Miracle-dz/UniFAR-FTUs huggingface dataset:
Training Millions of Personalized Dialogue Agents

Current dialogue systems fail at being engaging for users, especially when trained end-to-end without relying on proactive reengaging scripted strategies. Zhang et al. (2018) showed that the engagement level of end-to-end dialogue models increases when conditioning them on text personas providing some personalized back-story to the model. However, the dataset used in Zhang et al. (2018) is synthetic and only contains around 1k different personas. In this paper we introduce a new dataset providing 5 million personas and 700 million persona-based dialogues. Our experiments show that, at this scale, training using personas still improves the performance of end-to-end systems. In addition, we show that other tasks benefit from the wide coverage of our dataset by fine-tuning our model on the data from Zhang et al. (2018) and achieving state-of-the-art results.
Dietary Protein Restriction Reprograms Tumor-Associated Macrophages and Enhances Immunotherapy

Purpose: Diet and healthy weight are established means of reducing cancer incidence and mortality. However, the impact of diet modifications on the tumor microenvironment and antitumor immunity is not well defined. Immunosuppressive tumor-associated macrophages (TAMs) are associated with poor clinical outcomes and are potentially modifiable through dietary interventions. We tested the hypothesis that dietary protein restriction modifies macrophage function toward antitumor phenotypes. Experimental Design: Macrophage functional status under different tissue culture conditions and in vivo was assessed by Western blot, immunofluorescence, qRT-PCR, and cytokine array analyses. Tumor growth in the context of protein or amino acid (AA) restriction and immunotherapy, namely, a survivin peptide–based vaccine or a PD-1 inhibitor, was examined in animal models of prostate (RP-B6Myc) and renal (RENCA) cell carcinoma. All tests were two-sided. Results: Protein or AA-restricted macrophages exhibited enhanced tumoricidal, proinflammatory phenotypes, and in two syngeneic tumor models, protein or AA-restricted diets elicited reduced TAM infiltration, tumor growth, and increased response to immunotherapies. Further, we identified a distinct molecular mechanism by which AA-restriction reprograms macrophage function via a ROS/mTOR-centric cascade. Conclusions: Dietary protein restriction alters TAM activity and enhances the tumoricidal capacity of this critical innate immune cell type, providing the rationale for clinical testing of this supportive tool in patients receiving cancer immunotherapies.
Managing side effects in adjuvant endocrine therapy for breast cancer

ABSTRACT Introduction: Recent improvements in the survival of hormone-responsive breast cancer are strongly associated with therapeutic advances, particularly with the uptake of adjuvant endocrine therapy. Nevertheless, endocrine therapy is also linked with adverse effects that impact quality of life, social function, and adherence to treatment. Areas covered: This review examines the spectrum and consequences of adverse effects of tamoxifen and aromatase inhibitors, and the pharmacological and non-pharmacological approaches to mitigate some of the most frequent and disturbing side effects of endocrine therapy (including vasomotor, musculoskeletal, and vulvovaginal symptoms). The authors performed a qualitative analysis of English papers indexed in PubMed through May 2017, including meta-analysis, randomized controlled trials, observational studies, and systematic reviews. Expert commentary: Side effects of endocrine treatments are frequent and often underestimated in the care of breast cancer survivors, leading to a poor adherence to treatments that can compromise oncological outcomes. Many of the most common adverse events can be mitigated through pharmacological and non-pharmacological approaches that should be discussed and offered to patients in a dedicated setting of care.
Activation of Caenorhabditis elegans Levamisole-Sensitive and Mammalian Nicotinic Receptors by the Antiparasitic Bephenium

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels involved in neuromuscular transmission. In nematodes, muscle nAChRs are targets of antiparasitic drugs. Bephenium is an anthelmintic compound whose molecular action in the free-living nematode Caenorhabditis elegans, which is a model for anthelmintic drug discovery, is poorly known. We explored the effect of bephenium on C. elegans locomotion and applied single-channel recordings to identify its molecular target, mechanism of action, and selectivity between mammalian and C. elegans nAChRs. As in parasites, bephenium paralyzes C. elegans. A mutant strain lacking the muscle levamisole-sensitive nAChR (L-AChR) shows full resistance to bephenium, indicating that this receptor is the target site. Bephenium activates L-AChR channels from larvae muscle cells in the micromolar range. Channel activity is similar to that elicited by levamisole, appearing mainly as isolated brief openings. Our analysis revealed that bephenium is an agonist of L-AChR and an open-channel blocker at higher concentrations. It also activates mammalian muscle nAChRs. Opening events are significantly briefer than those elicited by ACh and do not appear in activation episodes at a range of concentrations, indicating that it is a very weak agonist of mammalian nAChRs. Recordings in the presence of ACh showed that bephenium acts as a voltage-dependent channel blocker and a low-affinity agonist. Molecular docking into homology-modeled binding-site interfaces represent the binding mode of bephenium that explains its partial agonism. Given the great diversity of helminth nAChRs and the overlap of their pharmacological profiles, unraveling the basis of drug receptor-selectivity will be required for rational design of anthelmintic drugs.
Interferon Gamma-Induced Protein (IP-10) as Potential Biomarker for Cancer-Related-Fatigue: Results from a 6-month Randomized Controlled Trial

Abstract We examined if serum concentrations Interferon gamma-induced protein (IP-10) is a potential clinical biomarker for cancer-related-fatigue (CRF). Fatigue scores and IP-10 concentrations were measured from curatively treated fatigued cancer patients randomized to either cognitive behavioral therapy (CBT, n = 26) or waiting-list (WL, n = 13). No correlation was found between baseline IP-10 level and fatigue severity and no significant differences in IP-10 serum levels were observed between fatigued and matched non-fatigued patients (n = 22). Relative changes in IP-10 concentrations from baseline to six-month follow-up were not significantly different between the CBT and WL conditions. In this study, IP-10 showed low potential as clinical CRF biomarker. Trial registration: This study is registered at ClinicalTrials.gov (NCT01096641).
A Bridge between Liquid and Social Welfare in Combinatorial Auctions with Submodular Bidders

We study incentive compatible mechanisms for Combinatorial Auctions where the bidders have submodular (or XOS) valuations and are budget-constrained. Our objective is to maximize the liquid welfare, a notion of efficiency for budgetconstrained bidders introduced by Dobzinski and Paes Leme (2014). We show that some of the known truthful mechanisms that best-approximate the social welfare for Combinatorial Auctions with submodular bidders through demand query oracles can be adapted, so that they retain truthfulness and achieve asymptotically the same approximation guarantees for the liquid welfare. More specifically, for the problem of optimizing the liquid welfare in Combinatorial Auctions with submodular bidders, we obtain a universally truthful randomized O(log m)-approximate mechanism, where m is the number of items, by adapting the mechanism of Krysta and Vöcking (2012). Additionally, motivated by large market assumptions often used in mechanism design, we introduce a notion of competitive markets and show that in such markets, liquid welfare can be approximated within a constant factor by a randomized universally truthful mechanism. Finally, in the Bayesian setting, we obtain a truthful O(1)-approximate mechanism for the case where bidder valuations are generated as independent samples from a known distribution, by adapting the results of Feldman, Gravin and Lucier (2014).
Posttraumatic stress disorder and cigarette smoking: A systematic review

Previous reviews of the PTSD and cigarette smoking literature showed high PTSD‐smoking comorbidity and problematic smoking outcomes (Feldner et al., 2007, Clinical Psychology Review, 27, 14–45; Fu et al., 2007, Nicotine & Tobacco Research, 9, 1071–1084). However, past reviews also noted several prominent gaps in the literature, including a lack of etiological work examining underlying mechanisms and research on specialized PTSD‐smoking treatments. The present review summarizes an extensive body of research conducted since the previous reviews targeting these areas of need.
Serum Calprotectin Level in Children: Marker of Obesity and its Metabolic Complications

Aim: Elevated calprotectin levels have been reported in obese adults but have not been evaluated in pediatric population. We investigated the characteristics of serum calprotectin in overweight and obese children and its association with metabolic comorbidities. Methods: We enrolled 131 children (11.7 ± 4.1 years). According to body mass index (BMI), the subjects were divided into 3 groups: obese > 95th percentile; overweight BMI 75th–95th percentile, and normal weight BMI < 75th percentile. Patients were classified as having Metabolic Syndrome if they met 3 or more of the following criteria for age and sex: BMI > 97th percentile, triglycerides > 95th percentile, high-density lipoprotein cholesterol < 5th percentile, systolic and/or diastolic blood pressure > 95th percentile, and impaired glucose tolerance. In all patients, calprotectin serum levels were also detected. Results: Calprotectin was higher in obese and overweight children than normal weight subjects (p < 0.001), with calprotectin in females being significantly higher than in males (p = 0.04). Increased calprotectin was related to pathological fasting blood glucose (p < 0.001) and insulin resistance (p = 0.03), while BMI (p = 0.001), and diastolic pressure (p = 0.001) are independent factors for increased calprotectin. Conclusions: Our findings confirm the association between increased calprotectin and obesity also in children and suggest the potential utility of this biomarker in the monitoring of its metabolic complications.
Diagnosis, management and prognosis of familial hypercholesterolaemia in a UK tertiary cardiac centre

ABSTRACT Objective: To describe demographic characteristics, current local clinical management and outcomes for patients with familial hypercholesterolaemia (FH) managed at the Royal Brompton and Harefield NHS Foundation Trust (RBHT), a specialist UK tertiary cardiac centre. Research design and methods: A local service evaluation of patients with FH was conducted by RBHT. Patients were identified from local FH databases and medical records based on pre-defined eligibility criteria. Descriptive statistics were performed. Main outcome measures: Proportion of patients with cardiovascular (CV) events during the period of follow-up; per cent change in low-density lipoprotein cholesterol (LDL-C) between highest untreated and most recent measurement; description of patient characteristics and treatment pathways. Results: The final evaluation sample included 306 patients whose first contact with the RBHT FH service was between November 1991 and February 2015. Patients were followed up until 2016 (median 4.4 years, range 1.2–24.9). Forty-three per cent (131/306) of patients had genetically confirmed FH and 56% (172/306) did not but meet a modified Simon Broome criteria. One fifth (20%, 60/306) had at least one CV event prior to their first contact with the service, mainly angioplasty (15%, 45/306) and MI (10%, 32/306). Thirty-five patients (11%) had CV events during the period of follow-up, occurring at a mean of 5.2 years after first contact. Of 269 “current” patients (i.e. patients with at least one contact with the service in the previous 3 years) 90% (241/269) were prescribed statins, with adverse events experienced by 30% (73/241). Eleven patients received lipoprotein apheresis. Only 34% (49/143) of patients had a reduction of ≥50% between the highest untreated and most recent LDL-C measurement. Conclusions: Results highlight the challenges of diagnosing and management of this high risk patient group whilst reducing CV events. Future work should focus on characterisation of patient subgroups and optimising treatment with novel therapeutic agents.
Administration of Nigella sativa during neonatal and juvenile growth period improved liver function of propylthiouracil-induced hypothyroid rats

Abstract Aim: Propylthiouracil (PTU) is frequently used as an antithyroid medication. It is also commonly used to induce hypothyroidism in rodents. PTU administration and hypothyroidism have been shown to affect the liver function. Nigella sativa (NS) has been suggested to have antioxidant and hepatoprotective effects. The objective of this study was to investigate the effects of NS extract administration during neonatal and juvenile growth period on liver function of PTU-induced hypothyroid rats. Methods: The pregnant rats were kept in separate cages. After delivery, the mothers and their offspring were randomly divided into five groups and were treated with the following programs: (1) control; (2) PTU, 0.005% in their drinking water (3–5); PTU-plus 100, 200, or 400 mg/kg NS extract. After lactation period, the offspring continued to receive the same experimental treatment for the first 8 weeks of their life. Ten offspring of each group were randomly selected and weighted at days 10, 30, and 60 after delivery. Their blood samples were collected and the liver tissues were removed. Results: Malondialdehyde (MDA) concentration was increased while, thiol concentration and superoxide dismutase (SOD) and catalase (CAT) activity were decreased in the liver tissues of PTU-treated rats. Serum aspartate amino transferase (AST), alkaline phosphatase (ALK-P), and alanine aminotransferase (ALT) levels in the PTU group were higher than the control group. Treatment with 200 and 400 mg/kg decreased MDA while increasing thiol concentration in the liver tissues compared to the PTU group. Treatment with all doses of the extract decreased serum ALK-P concentration compared with the PTU group. Treatment with 400 mg/kg NS increased CAT and SOD concentrations in the liver tissues and decreased serum AST and ALT concentrations compared to the PTU group. PTU decreased body weight gain of offspring and while, the extract increased the body weight gain of offspring rats. Conclusion: The results of this study demonstrated that administration of NS hydroalcoholic extract in the neonatal and juvenile growth period has an improving effect on the liver function of PTU- induced hypothyroid rats.
Effects of High-Intensity Inspiratory Muscle Training Associated with Aerobic Exercise in Patients Undergoing CABG: Randomized Clinical Trial

Objective Evaluate the interaction between high-intensity inspiratory muscle training (IMT) and aerobic exercise on physical capacity, respiratory muscle strength, peripheral muscle strength, and quality of life of patients who underwent coronary artery bypass grafting (CABG). Methods Twenty-four patients underwent CABG were randomized into two groups. During 36 sessions, one group received IMT associated with aerobic exercise and the other group received only aerobic exercise. Primary outcome was the distance in the six-minute walk distance (6MWD) test. Secondary outcomes included respiratory muscle strength, peripheral muscle strength, and quality of life. Measures were taken at the baseline, at the 12th session, the 24th session, and 36th session. Results Baseline characteristics were similar between the groups. There was no statistically significant difference between the two groups in any outcome [6MWD - P=0.935; peak oxygen consumption (PeakVO2) - P=0.853; maximal inspiratory pressure (MIP) - P=0.243; maximal expiratory pressure (MEP) - P=0.268; sitting-rising test (SRT) - P=0.212], but there was interaction in MIP (P=0.000) and all outcomes improved in the two groups (6MWD - P=0.000; PeakVO2 - P=0.000; MIP - P=0.000; MEP - P=0.000; SRT - P=0.000). Conclusion There was an improvement of all outcomes in both groups, but IMT was not able to provide additional benefits. The use of this combination should be used with caution to not generate higher costs in the rehabilitation process of these patients.
Quadrivalent Meningococcal Vaccine Uptake Among Men Who Have Sex With Men During a Meningococcal Outbreak in Los Angeles County, California, 2016-2017

Objective: The objective of our study was to assess meningococcal ACWY (MenACWY) vaccine uptake among men who have sex with men (MSM) during an ongoing, invasive meningococcal disease outbreak in Southern California. This research was important to inform future vaccination uptake interventions for this high-priority population. Methods: We conducted venue-based sampling to recruit and enroll MSM living in Los Angeles County, California, from December 2016 through February 2017. We conducted bivariate and multivariable analyses to evaluate associations between MenACWY vaccine uptake and other predetermined factors. Results: Of 368 participants, 138 (37.5%) reported receiving the MenACWY vaccine. In multivariable analyses, older age (adjusted odds ratio [aOR] = 2.57; 95% confidence interval [CI], 1.31-5.03), previous diagnosis of a sexually transmitted infection (aOR = 2.22; 95% CI, 1.14-4.30), belief that MenACWY vaccine is important (aOR = 3.49; 95% CI, 1.79-6.82), confidence in the MenACWY vaccine (aOR = 5.53; 95% CI, 3.11-9.83), and knowing someone who had been vaccinated (aOR = 5.82; 95% CI, 3.05-11.12) were significantly associated with MenACWY vaccine uptake. Conclusions: Our findings reflect low uptake of the recommended MenACWY vaccine among MSM after a local outbreak, despite public health efforts. In addition to ongoing, widespread campaigns to inform MSM about local outbreaks and vaccination recommendations, MSM may be responsive to direct outreach from peers who have been vaccinated.
The prognostic and therapeutic values of long noncoding RNA PANDAR in colorectal cancer

Long noncoding RNAs (lncRNAs) consist of 200 nucleotide sequences that play essential roles in different processes, including cell proliferation, and differentiation. There is evidence showing that the dysregulation of lncRNAs promoter of CDKN1A antisense DNA damage‐activated RNA (PANDAR) leads to the development and progression in several cancers including colorectal cancer, via p53‐dependent manner. This suggests that these lncRNAs may be of value as prognostic indices and a therapeutic target, as a high expression of lncRNAs PANDAR is associated with poor prognosis. Furthermore, modulating lncRNAs PANDAR has been reported to induce apoptosis and inhibit the tumor growth through modulation of cell cycle and epithelial‐mesenchymal transition (EMT) pathway. The aim of the current review was to provide an overview of the prognostic and therapeutic values of lncRNAs PANDAR in colorectal cancer
Right-lateralised lane keeping in young and older British drivers

Young adults demonstrate a small, but consistent, asymmetry of spatial attention favouring the left side of space (“pseudoneglect”) in laboratory-based tests of perception. Conversely, in more naturalistic environments, behavioural errors towards the right side of space are often observed. In the older population, spatial attention asymmetries are generally diminished, or even reversed to favour the right side of space, but much of this evidence has been gained from lab-based and/or psychophysical testing. In this study we assessed whether spatial biases can be elicited during a simulated driving task, and secondly whether these biases also shift with age, in line with standard lab-based measures. Data from 77 right-handed adults with full UK driving licences (i.e. prior experience of left-lane driving) were analysed: 38 young (mean age = 21.53) and 39 older adults (mean age = 70.38). Each participant undertook 3 tests of visuospatial attention: the landmark task, line bisection task, and a simulated lane-keeping task. We found leftward biases in young adults for the landmark and line bisection tasks, indicative of pseudoneglect, and a mean lane position towards the right of centre. In young adults the leftward landmark task biases were negatively correlated with rightward lane-keeping biases, hinting that a common property of the spatial attention networks may have influenced both tasks. As predicted, older adults showed no group-level spatial asymmetry on the landmark nor the line bisection task, but they maintained a mean rightward lane position, similar to young adults. The 3 tasks were not inter-correlated in the older group. These results suggest that spatial biases in older adults may be elicited more effectively in experiments involving complex behaviour rather than abstract, lab-based measures. More broadly, these results confirm that lateral biases of spatial attention are linked to driving behaviour, and this could prove informative in the development of future vehicle safety and driving technology.
Why Are Algal Viruses Not Always Successful?

Algal viruses are considered to be key players in structuring microbial communities and biogeochemical cycles due to their abundance and diversity within aquatic systems. Their high reproduction rates and short generation times make them extremely successful, often with immediate and strong effects for their hosts and thus in biological and abiotic environments. There are, however, conditions that decrease their reproduction rates and make them unsuccessful with no or little immediate effects. Here, we review the factors that lower viral success and divide them into intrinsic—when they are related to the life cycle traits of the virus—and extrinsic factors—when they are external to the virus and related to their environment. Identifying whether and how algal viruses adapt to disadvantageous conditions will allow us to better understand their role in aquatic systems. We propose important research directions such as experimental evolution or the resurrection of extinct viruses to disentangle the conditions that make them unsuccessful and the effects these have on their surroundings.
Validity of PowerTap P1 Pedals during Laboratory-Based Cycling Time Trial Performance

The use of mobile power measuring devices has become widespread within cycling, with a number of manufacturers now offering power measuring pedals. This study aimed to investigate the validity of PowerTap P1 pedals by comparing them with the previously validated Wattbike ergometer. Ten trained cyclists performed three simulated 10-mile (16-km) time trials on a Wattbike, while using PowerTap P1 pedals. There were no statistically significant differences (p > 0.05) between PowerTap P1 pedals and a Wattbike for maximum, minimum, and mean power output, or for maximum, minimum, and mean cadence. There were good to excellent levels of agreement between the PowerTap P1 pedals and Wattbike (ICC > 0.8) for all measured variables except minimum cadence (ICC = 0.619). This suggests that PowerTap P1 pedals provide a valid measurement of power output.