Miracle-dz/UniFAR-FTUs huggingface dataset:
Regional Transmission and Reassortment of 2.3.4.4b Highly Pathogenic Avian Influenza (HPAI) Viruses in Bulgarian Poultry 2017/18

Between 2017 and 2018, several farms across Bulgaria reported outbreaks of H5 HPAI viruses. In this study we use genomic and traditional epidemiological analyses to trace the origin and subsequent spread of these outbreaks within Bulgaria. Both methods indicate two separate incursions, one restricted to the North-Eastern region of Dobrich, and another largely restricted to Central and Eastern Bulgaria including places such as Plovdiv, Sliven and Stara Zagora, as well as one virus from the Western region of Vidin. Both outbreaks likely originate from different European 2.3. 4.4b virus ancestors circulating in 2017. The viruses were likely introduced by wild birds or poultry trade links in 2017 and have continued to circulate, but due to lack of contemporaneous sampling and sequences from wild bird viruses in Bulgaria, the precise route and timing of introduction cannot be determined. Analysis of whole genomes indicates complete lack of reassortment in all segments but the MP, which presents as multiple smaller clusters associated with different European 2.3. 4.4b viruses. Ancestral reconstruction of host states of the HA gene of viruses involved in the outbreaks suggests that transmission is driven by domestic ducks into galliform poultry. Thus, according to present evidence we suggest that surveillance of domestic ducks as epidemiologically relevant species for subclinical infection. Monitoring spread due to movement between farms within regions and links to poultry production systems in European countries can help to predict and prevent future outbreaks.
Hybrid Algorithm for Using Bipolar Junction Transistors as Primary Thermometers

This work introduces a novel hybrid algorithm, which allows computing the absolute temperature of a bipolar transistor device in thermal equilibrium for sensing ambient temperature. The proposed idea relies on the measured current-voltage characteristics of the device and it can be implemented in any computing platform. Experimental data obtained, using a broad collection of commercial devices, demonstrates the accuracy of the proposed algorithm.
Rethinking Convolutional Feature Extraction for Small Object Detection

Deep learning based object detection architectures have signiﬁcantly advanced the state of the art. However, a study of recent detection methods shows a wide gap between small object performance and performance on medium and large objects. This gap is prevalent across architectures and across backbones. We show that this gap is primarily due to reduction in the feature map size as we traverse the backbone. Through simple modiﬁcations to the backbone structure, we show a marked improvement in performance for small objects. In addition, we propose a dual-path conﬁguration with weight sharing for recovering large object performance. Compared to state of the art methods that rely on multi-scale training and network partitioning we show competitive performance without any bells and whistles on the MS COCO dataset. We show state of the art small object performance with a mobile object detector SSD Mobilenet v1.
Dependence and Perceived Difficulty in Daily Activities in Community-Living Stroke Survivors 2 Years After Stroke

Background and Purpose—There is a need for better understanding of the structure of instruments for functional outcome assessment after discharge from rehabilitation. One purpose of the study was to contribute to the analysis of instrumental dimensionality. Another purpose was to compare disability in stroke patients within the younger age range 2 years after onset of stroke with that at discharge with respect to both dependence and patients’ perceived difficulty and to extend the assessments with instrumental activities. Methods—We studied 68 stroke survivors aged 18 to 71 years at onset (59% aged <55 years) by means of interviews in their home, using activities from the Functional Independence Measure (FIM) and Instrumental Activity Measure (IAM) for ratings of dependence and perceived difficulty. Rasch analysis was used to construct calibrated linear measures and to evaluate the level of fit. Results—Acceptable models for comparison of dependence between discharge and follow-up were found for the physi.
Base-detail image inpainting

Recent advances in image inpainting have shown exciting promise with learning-based methods. Though they are effective in capturing features with some prior techniques, most of them fail to reconstruct reasonable base and detail information, so that the inpainted regions appear blurry, over-smoothed, and weird. Therefore, we propose a new "Divider and Conquer" model called Base-Detail Image Inpainting, which combines the reconstructed base and detail layers to generate the ﬁnal subjective perception images. The base layer with low-frequency information can grasp the basic distribution while the detail layer with high-frequency information assists with the details. The joint generator overall would beneﬁt from these two as guided anchors. In addition, we evaluate our two models over three publicly available datasets, and our experiments demonstrate that our method outperforms current state-of-the-art techniques quantitatively and qualitatively.
Attraction-Rejection Model for Facility Location

Location of small and large stores requires a market study to determine the demand for a product in a particular region, as well as the selection of the target population. However, it is common to forget analyzing the impact of the competition regarding the suitability of locating facilities. The objective of this work is to propose a model that can be a tool to study the market; analyzing both demands as attraction factor and competition as rejection factor. The methodology used consists on the proposal of an exact model and a group of tests to prove its functionality. The model has characteristics that have not been considering before like a service radio where a new location can be open and is affected by customers and competitors. The results obtained demonstrated that the model suggests opening the facilities with fewer competitors and higher demand. This model is new because no other model considers how a new location is affected by competitors (rejection) and by customers (attraction), both located in a service radio area.
Transient receptor potential canonical 1 channel mediates the mechanical stress-induced epithelial-mesenchymal transition of human bronchial epithelial (16HBE) cells

Airway remodeling is a central event in the pathology of chronic obstructive pulmonary disease (COPD) that leads to airway narrowing and subsequently, to increased mechanical pressure. High mechanical pressure can exacerbate airway remodeling. Thus, a treatment regimen aimed at disrupting this high-pressure airway remodeling vicious cycle may improve the prognosis of patients with COPD. Recent studies have demonstrated that mechanical stress induces lung epithelial-mesenchymal transition (EMT), which is commonly present in airway epithelial cells of patients with COPD. As TRPC1 functions as a mechanosensitive channel that mediates non-selective cation entry in response to increased membrane stretch, the present study investigated the role of TRPC1 in the occurrence of EMT induced by mechanical stress. In the present study, the expression of TRPC1 in the bronchial epithelium was examined in vivo by immunohistochemistry. In vitro, human bronchial epithelial (16HBE) cells were subjected to mechanical stretching for up to 48 h, and TRPC1 expression was then examined by RT-qPCR and western blot analysis. In addition, TRPC1 receptor function was assessed by Ca2+ imaging and siRNA transfection. EMT was identified using immunofluorescence, western blot analysis and RT-qPCR. It was found that TRPC1 expression was upregulated in patients with COPD and in 16HBE cells subjected to mechanical stretch. The mechanical stress-induced activation of TRPC1 in 16HBE cells increased the intracellular calcium concentration and subsequently decreased the expression of cytokeratin 8 and E-cadherin, and increased the expression of α-smooth muscle actin, indicating the occurrence of EMT. On the whole, the findings of the present study demonstrate that TRPC1 plays a key role in the occurrence of EMT in human lung epithelial cells in response to mechanical stretch; thus, this protein may serve as a novel therapeutic target for progressive airway remodeling in COPD.
MicroRNA-93 promotes angiogenesis and attenuates remodeling via inactivation of the Hippo/Yap pathway by targeting Lats2 after myocardial infarction

Inactivation of the Hippo pathway protects the myocardium from cardiac ischemic injury. MicroRNAs (miRs) have been reported to play pivotal roles in the progression of myocardial infarction (MI). The present study examined whether miR-93 could promote angiogenesis and attenuate remodeling after MI via inactivation of the Hippo/Yes-associated protein (Yap) pathway, by targeting large tumor suppressor kinase 2 (Lats2). It was identified that transfection of human umbilical vein endothelial cells with miR-93 mimic significantly decreased Lats2 expression and Yap phosphorylation, increased cell viability and migration, and attenuated cell apoptosis following hypoxia/reoxygenation injury. Moreover, increased expression of miR-93 resulted in an improvement of cardiac function, promotion of angiogenesis and attenuation of remodeling after MI. Additionally, miR-93 overexpression significantly decreased intracellular adhesion molecule 1 and vascular cell adhesion protein 1 expression levels, as well as attenuated the infiltration of neutrophils and macrophages into the myocardium after MI. Furthermore, it was found that miR-93 overexpression significantly suppressed Lats2 expression and decreased the levels of phosphorylated Yap in the myocardium after MI. Collectively, the present results suggested that miR-93 may exert a protective effect against MI via inactivation of the Hippo/Yap pathway by targeting Lats2.
Clinical Spectrum of KCNA1 Mutations: New Insights into Episodic Ataxia and Epilepsy Comorbidity

Mutations in the KCNA1 gene, which encodes voltage-gated Kv1.1 potassium channel α-subunits, cause a variety of human diseases, complicating simple genotype–phenotype correlations in patients. KCNA1 mutations are primarily associated with a rare neurological movement disorder known as episodic ataxia type 1 (EA1). However, some patients have EA1 in combination with epilepsy, whereas others have epilepsy alone. KCNA1 mutations can also cause hypomagnesemia and paroxysmal dyskinesia in rare cases. Why KCNA1 variants are associated with such phenotypic heterogeneity in patients is not yet understood. In this review, literature databases (PubMed) and public genetic archives (dbSNP and ClinVar) were mined for known pathogenic or likely pathogenic mutations in KCNA1 to examine whether patterns exist between mutation type and disease manifestation. Analyses of the 47 deleterious KCNA1 mutations that were identified revealed that epilepsy or seizure-related variants tend to cluster in the S1/S2 transmembrane domains and in the pore region of Kv1.1, whereas EA1-associated variants occur along the whole length of the protein. In addition, insights from animal models of KCNA1 channelopathy were considered, as well as the possible influence of genetic modifiers on disease expressivity and severity. Elucidation of the complex relationship between KCNA1 variants and disease will enable better diagnostic risk assessment and more personalized therapeutic strategies for KCNA1 channelopathy.
Hepatitis B Surface Antigen Levels Can Be Used to Rule Out Cirrhosis in Hepatitis B e Antigen-Positive Chronic Hepatitis B: Results From the SONIC-B Study

Abstract Background Serum hepatitis B surface antigen (HBsAg) levels correlate with the duration of chronic hepatitis B virus (HBV) infection and may predict the extent of hepatic fibrosis. Methods We analyzed data from the SONIC-B database, which contains data from 8 global randomized trials and 2 large hepatology centers. Relationship between HBsAg levels and presence of significant fibrosis (Ishak 3–4) or cirrhosis (Ishak 5–6) were explored, and clinically relevant cutoffs were identified to rule out cirrhosis. Results The dataset included 2779 patients: 1866 hepatitis B e antigen (HBeAg)-positive; 322 with cirrhosis. Among HBeAg-positive patients, lower HBsAg levels were associated with higher rates of significant fibrosis (odds ratio [OR], 0.419; P < .001) and cirrhosis (OR, 0.435; P < .001). No relationship was observed among HBeAg-negative patients. Among HBeAg-positive patients, genotype-specific HBsAg cutoffs had excellent negative predictive values (>97%) and low misclassification rates (≤7.1%) and may therefore have utility in ruling out cirrhosis. Diagnostic performance of the HBsAg cutoffs was comparable among patients in whom cirrhosis could not be ruled out with fibrosis 4 (FIB-4). Conclusions Hepatitis B virus genotype-specific HBsAg cutoffs may have utility in ruling out presence of cirrhosis in HBeAg-positive patients with genotypes B, C, and D and can be an adjunct to FIB-4 to reduce the need for further testing.
The Growing Importance of Tuberculosis Preventive Therapy and How Research and Innovation Can Enhance Its Implementation on the Ground

Ending the tuberculosis (TB) epidemic by 2030 requires two key actions: rapid diagnosis and effective treatment of active TB and identification and treatment of latent TB infection to prevent progression to active disease. We introduce this perspective by documenting the growing importance of TB preventive therapy on the international agenda coupled with global data showing poor implementation of preventive activities in programmatic settings. We follow this with two principal objectives. The first is to examine implementation challenges around diagnosis and treatment of active TB. Within this, we include recent evidence about the continued morbidity and heightened mortality that persists after TB treatment is successfully completed, thus elevating the importance of TB preventive therapy. The second objective is to outline how current TB preventive therapy activities have been shaped and are managed and propose how these can be improved through research and innovation. This includes expanding and giving higher priority to certain high-risk groups including those with fibrotic lung lesions on chest X-ray, showcasing the need to develop and deploy new biomarkers to more accurately predict risk of disease and making shorter treatment regimens, especially with rifapentine-isoniazid, more user-friendly and widely available. Ending the TB epidemic requires not only cure of the disease but preventing it before it even begins.
Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives

Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the regulation of insulin secretion in pancreatic β-cells, stimulating their proliferation and promoting the expression of anti-apoptotic proteins. Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the PL secretion pattern. Whereas obesity is most often associated with lower PL serum concentrations, diabetes results in increased PL blood levels. Disruptions in PL secretion are thought to be associated with an increased prevalence of gestational complications, such as placental dysfunction, diabetic retinopathy, and abnormalities in fetal growth. PL is believed to be positively correlated with birth weight. The impaired regulation of PL secretion could contribute to an increased incidence of both growth retardation and fetal macrosomia. Moreover, the dysregulation of PL production during the intrauterine period could affect the metabolic status in adulthood. PL concentration measurement could be useful in the prediction of fetal macrosomia in women with normal oral glucose tolerance test (OGTT) results or in evaluating the risk of fetal growth restriction, but its application in standard clinical practice seems to be limited in the era of ultrasonography.
CircSAMD4A regulates cell progression and epithelial-mesenchymal transition by sponging miR-342-3p via the regulation of FZD7 expression in osteosarcoma

Osteosarcoma (OS) is a primary malignant tumor with a complex etiology. Therefore, research into the pathogenesis of osteosarcoma is considered a priority. Circular RNAs play important roles in cell metabolism and in the immune response and are closely associated with cancer treatment. However, research into the association of circular RNAs with osteosarcoma is limited. In the present study, CircSAMD4A was validated by RT-qPCR and agarose gel electrophoresis. CircSAMD4A and miR-342-3p expression was detected by RT-qPCR. The relative protein expression levels were measured by western blot analysis. MTT assay and flow cytometry were used to detect cell cytotoxicity and apoptosis, respectively. Transwell assay was applied to assess cell migration and invasion. Dual-luciferase reporter assay was used to determine the association among CircSAMD4A, Frizzled-7 (FZD7) and miR-342-3p. In vivo, subcutaneous tumor formation assay was performed in an experiment with nude mice. The results revealed that the expression levels of CircSAMD4A and FZD7 were upregulated, while those of miR-342-3p were downregulated in OS tissues and cells. The inhibition of CircSAMD4A suppressed cell progression and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in OS. The reduction of miR-342-3p reversed the effects of CircSAMD4A downregulation on cell cytotoxicity, migration, invasion, apoptosis and EMT in OS, while FZD7 overexpression blocked the effect of miR-342-3p upregulation on OS progression. The suppressive effect of sh-CircSAMD4A on tumor growth was thus verified in OS. Overall, the present study demonstrated that CircSAMD4A affected cell cytotoxicity, invasion, apoptosis, migration and EMT by regulating the miR-342-3p/FDZ7 axis in OS, thereby providing a novel regulatory mechanism and a potential therapeutic target for OS.
A cognitive behavioural group therapy for bipolar disorder using daily mood monitoring

Abstract Background and aim: This study investigated the effects of group cognitive behavioural therapy (CBT) for patients with bipolar disorder. The development of CBT for this disorder is relatively under-explored. Method: Participants with bipolar I or II disorder were treated with group CBT in addition to treatment as usual. The effectiveness of the protocol was explored through sequence analysis of daily mood monitoring prior to, during and after the intervention. Also, a repeated measures design was used assessing symptomatology, dysfunctional attitudes, sense of mastery, psychosocial functioning, and quality of life at start and end of intervention, and at follow-up 2 and 12 months later. Results: The results indicate that variation in mood states diminished over the course of the intervention. Also, there was a change from depressive states to more euthymic states. Greater number of reported lifetime depressive episodes was associated with greater diversity of mood states. There was an increase in overall psychosocial functioning and self-reported psychological health following the intervention. Improvement continued after treatment ended until follow-up at 2 months, and measured 1 year later, for outcomes representing depression, general psychosocial functioning and self-reported psychological health. Due to small sample size and the lack of a control group the results are preliminary. Conclusions: The results of this pilot study suggest that both offering CBT in group interventions and sequence analysis of time series data are helpful routes to further explore when improving standard CBT interventions for patients suffering from bipolar disorder.
Social Stress Increases Vulnerability to High-Fat Diet-Induced Insulin Resistance by Enhancing Neutrophil Elastase Activity in Adipose Tissue

Social stress (SS) has been linked to the development of cardiovascular disease (CVD), which is closely associated with insulin resistance (IR); however, the causal effect of SS on IR remains unclear. The 8-week-old male C57BL/6 mice were exposed to SS by housing with a larger CD-1 mouse in a shared home cage without physical contact for 10 consecutive days followed by high-fat diet (HFD) feeding. Control mice were housed in the same cage without a CD-1 mouse. After 6 weeks of HFD, insulin sensitivity was significantly impaired in stressed mice. While the percentage of classically activated macrophages in epididymal white adipose tissue (eWAT) was equivalent between the two groups, the percentage of lymphocyte antigen 6 complex locus G6D (Ly-6G)/neutrophil elastase (NE)-double positive cells markedly increased in stressed mice, accompanied by augmented NE activity assessed by ex vivo eWAT fluorescent imaging. Treatment with an NE inhibitor completely abrogated the insulin sensitivity impairment of stressed mice. In vitro NE release upon stimulation with a formyl peptide receptor 1 agonist was significantly higher in bone marrow neutrophils of stressed mice. Our findings show that SS-exposed mice are susceptible to the development of HFD-induced IR accompanied by augmented NE activity. Modulation of neutrophil function may represent a potential therapeutic target for SS-associated IR.
Changes at global and site-specific DNA methylation of MLH1 gene promoter induced by waterpipe smoking in blood lymphocytes and oral epithelial cells

Abstract Objective: Cigarette tobacco smoking has been shown to cause cancer through different mechanisms that include epigenetic modulation of tumor-suppressor genes. In the present study, the association between global and MLH1 gene promoter methylation and waterpipe tobacco smoking was investigated. Materials and Methods: Blood lymphocytes and oral epithelium were sampled from 150 pure waterpipe smokers and 150 never-smokers from Jordan. Methylation assessment was performed using the methylation-specific PCR technique for MLH1 gene and ELISA for global DNA methylation. Results: Significant increases were shown in global DNA methylation as measured in blood lymphocytes (p < 0.01). In addition, increases in MLH1 gene promoter methylation among waterpipe smokers compared to nonsmokers (p < 0.001) in both oral epithelium and blood lymphocytes was also observed. In addition, strong correlation was found between LWDS-10J dependence score and magnitude of promoter specific methylation of MLH1 (r2 = 0.74–0.78, p < 0.001). Moreover, the percentage of methylated MLH1 promoter was not affected by age or gender (p > 0.05). Discussion and Conclusion: Collectively, the results indicate that waterpipe tobacco use is associated with epigenetic changes that might predispose users to lung and blood cancers. The results highlight the need for actions to discourage waterpipe smoking and can be used in cessation interventions that target this type of smoking.