Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergies between the Developmental Origins of Health and Disease framework and multiple branches of evolutionary anthropology

The Developmental Origins of Health and Disease (DOHaD) hypothesis derives from the epidemiological and basic/mechanistic health sciences. This well‐supported hypothesis holds that environment during the earliest stages of life—pre‐conception, pregnancy, infancy—shapes developmental trajectories and ultimately health outcomes across the lifespan. Evolutionary anthropologists from multiple subdisciplines are embracing synergies between the DOHaD framework and developmentalist approaches from evolutionary biology. Even wider dissemination and employment of DOHaD concepts will benefit evolutionary anthropological research. Insights from experimental DOHaD work will focus anthropologists' attention on biochemical/physiological mechanisms underpinning observed links between growth/health/behavioral outcomes and environmental contexts. Furthermore, the communication tools and wide public appeal of developmentalist health scientific research may facilitate the translation/application of evolutionary anthropological findings. Evolutionary Anthropology, in turn, can increase mainstream DOHaD research's use of evolutionary theory; holistic, longitudinal, and community‐based perspectives; and engagement with populations whose environmental exposures differ from those most commonly studied in the health sciences.
O-Glycan-Altered Extracellular Vesicles: A Specific Serum Marker Elevated in Pancreatic Cancer

Simple Summary Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the serum of PC patients. These specific EVs with O-glycans can act as potential biomarkers in a liquid biopsy for PC patients screening. Abstract Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.
The Impact of Natural Dietary Compounds and Food-Borne Mycotoxins on DNA Methylation and Cancer

Cancer initiation and progression is an accumulation of genetic and epigenetic modifications. DNA methylation is a common epigenetic modification that regulates gene expression, and aberrant DNA methylation patterns are considered a hallmark of cancer. The human diet is a source of micronutrients, bioactive molecules, and mycotoxins that have the ability to alter DNA methylation patterns and are thus a contributing factor for both the prevention and onset of cancer. Micronutrients such as betaine, choline, folate, and methionine serve as cofactors or methyl donors for one-carbon metabolism and other DNA methylation reactions. Dietary bioactive compounds such as curcumin, epigallocatechin-3-gallate, genistein, quercetin, resveratrol, and sulforaphane reactivate essential tumor suppressor genes by reversing aberrant DNA methylation patterns, and therefore, they have shown potential against various cancers. In contrast, fungi-contaminated agricultural foods are a source of potent mycotoxins that induce carcinogenesis. In this review, we summarize the existing literature on dietary micronutrients, bioactive compounds, and food-borne mycotoxins that affect DNA methylation patterns and identify their potential in the onset and treatment of cancer.
A Novel Multiresolution-Statistical Texture Analysis Architecture: Radiomics-Aided Diagnosis of PDAC Based on Plain CT Images

Early screening of PDAC (pancreatic ductal adenocarcinoma) based on plain CT (computed tomography) images is of great significance. Therefore, this work conducted a radiomics-aided diagnosis analysis of PDAC based on plain CT images. We explored a novel MSTA (multiresolution-statistical texture analysis) architecture to extract texture features and built machine learning models to classify PDACs and HPs (healthy pancreases). We also performed significance tests of differences to analyze the relationships between histopathological characteristics and texture features. The MSTA architecture originates from the analysis of histopathological characteristics and combines multiresolution analysis and statistical analysis to extract texture features. The MSTA architecture achieved better experimental results than the traditional architecture that scales the coefficient matrices of the multiresolution analysis. In the validation of the classifications, the MSTA architecture achieved an accuracy of 81.19% and an AUC (area under the ROC (receiver operating characteristic) curve) of 0.88 (95% confidence interval: 0.84-0.92). In the test of the classifications, it achieved an accuracy of 77.66% and an AUC of 0.79 (95% confidence interval: 0.71-0.87). Moreover, the significance tests of differences showed that the extracted texture features may be relevant to the histopathological characteristics. The MSTA architecture is beneficial for the radiomics-aided diagnosis of PDAC based on plain CT images. Its texture features can potentially enhance radiologists’ imaging interpretation abilities.
Van der Waals Epitaxy of III-Nitrides and Its Applications

III-nitride semiconductors have wide bandgap and high carrier mobility, making them suitable candidates for light-emitting diodes (LEDs), laser diodes (LDs), high electron mobility transistors (HEMTs) and other optoelectronics. Compared with conventional epitaxy technique, van der Waals epitaxy (vdWE) has been proven to be a useful route to relax the requirements of lattice mismatch and thermal mismatch between the nitride epilayers and the substrates. By using vdWE, the stress in the epilayer can be sufficiently relaxed, and the epilayer can be easily exfoliated and transferred, which provides opportunities for novel device design and fabrication. In this paper, we review and discuss the important progress on the researches of nitrides vdWE. The potential applications of nitride vdWE are also prospected.
Healthcare Access and Utilization Among Persons Who Inject Drugs in Medicaid Expansion and Nonexpansion States: 22 United States Cities, 2018.

BACKGROUND Medicaid expansion under the Affordable Care Act increased insurance coverage, access to healthcare, and substance use disorder treatment, for many Americans. We assessed differences in healthcare access and utilization among persons who inject drugs (PWID) by state Medicaid expansion status. METHODS In 2018, PWID were interviewed in 22 US cities for National HIV Behavioral Surveillance. We analyzed data from PWID aged 18-64 years who reported illicit use of opioids (n = 9957) in the past 12 months. Poisson regression models with robust standard errors were used to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were used to examine differences by Medicaid expansion status in indicators of healthcare access and utilization. RESULTS Persons who inject drugs in Medicaid expansion states were more likely to have insurance (87% vs 36%; aPR, 2.3; 95% CI, 2.0-2.6), a usual source of healthcare (53% vs 34%; aPR, 1.5; 95% CI, 1.3-1.9), and have used medication-assisted treatment (61% vs 36%; aPR, 1.4; 95% CI, 1.1-1.7), and they were less likely to have an unmet need for care (21% vs 39%; aPR, 0.6; 95% CI, 0.4-0.7) than those in nonexpansion states. CONCLUSIONS Low insurance coverage, healthcare access, and medication-assisted treatment utilization among PWID in some areas could hinder efforts to end the intertwined human immunodeficiency virus and opioid overdose epidemics.
Promiscuous DNA cleavage by HpyAII endonuclease is modulated by the HNH catalytic residues

Abstract Helicobacter pylori is a carcinogenic bacterium that is responsible for 5.5% of all human gastric cancers. H. pylori codes for an unusually large number of restriction–modification (R–M) systems and several of them are strain-specific and phase-variable. HpyAII is a novel Type IIs phase-variable restriction endonuclease present in 26695 strain of H. pylori. We show that HpyAII prefers two-site substrates over one-site substrates for maximal cleavage activity. HpyAII is less stringent in metal ion requirement and shows higher cleavage activity with Ni2+ over Mg2+. Mutational analysis of the putative residues of the HNH motif of HpyAII confirms that the protein has an active HNH site for the cleavage of DNA. However, mutation of the first Histidine residue of the HNH motif to Alanine does not abolish the enzymatic activity, but instead causes loss of fidelity compared with wildtype HpyAII. Previous studies have shown that mutation of the first Histidine residue of the HNH motif of all other known HNH motif motif-containing enzymes completely abolishes enzymatic activity. We found, in the case of HpyAII, mutation of an active site residue leads to the loss of endonuclease fidelity. The present study provides further insights into the evolution of restriction enzymes.
Biomarker Optimization of Spinal Cord Stimulation Therapies

We are in the process of designing and testing an intradural stimulation device that will shorten the distance between the location of the electrode array and the targeted neural tissue, thus improving the efficacy of electrical current delivery. Identifying a biomarker that accurately reflects the response to this intervention is highly valued because of the potential to optimize interventional parameters or predict a response before it is clinically measurable. In this report, we summarize the findings pertaining to the study of biomarkers so that we and others will have an up‐to‐date reference that critically evaluates the current approaches and select one or several for testing during the development of our device.
EFFECTS OF TWO ARGININE ENANTIOMERS (L AND D) PRE-TREATMENT ON SOME PHYSIOLOGICAL PARAMETERS AND THE EXPRESSION OF ARGINASE 1 GENE IN TOMATO PLANTS UNDER DROUGHT STRESS

Arginine (Arg) is reported to contribute in reduction of destructive effects of biotic and abiotic stresses through three pathways and their end products (proline, polyamine and nitric oxide). Two isomers of arginine (L and D) have been applied as pre-treatment and then tomato plants were subjected to drought stress. The effects of these isomers on some physiological parameters and expression of arginase 1 (ARG I) (one of the enzymes in proline biosynthesis) pathway have been investigated. The results showed that leaf relative water content (RWC) of tomato plants under drought stress decreased and pre-treatment with L-Arg improved RWC, but D-Arg did not. Drought stress caused a significant decrease in photosynthetic pigments but arginine had no effect on these parameters. Sugar content and lipid peroxidation level increased under stress. However, arginine treatment caused decrease in lipid peroxidation while it did not change sugar content significantly. Proline also significantly increased under drought stress and L-Arg many time increased it content. Increment in expression of arginase1 may be the cause for this increment. On the other hand, the expression of arginase1 and proline content with D-Arg was less obvious. The results of the present study indicate that in tomato plant in addition of L-Arg, arginase can use D-Arg substrate to produce proline. However D-Arg has been reported as an analog of L-Arg which could block ADC pathway. Our molecular and biochemical results showed that this enantiomer could not inhibit arginase pathway.
Root Exuded Benzoxazinoids: Uptake and Translocation in Neighbouring Plants.

Plants have evolved advanced chemical defence mechanisms, including root exudation, which enables them to respond to changes occurring in their surroundings rapidly. Yet, it remains unresolved how root exudation effects belowground plant-plant interactions. The objective of this study was to elucidate the fate of benzoxazinoids (BXs) exuded from roots of rye (Secale cereale L.) plants grown with hairy vetch (Vicia villosa). A rapid method that allows non-destructive and reproducible chemical profiling of the root exudates was developed. Targeted chemical analysis with HPLC-MS/MS was performed to investigate the changes in the composition and concentration of BXs in the rye plant and its root exudate in response to co-cultivation with hairy vetch. Furthermore, hairy vetch plants were screened for possible uptake of BXs from the rhizosphere and their translocation to the shoot. Rye significantly increased the production and root exudation of BXs, in particular 2-β-D-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one (DIBOA-glc) and 2-β-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-glc), in response to co-cultivation with hairy vetch. DIBOA-glc and DIMBOA-glc were absorbed by the roots of the co-cultivated hairy vetch plants and translocated to the shoots. These findings will strongly improve our understanding about the exudation of BXs from rye plant and their role in interaction with other plant species. Keywords: Benzoxazinoids; DIBOA-glc; DIMBOA-glc; Root exudate; Plant-plant interactions.
Pharmacokinetics and Tissue Distribution of Loratadine, Desloratadine and Their Active Metabolites in Rat based on a Newly Developed LC-MS/MS Analytical Method

Abstract Loratadine (LOR) and its major metabolite, desloratadine (DL) are new-generation antihistamines. The hydroxylated metabolites of them, 6-OH-DL, 5-OH-DL and 3-OH-DL are also active because of their ability to inhibit binding of pyrilamine to brain H1 receptors and a tendency for distributing to specific immune-regulatory tissues. In this study, a new validated LC-MS/MS method to simultaneously quantify LOR, DL, 6-OH-DL, 5-OH-DL and 3-OH-DL in plasma and tissues was established and applied to an investigation of their pharmacokinetics and target-tissue distribution tendency for the first time. Pharmacokinetics parameters in rat were measured and the results suggest that the body’s exposure to active metabolites were much higher than to the prodrug with LOR, but much lower with DL. The tissue distribution study shows that LOR, DL and their active metabolites were widely distributed in the liver, spleen, thymus, heart, adrenal glands and pituitary gland. For immune-regulatory tissues, the concentrations of LOR, DL and their active metabolites in the spleen were much higher than in the thymus, which is related to the spleen, one of the sites where immune responses occur. LOR and its metabolites might inhibit immune-mediated allergic inflammation through the hypothalamic-pituitary-adrenal (HPA) axis. It was also found that the concentration of LOR in the heart was highest after liver and adrenal glands while those of DL, 6-OH-DL and 5-OH-DL in the liver, adrenal glands and spleen were all higher than those in the heart, which suggests that LOR may have a greater tendency to distribute in the heart than its metabolites.
Decoding the Role of CD271 in Melanoma

The evolution of melanoma, the most aggressive type of skin cancer, is triggered by driver mutations that are acquired in the coding regions of particularly BRAF (rat fibrosarcoma serine/threonine kinase, isoform B) or NRAS (neuroblastoma-type ras sarcoma virus) in melanocytes. Although driver mutations strongly determine tumor progression, additional factors are likely required and prerequisite for melanoma formation. Melanocytes are formed during vertebrate development in a well-controlled differentiation process of multipotent neural crest stem cells (NCSCs). However, mechanisms determining the properties of melanocytes and melanoma cells are still not well understood. The nerve growth factor receptor CD271 is likewise expressed in melanocytes, melanoma cells and NCSCs and programs the maintenance of a stem-like and migratory phenotype via a comprehensive network of associated genes. Moreover, CD271 regulates phenotype switching, a process that enables the rapid and reversible conversion of proliferative into invasive or non-stem-like states into stem-like states by yet largely unknown mechanisms. Here, we summarize current findings about CD271-associated mechanisms in melanoma cells and illustrate the role of CD271 for melanoma cell migration and metastasis, phenotype-switching, resistance to therapeutic interventions, and the maintenance of an NCSC-like state.
Schrödinger’s Worker: Are They Positive or Negative for SARS-CoV-2?

In these days of 2020, tests for the diagnosis of SARS-CoV-2, and their use in the context of health surveillance of workers, are becoming popular. Nevertheless, their sensitivity and specificity could vary on the basis of the type of test used and on the moment of infection of the subject tested. The aim of this viewpoint paper is to make employers, workers, occupational physicians, and public health specialists think about the limits of diagnostic tests currently available, and the possible implication related to the erroneous and incautious assignment of “immunity passports” or “risk-free certificates” to workers during screening campaigns in workplaces.
Electrical Impedance Spectroscopy for Monitoring Chemoresistance of Cancer Cells

Electrical impedance spectroscopy (EIS) is an electrokinetic method that allows for the characterization of intrinsic dielectric properties of cells. EIS has emerged in the last decade as a promising method for the characterization of cancerous cells, providing information on inductance, capacitance, and impedance of cells. The individual cell behavior can be quantified using its characteristic phase angle, amplitude, and frequency measurements obtained by fitting the input frequency-dependent cellular response to a resistor–capacitor circuit model. These electrical properties will provide important information about unique biomarkers related to the behavior of these cancerous cells, especially monitoring their chemoresistivity and sensitivity to chemotherapeutics. There are currently few methods to assess drug resistant cancer cells, and therefore it is difficult to identify and eliminate drug-resistant cancer cells found in static and metastatic tumors. Establishing techniques for the real-time monitoring of changes in cancer cell phenotypes is, therefore, important for understanding cancer cell dynamics and their plastic properties. EIS can be used to monitor these changes. In this review, we will cover the theory behind EIS, other impedance techniques, and how EIS can be used to monitor cell behavior and phenotype changes within cancerous cells.
The Landscape of Genomic Imprinting at the Porcine SGCE/PEG10 Locus from Methylome and Transcriptome of Parthenogenetic Embryos

In mammals, imprinted genes often exist in the form of clusters in specific chromosome regions. However, in pigs, genomic imprinting of a relatively few genes and clusters has been identified, and genes within or adjacent to putative imprinted clusters need to be investigated including those at the SGCE/PEG10 locus. The objective of this study was to, using porcine parthenogenetic embryos, investigate imprinting status of genes within the genomic region spans between the COL1A2 and ASB4 genes in chromosome 9. Whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) were conducted with normal and parthenogenetic embryos, and methylome and transcriptome were analyzed. As a result, differentially methylated regions (DMRs) between the embryos were identified, and parental allele-specific expressions of the SGCE and PEG10 genes were verified. The pig imprinted interval was limited between SGCE and PEG10, since both the COL1A2 and CASD1 genes at the centromere-proximal region and the genes between PPP1R9A and ASB4 toward the telomere were non-imprinted and biallelically expressed. Consequently, our combining analyses of methylome, transcriptome, and informative polymorphisms revealed the boundary of imprinting cluster at the SGCE/PEG10 locus in pig chromosome 9 and consolidated the landscape of genomic imprinting in pigs.
Association Between Body Size Phenotypes and Subclinical Atherosclerosis

Abstract Context The underlying relationship between body mass index (BMI), cardiometabolic disorders, and subclinical atherosclerosis is poorly understood. Objective To evaluate the association between body size phenotypes and subclinical atherosclerosis. Design Cross-sectional. Setting Cardiovascular disease-free cohort. Participants Middle-aged asymptomatic subjects (n = 3909). A total of 6 cardiometabolic body size phenotypes were defined based on the presence of at least 1 cardiometabolic abnormality (blood pressure, fasting blood glucose, triglycerides, low high-density lipoprotein cholesterol, homeostasis model assessment-insulin resistance index, high-sensitivity C-reactive protein) and based on BMI: normal-weight (NW; BMI <25), overweight (OW; BMI = 25.0-29.9) or obese (OB; BMI >30.0). Main Outcome Measures Subclinical atherosclerosis was evaluated by 2D vascular ultrasonography and noncontrast cardiac computed tomography. Results For metabolically healthy subjects, the presence of subclinical atherosclerosis increased across BMI categories (49.6%, 58.0%, and 67.7% for NW, OW, and OB, respectively), whereas fewer differences were observed for metabolically unhealthy subjects (61.1%, 69.7%, and 70.5%, respectively). When BMI and cardiometabolic abnormalities were assessed separately, the association of body size phenotypes with the extent of subclinical atherosclerosis was mostly driven by the coexistence of cardiometabolic risk factors: adjusted OR = 1.04 (95% confidence interval [CI], 0.90-1.19) for OW and OR = 1.07 (95% CI, 0.88-1.30) for OB in comparison with NW, whereas there was an increasing association between the extent of subclinical atherosclerosis and the number of cardiometabolic abnormalities: adjusted OR = 1.21 (95% CI, 1.05-1.40), 1.60 (95% CI, 1.33-1.93), 1.92 (95% CI, 1.48-2.50), and 2.27 (95% CI, 1.67-3.09) for 1, 2, 3, and >3, respectively, in comparison with noncardiometabolic abnormalities. Conclusions The prevalence of subclinical atherosclerosis varies across body size phenotypes. Pharmacologic and lifestyle interventions might modify their cardiovascular risk by facilitating the transition from one phenotype to another.