Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Synaptic Strength and mGlu2/3 Receptor Plasticity on Mouse Prefrontal Cortex Intra-telencephalic Pyramidal Cells Following Intermittent Access to Ethanol.

BACKGROUND The medial prefrontal cortex (PFC) is crucial for regulating cravings and alcohol-seeking in alcohol use disorder (AUD) patients and animal models. Maladaptive changes in volitional ethanol intake have been associated with PFC function, yet synaptic adaptations within PFC have not been consistently detected in voluntary drinking rodent models. At least 80% of the neurons in PFC are glutamatergic pyramidal cells. Pyramidal cells provide the predominant cortical output to several brain regions relevant to alcohol use disorder, including structures within the telencephalon (IT; e.g. basal ganglia, amygdala, other neocortical regions,) and also outside the telencephalon (ET; e.g. lateral hypothalamus, midbrain monoaminergic structures, thalamus). METHODS In addition to their anatomical distinctions, studies from several laboratories have revealed that prefrontal cortical IT and ET pyramidal cells may be separated by specific electrophysiological parameters. These distinguishable parameters provide opportunities to readily classify pyramidal cells into separable subtypes. Here, we employed and validated the hyperpolarization sag ratio as a diagnostic proxy for separating ET (Type A) and IT (Type B) neurons. We recorded from deep layer prelimbic PFC pyramidal cells of mice one day after 4-5 weeks of intermittent access (IA) ethanol exposure. RESULTS Membrane properties were not altered by IA ethanol, but excitatory postsynaptic strength onto IT Type B neurons was selectively enhanced in slices from IA ethanol mice. The increased excitatory drive was accompanied by enhanced mGlu2/3 receptor plasticity on IT Type B neurons, providing a potential translational approach to mitigate cognitive and motivational changes to PFC function related to binge drinking. CONCLUSIONS Together, these studies provide insight into the specific PFC neurocircuits altered by voluntary drinking. In addition, these findings provide additional rationale for developing compounds that potentiate mGlu2 and/or mGlu3 receptor function as potential treatments for AUD.
Caffeoylquinic Acid Derivatives of Purple Sweet Potato as Modulators of Mitochondrial Function in Mouse Primary Hepatocytes

Owing to their antioxidant properties, caffeoylquinic acid (CQA)-derivatives could potentially improve the impaired metabolism in hepatic cells, however, their effect on mitochondrial function has not been demonstrated yet. Here, we evaluated the impact of three CQA-derivatives extracted from purple sweet potato, namely 5-CQA, 3,4- and 4,5-diCQA, on mitochondrial activity in primary hepatocytes using an extracellular flux analyzer. Notably, an increase of maximal respiration and spare respiratory capacity were observed when 5-CQA and 3,4-diCQA were added to the system indicating the improved mitochondrial function. Moreover, 3,4-diCQA was shown to considerably increase glycolytic reserve which is a measure of cell capability to respond to an energy demand through glycolysis. Conversely, 4,5-diCQA did not modify mitochondrial activity but increased glycolysis at low concentration in primary hepatocytes. All compounds tested improved cellular capacity to oxidize fatty acids. Overall, our results demonstrated the potential of test CQA-derivatives to modify mitochondrial function in hepatic cells. It is especially relevant in case of dysfunctional mitochondria in hepatocytes linked to hepatic steatosis during obesity, diabetes, and metabolic syndrome.
Injection molded glass fiber reinforced poly(trimethylene terephthalate) composites: Fabrication and properties evaluation

Injection-molded composite materials as fabricated from chopped glass fiber and poly(trimethylene terephthalate), PTT, are evaluated through physicomechanical and thermomechanical analysis. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) were used to measure the thermal properties of the above composites. The mechanical properties including impact properties, tensile properties, and flexure properties of these composites were tested with a United Testing System SFM-20. Results showed that impact strength, tensile strength and modulus, flexure strength, and modulus of glass fiber reinforced PTT composites were improved significantly with increasing fiber content. The simultaneous improvement of both stiffness and toughness of composite materials is one of the important findings of this investigation. It was found that the crystallization temperature of PTT increased and heat deflection temperature doubled through reinforcement with glass fiber. The tensile fractured surfaces a.
Strengthening patient outcome evidence in health technology assessment: a coproduction approach

Abstract The National Institute for Health and Care Excellence (NICE) worked with patients and staff from six patient organizations to review existing health technology assessment (HTA) methods and coproduce proposals to improve the following: patient involvement, how patient evidence is identified and considered by committees, and the support offered to patient stakeholders. This engagement identified important factors that HTA bodies need to understand to enable meaningful patient and public involvement (PPI), such as having clearly documented processes, appropriate evidence submission processes, transparent decisions, and suitable support. This work demonstrated the benefits of HTA bodies working collaboratively with patient stakeholders to improve PPI. By doing so, HTA bodies can increase their knowledge and understanding of the barriers faced by patient stakeholders to develop appropriate solutions to remove them. The coproduction approach improved stakeholder engagement methods, provided a better analysis of data, supported the development of meaningful conclusions, and improved stakeholder relationships.
Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury

Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3–4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl2 model had significantly higher Green–Lagrange circumferential cyclic strain in PGG-treated animals (p < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl2 model. These findings highlight the continued need for improved understanding of PGG’s effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation.
Enzymatic hydrolysis of black cricket (Gryllus assimilis) proteins positively affects their antioxidant properties.

The development of innovative ingredients through biotechnological routes has established insect proteins as an emerging source of bioactive peptides. The current study aimed to evaluate the antioxidant properties of black cricket (Gryllus assimilis) protein hydrolysates produced using the proteases FlavourzymeTM 500L, AlcalaseTM 2.4L, and NeutraseTM 0.8L, either individually or in binary/ternary combinations. The enzymatic hydrolysis promoted an increase of approximately 160% in total antioxidant capacity and 93% in the ferric reducing antioxidant power. The isolated use of the enzyme FlavourzymeTM 500L showed the most prominent positive effect on the antioxidant properties, presenting an IC50 value of 455 and 71 µg/mL for DPPH and ABTS radicals scavenging activities, respectively. This sample was composed mainly of small peptides (MW < 3 kDa), in which the antioxidant properties increased after fractionation by ultrafiltration. Gel electrophoresis analysis showed protein hydrolysates composed mainly of polypeptide chains with a mass of less than 14 kDa. Finally, the enzymatic treatment proved to be an efficient process to improve the antioxidant properties of black cricket proteins, increasing the possibility of applying these hydrolysates as bioactive ingredients in food or nutraceutical products. PRACTICAL APPLICATION: Insects represent an alternative source of proteins. Their modification through hydrolysis allows for the acquisition of compounds with great potential in industrial applications, such as functional ingredients or for nutraceutical purposes. The use of our experimental design proved to be an adequate tool for defining the best process conditions required for increasing the attainment of biologically active compounds.
Oridonin interrupts cellular bioenergetics to suppress glioma cell growth by down‐regulating PCK2

We aim to evaluate the tumor metabolic suppressive activity of Oridonin (extract of Rabdosia rubescens) in glioma and elucidate its potential mechanism. Effects of Oridonin on U251/U87 cells were determined by CCK8, RTCA, colony formation, flow cytometry, wound healing, and Transwell assay. Xenograft tumor model to evaluate the effect of Oridonin on glioma cells in vivo. Cellular bioenergetics were measured by Seahorse. RNA‐seq was performed to screen potential biological pathways in Oridonin treated cells. Bioinformatics analysis of PCK2 in glioma was performed based on TCGA/CGGA. Endogenous PCK2 was knocked‐down by lentivirus packaged shRNA. We found Oridonin significantly inhibited cell growth in U251/U87 in vitro and in vivo. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were decreased in Oridonin‐treated U251/U87 cells. Oridonin treatment led to PCK2 down‐regulation. Additionally, PCK2 was up‐regulated in higher grade glioma and correlated with poor outcomes. Furthermore, PCK2 depletion significantly inhibited cell growth and decreased OCR/ECAR in U251/U87 which coincided with the effects of Oridonin. Therefore, we evaluated the potent anti‐tumor property of Oridonin in glioma. Importantly, we demonstrated that PCK2 might be a novel target of Oridonin on glioma by inducing energy crisis and increasing oxidative stress.
Drivers of expectations: Why are Norwegian general practitioners skeptical of a prospective electronic health record?

While expectations are well-known drivers of electronic health record (EHR) adoption, the drivers of expectations are more elusive. On the basis of interviews with general practitioners (GPs), we investigate how the early implementation process drives their expectations of an EHR that is being implemented in Norway. The GPs’ expectations of the prospective EHR are driven by (a) satisfying experiences with their current system, (b) the transfer of others’ experiences with the prospective EHR, (c) a sense of alignment, or lack thereof, with those in charge of the implementation process, (d) uncertainty about the inclusion of GP needs, and (e) competing technological futures. To manage expectations, starting early is important. Mismanaged expectations produce a need for convincing people to reverse their expectations. This appears to be the situation in Norway, where the GPs are currently skeptical of the prospective EHR.
Immune cell score, PD-L1 expression and prognosis in esophageal cancer

Anna Junttila , Juha P. V€ayrynen , Maarit Ahtiainen, Teijo Kuopio, Johanna Mrena, Eero Sihvo and Olli Helminen Department of Surgery, Central Finland Central Hospital, Jyv€askyl€a, Finland; Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland; Department of Education and Research, Central Finland Health Care District, Jyv€askyl€a, Finland; Department of Pathology, Central Finland Central Hospital, Jyv€askyl€a, Finland; Department of Biological and Environmental Science, University of Jyv€askyl€a, Jyv€askyl€a, Finland
Molecular and biochemical characterizations of a new cold-active and mildly alkaline β-Mannanase from Verrucomicrobiae DG1235

Abstract Mannanases catalyze the cleavage of β-1,4-mannosidic linkages in mannans and have various applications in different biotechnological industries. In this study, a new β-mannanase from Verrucomicrobiae DG1235 (ManDG1235) was biochemically characterized and its enzymatic properties were revealed. Amino acid alignment indicated that ManDG1235 belonged to glycoside hydrolase family 26 and shared a low amino acid sequence identity to reported β-mannanases (up to 50% for CjMan26C from Cellvibrio japonicus). ManDG1235 was expressed in Escherichia coli. Purified ManDG1235 (rManDG1235) exhibited the typical properties of cold-active enzymes, including high activity at low temperature (optimal at 20 °C) and thermal instability. The maximum activity of rManDG1235 was achieved at pH 8, suggesting that it is a mildly alkaline β-mannanase. rManDG1235 was able to hydrolyze a variety of mannan substrates and was active toward certain types of glucans. A structural model that was built by homology modeling suggested that ManDG1235 had four mannose-binding subsites which were symmetrically arranged in the active-site cleft. A long loop linking β2 and α2 as in CjMan26C creates a steric border in the glycone region of active-site cleft which probably leads to the exo-acting feature of ManDG1235, for specifically cleaving mannobiose from the non-reducing end of the substrate.
Assessment of Grouped Weighted Quantile Sum Regression for Modeling Chemical Mixtures and Cancer Risk

Individuals are exposed to a large number of diverse environmental chemicals simultaneously and the evaluation of multiple chemical exposures is important for identifying cancer risk factors. The measurement of a large number of chemicals (the exposome) in epidemiologic studies is allowing for a more comprehensive assessment of cancer risk factors than was done in earlier studies that focused on only a few chemicals. Empirical evidence from epidemiologic studies shows that chemicals from different chemical classes have different magnitudes and directions of association with cancers. Given increasing data availability, there is a need for the development and assessment of statistical methods to model environmental cancer risk that considers a large number of diverse chemicals with different effects for different chemical classes. The method of grouped weighted quantile sum (GWQS) regression allows for multiple groups of chemicals to be considered in the model such that different magnitudes and directions of associations are possible for each group of chemicals. In this paper, we assessed the ability of GWQS regression to estimate exposure effects for multiple chemical groups and correctly identify important chemicals in each group using a simulation study. We compared the performance of GWQS regression with WQS regression, the least absolute shrinkage and selection operator (lasso), and the group lasso in estimating exposure effects and identifying important chemicals. The simulation study results demonstrate that GWQS is an effective method for modeling exposure to multiple groups of chemicals and compares favorably with other methods used in mixture analysis. As an application, we used GWQS regression in the California Childhood Leukemia Study (CCLS), a population-based case-control study of childhood leukemia in California to estimate exposure effects for many chemical classes while also adjusting for demographic factors. The CCLS analysis found evidence of a positive association between exposure to the herbicide dacthal and an increased risk of childhood leukemia.
Studying chromosome biology with single-molecule resolution in Xenopus laevis egg extracts

Abstract Cell-free extracts from Xenopus laevis eggs are a model system for studying chromosome biology. Xenopus egg extracts can be synchronised in different cell cycle stages, making them useful for studying DNA replication, DNA repair and chromosome organisation. Combining single-molecule approaches with egg extracts is an exciting development being used to reveal molecular mechanisms that are difficult to study using conventional approaches. Fluorescence-based single-molecule imaging of surface-tethered DNAs has been used to visualise labelled protein movements on stretched DNA, the dynamics of DNA–protein complexes and extract-dependent structural rearrangement of stained DNA. Force-based single-molecule techniques are an alternative approach to measure mechanics of DNA and proteins. In this essay, the details of these single-molecule techniques, and the insights into chromosome biology they provide, will be discussed.
Percentage of energy contribution according to the degree of industrial food processing and associated factors in adolescents (EVA-JF study, Brazil)

Abstract Objective: To evaluate energetic contribution according to the degree of industrial food processing and its association with sociodemographic, anthropometric, biochemical, clinical and behavioural characteristics in adolescents. Design: Cross-sectional study (Adolescent Lifestyle Study). Food consumption was assessed using 24-h dietary recalls, with foods classified by degree of industrial progressing. The usual diet was estimated using the Multiple Source Method. In a linear regression model, the energy percentage (E %) was associated with sociodemographic, anthropometric, biochemical, clinical and behavioural characteristics, after adjustment for sex and age. Setting: Juiz de Fora, Brazil. Participants: Eight hundred and four adolescents, of both sexes, 14–19 years of age, enrolled in public schools. Results: The E % of unprocessed or minimally processed foods corresponded to 43·1 %, processed foods to 11·0 % and the ultraprocessed foods to 45·9 %. E % of unprocessed foods was associated with socio-economic stratum (adjusted β = −0·093; P = 0·032), neck circumference (adjusted β = 0·017; P = 0·049), screen time (adjusted β = −0·247; P = 0·036) and HDL-cholesterol (adjusted β = −0·156; P = 0·003). E % of ultraprocessed foods was associated with socio-economic stratum (adjusted β = 0·118; P = 0·011), screen time (adjusted β = 0·375; P = 0·003), BMI (adjusted β = −0·029; P = 0·025), neck circumference (adjusted β = −0·017; P = 0·028) and HDL-cholesterol (adjusted β = 0·150; P = 0·002). Conclusions: There was a high E % of ultraprocessed foods in the diet of the adolescents. Actions are needed to raise the awareness of adopting healthy eating habits.
Cold Atmospheric Plasma, a Novel Approach against Bladder Cancer, with Higher Sensitivity for the High-Grade Cell Line

Simple Summary Bladder cancer has a high incidence and mortality. Besides this, currently available therapies for this type of cancer have low efficacy and show considerable adverse effects, urging the need of new therapeutic approaches. Cold Atmospheric Plasma treatment presents itself as a promising alternative, having demonstrated antitumor effects against several types of cancer. The present work arises from a multidisciplinary team, namely, medical doctors and researchers, in an attempt to find new therapeutic strategies to fight bladder cancer. Therefore, our main objective is to evaluate Cold Atmospheric Plasma effects against bladder cancer, as well as the mechanisms by which it exerts its effects. The results obtained demonstrate that Cold Atmospheric Plasma treatment has a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line. This new approach using Cold Atmospheric Plasma for the treatment of bladder cancer presents enormous clinical benefits, since it is able to selectively treat the tumor tissue, sparing the normal urothelium, with an additional glaring positive economic impact, since it entails a decrease in the cost of therapy in comparison with conventional therapeutic options. Abstract Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on the exposure time, with small differences for both cell lines, but overall, they were more pronounced in the TCCSUP cell line. CAP showed to have a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line.
Random forests for predicting species identity of forensically important blow flies (Diptera: Calliphoridae) and flesh flies (Diptera: Sarcophagidae) using geometric morphometric data: Proof of concept

Wing shape variation has been shown to be useful for delineating forensically important fly species in two Diptera families: Calliphoridae and Sarcophagidae. Compared to DNA‐based identification, the cost of geometric morphometric data acquisition and analysis is relatively much lower because the tools required are basic, and stable softwares are available. However, to date, an explicit demonstration of using wing geometric morphometric data for species identity prediction in these two families remains lacking. Here, geometric morphometric data from 19 homologous landmarks on the left wing of males from seven species of Calliphoridae (n = 55), and eight species of Sarcophagidae (n = 40) were obtained and processed using Generalized Procrustes Analysis. Allometric effect was removed by regressing centroid size (in log10) against the Procrustes coordinates. Subsequently, principal component analysis of the allometry‐adjusted Procrustes variables was done, with the first 15 principal components used to train a random forests model for species prediction. Using a real test sample consisting of 33 male fly specimens collected around a human corpse at a crime scene, the estimated percentage of concordance between species identities predicted using the random forests model and those inferred using DNA‐based identification was about 80.6% (approximate 95% confidence interval = [68.9%, 92.2%]). In contrast, baseline concordance using naive majority class prediction was 36.4%. The results provide proof of concept that geometric morphometric data has good potential to complement morphological and DNA‐based identification of blow flies and flesh flies in forensic work.