Miracle-dz/UniFAR-FTUs huggingface dataset:
An inducible system for highly efficient production of recombinant adeno-associated virus (rAAV) vectors in insect Sf9 cells

Production of clinical-grade gene therapy vectors for human trials remains a major hurdle in advancing cures for a number of otherwise incurable diseases. We describe a system based on a stably transformed insect cell lines harboring helper genes required for vector production. Integrated genes remain silent until the cell is infected with a single baculovirus expression vector (BEV). The induction of expression results from a combination of the amplification of integrated resident genes (up to 1,200 copies per cell) and the enhancement of the expression mediated by the immediate-early trans-regulator 1 (IE-1) encoded by BEV. The integration cassette incorporates an IE-1 binding target sequence from wild-type Autographa californica multiple nuclear polyhedrosis virus, a homologous region 2 (hr2). A feed-forward loop is initiated by one of the induced proteins, Rep78, boosting the amplification of the integrated genes. The system was tested for the coordinated expression of 7 proteins required to package recombinant adeno-associated virus (rAAV)2 and rAAV1. The described arrangement provided high levels of Rep and Cap proteins, thus improving rAAV yield by 10-fold as compared with the previously described baculovirus/rAAV production system.
The molecular phenotypes of rejection in kidney transplant biopsies

Purpose of reviewThe recent emergence of a system for distinguishing T-cell–mediated rejection (TCMR) from antibody-mediated rejection (ABMR), including C4d-negative ABMR, allows us to map the molecular features of these conditions. Recent findingsThe TCMR landscape is dominated by molecules expressed in effector T cells, antigen-presenting cells (macrophages, dendritic cells, B cells) and interferon-gamma (IFNG)-induced genes. A surprising finding is the association of transcripts for inhibitory molecules such as CTLA4 and PDL1 with TCMR, indicating that this tubulo-interstitial inflammatory compartment is actively controlled. ABMR is dominated by endothelial transcripts related to angiogenesis, reflecting endothelial injury; natural killer (NK)-cell transcripts; and selected IFNG-regulated transcripts. This suggests a cognate unit of NK cells engaging donor-specific antibody bound to donor human leukocyte antigen antigens through their CD16a (FCGR3A) Fc receptors, triggering IFNG release. TCMR and ABMR share many rejection-associated transcripts, mainly IFNG-induced genes and transcripts shared between NK cells and CD8 effector T cells (e.g., KLRD1). In addition, acute kidney injury transcripts, which reflect the parenchymal response to injury, are shared between different forms of rejection and are indicative of disease progression. SummaryMicroarray assessment provides a new dimension in biopsy assessment for diagnosis that offers mechanistic insights and sometimes challenges histology assessments.
The population impact on incidence of suicide and non-fatal self harm of regulatory action against the use of selective serotonin reuptake inhibitors in under 18s in the United Kingdom: ecological study

Objective To investigate the population impact on the incidence of suicide and non-fatal self harm of regulatory action in 2003 to restrict the use of selective serotonin reuptake inhibitors (SSRIs) in under 18s. Design Ecological time series study. Setting United Kingdom. Populations Young people in the UK aged 12-19 years (prescribing trends), in England and Wales aged 12-17 years (mortality), and in England aged 12-17 years (hospital admissions). Main outcome measures Deaths from suicide and hospital admissions for self harm. Results Antidepressant prescribing doubled between 1999 and 2003 but fell to the 1999 level between 2004 and 2005. These large changes in prescribing did not seem to be associated with temporal trends in suicide or self harm. In the years 1993 to 2005 the annual percentage reduction for suicide among 12-17 year olds was −3.9% (95% confidence interval −6.2% to −1.5%) in males and −3.0% (−6.6% to 0.6%) in females, with no indication of a substantial change in this rate of decrease during that period. Similarly, hospital admission rates for self harm in the years 1999 to 2005 indicated an annual percentage increase for males of 1.1% (−0.5% to 2.7%) and for females of 5.7% (3.6% to 7.8%), again with no statistical evidence of a change in rate after the regulatory action. Conclusions The noticeable reduction in prescribing of antidepressants since regulatory action in 2003 to restrict the use of SSRIs in under 18s does not seem to have been associated with changes in suicidal behaviour in young people. Specifically, these data for England do not indicate that reductions in antidepressant use have led to an increase in suicidal behaviour.
Pattern of morbidity and mortality of newborns admitted into the sick and special care baby unit of Enugu State University Teaching Hospital, Enugu state.

BACKGROUND Being the highest contributor to under-5 mortality, neonatal mortality and morbidity has great impact to the attainment of millennium development goals 4 (MDG 4). In Nigeria and other developing countries, this indicator strongly poses a major challenge in achieving this goal. OBJECTIVES To determine the morbidity and mortality pattern of admitted babies in the special care baby unit (SCBU) of Enugu State University Teaching Hospital (ESUTH). MATERIALS AND METHODS This is a comparative and descriptive longitudinal study of causes of morbidity and mortality between babies born within (inborn) and outside our hospital facilities (outborn) based on information on place of birth, APGAR scores, age on admission, diagnosis on admission, duration of hospital stay, and outcome of newborns admitted into the sick and SCBU over a 1 year period. RESULTS A total of 261 neonates were admitted during the period under review. The common causes of admissions seen from the study were perinatal asphyxia (80, 30.7%), low birth weight (64, 24.5%), neonatal sepsis (44, 16.9%), and neonatal jaundice (16, 0.06%). A total of 37 (14.2%) deaths were recorded during the period. The leading causes of deaths were severe form of perinatal asphyxia (18, 52.9%), neonatal sepsis (10, 29.4%), and very low birth weight (two, 0.06%). Fifty-five percent of all the deaths occurred within 24 h of admission. Death due to asphyxia was more in babies born outside the hospital (outborn) than in babies born within the hospital (inborn). Equal number of outborn and inborn babies died from neonatal sepsis. The age at presentation to the sick baby unit was significantly lower in inborn (P = 0.004), while age at death was not different in both group of newborns (P = 0.876). CONCLUSION The neonatal mortality rate and the causes of death in this study are similar to those documented by other studies in Nigeria and are largely preventable. Strengthening perinatal care, emergency obstetric services, and enhancement of neonatal resuscitation skills to traditional birth attendants (TBAs) and other community health workers are necessary to reduce the neonatal mortality in our setting and other rural settings across developing countries.
Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice

The Morris Water Maze (MWM) was first established by neuroscientist Richard G. Morris in 1981 in order to test hippocampal-dependent learning, including acquisition of spatial memoryand long-term spatial memory 1. The MWM is a relatively simple procedure typically consisting of six day trials, the main advantage being the differentiation between the spatial (hidden-platform) and non-spatial (visible platform) conditions 2-4. In addition, the MWM testing environment reduces odor trail interference 5. This has led the task to be used extensively in the study of the neurobiology and neuropharmacology of spatial learning and memory. The MWM plays an important role in the validation of rodent models for neurocognitive disorders such as Alzheimer’s Disease 6, 7. In this protocol we discussed the typical procedure of MWM for testing learning and memory and data analysis commonly used in Alzheimer’s disease transgenic model mice.
The Diverse Roles of Arrestin Scaffolds in G Protein–Coupled Receptor Signaling

The visual/β-arrestins, a small family of proteins originally described for their role in the desensitization and intracellular trafficking of G protein–coupled receptors (GPCRs), have emerged as key regulators of multiple signaling pathways. Evolutionarily related to a larger group of regulatory scaffolds that share a common arrestin fold, the visual/β-arrestins acquired the capacity to detect and bind activated GPCRs on the plasma membrane, which enables them to control GPCR desensitization, internalization, and intracellular trafficking. By acting as scaffolds that bind key pathway intermediates, visual/β-arrestins both influence the tonic level of pathway activity in cells and, in some cases, serve as ligand-regulated scaffolds for GPCR-mediated signaling. Growing evidence supports the physiologic and pathophysiologic roles of arrestins and underscores their potential as therapeutic targets. Circumventing arrestin-dependent GPCR desensitization may alleviate the problem of tachyphylaxis to drugs that target GPCRs, and find application in the management of chronic pain, asthma, and psychiatric illness. As signaling scaffolds, arrestins are also central regulators of pathways controlling cell growth, migration, and survival, suggesting that manipulating their scaffolding functions may be beneficial in inflammatory diseases, fibrosis, and cancer. In this review we examine the structure–function relationships that enable arrestins to perform their diverse roles, addressing arrestin structure at the molecular level, the relationship between arrestin conformation and function, and sites of interaction between arrestins, GPCRs, and nonreceptor-binding partners. We conclude with a discussion of arrestins as therapeutic targets and the settings in which manipulating arrestin function might be of clinical benefit.
Possible preventive effect of high doses of folic acid for isolated hypospadias: A national population‐based case–control study

Hypospadias is a common structural birth defect (congenital abnormality) of the male genital organ. The objective of this study was to test the hypothesis regarding the possible preventive effect of folic acid for isolated hypospadias (IH). Folic acid use was compared in 3,038 cases with IH and 24,814 male controls without any defects in the national population‐based Hungarian Case–Control Surveillance of Congenital Abnormalities, 1980–1996. In Hungary only one kind of folic acid tablet, containing 3 mg/tablet was available during the study period. Hungarian obstetricians recommended daily use of 1–3 tablets, that is, 3–9 mg of folic acid during pregnancy; the estimated daily dose was 5.7 or 5.6 mg in the mothers of cases with IH and controls, respectively. Of 3,038 mothers of cases 1,474 (48.5%) were supplemented with high doses of folic acid during pregnancy and 13,509/24,814 mothers of controls (54.9%) as reference were supplemented at this level as well (OR 95% CI: 0.79, 0.73–0.85). If only medically recorded folic acid use in the critical period of IH was evaluated, the preventive effect was more apparent (OR 95% CI: 0.36, 0.32–0.41). The intake of folic acid among mothers of infants with severe IH was lower than among mothers of infants with mild IH, suggesting a dose–response relationship. In conclusion, this study suggests that high doses of folic acid are associated with a reduced risk of IH. However, this analysis was based on observational data; therefore, confirmation in a well‐controlled study is needed. © 2014 Wiley Periodicals, Inc.
Similarity is closeness: Metaphorical mapping in a conceptual task

The conceptual metaphor theory states that abstract concepts are represented by image schemas from concrete domains. In the present study we investigated the mapping for SIMILARITY IS CLOSENESS using tasks with nonlinguistic materials. In Experiments 1 and 2 participants decided whether two squares were similar or dissimilar in colour. The spatial distance between the squares was varied. Performance to similar colours was better at shorter distances, whereas performance to dissimilar colours was better at longer distances. In Experiments 3 and 4 participants made distance decisions to similar and dissimilar colours squares. Performance was not affected by similarity. These results show that metaphorical mappings can be found even beyond the context of linguistic metaphors and that the mapping between SIMILARITY and CLOSENESS is asymmetrical.
Do neonates with genetic abnormalities have an increased morbidity and mortality following cardiac surgery?

INTRODUCTION Genetic abnormalities occur in approximately 20% of children with congenital heart disease. The purpose of this study was to evaluate the effect of genetic abnormalities on short-term outcomes following neonatal cardiac surgery. METHODS Retrospective review of all neonates (n = 609) undergoing cardiac surgery from January 2003 to December 2006. Genetic abnormalities were identified in 93 neonates (15%). Genetic abnormalities identified were 22q11.2 deletion (23), chromosomal abnormalities including various monosomies, trisomies, deletions, duplications, and inversions (17), dysmorphic undefined syndrome without recognized chromosomal abnormality (27), Down syndrome (9), laterality sequences (9), recognixed syndromes and genetic etiology including Mendelian (i.e. Alagille, CHARGE) (8). RESULTS Neonates with genetic abnormalities had lower birth weights and were older at time of surgery. There was no difference in operative variables, duration of mechanical ventilation or ICU length of stay between the two groups. There was an increase in total hospital length of stay and postoperative complications in the neonates with genetic abnormalities. Importantly, in hospital mortality was not different. CONCLUSION Neonates with genetic abnormalities have a higher risk of postoperative complications and a longer hospital length of stay. However, there is no increase in hospital mortality. This information may aid in patient management decisions and parental counseling. Longer-term studies are needed for understanding the total impact of genetic abnormalities on neonates with congenital heart disease.
Relative frequency of human papillomavirus genotypes and related sociodemographic characteristics in women referred to a general hospital in Tehran, 2014-2015: A cross-sectional study

Background: Human papilloma virus (HPV) is one of the major public health problems and the main causes of cervical cancer. The prevalence HPV infection in developing countries with low financial resources is high. Objective: This study aimed to determine the relative frequency of HPV genotypes and its sociodemographic characteristics in women referred to a general hospital in Tehran, Iran from 2014-2015. Materials and Methods: This cross-sectional study was performed in 400 women with Pap smear samples, referring to to a general hospital in Tehran, Iran from 2014-2015. The detection of 28 HPV genotypes was performed by using the Multiplex PCR technique. The sociodemographic survey was conducted for each HPV positive woman. Results: HPV-positive infection was detected in 155 (38.75%) women aged 17-85 years. HPV 16 (19.1%) was the most prevalent type, followed by HPV 39 (12.5%) and HPV 18 (8.9%). The highest rate of HPV infection was observed at the age of 36 years (7.7%). The level of education and economic situation of each woman were showed most of HPV-positive women had a high school diploma (34.6%) and average economic situation (67,9%). 60.9% of these women were a housewife, and 67.3% lived in the capital . Conclusion: Determination of HPV genotype and risk factor related to HPV infection in each geographical region can lead to the production of effective vaccines against the HPV virus. It can also be useful for disease management and high sensitivity diagnosis of cervical intraepithelial neoplasia.
[Antibiotic resistance of Escherichia coli strains isolated from raw chicken meat in Senegal].

INTRODUCTION Antimicrobial-resistant Escherichia coli and others pathogens bacteria can be transferred from animals to humans through consumption of contaminated food and foods products and thus present a public health risk. The increase in E. coli resistance to commonly used antimicrobials both in the public health and veterinary sectors is one of the major threats of health care worldwide. The present study was undertaken to estimate the antimicrobial resistance of E. coli isolates from raw chicken meat in Dakar. MATERIAL AND METHOD Levying of skin and muscle have been carried out on 120 chicken carcasses bought from 13 sale points and 23 flocks beetween November 2003 and April 2004. 102 Escherichia coli strains have been isolated, among which, 90 were tested for their susceptibilities to 16 selected antibiotics by agar diffusion method. RESULTS All Escherichia coli strains (100%), were resistant to one or more antibiotic; 60 strains (66.66%) being resistant to more than five antibiotics. Those frequently encountererd are: ampicillin, trimethoprim, trimethoprim-sulfametoxazole, tetracycline, sulfonamides, streptomycin, nalidixic acid. Multiple resistances to 12 antibiotics were also observed. The lowest resistances were noted with gentamicin (3.33%) and neomycin (5.56%). CONCLUSION This study showed the significance of chicken meat as source of Escherichia coli strains with a simple or multiple resistance to various antibiotics tested. Further studies are necessary in order to determine bacterium mechanisms of resistance.
Effects of hepatic function and hepatitis C virus on the nervous system assessment of advanced-stage HIV-infected individuals

Objectives:To examine the effects of liver function and hepatitis C virus (HCV) serostatus on neurological, neuropsychological, and psychiatric abnormalities in an advanced-stage HIV-infected cohort. Design:A correlational analysis of baseline data accumulated on 137 participants in the Manhattan HIV Brain Bank, a longitudinal study of HIV-infected individuals. Methods:Patients underwent a battery of neuropsychological tests, a semi-structured psychiatric interview, and a neurological examination. The resulting diagnostic data were correlated with biochemical indices of hepatic function and HCV serostatus. Results:Biochemical indices of liver function correlated with motor dysfunction determined by neurological evaluation, but not with neuropsychological or psychiatric disorders. Discrete neurological diagnostic entities showed no relationship with biochemical indices, with one exception: patients with cryptococcal leptomeningitis had worse liver function than those without. HCV had no relationship with any neurological disorder or symptom complex. In contrast, HCV serostatus was related to neuropsychological and psychiatric abnormalities, and indices of liver function were not. HCV-seropositive patients were more likely to have histories of opiate, cocaine or stimulant dependency, to have greater impairment in executive functioning, and to meet diagnostic criteria for AIDS dementia, compared with HCV-negative individuals of similar immunological and virological status. Conclusions:HCV and biochemical indices of liver function associate differentially with nervous system abnormalities in this HIV-infected population. Neurological abnormalities correlate with biochemical indices of liver function, whereas neuropsychological and psychiatric dysfunction are linked to HCV infection. We postulate that multifactorial impacts of HCV and liver disease on HIV-related nervous system disorders may originate in different anatomical and cellular compartments.
Ray tracing simulation tool for portal-based millimeter-wave security systems using the NVIDIA® OptiX™ ray tracing engine

Summary form only given. Person-borne weapons and explosives present major security threats at civil infrastructures such as airports. Millimeter-wave whole body imaging systems are used to identify anomalous objects hidden underneath people's clothing. Improvements to these systems can be investigated using electromagnetic computational models. Such forward models allow prediction of scattering from objects and give insight into the most effective sensor configurations and imaging techniques. Conventional full-wave simulation methods such as Finite Difference Frequency Domain and the Method of Moments provide extremely accurate solutions but are usually slow, ranging from minutes to hours in 3D depending on the domain size and frequency range. Less accurate but faster methods include physical optics and the Modified Equivalent Current Approximation (MECA). Simulating a portal-based scanning system involves evaluating the scattered field from the human body at multiple frequencies and at multiple receiver points, which is computationally expensive when using these methods. This work presents a fast forward ray tracing simulation tool. Rays are launched in the direction of a simulated tessellated human body and traced until reaching simulated system receivers. The scattered field at these receivers is computed by using the pathlength phase of each ray and adding ray fields within finite size receiver elements. Although the algorithm presented in this work excludes the modeling of phenomena such as refraction and diffraction, the path distance information encoded in reflected rays gives acceptable accuracy in scattered field amplitude and phase data and for images processed with SAR methods. The figure shows reflectivity magnitude of 2D SAR of a human body, using field data generated from ray tracing (left) and a 2D Method of Moments (right). The green contour is the true transverse body profile with torso and arms.
MicroRNA‐142‐5p induces cancer stem cell‐like properties of cutaneous squamous cell carcinoma via inhibiting PTEN

Cutaneous squamous cell carcinoma (cSCC) is a malignancy of keratinocyte‐derived skin tumor, which is regarded as the second most common skin cancer worldwide. Accumulating evidence has established that microRNAs (miRNAs) can play a critical role in tumor initiation, progression, and metastasis including cSCC. Abnormal expression of hsa‐miR‐142‐5p has been elaborated in various tumors. Nevertheless, its expression and function in the development of cSCC remain unclear. In our study, we found that the expression of hsa‐miR‐142‐5p in cSCC cells were greatly overexpressed compared to human benign epidermal keratinocyte cells. Moreover, inhibited hsa‐miR‐142‐5p can repress cSCC cell growth and induce apoptosis while upregulated hsa‐miR‐142‐5p exhibited a reverse phenomenon. Recently, cancer stem cells (CSCs) which possess the ability of self‐renewal and proliferation and are able to produce cancer cells have been widely reported. However, the correlation between hsa‐miR‐142‐5p and CSCs in cSCC is still unknown. Interestingly, we observed that overexpressing hsa‐miR‐142‐5p can induce CSC‐like properties in cSCC via activating Wnt signaling. In addition, the luciferase reporter assay data and bioinformatics analysis demonstrated that hsa‐miR‐142‐5p can target the 3′UTR of PTEN mRNA. Taken these together, we draw a conclusion that hsa‐miR‐142‐5p can trigger cancer stem cell‐like properties of cSCC through inhibition of PTEN. Our findings may provide hsa‐miR‐142‐5p as a new therapeutic target for cSCC.