Miracle-dz/UniFAR-FTUs huggingface dataset:
Conditional Inactivation of Pen-2 in the Developing Neocortex Leads to Rapid Switch of Apical Progenitors to Basal Progenitors

The transition of apical progenitors (APs) to basal progenitors (BPs) is an important neurogenic process during cortical expansion. Presenilin enhancer 2 (Pen-2, also named as Psenen) is a key subunit of γ-secretase and has been implicated in neurodevelopmental disease. However, it remains unknown how Pen-2 may regulate the maintenance of APs. To address this question, we generated a conditional KO (cKO) mouse in which Pen-2 is specifically inactivated in neural progenitor cells in the telencephalon. Both male and female embryos were used. We show that Pen-2 cKO cortices display remarkable depletion of Aps, but transient increase on BPs, compared with controls. We demonstrate that the proliferation rate of APs or BPs is not changed, but the switch of APs to BPs is dramatically accelerated in Pen-2 cKO cortices. Molecular analyses reveal decreased levels of Hes1 and Hes5 but increased levels of Ngn2 and NeuroD1 in Pen-2 KO cells. We report that expression of Notch1 intracellular domain in Pen-2 cKO cortices restores the population of APs and BPs. In summary, these findings highlight a central role of the Notch signaling in Pen-2-dependent maintenance of neural stem cells in the developing neocortex. SIGNIFICANCE STATEMENT Presenilin enhancer 2 (Pen-2) has been implicated in neurodevelopmental disease. However, mechanisms by which Pen-2 regulates cortical development are not understood. In this study, we generated neural progenitor cell-specific Pen-2 conditional KO mice. We observe depletion of apical progenitors and transiently increased the number of basal progenitors in the developing neocortex of Pen-2 mutant mice. Mechanistic analyses reveal decreased levels of Hes1 and Hes5, but increased levels of neurogenic transcription factors in Pen-2 mutant cortices, compared with controls. We demonstrate that reintroduction of Notch intracellular domain into mutant mice restores the population of apical progenitors to basal progenitors. The above findings strongly suggest that the Pen-2-Notch pathway plays an essential role in the maintenance of neural stem cells during cortical development.
The Impact of Ramadan Fasting on the Reduction of PASI Score, in Moderate-To-Severe Psoriatic Patients: A Real-Life Multicenter Study

Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the “Psoriasis Area and Severity Index” (PASI) score after the Ramadan fasting (mean difference = −0.89 ± 1.21, p < 0.0001) was found. At the multivariate regression, the use of cyclosporine (p = 0.0003), interleukin-17 or IL-17 blockers (p < 0.0001), and tumor necrosis factor or TNF blockers (p = 0.0107) was independently associated with a low PASI score, while the use of apremilast (p = 0.0009), and phototherapy (p = 0.0015) was associated with a high PASI score before the Ramadan fasting. Similarly, the consumption of cyclosporine (p < 0.0001), IL-17 blockers (p < 0.0001), mammalian target of rapamycin or mTOR inhibitors (p = 0.0081), and TNF blockers (p = 0.0017) predicted a low PASI score after the Ramadan fasting. By contrast, narrow band ultraviolet light B or NB-UVB (p = 0.0015) was associated with a high PASI score after Ramadan fasting. Disease duration (p = 0.0078), use of apremilast (p = 0.0005), and of mTOR inhibitors (p = 0.0034) were independent predictors of the reduction in the PASI score after the Ramadan fasting. These findings reflect the influence of dieting strategy, the biological clock, and circadian rhythm on the treatment of plaque psoriasis.
Effect of in ovo administration of different synbiotics on carcass and meat quality traits in broiler chickens

&NA; The aim of this study was to examine the effect of in ovo synbiotic administration on slaughter performance and meat quality traits of broiler chickens. On day 12 of incubation, 5,850 eggs (Cobb 500 FF) were randomly divided into 3 experimental groups and automatically injected in ovo with physiological saline (control, C) and 2 different synbiotic formulations (SYN1: Lactobacillus salivarius + galactooligosaccharides; SYN2: Lactobacillus plantarum + raffinose family oligosaccharides). After hatching, 240 males were randomly chosen (80 chicks per group) and split into 8 replicate pens (10 birds per pen). At 42 d of age, 15 birds per treatment were weighed and slaughtered. In ovo synbiotic administration had a low effect on investigated traits, but depends on the kind of synbiotic administered. Both synbiotic formulations did not affect final BW, weight, and yield of carcass and pectoral muscle (PM); likewise, physicochemical properties (pH, color, water holding capacity), intramuscular collagen properties, and cholesterol content of PM were not affected by treatment. Synbiotic administration reduced (P = 0.061) the lipid content compared with C group, markedly (P < 0.05) with synbiotic SYN2. Meat from SYN1 birds displayed a higher (P < 0.01) content of saturated fatty acids (SFA), lower monounsaturated fatty acids (P < 0.05 compared only to SYN2), and lower (P < 0.01 and P < 0.05) polyunsaturated fatty acids (PUFA), n‐6 PUFA and n‐3 PUFA compared to C and SYN2 groups. The ratio of n‐6 to n‐3 PUFA was affected by the synbiotic administration (P = 0.039). Meat from C and SYN2 groups displayed a higher (P < 0.01) ratio of PUFA to SFA and lower (P < 0.01) atherogenic and thrombogenic indices compared to SYN1. In conclusion, this study has shown that in ovo administration of synbiotics did not negatively affect slaughter performance and physicochemical properties of meat. However, meat from C and SYN2 birds showed a preferable fatty acid profile, with a positive effect on nutritional properties of chicken meat.
Genotyping Human Papillomavirus in Women Attending Cervical Cancer Screening Clinic in Harare, Zimbabwe

Aim: To determine the prevalence of human papillomavirus genotypes in women attending a cervical cancer screening VIAC (visual inspection with acetic acid) clinic. Study Design: Cross-sectional study. Place and Duration of Study: VIAC clinic at Parirenyatwa Referral Hospital in Harare in Zimbabwe between February and April 2015. Methodology: Sexually active women were recruited and they provided their socio-demographic data and self-collected vaginal swabs. HIV status of the participants was determined. DNA was Original Research Article Matuvhunye et al.; BMRJ, 16(6): 1-9, 2016; Article no.BMRJ. 28481 2 extracted from the swabs using the standard phenol-chloroform method. HPV DNA was detected using the standard consensus MY09/11-GP5+/GP6+ nested polymerase chain reaction. Amplicons were sequenced and sequences analyzed using bioinformatics tools to identify the HPV genotypes. Results: Sixty women were recruited. Their age ranged from 21-83 years, with a mean of 40.1 years. Most of the women were married and resided in the urban areas. Of the 60 participants, 50% (30/60) were HIV-positive. The prevalence of HPV genotypes in the study subjects was 56.7% (34/60). HPVs were most prevalent in women aged 30 years and below, and became less prevalent as the age increased. The predominant genotypes detected were HPV-16, -58, -52, -45, 18, -33, -51, -6, -81, -11, -70, -62, -32 and -40. Conclusion: A number of HPV genotypes were detected in half of women tested. There was no significance association between risk-factors (parity, level of education, residence, history of STI, contraceptive use and sexual debut) and HPV infection. The findings of this study showed that consensus nested PCR and DNA sequencing could be used to detect HPV genotypes in women in cervical cancer screening programs. Although this method is sensitive, it is inefficient at detecting multiple HPV infections.
Oral diseases and inflammatory burden and Alzheimer's disease among subjects aged 75 years or older

AIM To study whether dental caries, periodontal disease, and stomatitis, and the related inflammatory burden associate with diagnosed Alzheimer's disease (AD) and dementia among older people. METHODS The study population included 170 individuals aged ≥75 years. The primary outcome was diagnosed AD and the secondary outcome was any types of diagnosed dementia. Information about participants' oral diseases and the related inflammatory burden was based on the clinical oral examination. Relative risks (RRs) and confidence intervals (CIs) were estimated using regression models. RESULTS Dental caries, the presence of ≥3 carious teeth (RR: 3.47, 95% CI: 1.09-11.1) and the number of carious teeth (RR: 1.24, CI: 1.11-1.39), and inflammatory burden (RR: 1.44, CI: 1.04-2.01) were associated with a higher likelihood of having AD. Also, periodontal disease and stomatitis were associated, although nonstatistically, with AD and dementia. The risk estimates for any type of dementia were in most cases lower than for AD. CONCLUSION Oral diseases and the related inflammatory burden were in most cases associated more strongly with diagnosed AD than dementia in general. Of the oral diseases studied, the strongest association was between dental caries and AD.
Improving Patient Access to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment through an Integrated Collaborative Team Care Approach

Aim: Intravitreal anti-vascular endothelial growth factor (Anti-VEGF) has become a mainstream treatment for many ophthalmic conditions. Consequently, the demand for the treatment has significantly increased. The significant resource constrained environment necessitated the Palmerston North Hospital Eye Department (PNHED) to introduce solutions to address this increased demand. The two main initiatives adopted were: senior nurse-led macular review clinic (MRC) and nurse-led intravitreal injection clinic. This article will review our current service accessibility and to directly compare it to the results shown in the previous two audits. Method: The data were collected on an updated macular review clinic patient prospective database and Zeiss optical coherence topography (OCT) forum viewer. The study population was determined by those who have received the intravitreal injection treatment (IVT) between January 2015 and November 2017. Results: The average waiting times between IVT and subsequent review clinic as well as review clinic and subsequent IVT have been reduced when compared to the previous audit findings. The average period for the unintended delay between the IVT sessions is 6.07 days. The number of IVT given per year has also increased dramatically every year. Conclusion: PNHED has successfully incorporated both nurses-led MRC clinics and nurse-led IVT clinics. They resulted in a reduction in unintended delays for both reviews and treatment. A secondary benefit of this resource reallocation has been to improve the accessibility of senior medical officer (SMO) clinic appointments. This has reduced the wait time for new patients requiring initial SMO assessment before starting on IVT.
US Guideline Criteria for HIV Pre-Exposure Prophylaxis: Clinical Considerations and Caveats.

Clinical guidelines for HIV pre-exposure prophylaxis (PrEP) developed by the US Centers for Disease Control and Prevention have been instrumental to the implementation of PrEP in medical practices throughout the country. However, the eligibility criteria contained within may inadvertently limit PrEP access for some patients. We describe key considerations and caveats surrounding these criteria: (1) promotion of a selective vs. universal approach to sexual health education involving PrEP; (2) misalignment between criteria stated in the table and text boxes; (3) problematic categorization and confounding of sexual orientation, gender identity, and risk behavior; (4) underemphasis of network/community-level drivers of HIV transmission; (5) oversimplification of serodiscordant risk; and (6) lack of clarity surrounding the relevance of condoms to PrEP eligibility. We offer concrete recommendations to address the identified issues and strengthen future iterations of the guidelines, applying these recommendations in an alternative table of "criteria. "
Goiter in school children versus use of iodized salt in Peshawar.

Iodine Deficiency Disorders (IDD) among children in Pakistan has been recognized as a major health problem since long. Health Ministry in collaboration with UN Childrens Fund initiated a mass scale awareness and Universal salt iodization program in early 90s. This report pertains to a survey conducted in schools of Peshawar University Campus to highlight the current status of IDD in children and practice of iodized salt use by their families. Overall prevalence of goiter has been found to be over 20% still needing urgent correction. Iodized salt use has reached a level of 80% in the educated community of the province after 5-6 years of extensive promotion campaign. 50% salt sold in the market is still uniodized or contains very little amount of iodine. Situation needs re-evaluation and strategies need further improvement. Sustainability of the campaign with inclusion of other modes of motivation and promotion is suggested. (authors)
Pinocytotic engulfment of lipoproteins by macrophages

Atherosclerosis is a major cause of acute coronary syndrome and stroke. Foam cell formation in macrophages is involved in controlling plaque stability and the pathogenesis of atherosclerosis. Accordingly, many studies have examined the processes of lipid incorporation, such as scavenger receptor-mediated uptake of oxidized low-density lipoprotein, in cells. In addition to receptor-mediated machinery, growing evidence has suggested that pinocytosis, which is a receptor-independent endocytic pathway, is associated with foam cell formation when a sufficient number of lipoproteins is accumulated around cells. Pinocytotic engulfment of nanoparticles is initiated by plasma membrane ruffling in a phosphatidylinositol-3 kinase-dependent manner. Subsequent to pinosome closure, the majority of pinosomes are internalized through endocytic processes, and they can be recycled into the plasma membrane. These pinocytotic processes are modulated by small GTPases and their cytoskeletal rearrangement. Moreover, pinocytotic abilities may vary between immunological subsets in cells. Accordingly, macrophages may show diverse pinocytotic abilities depending on the surrounding microenvironment. This review summarizes the current understanding of pinocytotic engulfment of lipoprotein in macrophages, and discusses how this endocytic process is governed under hypercholesterolemic conditions.
Processing Visual Temporal Information and Its Relationship to Psychometric Intelligence Converging Evidence for the Temporal Resolution Power Hypothesis of Intelligence

According to previous studies there is a well-established functional relationship between temporal resolution power (TRP), assessed by auditory psychophysical timing tasks, and psychometric intelligence. Here we investigated whether the relationship between psychometric intelligence and temporal information processing can be also observed in the visual modality. For this purpose, performance on four visual psychophysical timing tasks (duration discrimination with filled and empty intervals, temporal generalization, and rhythm perception) was examined and related to performance on a psychometric test of intelligence. Correlational analyses indicated a reliable positive association between performance on each of the four temporal tasks and psychometric intelligence. Structural equation modeling suggested that performance on the four tasks can be assigned to one latent variable, referred to as TRP, which explained 16.5% of variance of psychometric intelligence. Findings indicate that the functional relations.
The Effect of Interval Training on Cardiac Angiogenesis Capacity in Rats with Myocardial Infarction

Introduction: Myocardial infarction (MI) is the destruction and permanent and irreversible cell death of part of the cardiac muscle (myocardium) which occurs due to loss of blood flow to the heart. The condition disrupts individuals’ daily life and limits their performance. Evidence indicates the likely effect of exercise on increasing the capillary density of skeletal muscle and myocardium. Vascular endothelial growth factor (VEGF) and endostatin as well as their common receptors (Flt-1) are the most important factors involved in angiogenesis. Therefore, this research aimed to evaluate the effect of 6 weeks of interval training on the VEGF, Flt-1 and collagen 18 in rats with MI. Methods: 12 male Wistar rats with mean age of 10weeks and average weight of 250300 gr were infected with myocardial infarction and were assigned into two groups of (1) experimental (60 minutes of interval running on treadmill, each interval 4 minutes with the 6075 percent of Vo2max and 2 minutes of active rest at 5060 percent of Vo2max for four days in a week for a period of 6 weeks) and (2) control group (without any training). Gene expression was investigated by the PCR technique and Ejection fraction and Shortening fraction were investigated by echocardiograph. Data were analyzed by SPSS 18 using independent samples t-test (p≤0.05). Results: Results showed that low intensity interval training had a significant effect on increasing the expression level of Flt-1 (P=0.02) and VEGF (P=0.01) genes and no significant change in collagen 18 (P=0.34). Conclusion: The overall results of the study supported the role of lowintensity interval training in increasing the basic factors affecting the process of angiogenesis after MI.
Lifting the fog on 'chemobrain' : a prospective cohort study of chemotherapy-related cognitive changes in women with early breast cancer

The purpose of this prospective study was to evaluate whether women treated with chemotherapy for early breast cancer would show significantly poorer cognitive functioning following treatment than women not treated with chemotherapy. A comprehensive clinical neuropsychological assessment designed to be sensitive to mild cognitive impairment and change in six cognitive domains was conducted in order to uncover any profile of chemotherapy-related cognitive impairment. Women with early breast cancer scheduled to receive adjuvant chemotherapy completed a detailed assessment: before commencing chemotherapy (Time 1: n = 30); after completing chemotherapy (Time 2: n = 30); and again 9 months later (Time 3: n = 29). A control group of women with early breast cancer not receiving chemotherapy were tested at matched timepoints (Time 1: n = 15; Time 2: n = 16; Time 3: n = 16). Prior to the group analysis, a multivariate statistical approach called Principal Components Analysis (PCA) was used to examine the entire set of relationships among neuropsychological outcome measures within a cognitive domain. This enabled the underlying dimensions that explain the correlations among the set of measures to be identified. From this a smaller set of neuropsychologically meaningful summarized outcome measures were derived, using the first principal component summary score, for use in subsequent analyses involving AN OVA and regression. Two approaches were used for the analyses of individual deficits. For the first, individual test scores were screened for 'cognitive complications' at each timepoint, defined as a score of more than 2 standard deviations (SD) below the mean of age-standardized normative data for each test. An overall 'lower than expected performance' score was also calculated for each individual from the mean of all scores that were :::;1.5 SD below their estimated premorbid intelligence. Findings from the group analyses provided limited support at the 95% confidence level for the hypothesis that women treated with chemotherapy would demonstrate significantly worse cognitive functioning over a 9-month post treatment follow-up period relative to women not treated with chemotherapy for breast cancer. Only verbal recall discriminability, derived from new more sensitive measures of verbal recall accuracy and
Quality of life of Turkish patients with head and neck cancer

In the past decade there has been a considerable increase of interest in quality of life (QoL) issues of oncology. This study was planned to investigate whether localization side and stage of cancer, treatment type and radiotherapy doses have effect on quality of life in head and neck (HN37(4):129-136]
Distributed Universality: Contention-Awareness, Wait-freedom, Object Progress, and Other Properties

A notion of a universal construction suited to distributed computing has been introduced by M. Herlihy in his celebrated paper "Wait-free synchronization" (ACM TOPLAS, 1991). A universal construction is an algorithm that can be used to wait-free implement any object defined by a sequential specification. Herlihy's paper shows that the basic system model, which supports only atomic read/write registers, has to be enriched with consensus objects to allow the design of universal constructions. The generalized notion of a k-universal construction has been recently introduced by Gafni and Guerraoui (CONCUR, 2011). A k-universal construction is an algorithm that can be used to simultaneously implement k objects (instead of just one object), with the guarantee that at least one of the k constructed objects progresses forever. While Herlihy's universal construction relies on atomic registers and consensus objects, a k-universal construction relies on atomic registers and k-simultaneous consensus objects (which are wait-free equivalent to k-set agreement objects in the read/write system model). This paper significantly extends the universality results introduced by Herlihy and Gafni-Guerraoui. In particular, we present a k-universal construction which satisfies the following five desired properties, which are not satisfied by the previous k-universal construction: (1) among the k objects that are constructed, at least l objects (and not just one) are guaranteed to progress forever; (2) the progress condition for processes is wait-freedom, which means that each correct process executes an infinite number of operations on each object that progresses forever; (3) if any of the k constructed objects stops progressing, all its copies (one at each process) stop in the same state; (4) the proposed construction is contention-aware, in the sense that it uses only read/write registers in the absence of contention; and (5) it is generous with respect to the obstruction-freedom progress condition, which means that each process is able to complete any one of its pending operations on the k objects if all the other processes hold still long enough. The proposed construction, which is based on new design principles, is called a (k, l)-universal construction. It uses a natural extension of k-simultaneous consensus objects, called (k, l)-simultaneous consensus objects ((k, l)-SC). Together with atomic registers, (k, l)-SC objects are shown to be necessary and sufficient for building a (k, l)-universal construction, and, in that sense, (k, l)-SC objects are (k, l)-universal.
Recurrent Experience Replay in Distributed Reinforcement Learning

Building on the recent successes of distributed training of RL agents, in this paper we investigate the training of RNN-based RL agents from distributed prioritized experience replay. We study the effects of parameter lag resulting in representational drift and recurrent state staleness and empirically derive an improved training strategy. Using a single network architecture and ﬁxed set of hyper-parameters, the resulting agent, Recurrent Replay Distributed DQN, quadruples the previous state of the art on Atari-57, and matches the state of the art on DMLab-30. It is the ﬁrst agent to exceed human-level performance in 52 of the 57 Atari games.