Miracle-dz/UniFAR-FTUs huggingface dataset:
RE-PERG in early-onset Alzheimer’s disease: A double-blind, electrophysiological pilot study

Purpose To evaluate the ability of re-test pattern electroretinogram (RE-PERG), a non-invasive and fast steady-state PERG, to detect inner retinal bioelectric function anomalies in patients with early-onset Alzheimer’s disease (AD). Methods The study population consisted of 17 patients with AD-related mild cognitive impairment (MCI), 16 patients with vascular dementia (VD)-related MCI, both assessed using the neuropsychological Mini-Mental State Examination (MMSE) and by structural magnetic resonance imaging, and 19 healthy, age-matched normal controls (NC). All participants were visually asymptomatic, had normal or near-normal general cognitive functioning and no or minimal impairments in daily life activities. Visual field (VF) test, optical coherence tomography (OCT) and RE-PERG, sampled in five consecutive blocks of 130 events, were performed. Results There was no statistically significant difference among the three groups with respect to age, VF parameters (mean and pattern standard deviations) and OCT parameters (ganglion cell complex thickness and retinal nerve fiber layer thickness). The mean amplitude in the RE-PERG was significantly lower, but only weakly in the AD group than in NC (p = 0.1) whereas the intrinsic variability of the 2nd harmonic phase was significantly higher in the AD group than in either the VD or NC group (p<0.001). Conclusions RE-PERG is altered in early-stage AD, showing a reduced amplitude with high intrinsic phase variability. It also allows the discrimination of AD from VD. A high intrinsic variability in the PERG signal, determined using RE-PERG, may thus be a new promising test for neurodegenerative diseases.
Photo-Cleavable Peptide-Poly(Ethylene Glycol) Conjugate Surfaces for Light-Guided Control of Cell Adhesion

Photo-responsive cell attachment surfaces can simplify patterning and recovery of cells in microdevices for medicinal and pharmaceutical research. We developed a photo-responsive surface for controlling the attachment and release of adherent cells on a substrate under light-guidance. The surface comprises a poly(ethylene glycol) (PEG)-based photocleavable material that can conjugate with cell-adhesive peptides. Surface-bound peptides were released by photocleavage in the light-exposed region, where the cell attachment was subsequently suppressed by the exposed PEG. Simultaneously, cells selectively adhered to the peptide surface at the unexposed microscale region. After culture, the adhered and spread cells were released by exposure to a light with nontoxic dose level. Thus, the present surface can easily create both cell-adhesive and non-cell-adhesive regions on the substrate by single irradiation of the light pattern, and the adhered cells were selectively released from the light-exposed region on the cell micropattern without damage. This study shows that the photo-responsive surface can serve as a facile platform for the remote-control of patterning and recovery of adherent cells in microdevices.
Style Transfer with Neural Networks

Neural network models are powerful tools in the world of machine learning. In this paper I attempt to peel back the layers of complexity and examine the underlying math of this class of models. I extend this examination to convolutional neural networks and how they achieve state-of-the-art performance on image classiﬁcation problems. Finally, I apply convolutional neural networks to a problem called neural style transfer, which creates image combinations from diﬀerent content and style images.
Synthesis, Docking, Computational Studies, and Antimicrobial Evaluations of New Dipeptide Derivatives Based on Nicotinoylglycylglycine Hydrazide

Within a series of dipeptide derivatives (5–11), compound 4 was refluxed with d-glucose, d-xylose, acetylacetone, diethylmalonate, carbon disulfide, ethyl cyanoacetate, and ethyl acetoacetate which yielded 5–11, respectively. The candidates 5–11 were characterized and their biological activities were evaluated where they showed different anti-microbial inhibitory activities based on the type of pathogenic microorganisms. Moreover, to understand modes of binding, molecular docking was used of Nicotinoylglycine derivatives with the active site of the penicillin-binding protein 3 (PBP3) and sterol 14-alpha demethylase’s (CYP51), and the results, which were achieved via covalent and non-covalent docking, were harmonized with the biological activity results. Therefore, it was extrapolated that compounds 4, 7, 8, 9, and 10 had good potential to inhibit sterol 14-alpha demethylase and penicillin-binding protein 3; consequently, these compounds are possibly suitable for the development of a novel antibacterial and antifungal therapeutic drug. In addition, in silico properties of absorption, distribution, metabolism, and excretion (ADME) indicated drug likeness with low to very low oral absorption in most compounds, and undefined blood–brain barrier permeability in all compounds. Furthermore, toxicity (TOPKAT) prediction showed probability values for all carcinogenicity models were medium to pretty low for all compounds.
Health-related quality of life and multidimensional fitness profile in polio survivors

Abstract Purpose To assess and compare the HRQoL and physical fitness of polio survivors with healthy individuals. Methods Thirty-seven polio survivors and 40 healthy individuals were recruited in this cross-sectional study. The Fatigue Severity Scale (FSS) was used to evaluate participant’s level of fatigue; Short Form 36 (SF-36) was used for evaluating HRQoL, and hand-grip strength, lumbar trunk muscle endurance, flexibility, balance, and aerobic endurance were used as measures for physical fitness. Results Polio survivors had lower HRQoL in most of the dimensions of the SF-36, and they showed a lower level of physical fitness than controls. In particular, mobility-related variables were 20–40% lower in people with PP. Conclusions Subjects with PP had lower scores for the physical component of the HRQoL questionnaire, reduced physical fitness, increased fatigue, less mobility, and a higher fall risk than controls. The outcomes of the study can be useful to the design of future programs tailored specifically to improve the assessment of the physical fitness of subjects with paralytic polio and to facilitate interventions based on appropriate physical exercise regimens. Implications for rehabilitation Post-polio syndrome is a disabling disease that impacts in fitness, physical and psychological health-related quality of life of polio survivors. Polio survivors should undergo physical activity programs that focus on improving mainly their mobility and physical functioning (walking, self-care, and climbing stairs), thereby reducing fall risk and fatigue. Individual tailored physical exercise programs should be promoted in order to improve HRQoL in this population.
Religious-service attendance and subsequent health and well-being throughout adulthood: evidence from three prospective cohorts

Abstract Background Religious-service attendance has been linked with a lower risk of all-cause mortality, suicide and depression. Yet, its associations with other health and well-being outcomes remain less clear. Methods Using longitudinal data from three large prospective cohorts in the USA, this study examined the association between religious-service attendance and a wide range of subsequent physical health, health behaviour, psychological distress and psychological well-being outcomes in separate cohorts of young, middle-aged and older adults. All analyses adjusted for socio-demographic characteristics, prior health status and prior values of the outcome variables whenever data were available. Bonferroni correction was used to correct for multiple testing. Results Estimates combining data across cohorts suggest that, compared with those who never attended religious services, individuals who attended services at least once per week had a lower risk of all-cause mortality by 26% [95% confidence interval (CI): 0.65 to 0.84], heavy drinking by 34% (95% CI: 0.59 to 0.73) and current smoking by 29% (95% CI: 0.63 to 0.80). Service attendance was also inversely associated with a number of psychological-distress outcomes (i.e. depression, anxiety, hopelessness, loneliness) and was positively associated with psychosocial well-being outcomes (i.e. positive affect, life satisfaction, social integration, purpose in life), but was generally not associated with subsequent disease, such as hypertension, stroke, and heart disease. Conclusions Decisions on religious participation are generally not shaped principally by health. Nevertheless, for individuals who already hold religious beliefs, religious-service attendance may be a meaningful form of social integration that potentially relates to greater longevity, healthier behaviours, better mental health and greater psychosocial well-being.
A Noncanonical Hippo Pathway Regulates Spindle Disassembly and Cytokinesis During Meiosis in Saccharomyces cerevisiae

Meiosis in the budding yeast Saccharomyces cerevisiae is used to create haploid yeast spores from a diploid mother cell. During meiosis II, cytokinesis occurs by closure of the prospore membrane, a membrane that initiates at the spindle pole body and grows to surround each of the haploid meiotic products. Timely prospore membrane closure requires SPS1, which encodes an STE20 family GCKIII kinase. To identify genes that may activate SPS1, we utilized a histone phosphorylation defect of sps1 mutants to screen for genes with a similar phenotype and found that cdc15 shared this phenotype. CDC15 encodes a Hippo-like kinase that is part of the mitotic exit network. We find that Sps1 complexes with Cdc15, that Sps1 phosphorylation requires Cdc15, and that CDC15 is also required for timely prospore membrane closure. We also find that SPS1, like CDC15, is required for meiosis II spindle disassembly and sustained anaphase II release of Cdc14 in meiosis. However, the NDR-kinase complex encoded by DBF2/DBF20 MOB1 which functions downstream of CDC15 in mitotic cells, does not appear to play a role in spindle disassembly, timely prospore membrane closure, or sustained anaphase II Cdc14 release. Taken together, our results suggest that the mitotic exit network is rewired for exit from meiosis II, such that SPS1 replaces the NDR-kinase complex downstream of CDC15.
Epidemiology of SARS-CoV-2 in Egypt.

Background On 30 January 2020, the World Health Organization declared the novel severe acute respiratory syndrome coronavirus-2 to be a Public Health Emergency of International Concern. Egypt is among the five countries reporting the highest number of cases in Africa. Aims We aimed to provide an overview of the epidemic features of COVID-19 in Egypt in order to help guide an effective lockdown-exit strategy. Methods The incidence proportions, case fatality rates (CFR), growth rates, doubling time (Td), basic reproductive number (R0) and Herd Immunity Threshold (HIT) were calculated weekly and reviewed. Results As of 21 May 2020, the epidemic growth rate and R0 have decreased significantly; the averages (±SD) were 0.35 (±0.33) and 2.6 (±1.55) respectively. However, the incidence proportion has increased to 14 cases /100 000 population. Conclusion COVID-19 transmissibility has declined but the incidence rate has increased, underscoring that any lockdown-exit strategy should include measures to strengthen physical distancing, and case-based interventions to prevent an uncontrolled upsurge of COVID-19 cases.
Transfection of hPSC-Cardiomyocytes Using Viafect™ Transfection Reagent

Twenty years since their first derivation, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown promise in disease modelling research, while their potential for cardiac repair is being investigated. However, low transfection efficiency is a barrier to wider realisation of the potential this model system has to offer. We endeavoured to produce a protocol for improved transfection of hPSC-CMs using the ViafectTM reagent by Promega. Through optimisation of four essential parameters: (i) serum supplementation, (ii) time between replating and transfection, (iii) reagent to DNA ratio and (iv) cell density, we were able to successfully transfect hPSC-CMs to ~95% efficiencies. Transfected hPSC-CMs retained high purity and structural integrity despite a mild reduction in viability, and preserved compatibility with phenotyping assays of hypertrophy. This protocol greatly adds value to the field by overcoming limited transfection efficiencies of hPSC-CMs in a simple and quick approach that ensures sustained expression of transfected genes for at least 14 days, opening new opportunities in mechanistic discovery for cardiac-related diseases.
Posture and Time Arrangement Influence Shank Circumference Reduction When Performing Leg Raising Exercise

This study recruited nine young women who performed a leg raising exercise under six test combinations of three holding postures (lying supine, placing the shanks on a yoga ball, and elevating the legs at 60° against the wall) and two time arrangements (continuous vs. intermittent) for a period of 15 min. The intermittent arrangement included an additional 1-min rest set in the middle of the 15 min test. The participants’ shank circumference (SC) reductions and discomfort ratings were measured after each test combination was performed. Results indicated that the most efficient method for SC reduction was the yoga ball (5.4 mm), followed by the supine lying posture (4.6 mm) and wall-supported leg raising (3.1 mm). A significant interaction of posture × time arrangement (p < 0.01) implied that the yoga ball method combined with a 1-min rest produced the greatest SC reduction (6.7 mm). Our results also showed that participants experienced the greatest discomfort (score: 4.96) when performing wall-supported leg raising, compared with both lying supine (score: 1.34) and the yoga ball (score: 1.32). This study suggests that the effectiveness of leg raising as conventionally practiced for eliminating leg fatigue or swelling requires further consideration.
Broad proteomic screen reveals shared serum proteomic signature in patients with psoriatic arthritis and psoriasis without arthritis

Abstract Objective To identify novel serum proteins involved in the pathogenesis of PsA as compared with healthy controls, psoriasis (Pso) and AS, and to explore which proteins best correlated to major clinical features of the disease. Methods A high-throughput serum biomarker platform (Olink) was used to assess the level of 951 unique proteins in serum of patients with PsA (n = 20), Pso (n = 18) and AS (n = 19), as well as healthy controls (HC, n = 20). Pso and PsA were matched for Psoriasis Area and Severity Index (PASI) and other clinical parameters. Results We found 68 differentially expressed proteins (DEPs) in PsA as compared with HC. Of those DEPs, 48 proteins (71%) were also dysregulated in Pso and/or AS. Strikingly, there were no DEPs when comparing PsA with Pso directly. On the contrary, hierarchical cluster analysis and multidimensional scaling revealed that HC clustered distinctly from all patients, and that PsA and Pso grouped together. The number of swollen joints had the strongest positive correlation to ICAM-1 (r = 0.81, P < 0.001) and CCL18 (0.76, P < 0.001). PASI score was best correlated to PI3 (r = 0.54, P < 0.001) and IL-17 receptor A (r = –0.51, P < 0.01). There were more proteins correlated to PASI score when analysing Pso and PsA patients separately, as compared with analysing Pso and PsA patients pooled together. Conclusion PsA and Pso patients share a serum proteomic signature, which supports the concept of a single psoriatic spectrum of disease. Future studies should target skin and synovial tissues to uncover differences in local factors driving arthritis development in Pso.
$\alpha$-divergence Improves the Entropy Production Estimation via Machine Learning

Recent years have seen a surge of interest in the algorithmic estimation of stochastic entropy production (EP) from trajectory data via machine learning. A crucial element of such algorithms is the identification of a loss function whose minimization guarantees the accurate EP estimation. In this study, we show that there exists a host of loss functions, namely those implementing a variational representation of the $\alpha$-divergence, which can be used for the EP estimation. By fixing $\alpha$ to a value between $-1$ and $0$, the $\alpha$-NEEP (Neural Estimator for Entropy Production) exhibits a much more robust performance against strong nonequilibrium driving or slow dynamics, which adversely affects the existing method based on the Kullback-Leibler divergence ($\alpha = 0$). In particular, the choice of $\alpha = -0.5$ tends to yield the optimal results. To corroborate our findings, we present an exactly solvable simplification of the EP estimation problem, whose loss function landscape and stochastic properties give deeper intuition into the robustness of the $\alpha$-NEEP.
Low-level HIV viremia is associated with low antiretroviral prescription refill rates and social deprivation

ABSTRACT Optimal management of patients experiencing persistent low-level viremia (LLV) remains challenging and poorly understood. This study aimed to assess the association between poor antiretroviral treatment (ARV) adherence and persistent LLV. ADHELOW is a sub-study of the ECHEC cohort comprising HIV-infected adults with virological failure (viral load>50 copies/mL). Patients were recruited in 2013–2015 from 4 French university hospitals. Those with LLV (i.e., ≥2 viral load measurements between 50 and 500 copies/mL) were selected and matched on age and sex to 3 controls with virological suppression. The adherence rate was estimated using pharmacy-delivered prescription refills over one year. Overall, 60 patients were included (15 LLV and 45 controls). Mean age was 50.20 years, M/F sex ratio was 14 and mean EPICES (social deprivation) score was 42.90. In univariable analyses, LLV patients had significantly lower adherence (<80%: 53.30% vs. 6.67%, p < 0.01) and were more likely to have an EPICES score >40.2 (60.00% vs. 24.44%, p < 0.01). In multivariable analysis, these two variables remained significantly associated with LLV (OR 31.49, CI 95% [4.54–218.70]) and OR 11.00 (CI 95% [1.87–218.70], respectively). Poor long-term treatment adherence, estimated by prescription refills, was strongly associated with LLV. This reinforces the message that adherence counseling should be the primary intervention to overcome LLV.
Capturing Biologically Complex Tissue-Specific Membranes at Different Levels of Compositional Complexity

Plasma membranes (PMs) contain hundreds of different lipid species that contribute differently to overall bilayer properties. By modulation of these properties, membrane protein function can be affected. Furthermore, inhomogeneous lipid mixing and domains of lipid enrichment/depletion can sort proteins and provide optimal local environments. Recent coarse-grained (CG) Martini molecular dynamics efforts have provided glimpses into lipid organization of different PMs: an “Average” and a “Brain” PM. Their high complexity and large size require long simulations (∼80 μs) for proper sampling. Thus, these simulations are computationally taxing. This level of complexity is beyond the possibilities of all-atom simulations, raising the question—what complexity is needed for “realistic” bilayer properties? We constructed CG Martini PM models of varying complexity (63 down to 8 different lipids). Lipid tail saturations and headgroup combinations were kept as consistent as possible for the “tissues’” (Average/Brain) at three levels of compositional complexity. For each system, we analyzed membrane properties to evaluate which features can be retained at lower complexity and validate eight-component bilayers that can act as reliable mimetics for Average or Brain PMs. Systems of reduced complexity deliver a more robust and malleable tool for computational membrane studies and allow for equivalent all-atom simulations and experiments.
Comparison of the histological structure of the tibial nerve and its terminal branches in the fresh and fresh-frozen cadavers.

BACKGROUND The aim of this study was to compare the histological structure (cross-sectional area (CSA) and number of nerve fascicles) of the distal part of the tibial nerve (TN) and its terminal branches (medial plantar nerve [MPN], lateral plantar nerve [LPN]) in the fresh and fresh-frozen cadavers using computer assisted image analysis. MATERIALS AND METHODS The tibial nerve with terminal branches (medial and lateral plantar nerves) were dissected from the fresh and fresh-frozen cadavers. Each nerve was harvested 5 mm proximally and respectively 5 mm distally from the tibial nerve bifurcation, marked, dehydrated, embedded in paraffin, sectioned at 2 µm slices and stained with haematoxylin and eosin. Then the specimens were photographed and analyzed using Olympus cellSens software. RESULTS The fresh cadavers group comprised 60 feet (mean age 68.1 ± 15.2 years). The mean CSA and the number of nerve fascicles were respectively 15.25 ± 4.6 mm², 30.35 ± 8.45 for the tibial nerve, 8.76 ± 1.93 mm², 20.75 ± 7.04 for the medial plantar nerve and 6.54 ± 2.02 mm², 13.40 ± 5.22 for the lateral plantar nerve. The fresh-frozen cadavers group comprised 21 feet (mean age 75.1 ± 9.0 years). The mean CSA and the number of nerve fascicles were respectively 13.71 ± 5.66 mm², 28.57 ± 8.00 for the tibial nerve, 7.55 ± 3.25 mm², 18.00 ± 6.72 for the medial plantar nerve and 4.29 ± 1.93 mm², 11.33 ± 1.93 for the lateral plantar nerve. Only lateral plantar nerves showed statistical differences in the CSA and the number of nerve fascicles between examined groups (p = 0.000, p = 0.037 respectively). A positive correlation was found between donors age and tibial nerve CSA in the fresh cadavers group (r = 0.44, p = 0.000). A statistical difference was found between the medial and lateral plantar nerves both in the CSA and the number of nerve fascicles ( p < 0.001, p < 0.001 respectively). CONCLUSIONS The CSA and the number of nerve fascicles of the tibial and medial plantar nerves were similar in the fresh and fresh-frozen cadavers whilst different in the lateral plantar nerve. The tibial nerve showed increasing CSA with the advanced age in the fresh cadavers. The medial plantar nerve had larger CSA and more nerve fascicles than the lateral plantar nerve.
The Crystallization Mechanism of Zr-Based Bulk Metallic Glass during Electron Beam Remelting

Bulk metallic glasses (BMGs) are promising for multifunctional and structural application in different industries. However, the limited size of BMGs hinders their further application. The welding of BMGs has shown the possibility of getting rid of the casting size limitation. The heat-affected zone (HAZ) and fusion zone (FZ) often undergo severe crystallization during the welding process. It is still unclear whether the crystallization occurs during the heating process or the cooling process. To figure out the crystallization mechanisms of Zr-based BMGs during the electron beam welding process, the Zr-based BMGs with the composition of Zr41.2Ti13. 8Cu12.5Ni10Be22. 5 were remelted by electron beam. The microstructures of the HAZ and the remelting zone (RZ) were analyzed. The thermal field of the electron beam welding was obtained by the finite element method (FEM). The critical conditions for crystallization during the heating and cooling processes were obtained by differential scanning calorimetry (DSC) and the Kissinger equation. The results show that the Zr41.2Ti13. 8Cu12.5Ni10Be22. 5 in the HAZ undergoes severe crystallization, while the Zr41.2Ti13. 8Cu12.5Ni10Be22. 5 in RZ keeps amorphous state after the remelting process. The low cooling rate in the HAZ is responsible for its crystallization.