Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrochemical Biosensors Based on S-Layer Proteins

Designing and development of electrochemical biosensors enable molecule sensing and quantification of biochemical compositions with multitudinous benefits such as monitoring, detection, and feedback for medical and biotechnological applications. Integrating bioinspired materials and electrochemical techniques promote specific, rapid, sensitive, and inexpensive biosensing platforms for (e.g., point-of-care testing). The selection of biomaterials to decorate a biosensor surface is a critical issue as it strongly affects selectivity and sensitivity. In this context, smart biomaterials with the intrinsic self-assemble capability like bacterial surface (S-) layer proteins are of paramount importance. Indeed, by forming a crystalline two-dimensional protein lattice on many sensors surfaces and interfaces, the S-layer lattice constitutes an immobilization matrix for small biomolecules and lipid membranes and a patterning structure with unsurpassed spatial distribution for sensing elements and bioreceptors. This review aims to highlight on exploiting S-layer proteins in biosensor technology for various applications ranging from detection of metal ions over small organic compounds to cells. Furthermore, enzymes immobilized on the S-layer proteins allow specific detection of several vital biomolecules. The special features of the S-layer protein lattice as part of the sensor architecture enhances surface functionalization and thus may feature an innovative class of electrochemical biosensors.
Antimicrobial Activity and Mechanism of Action of the Amaranthus tricolor Crude Extract against Staphylococcus aureus and Potential Application in Cooked Meat

Amaranthus tricolor has been reported to contain some antimicrobial compounds, such as alkaloids, polyphenols, and terpenoids. However, its effect on Staphylococcus aureus has been less well researched. Therefore, this study was designed to evaluate the antimicrobial activity and possible mechanism of action of the Amaranthus tricolor crude extract (ATCE) against S. aureus and potential application in cooked meat. The antimicrobial activity against S. aureus was assessed by disk diffusion, minimum inhibitory concentration (MIC) determinations, and growth curve. The changes of bacterial membrane potential, intracellular pH (pHin), content of bacterial protein and DNA, and cell morphology were measured to indicate its antimicrobial mechanism of action. The effects of different concentrations of ATCE on bacterial counts, pH, and color of lean cooked pork during 6 d storage were assessed. The results showed that the diameter of inhibition zone (DIZ) and MIC of ATCE against S. aureus were 12.63 ± 0.34 to 12.94 ± 0.43 mm and 80 mg/mL, respectively. The mechanism of action of ATCE against S. aureus was associated with cell membrane depolarization, reduction of pHin, decrease of bacterial protein content, cleavage of cell DNA, and leakage of cytoplasm. Besides, ATCE resulted in a reduction of 1.02 log CFU/g from 3 log CFU/g in S. aureus-inoculated lean cooked pork. The pH values of lean cooked pork treated with ATCE did not show significant changes as the storage time increased, but there was a slight and significant decrease seen with the application of 1 and 2 MIC of ATCE. After treating with ATCE, the color of lean cooked pork showed less lightness (L*), more redness (a∗), similar yellowness (b*), stronger chroma (C*), and weaker hue angle (h*) during 6 days of storage. Therefore, these findings indicate that ATCE has antimicrobial activities against S. aureus and possesses latent energy to become a natural preservative to maintain the quality of lean cooked pork.
ECE2 regulates neurogenesis and neuronal migration during human cortical development

During embryonic development, excitatory projection neurons migrate in the cerebral cortex giving rise to organised layers. Periventricular heterotopia (PH) is a group of aetiologically heterogeneous disorders in which a subpopulation of newborn projection neurons fails to initiate their radial migration to the cortex, ultimately resulting in bands or nodules of grey matter lining the lateral ventricles. Although a number of genes have been implicated in its cause, currently they only satisfactorily explain the pathogenesis of the condition for 50% of patients. Novel gene discovery is complicated by the extreme genetic heterogeneity recently described to underlie its cause. Here, we study the neurodevelopmental role of endothelin‐converting enzyme‐2 (ECE2) for which two biallelic variants have been identified in two separate patients with PH. Our results show that manipulation of ECE2 levels in human cerebral organoids and in the developing mouse cortex leads to ectopic localisation of neural progenitors and neurons. We uncover the role of ECE2 in neurogenesis, and mechanistically, we identify its involvement in the generation and secretion of extracellular matrix proteins in addition to cytoskeleton and adhesion.
THE EFFECTS OF CIGARETTE SMOKING ON GLYCOSYLATED HEMOGLOBIN (HbA1C) IN NON-DIABETIC INDIVIDUALS

Abstract : Background Cigarette smoking is associated with an increased risk of Type 2 diabetes mellitus. Cigarette smoking is known to cause a transient elevation in blood glucose concentration. Glycosylated hemoglobin (HbA1c) is a marker of long-term glucose homeostasis reflecting an average blood glucose concentration in past 2-3 months. The effect of cigarette smoking on average blood glucose levels as measured by glycosylated hemoglobin have yet received little attention. Aim and Objective This study was done to assess the effect of smoking on blood glucose concentration by comparing glycosylated hemoglobin (HbA1c) between non-diabetic c igarette smokers and nonsmokers. Materials and Methods This is a cross sectional case control study involving 60 participants. Of them case group consists of 30 non-obese, non-diabetic males of age group between 20-40 years who smoke 10 filter cigarettes per day or more for not less than 5 years. 30 healthy age matched non-obese males who do not smoke cigarette were recruited for control group. After an overnight fast of 12 hours the serum glucose concentration and the glycosylated hemoglobin levels were estimated in all subjects and the values were compared between the cases and control using students t test.Results There is no significant increase in the fasting serum glucose levels between the cases100.212. 37 and the controls 103.19. 64. There is a significant increase in the glycosylated hemoglobin level in smokers 5.480. 83 when compared with the non-smokers 4.560. 34 with p-value 0.001. Conclusion The results from the present study suggest that the level of glycosylated hemoglobin is increased in the non-diabetic smokers when compared to the non-smokers. Keyword :Key wordsCigarette smokers, non-smokers, non-diabetic, glycosylated hemoglobin.
The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.
Differences in hypertension phenotypes between Africans and Europeans: role of environment.

OBJECTIVES Hypertension phenotypes differ between Africans and Europeans, with a greater prevalence of low renin salt-sensitive hypertension and greater predisposition to adverse cardiac remodelling in Africans. To elucidate the roles of inheritance and environment in determining hypertension phenotypes in sub-Saharan Africans and white Europeans, we compared phenotypes in white individuals in the UK (n = 132) and in African individuals in the UK (n = 158) and Nigeria (n = 179). METHODS Biochemistry, blood pressure, left ventricular structure (echocardiography) and 24-h urinary collections of sodium and potassium were measured. RESULTS Twenty-four-hour urinary sodium/potassium ratio was lower in individuals living in Europe (both African and white: 2.32 ± 0.15 and 2.28 ± 0.17) than in individuals in Nigeria (4.09 ± 0.26, both P < 0.001) reflecting proportionately higher potassium intake in Europeans (African or white) than African residents. Plasma renin was lower in Africans irrespective of residency than white Europeans, but aldosterone was higher in Africans in Europe than those in Africa (466.15 ± 32.95 vs. 258.60 ± 17.42 pmol/l, P < 0.001). Left ventricular mass index adjusted for blood pressure and other confounders was greatest in Africans in Europe (103.27 ± 2.32 g/m) compared with those in Africa (89.28 ± 1.98 g/m) or white Europeans (86.77 ± 2.63 g/m, both P < 0.001). CONCLUSION Despite a similar low renin state in African origin individuals living in Europe and Africa, a higher aldosterone level, possibly related to higher potassium intake or other environmental factors, may contribute to greater cardiac remodelling in Africans in Europe.
Solver–Critic: A Reinforcement Learning Method for Discrete-Time-Constrained-Input Systems

In this article, a solver–critic (SC) architecture is developed for optimal control problems of discrete-time (DT)-constrained-input systems. The proposed design consists of three parts: 1) a critic network; 2) an action solver; and 3) a target network. The critic network first approximates the action-value function using the sum-of-squares (SOS) polynomial. Then, the action solver adopts the SOS programming to obtain control inputs within the constraint set. The target network introduces the soft update mechanism into policy evaluation to stabilize the learning process. By using the proposed architecture, the constrained-input control problem can be solved without adding the nonquadratic functionals into the reward function. In this article, the theoretical analysis of the convergence property is presented. Besides, the effects of both different initial $Q$ -functions and different discount factors are investigated. It is proven that the learned policy converges to the optimal solution of the Hamilton–Jacobi–Bellman equation. Four numerical examples are provided to validate the theoretical analysis and also demonstrate the effectiveness of our approach.
Identification of Putative Early Atherosclerosis Biomarkers by Unsupervised Deconvolution of Heterogeneous Vascular Proteomes.

Coronary artery disease remains a leading cause of death in industrialized nations, and early detection of disease is a critical intervention target in order to effectively treat patients and manage risk. Proteomic analysis of mixed tissue homogenates may obscure subtle protein changes that occur uniquely in underlying tissue subtypes. The unsupervised 'convex analysis of mixtures' (CAM) tool has previously been shown to effectively segregate cellular subtypes from mixed expression data. In this study, we hypothesized that CAM would identify proteomic information specifically informative to early atherosclerosis lesion involvement that could lead to potential markers of early disease detection. We quantified the proteome of 99 paired Abdominal Aorta (AA) and Left Anterior Descending Coronary Artery (LAD) specimens (N=198 specimens total) acquired during autopsy of young adults free of diagnosed cardiac disease. The CAM tool was then used to segregate protein subsets uniquely associated with different underlying tissue types, yielding markers of normal and fibrous plaque (FP) tissues in LAD and AA (N=62 lesions markers). CAM-derived FP marker expression was validated against pathologist estimated luminal surface involvement of FP, as well as in an orthogonal cohort of 'pure' fibrous plaque, fatty streak, and normal vascular specimens. A targeted mass spectrometry (MS) experiment quantified 39 of 62 CAM-FP markers in plasma from women with angiographically verified coronary artery disease (CAD, N=46) or free from apparent CAD (control, N=40). Elastic net variable selection with logistic regression reduced this list to 10 proteins capable of classifying CAD status in this cohort with <6% misclassification error, and a mean area under the receiver operating characteristic curve of 0.992 (Confidence Interval 0.968-0.998) after cross validation. The proteomics-CAM workflow identified lesion-specific molecular biomarker candidates by distilling the most representative molecules from heterogenous tissue types.
Anti-Breast Cancer Activities of 8-Hydroxydaidzein by Targeting Breast Cancer Stem-Like Cells.

PURPOSE Cancer stem cells (CSCs) play an important role in various stages of cancer development and therapy refractoriness. 8-Hydroxydaidzein (8-OHD) has revealed anti-cancer activity in different tumors. Accordingly, we aimed to assess the effects of 8-OHD on the suppression of breast cancer stem-like cells (BCSCs). METHODS The anti-proliferative and pro-apoptotic properties of 8-OHD were examined by MTS assay and flowcytometry. The expression levels of stemness markers and JAK2/STAT proteins were measured by quantitative real time-PCR (qRT-PCR) and western blotting, respectively. RESULTS 8-OHD significantly decreased three out of six stemness markers and remarkably reduced viability and induced apoptosis of spheroidal and parental cells compared to controls. Further experiments using CD95L, as a death ligand, and ZB4 antibody, as an extrinsic apoptotic pathway blocker, showed that 8-OHD induced apoptosis through the intrinsic pathway, proposing a mechanism by which 8-OHD triggers apoptosis. Results of western blot analysis also revealed a marked decline in the phosphorylation of JAK2 and STAT proteins. CONCLUSION Our study, for the first time, elucidated an anti-BCSC activity for 8-OHD via decreasing stemness markers, inducing toxicity and stimulating apoptosis in these cells and parental cells. Our results also suggested a novel mechanism by which 8-OHD induces apoptosis in BCSCs.
Intrathecal transplantation of autologous bone marrow mononuclear cells in patients with sub-acute and chronic spinal cord injury: An open-label study

Objective: The objective of the study was to analyze the effect of intrathecal transplantation of autologous bone marrow-derived mononuclear cells (BMMNCs) in functional recovery of spinal cord injury (SCI) patients along with neurorehabilitation and to evaluate various factors influencing the outcome of cellular therapy. Methods: We conducted an open-label study including 180 sub-acute and chronic SCI patients. All patients received intrathecal autologous BMMNCs along with neurorehabilitation. 80–100 mL of bone marrow was aspirated and BMMNCs were obtained using density gradient separation. An average of 1.06 × 108 cells with 97% viability was administered through lumbar puncture immediately. After transplantation, all patients underwent neurorehabilitation. Patients were followed up after an average of 9 ± 7 months. They were assessed for functional symptomatic changes and the outcome measures used were functional independence measure (FIM) and walking index for SCI (WISCI). Results: Patients showed symptomatic improvement in sitting/standing balance, bed mobility, trunk stability, upper limb function, mobility, sensation, bowel/bladder functions, and activities of daily living with no serious adverse events. Scores on FIM and WISCI showed statistically significant improvement. On subgroup analysis, it was found that early intervention and more than one dose of BMMNCs demonstrate a better functional outcome. Younger patients demonstrated better improvements in functional independence. Both cervical and dorsolumbar levels of injury show significant improvements in motor and sensory deficits. Conclusions: Autologous BMMNC transplantation with neurorehabilitation is safe, effective, enhances functional recovery, and improves the quality of life of SCI patients in sub-acute and chronic stage.
Radiation in the Treatment of Oligometastatic and Oligoprogressive Disease

Abstract The use of local ablative therapy or metastasis-directed therapy is an emerging management paradigm in oligometastatic and oligoprogressive cancer. Recent randomized evidence has demonstrated that stereotactic ablative radiotherapy (SABR) targeting all metastatic deposits is tolerable and can improve progression-free and overall survival. While SABR is noninvasive, minimally toxic, and generally safe, rare grade 5 events have been reported. Given this and recognizing the often-uncertain prognosis of patients with metastatic disease, equipoise persists regarding the therapeutic window within which to deploy SABR for this indication. Ongoing phase III trials are aimed at validating the demonstrated safety, tolerability, and survival benefits while also refining patient selection, possibly with the aid of novel biomarkers. This narrative review of the role of SABR in oligometastatic and oligoprogressive disease summarizes recent randomized evidence and ongoing clinical trials, discusses our rationale for treatment and key management principles, and posits that SABR should be considered the preferred modality for multisite, metastasis-directed ablative therapy.
Predicting Glioblastoma Recurrence from Preoperative MR Scans Using Fractional-Anisotropy Maps with Free-Water Suppression

Diffusion tensor imaging (DTI), and fractional-anisotropy (FA) maps in particular, have shown promise in predicting areas of tumor recurrence in glioblastoma. However, analysis of peritumoral edema, where most recurrences occur, is impeded by free-water contamination. In this study, we evaluated the benefits of a novel, deep-learning-based approach for the free-water correction (FWC) of DTI data for prediction of later recurrence. We investigated 35 glioblastoma cases from our prospective glioma cohort. A preoperative MR image and the first MR scan showing tumor recurrence were semiautomatically segmented into areas of contrast-enhancing tumor, edema, or recurrence of the tumor. The 10th, 50th and 90th percentiles and mean of FA and mean-diffusivity (MD) values (both for the original and FWC–DTI data) were collected for areas with and without recurrence in the peritumoral edema. We found significant differences in the FWC–FA maps between areas of recurrence-free edema and areas with later tumor recurrence, where differences in noncorrected FA maps were less pronounced. Consequently, a generalized mixed-effect model had a significantly higher area under the curve when using FWC–FA maps (AUC = 0.9) compared to noncorrected maps (AUC = 0.77, p < 0.001). This may reflect tumor infiltration that is not visible in conventional imaging, and may therefore reveal important information for personalized treatment decisions.
Formulation and evaluation of floating matrix tablets of acyclovir

A controlled drug delivery system is usually designed to deliver the drug at particular rate. Safe and effective blood levels are maintained for a period as long as the system continues to deliver the drug. Controlled drug delivery usually results in substantially constant blood levels of the active ingredient as compared to the uncontrolled fluctuations observed when multiple doses of quick releasing conventional dosage forms are administered to a patient [1].
Dialogue Journal as a Significant Technique In Teaching Writing Composition

This study tries to investigate the impact of using a new strategy (Dialogue Journal) (DJ) in teaching writing in English as a foreign language. It is a broad composition book in which each student carries on a private written conversation with the teacher for an extended period of time (school year ،semester). The (DJ) is intended to improve the students' skills in writing through providing them with opportunities to learn by writing and be in touch with their teachers and peers. It is hypothesized that there is no statistical significant difference between the achievement scores of the students who are taught by using the paragraph pattern method (PPM) (traditional method) and those who are taught by using (DJ) according to their – and post – tests results. To achieve the hypothesis of the study ،the researcher designed a pre – test to comprehend the level of the students in writing and a post – test to discover the impact of using the new technique in writing. The second year students of the English Department ،College of Basic Education/ University of Babylon are the subjects of the study. The experimental design of the study comprises two groups ،i.e ،a control group and an experimental group.Each group consists of (40) students. The experiment has started on the 15th March ،2010 and ended on the 15th May 2011. The experimental group is taught by the researcher himself. T. test formula is used to analyze the data. It is found that there is a significant statistical difference between the two groups in favour at the of the experimental group i.e the students of the experimental group are better than those of the control group. This indicates that teaching writing by using (DJ) is more effective than teaching by traditional ones.
Transition from Pediatric to Adult HIV Care for Young Women Living with HIV

Transitioning from pediatric to adult care is a complicated process for youth with chronic illnesses. This study elucidates the unique factors affecting transition preparedness and perception of adult HIV care among a cohort of young women with HIV. Between 2013 and 2015, 48 women with HIV, who had experience with pediatric HIV care, were enrolled in a large Canadian cohort study. Variables were self-reported during peer-administered surveys. Only 60% reported feeling prepared for transition. Having never had contact with child protection services (P = .049), never been in foster care (P = .011), never been in a group home (P = .036), reporting a higher current CD4 count (P = .033), and reporting a younger ideal age for transition (P = .041) were associated with transition preparedness. Eighty-four percent reported equivalent or better HIV care following transition. Correlates of equivalent/better care following transition included lower personal income (P = .023), higher CD4 count (P = .021), care by an adult infectious diseases specialist (P = .002), and transition preparedness (P = .005). Our findings highlight the importance of adequate transition preparation and its effect on perception of care following transition.