Miracle-dz/UniFAR-FTUs huggingface dataset:
Destabilization of the A1 Domain in von Willebrand Factor Dissociates the A1A2A3 Tri-domain and Provokes Spontaneous Binding to Glycoprotein Ibα and Platelet Activation under Shear Stress*

This study used recombinant A1A2A3 tri-domain proteins to demonstrate that A domain association in von Willebrand factor (VWF) regulates the binding to platelet glycoprotein Ibα (GPIbα). We performed comparative studies between wild type (WT) A1 domain and the R1450E variant that dissociates the tri-domain complex by destabilizing the A1 domain. Using urea denaturation and differential scanning calorimetry, we demonstrated the destabilization of the A1 domain structure concomitantly results in a reduced interaction among the three A domains. This dissociation results in spontaneous binding of R1450E to GPIbα without ristocetin with an apparent KD of 85 ± 34 nm, comparable with that of WT (36 ± 12 nm) with ristocetin. The mutant blocked 100% ristocetin-induced platelet agglutination, whereas WT failed to inhibit. The mutant enhanced shear-induced platelet aggregation at 500 and 5000 s−1 shear rates, reaching 42 and 66%, respectively. Shear-induced platelet aggregation did not exceed 18% in the presence of WT. A1A2A3 variants were added before perfusion over a fibrin(ogen)-coated surface. At 1500 s−1, platelets from blood containing WT adhered <10% of the surface area, whereas the mutant induced platelets to rapidly bind, covering 100% of the fibrin(ogen) surface area. Comparable results were obtained with multimeric VWF when ristocetin (0.5 mg/ml) was added to blood before perfusion. EDTA or antibodies against GPIbα and αIIbβ3 blocked the effect of the mutant and ristocetin on platelet activation/adhesion. Therefore, the termination of A domain association within VWF in solution results in binding to GPIba and platelet activation under high shear stress.
A Global Game with Strategic Substitutes and Complements: Note

In a 2007 paper, “A global game with strategic substitutes and complements”, by Karp, L. , I.H. Lee, and R. Mason, Games and Economic Behavior, 60(1), 155-175, an argument is made to show existence of Bayesian-Nash equilibrim in global games that may include both strategic substitutes and complements. This note documents a gap in the proof of that statement and presents an alternative proof for a finite player version of their model.
Thyroid function and left ventricular structure and function in the Framingham Heart Study.

BACKGROUND Thyroid hormone acts on the heart and peripheral vasculature in multiple ways. Even in patients with subclinical hypo- or hyperthyroidism, subclinical alterations in left ventricular (LV) structure and function may be associated with important clinical effects. Our objective was to determine whether thyroid function is related to echocardiographic indices of LV structure and function. METHODS Cross-sectional association of serum thyroid-stimulating hormone (TSH) with two-dimensional-guided M-mode echo LV dimensions and function. Participants were 1376 Framingham Heart Study participants (61% women, mean age 69 years) who attended a routine examination 1979-1981. We excluded participants with myocardial infarction or heart failure, renal insufficiency, and missing data, and those using thyroid hormone or antithyroid medications. Serum TSH was measured 1977-1979. The following echocardiographic measurements were analyzed both as continuous variables and dichotomized at the top quintile: LV end-diastolic dimensions, LV wall thickness, LV mass, LV fractional shortening (an indicator of systolic function), and left atrial diameter. Sex-specific multiple regression models were adjusted for age, height, weight, blood pressure, heart rate, total to high-density lipoprotein cholesterol ratio, and the presence of diabetes, hypertension treatment, and valve disease. RESULTS In multivariable linear models, log-TSH was not related to LV mass, LV wall thickness, or left atrial size in either sex, or to LV systolic function in men. Log-TSH had a borderline inverse association with fractional shortening (p = 0.06) in women. In multivariable logistic models, women with TSH <0.5 mU/L (n = 81) had a greater odds of being in the highest quintile of fractional shortening compared to euthyroid subjects (odds ratio 2.2, 95% confidence interval 1.3-3.8, p = 0.01). CONCLUSIONS In our moderate-sized community-based sample, TSH concentration was not associated with LV structure in either sex, but was inversely related to LV contractility, consistent with the known inotropic effects of thyroid hormone.
The vitamin D pathway: a new target for control of the skin’s immune response?

Abstract: The surface of our skin is constantly challenged by a wide variety of microbial pathogens, still cutaneous infections are relatively rare. Within cutaneous innate immunity the production of antimicrobial peptides (AMPs) is a primary system for protection against infection. Many AMPs can be found on the skin, and these include molecules that were discovered for their antimicrobial properties, and other peptides and proteins first known for activity as chemokines, enzymes, enzyme inhibitors and neuropeptides. Cathelicidins were among the first familiesf of AMPs discovered on the skin. They are now known to have two distinct functions; they have direct antimicrobial activity and will initiate a host cellular response resulting in cytokine release, inflammation and angiogenesis. Dysfunction of cathelicidin is relevant in the pathogenesis of several cutaneous diseases including atopic dermatitis where cathelicidin induction is suppressed, rosacea, where cathelicidin peptides are abnormally processed to forms that induce cutaneous inflammation and a vascular response, and psoriasis, where a cathelicidin peptide can convert self‐DNA to a potent stimulus of an autoinflammatory cascade. Recent work has unexpectedly identified vitamin D3 as a major factor involved in the regulation of cathelicidin expression. Therapies targeting the vitamin D3 pathway and thereby cathelicidin may provide new treatment modalities in the management of infectious and inflammatory skin diseases.
Real Earnings Management before and after Reporting SOX 404 Material Weaknesses

SYNOPSIS: The purpose of this study is to investigate whether SOX Section 404 material weaknesses manifest in real earnings management behavior. The empirical findings indicate that, compared to companies with effective internal controls, companies with existing material weaknesses in their internal controls engage in more manipulation of real activities (particularly inventory overproduction). This implies that the weak commitment by management to provide effective internal control system and high-quality financial information relates to a tendency to use real earnings management methods. Moreover, we find evidence suggesting that companies employ real earnings management (overproduction and reduction of discretionary expenses) after disclosing previous year's material weaknesses. We conjecture that the public disclosure of material weaknesses induces management to strive to mitigate the expected negative reactions of stakeholders to the disclosure by engaging in real earnings management, which is not ea.
A Construct Validation Study of the Human Figure Drawing Test

To assess whether the Human Figure Drawing Test provides an assessment of nonverbal cognitive maturity, correlations for 31 youngsters who ranged in age from 6–0 to 10–10 on the Human Figure Drawing Test and the Verbal, Performance, and Full Scale IQs of the Wechsler Intelligence Scale for Children—Revised (WISC—R) were examined. Significant correlations were observed for each of the scales, but the value of . 69 for drawings and WISC—R Performance IQs was significant, suggesting the assessment that these tests are largely nonverbal. Implications for the role of language were posited.
Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity.

BACKGROUND Current cytotoxic assays, including Cr release and fluorescent assays, do not directly measure the proportion of target cells which are killed by apoptosis. Cell-mediated cytotoxicity induced by CTLs and NK cells is mainly regulated by the perforin-granzyme, the Fas ligand (Fas L), and the Tumor Necrosis Factor (TNF)-alpha pathways. Perforin generates pores in the membrane of target cells, allowing granzyme B to enter and initiate apoptosis. The other effectors, Fas L and TNF-alpha act by an apoptosis mechanism, leading to DNA fragmentation. A three color flow cytometric method to measure cell-mediated cytotoxicity induced by CTLs or NK cells is described. METHODS The fluorochromes used are: PKH-26, a stable membrane dye for the labeling of the effector cells, annexin V-FITC which allows the direct evaluation of early apoptotic cells and propidium iodide which distinguishes membrane permeabilized and late apoptotic cells. RESULTS By eliminating through gating PKH-26 positive effector cells, we obtain a direct estimation of the percentage of target cells in the early stages of apoptosis as well as the percentage of target cells dying after late apoptosis and membrane permeabilization. The cytotoxic activity of IL-2 stimulated PBL against K562, Jurkat and KYM-1 was evaluated. CONCLUSIONS This rapid and novel assay permits the discrimination of the cell death mechanisms occurring during a cytotoxic response and to precisely evaluate the contribution of apoptosis in the early phases of cell-mediated cytotoxicity.
Smoking but not homozygosity for CYP1A2 g‐163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda

Please cite this paper as: Smoking but not homozygosity for CYP1A2 g‐163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda. Experimental Dermatology 2010. Experimental Dermatology 2010; 19: e326–e328.
Cardiac output and ductal reopening during phototherapy in preterm infants

Left ventricular output (LVO), left pulmonary artery blood flow (LPA) and patency of the ductus arteriosus (PDA) were studied with 2D/pulsed Doppler ultrasound before, during and after phototherapy treatment in 27 preterm infants (gestational age ≤ 32 wk), who were exposed for a minimum of 12 h to phototherapy for non‐haemolytic hyperbilirubinemia. In 14 infants (52%) the ductus arteriosus reopened during phototherapy, but ductal patency was not of haemodynamic importance. LVO initially decreased in preterm infants in whom the ductus did not reopen. From 12 h until discontinuation of phototherapy, LVO and LPA were higher than before phototherapy in all infants. After withdrawal of phototherapy, LVO and LPA returned to pre‐phototherapy values. □Cardiac output, patent ductus arteriosus, phototherapy, preterm
Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States.

BACKGROUND Hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. This relationship has not been investigated at the population level, and its biological mechanism remains unknown. OBJECTIVE To examine the prevalence of type 2 diabetes among persons with HCV infection in a representative sample of the general adult population of the United States. DESIGN Cross-sectional national survey. SETTING The Third National Health and Nutrition Examination Survey, 1988-1994. PARTICIPANTS 9841 persons older than 20 years of age for whom data on HCV infection and diabetes were complete. MEASUREMENTS The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting plasma glucose measurement and medication history. Presence of HCV infection was assessed by testing for serum HCV-specific antibodies (anti-HCV). RESULTS Of the 9841 persons evaluated, 8.4% had type 2 diabetes and 2.1% were anti-HCV positive. Type 2 diabetes occurred more often in persons who were older, were nonwhite, had a high body mass index, and had low socioeconomic status. Type 2 diabetes was less common in persons who acknowledged previous illicit drug use. After adjustment for these factors, persons 40 years of age or older with HCV infection were more than three times more likely than those without HCV infection to have type 2 diabetes (adjusted odds ratio, 3.77 [95% CI, 1.80 to 7.87]). None of the 19 persons with type 1 diabetes were anti-HCV positive. CONCLUSION In the United States, type 2 diabetes occurs more often in persons with HCV infection who are older than 40 years of age.
Prognostic factors of peptic ulcer perforation.

OBJECTIVES Today a perforated peptic ulcer (PPU) is a rare condition. However, emergency surgery for perforated ulcer presently carries a mortality risk of up to 30%. The aim of this study is to analyze and define factors influencing surgical prognosis in patients operated upon for PPU. METHODS We performed a retrospective analysis of 62 patients treated for PPU in Suleyman Demirel University, Surgical Department between January 1995 to January 2004. Univariate analysis was performed to determine risk factors for mortality in PPU by chi-square test, Pearson and Spearman correlation tests using SPSS for Windows statistical software. We accepted statistical significance for p values <0.05. RESULTS The overall mortality rate was 17.7%. The present study confirms the age, sex, American Society of Anesthesiology (ASA) classification, coexisting medical disease, elapsed time from symptoms to operation, blood pressure, pulse, serum albumin and creatinine levels, hemoglobin level and diameter of perforation as valid prognostic factors in whole series, whereas a previous history of peptic ulcer disease, chronic ingestion history of nonsteroidal anti-inflammatory drugs, alcohol ingestion, smoking habits, site of perforation, type of surgical treatment (simple suture or resection), postoperative complications did not appear to be related to prognosis. CONCLUSION Age, gender, ASA classification, coexisting medical disease, elapsed time from symptoms to operation, blood pressure, pulse, serum albumin and creatinine levels, hemoglobin level and diameter of perforation are factors significantly associated with fatal outcomes in patients undergoing emergency surgery for PPU. Thus, such factors need to be carefully taken into account during the general workup of patients admitted for PPU.
How Does Group Affiliation Affect The Diversification Performance Of Family-Controlled Firms In Malaysia? â€“ A Governance Perspective

This paper examines the roles of business group affiliations and whether the size and ownership structure of business groups influence the performance outcomes of diversification among family-controlled firms in Malaysia. It presents evidence that agency-driven and thus performance-diminishing firm diversification is more likely to take place in firms affiliated with a family-controlled business group than in independent firms. The findings support the hypothesis that if the benefits of diversification can be captured through group-level diversification, then diversification at the firm level is more of an act of expropriation. In Malaysia, the undue political interference in business that to a certain extent has contributed to a weak enforcement of rules causes the enhanced control of family ownership through the formation of large and structurally complicated business groups to go unchecked. This grants the controlling families opportunities to pursue sub-optimal firm diversification policies that bring them more self-interested benefits at the expense of firm performance.
The distribution of income, health and health care: a review of some recent literature

This paper summarizes some of the recent literature on the relationships between income, health and health care spending. At the population level, the associations (or the lack of it) between these variables are well-known. Wealthier developing nations are healthier, though there appear to be decreasing marginal returns to scale: above a certain income level, the association becomes very weak. More recently, some researchers have turned from the analysis of levels to the analysis of distributions across population groups. Many research findings have suggested that the hypothesis that the extent of relative income inequality adversely affects health cannot be rejected. The evidence from the ecological studies on aggregate data awaits confirmation from longitudinal studies at the individual level. Although it seems premature to conclude that mortality rates in high-income, developed countries can be lowered by redistributing income, the body of evidence that has accumulated is sufficiently large to merit further empirical investigation.
Moderate versus aggressive chemotherapy of nodular lymphocytic poorly differentiated lymphoma.

One hundred twenty-eight patients with purely nodular lymphocytic poorly differentiated lymphoma (NLPDL) without any prior therapy, entered on Eastern Cooperative Oncology Group protocol EST 2474, were analyzed for response, progression-free and overall survival. The restaged complete response rates with cyclophosphamide-prednisone (CP) (moderate regimen) of 54% compared favorably with those of the more intensive regimens; cyclophosphamide, vincristine, procarbazine and prednisone (COPP) (56%) and BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) (53%). The toxicity of the regimens decreased from BCVP to COPP to CP. The median survival rate for the entire group was 7.8 years. Estimated progression-free survival at five years by regimen was COPP, 57%; BCVP, 26%; CP, 22% (P = .02). No other prognostic parameter significantly affected progression-free survival. In spite of the better progression-free survival of COPP-treated patients, the overall survival rates with the different induction regimens were similar. Maintenance therapy for patients in complete response at the end of induction therapy with periodic BCVP reinduction did not significantly affect the disease-free or overall survival. Cyclophosphamide-prednisone is a minimally toxic regimen effective in the treatment of NLPDL, but COPP, in view of its acceptable toxicity in this patient population and apparent superiority in providing a longer disease-free state, deserves further testing.
Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in healthy men: role of visceral fat accumulation.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome that is closely associated with obesity, dyslipidemia, insulin resistance, and type 2 diabetes, thus suggesting that NAFLD represents another component of the metabolic syndrome (1,2). Because it is now recognized that individuals with the metabolic syndrome are at increased cardiovascular risk (3–5), it is possible to hypothesize that NAFLD patients might portend a greater cardiovascular disease (CVD) risk. Ultrasonographically measured carotid intima-media thickness (CIMT), as a reliable index of subclinical atherosclerosis (6), can be used to characterize the CVD risk of patients with NAFLD. However, the available data on this specific topic are lacking. We compared CIMT values in subjects with and without nonalcoholic hepatic steatosis (HS) and examined whether such differences were mediated by one or more metabolic disorders typically clustering in these subjects. We studied 85 male volunteers who were randomly selected among those who agreed to have an evaluation of their liver and intra-abdominal fat by ultrasonography and computed tomography (CT) scan, respectively. The exclusion criteria were as follows: age >50 years combined with an alcohol consumption ≥20 g/day, taking any drugs, and a history of recent acute illness or clinical evidence suggestive of any cardiovascular events, diabetes, or kidney or liver disorders. All individuals were clinically healthy. Most subjects were abstainers ( n = 68) or drank minimally …
Changes in Blood Pressure and Cardiac Output during Cesarean Delivery: The Effects of Oxytocin and Carbetocin Compared with Placebo

Background:Little is known about maternal hemodynamics after Cesarean delivery. Uterine contractions may increase cardiac output. Oxytocin is the first-line treatment for uterine atony, although the effects of the long-acting oxytocin analogue carbetocin are comparable with that of oxytocin. The authors analyzed the effects of i.v. oxytocin 5 U, carbetocin 100 µg, and placebo on hemodynamics, uterine tone, adverse events, and blood loss after Cesarean delivery. Methods:This was a randomized, double-blinded, placebo-controlled, parallel-group comparison of carbetocin and oxytocin after elective Cesarean delivery of singletons under spinal anesthesia (n = 76). Continuously measured invasive systolic arterial pressure was the primary outcome measure. Results:The mean systolic arterial pressure decrease was 28 mmHg (95% CI, 22–34) after oxytocin and 26 mmHg (95% CI, 20–31) after carbetocin. The decrease was greatest after 80 (95% CI, 71–89) and 63 s (95% CI, 55–72), respectively (P = 0.006). The differences were nearly undetectable after 2.5 min, although the effect of carbetocin was slightly greater than placebo (P < 0.001). The group differences in systolic arterial pressure decreased over 5 min and were gone at 1 h. Heart rate and cardiac output increased in all three groups. Stroke volume increased after oxytocin and carbetocin but was unchanged after placebo. Conclusions:The hemodynamic side effects of oxytocin 5 U and carbetocin 100 µg were comparable. The lack of an increase in stroke volume in the placebo group challenges the theory that uterine contraction causes autotransfusion of uterine blood, leading to an increase in preload.
Long-term voluntary counseling and testing (VCT) uptake dynamics in a multicountry HIV workplace program in sub-Saharan Africa

Abstract High uptake of HIV voluntary counseling and testing (VCT) services is important for the success of HIV workplace programs in sub-Saharan Africa. From 2001 onwards, Heineken, a multinational brewing company, implemented a comprehensive HIV prevention and treatment program for employees and their dependents of its African subsidiaries. Confidential in-house VCT is part of this program. VCT uptake dynamics over time, and factors associated with early uptake were studied. Between September 2001 and December 2007, 9723 adult beneficiaries were tested for HIV in 14 company sites in five African countries. Three hundred and seventy (3.8%) of tested persons were infected with HIV-1. During the first 12 months 1412 tests were done, compared to 8311 tests in the subsequent years. The annual average uptake of testing among eligible persons varied between 15 and 32%. The coverage was higher among female compared to male employees, and higher among female compared to male spouses. Distinct peaks in uptake were linked to specific local events. HIV-1 infected persons were significantly more likely to be tested in the early period. The proportion of HIV-1 infected persons among testees was 8.8% in the first 12 months compared to 3.0% in the subsequent period (p<0.001). HIV-1 infected persons diagnosed in the early period were in a more advanced clinical stage, and had a significantly lower CD4 count than those tested later (median CD4 count 227 vs. 314 cells/µl; p=0.002). In this workplace program, HIV-1 infected individuals came earlier for an HIV test than uninfected people, and people with advanced infection came earlier than those with less advanced disease. Employees’ spouses are harder to reach than employees and extra efforts should be undertaken to reach them as well. Uptake of HIV testing can be actively influenced by educational or promotional activities.