Miracle-dz/UniFAR-FTUs huggingface dataset:
Nicotinamide Improves Cognitive Function in Mice With Chronic Cerebral Hypoperfusion

Normal brain function requires steady blood supply to maintain stable energy state. When blood supply to the brain becomes suboptimal for a long period of time, chronic cerebral hypoperfusion (CCH) and a variety of brain changes may occur. CCH causes white matter injury and cognitive impairment. The present study investigated the effect of nicotinamide (NAM) on CCH-induced cognitive impairment and white matter damage in mice. Male C57Bl/6J mice aged 10–12 weeks (mean age = 11 ± 1 weeks) and weighing 24 - 29 g (mean weight = 26.5 ± 2.5 g) were randomly assigned to three groups (eight mice/group): sham group, CCH group and NAM group. Chronic cerebral hypoperfusion (CCH) was induced using standard methods. The treatment group mice received intraperitoneal injection of NAM at a dose of 200 mg/kg body weight (bwt) daily for 30 days. Learning, memory, anxiety, and depression-like behaviors were measured using Morris water maze test (MWMT), open field test (OFT), sucrose preference test (SPT), and forced swim test (FST), respectively. White matter damage and remodeling were determined via histological/ immunohistochemical analyses, and western blotting, respectively. The results showed that the time spent in target quadrant, number of crossings and escape latency were significantly lower in CCH group than in sham group, but they were significantly increased by NAM (p < 0.05). Mice in NAM group moved significantly faster and covered longer distances, when compared with those in CCH group (p < 0.05). The percentage of time spent in open arms and the number of entries to the open arms were significantly lower in CCH group than in NAM group (p < 0.05). Moreover, anhedonia and histologic scores (index of myelin injury) were significantly higher in CCH group than in sham group, but they were significantly reduced by NAM (p < 0.05). The results of immunohistochemical staining and Western blotting showed that the protein expressions of 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) and synaptophysin were significantly downregulated in CCH group, relative to sham group, but they were significantly upregulated by NAM (p < 0.05). These results indicate that NAM improves cognitive function in mice with CCH.
Computerized Adaptive Testing for Schizotypal Personality Disorder: Detecting Individuals at Risk

As schizotypal personality disorder (SPD) increasingly prevails in the general population, a rapid and comprehensive measurement instrument is imperative to screen individuals at risk for SPD. To address this issue, we aimed to develop a computerized adaptive testing for SPD (CAT-SPD) using a non-clinical Chinese sample (N = 999), consisting of a calibration sample (N1 = 497) and a validation sample (N2 = 502). The item pool of SPD was constructed from several widely used SPD scales and statistical analyses based on the item response theory (IRT) via a calibration sample using a graded response model (GRM). Finally, 90 items, which measured at least one symptom of diagnostic criteria of SPD in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and had local independence, good item fit, high slope, and no differential item functioning (DIF), composed the final item pool for the CAT-SPD. In addition, a simulated CAT was conducted in an independent validation sample to assess the performance of the CAT-SPD. Results showed that the CAT-SPD not only had acceptable reliability, validity, and predictive utility but also had shorter but efficient assessment of SPD which can save significant time and reduce the test burden of individuals with less information loss.
Gambling in COVID-19 Lockdown in the UK: Depression, Stress, and Anxiety

To combat the spread of COVID-19, the UK Government implemented a range of “lockdown” measures. Lockdown has necessarily changed the gambling habits of gamblers in the UK, and the impact of these measures on the mental health of gamblers is unknown. To understand the impact of lockdown on gamblers, in April 2020, after ~6 weeks of lockdown, participants (N = 1,028, 72% female) completed an online questionnaire. Gambling engagement data was collected for pre-lockdown via the Brief Problem Gambling Screen (BPGS) allowing participants to be classified as Non-Gamblers (NG), Non-Problem Gamblers (NPG) or Potential Problem Gamblers (PPG). The Depression, Stress, and Anxiety Scale (DASS21) was used to measure depression, stress, and anxiety scores both pre- and during-lockdown. Results indicate that depression, stress and anxiety has increased across the whole sample. Participants classified in the PPG group reported higher scores on each sub scale at both baseline and during lockdown. Increases were observed on each DASS21 subscale, for each gambler group, however despite variable significance and effect sizes, the magnitude of increases did not differ between groups. Lockdown has had a significant impact on mental health of participants; whilst depression stress and anxiety remain highest in potential problem gamblers, pre-lockdown gambler status did not affect changes in DASS21 scores.
Modeling radiation heat transfer with participating media in solid oxide fuel cells

Solid oxide fuel cell (SOFC) technology has been shown to be viable, but its profitability has not yet been seen. To achieve a high net efficiency at a low net cost, a detailed understanding of the transport processes both inside and outside of the SOFC stack is required. Of particular significance is an accurate determination of the temperature distribution because material properties, chemical kinetics, and transport properties depend heavily on the temperature. Effective utilization of the heat can lead to a substantial increase in overall system efficiency and decrease in operating cost. Despite the extreme importance in accurately predicting temperature, the SOFC modeling community appears to be uncertain about the importance of incorporating radiation into their models. Although some models have included it, the majority of models ignore radiative heat transfer. SOFCs operate at temperatures around or above 1200 K, where radiation effects can be significant. In order to correctly predict the radiation heat transfer, participating gases must also be included. Water vapor and carbon dioxide can absorb, emit, and scatter radiation, and are present at the anode in high concentrations. This paper presents a simple thermal transport model for analyzing heat transfer and improving thermal management within planar SOFCs. The model was implemented using a commercial computational fluid dynamic code and includes conduction, convection, and radiation in a participating media. It is clear from this study that radiation must be considered when modeling solid oxide fuel cells. The effect of participating media radiation was shown to be minimal in this geometry, but it is likely to be more important in tubular geometries.
Effects of Grazing Enclosures on Species Diversity, Phenology, Biomass, and Carrying Capacity in Borana Rangeland, Southern Ethiopia

A grazing enclosure (GE) is one of the most effective techniques for restoring degraded rangelands by modifying the composition, abundance, and diversity of species. However, the effect of GEs on different grazing intensities and durations compared to open-grazing (OG) rangelands is not well known. We aimed to assess the effect of GE on the characteristics of plant species. We established five plots in a short-term enclosure, a long-term enclosure, and an OG treatment to examine the effect of GE on vegetation species’ height, abundance, diversity, phenology, biomass, heterogeneity, and the carrying capacity (CC) of rangeland under grazed and enclosed conditions. We found that GE significantly (P < 0.05) increased vegetation height, abundance, biomass, CC, phenological period, and species diversity. However, the increase in height, diversity, and phenological periods were not consistent with enclosure duration, and higher increments were recorded at the short-term enclosure site. The highest Shannon index value recorded at StGE (2.45) was 28.6 and 12.2% greater than the LtGE (1.75) and OG (2.15) sites, respectively. The advanced phenological periods were higher at the StGE site and showed 22.6 and 60.3% higher values than the LtGE and OG sites, respectively. The highest carrying capacities of 23.4 and 114.3% for livestock were observed at the LtGE compared to the StGE and OG grazing sites. In addition, the heterogeneity of the plants’ community was significantly higher in the long-term GE, due to the decrease in species’ diversity. In conclusion, this paper further contributes to the development of the theoretical basis on the effects of GEs and recommends strategies like rotational grazing and reseeding to be used in tandem with a GE for sustainable management of rangelands.
Macrophage Control of Incipient Bone Formation in Diabetic Mice

Both soft and hard tissue wound healing are impaired in diabetes. Diabetes negatively impacts fracture healing, bone regeneration and osseointegration of endosseous implants. The complex physiological changes associated with diabetes often manifest in immunological responses to wounding and repair where macrophages play a prominent role in determining outcomes. We hypothesized that macrophages in diabetes contribute toward impaired osseous wound healing. To test this hypothesis, we compared osseous wound healing in the mouse calvaria defect model using macrophages from C57BL/6J and db/db mice to direct osseous repair in both mouse strains. Initial analyses revealed that db/db mice macrophages showed an inflamed phenotype in its resting state. Incipient bone regeneration evaluated by μCT indicated that bone regeneration was relatively impaired in the db/db mouse calvaria and in the calvaria of C57BL/6J mice supplemented with db/db macrophages. Furthermore, osteogenic differentiation of mouse mesenchymal stem cells was negatively impacted by conditioned medium from db/db mice compared to C57BL/6J mice. Moreover, miR-Seq analysis revealed an altered miRNA composition in db/db macrophages with up regulated pro-inflammatory miRNAs and down regulated anti-inflammatory miRNAs. Overall, this study represents a direct step toward understanding macrophage-mediated regulation of osseous bone regeneration and its impairment in type 2 diabetes mellitus.
Regulated Tristetraprolin Overexpression Dampens the Development and Pathogenesis of Experimental Autoimmune Uveitis

Non-infectious uveitis, a common cause of blindness in man, is often mediated by autoimmunity, a process in which cytokines play major roles. The biosynthesis and secretion of pro-inflammatory cytokines are regulated in part by tristetraprolin (TTP), an endogenous anti-inflammatory protein that acts by binding directly to specific sequence motifs in the 3’-untranslated regions of target mRNAs, promoting their turnover, and inhibiting synthesis of their encoded proteins. We recently developed a TTP-overexpressing mouse (TTPΔARE) by deleting an AU-rich element (ARE) instability motif from the TTP mRNA, resulting in increased accumulation of TTP mRNA and protein throughout the animal. Here, we show that homozygous TTPΔARE mice are resistant to the induction of experimental autoimmune uveitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP), an established model for human autoimmune (noninfectious) uveitis. Lymphocytes from TTPΔARE mice produced lower levels of the pro-inflammatory cytokines IFN-γ, IL-17, IL-6, and TNFα than wild type (WT) mice. TTPΔARE mice also produced lower titers of antibodies against the uveitogenic protein. In contrast, TTPΔARE mice produced higher levels of the anti-inflammatory cytokine IL-10, and had higher frequencies of regulatory T-cells, which, moreover, displayed a moderately higher per-cell regulatory ability. Heterozygous mice developed EAU and associated immunological responses at levels intermediate between homozygous TTPΔARE mice and WT controls. TTPΔARE mice were able, however, to develop EAU following adoptive transfer of activated WT T-cells specific to IRBP peptide 651–670, and naïve T-cells from TTPΔARE mice could be activated by antibodies to CD3/CD28. Importantly, TTPΔARE antigen presenting cells were significantly less efficient compared to WT in priming naïve T cells, suggesting that this feature plays a major role in the dampened immune responses of the TTPΔARE mice. Our observations demonstrate that elevated systemic levels of TTP can inhibit the pathogenic processes involved in EAU, and suggest the possible use of TTP-based treatments in humans with uveitis and other autoimmune conditions.
The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay. Aim of the study was to evaluate DP-compatibility beyond the established TCE3 algorithm by assessing the combined effect of several DP-mismatch parameters on post-transplant outcome. We implemented an extended DP-mismatch assessment model where TCE3, DP allotype expression with respect to rs9277534, mismatch vector and number of mismatches were conjointly taken into consideration. In this model, non-permissive HLA-DPB1 mismatches showed significantly increased aGvHD risk if they were accompanied by two HLA-DPB1 mismatches in GvH direction (HR: 1.46) or one mismatched highly expressed patient allotype (HR: 1.53). As previously reported, non-permissive HLA-DPB1 mismatches associated with a significantly higher risk of aGvHD and non-relapse mortality (HR 1.36 and 1.21, respectively), which in turn translated into worse GvHD and relapse free survival (HR 1.13). Effects on GvL and GvHD appeared strongest in GvH-directed non-permissive mismatches. Our study results support the consideration of additional HLA-DPB1 mismatch parameters along with the established TCE3 matching algorithm for refinement of future donor selection. In particular, our findings suggest that DP non-permissiveness associated with two HLA-DPB1 mismatches or at least on highly expressed mismatched patient allotype should be avoided.
Diagnostic Performance of Theranostic Radionuclides Used in Transarterial Radioembolization for Liver Cancer

Primary liver tumor with hepatocellular carcinoma accounting for 75–80% of all such tumors, is one of the global leading causes of cancer-related death, especially in cirrhotic patients. Liver tumors are highly hypervascularized via the hepatic artery, while normal liver tissues are mainly supplied by the portal vein; consequently, intra-arterially delivered treatment, which includes transarterial chemoembolization (TACE) and transarterial radioembolization (TARE), is deemed as a palliative treatment. With the development of nuclear technology and radiochemistry, TARE has become an alternative for patients with hepatic cancer, especially for patients who failed other therapies, or for patients who need tumor downstaging treatment. In practice, some radionuclides have suitable physicochemical characteristics to act as radioactive embolism agents. Among them, 90Y emits β rays only and is suitable for bremsstrahlung single photon emission computed tomography (BS SPECT) and positron emission tomography (PET); meanwhile, some others, such as 131I, 153Sm, 166Ho, 177Lu, 186Re, and 188Re, emit both β and γ rays, enabling embolism beads to play a role in both therapy and single photon emission computed tomography (SPECT) imaging. During TARE, concomitant imaging provide additive diagnostic information and help to guide the course of liver cancer treatment. Therefore, we review the theranostic radionuclides that have been used or could potentially be used in TARE for liver cancer and focus on the clinical benefits of diagnostic applications, including real-time monitoring of embolism beads, evaluating irradiation dose, predicting therapy effects, and corresponding adjustments to TARE.
Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins—An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic

Owing to the high mortality and the spread rate, the infectious disease caused by SARS-CoV-2 has become a major threat to public health and social economy, leading to over 70 million infections and 1. 6 million deaths to date. Since there are currently no effective therapeutic or widely available vaccines, it is of urgent need to look for new strategies for the treatment of SARS-CoV-2 infection diseases. Binding of a viral protein onto cell surface heparan sulfate (HS) is generally the first step in a cascade of interaction that is required for viral entry and the initiation of infection. Meanwhile, interactions of selectins and cytokines (e.g., IL-6 and TNF-α) with HS expressed on endothelial cells are crucial in controlling the recruitment of immune cells during inflammation. Thus, structurally defined heparin/HS and their mimetics might serve as potential drugs by competing with cell surface HS for the prevention of viral adhesion and modulation of inflammatory reaction. In this review, we will elaborate coronavirus invasion mechanisms and summarize the latest advances in HS–protein interactions, especially proteins relevant to the process of coronavirus infection and subsequent inflammation. Experimental and computational techniques involved will be emphasized.
Human Dental Pulp Stem Cells Display a Potential for Modeling Alzheimer Disease-Related Tau Modifications

We present here the first description of tau in human dental pulp stem cells (DPSCs) evidenced by RT-PCR data on expression of the gene MAPT and by immunocytochemical detection of epitopes by 12 anti-tau antibodies. The tau specificity of eight of these antibodies was confirmed by their affinity to neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) postmortem brain samples. We therefore used DPSCs and AD brain samples as a test system for determining the probability of the involvement of tau epitopes in the mechanisms converting tau into NFT in AD. Three antibodies to non-phosphorylated and seven antibodies to phosphorylated epitopes bound tau in both DPSCs and AD NFTs, thus suggesting that their function was not influenced by inducers of formation of NFTs in the AD brain. In contrast, AT100, which recognizes a hyperphosphorylated epitope, did not detect it in the cytoplasm of DPSCs but detected it in AD brain NFTs, demonstrating its AD diagnostic potential. This indicated that the phosphorylation/conformational events required for the creation of this epitope do not occur in normal cytoplasm and are a part of the mechanism (s) leading to NFT in AD brain. TG3 bound tau in the cytoplasm and in mitotic chromosomes but did not find it in nuclei. Collectively, these observations characterize DPSCs as a novel tau-harboring neuronal lineage long-term propagable in vitro cellular system for the normal conformational state of tau sites, detectable by antibodies, with their state in AD NFTs revealing those involved in the pathological processes converting tau into NFTs in the course of AD. With this information, one can model the interaction of tau with inducers and inhibitors of hyperphosphorylation toward NFT-like aggregates to search for drug candidates. Additionally, the clonogenicity of DPSCs provides the option for generation of cell lineages with CRISPR-mutagenized genes of familial AD modeling.
Uncertain About Uncertainty: How Qualitative Expressions of Forecaster Confidence Impact Decision-Making With Uncertainty Visualizations

When forecasting events, multiple types of uncertainty are often inherently present in the modeling process. Various uncertainty typologies exist, and each type of uncertainty has different implications a scientist might want to convey. In this work, we focus on one type of distinction between direct quantitative uncertainty and indirect qualitative uncertainty. Direct quantitative uncertainty describes uncertainty about facts, numbers, and hypotheses that can be communicated in absolute quantitative forms such as probability distributions or confidence intervals. Indirect qualitative uncertainty describes the quality of knowledge concerning how effectively facts, numbers, or hypotheses represent reality, such as evidence confidence scales proposed by the Intergovernmental Panel on Climate Change. A large body of research demonstrates that both experts and novices have difficulty reasoning with quantitative uncertainty, and visualizations of uncertainty can help with such traditionally challenging concepts. However, the question of if, and how, people may reason with multiple types of uncertainty associated with a forecast remains largely unexplored. In this series of studies, we seek to understand if individuals can integrate indirect uncertainty about how “good” a model is (operationalized as a qualitative expression of forecaster confidence) with quantified uncertainty in a prediction (operationalized as a quantile dotplot visualization of a predicted distribution). Our first study results suggest that participants utilize both direct quantitative uncertainty and indirect qualitative uncertainty when conveyed as quantile dotplots and forecaster confidence. In manipulations where forecasters were less sure about their prediction, participants made more conservative judgments. In our second study, we varied the amount of quantified uncertainty (in the form of the SD of the visualized distributions) to examine how participants’ decisions changed under different combinations of quantified uncertainty (variance) and qualitative uncertainty (low, medium, and high forecaster confidence). The second study results suggest that participants updated their judgments in the direction predicted by both qualitative confidence information (e.g., becoming more conservative when the forecaster confidence is low) and quantitative uncertainty (e.g., becoming more conservative when the variance is increased). Based on the findings from both experiments, we recommend that forecasters present qualitative expressions of model confidence whenever possible alongside quantified uncertainty.