tbuckley/cabot-search huggingface dataset:
Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta
Authors: Grazia Anna Niro, Alessia Ciancio, Giovanni Battista Gaeta, Antonina Smedile, Aldo Marrone, Antonella Olivero, Maria Stanzione, Ezio David, Giuseppina Brancaccio, Rosanna Fontana, Francesco Perri, Angelo Andriulli, Mario Rizzetto
Journal: Hepatology (2006)

Therapy of chronic hepatitis delta with standard interferon therapy has met with limited efficacy. This study was designed to examine the efficacy and safety of peginterferon with or without ribavirin. Thirty-eight serum hepatitis B surface antigen- and HDV RNA-positive patients with alanine aminotransferase (ALT) more than 1.5 times the upper normal limit received peginterferon alpha-2b (1.5 μg/kg) alone as monotherapy (n = 16) or in combination with ribavirin (n = 22), for 48 weeks. Thereafter, all the patients were maintained on peginterferon for 24 weeks and followed for 24 weeks off therapy. The primary end point studied was the virological and biochemical response at the end of follow-up. HDV RNA was determined by single or nested polymerase chain reaction assays. Twenty-seven patients (71%), 11 receiving monotherapy and 16 receiving the combination treatment, completed the follow-up. At the end of treatment, a virological response was observed in 3 of the patients treated with peginterferon (19%) and in 2 of the patients treated with combination therapy (9%), and a biochemical response was observed in 6 (37.5%) and 9 patients (41%), respectively. In nonresponders, ALT diminished from a mean of 174 ± 53 to 86 ± 41 IU/L. At the end of follow-up, serum HDV RNA was negative in 8 patients (21%), and a biochemical response was detected in 10 patients (26%). Treatment was discontinued in 25% of the patients, and dosing was modified in 58%. In conclusion , a prolonged course of peginterferon alpha-2b resulted in clearance of serum HDV RNA and ALT normalization in a fifth of patients with chronic hepatitis D, while ribavirin had no effect on the viral clearance rate. Overall tolerance of therapy was poor.
Is treatment with ICS and LABA cost-effective for COPD? Multinational economic analysis of the TORCH study
Authors: A. H. Briggs, H. A. Glick, G. Lozano-Ortega, M. Spencer, P. M. A. Calverley, P. W. Jones, J. Vestbo
Journal: European Respiratory Journal (2009)

The TOwards a Revolution in COPD Health (TORCH) study was a 3-yr multicentre trial of 6,112 patients randomised to salmeterol (Salm), fluticasone propionate (FP), a Salm/FP combination (SFC) or placebo (P). Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed. For four regions, 3-yr all-cause hospitalisation, medication and outpatient care costs were calculated. The sample was restricted to the 21 countries (n = 4,237) in which European quality of life five-dimension (EQ-5D) data were collected in order to estimate the number of quality-adjusted life years (QALYs). Regression models were fitted to survival, study medication cost, other medication cost and EQ-5D data in order to estimate total cost, number of QALYs and cost per QALY, adjusted for missing data and region. SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars (USD) compared with P (95% confidence interval 21,400–123,500 USD). Estimates for Salm versus P (197,000 USD) and FP versus P (78,000 USD) were less favourable. The US estimates were greater than those from other regions; for SFC versus P, the cost per QALY was 77,100 (46,200–241,700) USD compared to 24,200 (15,200–56,100) USD in Western Europe. Compared with P, SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone, and is, therefore, preferred to these monotherapies on the grounds of cost-effectiveness.
Service Use and Outcomes of First-Admission Patients With Psychotic Disorders in the Suffolk County Mental Health Project
Authors: Ramin Mojtabai, Daniel Herman, Ezra S. Susser, Nancy Sohler, Thomas J. Craig, Janet Lavelle, Evelyn J. Bromet
Journal: American Journal of Psychiatry (2005)

The purpose of the study was to examine the inpatient and outpatient service use and 4-year outcomes of newly admitted psychotic patients during a period of rapid change in the provision of psychiatric services in a well-defined catchment area in New York State in the 1990s.Subjects were 573 participants of the Suffolk County Mental Health Project. This group comprised patients with psychotic disorders first admitted between September 1989 and August 1995 to 12 inpatient facilities across Suffolk County, N.Y., and followed for up to 48 months. The subjects' service use, course of illness, symptomatic outcomes, suicide risk, homelessness risk, and satisfaction with care were compared across admission years.The length of inpatient stays decreased significantly across the years. However, the number of outpatient visits and therapy sessions did not vary. Although the patients admitted in later years were more symptomatic at admission to their first hospitalization, their course and outcomes over the follow-up period were not worse and they were not less satisfied with their care, compared with the patients admitted in earlier years.The clinical characteristics of patients and the role of inpatient care in the management of patients with psychotic disorders gradually changed during the 1990s. These changes, however, were not associated with changes in the use of outpatient services or outcomes. Nevertheless, shorter hospital stays and the presence of more severely ill patients highlight the need for more attention to linkage to aftercare and enhancement of support networks in the community.
Activation of Gαq-Coupled Signaling Pathways in Glomerular Podocytes Promotes Renal Injury
Authors: Liming Wang, Timothy A. Fields, Kathy Pazmino, Qunsheng Dai, James L. Burchette, David N. Howell, Thomas M. Coffman, Robert F. Spurney
Journal: Journal of the American Society of Nephrology (2005)

The glomerular podocyte plays a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by activation of cell surface G protein-coupled receptors (GPCR). Studies suggest that podocytes express GPCR that are implicated in the pathogenesis of glomerular diseases. Common to these GPCR systems is activation of phospholipase C through the Gq alpha-subunit (Galpha q). For investigating the role of Galpha q-coupled signaling pathways in promoting renal injury in podocytes, a constitutively active Galpha q subunit (Galpha qQ > L) was expressed in glomerular podocytes using the mouse nephrin promoter. Transgenic (TG) mice demonstrated albuminuria as well as a decrease in both kidney mass and nephron number. By light microscopy, a portion of the TG mice had glomerular abnormalities, including focal to diffuse hypercellularity and segmental sclerosis. Consistent with injury-promoting effects of Galpha qQ > L, there was a significant reduction in podocalyxin mRNA as well as nephrin mRNA and protein levels in glomeruli from TG mice compared with non-TG controls. Expression of the transgene also seemed to increase susceptibility to glomerular injury, because treatment with puromycin aminonucleoside enhanced proteinuria in TG mice compared with non-TG littermate controls (4.2 +/- 1.0 [TG] versus 1.6 +/- 0.3 [non-TG] mg/24 h; P = 0.0161). Thus, activation of Galpha q in glomerular podocytes caused alterations in glomerular histomorphology, albuminuria, decreased nephron mass, and reduced glomerular expression of both nephrin and podocalyxin as well as enhanced susceptibility to glomerular damage induced by puromycin aminonucleoside. It is speculated that Galpha q-coupled signaling cascades may be important effector pathways mediating renal injury.
Patterns of Segmental Duplication in the Human Genome
Authors: L. Zhang
Journal: Molecular Biology and Evolution (2004)

We analyzed the completed human genome for recent segmental duplications (size ≥ 1 kb and sequence similarity ≥ 90%). We found that approximately 4% of the genome is covered by duplications and that the extent of segmental duplication varies from 1% to 14% among the 24 chromosomes. Intrachromosomal duplication is more frequent than interchromosomal duplication in 15 chromosomes. The duplication frequencies in pericentromeric and subtelomeric regions are greater than the genome average by approximately threefold and fourfold. We examined factors that may affect the frequency of duplication in a region. Within individual chromosomes, the duplication frequency shows little correlation with local gene density, repeat density, recombination rate, and GC content, except chromosomes 7 and Y. For the entire genome, the duplication frequency is correlated with each of the above factors. Based on known genes and Ensembl genes, the proportion of duplications containing complete genes is 3.4% and 10.7%, respectively. The proportion of duplications containing genes is higher in intrachromosomal than in interchromosomal duplications, and duplications containing genes have a higher sequence similarity and tend to be longer than duplications containing no genes. Our simulation suggests that many duplications containing genes have been selectively maintained in the genome.
Bronchodilator testing: an endless story
Authors: R. Pellegrino, A. Antonelli, M. Mondino
Journal: European Respiratory Journal (2010)

The history of the bronchodilator test dates back to the late 1950s when airway diseases were classified as reversible or irreversible depending on the response to bronchodilators 1, 2. The hope to differentiate asthma from chronic obstructive pulmonary disease (COPD) on this basis was such that the test soon gained popularity in clinical practice. Two large trials published in the mid 1980s, however, dimmed the original enthusiasm on such a test because no clear cut-off was found between asthmatic and COPD patients 3, 4. In addition, the response depended on several factors, such as definition and severity of airflow obstruction and spirometric parameter considered for the functional response to the dilator agent together with its relevant threshold of natural variability. Finally, the test was scarcely reproducible over time in the individual patients. Somehow, these two studies challenged the common notion of that time that airway reversibility was a typical and unique feature of bronchial asthma.

After more than two decades of intensive study and a long series of negative and positive publications on this issue, bronchoreversibility testing is still largely used in clinical practice and deemed to guide the clinician through the diagnostic and follow-up process 5, 6. For instance, large increments in the forced expiratory volume in 1 s (FEV1) >400 mL after an acute dose of salbutamol support the diagnosis of asthma in patients with a history compatible with the disease 7, though prospective studies confirming the validity of such a threshold have never been published and the role of similar improvements in forced vital capacity (FVC) in this respect has not been documented. A positive response …
Assessing Risk for Pelvic Inflammatory Disease and Its Sequelae
Authors: A. Eugene Washington
Journal: JAMA (1991)

To assess the risk for pelvic inflammatory disease (PID), a practitioner must evaluate the likelihood that a woman has PID or will be exposed to a sexually transmitted disease causing PID. Successful risk assessment depends on accurate information about variables influencing risk of PID. To determine the current state of knowledge about PID risk variables, we examined data in published reports. Data on each risk variable were scrutinized to discern which link(s) in the PID risk chain it affects (acquisition of a sexually transmitted disease, development of PID, or development of PID sequelae) and whether it is a risk marker or a risk factor. Most PID risk variables, particularly sexual behaviors, are associated with acquisition of a sexually transmitted disease, rather than development of PID itself. With the exception of age, demographic and social indicators of risk appear to be risk markers, while contraceptive practices appear more often to be risk factors than risk markers. Additional data are needed for most PID risk variables confidently to categorize them as risk factors. Enough information is available, however, to begin assessing risk for PID, so that appropriate counseling can ensue and timely diagnosis can be made. (<i>JAMA</i>. 1991;266:2581-2586)
Hepatocyte growth factor activator inhibitor-2 (HAI-2) is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer
Authors: K. Nakamura, F. Abarzua, A. Hongo, J. Kodama, Y. Nasu, H. Kumon, Y. Hiramatsu
Journal: Annals of Oncology (2008)
Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle.
Authors: D W Liu, G A Gintant, C Antzelevitch
Journal: Circulation Research (1993)

Recent studies from our laboratory involving syncytial preparations have delineated electrophysiological distinctions between epicardium, endocardium, and a unique population of cells in the deep subepicardial to midmyocardial layers (M region) of the canine ventricle. In the present study, we used standard microelectrode, single microelectrode switch voltage-clamp, and whole-cell patch-clamp techniques to examine transmembrane action potentials, steady-state current-voltage relations, and the 4-aminopyridine-sensitive transient outward current (Ito1) in myocytes enzymatically dissociated from discrete layers of the free wall of the canine left ventricle. Action potential characteristics of myocytes isolated from the epicardium, M region, and endocardium were very similar to those previously observed in syncytial preparations isolated from the respective regions of the ventricular wall. A prominent spike and dome was apparent in myocytes from epicardium and the M region but not in myocytes from endocardium. Action potential duration-rate relations were considerably more pronounced in cells isolated from the M region. Current-voltage relations recorded from cells of epicardial, M region, and endocardial origin all displayed an N-shaped configuration with a prominent negative slope-conductance region. The magnitude of the inward rectifier K+ current (IK1) was 392 +/- 86, 289 +/- 65, and 348 +/- 115 pA in epicardial, M region, and endocardial myocytes, respectively, when defined as steady-state current blocked by 10 mM Cs+. Similar levels were obtained when IK1 was defined as the steady-state difference current measured in the presence (6 mM) and absence of extracellular K+. Ito1 was significantly greater in epicardial and M region myocytes than in endocardial myocytes. At a test potential of +70 mV (holding potential, -80 mV), Ito1 amplitude was 4,203 +/- 2,370, 3,638 +/- 1,135, and 714 +/- 286 pA in epicardial, M region, and endocardial cells, respectively. No significant differences were observed in the voltage dependence of inactivation of Ito1 in the three cell types. The time course of reactivation of Ito1 was slower in cells from the M region compared with either epicardial or endocardial cells. Our data suggest that prominent heterogeneity exists in the electrophysiology of cells spanning the canine ventricular wall and that differences in the intensity of the transient outward current contribute importantly, but not exclusively, to this heterogeneity. These findings should advance our understanding of basic heart function and the ionic bases for the electrocardiographic J wave, T wave, U wave, and long QT intervals as well as improve our understanding of some of the complex factors contributing to the development of cardiac arrhythmias.
Is the multi-joint pointing movement model applicable to equilibrium control during upper trunk movements?
Authors: Alexey Alexandrov, Alexander Frolov, Jean Massion
Journal: Behavioral and Brain Sciences (1995)

Abstract Two aspects of the target article, (1) the extension of the equilibrium point theory to multi-joint movements, and (2) the consequence that the EMG pattern is not directly controlled by the central nervous system (CNS), are discussed in light of the experiments on upper trunk bending in humans. The principle component kinematic analysis and the analysis of the EMG data, obtained under microgravity and additional loading conditions, support the application of Feldman and Levin's for multi-joint pointing movement to equilibrium control during upper trunk movement.
Genetic control of cell-mediated responsiveness to an AKR tumor-associated antigen: mapping of the locus involved to the I region of the H-2 complex.
Authors: D Meruelo, B Deak, H O McDevitt
Journal: The Journal of Experimental Medicine (1977)

The role of H-2-linked genes in controlling resistance to murine leukemia viruses has been studied by measuring the cell-mediated immune response of F1 hybrid mice (between AKR and various C3H and C57BL/10 derived, H-2 congenic strains) to an AKR tumor cell line, BW5147. The studies have shown that the ability to generate a primary or secondary cell-mediated response to an AKR tumor cell antigenic determinant is under H-2 linked control. The locus determining CML responsiveness maps in the I-J subregion. Nonresponsiveness is associated with the H-2q/k and H-2b/k hybrid genotypes, whereas responsiveness is associated with the H-2k/k homozygous genotype. Nonresponsiveness may result from (a) dominant suppression; (b) recessive responsiveness; or (c) an alternate mechanism not yet understood. This type of control may be one of several H-2-associated mechanisms of defense against virus-induced neoplasms.
Parental smoking and development of allergic sensitization from birth to adolescence
Authors: J. D. Thacher, O. Gruzieva, G. Pershagen, Å. Neuman, M. van Hage, M. Wickman, I. Kull, E. Melén, A. Bergström
Journal: Allergy (2015)

The relation between secondhand tobacco smoke (SHS) exposure and the development of allergic sensitization in children is unclear. The aim of this study was to determine whether maternal smoking during pregnancy and postnatal SHS exposure contributes to the development of allergic sensitization in children and adolescents up to 16 years of age.We included 3316 children from a birth cohort followed up for 16 years. SHS exposure and symptoms of allergic disease were assessed using repeated parental questionnaires. Serum immunoglobulin E against eight common inhalant and six food allergens was assessed at ages 4, 8, and 16 years with ImmunoCAP. The association between SHS exposure and sensitization was explored using logistic regression and generalized estimating equations.Exposure to SHS in infancy without prior exposure in utero was associated with an excess risk of food sensitization at age 4 years (OR 1.47, 95% CI 1.08-2.00), with comparable ORs at ages 8 and 16 years. In longitudinal analyses, an overall association was indicated between SHS in infancy and food sensitization up to age 16 years (OR 1.24, 95% CI 0.98-1.56). Maternal smoking during pregnancy was unrelated to sensitization up to 16 years of age. When sensitization was combined with concurrent symptoms of allergic disease, SHS in infancy was associated with an overall elevated risk of eczema with sensitization (OR 1.62, 95% CI 1.20-2.18).SHS exposure in infancy appears to increase the risk of sensitization to food allergens up to age 16 years, as well as eczema in combination with sensitization.
Peer review system must be overhauled and improved, say MPs
Authors: A. O'Dowd
Journal: BMJ (2011)

The peer review system used by many medical journals before they publish new research is in need of a radical overhaul with more checks, transparency, regulation, and sharing of best practice, recommends a report from MPs.

Prepublication peer review has evolved in a “piecemeal and haphazard” way, says the report Peer review in scientific publications , published on 28 July by the parliamentary science and technology select committee.

The committee has concluded from its inquiry into peer review that to allow clinicians and scientists to follow and build on research findings, they should aim for a gold standard of making their data fully disclosed and publically available.

Peer review is vital to the reputation and reliability of medical research, said the committee, but the system is far from perfect, and the quality of peer review varies …
Protective Effects of Swainsonine on Murine Survival and Bone Marrow Proliferation During Cytotoxic Chemotherapy
Authors: O. A. Oredipe, S. L. White, K. Grzegorzewski, B. L. Gause, J. K. Cha, V. A. Miles, K. Olden
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Protective Effects of Swainsonine on Murine Survival and Bone Marrow Proliferation During Cytotoxic Chemotherapy Get access Oladipo A. Oredipe, Oladipo A. Oredipe Howard University Cancer Center, Howard University College of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sandra L. White, Sandra L. White Howard University Cancer Center, Howard University College of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Krzysztof Grzegorzewski, Krzysztof Grzegorzewski Howard University Cancer Center, Howard University College of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Barry L. Gause, Barry L. Gause Howard University Cancer Center, Howard University College of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jin K. Cha, Jin K. Cha Howard University Cancer Center and Department of Microbiology, Howard University College of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Vitilla A. Miles, Vitilla A. Miles Howard University of Cancer Center and Department of Internal Medicine, Howard University College of MedicineWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth Olden Kenneth Olden * Department of Chemistry, Vanderbilt UniversityNashville, Tenn * Correspondence to: Kenneth Olden, Ph.D., National Institute of Environmental Health Science, National Institutes of Health, P.O.Box 12233, Research Triangle Park, NC 27707. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 16, 21 August 1991, Pages 1149–1156, https://doi.org/10.1093/jnci/83.16.1149 Published: 21 August 1991 Article history Received: 13 May 1991 Accepted: 21 May 1991 Published: 21 August 1991
Surveillance for hepatocellular carcinoma is associated with increased survival: Results from a large cohort in the Netherlands
Authors: Suzanne van Meer, Robert A. de Man, Minneke J. Coenraad, Dave Sprengers, Karin M.J. van Nieuwkerk, Heinz-Josef Klümpen, Peter L.M. Jansen, Jan N.M. IJzermans, Martijn G.H. van Oijen, Peter D. Siersema, Karel J. van Erpecum
Journal: Journal of Hepatology (2015)
KCNQ1 Assembly and Function Is Blocked by Long-QT Syndrome Mutations That Disrupt Interaction With Calmodulin
Authors: Smita Ghosh, Deborah A. Nunziato, Geoffrey S. Pitt
Journal: Circulation Research (2006)

Calmodulin (CaM) has been recognized as an obligate subunit for many ion channels in which its function has not been clearly established. Because channel subunits associate early during channel biosynthesis, CaM may provide a mechanism for Ca(2+)-dependent regulation of channel formation. Here we show that CaM is a constitutive component of KCNQ1 K+ channels, the most commonly mutated long-QT syndrome (LQTS) locus. CaM not only acts as a regulator of channel gating, relieving inactivation in a Ca(2+)-dependent manner, but it also contributes to control of channel assembly. Formation of functional tetramers requires CaM interaction with the KCNQ1 C-terminus. This CaM-regulated process is essential: LQTS mutants that disrupt CaM interaction prevent functional assembly of channels in a dominant-negative manner. These findings offer a new mechanism for LQTS defects and provide a basis for understanding novel ways that intracellular Ca2+ and CaM regulate ion channels.