Adaptive Testing and Performance Analysis Using Naive Bayes Classifier

AbstractThe highlight of this paper is to demonstrate the concept of adaptive tests which are an efficient way to produce the desired result as compared to the traditional static tests. The algorithm learns to adapt to the user's knowledge, and thus, calculates the true ability of the user. Our test system also provides the user with his performance review in specific categories, thereby giving him an understanding of his current knowledge for the same. Thus, our model can improve the user‟s efficacy over a prolonged period of time

Influence of polymorphisms in TNF-α and IL1β on susceptibility to alcohol induced liver diseases and therapeutic potential of miR-124-3p impeding TNF-α/IL1β mediated multi-cellular signaling in liver microenvironment

Background and aimsAlcoholic liver disease (ALD) is the leading cause of the liver cirrhosis related death worldwide. Excessive alcohol consumption resulting enhanced gut permeability which trigger sensitization of inflammatory cells to bacterial endotoxins and induces secretion of cytokines, chemokines leading to activation of stellate cells, neutrophil infiltration and hepatocyte injury followed by steatohepatitis, fibrosis and cirrhosis. But all chronic alcoholics are not susceptible to ALD. This study investigated the causes of differential immune responses among ALD patients and alcoholic controls (ALC) to identify genetic risk factors and assessed the therapeutic potential of a microRNA, miR-124-3p.Materials and methodsBio-Plex Pro™ Human Chemokine analysis/qRT-PCR array was used for identification of deregulated immune genes. Sequencing/luciferase assay/ELISA detected and confirmed the polymorphisms. THP1 co-cultured with HepG2/LX2/HUVEC and apoptosis assay/qRT-PCR/neutrophil migration assay were employed as required.ResultsThe combined data analysis of the GSE143318/Bio-Plex Pro™ Human Chemokine array and qRT-PCR array revealed that six genes (TNFα/IL1β/IL8/MCP1/IL6/TGFβ) were commonly overexpressed in both serum/liver tissue of ALD-patients compared to ALC. The promoter sequence analysis of these 6 genes among ALD (n=322)/ALC (n=168) samples revealed that only two SNPs, rs361525(G/A) at -238 in TNF-α/rs1143627(C/T) at -31 in IL1β were independently associated with ALD respectively. To evaluate the functional implication of these SNPs on ALD development, the serum level of TNF-α/IL1β was verified and observed significantly higher in ALD patients with risk genotypes TNF-α-238GA/IL1β-31CT+TT than TNF-α-238GG/IL1β-31CC. The TNF-α/IL1β promoter Luciferase-reporter assays showed significantly elevated level of luciferase activities with risk genotypes -238AA/-31TT than -238GG/-31CC respectively. Furthermore, treatment of conditioned medium of TNF-α/IL1β over-expressed THP1 cells to HepG2/LX2/HUVEC cells independently showed enhanced level of ER stress and apoptosis in HepG2/increased TGFβ and collagen-I production by LX2/huge neutrophil infiltration through endothelial layer. However, restoration of miR-124-3p in THP1 attenuated such inter-cellular communications and hepatocyte damage/collagen production/neutrophil infiltration were prohibited. Target analysis/luciferase-reporter assays revealed that both TNF-α/IL1β were inhibited by miR-124-3p along with multiple genes from TLR4 signaling/apoptosis/fibrogenesis pathways including MYD88, TRAF3/TRADD, Caspase8/PDGFRA, TGFβR2/MCP1, and ICAM1 respectively.ConclusionThus, rs361525(G/A) in TNF-α and rs1143627(C/T) in IL1β gene may be used as early predictors of ALD susceptibility among East Indian population. Impeding overexpressed TNF-α/IL1β and various genes from associated immune response pathways, miR-124-3p exhibits robust therapeutic potential for ALD patients

Multi-state gene cluster switches determine the adaptive mitochondrial and metabolic landscape of breast cancer

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering (MCbiclust) and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labelled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

Curcumin: A Review of Its’ Effects on Human Health

Turmeric, commonly referred to as “Indian saffron” or the “golden spice”, is a rhizomatous herbaceous perennial plant (Curcuma longa) and belongs to the ginger family. Spices made from the ground roots of the plant are available commercially. It has been used an active ingredient for formulating various medicinal preparations, and finds regular use in Ayurveda and Chinese medicine. Turmeric,  and its constituent ingredients are being considered as multitargeted phytochemicals in the treatment of cancer as cell functions like apoptosis, autophagy, and cell cycle arrest are affected by its use. It has been shown to improve systemic markers of oxidative stress  and its effect on free radicals is carried out by several different mechanisms. This brief review discusses the health benefits of curcumin as well as its medicinal use

An innovative framework for the recognition of human activity in smart healthcare

Health services are one of the most difficult aspects of the massive influx of people into urban centers. With global digitization, especially in healthcare, the ability to collect, receive and present data has become a top priority. Currently, many applications in the healthcare business use Machine Learning to give individualized therapies, which will be more dynamic and efficient once personal health and predictive analytics are combined.  Furthermore, machine learning-based tools aid in the treatment of patients starting at the ground level, with clinical practice diagnosis and suggestions. Massive amounts of data may be collected from smart devices in our digital age. Human activity recognition is a classification problem in which data is used to identify events performed by humans. This data is categorized and analyzed to discover patterns in the data that may be used to create future predictions. In theory, activity detection can provide significant societal benefits. Activity recognition and pattern discovery are two aspects of human activity comprehension. The first is concerned with detecting human activities accurately using a specified activity model

Head-to-Head Comparison of SSTR Antagonist [⁶⁸Ga]Ga-DATA^5m-LM4 with SSTR Agonist [⁶⁸Ga]Ga-DOTANOC PET/CT in Patients with Well Differentiated Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Imaging Study

Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [68Ga]Ga-DOTANOC and [68Ga]Ga-DATA5m-LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs. Histologically proven GEP-NET patients underwent [68Ga]Ga-DOTANOC & [68Ga]Ga-DATA5m-LM4 PET/CT scans, which were analyzed. The qualitative analysis involved the visual judgment of radiotracer uptake validated by the morphological findings using CT, which was considered as the reference standard. Quantitative comparisons were presented as the standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratios (TBR). In total, 490 lesions were confirmed via diagnostic CT. The lesion-based sensitivity of [68Ga]Ga-DATA5m-LM4 PET/CT was 94.28% (462/490) and 83.46% (409/490) for [68Ga]Ga-DOTANOC PET/CT (p 68Ga]Ga-DATA5m-LM4 had statistical significance over [68Ga]Ga-DOTANOC in liver metastases [100% vs. 89.4%; p p = 0.005 (45 vs. 34 {41 lesions on CT})]. Statistical significance was also noted for the TBR SULpeak of the primary and liver lesions. [68Ga]Ga-DATA5m-LM4 showed better sensitivity and a higher target-to-background ratio than [68Ga]Ga-DOTANOC PET/CT. [68Ga]Ga-DATA5m-LM4 PET/CT can be used to quantify the extent of skeletal and liver metastases for better planning of SSTR agonist- or antagonist-based therapy

Development of the external genitalia: perspectives from the spotted hyena (Crocuta crocuta).

This review/research paper summarizes data on development of the external genitalia of the spotted hyena, a fascinating mammal noted for extreme masculinization of the female external genitalia. The female spotted hyena is the only extant mammal that mates and gives birth through a pendulous penis-like clitoris. Our studies indicate that early formation of the phallus in both males and females is independent of androgens; indeed the phallus forms before the fetal testes or ovaries are capable of synthesizing androgens. Likewise, pre- and postnatal growth in length of the penis and clitoris is minimally affected by androgen status. Nonetheless, several internal morphologies, as well as external surface features of the phallus, are androgen-dependent and thus account for dimorphism between the penis and clitoris. Finally, estrogens play a critical role in penile and clitoral development, specifying the position of the urethral orifice, determining elasticity of the urethral meatus, and facilitating epithelial-epithelial fusion events required for proper formation of the distal urethra/urogenital sinus and prepuce. Accordingly, prenatal inhibition of estrogen synthesis via administration of letrozole (an aromatase inhibitor) leads to malformations of the glans as well as the prepuce (hypospadias). The effects of prenatal androgens, anti-androgens and impaired estrogen synthesis correlated with the tissue expression of androgen and estrogen receptors