Miracle-dz/UniFAR-FTUs huggingface dataset:
Protective effect of Diosmin against benzo(a)pyrene‐induced lung injury in Swiss Albino Mice

Diosmin, a naturally occurring flavonoid commonly present in citrus fruit, is known to exhibit anti‐inflammatory, antimutagenic, antioxidant, and free radical scavenging as well as blood lipid lowering activities among others. Diosmin has also been used for the treatment of various diseases including diabetes mellitus and Alzheimer's disease. Our study explores the role of Diosmin in pulmonary toxicity (lung injury) induced by environmental contaminant benzo(a)pyrene [B(a)P]. Swiss Albino Mice (SAM) were administered with either Diosmin 100 or 200 mg/kg body weight daily for 14 days and then challenged with a single dose of B(a)P. On the 15th day, animals were sacrificed; lung tissues and blood were collected for molecular analysis. B(a)P administration in mice induced the thickening of lung epithelium, damaged alveolar architecture, and promoted inflammatory cell infiltration in the lung tissues. Also, B[a]P significantly increased the expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins and decreased antioxidant enzyme levels. Diosmin‐100 and Diosmin‐200 significantly attenuated the damage to lung epithelium, alveolar architecture, and reduced inflammatory cell infiltration in the lung tissues of mice. Diosmin significantly (P < .05) attenuated the levels of oxidative stress markers: lactate dehydrogenase and xanthine oxidase. A decrease in expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins in mice was challenged with B[a]P. Diosmin thus could be a promising therapeutic adjuvant against B[a]P‐induced oxidative stress and lung damage.
2020 National Vaccine Plan Development: Recommendations From the National Vaccine Advisory Committee

Executive Summary The National Vaccine Plan (NVP) serves as a roadmap for the 21st-century vaccines and immunization enterprise. Mandated by Congress in 1987, the NVP has provided the nation with a comprehensive strategy for enhancing all aspects of vaccination for more than 30 years. The most recent version of the plan was released in 2010. As the immunization landscape and vaccination system continue to evolve, the US Department of Health and Human Services (HHS) intends to release an updated NVP in 2020. The plan will encompass a lifespan approach, covering vaccination from before birth into old age, to immunization policy and practice for the next 5 years. To support this effort, the Assistant Secretary for Health (ASH) charged the National Vaccine Advisory Committee (NVAC) on March 25, 2019, with developing a report and recommendations to guide the development of the updated NVP. The charge called on NVAC to assess the relevance of existing plan goals, integrate adult immunization goals, prioritize the top objectives within each goal, and identify stakeholders for engagement in the plan’s development. In response to this charge, NVAC established the NVP Development Subcommittee, which comprised NVAC members, several persons from the private sector with relevant expertise, and HHS staff members. The recommendations in this report will be part of a rigorous process used to inform the final plan, which the HHS Office of Infectious Disease and HIV/AIDS Policy (OIDP) will release in 2020. After careful assessment of the current NVP, the National Adult Immunization Plan (NAIP), and midcourse reviews conducted by HHS and NVAC of the NVP, the subcommittee developed recommendations in support of a 5-year plan that reflects immunization priorities across the lifespan (Table 1). These recommendations include changes to each goal, as well as identifying the top 3 priorities poised to make the greatest impact within each goal. To complete the charge from the ASH, NVAC also recommended stakeholders to engage during development of the NVP (Recommendations 2-5). The NVAC recommendations in this report will provide a strong foundation for the development of the 2020 NVP.
Integration of mitochondrial energetics in heart with mathematical modelling

It has been an unsolved question how cardiac mitochondrial energetics is regulated during working transition. Mathematical modelling is a powerful tool for exploring the complicated networks of mitochondrial metabolism. We summarize the recent progress and remaining questions about mitochondrial energetics in heart, especially focusing on approaches utilizing mathematical modelling. Feedback activation by ADP and/or inorganic phosphate is an old but still attractive hypothesis for explaining the regulation mechanisms of cardiac mitochondrial energetics. However, this hypothesis has not been fully validated by experiments because rises of ADP and/or inorganic phosphate concentrations during cardiac workload increase have not been detected in many experiments. The hypothesis of intracellular energetic units is an extended version of feedback activation, which has a similar problem. The each‐step activation hypothesis beautifully reproduces metabolite constancy, although such master regulators have not been identified yet. Ca2+ has been the most plausible candidate because some of the mitochondrial dehydrogenases are activated by it. Recent experimental and simulation studies, however, throw doubt on its physiological relevance. Finally, we discuss issues to be solved to obtain a better view of cardiac mitochondrial energetics.
Incidence, Pathotyping, and Antibiotic Susceptibility of Avian Pathogenic Escherichia coli among Diseased Broiler Chicks

A total of 54 broiler flocks during the first two weeks of life was used to investigate the incidence of avian pathogenic E. coli in Egypt; 28 isolates (51.85%) were revealed by colony morphology and biochemical identification which then investigated for their serogroups and only 18/28 isolates were serotyped. The most prevalent serotypes were O115, O142, O158, O55, O125, O114, O27, O20, and O15. By application of polymerase chain reaction (PCR), 83.3% (15/18) of the serotyped isolates were confirmed to be E. coli, and 93.3% (14/15), 46.6% (7/15), and 20% (3/15) of isolates harbored the iss, iutA, and fimH genes, respectively. Virulence testing of the selected 13 APEC isolates on the specific-pathogen-free (SPF) chicks revealed them to be highly virulent (15.4%), moderately virulent (23.1%), and avirulent (61.5%); however, all isolates (100%) were extremely virulent towards SPF embryonated chicken eggs. Antibiotic resistance (100% of isolates (n = 13)) was observed for ampicillin, amoxycillin–clavulanic acid, and tetracyclines, colistin (92.31%; 12/13), doxycycline and spiramycin (84.62%; 11/13), florfenicol (69.23%; 9/13), cefotaxime (61.54%; 8/13), and ciprofloxacin (53.85%; 7/13). The highest percentage of sensitivity (53.85% of isolates; 7/13) was recorded for ofloxacin and enrofloxacin followed by gentamycin (46.15%; 6/13). The results suggest that the diagnosis of APEC with PCR is rapid and more accurate than traditional methods for E. coli identification; moreover, the presence or absence of iss, iutA, and/or fimH genes is not an indicator of in vivo pathogenicity of APEC. Thus, further studies, including a wider range of virulence genes and gene sequencing, are required. In addition, serotyping has no effect on the virulence of APEC.
Rational Engineering of the Substrate Specificity of a Thermostable D-Hydantoinase (Dihydropyrimidinase)

D-hydantoinases catalyze an enantioselective opening of 5- and 6-membered cyclic structures and therefore can be used for the production of optically pure precursors for biomedical applications. The thermostable D-hydantoinase from Geobacillus stearothermophilus ATCC 31783 is a manganese-dependent enzyme and exhibits low activity towards bulky hydantoin derivatives. Homology modeling with a known 3D structure (PDB code: 1K1D) allowed us to identify the amino acids to be mutated at the substrate binding site and in its immediate vicinity to modulate the substrate specificity. Both single and double substituted mutants were generated by site-directed mutagenesis at appropriate sites located inside and outside of the stereochemistry gate loops (SGL) involved in the substrate binding. Substrate specificity and kinetic constant data demonstrate that the replacement of Phe159 and Trp287 with alanine leads to an increase in the enzyme activity towards D,L-5-benzyl and D,L-5-indolylmethyl hydantoins. The length of the side chain and the hydrophobicity of substrates are essential parameters to consider when designing the substrate binding pocket for bulky hydantoins. Our data highlight that D-hydantoinase is the authentic dihydropyrimidinase involved in the pyrimidine reductive catabolic pathway in moderate thermophiles.
Impact of complex care management on spending and utilization for high-need, high-cost Medicaid patients.

OBJECTIVES Complex care management programs have emerged as a promising model to better care for high-need, high-cost patients. Despite their widespread use, relatively little is known about the impact of these programs in Medicaid populations. This study evaluated the impact of a complex care management program on spending and utilization for high-need, high-cost Medicaid patients. STUDY DESIGN Randomized quality improvement trial conducted at CareMore Health in Memphis, Tennessee. A total of 253 high-need, high-cost Medicaid patients were randomized in a 1:2 ratio to complex care management or usual care. METHODS Intention-to-treat analysis compared regression-adjusted rates of spending and utilization between patients randomized to the complex care program (n = 71) and those randomized to usual care (n = 127) over the 12 months following randomization. Primary outcomes included total medical expenditures (TME) and inpatient (IP) days. Secondary outcomes included IP admission, emergency department (ED) visits, care center visits, and specialist visits. RESULTS Compared with patients randomized to usual care, patients randomized to complex care management had lower TME (adjusted difference, -$7732 per member per year [PMPY]; 95% CI, -$14,914 to -$550; P = .036), fewer IP bed days (adjusted difference, -3.46 PMPY; 95% CI, -4.03 to -2.89; P <.001), fewer IP admissions (adjusted difference, -0.32 PMPY; 95% CI, -0.54 to -0.11; P = .014), and fewer specialist visits (adjusted difference, -1.35 PMPY; 95% CI, -1.98 to 0.73; P <.001). There was no significant impact on care center or ED visits. CONCLUSIONS Carefully designed and targeted complex care management programs may be an effective approach to caring for high-need, high-cost Medicaid patients.
Table Olives More than a Fermented Food

Table olives are one of the oldest vegetable fermented foods in the Mediterranean area. Beside their economic impact, fermented table olives represent also an important healthy food in the Mediterranean diet, because of their high content of bioactive and health-promoting compounds. However, olive fermentation is still craft-based following traditional processes, which can lead to a not fully predictable final product with the risk of spontaneous alterations. Nowadays, food industries have to face consumer demands for safe and healthy products. This review offers an overview about the main technologies used for olive fermentation and the role of lactic acid bacteria and yeasts characterizing this niche during the fermentation. Particular attention is offered to the selection and use of microorganisms as starter cultures to fasten and improve the safety of table olives. The development and implementation of multifunctional starter cultures in order to obtain heath-oriented table olives is also discussed.
Design, microwave‐assisted synthesis, biological evaluation and molecular modeling studies of 4‐phenylthiazoles as potent fatty acid amide hydrolase inhibitors

Endocannabinoids, anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG), are endogenous lipids that activate cannabinoid receptors. Activation of these receptors produces anti‐inflammatory and analgesic effects. Fatty acid amide hydrolase (FAAH) is a membrane enzyme that hydrolases endocannabinoids; thus, inhibition of FAAH represents an attractive approach to develop new therapeutics for treating inflammation and pain. Previously, potent rat FAAH inhibitors containing 2‐naphthyl‐ and 4‐phenylthiazole scaffolds were identified, but up to the present time, very little structure–activity relationship studies have been performed on these moieties. We designed and synthesized several analogs containing these structural motifs and evaluated their inhibition potencies against human FAAH enzyme. In addition, we built and validated a homology model of human FAAH enzyme and performed docking experiments. We identified several inhibitors in the low nanomolar range and calculated their ADME predicted values. These FAAH inhibitors represent promising drug candidates for future preclinical in vivo studies.
Role of Molecular Biomarkers in Liver Transplantation for Hepatocellular Carcinoma

Patient selection and organ allocation for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) relies predominantly on clinical parameters, such as tumor burden (ie, radiological imaging). Patients transplanted within Milan criteria have outstanding outcomes with a 5‐ and 10‐year survival of 70% and 55%, respectively. Tumor recurrence after transplantion is rare in these patients (10%); however, treatment options upon recurrence are generally limited, and outcomes are poor. There are also several studies showing how a subgroup of patients with tumors outside the Milan criteria might achieve comparable outcomes to patients within Milan criteria. In other words, the size and number of tumor nodules does not always reflect tumor biology, which could be better captured using molecular proxies for cancer aggressiveness. Over the last decade, we have significantly improved our understanding of the molecular landscape of early stage HCC. This includes the development of molecular classification, identification of prognostic and mutational signatures, and potential mechanisms of hepatocarcinogenesis. Some molecular markers have already proven useful to predict tumor‐related outcomes in HCC patients after LT. Most of these analyses are limited to tissue‐derived biomarkers, which limits their implementation in clinical practice because tissue biopsy is not required for HCC diagnosis. Minimally invasive alternative tools, such as liquid biopsy, are being increasingly explored and could help to individualize risk stratification for patients with HCC who will benefit from LT despite being outside the accepted clinical criteria.
Early Marriage and Negative Life Events Affect on Depression in Young Adults and Adolescents.

BACKGROUND Negative life events (NLEs) and early marriage (EM), a worldwide social silent problem, are increasing in prevalence globally. Evidence is lacking regarding their impact on depression. We assessed the impact of EM and NLEs on depression among adolescents, young adults and adults in Iran. METHODS A population-based descriptive study was performed among urban and rural population aged 13-40 years. Beck depression inventory scale II and life event questionnaire were used to assess the severity of depression and NLEs, respectively. EM was defined as a marriage or union between two persons in which one or both parties are younger than 18. RESULTS In a total of 530 participants (300 female and 230 male) with a mean age of 26.78 ± 5.06, almost 46% had depressive symptoms. A trend was found between rising age and depression so that among the three groups of study subjects, adults had the highest prevalence rate (49.34%). After adjusting for age, residence, substance abuse, alcohol abuse, unemployment and other NLEs by multiple regression, we found statistically significant relationships between depression and EM (2.77; CI: 1.75-4.57), and NLEs (2.78; CI: 1.85-4.19). Among types of NLEs, marital conflicts (5.8; CI: 1.60-20.81), loss of loved ones (6.12; CI: 1.28-28.26) and financial problems (13.79; CI: 1.72-108.17) were associated with depression risk. CONCLUSION Life skills improving program with intersectoral collaborative care to reduce determinants of EM and NLEs in the community, as well as training and screening for depression among adolescents and adulthood are necessary.
Phenolic Amides with Immunomodulatory Activity from the Nonpolysaccharide Fraction of Lycium barbarum Fruits.

The fruits of Lycium barbarum have a long history as an edible and medicinal food in Asian regions and have multiple consumption methods, the polysaccharides (LBPs) are commonly considered as their major immunological constituents. The current study revealed that the total phenolic amide moieties from L. barbarum fruits showed greater potential immunomodulatory activity in vivo than that of LBPs. Though subsequent investigation on the immunological bioactive phenolic amides, three new phenolic amides, lyciumamides L-N (1-3), as well as twelve analogs, were obtained from the total phenolic amide fraction. Extensive spectroscopic methods were used to elucidate the new structures. Compounds 4-6 and 15 significantly promoted LPS-stimulated B splenocyte, while compounds 4-6 displayed accelerative effects on the proliferation of Con A-stimulated T lymphocytes at a concentration of 20.0 μg/mL. These data indicated that extracts from L. barbarum fruits enriched with phenolic amides could be developed as a nutritional dietary supplement for immunocompromised individuals.
Qualitative and quantitative comparison of Thiel and phenol‐based soft‐embalmed cadavers for surgery training

Surgical skills training has traditionally been limited to formalin embalming that does not provide a realistic model. The aim of this study was to qualitatively and quantitatively compare Thiel and phenol‐based soft‐embalming techniques: qualitatively in a surgical training setup, and quantitatively by comparing the mechanical and histomorphometric properties of skin specimens embalmed using each method.
Bayesian inference and comparison of stochastic transcription elongation models

Transcription elongation can be modelled as a three step process, involving polymerase translocation, NTP binding, and nucleotide incorporation into the nascent mRNA. This cycle of events can be simulated at the single-molecule level as a continuous-time Markov process using parameters derived from single-molecule experiments. Previously developed models differ in the way they are parameterised, and in their incorporation of partial equilibrium approximations. We have formulated a hierarchical network comprised of 12 sequence-dependent transcription elongation models. The simplest model has two parameters and assumes that both translocation and NTP binding can be modelled as equilibrium processes. The most complex model has six parameters makes no partial equilibrium assumptions. We systematically compared the ability of these models to explain published force-velocity data, using approximate Bayesian computation. This analysis was performed using data for the RNA polymerases of E. coli, S. cerevisiae and Bacteriophage T7. Our analysis indicates that the polymerases differ significantly in their translocation rates, with the rates in T7 pol being fast compared to E. coli RNAP and S. cerevisiae pol II. Different models are applicable in different cases. We also show that all three RNA polymerases have an energetic preference for the posttranslocated state over the pretranslocated state. A Bayesian inference and model selection framework, like the one presented in this publication, should be routinely applicable to the interrogation of single-molecule datasets. Author summary Transcription is a critical biological process which occurs in all living organisms. It involves copying the organism’s genetic material into messenger RNA (mRNA) which directs protein synthesis on the ribosome. Transcription is performed by RNA polymerases which have been extensively studied using both ensemble and single-molecule techniques (see reviews: [1, 2]). Single-molecule data provides unique insights into the molecular behaviour of RNA polymerase. Transcription at the single-molecule level can be computationally simulated as a continuous-time Markov process and the model outputs compared with experimental data. In this study we use Bayesian techniques to perform a systematic comparison of 12 stochastic models of transcriptional elongation. We demonstrate how equilibrium approximations can strengthen or weaken the model, and show how Bayesian techniques can identify necessary or unnecessary model parameters. We describe publicly accessible and open-source software that can a) simulate, b) perform inference on, and c) compare models of transcription elongation.
Biomass-derived carbons for sodium-ion batteries and sodium-ion capacitors.

In the past decade, the rapid development of portable electronic devices, electric vehicles and electrical devices has stimulated extensive interests in fundamental research and commercialization of electrochemical energy storage systems. Biomass-derived carbon has garnered significant research attention as an efficient, inexpensive and eco-friendly active material for energy storage systems. Therefore, high-performance carbonaceous materials, derived from renewable sources, have been utilized as electrode materials in sodium-ion batteries and sodium-ion capacitors. In this review, we summarize the charge storage mechanism and utilization of biomass-derived carbon for sodium storage in batteries and capacitors. In particular, the structure-performance relationship of biomass-derived carbon for sodium storage in the form of batteries and capacitors is discussed. Despite the fact that further research is required to optimize the process and application of biomass-derived carbon in energy storage devices, the current review demonstrates the potential of carbonaceous materials for next-generation sodium-involved energy storage applications.