Miracle-dz/UniFAR-FTUs huggingface dataset:
Research Advances in the Use of Bioactive Compounds from Vitis vinifera By-Products in Oral Care

Oral health is considered an important factor of general health and it contributes to the quality of life. Despite the raising awareness of preventive measures, the prevalence of oral health conditions continues to increase. In this context, a growing interest in investigating natural resources like Vitis vinifera (V. vinifera) phenolic compounds (PhCs) as oral health promoters has emerged. This paper aims to review the evidence about the bioactivities of V. vinifera by-products in oral health. Up to date, a high number of studies have thoroughly reported the antimicrobial and antiplaque activity of V. vinifera extracts against S. mutans or in multi-species biofilms. Moreover, the bioactive compounds from V. vinifera by-products have been shown to modulate the periodontal inflammatory response and the underlying oxidative stress imbalance induced by the pathogenic bacteria. Considering these beneficial effects, the utility of V. vinifera by-products in the maintaining of oral health and the necessary steps towards the development of oral care products were emphasized. In conclusion, the high potential of V. vinifera by-products could be valorized in the development of oral hygiene products with multi-target actions in the prevention and progression of several oral conditions.
Development of a VLP-Based Vaccine Displaying an xCT Extracellular Domain for the Treatment of Metastatic Breast Cancer

Metastatic breast cancer (MBC) is the leading cause of cancer death in women due to recurrence and resistance to conventional therapies. Thus, MBC represents an important unmet clinical need for new treatments. In this paper we generated a virus-like particle (VLP)-based vaccine (AX09) to inhibit de novo metastasis formation and ultimately prolong the survival of patients with MBC. To this aim, we engineered the bacteriophage MS2 VLP to display an extracellular loop of xCT, a promising therapeutic target involved in tumor progression and metastasis formation. Elevated levels of this protein are observed in a high percentage of invasive mammary ductal tumors including triple negative breast cancer (TNBC) and correlate with poor overall survival. Moreover, xCT expression is restricted to only a few normal cell types. Here, we tested AX09 in several MBC mouse models and showed that it was well-tolerated and elicited a strong antibody response against xCT. This antibody-based response resulted in the inhibition of xCT’s function in vitro and reduced metastasis formation in vivo. Thus, AX09 represents a promising novel approach for MBC, and it is currently advancing to clinical development.
Megalencephalic Leukoencephalopathy with Subcortical Cysts Disease-Linked MLC1 Protein Favors Gap-Junction Intercellular Communication by Regulating Connexin 43 Trafficking in Astrocytes

Astrocytes, the most numerous cells of the central nervous system, exert critical functions for brain homeostasis. To this purpose, astrocytes generate a highly interconnected intercellular network allowing rapid exchange of ions and metabolites through gap junctions, adjoined channels composed of hexamers of connexin (Cx) proteins, mainly Cx43. Functional alterations of Cxs and gap junctions have been observed in several neuroinflammatory/neurodegenerative diseases. In the rare leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC), astrocytes show defective control of ion/fluid exchanges causing brain edema, fluid cysts, and astrocyte/myelin vacuolation. MLC is caused by mutations in MLC1, an astrocyte-specific protein of elusive function, and in GlialCAM, a MLC1 chaperon. Both proteins are highly expressed at perivascular astrocyte end-feet and astrocyte-astrocyte contacts where they interact with zonula occludens-1 (ZO-1) and Cx43 junctional proteins. To investigate the possible role of Cx43 in MLC pathogenesis, we studied Cx43 properties in astrocytoma cells overexpressing wild type (WT) MLC1 or MLC1 carrying pathological mutations. Using biochemical and electrophysiological techniques, we found that WT, but not mutated, MLC1 expression favors intercellular communication by inhibiting extracellular-signal-regulated kinase 1/2 (ERK1/2)-mediated Cx43 phosphorylation and increasing Cx43 gap-junction stability. These data indicate MLC1 regulation of Cx43 in astrocytes and Cx43 involvement in MLC pathogenesis, suggesting potential target pathways for therapeutic interventions.
Grief symptoms and primary care use: a prospective study of family caregivers

Background Family caregivers to patients who are severely ill have high use of primary health care and psychotropic medication. However, it remains sparsely investigated whether healthcare services target the most vulnerable caregivers. Aim This study aimed to examine associations between family caregivers’ grief trajectories of persistent high-grief symptom level (high-grief trajectory) versus persistent low-grief symptom level (low-grief trajectory), as well as early contacts with GPs or psychologists and the use of psychotropic medication. Design & setting A population-based cohort study of family caregivers (n = 1735) in Denmark was undertaken. Method The Prolonged Grief-13 (PG-13) scale measured family caregivers’ grief symptoms at inclusion (during the patient's terminal illness), 6 months after bereavement, and 3 years after bereavement. Multinomial regression was used to analyse register-based information on GP consultations, psychologist sessions, and psychotropic medication prescriptions in the 6 months before inclusion. Results A total of 1447 (83.4%) family caregivers contacted their GP, and 91.6% of participants in the high-grief trajectory had GP contact. Compared with family caregivers in the low-grief trajectory, family caregivers in the high-grief trajectory had ≥4 face-to-face GP consultations (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.3 to 5.0), more GP talk therapy (OR =4.4; 95% CI = 1.9 to 10.0), and more psychotropic medication, but not significantly more psychologist sessions (OR = 1.7; 95% CI = 0.5 to 6.6). Conclusion Family caregivers in the high-grief trajectory had more contact with their GP, but their persisting grief symptoms suggest that primary care interventions for family caregivers should be optimised. Future research is warranted in such interventions and in the referral patterns to specialised mental health care.
Application of erythrocyte lysing buffer (ELB) has detrimental effects on human sperm quality parameters, DNA fragmentation and chromatin structure

Erythrocyte lysing buffer (ELB) facilitates the search for spermatozoa by eliminating erythrocytes in testicular suspension used during the ICSI procedure. This study investigates the effects of ELB on sperm quality parameters, sperm chromatin and sperm DNA fragmentation. Normal ejaculations were used as the model for testicular spermatozoa in this study. After swim‐up, the sperm pellets were divided into two parts. Part I, the control (Group A), was diluted with culture media; and Part II, the intervention group (Group B), was diluted with ELB for 10 min. After centrifugation in both groups, the sperm pellets were re‐suspended with culture media. The samples were immediately evaluated (A0 and B0) and then evaluated again after 1 hr (A1 and B1). The results indicated ELB decreased the progressive motility (81.60 ± 8.69 vs. 64.69 ± 19.08) and viability (97.62 ± 3.02 vs. 85.91 ± 11.46), in Group A and B, respectively, both immediately and 1 hr after preparation. Also, ELB engendered a significant increase in the DNA fragmentation index both immediately (9.68 ± 3.55 vs. 14.38 ± 6.52) and after 1 hr (10.37 ± 5.03 vs. 19.38 ± 6.39). In conclusion, ELB may damage sperm cells, shown by a decreased motility and viability, and it increased DNA fragmentation. Therefore, the use of ELB in testicular semen handling should be discouraged.
Does the phylogeny of pelomedusoid turtles reflect vicariance due to continental drift?

The turtle hyperfamily Pelomedusoides has been long regarded as one of the best reptilian examples of the shared biological history of Africa and South America, and of vicariance due to continental drift. The currently accepted phylogeny of the Pelomedusoides is based on morphological and serological evidence. This study uses molecular data to examine the relationships within the Pelomedusoides and tests the hypothesis that the speciation within this group was caused by the separation of the Gondwanan continents.
Longitudinal Associations Between Body Mass Index During Young Adulthood, Subsequent Weight Change, and Incident Diabetes During Mid- and Older-Adulthood in Non-Hispanic White and African American Populations: The Atherosclerosis Risk in Communities Study.

Background: Excess body mass index (BMI) and weight gain are well-known risk factors for diabetes. Nevertheless, the associations of BMI and weight gain in young adulthood with subsequent diabetes in African Americans, and the standardized effects of these weight variables have not been well studied. Methods: We studied 12,672 white and African American men and women 45-64 years of age (i.e., during mid-adulthood) who participated in the Atherosclerosis Risk in Communities Study visit 1 (1987-1989), and were reexamined at three follow-up examinations. Associations between recalled BMI at age 25 (i.e., during young adulthood) and subsequent weight change with incident diabetes at ages 45 and above (i.e., during mid-adulthood to older adulthood) were examined using Cox proportional hazard models. Results: Over the 9-year follow-up, we identified 1,501 cases of incident diabetes. The incidence rates were higher among African Americans (men: 24.5 and women: 26.3 per 1,000 person-years) compared to whites (men: 16.3 and women: 10.5 per 1,000 person years). Compared to normal-weight individuals at age 25, those who were overweight or obese and those who gained more weight after age 25 had a higher risk of developing diabetes later in all four race-sex groups with the highest risk in African Americans. In the race-sex groups combined, the mutually adjusted hazard ratio for BMI at age 25 and percent weight change were 1.97 (1.79-2.17) and 2.89 (2.59-3.11), respectively, comparing the 85th to the 15th percentiles of the exposures. Conclusions: African Americans were at higher risk of diabetes than whites. Both higher BMI at age 25 and subsequent weight gain were independently associated with higher risk for diabetes in all the race-sex groups; however, overall weight gain was more potent than BMI.
Interocular asymmetry of foveal avascular zone morphology and parafoveal capillary density in sickle cell retinopathy

Objectives To examine interocular asymmetry of foveal avascular zone (FAZ) and parafoveal capillary density metrics in sickle cell retinopathy (SCR) using optical coherence tomography angiography (OCT-A). Methods This cross-sectional, retrospective study evaluated SCR patients and unaffected controls who underwent 3x3mm macular OCT-A imaging using a spectral domain-OCT system. FAZ (area, perimeter, and acircularity index) and parafoveal capillary density metrics were computed for both eyes of each participant. In unaffected controls, interocular difference in FAZ and parafoveal capillary density metrics were evaluated using Bland-Altman plots. SCR patients with interocular difference outside the upper 97.5% and lower 2.5% limits of agreement from controls were defined as having interocular asymmetry. Area under receiver operating characteristic curve (AROC) was also performed to determine the ability of the absolute interocular difference to differentiate between subjects with SCR—including non-proliferative SCR (NP-SCR) and proliferative SCR (P-SCR)–and unaffected controls. Results Thirty-one patients with SCR (21 NP-SCR and 10 P-SCR) and 14 race-matched and age-matched controls were included for analysis. Interocular asymmetry was seen for all FAZ and parafoveal capillary density metrics in NP-SCR and P-SCR subjects. SCR subjects showed greater disease severity in the left-eye for FAZ and parafoveal capillary density metrics. Conclusions NP-SCR and P-SCR patients demonstrated quantifiable interocular asymmetry in FAZ and parafoveal capillary density metrics compared to unaffected subjects, with left-eye predominance in disease severity.
Pharmacogenetic considerations when prescribing cholinesterase inhibitors for the treatment of Alzheimer’s disease

ABSTRACT Introduction Cholinergic dysfunction, demonstrated in the late 1970s and early 1980s, led to the introduction of acetylcholinesterase inhibitors (AChEIs) in 1993 (Tacrine) to enhance cholinergic neurotransmission as the first line of treatment against Alzheimer’s disease (AD). The new generation of AChEIs, represented by Donepezil (1996), Galantamine (2001) and Rivastigmine (2002), is the only treatment for AD to date, together with Memantine (2003). AChEIs are not devoid of side-effects and their cost-effectiveness is limited. An option to optimize the correct use of AChEIs is the implementation of pharmacogenetics (PGx) in the clinical practice. Areas covered (i) The cholinergic system in AD, (ii) principles of AD PGx, (iii) PGx of Donepezil, Galantamine, Rivastigmine, Huperzine and other treatments, and (iv) practical recommendations. Expert opinion The most relevant genes influencing AChEI efficacy and safety are APOE and CYPs. APOE-4 carriers are the worst responders to AChEIs. With the exception of Rivastigmine (UGT2B7, BCHE-K), the other AChEIs are primarily metabolized via CYP2D6, CYP3A4, and UGT enzymes, with involvement of ABC transporters and cholinergic genes (CHAT, ACHE, BCHE, SLC5A7, SLC18A3, CHRNA7) in most ethnic groups. Defective variants may affect the clinical response to AChEIs. PGx geno-phenotyping is highly recommended prior to treatment.
The Effects of Improved Nutrition in Early Childhood on Adolescent and Early Adulthood Body Size, Composition, Maturity, and Function: Results From the First INCAP Follow-Up Study

The first follow-up study of the original Institute of Nutrition of Central America and Panama Longitudinal Study was conducted in 1988 to 1989 when participants were between the ages of 11 and 27 years. The longer term effects of the original supplementation in early life of either high protein and energy, Atole, or no protein and low energy, Fresco, were seen in anthropometry, skeletal maturation, physical work capacity, and intellectual development, with maximum benefit seen in those participants who had maximum exposure to the supplementation during prenatal and early postnatal years. No effects were observed in bone mineralization and menarche. The long-term positive effects are consistent with the promotion of improved nutrition during the first 1000 days and established the foundation for further follow-up studies as the participants move into adulthood and further develop their human capital.
Antimicrobial Resistance Surveillance in Low- and Middle-Income Countries: Progress and Challenges in Eight South Asian and Southeast Asian Countries

Antimicrobial resistance (AMR) is a serious global health threat and is predicted to cause significant health and economic impacts, particularly in low- and middle-income countries (LMICs). AMR surveillance is critical in LMICs due to high burden of bacterial infections; however, conducting AMR surveillance in resource-limited settings is constrained by poorly functioning health systems, scarce financial resources, and lack of skilled personnel. In 2015, the United Nations World Health Assembly endorsed the World Health Organization’s Global Action Plan to tackle AMR; thus, several countries are striving to improve their AMR surveillance capacity, including making significant investments and establishing and expanding surveillance networks. SUMMARY Antimicrobial resistance (AMR) is a serious global health threat and is predicted to cause significant health and economic impacts, particularly in low- and middle-income countries (LMICs). AMR surveillance is critical in LMICs due to high burden of bacterial infections; however, conducting AMR surveillance in resource-limited settings is constrained by poorly functioning health systems, scarce financial resources, and lack of skilled personnel. In 2015, the United Nations World Health Assembly endorsed the World Health Organization’s Global Action Plan to tackle AMR; thus, several countries are striving to improve their AMR surveillance capacity, including making significant investments and establishing and expanding surveillance networks. Initial data generated from AMR surveillance networks in LMICs suggest the high prevalence of resistance, but these data exhibit several shortcomings, such as a lack of representativeness, lack of standardized laboratory practices, and underutilization of microbiology services. Despite significant progress, AMR surveillance networks in LMICs face several challenges in expansion and sustainability due to limited financial resources and technical capacity. This review summarizes the existing health infrastructure affecting the establishment of AMR surveillance programs, the burden of bacterial infections demonstrating the need for AMR surveillance, and current progress and challenges in AMR surveillance efforts in eight South and Southeast Asian countries.
Getting Rid of Dichotomous Sex Estimations: Why Logistic Regression Should be Preferred Over Discriminant Function Analysis

Sex estimation is an important part of creating a biological profile for skeletal remains in forensics. The commonly used methods for developing sex estimation equations are discriminant function analysis (DFA) and logistic regression (LogR). LogR equations provide a probability of the predicted sex, while DFA relies on cutoff points to segregate males and females, resulting in a rigid dichotomization of the sexes. This is problematic because sexual dimorphism exists along a continuum and there can be considerable overlap in trait expression between the sexes. In this study, we used humeral measurements to compare the performance of DFA and LogR and found them to be very similar under multiple conditions. The overall cross‐validated (leave‐one‐out) accuracy of DFA (75.76–95.14%) was slightly higher than LogR (75.76–93.82%) for simple and multiple variable equations, and also performed better under varying sample sizes (94.03% vs. 93.78%). Three of five DFA equations outperformed LogR under the B index, while all five LogR equations outperformed the DFA equations under the Q index. Both methods saw an improvement in overall accuracy (DFA: 86.74–95.79%; LogR: 86.74–95.76%) when individuals with a classification probability lower than 0.80 were excluded. Additionally, we propose a method for calculating additional cutoff points (PMarks) based on posterior probability values. In conclusion, we recommend using LogR over DFA due to the increased flexibility, robusticity, and benefits for future users of the statistical models; however, if DFA is preferred, use of the proposed PMarks facilitates future analysis while avoiding unnecessary dichotomization.
Impact of combined exercise training on the development of cardiometabolic and neuroimmune complications induced by fructose consumption in hypertensive rats

This study evaluated the impact of combined exercise training on the development of cardiovascular and neuroimmune complications induced by fructose consumption (10% in the drinking water) in hypertensive rats (SHR). After weaning, SHR were divided into 3 groups: SHR (H), SHR+fructose (HF) and SHR+fructose+combined exercise training (treadmill+ladder, 40–60% of maximum capacity) (HFTC). Metabolic, hemodynamic, autonomic, inflammatory and oxidative stress parameters were evaluated in the subgroups (n = 6 group/time) at 7, 15, 30 and 60 days of protocol. Fructose consumption (H vs. HF groups) decreased spontaneous baroreflex sensitivity and total variance of pulse interval at day 7 (7 to 60); increased IL-6 and TNFα in the heart (at day 15, 30 and 60) and NADPH oxidase activity and cardiac lipoperoxidation (LPO) (day 60); increased white adipose tissue weight, reduced insulin sensitivity and increased triglycerides (day 60); induced an additional increase in mean arterial pressure (MAP) (days 30 and 60). Combined exercise training prevented such dysfunctions and sustained increased cardiac IL-10 (day 7) and glutathione redox balance (GSH/GSSG) for the entire protocol. In conclusion, combined exercise training performed simultaneously with exacerbated fructose consumption prevented early cardiovascular autonomic dysfunction, probably trigging positive changes in inflammation and oxidative stress, resulting in a better cardiometabolic profile in rats genetically predisposed to hypertension.
Wheat Immature Embryo Culture for Embryogenic Callus Induction

Four 2,4-D concentrations along with three embryo developmental stages were tested to determine the optimum morphogenesis of wheat immature embryo culture. Concentration of 2 mg L 2,4-D was found to be optimum level for 1 morphogenesis which was a good indicator of embryogenesis. Compact and nodular calli were observed in first and second developmental stages of 2 mg L 2,4-D concentration. In addition, five callus initiation media were tested to determine effects 1 of medium constituents on somatic embryogenesis of wheat (Triticum aestivum L.). The highest embryogenic callus formation was observed on MS+B5 medium (98.3%). Therefore, first and second developmental stages of 2 mg L 2,4-D concentration 1 along with MS+B5 medium is suitable for embryogenic callus production in wheat.
Disparities in Access to Autologous Breast Reconstruction

Background and objectives: This study aimed to determine if age, race, region, insurance, and comorbidities affect the type of breast reconstruction that patients receive. Materials and methods: This analysis used the Florida Inpatient Discharge Dataset from 1 January 2013 to 30 September 2017, which contains deidentified patient-level administrative data from all acute care hospitals in the state of Florida. We included female patients, diagnosed with breast cancer, who underwent mastectomy and a subsequent breast reconstruction. We performed an χ2 test and logistic regression in this analysis. Results: On the multivariable analysis, we found that age, race, patient region, insurance payer, and Elixhauser score were all variables that significantly affected the type of reconstruction that patients received. Our results show that African American (odds ratio (OR): 0.68, 95%CI: 0.58–0.78, p < 0.001) and Hispanic or Latino (OR: 0.82, 95%CI: 0.72–0.93, p = 0.003) patients have significantly lower odds of receiving implant reconstruction when compared to white patients. Patients with Medicare (OR: 1.57, 95%CI: 1.33–1.86, p < 0.001) had significantly higher odds and patients with Medicaid (OR: 0.61, 95%CI: 0.51–0.74, p < 0.001) had significantly lower odds of getting autologous reconstruction when compared to patients with commercial insurance. Conclusions: Our study demonstrated that, in the state of Florida over the past years, variables, such as race, region, insurance, and comorbidities, play an important role in choosing the reconstruction modality. More efforts are needed to eradicate disparities and give all patients, despite their race, insurance payer, or region, equal access to health care.