Miracle-dz/UniFAR-FTUs huggingface dataset:
Strategy Configurations Directly Linked to Higher Hepatitis C Virus Treatment Starts

Background: The Department of Veterans Affairs (VA) cares for more patients with hepatitis C virus (HCV) than any other US health care system. We tracked the implementation strategies that VA sites used to implement highly effective new treatments for HCV with the aim of uncovering how combinations of implementation strategies influenced the uptake of the HCV treatment innovation. We applied Configurational Comparative Methods (CCMs) to uncover causal dependencies and identify difference-making strategy configurations, and to distinguish higher from lower HCV treating sites. Methods: We surveyed providers to assess VA sites’ use of 73 implementation strategies to promote HCV treatment in the fiscal year 2015. CCMs were used to identify strategy configurations that uniquely distinguished higher HCV from lower HCV treating sites. Results: From the 73 possible implementation strategies, CCMs identified 5 distinct strategy configurations, or “solution paths. ” These were comprised of 10 individual strategies that collectively explained 80% of the sites with higher HCV treatment starts with 100% consistency. Using any one of the following 5 solution paths was sufficient to produce higher treatment starts: (1) technical assistance; (2) engaging in a learning collaborative AND designating leaders; (3) site visits AND outreach to patients to promote uptake and adherence; (4) developing resource sharing agreements AND an implementation blueprint; OR (5) creating new clinical teams AND sharing quality improvement knowledge with other sites AND engaging patients. There was equifinality in that the presence of any one of the 5 solution paths was sufficient for higher treatment starts. Conclusions: Five strategy configurations distinguished higher HCV from lower HCV treating sites with 100% consistency. CCMs represent a methodological advancement that can help inform high-yield implementation strategy selection and increase the efficiency and effectiveness of future implementation efforts.
Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

Cyanines derived from heptamethines were mainly discussed regarding their functionalization to broaden the solubility in different surroundings exhibiting either hydrophilic or hydrophobic properties and to tailor made the ΔGet photopysical properties with respect to absorption and fluorescence. Electrochemical properties were additionally considered for some selected examples. The cyanines chosen comprised as end groups either indolenine, benzo[e]- or benzo[cd]indolium pattern, which facilitated to shift the absorption between 750–1000 nm. This enabled their use in applications with light sources emitting in the near-infrared (NIR) region selected from high power LEDs or lasers with line-shaped focus. The absorbers considered were discussed regarding their function as sensitizer for applications related to Chemistry 4.0 standards. These were mainly photopolymer coatings, which can be found for applications in the graphic industry or to protect selected substrates. The huge release of heat on demand upon turning ON or OFF the NIR light source enables them for photothermal treatment in processes requesting heat to initiate either chemical (activated reactions) or physical (melting, evaporation) events.
The LSD1 inhibitor iadademstat (ORY-1001) targets SOX2-driven breast cancer stem cells: a potential epigenetic therapy in luminal-B and HER2-positive breast cancer subtypes

SOX2 is a core pluripotency-associated transcription factor causally related to cancer initiation, aggressiveness, and drug resistance by driving the self-renewal and seeding capacity of cancer stem cells (CSC). Here, we tested the ability of the clinically proven inhibitor of the lysine-specific demethylase 1 (LSD1/KDM1A) iadademstat (ORY-100) to target SOX2-driven CSC in breast cancer. Iadademstat blocked CSC-driven mammosphere formation in breast cancer cell lines that are dependent on SOX2 expression to maintain their CSC phenotype. Iadademstat prevented the activation of an LSD1-targeted stemness-specific SOX2 enhancer in CSC-enriched 3-dimensional spheroids. Using high-throughput transcriptional data available from the METABRIC dataset, high expression of SOX2 was significantly more common in luminal-B and HER2-enriched subtypes according to PAM50 classifier and in IntClust1 (high proliferating luminal-B) and IntClust 5 (luminal-B and HER2-amplified) according to integrative clustering. Iadademstat significantly reduced mammospheres formation by CSC-like cells from a multidrug-resistant luminal-B breast cancer patient-derived xenograft but not of those from a treatment-naïve luminal-A patient. Iadademstat reduced the expression of SOX2 in luminal-B but not in luminal-A mammospheres, likely indicating a selective targeting of SOX2-driven CSC. The therapeutic relevance of targeting SOX2-driven breast CSC suggests the potential clinical use of iadademstat as an epigenetic therapy in luminal-B and HER2-positive subtypes.
The effects of three different microplastics on enzyme activities and microbial communities in soil

Soils always receive microplastics (MPs) from plastic mulching, compost, and sewage irrigation, but the effects of MPs on soil environment remain largely unexplored. The objectives of this study were to investigate the effects of three MPs (membranous polyethylene (PE), fibrous polypropylene (PP), and microsphere PP) on enzyme activities and microbial community structure in one loamy and sandy soil. The concentration of microsphere PP (2 mg/g) was one‐tenth of those of the other two MPs (20 mg/g). The results showed that the effects of three MPs on urease, dehydrogenase, and alkaline phosphatase activities followed the order: fibrous PP > membranous PE > microsphere PP, membranous PE > microsphere PP > fibrous PP and fibrous PP > microsphere PP > membranous PE, respectively. Results from high‐throughput sequencing of 16S rRNA revealed that the membranous PE and fibrous PP raised the alpha diversities of the soil microbiota, whereas the diversity indexes of microbiota on MPs surfaces were significantly lower than those in the amended soils. MPs significantly altered the microbial community structure, especially for the enrichment of Acidobacteria and Bacteroidetes, the depletion of Deinococcus‐Thermus and Chloroflexi. Aeromicrobium, Streptomyces, Mycobacterium, Janibacter, Nocardia, Arthrobacter were prone to inhabit on the MPs surfaces.
Deep Active Learning for Surface Defect Detection

Most of the current object detection approaches deliver competitive results with an assumption that a large number of labeled data are generally available and can be fed into a deep network at once. However, due to expensive labeling efforts, it is difficult to deploy the object detection systems into more complex and challenging real-world environments, especially for defect detection in real industries. In order to reduce the labeling efforts, this study proposes an active learning framework for defect detection. First, an Uncertainty Sampling is proposed to produce the candidate list for annotation. Uncertain images can provide more informative knowledge for the learning process. Then, an Average Margin method is designed to set the sampling scale for each defect category. In addition, an iterative pattern of training and selection is adopted to train an effective detection model. Extensive experiments demonstrate that the proposed method can render the required performance with fewer labeled data.
Factors Affecting Smoking Initiation and Cessation Among Saudi Women Attending Smoking Cessation Clinics

Objectives Smoking is one of the most adaptable risk behaviours associated with increased mortality rates, yet over one billion individuals worldwide are smokers. This study aimed to examine self-reported reasons for starting and quitting smoking among women attending smoking cessation clinics in Saudi Arabia. Methods This cross-sectional study took place between January 2014 and January 2017 in Saudi Arabia using previously collected data. A survey was distributed to 3,000 female smokers attending smoking cessation programmes in 18 clinics from different regions in Saudi Arabia to determine self-reported reasons for smoking initiation and willingness/unwillingness to quit. Results A total of 2,190 women participated in the study (response rate = 73%). Overall, the most common reason for starting to smoke was friends (31.1%), while the predominant reason for willingness to quit was health concerns (45.5%). The most frequent reason for being unwilling to quit smoking was a fear of mood changes (28%). Conclusion Most Saudi women are socially-driven to start smoking, while the most common reason for quitting is health concerns. The latter finding is promising in that it shows that smokers are gaining awareness of the adverse effects of smoking.
Identification and characterization of novel SCR7‐based small‐molecule inhibitor of DNA end‐joining, SCR130 and its relevance in cancer therapeutics

Targeting DNA repair with small‐molecule inhibitors is an attractive strategy for cancer therapy. Majority of DNA double‐strand breaks in mammalian cells are repaired through nonhomologous end‐joining (NHEJ). It has been shown that small‐molecule inhibitors of NHEJ can block efficient repair inside cancer cells, leading to cell death. Previously, we have reported that SCR7, an inhibitor of NHEJ can induce tumor regression in mice. Later studies have shown that different forms of SCR7 can inhibit DNA end‐joining in Ligase IV‐dependent manner. Recently, we have derivatized SCR7 by introducing spiro ring into core structure. Here, we report the identification of a novel inhibitor of NHEJ, named SCR130 with 20‐fold higher efficacy in inducing cytotoxicity in cancer cell lines. SCR130 inhibited DNA end‐joining catalyzed by rat tissue extract. Specificity analysis revealed that while SCR130 was specific to Ligase IV, it showed minimal or no effect on Ligase III and Ligase I mediated joining. Importantly, SCR130 exhibited the least cytotoxicity in Ligase IV‐null cell line as compared with wild type, confirming Ligase IV‐specificity. Furthermore, we demonstrate that SCR130 can potentiate the effect of radiation in cancer cells when used in combination with γ‐radiation. Various cellular assays in conjunction with Western blot analysis revealed that treatment with SCR130 led to loss of mitochondrial membrane potential leading to cell death by activating both intrinsic and extrinsic pathways of apoptosis. Thus, we describe a novel inhibitor of NHEJ with higher efficacy and may have the potential to be developed as cancer therapeutic.
High-density diet improves growth performance and beef yield but affects negatively on serum metabolism and visceral morphology of Holstein steers.

The objective of this study was to evaluate the effect of different dietary densities on growth performance, carcass characteristics, meat quality, serum metabolism, ruminal papillae morphology and liver injuries of steers. For this purpose, a total of eighteen Holstein steers were randomly fed one of the three diets: high energy and protein diet (H), standard energy and protein diet (C), and low energy and protein diet (L) for 11 months fattening with three-step finishing strategy. Steers fed with H diet had higher (p < .05) average daily gain, feed efficiency, hot carcass weight, serum aspartate aminotransferase to alanine aminotransferase ratio, and monounsaturated fatty acids along with continuous low ruminal pH value, severer hepatic steatosis and ruminal papillae parakeratosis. Meanwhile, steers fed L diet increased the proportion of C20:0, C22:6n-3, saturated fatty acids and n-3 polyunsaturated fatty acids along with lower n-6 to n-3 ratio in longissimus dorsi muscle as compared to that of steers fed H diet. Dietary densities did not influence (p > .10) proximate nutrients and sensory characteristics of beef. The present study indicates that Holstein steers could achieve better growth and carcass performance under high-density diet, whereas they are under threat of visceral injuries and metabolic disorders. This study gives comprehensive relationship between productivity and animal health and suggests that a proper diet should be adopted for fattening Holstein steers in consideration of both beef quality and quantity and animal health.
Protein phosphatase PP2A regulates microtubule orientation and dendrite pruning in Drosophila

Pruning that selectively eliminates inappropriate projections is crucial for sculpting neural circuits during development. During Drosophila metamorphosis, ddaC sensory neurons undergo dendrite‐specific pruning in response to the steroid hormone ecdysone. However, the understanding of the molecular mechanisms underlying dendrite pruning remains incomplete. Here, we show that protein phosphatase 2A (PP2A) is required for dendrite pruning. The catalytic (Microtubule star/Mts), scaffolding (PP2A‐29B), and two regulatory subunits (Widerborst/Wdb and Twins/Tws) play important roles in dendrite pruning. Functional analyses indicate that PP2A, via Wdb, facilitates the expression of Sox14 and Mical prior to dendrite pruning. Furthermore, PP2A, via Tws, governs the minus‐end‐out orientation of microtubules (MTs) in the dendrites. Moreover, the levels of Klp10A, a MT depolymerase, increase when PP2A is compromised. Attenuation of Klp10A fully rescues the MT orientation defects in mts or pp2a‐29b RNAi ddaC neurons, suggesting that PP2A governs dendritic MT orientation by suppressing Klp10A levels and/or function. Taken together, this study sheds light on a novel function of PP2A in regulating dendrite pruning and dendritic MT polarity in sensory neurons.
Post-discharge surveillance of surgical site infections in teaching hospitals in Brazil.

OBJECTIVE Understanding the reality of surgical site infections post-discharge surveillance in Brazilian teaching hospitals. METHOD A cross-sectional study conducted by sending an online questionnaire to nurses from the Hospital Infection Control Committee of Brazilian teaching hospitals registered in the National Registry of Health Establishments. RESULTS Of the 193 teaching hospitals in Brazil, eight declined to take part as they did not conduct post-discharge surveillance and 36 did not respond. Twenty five of the remaining 149 hospitals provided detailed responses and 96% of responding institutions performed surgical site infection surveillance during hospitalization; active search (29.3%) was the main method, while 84% reported performing post-discharge surveillance mainly by telephone (42.8%). Both surveillance actions have nurses as the main responsible professionals. CONCLUSION Nurses play a prominent role in surgical site infection identification/screening actions, and active search during hospitalization allied with post-discharge surveillance by telephone were the preferred methods.
Carbonized Dehydroascorbic Acid: Aim for Targeted Repair of Graphene Defects and Bridge Connection of Graphene Sheets with Small Size

The thermal dissipation issue of electronics devices becomes increasingly prominent as they evolve to smaller sizes and more complicated structures. Therefore, the development of materials with excellent heat conduction properties and light weight turns out to be an urgent demand to solve the heat transfer problem of electronics devices with high performance. For this purpose, we put forward an innovative strategy that carbonized dehydroascorbic acid (CDA) be applied to graphene layers for the targeted repair of defects among them and bridge connection of the layers to produce graphene heat conduction materials with excellent properties. Firstly, hydrogen bonds formed from dehydroascorbic acid (DHAA, products of the oxidation of vitamin C) and each of ketone, carboxyl, and oxhydryl groups on graphene layers were absorbed at targeted locations where oxidation graphene produces defects, then targeted repair was conducted for those defects to be filled and for the graphene layers of a small size to grow into large sheet materials with improved continuity by CDA generated in thermally pressing reduction reaction at 800 °C. In our investigation, the planar thermal conductivity of rGO/VC membrane reached 1031.9 ± 10.2 Wm−1K−1, while the added mass content of vitamin C (VC) was 15%. Being a reference, the planar thermal conductivity of primitive graphene membrane was only 610.7 ± 11.7 Wm−1K−1.
Evaluation of the Role of hsa-mir-124 in Predicting Clinical Outcome in Breast Invasive Carcinoma Based on Bioinformatics Analysis

Purpose Breast invasive carcinoma (BRCA) is the most common malignant tumor. MiR-124 plays a tumor-suppressive role in human cancer. However, the clinical significance of miR-124 in BRCA remains unclear. The aim of this study was to evaluate the association of hsa-mir-124 expression and the clinicopathological characteristics in BRCA using database analysis. Methods The clinical data and expression profiles of hsa-mir-124 were obtained from the cancer genome atlas for BRCA (TCGA_BRCA). Then, the prognostic value of hsa-mir-124 in BRCA was investigated using the Cox Regression test, and the association of hsa-mir-124 and pathology TNM stages and pathologic stages were measured by the Kruskal–Wallis test and Wilcox. test. In addition, the association of hsa-mir-124 and tumor molecular phenotypes was performed using the Chi-Square test. Results We found that the overall survival of patients with high expression of hsa-mir-124-1 and hsa-mir-124-2 was better than that of patients with low expression of hsa-mir-124-1 and hsa-mir-124-2. And the expression of hsa-mir-124-1, hsa-mir-124-2, and hsa-mir-124-3 was mainly enriched in T1/T2 stages, NO/N1 stages, and M0 stages. Then, the expression of hsa-mir-124-1, hsa-mir-124-2, and hsa-mir-124-3 was negatively associated with tumor lymph node metastasis. Moreover, the expression of hsa-mir-124 was associated with tumor molecular phenotype in breast invasive carcinoma. Conclusion Our findings indicated that hsa-mir-124 expressions were associated with overall survival, TNM stages, pathologic characteristics, and tumor molecular phenotype in BRCA via TCGA_BRCA database, providing a new biomarker and a potential therapeutic target for BRCA patients.
Role of microRNAs in the Development of Cardiovascular Disease in Systemic Autoimmune Disorders

Rheumatoid Arthritis (RA), Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are the systemic autoimmune diseases (SADs) most associated with an increased risk of developing cardiovascular (CV) events. Cardiovascular disease (CVD) in SADs results from a complex interaction between traditional CV-risk factors, immune deregulation and disease activity. Oxidative stress, dyslipidemia, endothelial dysfunction, inflammatory/prothrombotic mediators (cytokines/chemokines, adipokines, proteases, adhesion-receptors, NETosis-derived-products, and intracellular-signaling molecules) have been implicated in these vascular pathologies. Genetic and genomic analyses further allowed the identification of signatures explaining the pro-atherothrombotic profiles in RA, SLE and APS. However, gene modulation has left significant gaps in our understanding of CV co-morbidities in SADs. MicroRNAs (miRNAs) are emerging as key post-transcriptional regulators of a suite of signaling pathways and pathophysiological effects. Abnormalities in high number of miRNA and their associated functions have been described in several SADs, suggesting their involvement in the development of atherosclerosis and thrombosis in the setting of RA, SLE and APS. This review focusses on recent insights into the potential role of miRNAs both, as clinical biomarkers of atherosclerosis and thrombosis in SADs, and as therapeutic targets in the regulation of the most influential processes that govern those disorders, highlighting the potential diagnostic and therapeutic properties of miRNAs in the management of CVD.
Detection of bovine herpesvirus type 1 and bovine ephemeral fever virus antigens in cattle lymph nodes using three immunological assays

Lymph nodes (Ln) are the preferred samples for virus isolation and detection. In the present study, carcass and visceral Ln of apparently healthy cattle were screened for the presence of bovine herpes virus type 1 (BHV-1) and bovine ephemeral fever virus (BEFV) antigens. A total of 198 Ln (114 carcasses Ln and 84 visceral Ln) were collected. Lymph node homogenates were assayed by agar gel precipitation test (AGPT), rapid Staphyloccocal protein A (SPA) agglutination test and Dot-ELISA. The overall results revealed that BHV-1 antigens were detected in 43.9%, 56.1% and in 68.4% of carcass Ln, and in 29.8%, 47.6% and 57.1% of visceral Ln collected from slaughtered cattle by AGPT, SPA agglutination test and Dot-ELISA respectively. On the other hand, BEFV antigens were detected in 5.3%, 38.6% and 52.6% of carcass Ln, and in 6%, 41.7% and 54.8 % of visceral Ln collected from slaughtered animals by AGPT, rapid SPA agglutination test and Dot-ELISA respectively. The results showed high percentage of positive samples with SPA agglutination test and DotELISA in comparison to AGPT for both BHV-1 and BEF.
Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol.

BACKGROUND Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. METHODS We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540. RESULTS A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent. CONCLUSIONS Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.).