tbuckley/cabot-search huggingface dataset:
Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS): Evidence for Impairment and Heritability of Neurocognitive Functioning in Families of Schizophrenia Patients
Authors: Monica E. Calkins, Ping Tepper, Ruben C. Gur, J. Daniel Ragland, Lambertus Klei, Howard W. Wiener, Jan Richard, Robert M. Savage, Trina B. Allen, Judith O'Jile, Bernie Devlin, Joseph Kwentus, Muktar H. Aliyu, L. DiAnne Bradford, Neil Edwards, Paul D. Lyons, Vishwajit L. Nimgaonkar, Alberto B. Santos, Rodney C.P. Go, Raquel E. Gur
Journal: American Journal of Psychiatry (2010)

Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder.Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains.The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention.Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies.
Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases.
Authors: Y Z Patt, L M Lamki, J Shanken, J M Jessup, C Charnsangavej, J A Ajani, B Levin, B Merchant, C Halverson, J L Murray
Journal: Journal of Clinical Oncology (1990)

We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma (18 with colon cancer, one with breast cancer, and one with Hodgkin's disease) and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 of the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.
Short, Highly Effective, and Inexpensive Standardized Treatment of Multidrug-resistant Tuberculosis
Authors: Armand Van Deun, Aung Kya Jai Maug, Md Abdul Hamid Salim, Pankaj Kumar Das, Mihir Ranjan Sarker, Paul Daru, Hans L Rieder
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Based on expert opinion, the global guidelines for management of multidrug-resistant tuberculosis impose lengthy and often poorly tolerated treatments.This observational study evaluates the effectiveness of standardized regimens for patients with proven multidrug-resistant tuberculosis previously untreated with second-line drugs in low-income countries.Consenting patients were sequentially assigned to one of six standardized treatment regimens. Subsequent cohorts were treated with regimens adapted according to results in prior cohorts. The study was designed to minimize failure and default while reducing total treatment duration without increasing relapse frequency.We report the treatment outcome of all patients with laboratory-confirmed, multidrug-resistant tuberculosis enrolled from May 1997 to December 2007. The most effective treatment regimen required a minimum of 9 months of treatment with gatifloxacin, clofazimine, ethambutol, and pyrazinamide throughout the treatment period supplemented by prothionamide, kanamycin, and high-dose isoniazid during an intensive phase of a minimum of 4 months, giving a relapse-free cure of 87.9% (95% confidence interval, 82.7-91.6) among 206 patients. Major adverse drug reactions were infrequent and manageable. Compared with the 221 patients treated with regimens based on ofloxacin and commonly prothionamide throughout, the hazard ratio of any adverse outcome was 0.39 (95% confidence interval, 0.26-0.59).Serial regimen formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with first-line treatment. Confirmatory formal trials in populations with high levels of human immunodeficiency virus coinfection and in populations with a higher initial prevalence of resistance to second-line drugs are required.
Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor- -stimulated collagen production by cardiac fibroblasts
Authors: N. Gellings Lowe, J. S. Swaney, K. M. Moreno, R. A. Sabbadini
Journal: Cardiovascular Research (2008)

Aims Following injury, fibroblasts transform into myofibroblasts and produce extracellular matrix (ECM).Excess production of ECM associated with cardiac fibrosis severely inhibits cardiac function.Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, regulates the function of numerous cell types.In this study, we determined the role of S1P in promoting pro-fibrotic actions of cardiac fibroblasts (CFs).Methods and results S1P-mediated effects on myofibroblast transformation, collagen production, and cross-talk with transforming growth factor-b (TGF-b) using mouse CF were examined.S1P increased a-smooth muscle actin (a myofibroblast marker) and collagen expression in a S1P 2 receptor-and Rho kinase-dependent manner.TGF-b increased sphingosine kinase 1 (SphK1; the enzyme responsible for S1P production) expression and activity.TGF-b-stimulated collagen production was inhibited by SphK1 or S1P 2 siRNA, a SphK inhibitor, and an anti-S1P monoclonal antibody.Conclusion These findings suggest that TGF-b-stimulated collagen production in CF involves 'inside-out' S1P signalling whereby S1P produced intracellularly by SphK1 can be released and act in an autocrine/ paracrine fashion to activate S1P 2 and increase collagen production.
Kenneth Sutherland Mackenzie
Authors: K. R. Mackenzie
Journal: BMJ (2015)

<h3>Summary</h3> Transcription factors (TFs) regulate gene expression by recognising and binding specific DNA sequences. At times, these regulatory elements may be occluded by nucleosomes, making them inaccessible for TF-binding. The competition for DNA occupancy between TFs and nucleosomes, and associated gene regulatory outputs, are important consequences of the cis-regulatory information encoded in the genome. However, these sequence patterns are subtle and remain difficult to interpret. Here, we introduce ChromWave, a deep-learning model that, for the first time, predicts the competing profiles for TF and nucleosomes occupancies with remarkable accuracy. Models trained using short- and long-fragment MNase-Seq data successfully learn the sequence preferences underlying TF and nucleosome occupancies across the entire yeast genome. They recapitulate nucleosome evictions from regions containing “strong” TF binding sites and knock-out simulations show nucleosomes gaining occupancy in the absence of these TFs, accompanied by lateral rearrangement of adjacent nucleosomes. At a local level, models anticipate with high accuracy the outcomes of detailed experimental analysis of partially unwrapped nucleosomes at the GAL4 UAS locus. Finally, we trained a ChromWave model that successfully predicts nucleosome positions at promoters in the human genome. We find that human promoters generally contain few sites at which simple sequence changes can alter nucleosome occupancies and that these positions align well with causal variants linked to DNase hypersensitivity. ChromWave is readily combined with diverse genomic datasets and can be trained to predict any output that is linked to the underlying genomic sequence.
Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies
Authors: Ruth M. Pfeiffer, Yikyung Park, Aimée R. Kreimer, James V. Lacey, David Pee, Robert T. Greenlee, Saundra S. Buys, Albert Hollenbeck, Bernard Rosner, Mitchell H. Gail, Patricia Hartge
Journal: PLoS Medicine (2013)

Ruth Pfeiffer and colleagues describe models to calculate absolute risks for breast, endometrial, and ovarian cancers for white, non-Hispanic women over 50 years old using easily obtainable risk factors. Please see later in the article for the Editors' Summary
ON SOME PRINCIPLES OF THERAPY
Authors: SYDNEY G. MARGOLIN
Journal: American Journal of Psychiatry (1958)

I should like to conclude by a restatement of the principles of therapy submitted for your consideration and which have been illustrated by several clinical examples. 1. Affects, moods or emotions are psycho-physiological states which tend to augment or decrease pathophysiological states. 2. The interaction of pharmacological agents with certain affects or emotions may be synergistic or antagonistic. 3. A patient reacts to his disease, to his treatment, and to his physician with manifest psychological, cultural, and—for want of a better term—physiological regression. Where the regression is not manifest there are obvious pathological efforts of the patient to obscure it. 4. By means of iatrogenically induced regression it is possible to bring about new affects or mood states. 5. The bodily functions which are psycho-physiologically excited or inhibited by the regression or the defenses against it either increase or oppose the pathophysiology of the disease.
The Effect of Alcohol Consumption on Insulin Sensitivity and Glycemic Status: A Systematic Review and Meta-analysis of Intervention Studies
Authors: Ilse C. Schrieks, Annelijn L.J. Heil, Henk F.J. Hendriks, Kenneth J. Mukamal, Joline W.J. Beulens
Journal: Diabetes Care (2015)

OBJECTIVE Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. This reduced risk might be explained by improved insulin sensitivity or improved glycemic status, but results of intervention studies on this relation are inconsistent. The purpose of this study was to conduct a systematic review and meta-analysis of intervention studies investigating the effect of alcohol consumption on insulin sensitivity and glycemic status. RESEARCH DESIGN AND METHODS PubMed and Embase were searched up to August 2014. Intervention studies on the effect of alcohol consumption on biological markers of insulin sensitivity or glycemic status of at least 2 weeks' duration were included. Investigators extracted data on study characteristics, outcome measures, and methodological quality. RESULTS Fourteen intervention studies were included in a meta-analysis of six glycemic end points. Alcohol consumption did not influence estimated insulin sensitivity (standardized mean difference [SMD] 0.08 [−0.09 to 0.24]) or fasting glucose (SMD 0.07 [−0.11 to 0.24]) but reduced HbA1c (SMD −0.62 [−1.01 to −0.23]) and fasting insulin concentrations (SMD −0.19 [−0.35 to −0.02]) compared with the control condition. Alcohol consumption among women reduced fasting insulin (SMD −0.23 [−0.41 to −0.04]) and tended to improve insulin sensitivity (SMD 0.16 [−0.04 to 0.37]) but not among men. Results were similar after excluding studies with high alcohol dosages (&amp;gt;40 g/day) and were not influenced by dosage and duration of the intervention. CONCLUSIONS Although the studies had small sample sizes and were of short duration, the current evidence suggests that moderate alcohol consumption may decrease fasting insulin and HbA1c concentrations among nondiabetic subjects. Alcohol consumption might improve insulin sensitivity among women but did not do so overall.
THE EXCRETION OF NITROGEN AFTER UPPER GASTROINTESTINAL TRACT OBSTRUCTION
Authors: Russell L. Haden, Thomas G. Orr
Journal: The Journal of Experimental Medicine (1927)

After obstruction of the cardiac end of the stomach and after obstruction and release of the pylorus there is a marked increase in non-protein nitrogen excretion. This increase is due to accelerated protein destruction, which may result from the great fluid loss, or to the action of some toxic body.
Hippocampal and Amygdalar Volumes in Psychotic and Nonpsychotic Unipolar Depression
Authors: Jennifer Keller, Lin Shen, Rowena G. Gomez, Amy Garrett, H. Brent Solvason, Allan Reiss, Alan F. Schatzberg
Journal: American Journal of Psychiatry (2008)

The limbic system is thought to underlie dysfunctional affective and cognitive processes in individuals with depression. Neuroanatomical studies of subjects with depression have often examined hippocampal and amygdalar structures, since they are two key structures of the limbic system. Research has often but not always found reduced hippocampal volume in patients with major depression. The purpose of the present study was to examine differences in hippocampal and amygdalar volumes in patients with depression subtypes relative to healthy comparison subjects.Participants were 1) patients with major depression with psychosis, 2) patients with major depression without psychosis, and 3) healthy comparison subjects. To examine hippocampal and amygdalar volumes, all participants underwent structural magnetic resonance imaging (MRI). The authors further examined the effects of clinical and chronicity data on these two brain structures.After age, gender, and total brain volume were controlled, depressed patients with psychosis had a significantly smaller mean amygdala volume relative to depressed patients without psychosis and healthy comparison subjects. There were no differences between depressed patients without psychosis and healthy comparison subjects. Correlational analyses suggested that age of depression onset was strongly associated with amygdala volume. No group differences in hippocampal volume were found.There were no differences between depressed patients and healthy comparison subjects in hippocampal volume. However, psychotic but not nonpsychotic depression was associated with reduced amygdala volume. Reduced amygdala volume was not associated with severity of depression or severity of psychosis but was associated with age at onset of depression. Smaller amygdala volume may be a risk factor for later development of psychotic depression. In addition, chronicity of depression and depression subtype might be two important factors associated with hippocampal and amygdalar volumes in depression.
Effect of Pioglitazone on Cardiovascular Outcome in Diabetes and Chronic Kidney Disease
Authors: Christian A. Schneider, Ele Ferrannini, Ralph DeFronzo, Guntram Schernthaner, John Yates, Erland Erdmann
Journal: Journal of the American Society of Nephrology (2007)

Patients with diabetes and chronic kidney disease (CKD) are at particularly high risk for cardiovascular disease (CVD). This post hoc analysis from the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) investigated the relationship between CKD and incident CVD in a population of patients with diabetes and documented macrovascular disease, as well as the effects of pioglitazone treatment on recurrent CVD. CKD, defined as an estimated GFR <60 ml/min per 1.73m(2), was present in 597 (11.6%) of 5154 patients. More patients with CKD reached the primary composite end point (all-cause mortality, myocardial infarction (MI), stroke, acute coronary syndrome, coronary/carotid arterial intervention, leg revascularization, or amputation above the ankle) than patients without CKD (27.5 versus 19.6%; P < 0.0001). Patients with CKD were also more likely to reach a secondary composite end point (all-cause mortality, MI, and stroke). Patients who had CKD and were treated with pioglitazone were less likely to reach the secondary end point (hazard ratio 0.66; 95% confidence interval 0.45 to 0.98), but this association was not observed among those with better renal function. In addition, there was a greater decline in estimated GFR with pioglitazone (between-group difference 0.8 ml/min per 1.73 m(2)/yr) than with placebo. In conclusion, CKD is an independent risk factor for cardiovascular events and death among patients with diabetes and preexisting macrovascular disease. Patients who had CKD and were treated with pioglitazone were less likely to reach a composite end point of all-cause death, MI, and stroke, independent of the severity of renal impairment.
Predictability of Adjuvant Trastuzumab Benefit in N9831 Patients Using the ASCO/CAP HER2-Positivity Criteria
Authors: Edith A. Perez, Amylou C. Dueck, Ann E. McCullough, Monica M. Reinholz, Kathleen S. Tenner, Nancy E. Davidson, Julie Gralow, Lyndsay N. Harris, Leila A. Kutteh, David W. Hillman, Robert B. Jenkins, Beiyun Chen
Journal: JNCI Journal of the National Cancer Institute (2011)

The 2007 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) joint guidelines defined criteria for HER2 positivity of tumors that modified those of the US Food and Drug Administration (FDA), causing some confusion and uncertainty among clinicians. Using data from the HER2-positive breast cancer adjuvant trial N9831, we compared eligibility for patients who met both criteria, and disease-free survival (DFS) was assessed by Cox proportional hazards regression. The number of patients in the N9831 trial retrospectively eligible for trastuzumab therapy was decreased when ASCO/CAP criteria vs FDA criteria were applied to immunohistochemistry and/or fluorescence in situ hybridization results (107 [3.7%] of 2904 patients with immunohistochemistry results, 37 [1.3%] of 2809 patients with fluorescence in situ hybridization results, and 47 [1.7%] of 2809 patients with both results). Improvement in DFS was similar among patients treated with trastuzumab under either set of criteria (concurrent trastuzumab and chemotherapy compared with chemotherapy alone: by ASCO/CAP criteria, hazard ratio of DFS = 0.59, 95% confidence interval = 0.48 to 0.73; by FDA criteria but not ASCO/CAP criteria, hazard ratio = 0.60, 95% confidence interval = 0.12 to 3.13; number needed to treat to prevent one additional DFS event at 5 years: 10 and 11.2 patients, respectively). Following the 2007 ASCO/CAP criteria for HER2 positivity would negate the option of potentially life-saving trastuzumab therapy for a small but meaningful group of patients. We recommend using FDA-approved HER2 criteria for therapeutic decision making.
Causal Inference in Public Health
Authors: Thomas A. Glass, Steven N. Goodman, Miguel A. Hernán, Jonathan M. Samet
Journal: Annual Review of Public Health (2013)

Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action's consequences rather than the less precise notion of a risk factor's causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world.
The Adrenal Androgen Androstenediol Is Present in Prostate Cancer Tissue after Androgen Deprivation Therapy and Activates Mutated Androgen Receptor
Authors: Atsushi Mizokami, Eitetsu Koh, Hiroshi Fujita, Yuji Maeda, Masayuki Egawa, Kiyoshi Koshida, Seijiro Honma, Evan T. Keller, Mikio Namiki
Journal: Cancer Research (2004)

Abstract Despite an initial response to androgen deprivation therapy, prostate cancer (PCa) progresses eventually from an androgen-dependent to an androgen-independent phenotype. One of the mechanisms of relapse is antiandrogen withdrawal phenomenon caused by mutation of 877th amino acid of androgen receptor (AR). In the present study, we established a method to measure the concentration of androstenediol (adiol) in prostate tissue. We found that adiol maintains a high concentration in PCa tissue even after androgen deprivation therapy. Furthermore, adiol is a stronger activator of mutant AR in LNCaP PCa cells and induces more cell proliferation, prostate-specific antigen (PSA) mRNA expression, and PSA promoter than dihydrotestosterone (DHT). Because antiandrogen, bicalutamide, blocked adiol activity in LNCaP cells, it was suggested that adiol effect was mediated through AR. However, high concentration of bicalutamide was necessary to block completely adiol activity. These effects were specific to LNCaP cells because adiol had less effect in PC-3 PCa cells transfected with wild-type AR than DHT and had similar effect in PC-3 cells transfected with mutant AR. The mechanism that adiol activates mutant AR in LNCaP cells did not result from the increased affinity to mutant AR or from AR’s association with coactivator ARA70. However, low concentration of adiol induced more AR nuclear translocation than DHT in LNCaP cells and not PC-3 cells transfected with AR. These results indicate that adiol may cause the progression of PCa even after hormone therapy.