Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of induced positive and negative affect on Pavlovian-instrumental interactions

ABSTRACT Across species, animals have an intrinsic drive to approach appetitive stimuli and to withdraw from aversive stimuli. In affective science, influential theories of emotion link positive affect with strengthened behavioural approach and negative affect with avoidance. Based on these theories, we predicted that individuals’ positive and negative affect levels should particularly influence their behaviour when innate Pavlovian approach/avoidance tendencies conflict with learned instrumental behaviours. Here, across two experiments – exploratory Experiment 1 (N = 91) and a preregistered confirmatory Experiment 2 (N = 335) – we assessed how induced positive and negative affect influenced Pavlovian-instrumental interactions in a reward/punishment Go/No-Go task. Contrary to our hypotheses, we found no evidence for a main effect of positive/negative affect on either approach/avoidance behaviour or Pavlovian-instrumental interactions. However, we did find evidence that the effects of induced affect on behaviour were moderated by individual differences in self-reported behavioural inhibition and gender. Exploratory computational modelling analyses explained these demographic moderating effects as arising from positive correlations between demographic factors and individual differences in the strength of Pavlovian-instrumental interactions. These findings serve to sharpen our understanding of the effects of positive and negative affect on instrumental behaviour.
Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles

Abstract Cancer vaccines critically rely on the availability of targetable immunogenic cancer‐specific neoepitopes. However, mutation‐based immunogenic neoantigens are rare or even non‐existent in subgroups of cancer types. To address this issue, we exploited a cancer‐specific aberrant transcription‐induced chimeric RNA, designated A‐Pas chiRNA, as a possible source of clinically relevant and targetable neoantigens. A‐Pas chiRNA encodes a recently discovered cancer‐specific chimeric protein that comprises full‐length astrotactin‐2 (ASTN2) C‐terminally fused in‐frame to the antisense sequence of the 18th intron of pregnancy‐associated plasma protein‐A (PAPPA). We used extracellular vesicles (EVs) from A‐Pas chiRNA‐transfected dendritic cells (DCs) to produce the cell‐free anticancer vaccine DEXA‐P. Treatment of immunocompetent cancer‐bearing mice with DEXA‐P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer‐specific transcription‐induced chimeric RNAs can be exploited to produce a cell‐free cancer vaccine that induces potent CD8+ T cell‐mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation‐based antigens. Moreover, this cell‐free anticancer vaccine approach may offer several practical advantages over cell‐based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life.
Response to pre-dilatation with POBA can predict target lesion revascularization after DCB angioplasty for de novo small coronary artery lesions

Objective To assess the determinants of target lesion revascularization (TLR) after drug-coated balloon (DCB) angioplasty for de novo small coronary artery lesions. Methods This retrospective study enrolled consecutive lesions from patients that were in a stable condition and had undergone successful DCB treatment for de novo small coronary artery lesions. The study endpoint was TLR and major adverse cardiac events at 12 months. Results A total of 68 patients with 83 lesions were enrolled in the study. Of these, 11 (13.3%) lesions required TLR. Mean ± SD pre-dilatation balloon diameters were similar in the non-TLR (2.33 ± 0.72 mm) and TLR (2.18 ± 0.36 mm) groups. A comparison of the two groups showed that post/pre-lumen area ratio during pre-dilatation (%) by plain old balloon angioplasty (POBA) was significantly and negatively associated with TLR and the optimal cut-off point was 170%. Cox proportional hazard and multivariate regression analyses showed that post/pre-lumen area ratio was the only independent predictor of TLR (hazard ratio 0.9318; 95% confidence interval 0.9001, 0.9645). Conclusion Greater pre-dilatation using POBA, assessed as the post/pre-lumen area ratio, may be independently associated with a lower 12-month TLR rate in patients undergoing DCB angioplasty for de novo small coronary lesions.
Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia

A central response to insufficient cerebral oxygen delivery is a profound reprograming of metabolism, which is mainly regulated by the Hypoxia Inducible Factor (HIF). Among other responses, HIF induces the expression of the atypical mitochondrial subunit NDUFA4L2. Surprisingly, NDUFA4L2 is constitutively expressed in the brain in non-hypoxic conditions. Analysis of publicly available single cell transcriptomic (scRNA-seq) data sets coupled with high-resolution multiplexed fluorescence RNA in situ hybridization (RNA F.I.S.H.) revealed that in the murine and human brain NDUFA4L2 is exclusively expressed in mural cells with the highest levels found in pericytes and declining along the arteriole-arterial smooth muscle cell axis. This pattern was mirrored by COX4I2, another atypical mitochondrial subunit. High NDUFA4L2 expression was also observed in human brain pericytes in vitro, decreasing when pericytes are muscularized and further induced by HIF stabilization in a PHD2/PHD3 dependent manner. In vivo, Vhl conditional inactivation in pericyte targeting Ng2-cre transgenic mice dramatically induced NDUFA4L2 expression. Finally NDUFA4L2 inactivation in pericytes increased oxygen consumption and therefore the degree of HIF pathway induction in hypoxia. In conclusion our work reveals that NDUFA4L2 together with COX4I2 is a key hypoxic-induced metabolic marker constitutively expressed in pericytes coupling mitochondrial oxygen consumption and cellular hypoxia response.
Impact of the COVID-19 pandemic on non–small-cell lung cancer pathologic stage and presentation

Background: It is believed that the cessation of normative cancer care services during the COVID-19 pandemic may be resulting in pathologic upstaging and higher long-term mortality rates. We aimed to understand how the pandemic has affected our patients diagnosed with non–small-cell lung cancer (NSCLC). Methods: We conducted a single-centre retrospective analysis to assess how the COVID-19 pandemic has affected patient referrals, pathologic stage of NSCLC, mortality rates and surgical procedures at our cancer care centre in Ontario, Canada. At our centre, physicians advocated for and followed recommendations that operations in cancer patients should be among the last procedures to be delayed. Patients were included if they were aged 18 years or older, were not receiving palliative care, and had been screened, diagnosed and treated for NSCLC (primary tumours). We compared outcomes between a prepandemic period (January 2019 to February 2020) and a period during the pandemic (March 2020 to February 2021). Results: A total of 695 patients were included for statistical analysis, of whom 650 underwent surgery. There was no statistically significant difference in any of the outcomes of interest between patients seen before (n = 330) and during (n = 320) the pandemic. Conclusion: Cancer care services at our centre were maintained during the COVID-19 pandemic, and potential adverse effects on prognosis and survival that have been seen in other countries were avoided. The results inform health care providers how the effects of future pandemics can be blunted by using proactive preservative strategies and surgeon advocacy.
High‐Throughput Cell‐Free Screening of Eukaryotic Membrane Proteins in Lipidic Mimetics

Membrane proteins (MPs) carry out important functions in the metabolism of cells, such as the detection of extracellular activities and the transport of small molecules across the plasma and organelle membranes. Expression of MPs for biochemical, biophysical, and structural analysis is in most cases achieved by overexpression of the desired target in an appropriate host, such as a bacterium. However, overexpression of MPs is usually toxic to the host cells and can lead to aggregation of target protein and to resistance to detergent extraction. An alternative to cell‐based MP expression is cell‐free (CF), or in vitro, expression. CF expression of MPs has several advantages over cell‐based methods, including lack of toxicity issues, no requirement for detergent extraction, and direct incorporation of target proteins in various lipidic mimetics. This article describes a high‐throughput method for the expression and purification of eukaryotic membrane proteins used in the author's lab. Basic Protocol 1 describes the selection and cloning of target genes into appropriate vectors for CF expression. Basic Protocol 2 describes the assembly of CF reactions for high‐throughput screening. Basic Protocol 3 outlines methods for purification and detection of target proteins. Support Protocols 1‐6 describe various accessory procedures: amplification of target, treatment of vectors to prepare them for ligation‐independent cloning, and the preparation of S30 extract, T7 RNA polymerase, liposomes, and nanodiscs. © 2022 Wiley Periodicals LLC.
The value of postoperative HLA-DR expression and high mobility group box 1 level in predictive diagnosis of sepsis in percutaneous nephrolithotomy surgery

Abstract Objective To analyze the value of postoperative human leukocyte antigen-DR (HLA-DR) expression and high mobility group box 1 (HMGB1) level in predictive diagnosis of postoperative sepsis for patients with percutaneous nephrolithotomy (PCNL) surgery. Methods The present prospective observational study included 387 patients with renal calculus who received PCNL surgery from January 2017 to October 2020 in our hospital. After exclusion criteria, 33 patients with sepsis and 78 patients with no sepsis remained. All patients received PCNL surgery. Sepsis definition is according to the third international consensus definitions for sepsis and septic shock (Sepsis-3). The data of the HMGB1, c-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and HLA-DR expression were collected within admission and 24 h and 72 h after surgery. Postoperative HMGB1 levels and HLA-DR expression at 24 h and 72 h were respectively compared between the two groups using t test. ROC cure was used to analyze the value of postoperative HLA-DR expression and HMGB1 level in predictive diagnosis of sepsis. Results The positive rate of urine culture and the time of hospitalization time in patients with sepsis were significantly higher than those in patients with no sepsis. Sepsis group had higher levels of HMGB1 at post-24 h ((93.07 ± 11.37) ng/mL vs (75.41 ± 4.85) ng/mL), p < 0.05) and 72 h ((96.58 ± 12.12) ng/mL vs (81.16 ± 8.86) ng/mL), p < 0.05) than nosepsis group. Meanwhile, sepsis group had lower expression of HLA-DR at post-24 h ((50.01 ± 7.42) % vs (69.32 ± 10.58) %), p < 0.05) and 72 h ((54.85 ± 9.45) % vs (69.98 ± 11.00) %), p < 0.05) than non-sepsis group. ROC analysis showed that the HLA-DR expression at postoperative 24 h had highest predictive value in the diagnosis of sepsis, the AUC of HLA-DR was 0.934, cutoff value 56.19%, with sensitivity 89.7%, specificity 81.8%. Conclusion Postoperative HLA-DR and HMGB1 can both be used as a predictive diagnosis of sepsis for patients with renal calculus received PCNL surgery. Highlights Sepsis group had higher levels of high mobility group box 1 at post-24 h and 72 h than nosepsis group. Sepsis group had lower expression of HLA-DR at post-24 h and 72 h than nosepsis group. Postoperative HLA-DR and HMGB1 can both be used as a predictive diagnosis of sepsis for patients with renal calculus received PCNL surgery.
Effects of common genetic variants of human uridine diphosphate glucuronosyltransferase subfamilies on irinotecan glucuronidation

Abstract The adverse effects (diarrhea and neutropenia) of irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) are associated with genetic variants of uridine diphosphate glucuronosyltransferase 1A subfamilies (UGT1As). UGT1As are enzymes that metabolize the active form of irinotecan, 7-ethyl-10 hydroxycamptothecin (SN-38), by glucuronidation in the liver. They are widely known as predictive factors of severe adverse effects, such as neutropenia and diarrhea. Some studies have suggested that variants of UGT1As affect SN-38 glucuronidation activities, thus exerting severe adverse effects. We aimed to identify UGT1A isoforms that show SN-38 glucuronidation activity and determine the relationship between UGT1A variants and SN-38 glucuronidation in vitro. We found that UGT1A1 and UGT1A6–UGT1A10 displayed SN-38 glucuronidation activity. Among these, UGT1A1 was the most active. Furthermore, the variants of these isoforms showed decreased SN-38 glucuronidation activity. In our study, we compared the different variants of UGT1As, such as UGT1A1.6, UGT1A1.7, UGT1A1.27, UGT1A1.35, UGT1A7.3, UGT1A8.4, UGT1A10M59I, and UGT1A10T202I, to determine the differences in the reduction of glucuronidation. Our study elucidates the relationship between UGT1A variants and the level of glucuronidation associated with each variant. Therefore, testing can be done before the initiation of irinotecan treatment to predict potential toxicities and adverse effects.
Measuring the digital divide among people with severe mental ill health using the essential digital skills framework

Aims: Amidst the vast digitalisation of health and other services during the pandemic, people with no digital skills are at risk for digital exclusion. This risk might not abide by the end of the pandemic. This paper seeks to understand whether people with severe mental ill health (SMI) have the necessary digital skills to adapt to these changes and avoid digital exclusion. Methods: 249 adults with SMI across England completed a survey online or offline. They provided information on their digital skills based on the Essential Digital Skills (EDS) framework, sociodemographic information, and digital access. This is the first time the EDS is benchmarked in people with SMI. Results: 42.2% had no Foundation Skills and 46.2% lacked skills for daily life (lacking Foundation or Life Skills). 23.0% of those working lacked skills for professional life (lacking Foundation or Work Skills). The most commonly missing skills were handling passwords and using the device settings (Foundation Skills) and online problem solving (Skills for Life). People were interested in learning more about approximately half of the skills they did not have. People were more likely to lack Foundation Skills if they were older, not in employment, had a psychosis-spectrum disorder, or had no Internet access at home. Conclusion: A significant portion of people with SMI lacked Foundation Skills in this objective and benchmarked survey. This points to a high risk for digital exclusion and the need for focused policy and tailored health sector support, to ensure people retain access to key services and develop digital skills and confidence. To our knowledge this is the first time this has been described using the Essential Digital Skills (EDS) framework. Services, including the NHS, need to be aware and mitigate the risks.
Near‐infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans

The final steps of the O2 cascade during exercise depend on the product of the microvascular‐to‐intramyocyte PO2${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ( DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ ). Non‐invasive methods to determine DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (m V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) recovery rate constant (k), measured by near‐infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW), and hypothesized that: (i) k in well oxygenated muscle (kHIGH) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH – kLOW) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half‐maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s−1 mg−1 (∼5.8 ml min−1 100 g−1). CD ranged 348 to 586 mm–2. kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min–1, P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = –0.10, P = 0.755). Δk ranged –0.26 to –2.55 min–1, and correlated with CD (r = –0.68, P = 0.015). m V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ . Assessment of muscle k and ∆k using NIRS provides a non‐invasive window on muscle oxidative and O2 diffusing capacity.
AI-derived quality of experience prediction based on physiological signals for immersive multimedia experiences: research proposal

This paper contains the research proposal of Sowmya Vijayakumar that was presented at the MMSys 2022 doctorial symposium. Multimedia applications can now be found across many application domains including but not limited to entertainment, communication, health, business, and education. It is becoming more and more important to understand the factors that influence user perceptual quality, and hence monitoring user quality of experience (QoE) for improving multimedia interaction and services is essential. In this PhD work, we propose advanced machine learning techniques to predict QoE from physiological signals for immersive multimedia experiences. The aim of this doctoral study is to investigate the utility of physiological responses for QoE assessment for different multimedia technologies. Here, the research questions and solutions proposed to address this challenge are presented. A multimodal QoE prediction model is being developed that integrates several physiological measurements to improve QoE prediction performance.
Expert Systems With Applications

The ongoing outbreak of SARS-CoV-2 has been deeply impacting health systems worldwide. In this context, it is pivotal to measure the efficiency of different nations’ response to the pandemic, whose insights can be used by governments and health authorities worldwide to improve their national COVID-19 strategies. Hence, we propose a network Data Envelopment Analysis (DEA) to estimate the efficiencies of fifty-five countries in the current crisis, including the thirty-seven Organisation for Economic Co-operation and Development (OECD) member countries, six OECD prospective members, four OECD key partners, and eight other countries. The network DEA model is designed as a general series structure with five single-division stages – population, contagion, triage, hospitalisation, and intensive care unit admission –, and considers an output maximisation orientation, denoting a social perspective, and an input minimisation orientation, denoting a financial perspective. It includes inputs related to health costs, desirable and undesirable intermediate products related to the use of personal protective equipment and infected population, respectively, and desirable and undesirable outputs regarding COVID-19 recoveries and deaths, respectively. To the best of the authors’ knowledge, this is the first study proposing a cross-country efficiency measurement using a network DEA within the context of the COVID-19 crisis. The study concludes that Estonia, Iceland, Latvia, Luxembourg, the Netherlands, and New Zealand are the countries exhibiting higher mean system efficiencies. Their national COVID-19 strategies should be studied, adapted, and used by countries exhibiting worse performances. In addition, the observation of countries with large populations presenting worse mean efficiency scores is statistically significant.
Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children

Objective To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. Design Multicentre retrospective cohort study. Setting 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. Patients Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). Main outcome measure Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. Results We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53–10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45–9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. Conclusion We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.