Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of universal health insurance coverage in Thailand on sales and market share of medicines for non-communicable diseases: an interrupted time series study

Objective In 2001, Thailand implemented the Universal Coverage Scheme (UCS), a public insurance system that aimed to achieve universal access to healthcare, including essential medicines, and to influence primary care centres and hospitals to use resources efficiently, via capitated payment for outpatient services and other payment policies for inpatient care. Our objective was to evaluate the impact of the UCS on utilisation of medicines in Thailand for three non-communicable diseases: cancer, cardiovascular disease and diabetes. Design Interrupted time-series design, with a non-equivalent comparison group. Setting Thailand, 1998–2006. Data Quarterly purchases of medicines from hospital and retail pharmacies collected by IMS Health between 1998 and 2006. Intervention UCS implementation, April–October 2001. Outcome measures Total pharmaceutical sales volume and percent market share by licensing status and National Essential Medicine List status. Results The UCS was associated with long-term increases in sales of medicines for conditions that are typically treated in outpatient primary care settings, such as diabetes, high cholesterol and high blood pressure, but not for medicines for diseases that are typically treated in secondary or tertiary care settings, such as heart failure, arrhythmias and cancer. Although the majority of increases in sales were for essential medicines, there were also postpolicy increases in sales of non-essential medicines. Immediately following the reform, there was a significant shift in hospital sector market share by licensing status for most classes of medicines. Government-produced products often replaced branded generic or generic competitors. Conclusions Our results suggest that expanding health insurance coverage with a medicine benefit to the entire Thai population increased access to medicines in primary care. However, our study also suggests that the UCS may have had potentially undesirable effects. Evaluations of the long-term impacts of universal health coverage on medicine utilisation are urgently needed.
DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment

In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.
Effectiveness of the Communication Program on Compliance in a Weekly Multimicronutrient Supplementation Program in Chiclayo, Peru

Background Compliance with daily micronutrient supplementation is usually poor and the question arises whether compliance with a weekly regimen would be better. Objectives The inputs (messages and channels), output (increase of knowledge), and outcome (behavior changes) of a communication campaign in a micronutrient supplementation program for women and adolescent girls 12 through 44 years of age and children under 5 years of age (primary audience) were analyzed. Methods The communication program addressed not only the primary, but also the secondary (facilitators) and tertiary audiences. Formative research and descriptive statistics were used to analyze the communication campaign. Results Nearly all women and adolescent girls (89%) and children (91%) took at least 75% of the supplements over the 3-month period. The incidence rates of reported negative side effects of supplementation in children and in women and adolescent girls were less than 10%. Knowledge of micronutrient nutrition among facilitators of all ages and education levels increased significantly (p < .001). Conclusions A thoroughly planned and implemented nutrition communication program can secure high compliance of the beneficiaries of micronutrient supplementation programs. The necessary supplies should be available at least 3 months before program implementation. With an adequate communication program, supplementation programs can be used to foster food-based approaches for the target audience.
Intra-Aortic Balloon Pump May Grant No Benefit to Improve the Mortality of Patients With Acute Myocardial Infarction in Short and Long Term

AbstractIntra-aortic balloon pump (IABP) has been extensively used in clinical practice as a circulatory-assist device. However, current literature demonstrated significantly varied indications for IABP application and prognosis.The objective of the study was to assess the potential benefits or risks of IABP treatment for acute myocardial infarction (AMI) complicated with or without cardiogenic shock.MEDLINE and EMBASE database were systematically searched until November 2014, using the terms as follows: IABP, IABC (intra-aortic balloon counterpulsation), AMI, heart infarction, coronary artery disease, ischemic heart disease, and acute coronary syndrome. Only randomized controlled trials (RCTs) that compared the use of IABP or non-IABP support in AMI with or without cardiogenic shock were included. Two researchers performed data extraction independently, and at the mean time, the risk of bias among those RCTs was also assessed.Of 3026 citations, 17 studies (n = 3226) met the inclusion criteria. There is no significant difference between IABP group and control group on the short-term mortality (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77–1.06; P = 0.214) and long-term mortality (RR, 0.91; 95% CI, 0.79–1.04; P = 0.155) in AMI patients with or without cardiogenic shock. These results were consistent when the analysis was performed on studies that only included patients with cardiogenic shock, both on short-term mortality (RR, 0.91; 95% CI, 0.77–1.08; P = 0.293) and long-term mortality (RR, 0.95; 95% CI, 0.83–1.10; P = 0.492). Similar result was also observed in AMI patients without cardiogenic shock. Furthermore, the risks of hemorrhage (RR, 1.49; 95% CI, 1.09–2.04; P = 0.013) and recurrent ischemia (RR 0.54, 95% CI 0.37 to 0.79; P = 0.002) were significantly higher in IABP group compared with control group.We did not observe substantial benefit from IABP application in reducing the short- and long-term mortality, while it might promote the risks of hemorrhage and recurrent ischemia. Therefore, IABP may be not an optimal therapy in AMI with or without cardiogenic shock until more elaborate classification is used for selecting appropriate patients.
The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor

Recent studies have identified a number of transcriptional regulators, including E proteins, EBF1, FOXO1, and PAX5, that act together to orchestrate the B-cell fate. However, it still remains unclear as to how they are linked at the earliest stages of B-cell development. Here, we show that lymphocyte development in HEB-ablated mice exhibits a partial developmental arrest, whereas B-cell development in E2A+/−HEB−/− mice is completely blocked at the LY6D− common lymphoid progenitor stage. We show that the transcription signatures of E2A- and HEB-ablated common lymphoid progenitors significantly overlap. Notably, we found that Foxo1 expression was substantially reduced in the LY6D− HEB- and E2A-deficient cells. Finally, we show that E2A binds to enhancer elements across the FOXO1 locus to activate Foxo1 expression, linking E2A and FOXO1 directly in a common pathway. In summary, the data indicate that the earliest event in B-cell specification involves the induction of FOXO1 expression and requires the combined activities of E2A and HEB.
Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate in septic shock.

CONTEXT Dehydroepiandrosterone (DHEA) replacement in sepsis has been advocated because of the sepsis-associated decrease in serum DHEA sulfate (DHEAS). However, experimental sepsis in rodents leads to down-regulation of DHEA sulfotransferase, which inactivates DHEA to DHEAS, theoretically resulting in higher DHEA levels. OBJECTIVE The objective of the study was to test whether serum DHEA and DHEAS are dissociated in septic shock and to determine their association with circulating cortisol in the context of severity of disease and mortality. DESIGN, SETTING, AND PARTICIPANTS This was a cross-sectional study consisting of 181 patients with septic shock, 31 patients with acute trauma, and 60 healthy controls. MAIN OUTCOME MEASURES Serum cortisol, DHEA, and DHEAS were measured before and 60 min after ACTH stimulation. RESULTS Serum cortisol was increased and DHEAS was decreased in both septic shock and trauma patients (all P < 0.001). However, compared with healthy controls, DHEA was significantly increased in sepsis but decreased after trauma (all P < 0.001). In sepsis, neither cortisol nor DHEA increased significantly after ACTH. Most severely ill patients had higher cortisol (P = 0.069) and lower DHEA (P = 0.076) and a significantly higher cortisol to DHEA ratio (P = 0.004). Similarly, the cortisol to DHEA ratio was significantly increased in nonsurvivors of septic shock (P = 0.026), whereas survivors did not differ from controls (P = 0.322). CONCLUSIONS The observed dissociation of DHEA and DHEAS in septic shock contradicts the previous concept of sepsis-associated DHEA deficiency. Increased DHEA levels may maintain the balance between glucocorticoid- and DHEA-mediated immune and vascular effects. However, most severe disease and mortality is associated with an increased cortisol to DHEA ratio, which may represent a novel prognostic marker in septic shock.
The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells

Increased osteoclast-mediated bone resorption is characteristic of osteoporosis, malignant bone disease and inflammatory arthritis. Targeted deletion of Sirtuin1 (Sirt1), a key player in aging and metabolism, in osteoclasts results in increased osteoclast-mediated bone resorption in vivo, making it a potential novel therapeutic target to block bone resorption. Sirt1 activating compounds (STACs) were generated and were investigated in animal disease models and in humans however their mechanism of action was a source of controversy. We studied the effect of SRT2183 and SRT3025 on osteoclastogenesis in bone-marrow derived macrophages (BMMs) in vitro, and discovered that these STACs inhibit RANKL-induced osteoclast differentiation, fusion and resorptive capacity without affecting osteoclast survival. SRT2183 and SRT3025 activated AMPK, increased Sirt1 expression and decreased RelA/p65 lysine310 acetylation, critical for NF-κB activation, and an established Sirt1 target. However, inhibition of osteoclastogenesis by these STACs was also observed in BMMs derived from sirt1 knock out (sirt1-/-) mice lacking the Sirt1 protein, in which neither AMPK nor RelA/p65 lysine 310 acetylation was affected, confirming that these effects require Sirt1, but suggesting that Sirt1 is not essential for inhibition of osteoclastogenesis by these STACs under these conditions. In sirt1 null osteoclasts treated with SRT2183 or SRT3025 Sirt3 was found to be down-regulated. Our findings suggest that SRT2183 and SRT3025 activate Sirt1 and inhibit RANKL-induced osteoclastogenesis in vitro however under conditions of Sirt1 deficiency can affect Sirt3. As aging is associated with reduced Sirt1 level and activity, the influence of STACs on Sirt3 needs to be investigated in vivo in animal and human disease models of aging and osteoporosis.
Population and survival characteristics of cats with hypertrophic cardiomyopathy: 260 cases (1990-1999).

OBJECTIVE To determine current population characteristics of, clinical findings in, and survival times for cats with hypertrophic cardiomyopathy (HCM). DESIGN Retrospective study. ANIMALS 260 cats with HCM. PROCEDURE Information was obtained from the medical records. Cats were classified into 1 of 4 clinical groups (congestive heart failure [CHF] group, arterial thromboembolism [ATE] group, syncope group, or cats without clinical signs [subclinical group]) on the basis of the primary clinical signs at the initial examination. RESULTS 120 cats were classified in the CHF group, 43 in the ATE group, 10 in the syncope group, and 87 in the subclinical group. Antecedent events that may have precipitated CHF included i.v. fluid administration, anesthesia, surgery, and recent corticosteroid administration. Median survival time was 709 days (range, 2 to 4,418 days) for cats that survived > 24 hours. Cats in the subclinical group lived the longest (median survival time, 1,129 days; range, 2 to 3,778 days), followed by cats in the syncope group (654 days; range, 28 to 1,505 days), cats in the CHF group (563 days; range, 2 to 4,418 days), and cats in the ATE group (184 days; range, 2 to 2,278 days). Causes of death included ATE (n = 56), CHF (49), sudden death (13), and noncardiac causes (27). In univariate analyses, survival time was negatively correlated with left atrial size, age, right ventricular enlargement, and thoracentesis. Cats with systolic anterior motion of the mitral valve lived longer than cats without this echocardiographic finding. In multivariate analyses, only age and left atrial size remained significant predictors of survival time. CONCLUSIONS AND CLINICAL RELEVANCE Although overall survival time for cats with HCM was similar to earlier reports, survival times for cats with CHF or ATE were longer than previously reported.
Measurement of atmospheric black carbon in the Vaal Triangle and highveld priority areas

Atmospheric black carbon is an important atmospheric pollutant; it has impacts on human health and a strong climate impact. Black carbon particles are functionally defined by their optical properties (viz. characteristics in light absorption). As a result, black carbon particles are derived from a wide range of sources, but are largely the result of incomplete combustion processes. In order to quantify the atmospheric load of black carbon particles, multi angle absorption photometer (MAAP) instruments have been installed in 8 of the ambient air quality monitoring stations in the Vaal Triangle and Highveld Priority areas. Three of the instruments have been in operation since 2012 and the other 5 were installed in August 2013. This paper presents an analysis of the initial black carbon monitoring data. The impacts of seasonality and meteorological conditions as well as the relationship of the black carbon concentration to PM10 and PM2.5 concentrations are discussed.
PICS: Probabilistic Inference for ChIP‐seq

Summary ChIP‐seq combines chromatin immunoprecipitation with massively parallel short‐read sequencing. While it can profile genome‐wide in vivo transcription factor‐DNA association with higher sensitivity, specificity, and spatial resolution than ChIP‐chip, it poses new challenges for statistical analysis that derive from the complexity of the biological systems characterized and from variability and biases in its sequence data. We propose a method called PICS (Probabilistic Inference for ChIP‐seq) for identifying regions bound by transcription factors from aligned reads. PICS identifies binding event locations by modeling local concentrations of directional reads, and uses DNA fragment length prior information to discriminate closely adjacent binding events via a Bayesian hierarchical t‐mixture model. It uses precalculated, whole‐genome read mappability profiles and a truncated t‐distribution to adjust binding event models for reads that are missing due to local genome repetitiveness. It estimates uncertainties in model parameters that can be used to define confidence regions on binding event locations and to filter estimates. Finally, PICS calculates a per‐event enrichment score relative to a control sample, and can use a control sample to estimate a false discovery rate. Using published GABP and FOXA1 data from human cell lines, we show that PICS' predicted binding sites were more consistent with computationally predicted binding motifs than the alternative methods MACS, QuEST, CisGenome, and USeq. We then use a simulation study to confirm that PICS compares favorably to these methods and is robust to model misspecification.
A dinocephalian therapsid fauna on the Ecca-Beaufort contact in Eastern Cape Province, South Africa : research letter

Systematic exploration of outcrops of the lowermost Beaufort Group for fossils of the oldest terrestrial vertebrates of South Africa, known only from the Permian age lIgEodicynodonl/Ig Assemblage Zone in Western Cape Province, has resulted in the discovery of a therapsid fauna in Eastern Cape Province that is dominated by advanced dinocephalians. The new discoveries include the skull and partial skeleton of a juvenile Anteosaurus , skull and skeletal elements of tapinocephalids, as well as the skull of a scylacosaurid therocephalian. The combined presence of advanced tapinocephalid dinocephalians, the anteosaur Anteosaurus , and scylacosaurid therocephalians suggests that the rocks of the lowermost Beaufort Group in the Eastern Cape Province can be assigned to the lIgTapinocephalusl/Ig Assemblage Zone, rather than to the lIgEodicynodonl/Ig Assemblage Zone, which appears to be restricted to the southwestern part of the Karoo Basin. This biozone identity permits the recognition of a younger age for the Ecca-Beaufort contact eastwards along the southern margin of the basin, thus demonstrating the diachronous nature of the Ecca-Beaufort contact in the southern Karoo.
Striking In Vivo Phenotype of a Disease-Associated Human SCN5A Mutation Producing Minimal Changes in Vitro

Background— The D1275N SCN5A mutation has been associated with a range of unusual phenotypes, including conduction disease and dilated cardiomyopathy, as well as atrial and ventricular tachyarrhythmias. However, when D1275N is studied in heterologous expression systems, most studies show near-normal sodium channel function. Thus, the relationship of the variant to the clinical phenotypes remains uncertain. Methods and Results— We identified D1275N in a patient with atrial flutter, atrial standstill, conduction disease, and sinus node dysfunction. There was no major difference in biophysical properties between wild-type and D1275N channels expressed in Chinese hamster ovary cells or tsA201 cells in the absence or presence of &bgr;1 subunits. To determine D1275N function in vivo, the Scn5a locus was modified to knock out the mouse gene, and the full-length wild-type (H) or D1275N (DN) human SCN5A cDNAs were then inserted at the modified locus by recombinase mediated cassette exchange. Mice carrying the DN allele displayed slow conduction, heart block, atrial fibrillation, ventricular tachycardia, and a dilated cardiomyopathy phenotype, with no significant fibrosis or myocyte disarray on histological examination. The DN allele conferred gene-dose–dependent increases in SCN5A mRNA abundance but reduced sodium channel protein abundance and peak sodium current amplitudes (H/H, 41.0±2.9 pA/pF at −30 mV; DN/H, 19.2±3.1 pA/pF, P<0.001 vs H/H; DN/DN, 9.3±1.1 pA/pF, P<0.001 versus H/H). Conclusions— Although D1275N produces near-normal currents in multiple heterologous expression experiments, our data establish this variant as a pathological mutation that generates conduction slowing, arrhythmias, and a dilated cardiomyopathy phenotype by reducing cardiac sodium current.
Evaluation of Puncture Types as Indicators of Boll Weevil (Coleoptera: Curculionidae) Oviposition in Cotton Squares

Abstract Reproductive boll weevil populations are typically identified by the presence of a frass seal and protuberance at the oviposition site in cotton squares. However, despite the occurrence of other oviposition puncture seal types and their use in previous fecundity studies, the relationship of these respective puncture seal types and oviposition has not been clearly examined. In this study, newly eclosed females (≤24 h old, but mated at 4 d of age) were fed fresh squares daily for 8 d to determine oviposition frequency in relation to individual puncture seal types. Puncture seal types were classified as unsealed; puncture with frass seal; puncture with wax seal; and puncture with wax seal and partially covered with frass. Overall, no significant associations were detected between the types of sealed punctures, and the frequency of oviposition in sealed punctures ranged from 64.6 (wax-seal with frass) to 72.9% (frass-sealed) during 2001 and 53.4 (wax-sealed) to 55.2% (wax-seal with frass) during 2002. Examination of individual trials revealed considerable variability in oviposition associated with all sealed puncture types. Oviposition also occurred in unsealed punctures by mated females in all trials. Because of the high degree of oviposition observed in punctures not normally associated as oviposition sites (i.e., wax-seal with frass, wax-seal), this study clearly shows the need to consider other puncture types as potential indicators of reproductive weevil populations. These results will be critical in boll weevil management programs where accurate detection of reproductive weevil populations is crucial for continued pest suppression.