tbuckley/cabot-search huggingface dataset:
Efficacy of Pharmacotherapy and Psychotherapy for Adult Psychiatric Disorders
Authors: Maximilian Huhn, Magdolna Tardy, Loukia Maria Spineli, Werner Kissling, Hans Förstl, Gabriele Pitschel-Walz, Claudia Leucht, Myrto Samara, Markus Dold, John M. Davis, Stefan Leucht
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> There is debate about the effectiveness of psychiatric treatments and whether pharmacotherapy or psychotherapy should be primarily used. <h3>Objectives</h3> To perform a systematic overview on the efficacy of pharmacotherapies and psychotherapies for major psychiatric disorders and to compare the quality of pharmacotherapy and psychotherapy trials. <h3>Evidence Review</h3> We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library (April 2012, with no time or language limit) for systematic reviews on pharmacotherapy or psychotherapy vs placebo, pharmacotherapy vs psychotherapy, and their combination vs either modality alone. Two reviewers independently selected the meta-analyses and extracted efficacy effect sizes. We assessed the quality of the individual trials included in the pharmacotherapy and psychotherapy meta-analyses with the Cochrane risk of bias tool. <h3>Findings</h3> The search yielded 45 233 results. We included 61 meta-analyses on 21 psychiatric disorders, which contained 852 individual trials and 137 126 participants. The mean effect size of the meta-analyses was medium (mean, 0.50; 95% CI, 0.41-0.59). Effect sizes of psychotherapies vs placebo tended to be higher than those of medication, but direct comparisons, albeit usually based on few trials, did not reveal consistent differences. Individual pharmacotherapy trials were more likely to have large sample sizes, blinding, control groups, and intention-to-treat analyses. In contrast, psychotherapy trials had lower dropout rates and provided follow-up data. In psychotherapy studies, wait-list designs showed larger effects than did comparisons with placebo. <h3>Conclusions and Relevance</h3> Many pharmacotherapies and psychotherapies are effective, but there is a lot of room for improvement. Because of the multiple differences in the methods used in pharmacotherapy and psychotherapy trials, indirect comparisons of their effect sizes compared with placebo or no treatment are problematic. Well-designed direct comparisons, which are scarce, need public funding. Because patients often benefit from both forms of therapy, research should also focus on how both modalities can be best combined to maximize synergy rather than debate the use of one treatment over the other.
Computer Simulation of Systemic Circulation and Clot Lysis Dynamics During Thrombolytic Therapy That Accounts for Inner Clot Transport and Reaction
Authors: Sriram Anand, Scott L. Diamond
Journal: Circulation (1996)

Background We developed a computer model to predict lysis rates of thrombi for intravenous thrombolytic regimens based on the convective/diffusive penetration of reacting and adsorbing fibrinolytic species from the circulation into the proximal face of a dissolving clot. Methods and Results Solution of a one-compartment plasma model provided the dynamic concentrations of fibrinolytic species that served as inlet conditions for simulation of the one-dimensional spatiodynamics within a dissolving fibrin clot of defined composition. The model predicted the circulating levels of tissue plasminogen activator (TPA) and plasminogen levels found in clinical trials for various intravenous therapies. To test the model predictions under in vitro conditions, plasma clots were perfused with TPA (0.1 μmol/L) and plasminogen (1.0 μmol/L) delivered at constant permeation velocity of 0.1 or 0.2 mm/min. The model provided an accurate prediction of the measured lysis front movement. For TPA administration regimens used clinically, simulations predicted clot dissolution rates that were consistent with observed reperfusion times. For unidirectional permeation, the continual accumulation of adsorbing species at the moving lysis front due to prior rounds of solubilization and rebinding was predicted to provide for a marked concentration of TPA and plasmin and the eventual depletion of antiplasmin and macroglobulin in an advancing (≈0.25 mm thick) lysis zone. Conclusions Pressure-driven permeation greatly enhances and is a primary determinant of the overall rate of clot lysis and creates a complex local reaction environment at the plasma/clot interface. With simulation of reaction and transport, it becomes possible to quantitatively link the administration regimen, plasminogena activator properties, and thrombolytic outcome.
An Unbiased Estimator of Gene Diversity in Samples Containing Related Individuals
Authors: M. DeGiorgio, N. A. Rosenberg
Journal: Molecular Biology and Evolution (2008)

Gene diversity is sometimes estimated from samples that contain inbred or related individuals. If inbred or related individuals are included in a sample, then the standard estimator for gene diversity produces a downward bias caused by an inflation of the variance of estimated allele frequencies. We develop an unbiased estimator for gene diversity that relies on kinship coefficients for pairs of individuals with known relationship and that reduces to the standard estimator when all individuals are noninbred and unrelated. Applying our estimator to data simulated based on allele frequencies observed for microsatellite loci in human populations, we find that the new estimator performs favorably compared with the standard estimator in terms of bias and similarly in terms of mean squared error. For human population-genetic data, we find that a close linear relationship previously seen between gene diversity and distance from East Africa is preserved when adjusting for the inclusion of close relatives.
Thioredoxin-like 2 regulates human cancer cell growth and metastasis via redox homeostasis and NF-κB signaling
Authors: Ying Qu, Jinhua Wang, Partha S. Ray, Hua Guo, Jian Huang, Miyung Shin-Sim, Bolanle A. Bukoye, Bingya Liu, Adrian V. Lee, Xin Lin, Peng Huang, John W. Martens, Armando E. Giuliano, Ning Zhang, Ning-Hui Cheng, Xiaojiang Cui
Journal: Journal of Clinical Investigation (2010)

Cancer cells have an efficient antioxidant system to counteract their increased generation of ROS. However, whether this ability to survive high levels of ROS has an important role in the growth and metastasis of tumors is not well understood. Here, we demonstrate that the redox protein thioredoxin-like 2 (TXNL2) regulates the growth and metastasis of human breast cancer cells through a redox signaling mechanism. TXNL2 was found to be overexpressed in human cancers, including breast cancers. Knockdown of TXNL2 in human breast cancer cell lines increased ROS levels and reduced NF-κB activity, resulting in inhibition of in vitro proliferation, survival, and invasion. In addition, TXNL2 knockdown inhibited tumorigenesis and metastasis of these cells upon transplantation into immunodeficient mice. Furthermore, analysis of primary breast cancer samples demonstrated that enhanced TXNL2 expression correlated with metastasis to the lung and brain and with decreased overall patient survival. Our studies provided insight into redox-based mechanisms underlying tumor growth and metastasis and suggest that TXNL2 could be a target for treatment of breast cancer.
Neoplastic and potentially prenoeplastic changes in the upper respiratory tract of rats and mice.
Authors: H R Brown
Journal: Environmental Health Perspectives (1990)

The National Toxicology Program (NTP) database was examined for tumor incidences and chemicals producing tumors in the nasal cavity, larynx, or trachea. Slides from appropriate studies were then examined in an attempt to unify terminology and make comparisons between induced and spontaneous tumors and hyperplastic or preneoplastic lesions produced in the upper respiratory system. An attempt was also made to compare the species affected, route of administration, and tumor types produced by different chemicals. The results are not meant to be all inclusive of the NTP database but to be representative of observed trends. General conclusions that emerged from this review were that rats are much more susceptible to epithelial tumors of the nasal cavity than mice; that only mice have been reported to have chemically induced hemangiomas and hemangiosarcomas of the nasal cavity; that tumors of the olfactory epithelium and squamous cell tumors of the respiratory epithelium are almost uniformly malignant and invasive, while other tumors of the respiratory epithelium are typically less invasive; that most chemically induced tumors of the olfactory region, either mesenchymal or epithelial, do not require an inhalation route of exposure but appear to occur by systemic targeting of this region; and that a uniform nomenclature for tumors of the nasal cavity is needed.
An unusual lineage of alpha/beta T cells that contains autoreactive cells.
Authors: H von Boehmer, J Kirberg, B Rocha
Journal: The Journal of Experimental Medicine (1991)

In male mice that express a transgenic alpha/beta T cell receptor (TCR) specific for a male-specific peptide presented by class I Db major histocompatibility complex (MHC) molecules, we describe an unusual lineage of alpha/beta T cells that are thymus dependent but do not require selection by Db MHC molecules on thymic epithelium in the absence of the specific peptide (positive selection). These cells express the transgenic alpha/beta TCR and have the CD4-8- or CD4-8low phenotype. Cells with the latter phenotype are only detected when hemopoietic cells express both the male-specific peptide as well as Db MHC molecules. In fact, these cells are autoreactive, as they expand relatively slowly after transfer into male nude mice. Also in male but not female alpha/beta TCR transgenic mice, the CD8+ cells with the transgenic TCR bear the Pgp1 marker characteristic of mature T cells activated by antigen. CD4-8- as well as CD4-8low cells do not respond significantly when cultured with male stimulator cells but proliferate vigorously when stimulated by TCR antibodies. By this latter criterion, cells in the periphery of male alpha/beta TCR transgenic mice differ from mature male-specific T cells from female alpha/beta TCR transgenic, which become intrinsically anergic when transferred into male nude mice and cannot be stimulated significantly by TCR antibodies. Thus, intrathymic deletion does not eliminate all autoreactive T cells and it is possible that cells with an apparently "benign" autoreactivity may be involved in certain forms of autoimmunity.
Antiarrhythmic Engineering of Skeletal Myoblasts for Cardiac Transplantation
Authors: M. Roselle Abraham, Charles A. Henrikson, Leslie Tung, Marvin G. Chang, Miguel Aon, Tian Xue, Ronald A. Li, Brian O’ Rourke, Eduardo Marbán
Journal: Circulation Research (2005)

Skeletal myoblasts are an attractive cell type for transplantation because they are autologous and resistant to ischemia. However, clinical trials of myoblast transplantation in heart failure have been plagued by ventricular tachyarrhythmias and sudden cardiac death. The pathogenesis of these arrhythmias is poorly understood, but may be related to the fact that skeletal muscle cells, unlike heart cells, are electrically isolated by the absence of gap junctions. Using a novel in vitro model of myoblast transplantation in cardiomyocyte monolayers, we investigated the mechanisms of transplant-associated arrhythmias. Cocultures of human skeletal myoblasts and rat cardiomyocytes resulted in reentrant arrhythmias (spiral waves) that reproduce the features of ventricular tachycardia seen in patients receiving myoblast transplants. These arrhythmias could be terminated by nitrendipine, an l -type calcium channel blocker, but not by the Na channel blocker lidocaine. Genetic modification of myoblasts to express the gap junction protein connexin43 decreased arrhythmogenicity in cocultures, suggesting a specific means for increasing the safety (and perhaps the efficacy) of myoblast transplantation in patients.
Impact of Age at First Childbirth on Glucose Tolerance Status in Postmenopausal Women: The 2008–2011 Korean National Health and Nutrition Examination Survey
Authors: Jin Hwa Kim, Yun Jung, Sang Yong Kim, Hak Yeon Bae
Journal: Diabetes Care (2013)

The objective of the current study was to determine whether there was an association between age at first childbirth and glucose tolerance status in postmenopausal women.This study was based on the data from the Korean National Health and Nutrition Examination Survey, conducted by the Korean Ministry of Health and Welfare from 2008-2011. Of 37,753 participants, data for 4,965 postmenopausal women were included in the analysis. Subjects were subdivided according to the age at first childbirth as follows: ≤19, 20-24, 25-29, and ≥30 years. Multivariate logistic regression analyses were used to identify whether there was an independent association between age at first childbirth and glucose tolerance status by adjusting for potential confounding factors.The prevalence of impaired fasting glucose (IFG) and diabetes was 21.8% (1.066 of 4.965) and 15.3% (774 of 4,965), respectively. Diabetes prevalence differed significantly between the subgroups and was higher with earlier age at first childbirth: it was 10.9% in subjects aged ≥30 years and 23.8% in subjects aged ≤19 years at first childbirth. After fully adjusting for potential confounding factors, including lifestyle, sociodemographic factors, known diabetes risk factors, and reproductive factors, age at first childbirth ≤19 years was significantly associated with diabetes (odds ratio 1.492 [95% CI 1.005-2.215]). No significant associations were found between age at first childbirth and IFG.Age at first childbirth influenced diabetes risk in postmenopausal women, and adolescent pregnancy was independently associated with a higher risk of diabetes in postmenopausal women.
Sentinel lymph node micrometastasis and other histologic factors that predict outcome in patients with thicker melanomas
Authors: Basil S. Cherpelis, Fadi Haddad, Jane Messina, Alan B. Cantor, Kristi Fitzmorris, Douglas S. Reintgen, Neil A. Fenske, L.Frank Glass
Journal: Journal of the American Academy of Dermatology (2001)
Adherence of Erythrocytes during Exflagellation of <i>Plasmodium falciparum</i> Microgametes Is Dependent on Erythrocyte Surface Sialic Acid and Glycophorins
Authors: Thomas J. Templeton, David B. Keister, Olga Muratova, Jo Lynn Procter, David C. Kaslow
Journal: The Journal of Experimental Medicine (1998)

Malaria male gametocytes within a newly ingested infected blood meal in the mosquito midgut emerge from erythrocytes and extrude approximately eight flagellar microgametes in a process termed exflagellation. In culture, and in blood removed from infected patients, emerging microgametes avidly adhere to neighboring uninfected and infected erythrocytes, as well as to emerged female macrogametes, creating "exflagellation centers". The mechanism of erythrocyte adherence is not known nor has it been determined for what purpose microgametes may bind to erythrocytes. The proposition of a function underlying erythrocyte adherence is supported by the observation of species-specificity in adhesion: microgametes of the human malaria Plasmodium falciparum can bind human erythrocytes but not chicken erythrocytes, whereas avian host Plasmodium gallinaceum microgametes bind chicken but not human erythrocytes. In this study we developed a binding assay in which normal, enzyme-treated, variant or null erythrocytes are identified by a cell surface fluorescent label and assayed for adherence to exflagellating microgametes. Neuraminidase, trypsin or ficin treatment of human erythrocytes eliminated their ability to adhere to Plasmodium falciparum microgametes, suggesting a role of sialic acid and one or more glycophorins in the binding to a putative gamete receptor. Using nulls lacking glycophorin A [En(a-)], glycophorin B (S-s-U-) or a combination of glycophorin A and B (Mk/Mk) we showed that erythrocytes lacking glycophorin B retain the ability to bind but a lack of glycophorin A reduced adherence by exflagellating microgametes. We propose that either the sialic acid moiety of glycophorins, predominantly glycophorin A, or a more complex interaction involving the glycophorin peptide backbone, is the erythrocyte receptor for adhesion to microgametes.
Splenectomized patients make IgG antibodies to 23-valent non-conjugated pneumococcal vaccine despite having reduced circulating CD27+ memory B cells
Authors: H.A. Wasserstrom, J.B. Bussel, L.C.L. Lim, N.T. Guerrero, M.H. Wissert, L. Radigan, C. Cunningham-Rundles
Journal: Journal of Allergy and Clinical Immunology (2005)
Comparison of Molecular Changes in Lung Cancers in HIV-Positive and HIV-Indeterminate Subjects
Authors: Ignacio I. Wistuba
Journal: JAMA (1998)

Context.— Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population. Objective.— To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic tumors"). Design.—Convenience sample.Subjects.— Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status. Setting.—University-based medical centers and affiliated hospitals.Main Outcome Measures.— Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences. Results.— The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas. Conclusions.— Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.
Life span and disability: a cross sectional comparison of Russian and Swedish community based data
Authors: Martin Bobak, Margareta Kristenson, Hynek Pikhart, Michael Marmot
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To compare levels of disability (in terms of physical function and self rated health) among middle aged and elderly people in Russia and Sweden, a country with high life expectancy. <b>Design</b> Cross sectional study. <b>Setting</b> General population of the Russian Federation and of two counties in southern Sweden. <b>Participants</b> Randomly selected men and women in Sweden (n = 9489) and Russia (n = 1599). <b>Main outcome measures</b> Official life table data; self rated health and physical functioning (subscale of the SF-36). <b>Results</b> The official life table data showed large differences in mortality—for example, 36% of Russian men aged 45-49 years would survive the next 25 years compared with 75% of Swedish men. The survey data showed, for both sexes, similar levels of self rated health and physical functioning in the two countries up to the age of about 45 years, but after that, the age related decline in both outcomes was much faster in Russia than in Sweden. By combining the national life tables with survey data on physical functioning we estimated that in the age group 45-49 years, 99% of Russian and 97% of Swedish men would be free of disability; of these, if these data were for a cohort, only 17% of Russians would be alive and free of disability 25 years later compared with 65% of Swedes. The difference in survival was similar in women. <b>Conclusions</b> Large differences exist in survival without disability between elderly Russians and Swedes. The short life span in Russia reflects high levels of ill health and disability and is associated with a rapid age related decline in physical functioning.
Bayesian Phylogenetic Model Selection Using Reversible Jump Markov Chain Monte Carlo
Authors: J. P. Huelsenbeck
Journal: Molecular Biology and Evolution (2004)

A common problem in molecular phylogenetics is choosing a model of DNA substitution that does a good job of explaining the DNA sequence alignment without introducing superfluous parameters. A number of methods have been used to choose among a small set of candidate substitution models, such as the likelihood ratio test, the Akaike Information Criterion (AIC), the Bayesian Information Criterion (BIC), and Bayes factors. Current implementations of any of these criteria suffer from the limitation that only a small set of models are examined, or that the test does not allow easy comparison of non-nested models. In this article, we expand the pool of candidate substitution models to include all possible time-reversible models. This set includes seven models that have already been described. We show how Bayes factors can be calculated for these models using reversible jump Markov chain Monte Carlo, and apply the method to 16 DNA sequence alignments. For each data set, we compare the model with the best Bayes factor to the best models chosen using AIC and BIC. We find that the best model under any of these criteria is not necessarily the most complicated one; models with an intermediate number of substitution types typically do best. Moreover, almost all of the models that are chosen as best do not constrain a transition rate to be the same as a transversion rate, suggesting that it is the transition/transversion rate bias that plays the largest role in determining which models are selected. Importantly, the reversible jump Markov chain Monte Carlo algorithm described here allows estimation of phylogeny (and other phylogenetic model parameters) to be performed while accounting for uncertainty in the model of DNA substitution.
Analysis of a Recent Hypothesis of Plasma Flow in Pericapillary Spaces
Authors: JOHN T. HOWE, YVONNE S. SHEAFFER
Journal: Circulation Research (1967)

The hypothesis that the observed fluid annulus outside the wall of some capillaries is the reservoir of plasma responsible for ratios of organ hematocrit to large vessel hematocrit less than 1 is examined hydrodynamically. The extent to which the hematocrits can be reconciled on the basis of flow through a single capillary is examined. Results show that ratios between 0.5 and 1.0 can be accounted for even if plasma and cells travel the same distance through a common capillary without a plasma annulus. But with the annulus, ratios as low as 0.27 can be explained (ratios as low as 0.35 have been measured), and the corresponding capillary pressure gradients agree better with those cited else-where. The ratio of organ hematocrit to large vessel hematocrit for the heart, lungs, brain, gut, and carcass can be explained on a single capillary basis with or without pericapillary plasma, but that for the liver and kidney requires the plasma annulus. The analysis predicts a linear relationship between pressure gradient and flow in the capillary with or without the annulus. The hydrodynamic result provides a plasma transit time along the annulus that agrees well with that observed between the "bulk" disappearance and subsequent reappearance of labeled plasma in the microcirculation.