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The role of the adenosine neurochemical system in human cognition is under-studied, despite such receptors being distributed throughout the brain. The aim of this study was to shed light on the role of the adenosine A2A receptors in human cognition using single-dose istradefylline. Twenty healthy male participants, aged 19-49, received 20 mg istradefylline and placebo, in a randomized, double-blind, placebo-controlled cross-over design. Cognition was assessed us-ing computerized cognitive tests, covering both cold (non-emotional) and hot (emotion-laden) domains. Cardiovascular data were recorded serially. Cognitive effects of istradefylline were explored using repeated measures analysis of variance and paired t-tests as appropriate. On the EMOTICOM battery, there was a significant effect of istradefylline versus placebo on the Social Information Preference task ( t = 2.50, p = 0.02, d =-0.59), indicating that subjects on istradefylline interpreted social situations more positively. No other significant effects were observed on other cognitive tasks, nor in terms of cardiovascular measures (pulse and blood pressure). De-briefing indicated that blinding was successful, both for participants and the research team. Further exploration of the role of adenosine A2A receptors in emotional pro-cessing may be valuable, given that abnormalities in related cognitive functions are implicated in neuropsychiatric disorders. The role of adenosine systems in human cognition requires fur-ther clarification, including with different doses of istradefylline and over different schedules of administration.(c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

BACKGROUND: The coronavirus disease 19 (COVID-19) has led to increased reliance on the internet. How problematic usage of the internet (PUI) and COVID-19 related stress and other clinical variables relate, is unknown. We hypothesised that higher PUI level would be significantly associated with higher levels of: (i) pandemic-related stress; and (ii) impulsive and compulsive symptoms and traits. METHODS: An online community-based cross-sectional survey was used for data collection. Relationships between PUI level and other variables were characterised using correlational analyses. Regression analyses determined the cumulative explanatory power of variables, with partial least squares structural equation modelling (PLS-SEM) to explore path loadings. ANOVA was used to investigate PUI level at varying lockdown levels. RESULTS: Data from 2110 participants (64.5% female), aged 18-64 years (mean: 24.3, SD: 8.1) suggested that approximately a quarter (n = 489, 23.2%) had medium to high level internet use problems. Impulsive and compulsive symptoms and traits, pandemic-stress, and age were all significantly related to PUI (p < 0.01). These associations (medium effect sizes) cumulatively explained 29% of PUI variance. PLS-SEM indicated significant contributory effects, with the association between age and PUI level mediated by impulsivity, pandemic-stress and compulsivity. DISCUSSION: Pandemic-stress, impulsive-compulsive symptoms and traits and age were related to PUI level. Enhancing resilience to stress, particularly in vulnerable populations, through lifestyle changes and implementation of adaptive coping strategies, is key to reduce risk for PUI during the COVID-19 pandemic and beyond.

Bone fractures are one of the most common traumatic large-organ injuries and although many fractures can heal on their own, 2-12% of fractures are slow healing or do not heal (non-unions). Autologous grafts are currently used for treatment of non-unions but are associated with limited healthy bone tissue. Tissue engineered cell-based products have promise for an alternative treatment method. It was previously demonstrated that cartilaginous microspheroids of periosteum-derived cells could be assembled into scaffold-free constructs and heal murine critically-sized long bone defects (non-unions). However, the handleability of such scaffold-free implants can be compromised when scaling-up. In this work, cartilaginous spheroids were combined with melt electrowritten (MEW) meshes to create an engineered cell-based implant, able to induce in vivo bone formation. MEW polycaprolactone meshes were tailored to contain pores (116 ± 28 µm) of a size that captured microspheroids (180 ± 15 µm). Periosteum-derived microspheroids pre-cultured for 4 days, were seeded on MEW meshes and gene expression analysis demonstrated up-regulation of chondrogenic (SOX9, COL2) and prehypertrophic (VEGF) gene markers after 14 days, creating a biohybrid sheet. When implanted subcutaneously (4 weeks), the biohybrid sheets mineralized (23 ± 3% MV/TV) and formed bone and bone marrow. Bone formation was also observed when implanted in a murine critically-sized long bone defect, though a high variation between samples was detected. The high versatility of this biofabrication approach lies in the possibility to tailor the scaffolds to shape and dimensions corresponding to the large bone defects and the individual patient using robust bone forming building blocks. These strategies are instrumental in the development of personalized regenerative therapies with predictive clinical outcomes. STATEMENT OF SIGNIFICANCE: Successful treatments for healing of large long bone defects are still limited and 2-12% of fractures do not heal properly. We combined a novel biofabrication technique: melt electrowriting (MEW), with robust biology: bone forming cartilaginous spheroids to create biohybrid sheets able to form bone upon implantation. MEW enabled the fabrication of scaffolds with micrometer-sized fibers in defined patterns which allowed the capturing of and merging with cartilaginous spheroids which had the potency to mature into bone via the developmental process of endochondral ossification. The present study contributes to the rapidly growing field of "Biofabrication with Spheroid and Organoid Materials'' and demonstrates design considerations that are of great importance for biofabrication of functional tissues through the assembly of cellular spheroids. ispartof: Acta Biomater vol:165 pages:111-124 ispartof: location:England status: published

Aminoglycosides are an important class of antibiotics that play a critical role in the treatment of life-threatening infections, but their use is limited by their toxicity. In fact, gentamicin causes severe nephrotoxicity in 17% of hospitalized patients. The kidney proximal tubule is particularly vulnerable to drug-induced nephrotoxicity due to its role in drug transport. In this work, we developed a perfused vascularized model of human kidney tubuloids integrated with tissue-embedded microsensors that track the metabolic dynamics of aminoglycoside-induced renal toxicity in real time. Our model shows that gentamicin disrupts proximal tubule polarity at concentrations 20-fold below its TC

Contains fulltext : 247514.pdf (Publisher’s version ) (Closed access) Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n = 35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomised, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms. 10 p.

Background:Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention.Methods:We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran’s Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 145 mg/day of nanocrystallized fenofibrate added to the standard of care.Results:SARS-CoV-2 infection produced transcriptional changes associated with increased glycolysis and lipid accumulation. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARα-dependent mechanism in both alpha and delta variants. Analysis of 3233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective non-randomized interventional open-label study was carried out on 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to patients admitted during the same period.Conclusions:Taken together, our data suggest that pharmacological modulation of PPARα should be strongly considered as a potential therapeutic approach for SARS-CoV-2 infection and emphasizes the need to complete the study of fenofibrate in large randomized controlled clinical trials.Funding:Funding was provided by European Research Council Consolidator Grants OCLD (project no. 681870) and generous gifts from the Nikoh Foundation and the Sam and Rina Frankel Foundation (YN). The interventional study was supported by Abbott (project FENOC0003).Clinical trial number:NCT04661930.

This paper presents a novel, low-cost, user-friendly Precision Agriculture platform that attempts to alleviate the drawbacks of limited battery life by carefully designing missions tailored to each field’s specific, time-changing characteristics. The proposed system is capable of designing coverage missions for any type of UAV, integrating field characteristics into the resulting trajectory, such as irregular field shape and obstacles. The collected images are automatically processed to create detailed orthomosaics of the field and extract the corresponding vegetation indices. A novel mechanism is then introduced that automatically extracts possible problematic areas of the field and subsequently designs a follow-up UAV mission to acquire extra information on these regions. The toolchain is finished by using a deep learning module that was made just for finding weeds in the close-examination flight. For the development of such a deep-learning module, a new weed dataset from the UAV’s perspective, which is publicly available for download, was collected and annotated. All the above functionalities are enclosed in an open-source, end-to-end platform, named Cognitional Operations of micro Flying vehicles (CoFly). The effectiveness of the proposed system was tested and validated with extensive experimentation in agricultural fields with cotton in Larissa, Greece during two different crop sessions.

Color comprises one of the most significant and dominant cues for various applications. As one of the most noticeable and stable attributes of vehicles, color can constitute a valuable key component in several practices of intelligent surveillance systems. In this paper, we propose a deep-learning-based framework that combines semantic segmentation masks with pixels clustering for automatic vehicle color recognition. Different from conventional methods, which usually consider only the features of the vehicle's front side, the proposed algorithm is able for view-independent color identification, which is more effective for the surveillance tasks. To the best of our knowledge, this is the first work that employs semantic segmentation masks along with color clustering for the extraction of the vehicle's color representative parts and the recognition of the dominant color, respectively. To evaluate the performance of the proposed method, we introduce a challenging multi-view dataset of 500 car-related RGB images extending the publicly available DSMLR Car Parts dataset for vehicle parts segmentation. The experiments demonstrate that the proposed approach achieves excellent performance and accurate results reaching an accuracy of 93.06% in the multi-view scenario. To facilitate further research, the evaluation dataset and the pre-trained models will be released at https://github.com/klearchos-stav/vehicle_color_recognition.

Chromatin licensing and DNA replication factor 1 (CDT1), a protein of the pre-replicative complex, is essential for loading the minichromosome maintenance complex (MCM) helicases onto the origins of DNA replication. While several studies have shown that dysregulation of CDT1 expression causes re-replication and DNA damage in cell lines, and CDT1 is highly expressed in several human cancers, whether CDT1 deregulation is sufficient to enhance tumorigenesis in vivo is currently unclear. To delineate its role in vivo, we overexpressed Cdt1 in the mouse colon and induced carcinogenesis using azoxymethane/dextran sodium sulfate (AOM/DSS). Here, we show that mice overexpressing Cdt1 develop a significantly higher number of tumors with increased tumor size, and more severe dysplastic changes (high-grade dysplasia), compared with control mice under the same treatment. These tumors exhibited an increased growth rate, while cells overexpressing Cdt1 loaded greater amounts of Mcm2 onto chromatin, demonstrating origin overlicensing. Adenomas overexpressing Cdt1 showed activation of the DNA damage response (DDR), apoptosis, formation of micronuclei, and chromosome segregation errors, indicating that aberrant expression of Cdt1 results in increased genomic and chromosomal instability in vivo, favoring cancer development. In line with these results, high-level expression of CDT1 in human colorectal cancer tissue specimens and colorectal cancer cell lines correlated significantly with increased origin licensing, activation of the DDR, and microsatellite instability (MSI). © 2022 The Pathological Society of Great Britain and Ireland.

The details presented in this article revolve around a sophisticated monitoring framework equipped with knowledge representation and computer vision capabilities, that aims to provide innovative solutions and support services in the healthcare sector, with a focus on clinical and non-clinical rehabilitation and care environments for people with mobility problems. In contemporary pervasive systems most modern virtual agents have specific reactions when interacting with humans and usually lack extended dialogue and cognitive competences. The presented tool aims to provide natural human-computer multi-modal interaction via exploitation of state-of-the-art technologies in computer vision, speech recognition and synthesis, knowledge representation, sensor data analysis, and by leveraging prior clinical knowledge and patient history through an intelligent, ontology-driven, dialogue manager with reasoning capabilities, which can also access a web search and retrieval engine module. The framework’s main contribution lies in its versatility to combine different technologies, while its inherent capability to monitor patient behaviour allows doctors and caregivers to spend less time collecting patient-related information and focus on healthcare. Moreover, by capitalising on voice, sensor and camera data, it may bolster patients’ confidence levels and encourage them to naturally interact with the virtual agent, drastically improving their moral during a recuperation process.

The Verifiability Approach is a lie detection method based on the insight that truth-tellers provide precise details whereas liars sometimes remain vague to avoid being exposed. We provide a game-theoretic foundation for the strategic effect that underlies this approach. We consider a speaker who wants to be acquitted and an investigator who prefers to find out the truth. The investigator can verify the speaker’s statement at some cost; verification gets more reliable the more details are provided. If, after a falsified statement, the investigator convicts, an additional penalty is imposed. Constructing precise but false statements is assumed to be cognitively costly. We derive all equilibria and thereby the conditions under which the investigator can infer valuable information from the speaker’s statement at face value. If cognitive costs are not prohibitively high, these require that liars are deterred from making false precise statements if always verified. Strategic information revelation by the speaker and verification by the investigator then necessarily work in tandem in a partially pooling equilibrium. Improvements in reliability result in more valuable information via the statements per se, whereas larger lying costs or a harsher penalty do not once the deterrence condition for the existence of this equilibrium is met.

The CoFly-WeedDB contains 201 RGB images (∼436 MB) from the attached camera of DJI Phantom Pro 4 from a cotton field in Larissa, Greece during the first stages of plant growth. The 1280 × 720 RGB images were collected while the Unmanned Aerial Vehicle (UAV) was performing a coverage mission over the field's area. During the designed mission, the camera angle was adjusted to -87°, vertically with the field. The flight altitude and speed of the UAV were equal to 5 m and 3 m/s, respectively, aiming to provide a close and clear view of the weed instances. All images have been annotated by expert agronomists using the LabelMe annotation tool, providing the exact boundaries of 3 types of common weeds in this type of crop, namely (i) Johnson grass, (ii) Field bindweed, and (iii) Purslane. The dataset can be used alone and in combination with other datasets to develop AI-based methodologies for automatic weed segmentation and classification purposes.

This cross-sectional study aimed to explore specific online behaviours and their association with a range of underlying psychological and other behavioural factors during the COVID-19 pandemic. Eight countries (Italy, Spain, the United Kingdom, Lithuania, Portugal, Japan, Hungary, and Brazil) participated in an international investigation involving 2223 participants (M = 33 years old; SD = 11), 70% of whom were females. Participants were surveyed for specific type of Internet use severity, appearance anxiety, self-compassion, and image and use of performance-enhancing drugs (IPEDs). Results were compared cross-culturally. The mean time spent online was 5 h (SD = ±3) of daily browsing during the pandemic. The most commonly performed activities included social networking, streaming, and general surfing. A strong association between these online behaviours and appearance anxiety, self-compassion, and IPEDs use was found after adjustment for possible confounders, with higher scores being associated with specific online activities. Significant cross-cultural differences also emerged in terms of the amount of time spent online during the initial stages of the COVID-19 pandemic.

Funder: UCLH Biomedical Research Centre, Funder: GlaxoSmithKline, Funder: Medical Research Council, Funder: Australian Research Council, Funder: National Institute for Health Research (NIHR), BACKGROUND: There is growing concern about how people with eating disorders are impacted by the widespread societal restructuring during the COVID-19 crisis. AIMS: We aimed to examine how factors relating to the impact of the pandemic associate with eating disorders and quantify this relationship while adjusting for concurrent and longitudinal parameters of risk. METHODS: We gathered demographic, behavioral and clinical data pre- and mid-pandemic as well as childhood trauma history from a longitudinal online survey of 489 adults (mean age 23.4 years) recruited from the Neuroscience in Psychiatry Network (NSPN). Using pre-pandemic (T1) and concurrent (T2) data we aimed to predict eating disorders at mid-pandemic (T2). We deployed hierarchical generalized logistic regression to ascertain the strength of longitudinal and concurrent associations. RESULTS: Pre-pandemic eating disorder scores strongly associated with concurrent eating disorder (z = 5.93). More conflict at home mid-pandemic (z = 2.03), pre- (lower sensation seeking z = -2.58) and mid-pandemic (higher lack of perseverance z = 2.33) impulsivity traits also associated with mid-pandemic eating disorder. CONCLUSION: Conflict at home mid-pandemic and specific aspects of impulsiveness significantly associated with concurrent eating disorder when adjusted for pre-pandemic eating disorder symptoms, baseline demographics, behavioral traits, history of traumatic experiences and concurrent psychopathology. These results provide insight into the struggles of those suffering with eating disorders during the COVID-19 pandemic and highlight the importance of impulsiveness traits and the immediate family environment in their experience of illness during the pandemic.

The paper presents a novel method of generating metamodels that can quantify the influence of urban form on the heating and cooling loads of dwellings for the Mediterranean climate. The goal of the...

Eating disorders are widespread illnesses with significant global impact. There is growing concern about how young people overuse online resources leading to mental health sequelae. We gathered data from 639 individuals from a population cohort. Participants were all young adults at the point of contact and were grouped as having probable eating disorder with excessive exercise (n = 37) or controls (n = 602). We measured obsessionality, compulsivity, impulsivity, and problematic internet use. Group differences in these domains were evaluated; and structural equation modelling (SEM) was used to assess structural relationships between variables. Cases had higher scores of obsessional thoughts of threat (Cohen's d = 0.94, p < 0.001), intolerance towards uncertainty (Cohen's d = 0.72; p < 0.001), thoughts of importance and control (Cohen's d = 0.65, p < 0.01), compulsivity (Cohen's d = 0.72; p < 0.001), negative urgency (Cohen's d = 0.75, p < 0.001), and higher problematic usage of the internet (Cohen's d = 0.73; p-corrected

In this current opinions article we synthesize recent evidence exploring neurocognitive deficits in problematic usage of the internet, which support the notion that inhibitory control and decision making deficits occur in problematic usage versus controls, strengthening its theoretical conceptualization. Potential confounders, notably IQ and the presence of comorbidities from the impulsive/compulsive spectrum may account for some of these identified deficits. Most studies focused on gaming, whereas other facets remain relatively understudied. The literature has high levels of methodological issues, such as using non-validated thresholds/instruments, examining only a narrow range of cognitive domains, and overlooking potentially confounding comorbid disorders. Longitudinal studies with rigorous methodologies are needed to address whether cognitive problems associated with problematic internet use play a role in vulnerability, chronicity, or both.

In this report, the overview of the runs during the TRECVID 2021 by the ITI-CERTH team arepresented. ITI-CERTH participated in the Ad-hoc Video Search (AVS) and Activities in ExtendedVideo (ActEV) tasks. For the AVS task, our participation is based on an attention-based cross-modaldeep network architecture. As part of training this architecture, we experimented with a new hard negative mining approach. For the ActEV task, we improve our framework, in terms of more accurateperformance, by addressing the classification problem as multi-label rather than a single-label.

We test whether anchoring affects people’s elicited valuations for a bottle of wine in individual decision-making and in markets. We anchor subjects by asking them if they are willing to sell a bottle of wine for a transparently uninformative random price. We elicit subjects’ Willingness-To-Accept for the bottle before and after the market. Subjects participate in a double auction market either in a small or a large trading group. The variance in subjects’ Willingness-To-Accept shrinks within trading groups. Our evidence supports the idea that markets have the potential to diminish anchoring effects. However, the market is not needed: our anchoring manipulation failed in a large sample. In a concise meta-analysis, we identify the circumstances under which anchoring effects of preferences can be expected.

Childhood Maltreatment (CM) is one of the strongest predictors of adult mental illness, though not all adults with CM develop psychopathology. Here, we describe the structure and function of emotional brain regions that may contribute to resilient functioning after CM. We review studies that report medial prefrontal cortex (mPFC), amygdala and hippocampus (‘limbic regions’) structure, function, and/or connections, in resilient (i.e., adults reporting CM without psychopathology) vs. vulnerable (i.e., adults reporting CM with psychopathology), or healthy adults (adults without CM with no psychopatology). We find that resilient adults have larger hippocampal grey and white matter volume, and increased connectivity between the central executive network and limbic regions. In addition, resilient adults have improved ability to regulate emotions through mPFC-limbic downregulation, lower hippocampal activation to emotional faces, and increased amygdala habituation to stress. We highlight the need for longitudinal designs that examine resilient functioning across domains and consider gender, type, timing, nature of CM assessments and further stressors, in order to further improve our understanding of the role of the emotional brain in resilient functioning after CM., ALvH is funded by the UK’s Royal Society (DH15017, RGF\EA\180029 & 567RGF\RI\180064), MQ (MQBFC/2), and the MRC MRF Emerging Leaders award. Part of this research was carried out by K.I. during a Fellowship awarded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research & Care (CLAHRC) East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. ADA was funded by the Aker Scholarship.

Mitochondrial inner NEET (MiNT) and the outer mitochondrial membrane (OMM) mitoNEET (mNT) proteins belong to the NEET protein family. This family plays a key role in mitochondrial labile iron and reactive oxygen species (ROS) homeostasis. NEET proteins contain labile [2Fe-2S] clusters which can be transferred to apo-acceptor proteins. In eukaryotes, the biogenesis of [2Fe-2S] clusters occurs within the mitochondria by the iron-sulfur cluster (ISC) system; the clusters are then transferred to [2Fe-2S] proteins within the mitochondria or exported to cytosolic proteins and the cytosolic iron-sulfur cluster assembly (CIA) system. The last step of export of the [2Fe-2S] is not yet fully characterized. Here we show that MiNT interacts with voltage-dependent anion channel 1 (VDAC1), a major OMM protein that connects the intermembrane space with the cytosol and participates in regulating the levels of different ions including mitochondrial labile iron (mLI). We further show that VDAC1 is mediating the interaction between MiNT and mNT, in which MiNT transfers its [2Fe-2S] clusters from inside the mitochondria to mNT that is facing the cytosol. This MiNT-VDAC1-mNT interaction is shown both experimentally and by computational calculations. Additionally, we show that modifying MiNT expression in breast cancer cells affects the dynamics of mitochondrial structure and morphology, mitochondrial function, and breast cancer tumor growth. Our findings reveal a pathway for the transfer of [2Fe-2S] clusters, which are assembled inside the mitochondria, to the cytosol.

Gambling in the modern era is pervasive owing to the variety of gambling opportunities available, including those that use technology (eg, online applications on smartphones). Although many people gamble recreationally without undue negative effects, a sizeable subset of individuals develop disordered gambling, which is associated with marked functional impairment including other mental health problems, relationship problems, bankruptcy, suicidality, and criminality. The National UK Research Network for Behavioural Addictions (NUK-BA) was established to promote understanding of, research into, and treatments for behavioural addictions including gambling disorder, which is the only formally recognised behavioural addiction. In this Health Policy paper, we outline the status of research and treatment for disordered gambling in the UK (including funding issues) and key research that should be conducted to establish the magnitude of the problem, vulnerability and resilience factors, the underlying neurobiology, long-term consequences, and treatment opportunities. In particular, we emphasise the need to: (1) conduct independent longitudinal research into the prevalence of disordered gambling (including gambling disorder and at-risk gambling), and gambling harms, including in vulnerable and minoritised groups; (2) select and refine the most suitable pragmatic measurement tools; (3) identify predictors (eg, vulnerability and resilience markers) of disordered gambling in people who gamble recreationally, including in vulnerable and minoritised groups; (4) conduct randomised controlled trials on psychological interventions and pharmacotherapy for gambling disorder; (5) improve understanding of the neurobiological basis of gambling disorder, including impulsivity and compulsivity, genetics, and biomarkers; and (6) develop clinical guidelines based on the best contemporary research evidence to guide effective clinical interventions. We also highlight the need to consider what can be learnt from approaches towards mitigating gambling-related harm in other countries.

Neural stem cells (NSCs) are important constituents of the nervous system, and they become constrained in two specific regions during adulthood: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. The SVZ niche is a limited-space zone where NSCs are situated and comprised of growth factors and extracellular matrix (ECM) components that shape the microenvironment of the niche. The interaction between ECM components and NSCs regulates the equilibrium between self-renewal and differentiation. To comprehend the niche physiology and how it controls NSC behavior, it is fundamental to develop in vitro models that resemble adequately the physiologic conditions present in the neural stem cell niche. These models can be developed from a variety of biomaterials, along with different biofabrication approaches that permit the organization of neural cells into tissue-like structures. This review intends to update the most recent information regarding the SVZ niche physiology and the diverse biofabrication approaches that have been used to develop suitable microenvironments ex vivo that mimic the NSC niche physiology. ispartof: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY vol:9 ispartof: location:Switzerland status: published

Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n = 35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomised, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms.

Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n=35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomized, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms.

Funder: UK Dementia Research Institute., The COVID-19 pandemic (including lockdown) is likely to have had profound but diverse implications for mental health and well-being, yet little is known about individual experiences of the pandemic (positive and negative) and how this relates to mental health and well-being, as well as other important contextual variables. Here, we analyse data sampled in a large-scale manner from 379,875 people in the United Kingdom (UK) during 2020 to identify population variables associated with mood and mental health during the COVID-19 pandemic, and to investigate self-perceived pandemic impact in relation to those variables. We report that while there are relatively small population-level differences in mood assessment scores pre- to peak-UK lockdown, the size of the differences is larger for people from specific groups, e.g. older adults and people with lower incomes. Multiple dimensions underlie peoples’ perceptions, both positive and negative, of the pandemic’s impact on daily life. These dimensions explain variance in mental health and can be statistically predicted from age, demographics, home and work circumstances, pre-existing conditions, maladaptive technology use and personality traits (e.g., compulsivity). We conclude that a holistic view, incorporating the broad range of relevant population factors, can better characterise people whose mental health is most at risk during the COVID-19 pandemic.

Viruses are efficient metabolic engineers that actively rewire host metabolic pathways to support their lifecycle, presenting attractive metabolic targets for intervention. Here we chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples. Bulk and single-cell analyses show that viral replication induces endoplasmic stress and lipid accumulation. Protein expression screen suggests a role for viral proteins in mediating this metabolic response even in the absence of replication. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication. Analysis of 3,233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective interventional open-label study was carried out in 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate (TriCor®) in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to control patients admitted during the same period and treated with the standard-of-care. Taken together, our data show that elevated lipid metabolism underlies critical aspects of COVID-19 pathogenesis, suggesting that pharmacological modulation of lipid metabolism should be strongly considered for the treatment of coronavirus infection.

The COVID-19 pandemic (including lockdown) is likely to have had profound but diverse implications for mental health and well-being, yet little is known about individual experiences of the pandemic (positive and negative) and how this relates to mental health and well-being, as well as other important contextual variables. Here, we analyse data sampled in a large-scale manner from 379,875 people in the United Kingdom (UK) during 2020 to identify population variables associated with mood and mental health during the COVID-19 pandemic, and to investigate self-perceived pandemic impact in relation to those variables. We report that while there are relatively small population-level differences in mood assessment scores pre- to peak-UK lockdown, the size of the differences is larger for people from specific groups, e.g. older adults and people with lower incomes. Multiple dimensions underlie peoples' perceptions, both positive and negative, of the pandemic's impact on daily life. These dimensions explain variance in mental health and can be statistically predicted from age, demographics, home and work circumstances, pre-existing conditions, maladaptive technology use and personality traits (e.g., compulsivity). We conclude that a holistic view, incorporating the broad range of relevant population factors, can better characterise people whose mental health is most at risk during the COVID-19 pandemic.

Problematic usage of the internet (PUI) describes maladaptive use of online resources and is recognized as a growing worldwide issue. Here, we refined the Internet Addiction Test (IAT) for use as a screening tool to measure generalized internet use problems in normative samples. Analysis of response data with parametric unidimensional item response theory identified 10 items of the IAT that measured most of the PUI latent trait continuum with high precision in a subsample of 816 participants with meaningful variance in internet use problems. Selected items may characterize minor, or early stages of, PUI by measuring a preoccupation with the Internet, motivations to use online activities to escape aversive emotional experiences and regulate mood, as well as secrecy, defensiveness, and interpersonal conflict associated with internet use. Summed scores on these 10 items demonstrated a strong correlation with full-length IAT scores and comparable, or better, convergence with measures of impulsivity and compulsivity. Proposed cut-off scores differentiated between individuals potentially at risk of developing PUI from those with few self-reported internet use problems with good sensitivity and specificity. Differential item function testing revealed measurement equivalence between the sexes, Caucasians and non-Caucasians. However, evidence for differential test functioning between independent samples drawn from South Africa and the United States of America suggests that raw scores cannot be meaningfully compared between different geographic regions. These findings have implications for conceptualization and measurement of PUI in normative samples., Public Significance Statement We provide recommendations for measuring symptoms of problematic usage of the internet, which can be identified in a subset of the population using our refined version of the IAT and suggested cut-off scores. Relevant self-reported internet use problems include a preference for online over face-to-face social interactions, use of the internet to regulate emotions, excessive online engagement, interpersonal conflict, and emotional withdrawal following cessation of internet use.

Decreased insulin secretion, associated with pancreatic β-cell failure, plays a critical role in many human diseases including diabetes, obesity, and cancer. While numerous studies linked β-cell failure with enhanced levels of reactive oxygen species (ROS), the development of diabetes associated with hereditary conditions that result in iron overload, e.g., hemochromatosis, Friedreich’s ataxia, and Wolfram syndrome type 2 (WFS-T2, a mutation in CISD2, encoding the [2Fe-2S] protein NAF-1), underscores an additional link between iron metabolism and β-cell failure. Here, using NAF-1-repressed INS-1E pancreatic cells, we observed that NAF-1 repression inhibited insulin secretion, as well as impaired mitochondrial and ER structure and function. Importantly, we found that a combined treatment with the cell permeant iron chelator deferiprone and the glutathione precursor N-acetyl cysteine promoted the structural repair of mitochondria and ER, decreased mitochondrial labile iron and ROS levels, and restored glucose-stimulated insulin secretion. Additionally, treatment with the ferroptosis inhibitor ferrostatin-1 decreased cellular ROS formation and improved cellular growth of NAF-1 repressed pancreatic cells. Our findings reveal that suppressed expression of NAF-1 is associated with the development of ferroptosis-like features in pancreatic cells, and that reducing the levels of mitochondrial iron and ROS levels could be used as a therapeutic avenue for WFS-T2 patients.

In this article, the problem of real-time robot exploration and map building (active SLAM) is considered. A single stereo vision camera is exploited by a fully autonomous robot to navigate, localiz...

Sacrococcygeal pilonidal sinus (SPS), a well-known “army” disease, is a relatively common condition affecting mostly males. Several factors have been described as contributing to the etiology of SPS, including irritation from trauma, obesity, a sedentary lifestyle, and intense hair growth in the intergluteal region. Over a period of 7 years (2010–2017), 1,100 patients with SPS underwent surgery using different surgical methods, the efficacy of which was evaluated by recording complications and recurrences and duration of hospitalization. The methods used were the semi-closed method (SCM) with marsupialization, the open method, the Limberg flap (LF) and the closed method (primary closure). Complications, including postoperative bleeding, abscess formation and cellulitis were recorded, and also recurrence at one year. The efficacy of the SCM modified marsupialization technique showed statistically significant superiority, with a shorter hospital stay and quicker recovery, and the lowest rate of complications (2.9%, p

Background Excessive use of the internet is increasingly recognised as a global public health concern. Individual studies have reported cognitive impairment in problematic internet use (PIU), but have suffered from various methodological limitations. Confirmation of cognitive deficits in PIU would support the neurobiological plausibility of this disorder.Aims To conduct a rigorous meta-analysis of cognitive performance in PIU from case-control studies; and to assess the impact of study quality, the main type of online behaviour (for example gaming) and other parameters on the findings.Method A systematic literature review was conducted of peer-reviewed case-controlled studies comparing cognition in people with PIU (broadly defined) with that of healthy controls. Findings were extracted and subjected to a meta-analysis where at least four publications existed for a given cognitive domain of interest.Results The meta-analysis comprised 2922 participants across 40 studies. Compared with controls, PIU was associated with significant impairment in inhibitory control (Stroop task Hedge's g = 0.53 (s.e. = 0.19-0.87), stop-signal task g = 0.42 (s.e. = 0.17-0.66), go/no-go task g = 0.51 (s.e. = 0.26-0.75)), decision-making (g = 0.49 (s.e. = 0.28-0.70)) and working memory (g = 0.40 (s.e. = 0.20-0.82)). Whether or not gaming was the predominant type of online behaviour did not significantly moderate the observed cognitive effects; nor did age, gender, geographical area of reporting or the presence of comorbidities.Conclusions PIU is associated with decrements across a range of neuropsychological domains, irrespective of geographical location, supporting its cross-cultural and biological validity. These findings also suggest a common neurobiological vulnerability across PIU behaviours, including gaming, rather than a dissimilar neurocognitive profile for internet gaming disorder.Declaration of interest S.R.C. consults for Cambridge Cognition and Shire. K.I.'s research activities were supported by Health Education East of England Higher Training Special interest sessions. A.E.G.'s research has been funded by Innovational grant (VIDI-scheme) from ZonMW: (91713354). N.A.F. has received research support from Lundbeck, Glaxo-SmithKline, European College of Neuropsychopharmacology (ECNP), Servier, Cephalon, Astra Zeneca, Medical Research Council (UK), National Institute for Health Research, Wellcome Foundation, University of Hertfordshire, EU (FP7) and Shire. N.A.F. has received honoraria for lectures at scientific meetings from Abbott, Otsuka, Lundbeck, Servier, Astra Zeneca, Jazz pharmaceuticals, Bristol Myers Squibb, UK College of Mental Health Pharmacists and British Association for Psychopharmacology (BAP). N.A.F. has received financial support to attend scientific meetings from RANZCP, Shire, Janssen, Lundbeck, Servier, Novartis, Bristol Myers Squibb, Cephalon, International College of Obsessive-Compulsive Spectrum Disorders, International Society for Behavioral Addiction, CINP, IFMAD, ECNP, BAP, the World Health Organization and the Royal College of Psychiatrists. N.A.F. has received financial royalties for publications from Oxford University Press and payment for editorial duties from Taylor and Francis. J.E.G. reports grants from the National Center for Responsible Gaming, Forest Pharmaceuticals, Takeda, Brainsway, and Roche and others from Oxford Press, Norton, McGraw-Hill and American Psychiatric Publishing outside of the submitted work.

Surveillance systems currently deploy a variety of devices that can capture visual content (such as CCTV, body-worn cameras, and smartphone cameras), thus rendering the monitoring of the video footage obtained from multiple such devices a complex task. This becomes especially challenging when monitoring social events that involve large crowds, particularly when there is a risk of crowd violence. This paper presents and demonstrates a crowd violence detection system that can process, analyze, and alert the potential stakeholders when violence-related content is identified in crowd-based video footage. Based on deep neural networks, the proposed end-to-end framework utilizes a 3D Convolutional Neural Network (CNN) to deal with the (near) real-time analysis of video streams and video files for crowd violence detection. The framework is trained, evaluated, and demonstrated using the most recent dataset related to crowd-violence, namely the Violent Flows dataset. The presented framework is provided as a standalone application for desktop environments and can analyze video streams and video files.

Background Double adenomas (DA) represents a distinct clinical entity of primary hyperparathyroidism (PHPT). DA may follow various embryologic distribution patterns and could be supernumerary and/or ectopic. Case presentation We describe the first case of PHPT which comes as a result of double ipsilateral adenoma, of which one was both ectopic and supernumerary. A 45 year-old Greek male patient with diagnosed PHPT due to a single lower right parathyroid adenoma was admitted to our department for surgical treatment. The preoperative tests (neck US, Sestamibi scan) were conclusive for single gland disease. The patient underwent focused parathyroidectomy. The frozen section revealed a parathyroid adenoma with a slight possibility for parathyroid carcinoma. Ten minutes after the excision, intact PTH (iPTH) dropped >50% related to preoperative values and was within normal range. Right hemithyroidectomy with additional ipsilateral central neck dissection was performed, because of the possibility for parathyroid carcinoma. The final pathology report showed that the first excised tissue proved to be a parathyroid adenoma, while a second subcapsular one and a normal right upper parathyroid gland were also found. Conclusions Preoperative localization of DA using routine imaging tests and the utility of intraoperative parathyroid hormone assay are still unreliable in detecting multiple adenomas. Furthermore, a slight possibility of a second and simultaneously supernumerary and ectopic adenoma maybe present. Therefore, it would be advisable to establish the use of more advanced imaging tests (such as 4D-CT, 4D-MRI) or other diagnostic tools when DA are suspected.