Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent Metabolomics Analysis in Tumor Metabolism Reprogramming

Metabolic reprogramming has been suggested as a hallmark of cancer progression. Metabolomic analysis of various metabolic profiles represents a powerful and technically feasible method to monitor dynamic changes in tumor metabolism and response to treatment over the course of the disease. To date, numerous original studies have highlighted the application of metabolomics to various aspects of tumor metabolic reprogramming research. In this review, we summarize how metabolomics techniques can help understand the effects that changes in the metabolic profile of the tumor microenvironment on the three major metabolic pathways of tumors. Various non-invasive biofluids are available that produce accurate and useful clinical information on tumor metabolism to identify early biomarkers of tumor development. Similarly, metabolomics can predict individual metabolic differences in response to tumor drugs, assess drug efficacy, and monitor drug resistance. On this basis, we also discuss the application of stable isotope tracer technology as a method for the study of tumor metabolism, which enables the tracking of metabolite activity in the body and deep metabolic pathways. We summarize the multifaceted application of metabolomics in cancer metabolic reprogramming to reveal its important role in cancer development and treatment.
A Comparative Analysis of Super-Enhancers and Broad H3K4me3 Domains in Pig, Human, and Mouse Tissues

Super-enhancers (SEs) and broad H3K4me3 domains (BDs) are crucial regulators in the control of tissue identity in human and mouse. However, their features in pig remain largely unknown. In this study, by integrative computational analyses of epigenomic and transcriptomic data, we have characterized SEs and BDs in six pig tissues and analyzed their conservation in comparison with human and mouse tissues. Similar to human and mouse, pig SEs and BDs display higher tissue specificity than their typical counterparts. Genes proximal to SEs and BDs are associated with tissue identity in most tissues. About 55–182 SEs (5–17% in total) and 99–309 BDs (8–16% in total) across pig tissues are considered as functionally conserved elements because they have orthologous SEs and BDs in human and mouse. However, these elements do not necessarily exhibit sequence conservation. The functionally conserved SEs are correlated to tissue identity in majority of pig tissues, while those conserved BDs are linked to tissue identity in a few tissues. Our study provides resources for future gene regulatory studies in pig. It highlights that SEs are more effective in defining tissue identity than BDs, which is contrasting to a previous study. It also provides novel insights on understanding the sequence features of functionally conserved elements.
Scarcity Mindset Neuro Network Decoding With Reward: A Tree-Based Model and Functional Near-Infrared Spectroscopy Study

Resource scarcity imposes challenging demands on the human cognitive system. Insufficient resources cause the scarcity mindset to affect cognitive performance, while reward enhances cognitive function. Here, we examined how reward and scarcity simultaneously contribute to cognitive performance. Experimental manipulation to induce a polar scarcity mindset and reward conditions within participants under functional near-infrared spectroscopy (fNIRS) recording was implemented to explore the mechanism underlying the scarcity mindset and reward in terms of behavior and neurocognition. Participants showed decreased functional connectivity from the dorsolateral prefrontal cortex (DLPFC) to the ventrolateral prefrontal cortex (VLPFC) with a scarcity mindset, a region often implicated in cognitive control. Moreover, under reward conditions, the brain activation of the maximum total Hb bold signal was mainly located in the left hemisphere [channels 1, 3, and 4, left ventrolateral prefrontal cortex (L-VLPFC) and channel 6, left dorsolateral prefrontal cortex (L-DLPFC)], and there was also significant brain activation of the right dorsolateral prefrontal cortex (R-DLPFC) in the right hemisphere (channel 17). Furthermore, these data indicate the underlying neural changes of the scarcity mentality and demonstrate that brain activities may underlie reward processing. Additionally, the base-tree machine learning model was trained to detect the mechanism of reward function in the prefrontal cortex (PFC). According to SHapley Additive exPlanations (SHAP), channel 8 contributed the most important effect, as well as demonstrating a high-level interrelationship with other channels.
Numerical Modelling of Shear Crack Angles in Frp Shear-Strengthened Reinforced Concrete Beams

Summary The shear crack angle is a key parameter in the calculation of the fibre-reinforced polymer (FRP) contribution to the shear capacity of a shear-strengthened reinforced concrete beam. In this study, a new approach is developed to estimate the shear crack angles for such a beam. The approach is based on the FRP/concrete interface response. A non-linear finite element model was developed to simulate the behaviour of six beams grouped in three sets according to their dimensions. One unstrengthened beam of each set was used as a benchmark and its behaviour was compared to that of a beam strengthened with a U-wrap scheme. It was found that the numerical model is able to successfully simulate the behaviour of the shear-strengthened beams. The numerical predictions compare very well with previously published experimental data in terms of load-deflection relationships and carbon FRP (CFRP) axial strain profiles along the sheet length. The analysis of the slip profiles along the CFRP strip is helpful to understand the bond behaviour between the concrete and CFRP strips. The interfacial slip profiles are used to predict the shear crack angle along the shear span, and these predictions agree very well with the experimental measurements. The numerical results give failure modes that are identical to those obtained experimentally.
Macrophages Are the Key Players in Promoting Hyper-Inflammatory Response in a Mouse Model of TB-IRIS

TB-IRIS is an abnormal inflammatory response in a subset of HIV-TB co-infected patients shortly after initiation of anti-retroviral therapy (ART). Therapy in these patients could have greatly improved the life expectancy as ART reconstitutes the function and number of CD4+ T cells and many patients see improvement in symptoms but paradoxically up to 54% of co-infected patients develop TB-IRIS. Different studies have indicated that both innate and adaptive immunity are involved in the pathology of IRIS but the role of macrophages in abnormal activation of CD4+ T cells is poorly understood. Since macrophages are one of the major antigen-presenting cells and are infected by M.tb at a high frequency, they are very much likely to be involved in the development of TB-IRIS. In this study, we have developed a mouse model of experimental IRIS, in which M.tb-infected T-cell knockout mice undergo a fatal inflammatory disease after CD4+ T cell reconstitution. Lung macrophages and blood monocytes from M.tb-infected TCRβ−/− mice showed upregulated expression of cell surface activation markers and also showed higher mRNA expression of inflammation-associated chemokines and matrix metalloproteases responsible for tissue damage. Furthermore, cytokine and TLR signaling feedback mechanism to control excessive inflammation was also found to be dysregulated in these macrophages under lymphopenic conditions. Previous studies have shown that hyperactive CD4+ T cells are responsible for disease induction and our study shows that somehow macrophages are in a higher activated state when infected with M.tb in an immune-deficient condition, which results in excessive activation of the adoptively transferred CD4+ T cells. Understanding of the mechanisms underlying the pathophysiology of TB-IRIS would facilitate identification of prospective biomarkers for disease development in HIV-TB co-infected patients before starting antiretroviral therapy.
Therapeutic Reference Ranges for Psychotropic Drugs: A Protocol for Systematic Reviews

Background: For many psychotropic drugs, monitoring of drug concentrations in the blood (Therapeutic Drug Monitoring; TDM) has been proven useful to individualize treatments and optimize drug effects. Clinicians hereby compare individual drug concentrations to population-based reference ranges for a titration of prescribed doses. Thus, established reference ranges are pre-requisite for TDM. For psychotropic drugs, guideline-based ranges are mostly expert recommendations derived from a conglomerate of cohort and cross-sectional studies. A systematic approach for identifying therapeutic reference ranges has not been published yet. This paper describes how to search, evaluate and grade the available literature and validate published therapeutic reference ranges for psychotropic drugs. Methods/Results: Following PRISMA guidelines, relevant databases have to be systematically searched using search terms for the specific psychotropic drug, blood concentrations, drug monitoring, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The search should be restricted to humans, and diagnoses should be pre-specified. Therapeutic references ranges will not only base upon studies that report blood concentrations in relation to clinical effects, but will also include implications from neuroimaging studies on target engagement. Furthermore, studies reporting concentrations in representative patient populations are used to support identified ranges. Each range will be assigned a level of underlying evidence according to a systematic grading system. Discussion: Following this protocol allows a comprehensive overview of TDM literature that supports a certain reference range for a psychotropic drug. The assigned level of evidence reflects the validity of a reported range rather than experts' opinions.
A Novel Immune-Gene Pair Signature Revealing the Tumor Microenvironment Features and Immunotherapy Prognosis of Muscle-Invasive Bladder Cancer

Immunotherapy has been a milestone for muscle-invasive bladder cancer (MIBC), but only a small portion of patients can benefit from it. Therefore, it is crucial to develop a robust individualized immune-related signature of MIBC to identify patients potentially benefiting from immunotherapy. The current study identified patients from the Cancer Genome Atlas (TCGA) and immune genes from the ImmPort database, and used improved data analytical methods to build up a 45 immune-related gene pair signature, which could classify patients into high-risk and low-risk groups. The signature was then independently validated by a Gene Expression Omnibus (GEO) dataset and IMvigor210 data. The subsequent analysis confirmed the worse survival outcomes of the high-risk group in both training (p < 0.001) and validation cohorts (p = 0.018). A signature-based risk score was proven to be an independent risk factor of overall survival (p < 0.001) and could predict superior clinical net benefit compared to other clinical factors. The CIBERSORT algorithm revealed the low-risk group had increased CD8+ T cells plus memory-activated CD4+ T-cell infiltration. The low-risk group also had higher expression of PDCD1 (PD-1), CD40, and CD27, and lower expression of CD276 (B7-H3) and PDCD1LG2 (PD-L2). Importantly, IMvigor210 data indicated that the low-risk group had higher percentage of “inflamed” phenotype plus less “desert” phenotype, and the survival outcomes were significantly better for low-risk patients after immunotherapy (p = 0.014). In conclusion, we proposed a novel and promising prognostic immune-related gene pair (IRGP) signature of MIBC, which could provide us a panoramic view of the tumor immune microenvironment of MIBC and independently identify MIBC patients who might benefit from immunotherapy.
Genetic Architecture of Novel Sources for Reproductive Cold Tolerance in Sorghum

Enhancements in reproductive cold tolerance of sorghum are essential to expand growing areas into both high-latitude temperate areas and tropical high-altitude environments. Here we present first insights into the genetic architecture of this trait via genome-wide association studies in a broad genetic diversity set (n = 330) phenotyped in multi-location field trials including high-altitude tropical (Mexico) and high-latitude temperate (Germany) environments. We observed a high degree of phenotypic variation and identified several novel, temperate-adapted accessions with superior and environmentally stable cold tolerance. Good heritability indicates strong potential for implementation of reproductive cold tolerance in breeding. Although the trait was found to be strongly quantitative, promising genomic regions with multiple-trait associations were found, including hotspots on chromosomes 3 and 10 which contain candidate genes implicated in different developmental and survival processes under abiotic stress conditions.
Intestinal Helminth Communities of Grey Partridge Perdix perdix and Common Pheasant Phasianus colchicus in Poland

Simple Summary The presence of intestinal parasites such as nematodes, cestodes, and trematodes is a serious problem for programmes for the conservation of partridges and pheasants, mainly involving the breeding of these birds and their release into the natural environment. These parasites can cause disease in these birds, whether farmed or free-living. The aim of this study was to describe the morphology of parasitic worms in the partridge, native to Poland, and the introduced pheasant, and to determine the level of infection of these birds with intestinal parasitic worms. The study showed that partridges are infected with several helminth species that had not previously been recorded in this species in Poland. Pheasants are more often infected by intestinal nematodes than are partridges. These worms can negatively affect the condition of partridges and increase their risk of infection with pathogenic protozoa. The results of parasitological examination should be used to develop programmes for diagnosis and monitoring of parasitic infections in order to keep flocks free of parasites. Abstract The aim of this study was to describe the morphology and means of identification of helminths in native partridges (65) and introduced pheasants (32) in Poland and to determine the level of intestinal infection of these birds by helminths using parasitological and ecological indices. The birds were acquired during the hunting season in the years 2015–2017. Nematodes, Capillaria phasianina, cestodes, Railietina friedbergeri, and one trematode, Brachylaima sp. were recorded for the first time in partridges in Poland. Our findings indicate that parasites are more prevalent in pheasants (prevalence 70.4%) than in partridges (prevalence 50.0%). The component community and infracommunity of parasites of partridges are more diverse (Simpson’s diversity index: 0.63 and mean Brillouin diversity index: 0.10 ± 0.17) and less dominated by a single parasite species (Capillaria sp., Berger-Parker dominance index: 0.53) than the pheasant parasite community (Simpson’s diversity index: 0.07, mean Brillouin diversity index: 0.005 ± 0.02, dominant species Heterakis gallinarum, Berger-Parker dominance index: 0.96). There were statistically significant differences between partridges and pheasants in the Brillouin diversity index and in the prevalence of Heterakis gallinarum (55.6% in pheasants vs. 19.0 in partridges). There were significant differences between wild and farmed partridges in the prevalence of infection by Capillaria sp. (4.3% vs. 37.5%) and H. gallinarum (39.1 vs. 6.2%). In conclusion, the pheasant was shown to be a reservoir, carrier, and shedder of nematodes, which may increase the risk of infection in partridges.
Guidelines for Identification of Hazardous Highway Curves

Curve-warning treatment can be extremely cost-effective because of the low cost of treatments, such as curve warning signs or markings, and the potentially large number of target crashes. However, measures are needed to identify and prioritize treatment of potentially hazardous rural curves. An empirical Bayes-based procedure is presented for prioritizing potential treatment sites on the basis of crashes that may be classified as occurring because of the presence of curves. The attractiveness of the procedure is enhanced by the fact that the data and calculations are also a part of the evaluation of treatment that may be applied to sites identified. Alternative levels of the procedure can be selected, depending on the data available. Ontario data were used to calibrate supporting models. It is hoped that experience gained from using the guidelines can lead to the development of procedures that can be incorporated into the U.S. Department of Transportation’s Manual on Uniform Traffic Control Devices.
The use of a long-acting tranquilizer (zuclopenthixol acetate) and live video monitoring for successful long-distance transport of caribou (Rangifer tarandus)

Long-distance transport of caribou (Rangifer tarandus) can result in morbidities and mortalities. This case report describes the use of a long-acting tranquilizer, zuclopenthixol acetate (ZA) and live video monitoring (LVM) to transport caribou over 2300 kilometers. Two groups of captive caribou were transported from Fort St. John, British Columbia to Dryden, Ontario (n=14; 28.5 h transport) and Anchorage, Alaska (n=11; 32 h transport). The day prior to transport, caribou were administered ZA at 1 mg/kg via deep intramuscular (IM) injection. Digital video cameras allowed for live observation of caribou during transport. Still images of videos from each compartment in the Ontario transport were analyzed for percentage (%) lying versus standing over three time periods (Day 1, Night, and Day 2). Overall, caribou spent 57% of the transport lying down, with the highest percentage occurring at night (73%). As group size and animal density decreased there was a trend for caribou to spend more time lying down. Three animals developed extrapyramidal effects to the ZA and were effectively treated with midazolam at 0.2 mg/kg IM. There were no significant visible injuries or mortalities during or up to 6 weeks post-transport. Zuclopenthixol acetate and LVM were used to successfully transport caribou over long distances and should be considered in future translocations to improve animal welfare during transport.
Disconnected Gas Transport in Steady‐State Three‐Phase Flow

We use high‐resolution three‐dimensional X‐ray microtomography to investigate fluid displacement during steady‐state three‐phase flow in a cm‐sized water‐wet sandstone rock sample. The pressure differential across the sample is measured which enables the determination of relative permeability; capillary pressure is also estimated from the interfacial curvature. Though the measured relative permeabilities are consistent, to within experimental uncertainty, with values obtained without imaging on larger samples, we discover a unique flow dynamics. The most non‐wetting phase (gas) is disconnected across the system: gas flows by periodically opening critical flow pathways in intermediate‐sized pores. While this phenomenon has been observed in two‐phase flow, here it is significant at low flow rates, where capillary forces dominate at the pore‐scale. Gas movement proceeds in a series of double and multiple displacement events. Implications for the design of three‐phase flow processes and current empirical models are discussed: the traditional conceptualization of three‐phase dynamics based on analogies to two‐phase flow vastly over‐estimates the connectivity and flow potential of the gas phase.
Early‐life exposure to selective serotonin reuptake inhibitors: Long‐term effects on pain and affective comorbidities

A growing body of evidence indicates that early‐life exposure to selective serotonin reuptake inhibitor has long‐term consequences on the offspring's pain in addition to affective disorders like anxiety disorder and major depression. Serotonin, besides its role in regulating pain and emotions, promotes neuronal network formation. The prefrontal cortex and the amygdala are two key brain regions involved in the modulation of pain and its affective comorbidities. Thus, the aim of this review is to understand how early‐life selective serotonin reuptake inhibitor exposure alters the developing prefrontal cortex and amygdala and thereby underlies the long‐term changes in pain and its affective comorbidities in later life. While there is still limited data on the effects of early‐life selective serotonin reuptake inhibitor exposure on pain, there is a substantial body of evidence on its affective comorbidities. From this perspective paper, four conclusions emerged. First, early‐life selective serotonin reuptake inhibitor exposure results in long‐term nociceptive effects, which needs to be consistently studied to clarify. Second, it results in enhanced depressive‐like behaviour and diminished exploratory behaviour in adult rodents. Third, early‐life selective serotonin reuptake inhibitor exposure alters serotonergic levels, transcription factors expression, and brain‐derived neurotrophic factor levels, resulting in hyperconnectivity within the amygdala and the prefrontal cortex. Finally, it affects antinociceptive inputs of the prefrontal cortex and the amygdala in the spinal cord. We conclude that early‐life selective serotonin reuptake inhibitor exposure affects the maturation of prefrontal cortex and amygdala circuits and thereby enhances their antinociceptive inputs in the spinal cord.
Characterization of Anti-Ana o 3 Monoclonal Antibodies and Their Application in Comparing Brazilian Cashew Cultivars

Ana o 3 is an immuno-dominant cashew nut allergen. Four monoclonal antibodies to Ana o 3 (2H5, 6B9C1, 19C9A2, and 5B7F8) were characterized by ELISA and in silico modeling. The 2H5 antibody was the only antibody specific for cashew nut extract. In addition to cashew nut extract, the 6B9C1 and 19C9A2 antibodies recognized pistachio extract, and the 5B7F8 recognized pecan extract. All four antibodies recognized both recombinant Ana o 3.0101 and native Ana o 3. ELISA assays following treatment of purified Ana o 3 with a reducing agent indicated that the 6B9C1 and 19C9A2 antibodies likely recognize conformational epitopes, while the 2H5 and 5B7F8 antibodies likely recognize linear epitopes. In silico modeling predicted distinct epitopes for each of the anti-Ana o 3 antibodies. Screening extracts from 11 Brazilian cashew nut cultivars using all four antibodies showed slight differences in Ana o 3 bindings, demonstrating that these antibodies could identify cultivars with varying allergen content.