasis of the tumor but instead a progression of genetic changes at separate sites probably due to the marked genetic instability existing in these tumors. Because of these discordant genetic changes, great caution should be taken when distinguishing between primary and metastatic tumors on the basis of microsatellite markers.
Lymphedema in Breast Cancer Survivors: Incidence, Degree, Time Course, Treatment, and Symptoms
Authors: Sandra A. Norman, A. Russell Localio, Sheryl L. Potashnik, Heather A. Simoes Torpey, Michael J. Kallan, Anita L. Weber, Linda T. Miller, Angela DeMichele, Lawrence J. Solin
Journal: Journal of Clinical Oncology (2008)

Purpose To examine the incidence, degree, time course, treatment, and symptoms of lymphedema in breast cancer survivors. Methods We conducted a 5-year, population-based prospective study of 631 randomly selected Philadelphia and Delaware County, Pennsylvania female residents with incident breast cancer who were diagnosed from 1999 to 2001. Using a questionnaire previously validated against physical therapists’ measurement-based clinical criteria, we assigned a score indicating the degree of lymphedema (none, mild, or moderate/severe) to each month of follow-up based on the respondent's perceived differences in hand/arm size. Standard survival analysis methods permitted maximum use of follow-up. Results Five-year cumulative incidence of lymphedema was 42 (42%) per 100 women. Among the 238 affected women, lymphedema first occurred within 2 years of diagnosis in 80% and within 3 years in 89%. Among 433 women observed for 3 years, 23% reported no more than mild lymphedema, 12% reported moderate/severe lymphedema, and 2% reported chronically moderate/severe lymphedema. Women with mild lymphedema were more than three times more likely to develop moderate/severe lymphedema than women with no lymphedema. Thirty-seven percent of women with mild lymphedema and 68% with moderate/severe lymphedema received treatment. Increasing proportions of women with increasing degree of lymphedema reported symptoms (eg, jewelry too tight, tired/thick/heavy arm). Symptoms present before the first occurrence of lymphedema were associated with a higher probability of later lymphedema (eg, hazard ratio for jewelry too tight = 7.37; 95% CI, 4.26 to 12.76). Conclusion Lymphedema after breast cancer is common but mostly mild. Subtle differences in self-reported hand/arm size and symptoms can be early signs of progressing lymphedema.
Randomized Phase II Trial of Custirsen (OGX-011) in Combination with Docetaxel or Mitoxantrone as Second-line Therapy in Patients with Metastatic Castrate-Resistant Prostate Cancer Progressing after First-line Docetaxel: CUOG Trial P-06c
Authors: Fred Saad, Sebastien Hotte, Scott North, Bernie Eigl, Kim Chi, Piotr Czaykowski, Lori Wood, Michael Pollak, Scott Berry, Jean-Baptiste Lattouf, Som D. Mukherjee, Martin Gleave, Eric Winquist
Journal: Clinical Cancer Research (2011)

Clusterin (CLU) is an antiapoptotic, stress-induced protein conferring treatment resistance when overexpressed. This study tested custirsen, a CLU inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing during or within 6 months of initial docetaxel therapy.Men were randomized to receive either docetaxel + prednisone + custirsen (DPC) or mitoxantrone + prednisone + custirsen (MPC).Forty-two patients received study treatment. Toxicity was similar in both arms. Twenty patients treated with DPC received a median of 8 cycles; overall survival (OS) was 15.8 months. Median time to pain progression (TTPP) was 10.0 months; 10 of 13 (77%) evaluable patients had pain responses. Three of 13 (23%) evaluable patients had objective partial responses. Prostate-specific antigen (PSA) declines of 90% or more, 50% or more, and 30% or more occurred in 4 (20%), 8 (40%), and 11 (55%) patients, respectively. Twenty-two patients treated with MPC received a median of 6 cycles; OS was 11.5 months. The median TTPP was 5.2 months; 6 of 13 (46%) evaluable patients had pain responses. No objective responses were observed. PSA declines of 50% or more and 30% or more occurred in 6 (27%) and 7 (32%) patients, respectively. Low serum CLU levels during treatment showed superior survival for patients based on modeling with proportional hazard regression with a time-dependent covariate and different landmarks.Custirsen plus either docetaxel or mitoxantrone was feasible in patients with progressive mCRPC following first-line docetaxel therapy. Pain relief was higher than expected, with interesting correlations between serum CLU and survival. A phase III trial evaluating the pain palliation benefit of custirsen with taxane therapy is ongoing.
Radiological manifestations of Reiter's syndrome.
Authors: W Martel
Journal: Annals of the Rheumatic Diseases (1979)

Reiter's syndrome (RS) presents with a broad spectrum of radiological manifestations.Although there is an overlap with other connective tissue diseases134, 214, 221, 248, 286 certain features appear to be characteristic, particularly when present in combination.This report concerns the radiological findings in 36 patients with RS.They are compared with the radiological manifestations of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PSA). Patients and methodsRecords of 36 patients were selected from the files of the department of radiology, University of Michigan Medical Center, on the basis of previously docu- mented positive radiological findings.The records were then reviewed to confirm the clinical diagnosis of RS.For the purpose of this study the diagnostic criteria were (1) objective evidence of arthritis of the appendicular joints, and (2) two of the following: mucocutaneous lesions, conjunctivitis, and urethritis.These features had to have occurred within six weeks of one another.It was recognised that the arthritis in patients with RS may be limited to the spine, but because of the difficulty in evaluating such arthritis, particularly in the early stages, such cases were not included in the study.Radiological joint surveys of the spine and appendicular joints were available in 20 cases.Six others had had fairly complete radiological evalua- tions, although not all joints were included.Films of the lumbosacral spine were available in all cases.Many patients had been followed-up clinically for several years, affording opportunities for extended periods of radiological observation.cases. REGIONAL OSTEOPOROSISThis was a striking finding in the early stages of the disease in three patients.It was limited to the foot in two cases (Fig. 4) and to the hand in one.A frequent feature was relative absence of osteoporosis despite extensive joint destruction.This was particularly evident in the foot.
Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
Authors: C. Parker, S. Nilsson, D. Heinrich, S.I. Helle, J.M. O'Sullivan, S.D. Fosså, A. Chodacki, P. Wiechno, J. Logue, M. Seke, A. Widmark, D.C. Johannessen, P. Hoskin, D. Bottomley, N.D. James, A. Solberg, I. Syndikus, J. Kliment, S. Wedel, S. Boehmer, M. Dall'Oglio, L. Franzén, R. Coleman, N.J. Vogelzang, C.G. O'Bryan-Tear, K. Staudacher, J. Garcia-Vargas, M. Shan, Ø.S. Bruland, O. Sartor
Journal: New England Journal of Medicine (2013)

Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases.
Sirtuins and Their Relevance to the Kidney
Authors: Chuan-Ming Hao, Volker H. Haase
Journal: Journal of the American Society of Nephrology (2010)

Sirtuins (silent information regulator 2 [Sir2] proteins) belong to an ancient family of evolutionary conserved nicotinamide adenine dinucleotide (NAD)(+)-dependent enzymes with deacetylase and/or mono-ADP-ribosyltransferase activity. They regulate DNA repair and recombination, chromosomal stability, and gene transcription, and most importantly mediate the health-promoting effects of caloric restriction (CR), which includes the retardation of aging. At least seven Sir2 homologs, sirtuins (SIRT) 1 to 7 have been identified in mammals. Mammalian SIRT1, the most extensively studied family member, couples protein deacetylation with NAD(+) hydrolysis and links cellular energy and redox state to multiple signaling and survival pathways. Cell-type and context-specific activation of sirtuins increases resistance to metabolic, oxidative, and hypoxic stress in different tissues. In particular, SIRT1 plays a central role in mediating the beneficial effects of CR, and its activation associates with longevity and the attenuation of metabolic disorders. SIRT1 in the kidney is cytoprotective and participates in the regulation of BP and sodium balance. Here, we review sirtuin biology and discuss how CR-triggered sirtuin-dependent pathways affect renal physiology and the pathogenesis of kidney diseases and related disorders.