Miracle-dz/UniFAR-FTUs huggingface dataset:
Nearly Optimal Reward-Free Reinforcement Learning

We study the reward-free reinforcement learning framework, which is particularly suitable for batch reinforcement learning and scenarios where one needs policies for multiple reward functions. This framework has two phases: in the exploration phase, the agent collects trajectories by interacting with the environment without using any reward signal; in the planning phase, the agent needs to return a near-optimal policy for arbitrary reward functions. We give a new efﬁcient algo-rithm, S taged S ampling + T runcated P lanning (SSTP), which interacts with the environment at most O (cid:16) S 2 A (cid:15) 2 poly log (cid:0) SAH(cid:15) (cid:1)(cid:17) episodes in the exploration phase, and guarantees to output a near-optimal policy for arbitrary reward functions in the planning phase, where S is the size of state space, A is the size of action space, H is the planning horizon, and (cid:15) is the target accuracy relative to the total reward. Notably, our sample complexity scales only logarithmically with H , in contrast to all existing results which scale polynomially with H . Furthermore, this bound matches the minimax lower bound Ω (cid:16) S 2 A (cid:15) 2 (cid:17) up to logarithmic factors. Our results rely on three new techniques : 1) A new sufﬁcient condition for the dataset to plan for an (cid:15) -suboptimal policy ; 2) A new way to plan efﬁciently under the proposed condition using soft-truncated planning; 3) Constructing extended MDP to maximize the truncated accumulative rewards efﬁciently.
Are We There Yet? - A Systematic Literature Review on Chatbots in Education

Chatbots are a promising technology with the potential to enhance workplaces and everyday life. In terms of scalability and accessibility, they also offer unique possibilities as communication and information tools for digital learning. In this paper, we present a systematic literature review investigating the areas of education where chatbots have already been applied, explore the pedagogical roles of chatbots, the use of chatbots for mentoring purposes, and their potential to personalize education. We conducted a preliminary analysis of 2,678 publications to perform this literature review, which allowed us to identify 74 relevant publications for chatbots’ application in education. Through this, we address five research questions that, together, allow us to explore the current state-of-the-art of this educational technology. We conclude our systematic review by pointing to three main research challenges: 1) Aligning chatbot evaluations with implementation objectives, 2) Exploring the potential of chatbots for mentoring students, and 3) Exploring and leveraging adaptation capabilities of chatbots. For all three challenges, we discuss opportunities for future research.
Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Treated With Liposomal Irinotecan

Background The NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this. Methods This real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology. Results There were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score <2. Liposomal irinotecan was administered as a doublet with 5-FU in a NAPOLI-1-based regimen in the first line (1L; 16%), 2L (42%), and 3L+ (42%) of the metastatic setting. For patients treated in 1L, 2L, and 3L+, median [95% confidence interval (CI)] OS was 8.0 [5.1, 11.2], 7.3 [5.3, 8.8], and 4.6 [4.0, 5.7] months, and median [95% CI] PFS was 4.2 [2.2, 6.6], 3.0 [2.6, 3.7], and 2.0 [1.7, 2.2] months, respectively. Conclusions Patients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.
Hypoxia-Induced Mitogenic Factor: A Multifunctional Protein Involved in Health and Disease

Hypoxia-induced mitogenic factor (HIMF), also known as resistin-like molecule α (RELMα) or found in inflammatory zone 1 (FIZZ1) is a member of the RELM protein family expressed in mice. It is involved in a plethora of physiological processes, including mitogenesis, angiogenesis, inflammation, and vasoconstriction. HIMF expression can be stimulated under pathological conditions and this plays a critical role in pulmonary, cardiovascular and metabolic disorders. The present review summarizes the molecular characteristics, and the physiological and pathological roles of HIMF in normal and diseased conditions. The potential clinical significance of these findings for human is also discussed.
Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Systemic Lupus Erythematosus and Pulmonary Arterial Hypertension: Evidence From Transcriptome Data

Background Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple systems. Pulmonary arterial hypertension (PAH) has a close linkage with SLE. However, the inter-relational mechanisms between them are still unclear. This article aimed to explore the shared gene signatures and potential molecular mechanisms in SLE and PAH. Methods The microarray data of SLE and PAH in the Gene Expression Omnibus (GEO) database were downloaded. The Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify the co-expression modules related to SLE and PAH. The shared genes existing in the SLE and PAH were performed an enrichment analysis by ClueGO software, and their unique genes were also performed with biological processes analyses using the DAVID website. The results were validated in another cohort by differential gene analysis. Moreover, the common microRNAs (miRNAs) in SLE and PAH were obtained from the Human microRNA Disease Database (HMDD) and the target genes of whom were predicted through the miRTarbase. Finally, we constructed the common miRNAs–mRNAs network with the overlapped genes in target and shared genes. Results Using WGCNA, four modules and one module were identified as the significant modules with SLE and PAH, respectively. A ClueGO enrichment analysis of shared genes reported that highly activated type I IFN response was a common feature in the pathophysiology of SLE and PAH. The results of differential analysis in another cohort were extremely similar to them. We also proposed a disease road model for the possible mechanism of PAH secondary to SLE according to the shared and unique gene signatures in SLE and PAH. The miRNA–mRNA network showed that hsa-miR-146a might regulate the shared IFN-induced genes, which might play an important role in PAH secondary to SLE. Conclusion Our work firstly revealed the high IFN response in SLE patients might be a crucial susceptible factor for PAH and identified novel gene candidates that could be used as biomarkers or potential therapeutic targets.
Heart Rate Variability During Physical Exercise Is Associated With Improved Cognitive Performance in Alzheimer's Dementia Patients—A Longitudinal Feasibility Study

Heart rate variability (HRV) rapidly gains attention as an important marker of cardiovascular autonomic modulation. Moreover, there is evidence for a link between the autonomic deficit measurable by reduced HRV and the hypoactivity of the cholinergic system, which is prominently affected in Alzheimer's disease (AD). Despite the positive influence of physical exercise on cognition and its promising association with HRV, previous studies did not explore the effect of long-term physical exercise in older adults with AD. Taking advantage of a longitudinal study we analyzed the effect of a 20-week dual task training regime (3 × 15-min per week) on the vagal mediated HRV index RMSSD (root mean square of successive RR interval differences) during physical exercise and the short-term memory performance in a AD cohort (N = 14). Each training contained physical exercise on a bicycle ergometer while memorizing 30 successively presented pictures as well as the associated post-exercise picture recognition memory test. Linear-mixed modeling revealed that HRV-RMSSD significantly increased over the intervention time. Moreover, the reaction time in the picture recognition task decreased while the accuracy remained stable. Furthermore, a significantly negative relationship between increased fitness measured by HRV-RMSSD and decreased reaction time was observed. This feasibility study points to the positive effects of a dual task regime on physical and cognitive fitness in a sample with impaired cognitive performance. Beyond this, the results show that the responsiveness of parasympathetic system as measured with HRV can be improved in patients with dementia.
Exogenous Ketone Salt Supplementation and Whole-Body Cooling Do Not Improve Short-Term Physical Performance

Exogenous ketone supplementation and whole-body cooling (WBC) have shown to independently influence exercise metabolism. Whether readily available ketone salts, with and without WBC, would provide similar metabolic benefits during steady-state aerobic and time-trial performances was investigated. Nine active males (VO2peak: 56.3 ± 2.2 mL·kg−1·min−1) completed three single-blind exercise sessions preceded by: (1) ingestion of placebo (CON), (2) ketone supplementation (0.3 g·kg−1 β-OHB) (KET), and (3) ketone supplementation with WBC (KETCO). Participants cycled in steady-state (SS, 60% Wmax) condition for 30-min, immediately followed by a 15-min time trial (TT). Skin and core temperature, cardio-metabolic, and respiratory measures were collected continuously, whereas venous blood samples were collected before and after supplementation, after SS and TT. Venous β-OHB was elevated, while blood glucose was lower, with supplementation vs. CON (p < 0.05). TT power output was not different between conditions (p = 0.112, CON: 190 ± 43.5 W, KET: 185 ± 40.4 W, KETCO: 211 ± 50.7 W). RER was higher during KETCO (0.97 ± 0.09) compared to both CON (0.88 ± 0.04, p = 0.012) and KET (0.88 ± 0.05, p = 0.014). Ketone salt supplementation and WBC prior to short-term exercise sufficiently increase blood β-OHB concentrations, but do not benefit metabolic shifts in fuel utilization or improve time trial performance.
Adaptation of the Compensatory Stepping Response Following Predictable and Unpredictable Perturbation Training

Background Effective training of the backward step response could be beneficial to improve postural stability and prevent falls. Unpredicted perturbation-based balance training (PBT), widely known as compensatory-step training, may enhance the fear of falling and the patterns of postural muscle co-contraction. Contrastingly, PBT with predictable direction or both direction and timing would suppress the fear and the co-contraction patterns during training, but the efficacy of predictable PBT for unpredictable perturbations is still unknown. Objective To compare the adaptation effects of compensatory-step training with and without predictable perturbations on backward stepping against unpredictable perturbations. Methods Thirty-three healthy young adults were randomly assigned to one of the following step training groups: Unpredicted, Predicted, and Self-initiated. In training sessions, participants were perturbed to induce a compensatory step with (Predicted group) or without (Unpredicted group) knowledge of the perturbation’s direction or while knowing both the direction and timing of the perturbation (Self-initiated group). In test sessions (pre- and post-training), participants were instructed to recover their postural stability in response to an unpredicted perturbation. The margin of stability (MOS), center of mass (COM) shift, and step characteristics were measured during a backward step in both test and training sessions. Results All three groups showed a significant increase in the step length and velocity in the post-training sessions compared to those in the pre-training sessions. Moreover, in the Unpredicted and Predicted groups, but not in the Self-initiated group, the MOS at step contact was significantly increased following the training session. In addition, the Self-initiated group showed a significant increase in COM shift at 50 ms after slip onset during training compared to the Unpredicted and Predicted groups. Conclusion Unpredicted and predicted PBT improve step characteristics during backward stepping against unpredictable perturbations. Moreover, the unpredictable PBT and PBT with direction-predictable perturbations enhance the feedback postural control reflected as the postural stability at step contact.
On the Importance of Density in ELPI Data Post-Treatment

This study compared number and mass concentrations obtained using two reference devices, a scanning mobility particle sizer (SMPS) and a tapered element oscillating microbalance (TEOM), with those calculated from raw electrical low-pressure impactor (ELPI) data. ELPI data post-treatment was performed assuming a mobility-dependent effective density and three constant densities: an average effective density, the raw material density, and the standard density (i.e., 1 g/cm3). For the mass concentration, whatever the density considered, the ELPI-determined value was close to the reference. For the number concentration, results indicate good agreement between SMPS and ELPI number concentrations when considering effective density and, to a lesser extent, average effective density. In contrast, with the raw material density or standard density, large uncertainties in number concentration measurements were produced. A good estimation of number concentration was obtained based on ELPI data when assuming a standard density only when there was fortuitous agreement between the number tested aerosol size distribution and its mobility-dependent effective density. Thus, contrary to what some authors recommend, a standard density cannot be universally used. Copyright © 2015 American Association for Aerosol Research
Patient-Reported Control of Asthma, Nasal Polyposis, and Middle-Ear Symptoms in NSAID-Exacerbated Respiratory Disease

Non-steroidal anti-inflammatory drug (NSAID)—exacerbated respiratory disease (NERD) is an adult-onset inflammatory condition of the upper and lower airways. It is characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to NSAIDs. Over one-fourth of patients also have symptoms of chronic middle-ear infection. The clinical course of NERD is often severe and generally requires multimodal treatment with recurrent surgical measures. Studies presenting the disease burden and subjective symptom control of NERD are limited. In this qualitative questionnaire study, we present the clinical characteristics of asthma, nasal polyposis, NSAID intolerance and possible recurrent or chronic middle-ear infection of 66 confirmed NERD patients treated at our tertiary referral center between January 2016 and May 2017. Additionally, we present the patient-reported disease control of asthma, nasal polyposis, and middle-ear symptoms on a four-category Likert scale. The proportion of NERD patients with recurrent or chronic middle-ear infection was 18%. The proportion of good or very good subjective disease control was 83% for asthma, 58% for nasal polyposis, and 33% for chronic middle-ear infection, if present. Chronic middle-ear infection is common among NERD patients and should more often be recognized as part of the entity. Together with nasal polyposis, chronic middle-ear infection seems to affect patients more than asthma. The patient's perspective of disease control should be considered when planning the interdisciplinary follow-up and treatment of NERD.
The Role of Macrophages During Mammalian Tissue Remodeling and Regeneration Under Infectious and Non-Infectious Conditions

Several infectious pathologies in humans, such as tuberculosis or SARS-CoV-2, are responsible for tissue or lung damage, requiring regeneration. The regenerative capacity of adult mammals is limited to few organs. Critical injuries of non-regenerative organs trigger a repair process that leads to a definitive architectural and functional disruption, while superficial wounds result in scar formation. Tissue lesions in mammals, commonly studied under non-infectious conditions, trigger cell death at the site of the injury, as well as the production of danger signals favouring the massive recruitment of immune cells, particularly macrophages. Macrophages are also of paramount importance in infected injuries, characterized by the presence of pathogenic microorganisms, where they must respond to both infection and tissue damage. In this review, we compare the processes implicated in the tissue repair of non-infected versus infected injuries of two organs, the skeletal muscles and the lungs, focusing on the primary role of macrophages. We discuss also the negative impact of infection on the macrophage responses and the possible routes of investigation for new regenerative therapies to improve the recovery state as seen with COVID-19 patients.
Examining the Effectiveness of the Fathers and Babies Intervention: A Pilot Study

There is increasing recognition of the importance of addressing the mental health of fathers, including during the perinatal period. Fathers exhibiting mental health concerns during the perinatal period are at heightened risk for future negative mental health outcomes and are less likely to engage in nurturing relationships with their children, leading to a sequalae of negative child outcomes during infancy and into adolescence. Although interventions have been developed for perinatal fathers, they typically do not focus directly on addressing paternal mental health. To fill this gap, we developed the Fathers and Babies intervention to be delivered to perinatal fathers whose partners (mothers) were enrolled in home visiting programs. A pre-post longitudinal study was conducted in which 30 father-mother dyads were recruited from home visiting programs. Fathers received the 12-session Fathers and Babies intervention while the mother concurrently received the Mothers and Babies intervention delivered to her by a home visitor. Baseline, 3- and 6-month self-report surveys were conducted with both fathers and mothers. Fathers and mothers had statistically significant decreases in perceived stress between baseline and both follow-up time points, with moderate effect sizes generated for both sexes. No statistically significant differences were found for depressive symptoms, anxiety symptoms, or perceived partner support, although we found small effects for reductions in depressive symptoms among fathers, as well as increases in the percentage of fathers and mothers who reported high levels of emotional and instrumental support post-intervention. While preliminary, these findings suggest the potential for Fathers and Babies to positively impact the mental health of fathers in the perinatal period, and also signal the viability of home visiting as a setting for delivering this intervention. Future research should employ a comparison group to generate stronger evidence of intervention effectiveness and include measurement of dyadic relationships and paternal parenting practices.
A Mycological and Molecular Epidemiologic Study on Onychomycosis and Determination In Vitro Susceptibilities of Isolated Fungal Strains to Conventional and New Antifungals

Background Onychomycosis is one of the most common and recurrent dermatological diseases worldwide. The antimycotic activity of prescribed medications varies according to the causative agents, and treatment failure rates exceeding 30%. This study aimed to assess the epidemiological profile of onychomycosis in Iran. Also, the susceptibilities to conventional and new antifungals were investigated. Methods In this descriptive cross-sectional study, during the period of 18 months starting from September 2019 until March 2020, 594 nail specimens were obtained from patients who presented nail changes compatible with a clinical diagnosis of onychomycosis. The patients were referred from different cities, including Tehran, Kermanshah, Arak, Kashan, Rasht, Qom, Urmia, Zahedan, Hamadan, Zanjan, Borujerd, Bushehr, and Yazd. All the samples were subjected to microscopic examination and fungal culture. Fungi identified were confirmed through the PCR-sequencing method. The susceptibility to itraconazole, fluconazole, terbinafine, griseofulvin, posaconazole, ravuconazole, efinaconazole, luliconazole, and tavaborole was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A3 for yeasts. Results 594 patients were included. Of these, in 179 cases (30.1%) (95% CI:0.3 ± 0.037) onychomycosis was confirmed. The majority of patients were ≥ 60 years of age (n=58, 32.6%) and female (n=113, 63.1%). Saprophytic fungi accounted for the vast majority of the nail isolates (n=92, 51.4%) (95% CI:0.051 ± 0.0.073), followed by dermatophytes (n=45, 25.1%) (95% CI:0.25 ± 0.063), and yeasts (n=42, 23.5%) (95% CI:0.23 ± 0.061). Diabetes mellitus (77.3%), hypothyroidism (18.2%), and solid tumors (4.5%) were documented as the most prevalent underlying conditions. Antifungal susceptibility testing was performed against 60 fungal isolates (20 each of Candida species, saprophytic fungi, and dermatophytes). Efinaconazole, ravuconazole, and luliconazole were the most active agents against Candida species. Also, luliconazole, posaconazole, and efinaconazole were most potent against dermatophytes. Luliconazole had the greatest antifungal activity against saprophytic fungi. Conclusions The prevalence of onychomycosis in Iranian patients was relatively high. LUL exhibited potent antifungal activity against the three groups of fungi tested, determining its broad-spectrum antimycotic activity and its probable use as the first-line therapy for onychomycosis.