Miracle-dz/UniFAR-FTUs huggingface dataset:
On the Similarity Between the Reinforcing and the Discriminative Properties of Intracranial Self-Stimulation

Rats work very hard for intracranial self-stimulation (ICSS) and tradeoff effort or time allocation for intensity and frequency parameters producing a sigmoidal function of the subjective reward magnitude of ICSS. Previous studies using electrical intracranial stimuli (ICS) as a discriminative cue focused on estimating detection thresholds or on the discrimination between intensities. To our knowledge, there is no direct comparison of the reinforcer tradeoff functions with the discriminative functions. Rats were trained to press and hold the lever for ICSS using the maximum reinforcing intensity below motor alterations or avoidance behavior. First, rats were trained to hold the lever for 1 s; after stability, they undergo trials where intensity or frequency was decreased on 0.1 log step. Thereafter, they undergo further training with a hold of 2 and later of 4 s to determine tradeoff with intensity or frequency. The same rats were trained on a discrimination task where the previously used ICSS signaled a lever where a 1 s hold response was followed by a reinforcing ICSS; on randomly alternating trials, a −0.6 log ICS signaled an alternate lever where a similar hold response led to a reinforcer. After mastering discrimination, generalization tests were carried out with varying intensity or frequency. Rats completed training with 2 and later 4 s hold response. After the completion of each task, the rats had different doses of a pimozide challenge while their intensity and hold-down requirement were varied. With regards to the rats’ tradeoff response time allocation as a function of intensity or frequency, sigmoid functions were displaced to the right when long responses were required. Rats that learned the discrimination task attained a discrimination index of 90–98%. Discrimination accuracy decreased slightly with the increase of hold requirement, but generalization gradients were not displaced to the right as a function of the response requirement. Pimozide induced a dose-dependent displacement of the time-allocation gradients, but it did not affect the generalization gradients. It is concluded that rats integrate response requirements as part of the reinforcement tradeoff function, but the response cost is not integrated into the discriminative function of ICSS.
Identification and Quantification of Iron Metabolism Landscape on Therapy and Prognosis in Bladder Cancer

The morbidity of bladder cancer (BLCA) is high and has gradually elevated in recent years. BLCA is also characterized by high recurrence and high invasiveness. Due to the drug resistance and lack of effective prognostic indicators, the prognosis of patients with BLCA is greatly affected. Iron metabolism is considered to be a pivot of tumor occurrence, progression, and tumor microenvironment (TME) in tumors, but there is little research in BLCA. Herein, we used univariate COX regression analysis to screen 95 prognosis-related iron metabolism-related genes (IMRGs) according to transcription RNA sequencing and prognosis information of the Cancer Genome Atlas (TCGA) database. TCGA-BLCA cohort was clustered into four distinct iron metabolism patterns (C1, C2, C3, and C4) by the non-negative matrix factorization (NMF) algorithm. Survival analysis showed that C1 and C3 patterns had a better prognosis. Gene set variant analysis (GSVA) revealed that C2 and C4 patterns were mostly enriched in carcinogenic and immune activation pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) also confirmed the level of immune cell infiltration in C2 and C4 patterns was significantly elevated. Moreover, the immune checkpoint genes in C2 and C4 patterns were observably overexpressed. Studies on somatic mutations showed that the tumor mutation burden (TMB) of C1 and C4 patterns was the lowest. Chemotherapy response assessment revealed that C2 pattern was the most sensitive to chemotherapy, while C3 pattern was the most insensitive. Then we established the IMRG prognosis signature (IMRGscore) by the least absolute shrinkage and selection operator (LASSO), including 13 IMRGs (TCIRG1, CTSE, ATP6V0A1, CYP2C8, RNF19A, CYP4Z1, YPEL5, PLOD1, BMP6, CAST, SCD, IFNG, and ASIC3). We confirmed IMRGscore could be utilized as an independent prognostic indicator. Therefore, validation and quantification of iron metabolism landscapes will help us comprehend the formation of the BLCA immunosuppressive microenvironment, guide the selection of chemotherapeutic drugs and immunotherapy, and predict the prognosis of patients.
Comparing a Robot Tutee to a Human Tutee in a Learning-By-Teaching Scenario with Children

Social robots are increasingly being studied in educational roles, including as tutees in learning-by-teaching applications. To explore the benefits and drawbacks of using robots in this way, it is important to study how robot tutees compare to traditional learning-by-teaching situations. In this paper, we report the results of a within-subjects field experiment that compared a robot tutee to a human tutee in a Swedish primary school. Sixth-grade students participated in the study as tutors in a collaborative mathematics game where they were responsible for teaching a robot tutee as well as a third-grade student in two separate sessions. Their teacher was present to provide support and guidance for both sessions. Participants’ perceptions of the interactions were then gathered through a set of quantitative instruments measuring their enjoyment and willingness to interact with the tutees again, communication and collaboration with the tutees, their understanding of the task, sense of autonomy as tutors, and perceived learning gains for tutor and tutee. The results showed that the two scenarios were comparable with respect to enjoyment and willingness to play again, as well as perceptions of learning gains. However, significant differences were found for communication and collaboration, which participants considered easier with a human tutee. They also felt significantly less autonomous in their roles as tutors with the robot tutee as measured by their stated need for their teacher’s help. Participants further appeared to perceive the activity as somewhat clearer and working better when playing with the human tutee. These findings suggest that children can enjoy engaging in peer tutoring with a robot tutee. However, the interactive capabilities of robots will need to improve quite substantially before they can potentially engage in autonomous and unsupervised interactions with children.
Physical Inactivity Is Associated With Post-discharge Mortality and Re-hospitalization Risk Among Swedish Heart Failure Patients—The HARVEST-Malmö Study

Background Several studies have examined the role of physical activity as a predictor of heart failure (HF) mortality and morbidity. Here, we aimed to evaluate the role of self-reported physical activity as an independent risk factor of post-discharge mortality and re-hospitalization in patients hospitalized for HF, as well as study the association between physical activity and 92 plasma proteins associated with cardiovascular disease (CVD). Methods Four-hundred-and-thirty-four patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 835 (interquartile range, 390–1,432) and 157 (43–583) days, respectively. Associations between baseline reported physical activity, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of <5%, and significant associations were taken forward to multivariate analyses. Results In the multivariate Cox regression model, physical inactivity, defined as physical activity time <1 h throughout the week was associated with increased risk of all-cause mortality (HR 1.71; CI95% 1.26–2.31; p = 5.9 × 10−4) as well as all-cause re-hospitalization (HR 1.27; CI95% 1.01–1.60; p = 0.038). Further, physical inactivity was associated with elevated plasma levels of Metalloproteinase inhibitor 4, Soluble interleukin 1 receptor-like 1, Elafin and Transferrin receptor protein 1, which are implicated in myocardial fibrosis, migration and apoptosis. Conclusions Self-reported low weekly physical activity is associated with increased risk of mortality and re-hospitalization in patients hospitalized for HF independent of traditional risk factors. Furthermore, physical inactivity was associated with elevated levels of 4 proteins linked to cardiovascular disease.
Approaches Involved in the Vegetable Crops Salt Stress Tolerance Improvement: Present Status and Way Ahead

Salt stress is one of the most important abiotic stresses as it persists throughout the plant life cycle. The productivity of crops is prominently affected by soil salinization due to faulty agricultural practices, increasing human activities, and natural processes. Approximately 10% of the total land area (950 Mha) and 50% of the total irrigated area (230 Mha) in the world are under salt stress. As a consequence, an annual loss of 12 billion US$ is estimated because of reduction in agriculture production inflicted by salt stress. The severity of salt stress will increase in the upcoming years with the increasing world population, and hence the forced use of poor-quality soil and irrigation water. Unfortunately, majority of the vegetable crops, such as bean, carrot, celery, eggplant, lettuce, muskmelon, okra, pea, pepper, potato, spinach, and tomato, have very low salinity threshold (ECt, which ranged from 1 to 2.5 dS m–1 in saturated soil). These crops used almost every part of the world and lakes’ novel salt tolerance gene within their gene pool. Salt stress severely affects the yield and quality of these crops. To resolve this issue, novel genes governing salt tolerance under extreme salt stress were identified and transferred to the vegetable crops. The vegetable improvement for salt tolerance will require not only the yield influencing trait but also target those characters or traits that directly influence the salt stress to the crop developmental stage. Genetic engineering and grafting is the potential tool which can improve salt tolerance in vegetable crop regardless of species barriers. In the present review, an updated detail of the various physio-biochemical and molecular aspects involved in salt stress have been explored.
Thyroid Status During Pregnancy in Women With Polycystic Ovary Syndrome and the Effect of Metformin

Objective Polycystic ovary syndrome (PCOS) and hypothyroidism are related conditions, and both are associated with adverse pregnancy outcomes. Knowledge is lacking about the complex interaction between thyroid status and PCOS during pregnancy. We investigated the thyroid status and its association with pregnancy complications in PCOS, and in relation to metformin treatment. Design Post-hoc analyses of two randomized, double-blind, placebo-controlled trials. Methods 288 pregnant women with PCOS were randomized to treatment with metformin or placebo from first trimester to delivery. We measured serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) at gestational week (gw) 5-12, 19, 32 and 36 and related to metformin treatment and pregnancy complications. Thyroid peroxidase antibodies (TPO-ab) were analyzed at inclusion and at gw 36. Results The overall prevalence of subclinical and overt hypothyroidism was 1.5% and 0%, respectively. The TSH level was not affected by metformin, whereas fT4 was significantly higher in the metformin group with less decrease throughout pregnancy compared to placebo, p<0.001. A lower decrease in fT4 during pregnancy correlated to less weight gain (r= -0.17, p=0.020) and tended to be associated with reduced odds ratio for gestational diabetes (OR 0.85 per 1 pmol/L, 95% CI 0.71;1.02). Conclusions In women with PCOS, metformin treatment during pregnancy was associated with less decrease in fT4 compared to placebo, while it did not affect TSH. A smaller decrease in fT4 correlated to less weight gain and tended to be associated with a lower risk of gestational diabetes. Clinical Trial Registration ClinicalTrials.gov, identifier NCT00159536 (The PregMet study); identifier NCT03259919 (The pilot study).
Functional Tricuspid Regurgitation: Behind the Scenes of a Long-Time Neglected Disease

Severe tricuspid valve regurgitation has been for a long time a neglected valve disease, which has only recently attracted an increasing interest due to the notable negative impact on the prognosis of patients with cardiovascular disease. It is estimated that around 90% of tricuspid regurgitation is diagnosed as “functional” and mostly secondary to a primary left-sided heart disease and, therefore, has been usually interpreted as a benign condition that did not require a surgical management. Nevertheless, the persistence of severe tricuspid regurgitation after left-sided surgical correction of a valve disease, particularly mitral valve surgery, has been associated to adverse outcomes, worsening of the quality of life, and a significant increase in mortality rate. Similar results have been found when the impact of isolated severe tricuspid regurgitation has been studied. Current knowledge is shifting the “functional” categorization toward a more complex and detailed pathophysiological classification, identifying various phenotypes with completely different etiology, natural history and, potentially, an invasive management. The aim of this review is to offer a comprehensive guide for clinicians and surgeons with a systematic description of “functional” tricuspid regurgitation subtypes, an analysis centered on the effectiveness of existing surgical techniques and a focus on the emergent percutaneous procedures. This latter may be an attractive alternative to a standard surgical approach in patients with high-operative risk or isolated tricuspid regurgitation.
SARM1 Suppresses Axon Branching Through Attenuation of Axonal Cytoskeletal Dynamics

Axon branching is a fundamental aspect of neuronal morphogenesis, neuronal circuit formation, and response of the nervous system to injury. Sterile alpha and TIR motif containing 1 (SARM1) was initially identified as promoting Wallerian degeneration of axons. We now report a novel function of SARM1 in postnatal sensory neurons; the suppression of axon branching. Axon collateral branches develop from axonal filopodia precursors through the coordination of the actin and microtubule cytoskeleton. In vitro analysis revealed that cultured P0-2 dorsal root ganglion sensory neurons from a SARM1 knockout (KO) mouse exhibit increased numbers of collateral branches and axonal filopodia relative to wild-type neurons. In SARM1 KO mice, cutaneous sensory endings exhibit increased branching in the skin in vivo with normal density of innervation. Transient axonal actin patches serve as cytoskeletal platforms from which axonal filopodia emerge. Live imaging analysis of axonal actin dynamics showed that SARM1 KO neurons exhibit increased rates of axonal actin patch formation and increased probability that individual patches will give rise to a filopodium before dissipating. SARM1 KO axons contain elevated levels of drebrin and cortactin, two actin regulatory proteins that are positive regulators of actin patches, filopodia formation, and branching. Live imaging of microtubule plus tip dynamics revealed an increase in the rate of formation and velocity of polymerizing tips along the axons of SARM1 KO neurons. Stationary mitochondria define sites along the axon where branches may arise, and the axons of SARM1 KO sensory neurons exhibit an increase in stationary mitochondria. These data reveal SARM1 to be a negative regulator of axonal cytoskeletal dynamics and collateral branching.
Update on Tenosynovial Giant Cell Tumor, an Inflammatory Arthritis With Neoplastic Features

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction and bone erosion. Even if many treatments were developed with success in the last decades, some patients fail to respond, and disease chronicity is still a burden. Mechanisms involved in such resistance may include molecular changes in stromal cells. Other explanations can come from observations of tenosynovial giant cell tumor (TGCT), first considered as an inflammatory arthritis, but with unusual neoplastic features. TGCT leads to synovium hypertrophy and hyperplasia with hemosiderin deposition. It affects young adults, resulting in secondary osteoarthritis and increased morbidity. TGCT shows clinical, histological and genetic similarities with RA but affecting a single joint. However, the monoclonality of some synoviocytes, the presence of translocations and rare metastases also suggest a neoplastic disease, with some features common with sarcoma. TGCT is more probably in an intermediate situation between an inflammatory and a neoplastic process, with a main involvement of the proinflammatory cytokine CSF-1/CSF1R signaling axis. The key treatment option is surgery. New treatments, derived from the RA and sarcoma fields, are emerging. The tyrosine kinase inhibitor pexidartinib was recently FDA-approved as the first drug for severe TGCT where surgery is not an option. Options directly targeting the excessive proliferation of synoviocytes are at a preclinical stage.
Effect of Pulmonary Rehabilitation for Patients With Post-COVID-19: A Systematic Review and Meta-Analysis

Background Evidence increasingly suggested that impaired respiratory function remained in about 40% of patients with coronavirus disease 2019 (COVID-19) after discharge, jeopardizing their activities of daily living and quality of life (QoL) in a long term. Pulmonary rehabilitation (PR) can improve exercise capacity and QoL in individuals with chronic lung disease; however, evidence on the effect of PR for patients with post-COIVD-19 was scarce. This study aimed to conduct a systematic review and meta-analysis to evaluate the effect of PR on lung impairment for patients with post-COVID-19. Methods Five databases were searched for all the published trials of PR for patients with post-COVID-19 from 2019 to October 2021. Data were extracted using a standardized form. The risks of bias of included studies were assessed using the Cochrane risk of the bias assessment tool. Data were synthesized where possible; otherwise, qualitative analysis was done. Results Among 6,000 retrieved studies, 3 studies with 233 patients after COVID-19 were included. The pooled estimate of PR effect on 6-min walk test (6-MWT) (50.41, 95% CI 34.34 to 66.48; p < 0.0001) was in favor of the experiment group with clinical importance. It is found that PR could improve the symptom of dyspnea and QoL; however, its effect on pulmonary function test was inconsistent across studies. The risk of bias of included studies varied, with major concerns on the risk of blinding of participants and interventions performers. Conclusion The review showed that PR could improve exercise capacity measured by 6-MWT among patients with mild-to-moderate lung impairment after COVID-19. The interpretation of effects on lung function, dyspnea, and QoL should be cautious due to inadequate and conflicting data reported across studies. Systematic Review Registration https://www.crd. york.ac. uk/prospero/display_record. php? ID=CRD42021289562, identifier: CRD42021289562.
The Effect of Antioxidants on Sperm Quality Parameters and Pregnancy Rates for Idiopathic Male Infertility: A Network Meta-Analysis of Randomized Controlled Trials

Purpose Male infertility is a global public health issue recognized by the WHO. Recently, antioxidants are increasingly used to treat idiopathic male infertility. However, the lack of available evidence has led to the inability to rank the effects of antioxidants on the sperm quality parameters and pregnancy rate of infertile men. This network meta-analysis studied the effects of different antioxidants on the sperm quality and pregnancy rate of idiopathic male infertility. Methods We searched PubMed, Embase, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables, respectively, with 95% CIs. The outcomes were sperm motility, sperm concentration, sperm morphology, and pregnancy rate. Results A total of 23 RCTs with 1,917 patients and 10 kids of antioxidants were included. l-Carnitine, l-carnitine+l-acetylcarnitine, coenzyme-Q10, ω-3 fatty acid, and selenium were more efficacious than placebo in sperm quality parameters. l-Carnitine was ranked first in sperm motility and sperm morphology (WMD 6.52% [95% CI: 2.55% to 10.05%], WMD 4.96% [0.20% to 9.73%]). ω-3 fatty acid was ranked first in sperm concentration (WMD 9.89 × 106/ml, [95% CI: 7.01 to 12.77 × 106/ml]). In terms of pregnancy rate, there was no significant effect as compared with placebo. Conclusions l-Carnitine was ranked first in sperm motility and sperm morphology. ω-3 fatty acid was ranked first in sperm concentration. Coenzyme-Q10 had better effective treatment on sperm motility and concentration. Furthermore, high-quality RCTs with adequate sample sizes should be conducted to compare the outcomes of different antioxidants.
Flipped Presentation of Authentic Audio-Visual Materials: Impacts on Intercultural Sensitivity and Intercultural Effectiveness in an EFL Context

Utilizing a pre-experimental pre-test post-test design, this study investigated the effect of an authentic audio-visual American sitcom (Friends) on the intercultural sensitivity (ICS) and intercultural effectiveness (ICE) of a sample of male and female upper-intermediate English students. To this aim, 34 Iranian EFL students were selected through convenient non-random sampling. In order to assure the participants' homogeneity in English proficiency, the selected students were given the Oxford Quick Placement Test prior to the intervention. Over a 10-week period, the participants were presented with nearly 30-min-long episodes of Friends in a flipped context, two episodes every week uploaded to the accompanying website. An online 10-item quiz on the day of watching and a next-day meeting were held. During the online discussion meetings, the participants discussed cultural questions tailored to the aims of the study. The required data were collected through the administration of the intercultural sensitivity scale (ISS) and intercultural effectiveness scale (IES) in pre- and post-test assessments. The analyses of the data indicated that both ICS and ICE improved significantly during the intervention. However, ICS indicated more improvement. In addition, a semi-structured interview was administered to the participants to examine their perception of the flipped classroom experience. Having analyzed the data using MAXQDA 2020, some significant themes emerged which are reported. On the whole, the participants portrayed positive attitudes toward using technology in flipped classes. The educational and practical implications are discussed.