Miracle-dz/UniFAR-FTUs huggingface dataset:
Geographic distribution and epidemiology of lung cancer during 2011 in Zhejiang province of China.

BACKGROUND To explore etiology for providing scientific clues for the prevention of lung cancer. MATERIALS AND METHODS Data for lung cancer incidence and meteorological geographic factors from 25 counties in Zhejiang province of China during 2011 were studied. Stepwise multiple regression and correlation analysis were performed to analyze the geographic distribution and epidemiology of lung cancer. RESULTS 8,291 new cases (5,998 in males and 2,293 females) of lung cancer during 2011 in Zhejiang province were reported in the 25 studied counties. Reported and standardized incidence rates for lung cancer were 58.0 and 47.0 per 100,000 population, respectively. The incidence of lung cancer increased with age. Geographic distribution analysis shows that the standardized incidence rates of lung cancer in northeastern Zhejiang province were higher than in the southwestern part, such as in Nanhu, Fuyang, Wuxing and Yuyao counties, where the rates were more than 50 per 100,000 population. In the southwestern Zhejiang province, for instance, in Yueqing, Xianju and Jiande counties, the standardized incidence rates of lung cancer were lower than 37 per 100,000 population. Spearman correlation tests showed that forest coverage rate, air quality index (AQI), and annual precipitation level are associated with the incidence of lung cancer. CONCLUSIONS Lung cancer in Zhejiang province shows obvious regional differences. High incidence appears associated with low forest coverage rate, poor air quality and low annual precipitation. Therefore, increasing the forest coverage rate and controlling air pollution may play an important role in lung cancer prevention.
p53 status influences response to tamoxifen but not to fulvestrant in breast cancer cell lines

Mutations in the tumor suppressor gene TP53 are associated with poor prognosis in breast cancer. This prognostic value may rely in part on the fact that p53 plays a role in the antiproliferative and apoptotic activities of chemotherapy regimens used to treat breast tumors. However, some studies suggested that p53 may also influence response to antihormone treatments. Here we investigate how p53 may affect response to antihormonal treatments, using estrogen‐dependent breast cancer cell‐lines with different p53 status. We show that p53 mutated cells were more resistant to cytotoxic effects of 4‐hydroxy‐tamoxifen (OHT) compared to p53 wild‐type cells. In contrast, p53 status did not significantly impact on response to fulvestrant. p53 mutated cells were also hypersensitive to proliferative effects of estradiol. Interestingly, OHT at doses in the low range had proliferative activities in p53 mutated cells (120–150% proliferation rate under 1 μM OHT treatment in low estrogen conditions). Using gene silencing or specific tyrosine kinase inhibitors, we show that the proliferative effects of OHT were estrogen receptor dependent and could be abrogated by the inhibition of EGFR and/or HER2 kinases. These findings suggest that loss of p53 function may increase cross‐talks between estrogen receptor and EGFR/HER2 pathways, contributing to a proliferative effect of OHT. These results bring new insights into the prognostic role of p53 in breast cancer and into possible mechanisms underlying tamoxifen resistance.
Persistent Infection of Rhesus Macaques by the Rev-Independent Nef(−) Simian Immunodeficiency Virus SIVmac239: Replication Kinetics and Genomic Stability

ABSTRACT We generated previously a Nef(−), replication-competent clone of SIVmac239 in which the Rev protein and the Rev-responsive element were replaced by the constitutive transport element (CTE) of simian retrovirus type 1 (A. S. von Gegerfelt and B. K. Felber, Virology 232:291–299, 1997). In the present report, we show that this virus was able to infect and replicate in rhesus macaques. The Rev-independent Nef(−) simian immunodeficiency virus induced a persistent humoral immune response in all monkeys, although viral loads were very low. Upon propagation in the monkeys, the genotype remained stable and the virus retained its in vitro growth characteristics. The infected monkeys showed normal hematological values and no signs of disease at more than 18 months post-virus exposure. Therefore, replacement of the essential Rev regulation by the CTE generated a virus variant that retained its replicative capacity both in vitro and in vivo, albeit at low levels.
The staphylococcal accessory regulator (sar ) represses transcription of the Staphylococcus aureus collagen adhesin gene (cna ) in an agr‐independent manner

Comparison of Staphylococcus aureus strains carrying mutations inactivating the staphylococcal accessory regulator (sar ) and/or the accessory gene regulator (agr ) suggests that sar is the primary regulatory element controlling transcription of the collagen adhesin gene (cna ) and that the regulatory effect of sar is independent of the interaction between SarA and agr. To test this hypothesis, we cloned the regions encoding each of the overlapping sar transcripts, all of which include the sarA open reading frame (ORF), and introduced each clone into cna‐positive sar and agr mutants. The introduction of each clone restored the expected sar transcripts and the temporal pattern of sar transcription. The introduction of each clone also complemented the defect in cna transcription and restored collagen binding to wild‐type levels. This was true even when the clones were introduced into a sar/agr double mutant. These results confirm the hypothesis that the sar‐mediated regulation of cna transcription occurs via an agr‐independent pathway. Direct evidence supporting this hypothesis comes from electrophoretic mobility shift assays demonstrating that SarA exhibits high‐affinity binding to cis elements upstream of the cna structural gene. We also examined the correlation between sar transcription and the production of SarA. Western blot analysis of two wild‐type strains indicated that SarA was produced in indistinguishable amounts during both the exponential and the post‐exponential growth phases.
The Cultural Formulation: A Model to Combine Nosology and Patients’ Life Context in Psychiatric Diagnostic Practice

This article discusses the experience of adapting and applying the Outline for a Cultural Formulation in DSM-IV to the Swedish context. Findings from a research project on the Cultural Formulation highlight the value of combining psychiatric nosological categorization with an understanding of patients’ cultural life context in order to increase the validity of categorization and to formulate individualized treatment plans. In clinical care practitioners need models and tools that help them take into account patients’ cultural backgrounds, needs, and resources in psychiatric diagnostic practice. We present a summary of a Swedish manual for conducting a Cultural Formulation interview. The need for further development of the Cultural Formulation is also discussed.
DNA Repair Mechanisms and the Bypass of DNA Damage in Saccharomyces cerevisiae

DNA repair mechanisms are critical for maintaining the integrity of genomic DNA, and their loss is associated with cancer predisposition syndromes. Studies in Saccharomyces cerevisiae have played a central role in elucidating the highly conserved mechanisms that promote eukaryotic genome stability. This review will focus on repair mechanisms that involve excision of a single strand from duplex DNA with the intact, complementary strand serving as a template to fill the resulting gap. These mechanisms are of two general types: those that remove damage from DNA and those that repair errors made during DNA synthesis. The major DNA-damage repair pathways are base excision repair and nucleotide excision repair, which, in the most simple terms, are distinguished by the extent of single-strand DNA removed together with the lesion. Mistakes made by DNA polymerases are corrected by the mismatch repair pathway, which also corrects mismatches generated when single strands of non-identical duplexes are exchanged during homologous recombination. In addition to the true repair pathways, the postreplication repair pathway allows lesions or structural aberrations that block replicative DNA polymerases to be tolerated. There are two bypass mechanisms: an error-free mechanism that involves a switch to an undamaged template for synthesis past the lesion and an error-prone mechanism that utilizes specialized translesion synthesis DNA polymerases to directly synthesize DNA across the lesion. A high level of functional redundancy exists among the pathways that deal with lesions, which minimizes the detrimental effects of endogenous and exogenous DNA damage.
A randomized trial to evaluate a management training program to prevent illegal alcohol sales.

AIMS To evaluate effects of a training program for owners/managers of alcohol establishments-Alcohol Risk Management (ARM)-on: (i) propensity to sell alcohol to obviously intoxicated patrons; and (ii) changing establishment-level policies/practices. DESIGN We assigned alcohol establishments randomly to intervention (full-ARM) and delayed-intervention/control (ARM Express) conditions. SETTING One large metropolitan area in Midwestern United States. PARTICIPANTS Owners and managers at 231 on-premise alcohol establishments (i.e. bars, restaurants). INTERVENTION Training programs consisted of one-to-one sessions with the owner/manager at each establishment. The goal of training was to help owners/managers to select and implement alcohol control policies in their establishments. The full-ARM training consisted of four one-to-one sessions and the ARM Express was a single session. MEASUREMENTS We measured intervention effects through baseline and follow-up pseudo-intoxicated alcohol purchase attempts (i.e. feigning intoxication while attempting to purchase alcohol) and telephone surveys of owners/managers at alcohol establishments. FINDINGS Sales rates to pseudo-intoxicated patrons reduced 23% (relative to delayed-intervention/control condition) at the first follow-up purchase attempt (P = 0.06) but returned to baseline levels 3 months later. On average, establishments selected 13 of 18 recommended policies, but in multivariate models we observed no significant differences at follow-up in reported policies/practices across establishments. CONCLUSIONS Reliance on manager training to promote responsible establishment alcohol policies is not sufficient to prevent illegal alcohol sales to obviously intoxicated patrons and to reduce alcohol-related problems.
Comparing influence of intermittent subglottic secretions drainage with/without closed suction systems on the incidence of ventilator associated pneumonia

Context: Intermittent subglottic drainage (ISD) of secretions is recommended for prevention of ventilator-associated pneumonia (VAP) as it reduces microaspiration from the area around the cuff. Poor suction techniques can contribute to VAP, hence closed suction system (CSS) may have theoretical benefit in VAP prevention. Combination of these two techniques may provide added advantage. Aims: To study the influence of ISD with/without CSS on the incidence of VAP. Materials and Methods: Data from 311 patients requiring mechanical ventilation (MV) for more than 72 hours were collected retrospectively. They were divided into four groups as follows: group A, no intervention; group B, only CSS; group C, only ISD; and group D, ISD with CSS. These groups were compared with respect to incidence of VAP, duration of MV, length of ICU and hospital stay and ICU mortality. Results: Patients in the four groups were comparable with respect to age, sex ratio and admission Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Incidence of VAP per 1000 ventilator days in groups A, B, C, and D were 25, 23.9, 15.7 and 14.3, respectively (P=0.04). There was no significant difference in the duration of MV (P=0.33), length of ICU (P=0.55) and hospital stay (P=0.36) and ICU mortality (P=0.9) among the four groups. Conclusions: ISD of secretions reduces the incidence of VAP. CSS alone or in combination with ISD has no significant effect on VAP incidence. Hence, ISD may be recommended for VAP prevention, but indications other than VAP prevention should determine the type of the suction system.
Partial power DC-DC converter for photovoltaic two-stage string inverters

In order to increase the conversion efficiency in photovoltaic (PV) systems, different configurations and topologies were developed. Depending on the application, the converters used for grid connection are built using one or two conversion stages. The advantages of the converters with a DC-stage are mainly the distributed maximum power point tracking algorithm per PV string, a wider range of operation, higher energy yield and, when required for grid connection, the possibility of voltage regulation. However, the conversion efficiency is lower than configurations with a single stage as the central inverter. Therefore, the proposed work presents a Partial Power DC-DC converter (PPC) which process part of the entire system power, and the surplus power is directly supplied to the output side. A topology is proposed and the details of its operation are explained based on the operating principle. Simulations are performed in order to evaluate the converter performance.
Non-Interest Income and Bank Efficiency in Ghana: A Two-Stage DEA Bootstrapping Approach

ABSTRACT This paper examines the effect of the inclusion of non-interest income on efficiency and economies of scale of Ghanaian banks in a two-stage analysis. The data envelopment analysis technique is employed to estimate efficiency scores with and without non-interest income of 26 Ghanaian banks from 2003 to 2011 in the first-stage analysis. In the second stage, a truncated bootstrapped regression is estimated to examine the effect of contextual variables on bootstrapped efficiency scores. The findings indicate that the exclusion of non-interest income as output variable leads to the under-estimation of efficiency scores. From the second-stage regression analysis, we find a curve-linear relationship between bank size and efficiency to suggest that bank efficiency increases as size also increase due to economies of scale but only up to an optimal point after which inefficiency sets. Market concentration, leverage, and loan loss provisions are also identified as the other significant determinants of efficiency. Policy implications for improving bank efficiency are discussed.
PPARδ activation by bexarotene promotes neuroprotection by restoring bioenergetic and quality control homeostasis

PPARδ activation by bexarotene in a mouse model of Huntington’s disease rescues defective oxidative metabolism and is neuroprotective. Defeating neurotoxicity with a repurposed drug PPARδ is a permissive nuclear receptor that heterodimerizes with the retinoid X receptor (RXR) to activate target genes. Interference with transcription of PPARδ target genes contributes to neurodegeneration in Huntington’s disease (HD). In new work, Dickey et al. evaluated the RXR agonist bexarotene in cellular models of HD and in an HD mouse model. They determined that bexarotene was effective at countering HD neurotoxicity in mouse primary neurons, human HD patient stem cell–derived neurons, and the BAC-HD mouse model. The authors then examined the basis for PPARδ’s neuroprotective effect and found that treatment with RXR/PPARδ agonists enhanced oxidative metabolism, promoted mitochondrial quality control, and boosted protein homeostasis by activating autophagy. Neurons must maintain protein and mitochondrial quality control for optimal function, an energetically expensive process. The peroxisome proliferator–activated receptors (PPARs) are ligand-activated transcription factors that promote mitochondrial biogenesis and oxidative metabolism. We recently determined that transcriptional dysregulation of PPARδ contributes to Huntington’s disease (HD), a progressive neurodegenerative disorder resulting from a CAG-polyglutamine repeat expansion in the huntingtin gene. We documented that the PPARδ agonist KD3010 is an effective therapy for HD in a mouse model. PPARδ forms a heterodimer with the retinoid X receptor (RXR), and RXR agonists are capable of promoting PPARδ activation. One compound with potent RXR agonist activity is the U.S. Food and Drug Administration–approved drug bexarotene. We tested the therapeutic potential of bexarotene in HD and found that bexarotene was neuroprotective in cellular models of HD, including medium spiny-like neurons generated from induced pluripotent stem cells (iPSCs) derived from patients with HD. To evaluate bexarotene as a treatment for HD, we treated the N171-82Q mouse model with the drug and found that bexarotene improved motor function, reduced neurodegeneration, and increased survival. To determine the basis for PPARδ neuroprotection, we evaluated metabolic function and noted markedly impaired oxidative metabolism in HD neurons, which was rescued by bexarotene or KD3010. We examined mitochondrial and protein quality control in cellular models of HD and observed that treatment with a PPARδ agonist promoted cellular quality control. By boosting cellular activities that are dysfunctional in HD, PPARδ activation may have therapeutic applications in HD and potentially other neurodegenerative diseases.
Distilling Model Knowledge

Top-performing machine learning systems, such as deep neural networks, large ensembles and complex probabilistic graphical models, can be expensive to store, slow to evaluate and hard to integrate into larger systems. Ideally, we would like to replace such cumbersome models with simpler models that perform equally well. In this thesis, we study knowledge distillation, the idea of extracting the knowledge contained in a complex model and injecting it into a more convenient model. We present a general framework for knowledge distillation, whereby a convenient model of our choosing learns how to mimic a complex model, by observing the latter's behaviour and being penalized whenever it fails to reproduce it. We develop our framework within the context of three distinct machine learning applications: (a) model compression, where we compress large discriminative models, such as ensembles of neural networks, into models of much smaller size; (b) compact predictive distributions for Bayesian inference, where we distil large bags of MCMC samples into compact predictive distributions in closed form; (c) intractable generative models, where we distil unnormalizable models such as RBMs into tractable models such as NADEs. We contribute to the state of the art with novel techniques and ideas. In model compression, we describe and implement derivative matching, which allows for better distillation when data is scarce. In compact predictive distributions, we introduce online distillation, which allows for significant savings in memory. Finally, in intractable generative models, we show how to use distilled models to robustly estimate intractable quantities of the original model, such as its intractable partition function.
Spinal dural arteriovenous fistulas: clinical experience with endovascular treatment as a primary therapeutic modality.

OBJECTIVE The aim of this study was to evaluate the efficacy of endovascular therapy as a primary treatment for spinal dural arteriovenous fistula (DAVF). METHODS The authors reviewed 18 patients with spinal DAVFs for whom endovascular therapy was considered as an initial treatment at a single institute between 1993 and 2006. NBCA embolization was considered the primary treatment of choice, with surgery reserved for patients in whom endovascular treatment failed. RESULTS Surgery was performed as the primary treatment in one patient because the anterior spinal artery originated from the same arterial pedicle as the artery feeding the fistula. Embolization was used as the primary treatment modality in 17 patients, with an initial success rate of 82.4%. Two patients with incomplete embolization had to undergo surgery. One patient underwent multiple embolizations, which failed to completely occlude the fistula but relieved the patient's symptoms. Spinal DAVF recurred in two patients (one collateral development and one recanalization) during the follow-up period. The collateral development was obliterated by repeated embolization, but the patient with recanalization refused further treatment. The overall clinical status improved in 15 patients (83.3%) during the follow-up period. CONCLUSION Endovascular therapy can be successfully used as a primary treatment for the majority of patients with spinal DAVFs. Although it is difficult to perform in some patients, endovascular embolization should be the primary treatment of choice for spinal DAVF.
Evaluation of NT-pro BNP and CT-ANP as markers of concentric hypertrophy in dogs with a model of compensated aortic stenosis.

BACKGROUND Serum C-terminal atrial natriuretic peptide (CT-ANP) and N-terminal pro B-type natriuretic peptide (NT-pro BNP) concentrations have not been measured serially in dogs with chronic pressure overload of the heart. HYPOTHESIS We investigated whether serial evaluation of CT-ANP and NT-pro BNP concentrations is a useful guide to the risk of cardiac remodeling in dogs with a model of aortic stenosis. ANIMALS Six male Beagles. METHODS After anesthesia, the aorta was constricted with a polyester band and mean left ventricular systolic pressure (LVPs) was 50 mmHg above baseline. Echocardiographic and intracardiac catheter examinations and blood sampling were performed before surgery and 3 and 6 months after surgery. RESULTS LVP and left ventricular end-diastolic pressure (LVEDP) were significantly higher at 6 months. Compared with baseline, end-diastolic intraventricular septum thickness (IVSd), left ventricular posterior wall thickness (LVPWd), and relative wall thickness (RWT) were significantly increased 3 and 6 months after aortic constriction. Serum CT-ANP concentrations were increased significantly at 3 months and serum NT-pro BNP concentrations were significantly higher 3 and 6 months after aortic constriction. Serum NT-pro BNP concentration was significantly correlated with LVEDP and IVSd whereas serum CT-ANP concentration was not correlated with any measurement. Stepwise regression analysis showed that LVEDP, IVSd, and RWT could predict serum NT-pro BNP. CONCLUSIONS AND CLINICAL IMPORTANCE This study indicated the differential regulation of NT-pro BNP and CT-ANP concentrations during pressure overload. NT-pro BNP assay may be used as an additional screening method to stratify early-stage ventricular remodeling because of aortic constriction.