Miracle-dz/UniFAR-FTUs huggingface dataset:
An Investigation Into the Effects of Destination Sensory Experiences at Visitors’ Digital Engagement: Empirical Evidence From Sanya, China

This study investigates the mechanism of how sensory experiences influence visitors’ digital engagement with a destination through establishing a strong bond and identification between a destination and tourist utilizing a two-step process. First, visitors’ sensory experiences in a destination are identified through a content analysis of online review comments posted by visitors. Afterward, the effects of those sensory experiences on visitors’ digital engagement through destination dependence and identification with that destination are examined. Findings suggest that sensory experiences are critical antecedents of visitors’ bond and identification with a destination. Visitors’ positive destination-related sensory experiences increase their dependence on and identification with the destination, and this dependence and identification positively influence their digital engagement behavior on social media.
Anticipatory and Anticipated Emotions in Regular and Non-regular Exercisers – A Qualitative Study

Future-oriented emotions could influence our decisions in everyday life and help understand why some individuals are physically active whilst others are not. Current literature distinguishes between two future-oriented emotion constructs: anticipatory and anticipated emotions. While anticipatory emotions are currently experienced emotions about a future event, anticipated emotions refer to the emotions that a person is expected to experience when confronted with a future event. The main aims of the present study were (1) to identify and describe (a) categories of anticipatory emotions experienced before exercise, and (b) categories of anticipated emotions expected to be experienced during and after exercise, and (2) to develop a theoretical model of anticipated emotion categories. Sixteen participants (Mage = 26.03, SD = 6.66) were recruited for semi-structured interviews, and their statements were analyzed using principles of the Grounded Theory. In total, 13 different anticipatory and anticipated emotion categories were identified, such as enjoyment, anxiety, pride, self-anger, and relief. Anticipatory emotions seem to reflect the current affective valence of exercising and may be influenced by daily factors. With regards to anticipated emotions, the results show that regular exercisers anticipated also negative emotions such as anxiety, disappointment, and self-anger, and non-regular exercisers also anticipated positive emotions such as enjoyment, pride, and satisfaction. Therefore, future research should not only focus on the valence of future-oriented emotions, but should investigate the possible impact of specific anticipated emotions on exercise behavior. In addition, a theoretical model of anticipated emotion categories in exercise behavior derived from the interviews. The model outlines different categories of anticipated emotions based on appraisal processes. In conclusion, we assume that this developmental process of anticipated emotions may be embedded in a broader, cyclical process within the context of exercising.
The Application of Platelet-Rich Plasma for Patients Following Total Joint Replacement: A Meta-Analysis of Randomized Controlled Trials and Systematic Review

Background The clinical efficacy of platelet-rich plasma (PRP) in the treatment of total joint replacement (TJR) remains inconclusive. In this paper, systematic review and meta-analysis was adopted to assess the efficacy of using PRP for the treatment of TJR. Methods A comprehensive search of Medline, Embase, and Cochrane library databases for randomized controlled trial (RCT) articles recording data of PRP for TJR was conducted from inception to February 2022. Outcomes concerned were pain, range of motion (ROM), WOMAC score, length of hospital stay (LOS), hemoglobin (Hb) drop, total blood loss, wound healing rate, and wound infection. The methodological quality of the included RCTs was evaluated by using the Cochrane Risk of Bias Tool 2.0 (RoB 2.0). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was utilized to assess the level of evidence for the outcomes. Subgroup analysis was conducted according to the type of TJR. Results Ten RCTs were included in the meta-analysis. In the TKA subgroup, the available data demonstrated that there were significant differences in the outcomes of pain and Hb drop, while it was the opposite of ROM, WOMAC score, LOS, total blood loss, wound healing rate, and wound infection. In the THA subgroup, no significant differences could be seen between two groups in the outcomes of LOS and wound infection. However, the PRP group gained a higher wound healing rate in the THA subgroup. Conclusion The application of PRP did not reduce blood loss but improved the wound healing rate. However, more prospective and multicenter studies are warranted to confirm these results.
Docking-Based Virtual Screening Enables Prioritizing Protein Kinase Inhibitors With In Vitro Phenotypic Activity Against Schistosoma mansoni

Schistosomiasis is a parasitic neglected disease with praziquantel (PZQ) utilized as the main drug for treatment, despite its low effectiveness against early stages of the worm. To aid in the search for new drugs to tackle schistosomiasis, computer-aided drug design has been proved a helpful tool to enhance the search and initial identification of schistosomicidal compounds, allowing fast and cost-efficient progress in drug discovery. The combination of high-throughput in silico data followed by in vitro phenotypic screening assays allows the assessment of a vast library of compounds with the potential to inhibit a single or even several biological targets in a more time- and cost-saving manner. Here, we describe the molecular docking for in silico screening of predicted homology models of five protein kinases (JNK, p38, ERK1, ERK2, and FES) of Schistosoma mansoni against approximately 85,000 molecules from the Managed Chemical Compounds Collection (MCCC) of the University of Nottingham (UK). We selected 169 molecules predicted to bind to SmERK1, SmERK2, SmFES, SmJNK, and/or Smp38 for in vitro screening assays using schistosomula and adult worms. In total, 89 (52.6%) molecules were considered active in at least one of the assays. This approach shows a much higher efficiency when compared to using only traditional high-throughput in vitro screening assays, where initial positive hits are retrieved from testing thousands of molecules. Additionally, when we focused on compound promiscuity over selectivity, we were able to efficiently detect active compounds that are predicted to target all kinases at the same time. This approach reinforces the concept of polypharmacology aiming for “one drug-multiple targets”. Moreover, at least 17 active compounds presented satisfactory drug-like properties score when compared to PZQ, which allows for optimization before further in vivo screening assays. In conclusion, our data support the use of computer-aided drug design methodologies in conjunction with high-throughput screening approach.
A wideband 3 decibels arbitrary phase difference branch line coupler

A wideband 3 dB branch line coupler with arbitrary phase difference between output ports is proposed. The wideband properties in both amplitude and phase are achieved by utilizing λ/4 coupled line sections. By designing different even and odd impedance of the coupled line matched in different ports, small phase imbalance can be achieved. For validation, two 3 dB couplers with different phase differences (60° and 120°) were designed and fabricated. They were measured to exhibit wide bandwidths of 40.2% and 44.6%, respectively.
Subregional Differences in Alcohol Modulation of Central Amygdala Neurocircuitry

Alcohol use disorder is a highly significant medical condition characterized by an impaired ability to stop or control alcohol use, compulsive alcohol seeking behavior, and withdrawal symptoms in the absence of alcohol. Understanding how alcohol modulates neurocircuitry critical for long term and binge-like alcohol use, such as the central amygdala (CeA), may lead to the development of novel therapeutic strategies to treat alcohol use disorder. In clinical studies, reduction in the volume of the amygdala has been linked with susceptibility to relapse to alcohol use. Preclinical studies have shown the involvement of the CeA in the effects of alcohol use, with lesions of the amygdala showing a reduction in alcohol drinking, and manipulations of cells in the CeA altering alcohol drinking. A great deal of work has shown that acute alcohol, as well as chronic alcohol exposure via intake or dependence models, alters glutamatergic and GABAergic transmission in the CeA. The CeA, however, contains heterogeneous cell populations and distinct subregional differences in neurocircuit architecture which may influence the mechanism by which alcohol modulates CeA function overall. The current review aimed to parse out the differences in alcohol effects on the medial and lateral subregions of the CeA, and what role neuroinflammatory cells and markers, the endocannabinoid system, and the most commonly studied neuropeptide systems play in mediating these effects. A better understanding of alcohol effects on CeA subregional cell type and neurocircuit function may lead to development of more selective pharmacological interventions for alcohol use disorder.
Clemastine Promotes Differentiation of Oligodendrocyte Progenitor Cells Through the Activation of ERK1/2 via Muscarinic Receptors After Spinal Cord Injury

The recovery of spinal cord injury (SCI) is closely associated with the obstruction of oligodendrocyte progenitor cell (OPC) differentiation, which ultimately induces the inability to generate newly formed myelin. To address the concern, drug-based methods may be the most practical and feasible way, possibly applying to clinical therapies for patients with SCI. In our previous study, we found that clemastine treatment preserves myelin integrity, decreases the loss of axons, and improves functional recovery in the SCI model. Clemastine acts as an antagonist of the muscarinic acetylcholine receptor (muscarinic receptor, MR) identified from a string of anti-muscarinic drugs that can enhance oligodendrocyte differentiation and myelin wrapping. However, the effects of clemastine on OPC differentiation through MRs in SCI and the underlying mechanism remain unclear. To explore the possibility, a rat model of SCI was established. To investigate if clemastine could promote the differentiation of OPCs in SCI via MR, the expressions of OPC and mature OL were detected at 7 days post injury (dpi) or at 14 dpi. The significant effect of clemastine on encouraging OPC differentiation was revealed at 14 dpi rather than 7 dpi. Under pre-treatment with the MR agonist cevimeline, the positive role of clemastine on OPC differentiation was partially disrupted. Further studies indicated that clemastine increased the phosphorylation level of extracellular signal–regulated kinase 1/2 (p-ERK1/2) and the expressions of transcription factors, Myrf and Olig2. To determine the relationship among clemastine, ERK1/2 signaling, specified transcription factors, and OPC differentiation, the ERK1/2 signaling was disturbed by U0126. The inhibition of ERK1/2 in SCI rats treated with clemastine decreased the expressions of p-ERK 1/2, Myrf, Olig2, and mature OLs, suggesting that ERK1/2 is required for clemastine on promoting OPC differentiation and that specified transcription factors may be affected by the activity of ERK1/2. Moreover, the impact of clemastine on modulating the level of p-ERK 1/2 was restricted following cevimeline pre-injecting, which provides further evidence that the role of clemastine was mediated by MRs. Altogether, our data demonstrated that clemastine, mediated by MRs, promotes OPC differentiation under the enhancement of Myrf and Olig2 by activating ERK1/2 signaling and suggests a novel therapeutic prospect for SCI recovery.
Exogenous Short Chain Fatty Acid Effects in APP/PS1 Mice

Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and amyloid burden as assessed by histochemistry and MSD ELISA. We report that SCFA treatment increased alpha-diversity and impacted the gut microbiome profile by increasing, in part, the relative abundance of several bacteria that typically produce SCFAs. However, SCFA treatment did not significantly affect behavior. Similarly, SCFAs did not affect cortical or hippocampal astrocyte activation observed in the APP/PS1 mice. Lastly, although robust levels of soluble and insoluble amyloid were present in the APP/PS1 mice, SCFA treatment had no effect on these indices. Overall, our findings are that SCFA treatment modifies the microbiome in a fashion that may increase further SCFA production. However, SCFA treatment did not alter behavior, astrocyte activation, nor amyloid neuropathology in APP/PS1 mice maintained with a conventional microbiome.
Expected Limits on the Potential for Carbon Dioxide Removal From Artificial Upwelling

Artificial upwelling, the engineered upward pumping of deep ocean water, has long been proposed as a technique to fertilize the ocean and, more recently, remove atmospheric carbon dioxide. This study investigated the potential of artificial upwelling to contribute to carbon dioxide removal using a simple model with high-resolution (1° × 1°) gridded monthly climatologies of upper ocean and deep ocean physical and chemical properties. The potential for carbon dioxide removal was explored across a range of observationally-informed carbon-to-nitrogen-to-phosphorus ratios for microalgae and macroalgae communities, providing information on the sensitivity of the estimates to any assumed carbon-to-nutrient ratios. Simulated carbon dioxide removal across the tropical-to-subpolar ocean did not exceed 0.66 tons per square kilometer per year for microalgae, and did not exceed 0.85 tons per square kilometer per year for macroalgae. Using current technology, the estimated global aggregate potential for carbon dioxide removal using microalgae was less than 50 megatons (0.05 gigatons) of carbon dioxide annually and the estimated global aggregate potential for carbon dioxide removal using macroalgae was approximately 100 megatons (0.1 gigatons) of carbon dioxide annually. While controlled field trials are needed to validate or invalidate the findings of this study, this study suggests that artificial upwelling is unlikely to support annual carbon dioxide removal at, or close to, the rate of one gigaton of carbon dioxide annually.
Substantial Increase in Heavy Precipitation Events Preceded by Moist Heatwaves Over China During 1961–2019

Both moist heatwaves (HWs) and heavy precipitation events (HP) have increased in both frequency and magnitude over China in recent decades. However, the relationship between HW and HP and changes in the lagged coincidence of events (i.e., the occurrence of an HP event several days after an HW event, noted HWHP) remain unknown. We show here that HWHP events account for nearly one-third of HP events over China in summer, with high values in North China, Northeast China, and the East arid zone. HWHP events assessed using the heat index and the wet-bulb temperature methods increased by 45.25 and 23.97% from 1961 to 2019, respectively. These concurrent HWHP events tend to be spatially clustered, and the areas affected simultaneously have grown significantly. The increase in HW is the major driver of these changes in HWHP events, except in the western arid zone and North China. Our findings provide an understanding of the spatiotemporal changes in HWHP events over China and their implications for disaster mitigation.
Olfactory Inspection of Female Reproductive States in Chimpanzees

In mammalian species, olfactory cues are important for within and between species communication. These cues can be part of multimodal signals indicating, for example, female fertility potentially perceived by male conspecifics. However, a large gap exists in our understanding of multimodal signaling in non-human catarrhines. Chimpanzees (Pan troglodytes) live in fission-fusion societies, mate promiscuously and express high levels of male-male competition. Females show a striking visual signal, an exaggerated sexual swelling, known to be a proxy of ovulation, while the maximum swelling is not matching the exact time of ovulation. The question remains if males use additional olfactory cues when being able to approach females closely. This would allow males to pinpoint the exact timing of ovulation and could be one reason why high-ranking males sire offspring more successfully than other males. Here, we present the first systematic test of such multimodal signaling by investigating male sniffing behavior directed to females in relation to their fertility in a group of 13 captive chimpanzees. Our results show that male sniffing behavior significantly increased with female swelling size, with female age as well as when fewer male competitors were present. Hence, odors might be part of a multimodal fertility cue, supporting the idea that males monitor both visual and olfactory cues to gain comprehensive information on female fertility.
A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma

Background The tumor microenvironment (TME) is a complex and evolving environment, and the tumor immune microenvironment in kidney renal clear cell carcinoma (KIRC) has a strong suppressive profile. This study investigates the potential prognostic role and value of genes of the tumor microenvironment in KIRC. Methods The transcriptome sequencing data of 530 cases and 39 cases of KIRC and the corresponding clinical prognosis information were downloaded from TCGA data and GEO data, respectively, and TME-related gene expression profiles were extracted. A prognostic signature was constructed and evaluated using univariate Cox regression analysis and LASSO regression analysis. Gene set enrichment analysis (GSEA) was used to obtain the biological process of gene enrichment in patients with high and low-risk groups. Results A prognostic signature consisting of eight TME-related genes (LRFN1, CSF1, UCN, TUBB2B, SERPINF1, ADAM8, ABCB4, CCL22) was constructed. Kaplan-Meier survival analysis yielded significantly lower survival times for patients in the high-risk group than in the low-risk group, and the AUC values for the ROC curves of this prognostic signature were essentially greater than 0.7, and univariate and multifactorial Cox regression analyses indicated that the risk score was independent risk factors for KIRC prognosis. GSEA analysis showed that immune-related biological processes were enriched in the high-risk group and that risk values were strongly associated with multiple immune cell scores and immune checkpoint-related genes (PDCD1, CTLA4). Conclusions The prognostic signature can accurately predict the prognosis of KIRC patients, which may provide new ideas for future precision immunotherapy of KIRC.
Higher Levels of Urinary Thiocyanate, a Biomarker of Cruciferous Vegetable Intake, Were Associated With Lower Risks of Cardiovascular Disease and All-Cause Mortality Among Non-smoking Subjects

Background Epidemiologic studies on cruciferous vegetable (CV) intake and cardiovascular disease (CVD) were inconclusive. Objective To investigate the associations of urinary thiocyanate, a biomarker of CV intake, with CVD and all-cause mortality among non-smoking adults. Methods This prospective cohort study comprised 10,489 non-smoking adults (weighted mean age, 46.8 years; 43.4% male) from the National Health and Nutrition Examination Survey 2001–2014. Non-smokers were defined as subjects with serum cotinine < 3 ng/mL. Urinary thiocyanate was measured with ion chromatography tandem mass spectrometry at baseline, and CVD and all-cause mortality were identified through linkage to National Death Index until December 31, 2015. Cox proportional hazards model was applied to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD and all-cause mortality. Results A total of 800 deaths, of which 136 died of CVD, were ascertained within a median 7.8 years of follow-up. Urinary thiocyanate was positively correlated with total CV intake among non-smoking adults (rs = 0.088, P < 0.001). Comparing extreme quartiles, the multivariate-adjusted HRs for CVD and all-cause mortality were 0.50 (95% CI: 0.29–0.85) and 0.75 (95% CI: 0.60–0.92), respectively. Each 1 μg/g creatinine increment of log-transformed urinary thiocyanate was associated with a 25% (HR: 0.75; 95% CI: 0.62–0.91) reduced CVD mortality risk and 12% (HR: 0.88; 95% CI: 0.81–0.96) reduced all-cause mortality risk. The documented inverse associations persisted in sensitivity analyses. Conclusion Increased levels of urinary thiocyanate, a candidate biomarker of CV intake, were associated with low risks of CVD and total mortality among non-smoking adults. This prospective biomarker-based study provided further evidence to support the cardiovascular benefits of CVs.
ISR8/IRF1-AS1 Is Relevant for IFNα and NF-κB Responses

The study of the interferon (IFN) α-induced cell transcriptome has shown altered expression of several long non-coding RNAs (lncRNAs). ISR8/IRF1-AS1 (IFN stimulated RNA 8), located close to IFN regulatory factor 1 (IRF1) coding gene, transcribes a lncRNA induced at early times after IFNα treatment or IRF1 or NF-κB activation. Depletion or overexpression of ISR8 RNA does not lead to detected deregulation of the IFN response. Surprisingly, disruption of ISR8 locus with CRISPR-Cas9 genome editing results in cells that fail to induce several key ISGs and pro-inflammatory cytokines after a trigger with IFNα or overexpression of IRF1 or the NF-κB subunit RELA. This suggests that the ISR8 locus may play a relevant role in IFNα and NF-κB pathways. Interestingly, IFNα, IRFs and NF-κB-responding luciferase reporters are normally induced in ISR8-disrupted cells when expressed from a plasmid but not when integrated into the genome. Therefore, IFNα and NF-κB pathways are functional to induce the expression of exogenous episomic transcripts but fail to activate transcription from genomic promoters. Transcription from these promoters is not restored with silencing inhibitors, by decreasing the levels of several negative regulators or by overexpression of inducers. Transcriptome analyses indicate that ISR8-disrupted cells have a drastic increase in the levels of negative regulators such as XIST and Zinc finger proteins. Our results agree with ISR8 loci being an enhancer region that is fundamental for proper antiviral and proinflammatory responses. These results are relevant because several SNPs located in the ISR8 region are associated with chronic inflammatory and autoimmune diseases including Crohn’s disease, inflammatory bowel disease, ulcerative colitis or asthma.