Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of COPD in five Colombian cities situated at low, medium, and high altitude (PREPOCOL study).

BACKGROUND The prevalence of COPD in Colombia is unknown. This study aimed to investigate COPD prevalence in five Colombian cities and measure the association between COPD and altitude. METHODS A cross-sectional design and a random, multistage, cluster-sampling strategy were used to provide representative samples of adults aged >or= 40 years. Each participant was interviewed (validated Spanish version of the Ferris Respiratory Questionnaire) and performed spirometry before and after 200 microg of inhaled salbutamol, using a portable spirometer according to American Thoracic Society recommendations. COPD definitions were as follows: (1) spirometric: fixed ratio (primary definition): FEV1/FVC < 70% after bronchodilator; (2) medical: a diagnosis of chronic bronchitis, emphysema, or COPD made by a physician; (3) clinical: cough and phlegm >or= 3 months every year during >or= 2 consecutive years (chronic bronchitis). Analysis was performed using statistical software. RESULTS A total of 5,539 orsubjects were included. The overall COPD prevalence using the primary definition (spirometric) was 8.9%, ranging from 6.2% in Barranquilla to 13.5% in Medellín. The prevalence measured by the spirometric definition was higher than medical (2.8%) and clinical (3.2%) definitions. After the logistic regression analysis, the factors related with COPD were age >or= 60 years, male gender, history of tuberculosis, smoking, wood smoke exposure >or= 10 years, and very low education level. There was a nonsignificant tendency toward larger prevalence with higher altitude. CONCLUSION COPD is an important health burden in Colombia. Additional studies are needed to establish the real influence of altitude on COPD prevalence.
Anti-endothelial cell antibodies in connective tissue diseases associated with pulmonary arterial hypertension.

OBJECTIVE To investigate the prevalence of anti-endothelial cell antibodies (AECA) in connective tissue diseases (CTD) associated with pulmonary arterial hypertension (PAH) and to corroborate the pathologic function of AECA in PAH-associated CTDs. METHODS AECA were detected by cellular enzyme-linked immunosorbent assay (ELISA) in sera of 19 PAH-associated CTD patients, 22 CTD patients without PAH involvement, and 20 age- and sex-matched healthy individuals as controls. Using IgG purified from the sera of AECA-positive, AECA-negative, and healthy subjects, the effects of AECA on the expression of ICAM-1 and the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in cultured endothelial cells were also evaluated. RESULTS A total of 12 of the 19 (63.2%) CTD patients with PAH, 9 of the 22 (40.9%) CTD patients without PAH, and 1 of the 20 (5%) healthy controls were positive for AECA, which were calculated as ELISA ratio (ER) values. ER values in PAH-associated CTD patients were significantly higher than those with CTD without PAH (3.68±2.05 versus 1.67±1.07, P<0.001). IgG purified from AECA-positive sera induced a significantly increased level of ICAM-1 expression after 48 h incubation (795.2±32.5 pg/mL) compared with AECA-negative or healthy control IgG (231.5±27.1 and 192.8±33.4 pg/mL, respectively; P<0.001). In addition, RANTES production by cultured human pulmonary arterial endothelial cells (HPAECs) increased in both a time- and concentration-dependent manner in response to incubation with purified AECA-positive IgG. CONCLUSIONS AECA could be involved in CTD and might participate in the pathogenesis of PAH-associated CTD.
Raf-1 Kinase Inhibitory Protein (RKIP) Mediates Ethanol-induced Sensitization of Secretagogue Signaling in Pancreatic Acinar Cells*

Background: The molecular mechanism by which ethanol (EtOH) sensitizes pancreatic acinar cells to secretagogue stimulation is largely undefined. Results: Ethanol stimulates PKC-dependent RKIP phosphorylation, and RKIP ablation prevents EtOH-induced sensitization of secretagogue Ca2+ signaling and aberrant chymotrypsin activation. Conclusion: RKIP mediates the cytotoxic effects of EtOH on pancreatic acinar cells. Significance: Modulation of RKIP expression may have therapeutic utility in the prevention or treatment of alcohol-associated pancreatitis. Excessive alcohol consumption is associated with most cases of chronic pancreatitis, a progressive necrotizing inflammatory disease that can result in pancreatic insufficiency due to acinar atrophy and fibrosis and an increased risk of pancreatic cancer. At a cellular level acute alcohol exposure can sensitize pancreatic acinar cells to secretagogue stimulation, resulting in dysregulation of intracellular Ca2+ homeostasis and premature digestive enzyme activation; however, the molecular mechanisms by which ethanol exerts these toxic effects have remained undefined. In this study we identify Raf-1 kinase inhibitory protein as an essential mediator of ethanol-induced sensitization of cholecystokinin- and carbachol-regulated Ca2+ signaling in pancreatic acinar cells. We show that exposure of rodent acinar cells to ethanol induces protein kinase C-dependent Raf-1 kinase inhibitory protein phosphorylation, sensitization of cholecystokinin-stimulated Ca2+ signaling, and potentiation of both basal and cholecystokinin-stimulated extracellular signal-regulated kinase activation. Furthermore, we show that either suppression of Raf-1 kinase inhibitory protein expression using short hairpin RNA or gene ablation prevented the sensitizing effects of ethanol on cholecystokinin- and carbachol-stimulated Ca2+ signaling and intracellular chymotrypsin activation in pancreatic acinar cells, suggesting that the modulation of Raf-1 inhibitory protein expression may have future therapeutic utility in the prevention or treatment of alcohol-associated pancreatitis.
Evaluation of Female Breast Cancer Risk Among the Betel Quid Chewer: A Bio-Statistical Assessment in Assam, India.

BACKGROUND Breast cancer is the most commonly diagnosed cancer among the female population of Assam, India. Chewing of betel quid with or without tobacco is common practice among female population of this region. Moreoverthe method of preparing the betel quid is different from other parts of the country.So matched case control study is conducted to analyse whetherbetel quid chewing plays a significant role in the high incidence of breast cancer occurrences in Assam. METHODS AND MATERIAL Here, controls are matched to the cases by age at diagnosis (±5 years), family income and place of residence with matching ratio 1:1. Conditional logistic regression models and odd ratios (OR) was used to draw conclusions. RESULTS It is observed that cases are more habituated to chewing habits than the controls.Further the conditional logistic regression analysis reveals that betel quid chewer faces 2.353 times more risk having breast cancer than the non-chewer with p value 0.0003 (95% CI 1.334-4.150). CONCLUSION Though the female population in Assam usually does not smoke, the addictive habits typical to this region have equal effect on the occurrence of breast cancer.
Increased nocturnal sodium excretion in obstructive sleep apnoea. Relation to nocturnal change in diastolic blood pressure

Objective. The mechanisms involved in the development and maintenance of hypertension in obstructive sleep apnoea (OSA) are not clear. We hypothesized that OSA patients have an abnormal renal handling of sodium and water during the night. Material and methods. We studied 29 OSA patients and 19 healthy controls at night with serial determinations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), arginine vasopressin (AVP), aldosterone (Aldo), fractional urinary excretion of sodium (FENa), free water clearance (CH2O), urinary excretion of aquaporin 2 (u‐AQP2), systolic blood pressure (SBP), diastolic blood pressure (DBP) and oxygen saturation. Results. OSA patients had a higher FENa (0.6 (0.4–1.0) versus 0.4 (0.3–0.6) %; p = 0.017), SBP (129 (114–145) versus 114 (106–122) mmHg; p = 0.001) and DBP (81 (72–87) versus 71 (65–74) mmHg; p<0.001) than healthy controls at night. In hypertensive OSA patients, the FENa correlated significantly with the change in nocturnal DBP (r2 = 0.411; p = 0.010). Mean level of AVP during the night was higher in OSA patients compared with healthy controls (1.1 (0.8–1.4) versus 0.8 (0.6–1.1) pmol/L; p = 0.033) and correlated with SBP. ANP, BNP, Aldo, CH2O and u‐AQP2 were the same in OSA and controls. Conclusions. We conclude that the higher fractional excretion of sodium in OSA is most likely attributable to pressure natriuresis. The correlation between mean AVP and blood pressure suggests that AVP may be part of the pathogenetic mechanism underlying hypertension in these patients.
Estimating Demand Using Space Elastic Demand Model for Retail Assortment Planning

A retailer assortment is defined as a mix of products stocked in a retail store. The identification of proper assortment has become difficult in the current consumer-centric environment. Assortment planning (AP) in a retail chain largely depends on the estimation of demand of various products under consideration. The knowledge of the true demand rates and substitution rates is important for a retailer for a variety of management decisions, such as the ideal assortment to carry, the quantum of each item to be stocked and how often to replenish the stock (Anupindi, Dada & Gupta, 1998). Space elastic demand model is one of the models which have been widely used for demand estimation in retail AP literature. However, there is paucity of empirical studies in this field of research. In this article, the demand has been estimated using space elastic demand model for two product categories comprising 11 products within the category. The study illustrates the methodology for estimation of demand using space elastic demand model. The results obtained are consistent with the results obtained in few of the empirical studies done in other contexts.
Guanosine triphosphate-sensitive adenylate cyclase of adrenocorticotrophic hormone- and prostaglandin-resistant human adrenocortical tumors.

The guanosine triphosphate (GTP)-sensitive adenylate cyclase was studied in the crude membranes of three adrenocorticotrophic hormone (ACTH)-resistant tumors and one prostaglandin E1 (PGE1)-resistant human adrenocortical tumor. In the ACTH-resistant tumors, the steroidogenesis of isolated adrenocortical cells was not stimulated by ACTH1–24 but was enhanced by PGE1; whereas in the PGE1-insensitive tumor, PGE1 had no effect but ACTH stimulated steroidogenesis. The cortisol production of cells from all four tumors was stimulated by N 6, O 2-dibutyryl cyclic adenosine 3′:5′-monophosphate. Binding studles with labeled ACTH1–24, ACTH11–24, and PGE1 reveaied that the hormone resistance was assoclated with a selective alteration of the ACTH or the PGE1 receptor. The adenylate cyclase activity of ACTH-resistant tumor membranes was not stimulated by ACTH but was normally stimulated by PGE1. Conversely, in the PGE1-insensitive tumor, the enzyme activity was not enhanced by PGE1 but was normally increased by ACTH1–24. In all four tumors, the adenylate cyclase activity was normal regarding basal levels and NaF stimulation. In addition 5′-guanylylimidodiphosphate and, to a lesser extent, GTP and 5′-guanylyl-methylenediphosphonate were effective in stimulating the basal adenylate cyclase activity of the four tumors and in enhancing the hormone effect on the intact hormone receptor complex ( i.e. , the PGE1 receptor of the ACTH-resistant tumors and the ACTH receptor of the PGE1-resistant tumor). Our results are thus consistent with the fact that, in human adrenocortical tumors, the ACTH and PGE1 receptors can be independently affected, the adenylate cyclase catalytic subunit and the GTP-sensitive subunit being unaltered by this selective tumoral process. This suggests that the GTP-sensitive subunit may be more closely related to the catalytic subunit of the enzyme than to the hormone-binding site.
Monetary Policy and Leverage Shocks

The current mainstream approach to monetary policy in the United States is based on the new Keynesian model and is expressed in terms of the federal funds rate. It ignores the role of financial intermediary leverage (or collateral rates). But as the federal funds rate has reached the zero lower bound, the issue is whether there is a useful role of leverage in monetary policy and business cycle analysis. Motivated by these considerations and by recent financial intermediary asset pricing theories, in this paper we investigate the macroeconomic effects of broker-dealer leverage and the interdependence between monetary policy and broker-dealer leverage in the context of a structural vector autoregression model, using quarterly U.S. data over the period from 1967:1 to 2014:3. We address the simultaneity problem of identifying monetary policy and leverage shocks by using a combination of short-run and long-run restrictions. We also use the sign restrictions approach to the identification of shocks to distinguish between leverage supply and leverage demand shocks, as one would expect the macroeconomic effects of these two types of leverage shocks to be quite different. Our results show that monetary policy and broker-dealer leverage demand shocks produce results that capture reasonable macroeconomic dynamics.
Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat

Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post‐injury time points, as compared with sham‐injured controls (P ≤ 0.05). Accumulation of β‐amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post‐injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase‐3 co‐labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post‐injury (P ≤ 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI.
Engagement of Toll‐like receptors by mycoplasmal superantigen: downregulation of TLR2 by MAM/TLR4 interaction

Mycoplasma arthritidis mitogen (MAM) is a superantigen (SAg) from M. arthritidis, an agent of murine toxic shock syndrome and arthritis. We previously demonstrated that C3H/HeJ and C3H/HeSnJ mice that differ in expression of TLR4 differed in immune reactivity to MAM. We show here that MAM directly interacts with TLR2 and TLR4 by using monoclonal antibodies to TLR2 and TLR4 which inhibit cytokine responses of THP‐1 cells to MAM. Also, using macrophages from C3H substrains and TLR2‐deficient mice, we confirmed that both TLR2 and TLR4 are used by MAM. Levels of IL‐6 in supernatants of MAM‐challenged macrophages were higher in mice which expressed only TLR2, lesser with both TLR2 and TLR4, and absent in mice lacking both TLR2 and TLR4. In addition, expression of TLR2 and TLR4 was moderately upregulated in wild‐type cells but cells lacking TLR4 showed a fivefold increase in TLR2 expression. Further, blockade of TLR4 on macrophages of C3H/HeN mice with antibody greatly increased expression of TLR2 and release of IL‐12p40 in response to MAM. These results indicate that the SAg, MAM, interacts with both TLR2 and TLR4 and that TLR4 signalling might downregulate the MAM/TLR2 inflammatory response.
An OLS Approach to Modelling the Determinants of Private Investment in Ghana

After independence, most developing countries embraced the development paradigm of import substitution. Nevertheless, in the 1980s, there was a shift in development paradigm from import substitution to the private sector-led development strategy to boost growth in developing countries. The study analyses the determinants of private investment in Ghana using a time series data from 1980 to 2010 with the aid of multiple linear regression model. It was revealed that factors that have a significant impact on private investment in Ghana were public investment, credit supply to the private sector, external debt, openness of the economy, corporate tax and democracy. Nevertheless, variables like: GDP growth, real interest rate, inflation and real exchange rate were not statistically significant. The study therefore recommends a tighter fiscal policy to reduce the crowding out effect on private investment. Foreign trade and trade liberalization must be encouraged to ameliorate private investment in Ghana.
Poxviral Protein A46 Antagonizes Toll-like Receptor 4 Signaling by Targeting BB Loop Motifs in Toll-IL-1 Receptor Adaptor Proteins to Disrupt Receptor:Adaptor Interactions*

Background: TLR4 signaling is inhibited by poxviral protein A46, but the mechanism is unknown. Results: We identify the protein interaction surfaces within the TLR4 complex that A46 antagonizes, and characterize the interaction between A46 and TRAM. Conclusion: A46 prevents receptor:adaptor interactions, and has a TRAM-specific interaction motif. Significance: This work reveals the molecular basis for poxviral antagonism of TLR4. Toll-like receptors (TLRs) have an anti-viral role in that they detect viruses, leading to cytokine and IFN induction, and as such are targeted by viruses for immune evasion. TLR4, although best known for its role in recognizing bacterial LPS, is also strongly implicated in the immune response to viruses. We previously showed that the poxviral protein A46 inhibits TLR4 signaling and interacts with Toll-IL-1 receptor (TIR) domain-containing proteins of the receptor complex. However the exact molecular mechanism whereby A46 disrupts TLR4 signaling remains to be established, and may yield insight into how the TLR4 complex functions, since viruses often optimally target key residues and motifs on host proteins for maximal efficiency. Here we show that A46 targets the BB loop motif of TIR proteins and thereby disrupts receptor:adaptor (TLR4:Mal and TLR4:TRAM), but not receptor:receptor (TLR4:TLR4) nor adaptor:adaptor (Mal:MyD88, TRAM:TRIF, and Mal:Mal) TIR interactions. The requirement for an intact BB loop for TIR adaptor interactions correlated with the protein:protein interfaces antagonized by A46. We previously discovered a peptide fragment derived from A46 termed VIPER (Viral Inhibitory Peptide of TLR4), which specifically inhibits TLR4 responses. Here we demonstrate that the region of A46 from which VIPER is derived represents the TLR4-specific inhibitory motif of the intact protein, and is essential for A46:TRAM interactions. This study provides the molecular basis for pathogen subversion of TLR4 signaling and clarifies the importance of TIR motif BB loops, which have been selected for viral antagonism, in the formation of the TLR4 complex.
Incubation phase of acute hepatitis B in man: Dynamic of cellular immune mechanisms

After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus‐specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single‐source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV‐specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV‐DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct ex vivo quantification of HBV‐specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus‐specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease.
Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases

The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.