tbuckley/cabot-search huggingface dataset:
Growth Differentiation Factor-15 in Idiopathic Pulmonary Arterial Hypertension
Authors: Nils Nickel, Tibor Kempf, Heike Tapken, Jörn Tongers, Florian Laenger, Ulrich Lehmann, Heiko Golpon, Karen Olsson, Martin R. Wilkins, J. Simon R. Gibbs, Marius M. Hoeper, Kai C. Wollert
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Growth-differentiation factor (GDF)-15 is a stress-responsive, transforming growth factor-β–related cytokine. Circulating levels of GDF-15 provide independent prognostic information in patients with acute pulmonary embolism and chronic left-sided heart failure.Objectives: To assess the prognostic value of GDF-15 in idiopathic pulmonary arterial hypertension.Methods: GDF-15 levels were determined in 76 treatment-naive patients at the time of baseline right heart catheterization. Patients were monitored for a median (range) of 48 (0–101) months (first cohort). Twenty-two additional patients were studied at baseline and 3 to 6 months after initiation of therapy (second cohort).Measurements and Main Results: Fifty-five percent of the patients in the first cohort presented with GDF-15 levels above 1,200 ng/L, the previously defined upper reference limit. The risk of death or transplantation at 3 years was 15 and 44% in patients with GDF-15 levels below or above 1,200 ng/L, respectively (P = 0.006). Elevated levels of GDF-15 were associated with increased mean right atrial and pulmonary capillary wedge pressures, a lower mixed venous oxygen saturation (SvO2), and higher levels of uric acid and N-terminal pro-brain natriuretic peptide (NT-proBNP). After adjustment for hemodynamic and biochemical variables, GDF-15 remained an independent predictor of adverse outcomes (P = 0.002). GDF-15 provided prognostic information in clinically relevant patient subgroups, and added prognostic information to hemodynamic variables and NT-proBNP. Changes in GDF-15 over time in the second cohort were related to changes in NT-proBNP (P = 0.031) and inversely related to changes in SvO2 (P < 0.001).Conclusions: GDF-15 is a promising new biomarker in idiopathic pulmonary arterial hypertension.
Recombination Drives the Evolution of GC-Content in the Human Genome
Authors: Julien Meunier, Laurent Duret
Journal: Molecular Biology and Evolution (2004)

Unraveling the evolutionary forces responsible for variations of neutral substitution patterns among taxa or along genomes is a major issue in the identification of functional sequence features. Mammalian genomes show large-scale regional variations of GC-content (the isochores), but the substitution processes at the origin of this structure are poorly understood. We have analyzed the pattern of neutral substitutions in 14.3 Mb of primate noncoding regions. We show that the GC-content toward which sequences are evolving is strongly correlated (r2 = 0.61, P ≤ 2 10−16) with the rate of crossovers (notably in females). This demonstrates that recombination drives the evolution of base composition in human (probably via the process of biased gene conversion). The present substitution patterns are very different from what they had been in the past, resulting in a major modification of the isochore structure of our genome. This non-equilibrium situation suggests that changes of recombination rates occur relatively frequently during evolution, possibly as a consequence of karyotype rearrangements. These results have important implications for understanding the spatial and temporal variations of substitution processes in a broad range of sexual organisms, and for detecting the hallmarks of natural selection in DNA sequences.
Societal Change to Prevent Obesity
Authors: Stuart P. Weisberg
Journal: JAMA (2002)

78% OF RESPONDENTS reported that their body weights were not a serious health concern. 1 Approximately one third of these respondents were obese, two thirds were overweight, and 15% of their children were overweight.This indifference is not appropriate.Obesity may soon replace smoking as the leading cause of preventable death in the United States.Obesity may be responsible for approximately 300000 US deaths per year, and, unlike smoking, the prevalence of obesity is rapidly increasing. 2 Public health officials now refer to obesity as an epidemic.Unlike infectious diseases, obesity kills and disables by gradually increasing the risk for diseases like diabetes, heart disease, stroke, and cancer.Recent studies estimate that obesity is more strongly associated with chronic medical conditions, and reduced health-related quality of life, than smoking, heavy drinking, or poverty. 3 Articles in this issue of MSJAMA emphasize the importance of societal change to address obesity.Tarayn Grizzard examines the undertreatment of obesity by American physicians.Susan Blumenthal, Jennifer Hendi, and Lauren Marsillo argue that a public health approach is required to address the myriad environmental and sociocultural factors contributing to obesity.Lawsuits have recently emerged to uncover and redress alleged food industry misconduct that may be contributing to the obesity problem.Richard Daynard, Lauren Hash, and Anthony Robbins discuss the future of this food litigation.The prevalence of obesity among children is also rapidly increasing and has been associated with hyperlipidemia, hypertension, and impaired glucose tolerance. 2Robert Carter reviews the rationale and the results of school-based obesity interventions.Ellen Fried and Marion Nestle argue that soda consumption makes an important contribution to childhood obesity.They describe marketing practices designed to increase soda consumption among schoolchildren and discuss recent political initiatives to restrict these practices.The burden imposed by overweight and obesity on the United States is very high.The estimated total cost of overweight and obesity in 2000 is estimated to have been $117 billion, nearly 10% of the US health care expenditure. 2By contrast, the United Nations estimates that the yearly costs of HIV/AIDS prevention and care in Africa, Asia, and Latin America will be $9.7 billion by 2005. 4 Given the exorbitant costs of obesity, more effective interventions are urgently needed to decrease its prevalence.The fact that most Americans are overweight, yet are not concerned about the health importance of their own body weights, suggests that there remains much room for improvement.
Hair nicotine, dust nicotelline, and lung function in adults with airway disease
Authors: John Balmes, Neal Benowitz, Peyton Jacob, Christopher Havel, Patricia Quinlan, Carlos Iribaren, Miriam Cisternas, Patricia Katz, Paul Blanc
Journal: European Respiratory Journal (2013)

Background: Secondhand smoke (SHS) has been difficult to quantify for exposure response assessment in airway disease.  Methods: In a cohort of adults with airway disease, we measured FEV1 (EasyOne, nnd, Andover MA, USA), obtained hair samples, and sampled settled dust in participant’s bedrooms. Using liquid chromatography-mass spectrometry, we assessed SHS exposure, analyzing hair for nicotine (N) and dust for N and nicotelline (NT), an alkaloid that is associated with tobacco smoke particulate matter. Dust analysis was limited to a random sample from the subset with detectable hair N. We estimated the Spearman correlations for FEV1, hair N, and dust N, NT.  Results: We analyzed home visit data for 291 participants (15 rhinitis only; 37 asthma only; 236 both). Sufficient hair was obtained for N analysis in 277 and was above the lower limit of detection (LLD) in 164 (59%). We analyzed dust for N and NT in 61, of whom 54 were non-smokers (SHS only). Hair N was negatively correlated with FEV1 % pred (r=-0.16; excluding 22 active smokers, r=-0.18; excluding LLD samples, r=-0.24; all p  Discussion: Cigarette smoke byproduct exposure is associated with poorer lung function in adults with asthma and rhinitis; dust nicotelline may be a useful marker of SHS exposure.  Clinical::Reducing exposure to cigarette smoke byproducts may beneficial for lung function in adults with airway disease.  Supported by NIH ES10906 and the Flight Attendants Medical Research Institute.
Lead Sources in Human Diet in Greenland
Authors: Peter Bjerregaard, Poul Johansen, Gert Mulvad, Henning Sloth Pedersen, Jens C. Hansen
Journal: Environmental Health Perspectives (2004)

Although blood lead levels have declined in Greenland, they are still elevated despite the fact that lead levels in the Greenland environment are very low. Fragments of lead shot in game birds have been suggested as an important source of dietary exposure, and meals of sea birds, particularly eider, contain high concentrations of lead. In a cross-sectional population survey in Greenland in 1993-1994, blood lead adjusted for age and sex was found to be associated with the reported consumption of sea birds. Participants reporting less than weekly intake of sea birds had blood lead concentrations of approximately 75 microg/L, whereas those who reported eating sea birds several times a week had concentrations of approximately 110 microg/L, and those who reported daily intake had concentrations of 170 microg/L (p = 0.01). Blood lead was not associated with dietary exposure to other local or imported food items.
Vitamin D and lung function
Authors: R P Young, R J Hopkins
Journal: Thorax (2014)

Afzal et al 1 recently reported that low plasma 25-hydroxyvitamin D is associated with a decline in lung function and chronic obstructive pulmonary disease (COPD). While this finding persisted after adjustment for possible confounding variables, and concurs with the findings of others,2 we believe it might still be spurious.

First, we suggest the association between plasma vitamin D and lung function is subject to a threshold effect, evident in both the cross-sectional data (figures 1 and 3, reference 1) and prospective data (figure 2 and table 2—see our figure 1 below), and primarily limited to the lowest two quintiles (ie, only for the 1st–2nd quintiles can a relationship be consistently identified). By contrast, for the …
Pattern of Frequent But Nontargeted Pharmacologic Thromboprophylaxis for Hospitalized Patients With Cancer at Academic Medical Centers: A Prospective, Cross-Sectional, Multicenter Study
Authors: Jeffrey I. Zwicker, Adam Rojan, Federico Campigotto, Nadia Rehman, Renee Funches, Gregory Connolly, Jonathan Webster, Anita Aggarwal, Dalia Mobarek, Charles Faselis, Donna Neuberg, Frederick R. Rickles, Ted Wun, Michael B. Streiff, Alok A. Khorana
Journal: Journal of Clinical Oncology (2014)

Purpose Hospitalized patients with cancer are considered to be at high risk for venous thromboembolism (VTE). Despite strong recommendations in numerous clinical practice guidelines, retrospective studies have shown that pharmacologic thromboprophylaxis is underutilized in hospitalized patients with cancer. Patients and Methods We conducted a prospective, cross-sectional study of hospitalized patients with cancer at five academic hospitals to determine prescription rates of thromboprophylaxis and factors influencing its use during hospitalization. Results A total of 775 patients with cancer were enrolled across five academic medical centers. Two hundred forty-seven patients (31.9%) had relative contraindications to pharmacologic prophylaxis. Accounting for contraindications to anticoagulation, the overall rate of pharmacologic thromboprophylaxis was 74.2% (95% CI, 70.4% to 78.0%; 392 of 528 patients). Among the patients with cancer without contraindications for anticoagulation, individuals hospitalized with nonhematologic malignancies were significantly more likely to receive pharmacologic thromboprophylaxis than those with hematologic malignancies (odds ratio [OR], 2.34; 95% CI, 1.43 to 3.82; P = .007). Patients with cancer admitted for cancer therapy were significantly less likely to receive pharmacologic thromboprophylaxis than those admitted for other reasons (OR, 0.37; 95% CI, 0.22 to 0.61; P &lt; .001). Sixty-three percent of patients with cancer classified as low risk, as determined by the Padua Scoring System, received anticoagulant thromboprophylaxis. Among the 136 patients who did not receive anticoagulation, 58.8% were considered to be high risk by the Padua Scoring System. Conclusion We conclude that pharmacologic thromboprophylaxis is frequently administered to hospitalized patients with cancer but that nearly one third of patients are considered to have relative contraindications for prophylactic anticoagulation. Pharmacologic thromboprophylaxis in hospitalized patients with cancer is commonly prescribed without regard to the presence or absence of concomitant risk factors for VTE.
Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis
Authors: David C Whitcomb, Jessica LaRusch, Alyssa M Krasinskas, Lambertus Klei, Jill P Smith, Randall E Brand, John P Neoptolemos, Markus M Lerch, Matt Tector, Bimaljit S Sandhu, Nalini M Guda, Lidiya Orlichenko, Samer Alkaade, Stephen T Amann, Michelle A Anderson, John Baillie, Peter A Banks, Darwin Conwell, Gregory A Coté, Peter B Cotton, James DiSario, Lindsay A Farrer, Chris E Forsmark, Marianne Johnstone, Timothy B Gardner, Andres Gelrud, William Greenhalf, Jonathan L Haines, Douglas J Hartman, Robert A Hawes, Christopher Lawrence, Michele Lewis, Julia Mayerle, Richard Mayeux, Nadine M Melhem, Mary E Money, Thiruvengadam Muniraj, Georgios I Papachristou, Margaret A Pericak-Vance, Joseph Romagnuolo, Gerard D Schellenberg, Stuart Sherman, Peter Simon, Vijay P Singh, Adam Slivka, Donna Stolz, Robert Sutton, Frank Ulrich Weiss, C Mel Wilcox, Narcis Octavian Zarnescu, Stephen R Wisniewski, Michael R O'Connell, Michelle L Kienholz, Kathryn Roeder, M Michael Barmada, Dhiraj Yadav, Bernie Devlin
Journal: Nature Genetics (2012)
Cowden disease and Lhermitte Duclos disease, markers of breast carcinoma: Report of two patients
Authors: A.C. Braud, A. de Rocquancourt, M. Marty, M. Espie
Journal: Annals of Oncology (1999)

Large data base registries have shown that up to 20% of women with breast cancer have one affected relative and estimate that 5% of breast cancers are attributable to major genes such as BRCA1 or BRCA2 [1]. The management of familial breast cancers requires a specific approach, aiming at early diagnosis, familial surveillance, and specific treatments adjusted to their specific natural history. BRCA1 and BRCA2 linked families have been identified as the commonest genetic condition predisposing to breast cancer but their treatment remain controvertial. Other inherited conditions have been recently identified as risk factors for breast carcinoma. Among them, genodermatosis are of specific interest. These inherited syndromes characterized by hamartomas of ectodermal, endodermal or mesodermal origin affect multiple organs. Most of them have an autosomal dominant pattern of inheritance. The increased incidence of carcinomas reported in these patients gives rise to specific interest. Cowden's disease (CD) and Lhermitte Duclos disease (LDD) are of particular interest, not only for their multisystem abnormalities, but also for their neoplastic risk. CD was initially described in 1962 by Llyod and Denys [2]. Skin, gingival, or digestive papules are considered pathognomonic but thyroid, breast, and the central nervous system can also be involved and need close monitoring [3]. As neurological abnormalities produce non specific symptoms, they appear underdiagnosed. Hydrocephaly, craniomegaly, epilepsy, intracranial hypertension, cerebellar syndrome or LD syndrome have been reported. LDD is a congenital benign cerebellar hamartoma described as a purkinjenoma or a gangliocytoma by Lhermitte and Duclos [4]. The occurrence of fullblown CD with thyroid, digestive or breast lesions in patients with LDD can not be considered as fortuitous. A strong linkage between these two phacomatosis have been commonly accepted. This close association should be recognized and has led to further genetic analysis, resulting in the identification of the Cowden's gene. We report two patients with breast cancer and Cowden or Lhermitte Duclos disease. We will discuss these two congenital disorders, their features, the risk of cancer and recent advances in genetic findings.
Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome
Authors: Anna Virginia Gulino, Daniele Moratto, Silvano Sozzani, Patrizia Cavadini, Karel Otero, Laura Tassone, Luisa Imberti, Silvia Pirovano, Lucia D. Notarangelo, Roberta Soresina, Evelina Mazzolari, David L. Nelson, Luigi D. Notarangelo, Raffaele Badolato
Journal: Blood (2004)
Two-Year Outcome of Psychotic Depression in Late Life
Authors: Alastair J. Flint, Sandra L. Rifat
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The purpose of this study was to determine whether elderly patients with psychotic depression differed in long-term outcome from patients with nonpsychotic depression. METHOD: The study group consisted of 19 patients with psychotic major depression who had responded to ECT (N=15), nortriptyline and perphenazine (N=2), or nortriptyline, perphenazine, and adjunctive lithium (N=2) and 68 nonpsychotic depressed patients who had responded to either nortriptyline alone (N=61) or nortriptyline and lithium (N=7). All patients were maintained on regimens of full-dose nortriptyline. When prescribed for the index episode, adjunctive lithium was also maintained, but perphenazine was withdrawn 16 weeks after response. Patients were followed on a monthly basis for 2 years or until relapse or recurrence, whichever occurred first. RESULTS: Patients with psychotic depression had a substantially higher frequency of relapse or recurrence of depression and a shorter time to these events than nonpsychotic depressed patients. At index assessment, patients with psychosis were more severely depressed and had had more prior episodes of depression, but these factors did not account for the difference in outcome between the two groups. Furthermore, before entering the study, none of the psychotic patients had received adequate treatment for the index episode of depression, and so their poor outcome could not be attributed to prior treatment resistance. CONCLUSIONS: Even when they achieved remission and were maintained on a regimen of full-dose antidepressant medication, older patients with psychotic depression were at greater risk of relapse or recurrence than were their nonpsychotic counterparts. In particular, continuation/maintenance treatment with tricyclic monotherapy following response to ECT had limited efficacy in this group of patients. These findings raise important questions about the optimal treatment of psychotic depression in late life. (Am J Psychiatry 1998; 155:178–183)
Prefrontal Broadband Noise, Working Memory, and Genetic Risk for Schizophrenia
Authors: Georg Winterer, Richard Coppola, Terry E. Goldberg, Michael F. Egan, Douglas W. Jones, Carmen E. Sanchez, Daniel R. Weinberger
Journal: American Journal of Psychiatry (2004)

It has been suggested that increased variability of prefrontal physiological responses may represent a fundamental mechanism underlying frontal lobe deficits in schizophrenia. Increased response variability ("noise") is thought to result from impaired phase resetting of stimulus-induced dynamic changes of ongoing rhythmic oscillations (field potentials) generated in the apical dendrites of pyramidal neurons. In the present study, the authors explored whether this particular physiological abnormality predicts working memory performance and is related to the genetic risk for schizophrenia.Prefrontal response variability of discrete frequency components was investigated across a broad frequency range (0.5-45.0 Hz) during processing of an oddball paradigm in patients with schizophrenia (N=66), their clinically unaffected siblings (N=115), and healthy comparison subjects (N=89).As hypothesized, prefrontal noise was negatively correlated with working memory performance across all subjects. In addition, it was observed that prefrontal noise possesses trait characteristics and is strongly associated with genetic risk for schizophrenia.Frontal lobe-related cognitive function depends on the ability to synchronize cortical pyramidal neurons, which is in part genetically controlled. Increased prefrontal "noise" is an intermediate phenotype related to genetic susceptibility for schizophrenia.
Follicular Rash on the Knees and Hyperkeratotic Palms
Authors: Irum Noor, Sara Braswell, Sandy Milgraum
Journal: JAMA Pediatrics (2015)

A healthy 7-year-old girl presented with a 2-month history of an itchy rash on her elbows, knees, hands, and feet. The patient was otherwise healthy with normal development and growth. She had no other medical problems and was not taking any medications. The rash started as small pink bumps on her knees and elbows, spreading to her hands and feet and progressively thickening. The patient’s history was otherwise unremarkable; she had no pets, had no recent travel outside the United States, and her vaccinations were up to
Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats
Authors: K. Kinoshita, Y. Iimuro, K. Otogawa, S. Saika, Y. Inagaki, Y. Nakajima, N. Kawada, J. Fujimoto, S. L Friedman, K. Ikeda
Journal: Gut (2006)

<b>Background:</b> Liver cirrhosis, which is caused by the accumulation of extracellular matrix materials, is a serious clinical problem that can progress to hepatic failure. Transforming growth factor-β (TGFβ) plays a pivotal role in extracellular matrix production, but bone morphogenetic protein (BMP)-7, a member of the TGFβ superfamily, can antagonise the fibrogenic activity of TGFβ. <b>Aim:</b> In this study, we examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGFβ in vitro and in vivo. <b>Methods and results:</b> In primary cultured rat stellate cells and the LX-2 human stellate cell line, induction of BMP-7 by Ad-BMP-7 infection decreased the expression of collagen 1A2 mRNA and smooth muscle α-actin in the presence or absence of TGFβ, via Smad 1/5/8 phosphorylation. BMP-7 triggered the mRNA expression of inhibitors of differentiation 2 (Id2) in LX-2. Although endogenous expression of BMP-7 was hardly detectable, Smad1 and Id2 overexpression increased BMP-7 expression in LX-2. A liver fibrosis model was induced by the repetitive intraperitoneal injection of thioacetamide (200 mg/kg body weight) twice per week for up to 7 weeks. In rats administered Ad-BMP-7 via the tail vein, hydroxyproline content and the areas stained by Sirius red dye in the liver were significantly reduced compared to controls. Ad-Id2 also reduced fibrosis. <b>Conclusion:</b> These data demonstrate that BMP-7, Smad 1/5/8 and Ids interact to antagonise hepatic fibrogenesis.
Additional requirements for a balanced social psychology
Authors: Siu L. Chow
Journal: Behavioral and Brain Sciences (2004)

Ambiguous data obtained by deception say nothing about social behavior. A balanced social psychology requires separating statistical hypotheses from substantive hypotheses. Neither statistical norms nor moral rules are psychological theories. Explanatory substantive theories stipulate the structures and processes underlying behavior. The Bayesian approach is incompatible with the requirement that all to-be-tested theories be given the benefit of the doubt.