Miracle-dz/UniFAR-FTUs huggingface dataset:
Normative reference values of handgrip strength for Brazilian older people aged 65 to 90 years: Evidence from the multicenter Fibra‑BR study

Background Handgrip strength (HGS) is an indicator of muscle strength, suited for evaluating the aging process. Its use depends on the availability of reliable normative reference values (NRV). The main objective of this study is to provide NRV of HGS for Brazilians aged 65 to 90 years. Methods Participants were from the Frailty in Brazilian Older People research. 2,999 successful aging (SA) participants comprised the development sample. HGS was measured using a hydraulic dynamometer. Obtaining NRV involved regressing HGS on age per sex-height strata, fitting separate fractional polynomial (FP) models for the mean and coefficient of variation. Model fit was assessed via standardized residuals, probability/quantile plots, and comparing observed to normal expected percentages of participants falling within specified centile intervals. For validation, the latter procedure was applied to 2,369 unsuccessfully aging (UA) participants. Results Across strata, the best-fitting models for the means were FP of power 1. FP models for the CV indicated age invariance, entailing steady heteroscedastic age decline in SD since coefficients for the means were negative and SD = CV×mean. All models adjusted well. Centiles distributions for the SA and UA populations showed anticipated patterns, respectively falling on and below the normative expected centile references. Results (NRV) are presented in tables and centile charts. Equations are also provided. Conclusion NRV/charts may be endorsed for routine use, while still tested further. They would aid professionals caring for older people, not only to identify those at risk and eligible for immediate provisions, but also in planning prevention and rehabilitation measures.
Effect of Feeding Barley, Corn, and a Barley/Corn Blend on Beef Composition and End-Product Palatability

This study evaluated the relationship among palatability attributes, volatile compounds, and fatty acid (FA) profiles in meat from barley, corn, and blended (50:50, barley and corn) grain-fed steers. Multiple correspondence analysis with three dimensions (Dim) explained 62.2% of the total variability among samples. The Dim 1 and 2 (53.3%) separated pure from blended grain-fed beef samples. Blended grain beef was linked to a number of volatiles including (E,E)-2,4-decadienal, hexanal, 1-octen-3-ol, and 2,3-octanedione. In addition, blended grain-fed beef was linked to fat-like and rancid flavors, stale-cardboard, metallic, cruciferous, and fat-like aroma descriptors, and negative categories for flavor intensity (FI), off-flavor, and tenderness. A possible combination of linoleic and linolenic acids in the blended diet, lower rumen pH, and incomplete biohydrogenation of blended grain-fed polyunsaturates could have increased (p ≤ 0.05) long-chain n-6 fatty acids (LCFA) in blended grain-fed beef, leading to more accumulation of FA oxidation products in the blended than in barley and corn grain-fed meat samples. The Dim 3 (8.9%) allowed corn separation from barley grain beef. Barley grain-fed beef was mainly linked to alkanes and beef positive FI, whereas corn grain-fed beef was associated with pyrazines, in addition to aldehydes related to n-6 LCFA oxidation.
Mechanical Properties, Wettability and Thermal Degradation of HDPE/Birch Fiber Composite

Wood–plastic composites have emerged and represent an alternative to conventional composites reinforced with synthetic carbon fiber or glass fiber–polymer. A wide variety of wood fibers are used in WPCs including birch fiber. Birch is a common hardwood tree that grows in cool areas such as the province of Quebec, Canada. The effect of the filler proportion on the mechanical properties, wettability, and thermal degradation of high-density polyethylene/birch fiber composite was studied. High-density polyethylene, birch fiber and maleic anhydride polyethylene as coupling agent were mixed and pressed to obtain test specimens. Tensile and flexural tests, scanning electron microscopy, dynamic mechanical analysis, differential scanning calorimetry, thermogravimetry analysis and surface energy measurement were carried out. The tensile elastic modulus increased by 210% as the fiber content reached 50% by weight while the flexural modulus increased by 236%. The water droplet contact angle always exceeded 90°, meaning that the material remained hydrophobic. The thermal decomposition mass loss increased proportional with the percentage of fiber, which degraded at a lower temperature than the HDPE did. Both the storage modulus and the loss modulus increased with the proportion of fiber. Based on differential scanning calorimetry, neither the fiber proportion nor the coupling agent proportion affected the material melting temperature.
Saliva Gene Promoter Hypermethylation as a Biomarker in Oral Cancer

Oral carcinogenesis is a multistep process characterized by a summation of multiple genetic and epigenetic alterations in key regulatory genes. The silencing of genes by aberrant promoter hypermethylation is thought to be an important epigenetic event in cancer development and progression which has great potential as a biomarker for early diagnosis, tumor molecular subtyping, prognosis, monitoring, and therapy. Aberrant DNA methylation has been detected in different liquid biopsies, which may represent a potential alternative to solid biopsies. The detection of methylated genes in saliva may have clinical application for noninvasive oral cancer screening and early diagnosis. Here, we review the current evidence on gene promoter hypermethylation in saliva.
Usnic Acid Treatment Changes the Composition of Mycobacterium tuberculosis Cell Envelope and Alters Bacterial Redox Status

The evaluation of mechanisms of mycobacterial response to natural products has been barely studied. However, it might be helpful to reveal bacterial adaptation strategies, which are eventually crucial for the discovery of new drug targets and, hence, understanding the resistance mechanisms. ABSTRACT Mycobacterium tuberculosis developed efficient adaptation mechanisms in response to different environmental conditions. This resulted in the ability to survive in human macrophages and in resistance to numerous antibiotics. To get insight into bacterial responses to potent antimycobacterial natural compounds, we tested how usnic acid, a lichen-derived secondary metabolite, would influence mycobacteria at transcriptomic and metabolomic levels. The analysis of expression of sigma factors revealed a profound impact of usnic acid on one of the primary genetic regulatory systems of M. tuberculosis. Combined liquid chromatography-mass spectrometry and nuclear magnetic resonance analyses allowed us to observe the perturbations in metabolic pathways, as well as in lipid composition, which took place within 24 h of exposure. Early bacterial response was related to redox homeostasis, lipid synthesis, and nucleic acid repair. Usnic acid treatment provoked disturbances of redox state in mycobacterial cells and increased production of structural elements of the cell wall and cell membrane. In addition, to increase the number of molecules related to restoration of redox balance, the rearrangements of the cell envelope were the first defense mechanisms observed under usnic acid treatment. IMPORTANCE The evaluation of mechanisms of mycobacterial response to natural products has been barely studied. However, it might be helpful to reveal bacterial adaptation strategies, which are eventually crucial for the discovery of new drug targets and, hence, understanding the resistance mechanisms. This study showed that the first-line mycobacterial defense against usnic acid, a potent antimicrobial agent, is the remodeling of the cell envelope and restoring redox homeostasis. Transcriptomic data correlated with metabolomics analysis. The observed metabolic changes appeared similar to those exerted by antibiotics.
PPARs and Tumor Microenvironment: The Emerging Roles of the Metabolic Master Regulators in Tumor Stromal–Epithelial Crosstalk and Carcinogenesis

Simple Summary The roles of peroxisome proliferator-activated receptors (PPARs) in carcinogenesis are increasingly appreciated. With the growing interest in tumor stromal-epithelial crosstalk, we aim to provide an up-to-date overview of the implications of PPARs in the tumor microenvironment. In the tumor stromal cells, the nuclear receptors exhibit critical, but functionally diverse activities, rendering it hard to ascribe either an exclusive pro- or anti-tumorigenic role for different PPAR isotypes. Based on the existing evidence, we also highlight the knowledge gaps and future prospects of targeting PPARs in the tumor microenvironment. Essentially, a PPAR-based anticancer approach holds a great deal of untapped potential, but its success relies on innovative strategies for cell-specific or tumor microenvironment-triggered drug delivery systems. Abstract Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for more than three decades. Consisting of three isotypes, PPARα, γ, and β/δ, these nuclear receptors are regarded as the master metabolic regulators which govern many aspects of the body energy homeostasis and cell fate. Their roles in malignancy are also increasingly recognized. With the growing interest in crosstalk between tumor stroma and epithelium, this review aims to highlight the current knowledge on the implications of PPARs in the tumor microenvironment. PPARγ plays a crucial role in the metabolic reprogramming of cancer-associated fibroblasts and adipocytes, coercing the two stromal cells to become substrate donors for cancer growth. Fibroblast PPARβ/δ can modify the risk of tumor initiation and cancer susceptibility. In endothelial cells, PPARβ/δ and PPARα are pro- and anti-angiogenic, respectively. Although the angiogenic role of PPARγ remains ambiguous, it is a crucial regulator in autocrine and paracrine signaling of cancer-associated fibroblasts and tumor-associated macrophages/immune cells. Of note, angiopoietin-like 4 (ANGPTL4), a secretory protein encoded by a target gene of PPARs, triggers critical oncogenic processes such as inflammatory signaling, extracellular matrix derangement, anoikis resistance and metastasis, making it a potential drug target for cancer treatment. To conclude, PPARs in the tumor microenvironment exhibit oncogenic activities which are highly controversial and dependent on many factors such as stromal cell types, cancer types, and oncogenesis stages. Thus, the success of PPAR-based anticancer treatment potentially relies on innovative strategies to modulate PPAR activity in a cell type-specific manner.
Elevated Sporulation Efficiency in Fission Yeast Schizosaccharomyces japonicus Strains Isolated from Drosophila

The fission yeast Schizosaccharomyces japonicus, comprising S. japonicus var. japonicus and S. japonicus var. versatilis varieties, has unique characteristics such as striking hyphal growth not seen in other Schizosaccharomyces species; however, information on its diversity and evolution, in particular mating and sporulation, remains limited. Here we compared the growth and mating phenotypes of 17 wild strains of S. japonicus, including eight S. japonicus var. japonicus strains newly isolated from an insect (Drosophila). Unlike existing wild strains isolated from fruits/plants, the strains isolated from Drosophila sporulated at high frequency even under nitrogen-abundant conditions. In addition, one of the strains from Drosophila was stained by iodine vapor, although the type strain of S. japonicus var. japonicus is not stained. Sequence analysis further showed that the nucleotide and amino acid sequences of pheromone-related genes have diversified among the eight strains from Drosophila, suggesting crossing between S. japonicus cells of different genetic backgrounds occurs frequently in this insect. Much of yeast ecology remains unclear, but our findings suggest that insects such as Drosophila might be a good niche for mating and sporulation, and will provide a basis for the understanding of sporulation mechanisms via signal transduction, as well as the ecology and evolution of yeast.
The Molecular Basis of Different Approaches for the Study of Cancer Stem Cells and the Advantages and Disadvantages of a Three-Dimensional Culture

Cancer stem cells (CSCs) are a rare tumor subpopulation with high differentiation, proliferative and tumorigenic potential compared to the remaining tumor population. CSCs were first discovered by Bonnet and Dick in 1997 in acute myeloid leukemia. The identification and isolation of these cells in this pioneering study were carried out through the flow cytometry, exploiting the presence of specific cell surface molecular markers (CD34+/CD38−). In the following years, different strategies and projects have been developed for the study of CSCs, which are basically divided into surface markers assays and functional assays; some of these techniques also allow working with a cellular model that better mimics the tumor architecture. The purpose of this mini review is to summarize and briefly describe all the current methods used for the identification, isolation and enrichment of CSCs, describing, where possible, the molecular basis, the advantages and disadvantages of each technique with a particular focus on those that offer a three-dimensional culture.
Uncommon Non-Candida Yeasts in Healthy Turkeys—Antimicrobial Susceptibility and Biochemical Characteristic of Trichosporon Isolates

The microbiota of the gastrointestinal tract of humans and animals is inhabited by a diverse community of bacteria, fungi, protozoa, and viruses. In cases where there is an imbalance in the normal microflora or an immunosuppression on the part of the host, these opportunistic microorganisms can cause severe infections. The study presented here evaluates the biochemical and antifungal susceptibility features of Trichosporon spp. , uncommon non-Candida strains isolated from the gastrointestinal tract of healthy turkeys. The Trichosporon coremiiforme and Trichosporon (Apiotrichum) montevideense accounted for 7.7% of all fungi isolates. The biochemical tests showed that Trichosporon coremiiforme had active esterase (C4), esterase-lipase (C8) valine arylamidase, naphthol-AS-BI phosphohydrolase, α-galactosidase, and β-glucosidase. Likewise, Trichosporon montevideense demonstrated esterase-lipase (C8), lipase (C14), valine arylamidase, naphthol-AS-BI phosphohydrolase, α-galactosidase, and β-glucosidase activity. T.coremiiforme and T. monteviidense isolated from turkeys were itraconazole resistant and amphotericin B, fluconazole, and voriconazole susceptible. Compared with human isolates, the MIC range and MIC values of turkey isolates to itraconazole were in a higher range limit in both species, while MIC values to amphotericin B, fluconazole, and voriconazole were in a lower range limit. Furthermore, the obtained ITS1—5.8rRNA—ITS2 fragment sequences were identical with T. coremiiforme and T. montevideense sequences isolated from humans indicating that these isolates are shared pathogens.
Die aktuelle Therapie des asbestassoziierten malignen Pleuramesothelioms – Ein Experten-Konsensuspapier

Zusammenfassung Asbestverursachte maligne Mesotheliome gehören in Deutschland mit etwa 1000 jährlichen Neuerkrankungen zu den häufigen arbeitsbedingten Krebserkrankungen. Die Prognose ist oftmals schlecht, da die Erkrankung lange symptomlos bleibt und deshalb meist erst als Zufallsbefund in bereits fortgeschrittenen Stadien diagnostiziert wird. Die deutsche gesetzliche Unfallversicherung (DGUV) hat in den letzten Jahren erhebliche Anstrengungen unternommen, eine Vorverlagerung des Diagnosezeitpunkts zu erreichen, um die Erkrankung möglichst in Frühstadien zu detektieren. Die aus diesen Bestrebungen resultierenden neuen medizinisch-wissenschaftlichen Erkenntnisse zeigen, dass die Kombination der Biomarker Calretinin und Mesothelin in einer Hochrisikogruppe die Vorverlegung der Diagnose um bis zu 12 Monaten ermöglicht. Die Diagnose eines Mesothelioms im Frühstadium wird idealerweise von der individuell bestmöglichen Therapie gefolgt. Die Standardtherapie basiert auf operativer Entfernung des Tumors und Chemotherapie, ergänzt um Strahlentherapie und Psychoonkologie. In den letzten Jahren wurden einige neue Therapieansätze entwickelt. Die Übersicht stellt den aktuellen Stand der Therapie des Mesothelioms, basierend auf den internationalen Leitlinien und neuen Studien, dar.
Effects of the Head Start Program on Socioecological Obesogenic Factors in American Children

Head Start is a nationwide developmental program for low-income families. This study aimed to investigate the association between the Head Start program and children’s BMI status, as well as their quality of life with respect to socioecological obesogenic factors. This cross-sectional study employed the Early Childhood Longitudinal Study-Kindergarten cohort (ECLS-K) in which the data were collected in 2007 and analyzed in 2019. Propensity-score matching analysis was performed to examine the association between the Head Start program and children’s BMI status, as well as the quality of life, controlling for socioecological obesogenic factors. A total of 3753 children (representing 1,284,209 at the population level) were recruited in this study (mean age: 13.69 years; girls: 49.42%). In the final matched model, the program did not have a statistically significant effect on children’s obesity. Fewer African American children participated in school-sponsored activities, perceived themselves as overweight, lived in a household with fewer family members, had less strict TV regulations, and were more likely to be overweight than their counterparts. Outcomes suggest that multiple dimensions of sociological obesogenic factors including individual, parental, familial, and community support factors affect the weight of children from low-income families and should be considered when establishing behavioral and policy interventions to thwart the childhood obesity epidemic.
Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus

There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that was previously demonstrated to be active against Influenza A virus, were evaluated against SARS-CoV-2. Intrinsic fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated naproxen binding to the nucleoprotein of SARS-Cov-2 as predicted by molecular modeling. Naproxen impeded recombinant N oligomerization and inhibited viral replication in infected cells. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen specifically inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2-induced damage. No inhibition of viral replication was observed with paracetamol or the COX-2 inhibitor celecoxib. Thus, among the NSAID tested, only naproxen combined antiviral and anti-inflammatory properties. Naproxen addition to the standard of care could be beneficial in a clinical setting, as tested in an ongoing clinical study.
Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model

Difficulties related to storage and transport of currently available live oral rotavirus vaccines can have detrimental consequences on the efficacy of the vaccines. Thus, there is a great need for thermostable vaccines that can eliminate the necessity for cold chain storage or reconstitution before administration. In this study, we developed a dissolvable oral polymeric film comprised of a live attenuated thermostable tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) powder and antacid (CaCO3). Immunogenicity and protective efficacy of the vaccine after buccal delivery was evaluated in the gnotobiotic pig model of human rotavirus (HRV) infection and diarrhea. Two doses of the vaccine were highly immunogenic and conferred strong protection against virus shedding and diarrhea upon challenge with a high dose of a virulent G1 HRV in gnotobiotic pigs. Those pigs vaccinated with the preserved film vaccine had significantly delayed onset of diarrhea; reduced duration and area under the curve of diarrhea; delayed onset of fecal virus shedding; and reduced duration and peak of fecal virus shedding titers compared to pigs in both the placebo and the reconstituted liquid oral RRV-TV vaccine groups. Associated with the strong protection, high titers of serum virus neutralization antibodies against each of the four RRV-TV mono-reassortants and G1 HRV-specific serum IgA and IgG antibodies, as well as intestinal IgA antibodies, were induced by the preserved film vaccine. These results demonstrated the effectiveness of our thermostable buccal film rotavirus vaccine and warrant further investigation into the promise of the novel technology in addressing drawbacks of the current live oral HRV vaccines.