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Abstract To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

Abstract Nowadays, the majority of media Internet traffic consists of H.264-encoded streaming videos due to its high compatibility. One of the most popular streaming technology used to deliver videos over Internet is Dynamic Adaptive Streaming over HTTP (DASH). It transmit the video as a sequence of independent short video segments tailored to the receiver’s limitations (related to several factors such as available bandwidth or resolution on reception), aiming to enhance the Quality of Experience. In this paper, we present two types of datasets created from 4065 video segments of 2 seconds. The first type consists of extracting features related to color, space, and time from the segments across different vertical resolutions (240, 360, 480, 720, 1080, 1440 and 4K). The second one includes several quality metrics obtained from the same segments when they are encoded with different compression levels in the different resolutions.

Abstract Background BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. Methods The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. Discussion BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. Trial registration: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.

Background: We evaluated outcomes in non-small cell lung cancer (NSCLC) patients who presented with brain-only metastatic (BOM) disease overall and by EGFR/ALK mutation status. Methods: We analyzed clinico-demographic, treatment and survival data for all NSCLC patients who presented to our center between 2014 and 2016 with BOM as their first presentation of metastatic disease. Differences in overall survival (OS) were evaluated using log-rank tests for NSCLC wildtype (NSCLCwt) versus NSCLC with an ALK-rearrangement/EGFR-mutation (NSCLCmut+). Results: Of 109 patients with BOM, median age was 68 years; 51 % were female; 69 % Caucasian; 76 % ever-smoker; 76 % adenocarcinoma; and 25 % NSCLCmut+. While 41 patients (38 %) had subsequent brain-only progressive disease (PD), 22 (20 %) developed extracranial metastases. A higher proportion of NSCLCmut+ (vs –wt) subsequently progressed outside the brain (37 % vs 15 %, p = 0.03). Median time-to-first-extracranial-metastases was 8.5 (NSCLCmut+) vs 21.0 months (NSCLCwt; p = 0.23).With 17.7 months median follow-up, median-OS was 15.9 months [95%CI: 11.5–21.3; all patients]; 12.3 [7.4–18.4; NSCLCwt] and 38.9 [21.3-not reached (NR); NSCLCmut+] (p = 0.09). In 33 of 80 patients with de novo BOM, the primary tumor was treated with surgery or radiotherapy. In patients with NSCLCwt, there was no OS benefit associated with local lung tumor treatment (p = 0.68), whereas in NSCLCmut + pts, local lung tumor treatment correlated with greater OS (median-OS NR vs 21.5 months; p = 0.05). Conclusion: In patients with NSCLCwt with BOM, we observed a -predominant pattern of brain-only secondary progression, however patients with NSCLCmut + more often progressed extracranially. In patients with NSCLCmut+ and BOM, definitive primary tumor treatment correlated with improved survival.

Abstract Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient’s blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4–5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, β-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.

Abstract Background Listeriosis is a severe foodborne infection caused by Listeria monocytogenes, an important foodborne pathogen of animals and humans. Listeriosis is a rare disease in cats. Objective To describe the clinical, diagnostic imaging, histological, and microbiological features of L. monocytogenes‐associated mesenteric lymphadenitis in a cat. Animals Listeria monocytogenes‐associated mesenteric lymphadenitis was confirmed in a cat by histology and microbiology. Results Two distinct isolates of L. monocytogenes were cultured from the affected mesenteric lymph node and whole genome sequencing was performed. Conclusion and Clinical Importance This report should alert veterinary clinicians and microbiologists to the syndrome, which may have implications for health and food safety in animals and humans.

Abstract Background Atopic dermatitis is a chronic inflammatory skin disease and inflammation has been implicated in development of other chronic diseases, but few studies have examined the relationship with dementia. Objectives This study examines associations of atopic dermatitis (AD) and systemic inflammation in adolescence measured using erythrocyte sedimentation rate (ESR), as well as AD diagnosed in adulthood, with dementia risk. Methods We used three Swedish register‐based cohorts. Cohort I (N = 795,680) comprised men, born in 1951–1968, who participated in the military conscription examinations with physician‐assessed AD and ESR; Cohort II (N = 1,757,600) included men and women, born in 1951–1968; and Cohort III (N = 3,988,783) included all individuals in Sweden, born in 1930–1968. We used Cox regression, estimating hazard ratios (HR), with the follow‐up from 50 years of age to dementia diagnosis, date of emigration, death, or 31 December 2018, whichever occurred first. Further, we used a sibling comparison design to adjust for unmeasured confounders shared among siblings. Results Cohort I: 1466 dementia events were accrued during follow‐up of 7.8 years, with a crude rate of 21.6 [95% confidence interval (CI): 20.6, 22.8] per 100,000 person‐years. Cohort II: 3549 dementia events were accrued during follow‐up of 7.4 years, with a crude rate of 23.7 (95% CI: 22.9, 24.5) per 100,000 person‐years. Cohort III: 120,303 dementia events were accrued during follow‐up of 23.7 years, with a crude rate of 180.3 (95% CI: 179.3, 181.3) per 100,000 person‐years. In multivariable analysis using Cohort I, there was no association between AD and dementia [HR 0.68 (95% CI 0.32, 1.43)], nor with moderate [HR 0.71 (95% CI: 0.46, 1.10)] or high [HR 1.23 (95% CI: 0.87, 1.75)] ESR. AD was not associated with dementia risk in Cohort II [HR 1.28 (0.97, 1.71)] or Cohort III [HR 1.01 (0.92, 1.11)]. Conclusions AD was not associated with dementia risk, neither was systemic inflammation measured by ESR in adolescence.

Abstract From an engineering point of view, non‐linear systems are essential to the operation of control systems, because all systems actually have a non‐linear state in nature. In reality, there are many different kinds of non‐linear systems hidden by this negative definition. For successful analysis and control, the identification of non‐linear systems using unknown models is typically necessary. Till now, numerous approaches are developed for identifying non‐linear systems, but it cannot be employed with a large number of components. Moreover, system identification is typically restricted to output and input signals alone, also such systems are rarely used in reality. This is the primary justification for using non‐linear systems in this research. So, this research proposed a non‐linear model of system identification for large‐scale systems under the consideration of two systems: bilinear system and Volterra system. Therefore, a novel algorithm named Self Adaptive Penguin Search Optimization (SAPeSO) is introduced to attain the system characteristics properly and minimize the output variation. Finally, the effectiveness of the proposed work is compared with existing works in terms of various error measures. This research mainly focuses on the application‐oriented engineering problems. In particular, the Mean Absolute Error (MAE) of the proposed work for the Volterra system at 4000 samples is 18.83%, 14.05%, 8.88%, 29.72%, 19.91%, and 6.70% which is better than the existing bald eagle search (BES), arithmetic optimization algorithm (AOA), whale optimization algorithm (WOA), nonlinear autoregressive moving average with exogenous inputs‐ frequency response function + principal component analysis (NARMAX‐FRF+PCA), Global Gravitational Search Algorithm‐Assisted Kalman Filter (CGS‐KF), and sparse regression and separable least squares method (SR‐SLSM) methods, respectively. Finally, the error is minimum for the proposed model when compared with the other traditional approaches.

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 ∼ 50–100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 ∼ 40–60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation.

Ants respond fast to changes in soil conditions in agricultural fields, thus they represent a practical, cheap, clean, and accurate tool to diagnose soil fertility before planting a crop. This study assesses the capacity of richness, occurrence, and activity of ant assemblages to indicate soil physicochemical properties in chayote monoculture in Veracruz, Mexico. Sampling was performed in 15 1-ha-plots and was replicated three times before planting chayote from August to October. Ants were collected using pit-fall traps and determined soil properties were texture, density, contents of organic matter (OM), nitrogen (N), and phosphorous (P), pH, and electrical conductivity (EC). In total, 20,385 ant workers belonging to 51 species, 28 genera, 9 tribes and 6 subfamilies were collected. Species richness significantly explained contents of OM, N, and P in a three-weeks sampling. Species occurrence explained clay percentage in the one-week sampling, N, and P contents in the two-weeks sampling and the aforementioned and percentages of sand and silt in the three-weeks sampling. Ant activity predicted more soil properties in the one-week sampling than in those that lasted two and three weeks.Richness, occurrence, and activity of ant assemblages are valuable tools for diagnosing texture, contents of OM, N, and P, and pH of soil before planting chayote monoculture. It contributes to the understanding of the role that ants play in agricultural fields. Therefore, soil management practices should consider indication capacity of ant assemblages to ensure growth and development of morphological structures such roots, stems, leaves, shoots, and fruits of cultivated plants.

Abstract Background Individuals with Attention‐Deficit/Hyperactivity Disorder (ADHD) face an elevated risk of criminal convictions compared to those without ADHD. However, understanding this link involves considering sex differences, coexisting psychiatric conditions, and unmeasured familial factors. This study aimed to explore the connection between ADHD and criminal convictions (both violent and non‐violent) in males and females, while also assessing the impact of comorbid psychiatric disorders and familial factors. Methods Using Swedish national registers, we identified individuals born between 1986 and 1997 (635,391 males and 600,548 females). ADHD was defined through clinical diagnosis and prescribed medications, while criminal convictions were determined based on Swedish lower court records. Unmeasured familial factors were accounted for using a sibling design approach. Results Findings revealed that individuals with ADHD had a notably higher absolute and relative risk of both violent and non‐violent criminal convictions compared to those without ADHD. While criminal convictions were more frequent among males with ADHD, females with ADHD exhibited higher relative risks (HR violent 10.50, non‐violent 4.04) than their male counterparts (HR violent 6.03, non‐violent 3.57). Additionally, lower socioeconomic status (SES) in individuals with ADHD was associated with increased relative risks for criminal convictions compared to individuals with ADHD who had higher SES. Adjusting for childhood and internalizing psychiatric disorders partially attenuated these associations, while substance use disorders (SUD) substantially attenuated them. SUD also contributed to an elevated absolute risk of criminal convictions in both male and female individuals with ADHD. Accounting for unmeasured shared familial factors slightly reduced the estimates, but the association between ADHD and criminal convictions persisted. Conclusion In conclusion, ADHD remains a potent independent risk factor for criminal convictions, with varying effects based on gender. This underscores the importance of tailored crime prevention strategies and early interventions for individuals with ADHD, especially when comorbid SUD is present.

Although social practices are widely considered to be essential building blocks in the construction of our social world, there is not much of an agreement regarding what kind of entities they are and what constitutes their nature. As an attempt to make progress in this direction, I provide here a general account of their ontology. By implementing specific resources from contemporary social ontology and collective intentionality, I argue that social practices are composite, material entities socially constructed by organised social groups through their individual members acting according to collective reasons. With this, I intend to contribute towards the understanding of both the reality of social practices and their role in the construction of other social entities; particularly, artifacts and institutions.

Abstract The efficient and accurate execution of clinical trials testing novel treatments for Alzheimer's disease (AD) is a critical component of the field's collective efforts to develop effective disease‐modifying treatments for AD. The lengthy and heterogeneous nature of clinical progression in AD contributes to the challenges inherent in demonstrating a clinically meaningful benefit of any potential new AD therapy. The failure of many large and expensive clinical trials to date has prompted a focus on optimizing all aspects of decision making, to not only expedite the development of new treatments, but also maximize the value of the information that each clinical trial yields, so that all future clinical trials (including those that are negative) will contribute toward advancing the field. To address this important topic the Alzheimer's Association Research Roundtable convened December 1–2, 2020. The goals focused around identifying new directions and actionable steps to enhance clinical trial decision making in planned future studies.

Abstract Criminal behaviour has previously been associated with an increased risk for several mental health problems, but little is known about the association between criminal behaviour and dementia. We aimed to examine how the criminal background (type of crime, number of convictions, length of the sentence) is associated with dementia and mild cognitive impairment (MCI), and how mental and physical health disorders and educational attainment influenced these associations. A nationwide cohort of 3,617,028 individuals born between 1932 and 1962 were linked with criminal and medical records using Swedish national registers. We used Cox regression models to examine the associations. Increased risks for dementia (Hazard ratios (HRs) 1.54, 95% confidence interval (CI) 1.50–1.57) and MCI (1.55, 1.50–1.61) were found in individuals with criminal background, particularly among those who committed violent or several crimes, or with long sentences. After full adjustment of covariates, the associations attenuated but remained statistically significant for dementia (1.25, 1.22–1.28) and MCI (1.27, 1.22–1.32). The attenuation was mostly explained by mental health problems -depression, anxiety, schizophrenia spectrum disorders, substance use disorder (SUD), and bipolar disorder- (dementia: 1.34, 1.31–1.37; MCI: 1.35, 1.30–1.40). SUD contributed the most to attenuate the associations. Our results may provide important insights to health and penal systems by showing the importance of considering the severity of the criminal background and life-course mental health when assessing the risk of neurodegenerative disorders.

Introduction:To present a complex case of giant meningoencephalocele after a canal wall down mastoidectomy and describe our preferred approach to repair meningoencephalic herniation of the temporal bone.Case Report:A 20-year-old patient, who had previously undergone type III tympanoplasty with total ossicular reconstruction prosthesis for an attic cholesteatoma, presents with clinical and imaging features compatible with the diagnosis of a giant temporal meningoencephalocele. We performed a combined approach –transmastoid plus minicraniotomy- to repair the skull base defect. A multilayer reconstruction of the defect with septal cartilage and temporal fascia was performed. After a 48 months follow-up, the patient remains symptom free without signs of tissue herniation.Conclusions:Transmastoid plus minicraniotomy combined approach is a safe and feasible technique in case of large and anterior skull base defects with low surgical morbidity, allowing a safe and multilayered reconstruction, even in the context of a simultaneous active chronic otitis media.

In the last years, guaranteeing the security in Internet of things communications has become an essential task. In this article, the bias of a wide set of oscillators has been studied to determine their suitability as both true random number generators (TRNGs) and physically unclonable functions (PUFs). For this purpose, a generic configurable structure has been proposed and implemented in an field programmable gate array (FPGA). With this implementation, by introducing some external signals it is possible to configure the system in different oscillator topologies. This way, we have managed to analyze 2730 oscillators composed by seven lookup tables (LUTs) without having to resynthesize the code each time. The performed analysis has included conventional ring oscillators, Galois ring oscillators, and newly proposed oscillator topologies. From this analysis, we have concluded that none of these oscillators behave as an ideal TRNG but ring oscillators present the closest to an ideal behavior. Regarding their suitability as PUFs, some of the newly proposed oscillators in this article present a high reproducibility, higher than that of conventional ring oscillator PUF (RO-PUF) and a high uniqueness. Furthermore, we have noticed that both their reproducibility and their uniqueness tend to improve when increasing the length of the oscillators, which opens the possibility of finding new oscillators with even better properties by studying oscillators of bigger lengths. Finally, by studying the spatial correlation of the bias of these oscillators, we have observed that they present a much lower spatial correlation compared to the ring oscillators, which opens the possibility of using these oscillators in PUF architectures that use more comparisons than typical RO-PUFs.

Abstract Background This phase II proof-of-concept study assessed the efficacy and safety of BI 425809, a novel selective glycine transporter-1 inhibitor, for the treatment of cognitive impairment associated with probable Alzheimer’s disease dementia. Methods This 12-week, multicenter, double-blind, placebo-controlled, parallel-group study randomized (1:1:1:1:1) patients with mild-to-moderate probable Alzheimer’s disease dementia to BI 425809 2, 5, 10, and 25 mg or placebo once daily. The primary efficacy endpoint was the change from baseline in Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11-item total score after 12 weeks of treatment. Safety was also assessed. Results Six hundred and ten male and female patients were randomized to BI 425809 2 mg (n = 123), 5 mg (n = 122), 10 mg (n = 122), and 25 mg (n = 123) or placebo (n = 120). Approximately 47% (n = 286) were male; the mean (standard deviation) age was 72.9 (7.7) years. Treatment compliance was above 97% for all dose groups. The Mini-Mental State Examination category on the median score was < 22 in 47% (n = 287) of patients and ≥ 22 in 53% (n = 322) of patients. No significant, non-flat dose–response relationship was detected for the primary endpoint (adjusted p-value > 0.76 for all models). BI 425809 was generally well-tolerated. Overall, 47.9% (n = 292) of patients reported at least one adverse event during the trial; the frequency of patients with investigator-defined drug-related adverse events was similar in all treatment groups, ranging from 15.4 to 19.5% across the BI 425809 treatment groups and 15.8% for placebo. Conclusions No clinically meaningful changes from baseline were observed following treatment with BI 425809 in patients with mild-to-moderate probable Alzheimer’s disease dementia. Trial registration ClinicalTrials.gov NCT02788513 (1346-0023). Registered on June 2, 2016. EU Clinical Trials Register 2015-005438-24. Registered on May 6, 2016

Digital twins are essential in Agriculture 5.0, providing an accurate digital representation of agricultural objects and processes, enabling data-driven decision-making, the simulation of future scenarios, and innovation for a more efficient and sustainable agriculture. The main objective of this article is to review and compare the main tools for the development of digital twins for Agriculture 5.0 applications using 3D point cloud models created from photogrammetry techniques. For this purpose, the most commonly used tools for the development of these 3D models are presented. As a methodological approach, a qualitative comparison of the main characteristics of these tools was carried out. Then, based on some images taken in an orange grove, a quality analysis of the 3D point cloud models obtained by each of the analyzed tools was carried out. We also obtained a synthetic quality index in order to have a way to categorize the different pieces of software. Finally, as a conclusion, we compared the performance of the different software tools and the point clouds obtained by considering objective metrics (from the 3D quality assessment) and qualitative metrics in the synthetic quality index. With this index, we found that OpenDroneMap was the best software in terms of quality-cost ratio. Also, the paper introduces the concept of Agriculture 6.0, exploring the integration of advancements from Agriculture 5.0 to envision the potential evolution of agricultural practices and technologies, considering their impact on social and economic aspects.

Abstract Attention‐deficit/hyperactivity disorder (ADHD) often co‐occurs with other psychiatric and physical diseases. However, available evidence on associations between ADHD and cardiovascular diseases (CVDs) is mixed. To systematically review, quantitatively synthesize, and appraise available evidence on the link between ADHD with CVDs, we searched relevant articles in PubMed, Embase, PsycINFO, and Web of Science from inception to May 1, 2022. Study quality was assessed by using the Newcastle‐Ottawa Scale, and random‐effects model meta‐analyses were performed. A total of 18,391,169 (ADHD: n = 421,224) individuals from 11 studies were included in our systematic review and 8,196,648 (ADHD = 332,619) individuals from five studies were included in the main meta‐analysis of adjusted estimates. Pooled estimates showed that ADHD was significantly associated with an increased risk of CVDs in analyses based on adjusted effect size (odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.19–2.23, Q = 140.74, PQ

Background Consistent evidence suggests a strong association between attention-deficit/hyperactivity disorder (ADHD) and subjectively reported sleep problems. However, the prevalence of clinically ascertained sleep disorder diagnoses and sleep medication prescriptions in individuals with ADHD remains unclear.Objective To determine the rates of sleep disorder diagnoses and sleep medication prescriptions in children, adolescents and adults with ADHD.Methods We linked Swedish national registers to create a cohort of individuals born 1945–2008. We estimated the absolute and relative risks (using logistic regression models) of different sleep disorder diagnoses and medication prescriptions in individuals with and without ADHD. The analyses were performed across five different age groups: children (5–11 years), adolescents (12–17 years), young adults (18–30 years), middle-aged adults (31–45 years) and older adults (46–60 years).Findings Among individuals with ADHD (N=145 490, 2.25% of the cohort), 7.5% had a sleep disorder diagnosis and 47.5% had been prescribed sleep medication. Individuals with ADHD, across all age groups, had a statistically significantly increased risk of having any sleep disorder diagnosis (ORrange=6.4–16.1) and any sleep medication prescription (ORrange=12.0–129.4) compared with individuals without ADHD. While rates of sleep disorders were highest in older adults, the relative risks were highest in youth.Conclusions Individuals with ADHD have a substantially increased risk of sleep disorder diagnoses and sleep medication prescriptions, from childhood into older adulthood.Clinical implications More clinical efforts are needed to tackle impairing sleep problems in individuals with ADHD via systematic sleep assessment, appropriate diagnosis, and pharmacological and non-pharmacological interventions. Sleep medication use should be informed by sleep disorder diagnosis.

ABSTRACT Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 104 and 1.4 × 104 gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE.

The computational and experimental data presented in this paper refer to the research article “First-Principles Calculations Integrated with Experimental Optical and Electronic Properties for MoS2-graphene Heterostructures and MoS2-graphene-Au Heterointerfaces”. The computational data includes structural information, electronic and optical properties, and data to calculate the work functions for various molybdenum disulfide and graphene heterostructures and their heterointerfaces with gold. The optical properties calculations include the frequency-dependent dielectric function, the refractive index, the reflectivity, the extinction coefficient, and the energy loss function. These properties were calculated using the independent particle approximation (IPA). As for the experimental optoelectronic properties, we measured photoluminescence spectra (optical), Raman spectra (vibrational), work function (surface electronic property), and local photoconductivity (semiconducting behavior) of graphene-MoS2 heterointerfaces in addition to individual graphene and MoS2 layers on gold. The variation in the exciton bands, the Raman bands, and in the average work function elucidated the semiconducting n-p junction behavior.

Video content on the Internet continues to grow. As a result, streaming platforms must ensure a certain level of quality when preparing their content. To this end, several metrics have been developed by the research community to evaluate video quality. This work integrates 14 video metrics and the SI-TI indicators into a container image to create a cross-platform tool, VQMTK. The tool offers a web interface and a Bash script that combines all metrics into a single tool. Performance tests have demonstrated that the tool is capable of handling all the integrated metrics using 4K video samples. The tool can be used in scientific and educational environments.

Resumen: Introducción: La drepanocitosis es una anemia emergente en Europa que condiciona una elevada morbilidad con complicaciones agudas y crónicas. El manejo de estos pacientes es complejo y requiere atención interdisciplinar. El objetivo del estudio es analizar las características y el manejo de los pacientes con drepanocitosis que ingresan por complicaciones agudas. Métodos: Estudio descriptivo retrospectivo de los ingresos por complicaciones agudas de pacientes con drepanocitosis menores de 16 años en un hospital terciario entre 2010 y 2020. Se revisaron los datos clínicos, analíticos y radiológicos. Resultados: Se incluyeron 71 ingresos correspondientes a 25 pacientes, el 40% diagnosticados por cribado neonatal. Los ingresos se incrementaron de forma progresiva durante este periodo. Los diagnósticos más frecuentes fueron la crisis vasooclusiva (35,2%), el síndrome febril (33,8%) y el síndrome torácico agudo (32,3%). Nueve pacientes precisaron ingreso en cuidados intensivos. En 20 ingresos se obtuvo documentación microbiológica, 60% bacterias. En el 86% se administró antibioterapia y 28% precisaron analgesia con opioides. El 89% cumplían la pauta de vacunación adecuada y el 41% recibían hidroxiurea previo al ingreso. Conclusiones: Las complicaciones agudas que precisan ingreso hospitalario son frecuentes en los pacientes con drepanocitosis, siendo las más habituales la crisis vasooclusiva y el síndrome febril. Esto conlleva un uso elevado de antibioterapia y opioides. El diagnóstico precoz facilita el reconocimiento de complicaciones de riesgo vital como el síndrome torácico agudo y el secuestro esplénico. A pesar de las medidas preventivas y los tratamientos indicados en la actualidad, estas complicaciones agudas precisan manejo hospitalario. Abstract: Introduction: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. Methods: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. Results: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. Conclusions: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management.

Introduction: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. Methods: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. Results: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. Conclusions: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management. Resumen: Introducción: La drepanocitosis es una anemia emergente en Europa que condiciona una elevada morbilidad con complicaciones agudas y crónicas. El manejo de estos pacientes es complejo y requiere atención interdisciplinar. El objetivo del estudio es analizar las características y el manejo de los pacientes con drepanocitosis que ingresan por complicaciones agudas. Métodos: Estudio descriptivo retrospectivo de los ingresos por complicaciones agudas de pacientes con drepanocitosis menores de 16 años en un hospital terciario entre 2010 y 2020. Se revisaron los datos clínicos, analíticos y radiológicos. Resultados: Se incluyeron 71 ingresos correspondientes a 25 pacientes, el 40% diagnosticados por cribado neonatal. Los ingresos se incrementaron de forma progresiva durante este periodo. Los diagnósticos más frecuentes fueron la crisis vasooclusiva (35,2%), el síndrome febril (33,8%) y el síndrome torácico agudo (32,3%). Nueve pacientes precisaron ingreso en cuidados intensivos. En 20 ingresos se obtuvo documentación microbiológica, 60% bacterias. En el 86% se administró antibioterapia y 28% precisaron analgesia con opioides. El 89% cumplían la pauta de vacunación adecuada y el 41% recibían hidroxiurea previo al ingreso. Conclusiones: Las complicaciones agudas que precisan ingreso hospitalario son frecuentes en los pacientes con drepanocitosis, siendo las más habituales la crisis vasooclusiva y el síndrome febril. Esto conlleva un uso elevado de antibioterapia y opioides. El diagnóstico precoz facilita el reconocimiento de complicaciones de riesgo vital como el síndrome torácico agudo y el secuestro esplénico. A pesar de las medidas preventivas y los tratamientos indicados en la actualidad, estas complicaciones agudas precisan manejo hospitalario.

SoilMERGE (SMERGE) is a root-zone soil moisture (RZSM) product that covers the entire continental United States and spans 1978 to 2019. Machine learning techniques, Random Forest (RF), eXtreme Gradient Boosting (XGBoost), and Gradient Boost (GBoost) downscaled SMERGE to spatial resolutions straddling the field scale domain (100 to 3000 m). Study area was northern Oklahoma and southern Kansas. The coarse resolution of SMERGE (0.125 degree) limits this product’s utility. To validate downscaled results in situ data from four sources were used that included: United States Department of Energy Atmospheric Radiation Measurement (ARM) observatory, United States Climate Reference Network (USCRN), Soil Climate Analysis Network (SCAN), and Soil moisture Sensing Controller and oPtimal Estimator (SoilSCAPE). In addition, RZSM retrievals from NASA’s Airborne Microwave Observatory of Subcanopy and Surface (AirMOSS) campaign provided a nearly spatially continuous comparison. Three periods were examined: era 1 (2016 to 2019), era 2 (2012 to 2015), and era 3 (2003 to 2007). During eras 1 and 2, RF outperformed XGBoost and GBoost, whereas during era 3 no model dominated. Performance was better during eras 1 and 2 as opposed to the pre-L band era 3. Improvements across all eras, regions, and models realized from downscaling included an increase in correlation from 0.03 to 0.42 and a decrease in ubRMSE from −0.0005 to −0.0118 m3/m3. This study demonstrates the feasibility of SMERGE downscaling opening the prospect for the development of a long-term RZSM dataset at a more desirable field-scale resolution with the potential to support diverse hydrometeorological and agricultural applications.

Abstract Growing evidence suggests that ADHD, an early onset neurodevelopmental disorder, is associated with poor somatic health in adulthood. However, the mechanisms underlying these associations are poorly understood. Here, we tested whether ADHD polygenic risk scores (PRS) are associated with mid-to-late life somatic health in a general population sample. Furthermore, we explored whether potential associations were moderated and mediated by life-course risk factors. We derived ADHD-PRS in 10,645 Swedish twins born between 1911 and 1958. Sixteen cardiometabolic, autoimmune/inflammatory, and neurological health conditions were evaluated using self-report (age range at measure 42–88 years) and clinical diagnoses defined by International Classification of Diseases codes in national registers. We estimated associations of ADHD-PRS with somatic outcomes using generalized estimating equations, and tested moderation and mediation of these associations by four life-course risk factors (education level, body mass index [BMI], tobacco use, alcohol misuse). Results showed that higher ADHD-PRS were associated with increased risk of seven somatic outcomes (heart failure, cerebro- and peripheral vascular disease, obesity, type 1 diabetes, rheumatoid arthritis, and migraine) with odds ratios ranging 1.07 to 1.20. We observed significant mediation effects by education, BMI, tobacco use, and alcohol misuse, primarily for associations of ADHD-PRS with cardiometabolic outcomes. No moderation effects survived multiple testing correction. Our findings suggests that higher ADHD genetic liability confers a modest risk increase for several somatic health problems in mid-to-late life, particularly in the cardiometabolic domain. These associations were observable in the general population, even in the absence of medical treatment for ADHD, and appear to be in part mediated by life-course risk factors.

BackgroundDigital inclusion and literacy facilitate access to health information and can contribute to self-care behaviors and informed decision-making. However, digital literacy is not an innate skill, but rather requires knowledge acquisition. ObjectiveThe present study aimed to develop, conduct, and measure the impact, on digital and health literacy, of a digital inclusion program aimed at community dwellers. MethodsThe program targeted the recruitment of people aged 55 and older that owned mobile devices with an internet connection in 3 cities in northern Portugal (Paredes de Coura, Guimarães, and Barcelos). The program was titled the Workshops for Online Technological Inclusion (OITO) project and, in each city, was promoted by the coordinator of municipal projects and organized as an in-person 8-workshop program, using mobile devices, smartphones, or tablets. A quasi-experimental design was used with a nonrandomized allocation of participants in each set of 8 workshops. Sociodemographic, health status, and mobile use information were collected at baseline. Digital and health literacy were measured via the Mobile Device Proficiency Questionnaire and the Health Literacy Scale questionnaires, respectively, at baseline (T1), program completion (T2), and a 1-month follow-up (T3). A self-reported measure of autonomy was evaluated at T1 and T2 using a visual scale. ResultsMost participants were women with primary schooling (up to 4 years) aged between 65 and 74 years and retired. The intervention had an 81% (97/120) recruitment rate, 53% (43/81) adherence, and 94% (67/71) satisfaction rate, with 81 participants completing the entire 8-workshop program. Most participants had owned their mobile device for more than one year (64/81, 79%), were frequent daily users (70/81, 86%), and had received their mobile device from someone else (33/64, 52%). Over 80% (71/81) of the participants who completed the intervention used Android smartphones. At baseline, participants had low baseline scores in digital literacy, but medium-high baseline scores in health literacy. They showed significant improvement in digital literacy at T2 and T3 compared to T1, but without a significant difference between T2 and T3, regardless of sex, age, or schooling. A significant improvement in self-reported autonomy was observed at T3 compared with baseline. Regarding health literacy, no significant differences were found at T2 or T3 compared to the baseline. ConclusionsThe feasibility indicators showed that the OITO project methodology had a substantial rate of recruitment and satisfaction. Program participants had significant improvement in digital literacy after 8 workshops and maintained their score 1 month after completing the intervention. There was no significant change in health literacy during the project period.

Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or progression compared to patients diagnosed initially as stage IV (de novo). We compared the presentation, treatments, and outcomes of patients with KRASG12C-mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history. When compared to patients with KRASG12C-mutated NSCLC who developed stage IV disease at recurrence (n = 38), de novo stage IV patients (n = 71) had worse ECOG performance status (p = 0.007), greater numbers of extra-thoracic metastatic sites (p = 0.001), and were less likely to receive 2nd/3rd line systemic therapy (p = 0.05, p = 0.002) or targeted therapy (p = 0.001). De novo metastatic patients had shorter overall survival than metastatic patients at recurrence (9.1 versus 24.2 months; adjusted-hazard-ratio=1.94 (95% CI: 1.14–3.28; p = 0.01)). There is a critical need for well-tolerated targeted therapies in the first-line setting for metastatic patients with de novo, high-burden, stage IV KRASG12C-mutated NSCLCs.

The balance between game difficulty and player skill in the evolving landscape of the video game industry is a significant factor in player engagement. This study introduces a deep learning (DL) approach to enhance gameplay by dynamically adjusting game difficulty based on a player’s skill level. Our methodology aims to prevent player disengagement, which can occur if the game difficulty significantly exceeds or falls short of the player’s skill level. Our evaluation indicates that such dynamic adjustment leads to improved gameplay and increased player involvement, with 90% of the players reporting high game enjoyment and immersion levels.

Delivery of adeno-associated viral vectors (AAVs) to cerebrospinal fluid (CSF) has emerged as a promising approach to achieve widespread transduction of the central nervous system (CNS) and peripheral nervous system (PNS), with direct applicability to the treatment of a wide range of neurological diseases, particularly lysosomal storage diseases. Although studies in small animal models have provided proof of concept and experiments in large animals demonstrated feasibility in bigger brains, there is not much information on long-term safety or durability of the effect. Here, we report a 7-year study in healthy beagle dogs after intra-CSF delivery of a single, clinically relevant dose (2 × 1013 vg/dog) of AAV9 vectors carrying the canine sulfamidase, the enzyme deficient in mucopolysaccharidosis type IIIA. Periodic monitoring of CSF and blood, clinical and neurological evaluations, and magnetic resonance and ultrasound imaging of target organs demonstrated no toxicity related to treatment. AAV9-mediated gene transfer resulted in detection of sulfamidase activity in CSF throughout the study. Analysis at tissue level showed widespread sulfamidase expression and activity in the absence of histological findings in any region of encephalon, spinal cord, or dorsal root ganglia. Altogether, these results provide proof of durability of expression and long-term safety for intra-CSF delivery of AAV-based gene transfer vectors encoding therapeutic proteins to the CNS.

Abstract Objective (1) investigate the associations of attention‐deficit/hyperactivity disorder (ADHD) with systolic and diastolic blood pressure, resting heart rate, pulse pressure (PP), physical fitness, and BMI; (2) explore whether cardiovascular risk factors and ADHD share genetic and environmental influences; (3) assess if pharmacological treatment for ADHD influences these associations. Methods We identified 395,978 individuals born between 1973 and 1991 who had military conscription examinations at a mean age of 18.3 years (SD = 0.57) and their full‐siblings within the same cohort (N = 208,060) by linking population‐based registers in Sweden. Results Significantly increased risk of ADHD was observed in individuals with low systolic blood pressure (SBP) and PP, low physical fitness, and in those who had overweight or obesity after adjustments (adjusted Odds Ratio [OR] ranging from 1.10 to 1.45). Full siblings of individuals with low SBP, low physical fitness, and obesity were more likely to receive an ADHD diagnosis compared to full siblings without those risk factors (OR ranging from 1.17 to 1.31). Additionally, analyses showed robust associations between ADHD and low SBP, low physical fitness, and obesity, even in ADHD medication‐naïve individuals. Conclusions Individuals with several cardiovascular risk factors are more often diagnosed with ADHD, regardless of psychiatric comorbidity. These association are not explained by ADHD pharmacotherapy, rather, they are in part due to shared familial risk factors.

Hybrid static and dynamic typing languages are aimed at combining the benefits of both kinds of languages: the early type error detection and compile-time optimizations of static typing, together with the runtime adaptability of dynamically typed languages. The StaDyn programming language is a hybrid typing language, whose main contribution is the utilization of the type information gathered by the compiler to improve compile-time error detection and runtime performance. StaDyn has been evaluated as the hybrid typing language for the .Net platform with the highest runtime performance and the lowest memory consumption. Although most optimizations are performed statically by the compiler, compilation time is yet lower than the existing hybrid languages implemented on the .Net platform.

Objective To assess the inverse relationship between acute appendicitis and ulcerative colitis (UC) using a sibling comparison design to adjust for unmeasured familial genetic and environmental factors.Design The cohort comprised 3.1 million individuals resident in Sweden between 1984 and 2018 with the linkage of several Swedish national registers. Fitting Cox hazards models, we calculated the risk for developing UC in individuals with and without acute appendicitis by the age 20 years adjusting for several potential confounding factors. Further, we performed sibling-stratified analyses to adjust for shared unmeasured familial confounding factors.Results During 57.7 million person-years of follow-up, 20 848/3 125 232 developed UC among those without appendicitis (3.63 (3.59–3.68) per 10 000 person-years), whereas only 59/35 848 people developed UC among those with appendicitis before age 20 years (1.66 (1.28–2.14) per 10 000 person-years). We found a decreased risk for developing UC in those with acute appendicitis by the age 20 years compared with individuals who did not have appendicitis by this age (HR=0.37 (95% CI 0.29 to 0.48)). When adjusting for shared familial confounders, we observed only a slight attenuation in this association (HR=0.46 (95% CI 0.32 to 0.66)).Conclusion Individuals who had acute appendicitis by late adolescence showed a decreased risk for developing UC compared with those who did not. Genetic and shared familial environmental factors seem to potentially play only a small role in this relationship. Our results suggest an independent association of acute appendicitis, or its underlying causes, with UC risk.

Introduction: Molecular profiling of tumor tissue is the gold standard for treatment decision-making in advanced non-small cell lung cancer (NSCLC). Results may be delayed or unavailable due to insufficient tissue, prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma testing in the initial diagnostic workup for patients with suspected advanced lung cancer. Methods: Patients with ⩽15 pack-year smoking history and suspected advanced lung cancer referred to the lung cancer rapid diagnostic program underwent plasma circulating-tumor DNA testing using a DNA-based mutation panel. Tissue testing was performed per standard of care, including comprehensive next-generation sequencing (NGS). The primary endpoint was time from diagnostic program referral to cancer treatment in stage IV NSCLC patients (Cohort A) compared to a contemporary cohort not enrolled in the study (Cohort B) and an historical pre-COVID cohort referred to the program between 2018 and 2019 (Cohort C). Results: From January to June 2021, 20 patients were enrolled in Cohort A; median age was 70.5 years (range 33–87), 70% were female, 55% Caucasian, 85% never smokers, and 75% were diagnosed with NSCLC. Seven had actionable alterations detected in plasma or tissue (4/7 concordant). Fusions, not tested in plasma, were identified by immunohistochemistry for three patients. Mean result turnaround time was 17.8 days for plasma NGS and 23.6 days for tissue ( p = 0.10). Mean time from referral to treatment initiation was significantly shorter in cohort A at 32.6 days (SD 13.1) versus 62.2 days (SD 31.2) in cohort B and 61.5 days (SD 29.1) in cohort C, both p

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P = 0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

Physically unclonable functions avoid storing secret information in non-volatile memories and only generate a key when it is necessary for an application, rising as a promising solution for the authentication of resource-constrained IoT devices. However, the need to minimize the predictability of physically unclonable functions is evident. The main purpose of this work is to determine the optimal way to construct a physically unclonable function. To do this, a ring oscillator physically unclonable function based on comparing oscillators in pairs has been implemented in an FPGA. This analysis shows that the frequencies of the oscillators greatly vary depending on their position in the FPGA, especially between oscillators implemented in different types of slices. Furthermore, the influence of the chosen locations of the ring oscillators on the quality of the physically unclonable function has been analyzed and we propose five strategies to select the locations of the oscillators. Among the strategies proposed, two of them stand out for their high uniqueness, reproducibility, and identifiability, so they can be used for authentication purposes. Finally, we have analyzed the reproducibility for the best strategy facing voltage and temperature variations, showing that it remains stable in the studied range.

La investigación tuvo como propósito analizar las propiedades psicométricas de la Escala Breve de Resiliencia Connor-Davidson (CD-RISC 10). La muestra constó de 345 universitarios de ambos sexos de una universidad privada, con edades comprendidas entre los 18 a 50 años provenientes de Lima Metropolitana (Perú). Los instrumentos utilizados fueron la escala breve de resiliencia CD-RISC 10, la Escala de Estrés Percibido (EEP-10) y la Escala de Autoeficacia General (EAG). Para analizar la validez de constructo se realizó un análisis factorial que demostró que el modelo unifactorial explica el 47 % la varianza total acumulada, posteriormente se pasó a corroborar el modelo propuesto a través del análisis factorial confirmatorio que arrojó valores óptimos de ajuste. Se estudió la validez convergente con las variables autoeficacia general (r = .664, p = .000) y una validez divergente con estrés percibido (r = -.402, p = .000). La confiabilidad se estableció a través de los coeficientes de alfa de Cronbach (α = .827) y Omega de McDonald (Ω = .827). Los resultados permiten concluir que el instrumento presenta evidencias de validez y que sus puntuaciones son consistentes.

An important aspect of the design of effective machine learning algorithms is the complexity analysis of classification problems. In this paper, we propose a study aimed at determining the relation between the number of adjacent inputs with different labels and the required number of examples for the task of inducing a classification model. To this aim, we first quantified the adjacent inputs with different labels as a property, using a measure denoted as Neighbour Input Variation (NIV). We analyzed the relation that NIV has to random data and overfitting. We then demonstrated that a threshold of NIV may determine if a classification model can generalize to unseen data. We also presented a case study aimed at analyzing threshold neural networks and the required first hidden layer size in function of NIV. Finally, we performed experiments with five popular algorithms analyzing the relation between NIV and the classification error on problems with few dimensions. We conclude that functions whose similar inputs have different outputs with high probability, considerably reduce the generalization capacity of classification algorithms.

Since the discovery of the physical random functions and their subsequent refinement into physical unclonable functions (PUF), a great effort has been made in developing and characterizing these objects attending to their physical properties as well as conceiving a myriad of different examples in the search for a better application-specificity and suitability. However, comparatively little time has been devoted to the analysis of entropy extraction algorithms beyond the recognition of some limitations due to the environment influencing the PUF behavior. In this article we focus on well known PUF candidates based on ring oscillator delay, which are ideal for FPGA prototyping due to their tolerance to asymmetries in routing. We have studied the impact that different digitization algorithms of the responses have over their security properties. Specifically, we have analyzed the response probability distributions that arise from some popular techniques of digitization called “compensated measuring” methods, highlighting their lack of uniformity and how this might translate into cryptanalytically exploitable vulnerabilities. Furthermore, we propose a new family of digitization schemes named k-modular that exhibit both uniformity in response distribution and high entropy density on both physical and response space.

Introduction: Despite conization, high-grade squamous intraepithelial lesion can recur. Persistent human papilloma virus infection is an important factor of recurrence. We analyse different situations that could favor the persistence of this infection. Methods: A retrospective case-control study of 256 patients who underwent conization between 2015 and 2020 was conducted. Depending on positive or negative result of HPV test after the first 6 months post conization, two groups were defined and compared: 1) control group HPV-negative patients, 2) case group HPV-positive patients. Age, parity, smoking habit, menopause, body mass index (BMI), vaccination, HPV genotypes and exo and endocervical margin status were analysed. Results: 63 of the 256 patients studied, (24.6%) persisted positive for HPV after conization, while 193 (75.4%) became negative for HPV. Patients over 35 years old had a significantly higher risk of persistence of HPV after conization (OR 1.9). Being menopausal was also significantly associated with the persistence of HPV (OR 2.5). The presence of affected resection margins in cone specimen proved to be a risk factor for the persistence of HPV (OR 2.3). The coexistence of multiple HPV genotypes before conization seemed to be a protective factor for HPV persistence (OR 0.3). The rest of clinical characteristics studied failed to demonstrate statistical significance; therefore, it was not possible to classify them as risk and/or protective factors. Conclusions: Age over 35, menopause and affected resection margins of conization were significantly associated (p< 0.05) with the persistence of HPV infection; however, HPV vaccination was not among the risk factors.

Abstract Background Previous research has indicated that attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk for dementia, but studies are scarce and inconclusive. We aimed to investigate the association between ADHD, and dementia and mild cognitive impairment (MCI). Additionally, we aimed to investigate the impact of comorbid conditions, educational attainment, head injuries, other developmental disorders, and sex on the association. Methods The study population consisted of 3,591,689 individuals born between 1932 and 1963, identified from Swedish population-based registers. Cases of ADHD, dementia and MCI were defined according to ICD diagnostic codes and ATC codes for medication prescriptions. A Cox proportional hazards model was used to test the associations between ADHD, and dementia and MCI. Results Individuals with ADHD had an increased risk for dementia and MCI. After adjusting for sex and birth year, a hazard ratio (HR) was 2.92 (95% confidence interval 2.40–3.57) for dementia, and 6.21 (5.25–7.35) for MCI. Additional adjustment for psychiatric disorders (depression, anxiety, substance use disorder, and bipolar disorder) substantially attenuated the associations, HR = 1.62 (1.32–1.98) for dementia, and 2.54 (2.14–3.01) for MCI. Common metabolic disorders (hypertension, type 2 diabetes, and obesity), sleep disorders, head injuries, educational attainment, and other developmental disorders, had a limited impact on the association. The association between ADHD and dementia was stronger in men. Conclusions ADHD is a potential risk factor for dementia and MCI, although the risk significantly attenuates after controlling for psychiatric disorders. Further research is needed to confirm these findings and to explore underlying mechanisms of the associations.

Parsers are used in different software development scenarios such as compiler construction, data format processing, machine-level translation, and natural language processing. Due to the widespread usage of parsers, there exist different tools aimed at automizing their generation. Two of the most common parser generation tools are the classic Lex/Yacc and ANTLR. Even though ANTLR provides more advanced features, Lex/Yacc is still the preferred choice in many university courses. There exist different qualitative comparisons of the features provided by both approaches, but no study evaluates empirical features such as language implementor productivity and tool simplicity, intuitiveness, and maintainability. In this article, we present such an empirical study by conducting an experiment with undergraduate students of a Software Engineering degree. Two random groups of students implement the same language using a different parser generator, and we statistically compare their performance with different measures. Under the context of the academic study conducted, ANTLR has shown significant differences for most of the empirical features measured.

In some encryption systems it is necessary to preserve the format and length of the encrypted data. This kind of encryption is called FPE (Format Preserving Encryption). Currently, only two AES (Advanced Encryption Standard) modes of operation recommended by the NIST (National Institute of Standards and Technology) are able to implement FPE algorithms, FF1 and FF3. These modes work in an electronic codebook fashion and can be configured to encrypt databases with an arbitrary format and length. However, there are no stream cipher proposals able to implement FPE encryption for high data rate information flows. The main novelty of this work is a new block cipher operation mode proposal to implement an FPE algorithm in a stream cipher fashion. It has been called CTR-MOD and it is based on a standard block cipher working in CTR (Counter) mode and a modulo operation. The confidentiality of this mode is analyzed in terms of its IND- CPA (Indistinguishability under Chosen Plaintext Attack) advantage of any adversary attacking it. Moreover, the encryption scheme has been implemented on an FPGA (Field Programmable Gate Array) and has been integrated in a Gigabit Ethernet interface to test an encrypted optical link with a real high data rate traffic flow.

In this work a new self-synchronized symmetric encryption solution for high speed communication systems necessary to preserve the format of the plaintext is proposed, developed and tested. This new encryption mechanism is based on the block cipher operation mode called PSCFB (Pipelined Statistical Cipher Feedback) and the modulo operation. The confidentiality of this mode is analyzed in terms of its IND-CPA (Indistinguishability under Chosen-Plaintext Attack) advantage, concluding that it can be considered secure in the same way as traditional modes are. The encryption system has been integrated in the physical layer of a 1000Base-X Gigabit Ethernet Interface, where the 8b/10b symbol flow is encrypted at line rate. Moreover, an implementation of the proposed system has been carried out in an FPGA (Field Programmable Gate Array) device. Finally, an encrypted optical link has been tested with real Ethernet frames, getting maximum throughput and protecting the data traffic from passive eavesdroppers.

In this article, the possibility of using Galois ring oscillators to construct physically unclonable functions (PUFs) has been studied. The idea is to use novel PUF architectures, similar as the ring oscillator PUFs that, instead of comparing frequencies, compare the statistical bias of pairs of oscillators implemented in different locations. To study the viability of these systems, three different Galois oscillators have been implemented in several locations in several FPGAs and we have studied the main properties of their bias: repeatability, variability with the location, variability with the FPGA and spatial autocorrelation. Based on this study, we have determined that the bias of these oscillators meet the requirements that are needed to be used to construct a PUF. Finally, a PUF based on comparing the bias of neighboring 7-LUT Galois ring oscillators have been implemented and analyzed. The experimental results show that this PUF generates uniform responses that are highly reproducible and unique, making this PUF suitable for being used in identification applications.

Students’ participation and motivation are of great importance in their learning process. The decrease in attendance and difficulties in stimulating students’ activity makes it necessary to find new methodologies that can solve these problems. The use of game mechanics in non-ludic environments (Gamification) has begun to be of great interest in research, since it could increase the motivation and therefore the activity of the students. This study tries to verify if there is an existing relationship between gamification and a possible increase in student activity or between the cessation of gamification and student activity. In addition, it evaluates whether a greater student activity corresponds to a greater learning improvement. In the obtained results, no significant differences were found between the methodology or the activity with a learning improvement. According to the study, the simple use of gamified elements does not necessarily imply a solution to the problems posed. The students’ activity in a course of these characteristics does not imply a better learning improvement, the importance lies in the quality of the activity generated and not in the quantity.

The use of the mechanics and elements of games in non-ludic environments (Gamification) has increased in non-ludic contexts in various areas including education. This study focused on the perception that students have of the different elements of gamification in three different experiences, after which students were asked to answer a survey about the gamified elements of the course in which they participated. In the three experiences, Feedback, levels, points and missions stand out as the best valued, despite the fact that, for example, “time limit” were little valued by the students, it can be useful in the design of a gamified experience, but its use must be well regulated to avoid possible negative aspects and favor a good experience for the student. On the other hand, though badges were also been well valued by students in the longest experiences, in the shortest experience, it was one of the worst rated elements. Finally, the elements that students liked the least of all those analyzed, were the leaderboard and the blocked content.

A simple precipitation-reduction method was used to prepare cubic and polyhedral Cu2O structures. Their morphological, structural, optical and electronic properties were analyzed and compared with those of commercial Cu2O by means of SEM, TEM, XRD, UV–vis DRS, Photoluminescence Spectroscopy and Time Resolved Microwave Conductivity. Methyl orange (MO) photodegradation with visible light (blue-light LEDs, λ = 450–470 nm) was taken as a model reaction to study the photocatalytic activity. According to the results, Cu2O edge-and corner-truncated polyhedral particles significantly decreased the MO initial concentration by adsorption and photocatalysis, whereas, Cu2O cubic particles did not show MO adsorption but slightly higher photocatalytic activity than the polyhedral particles. Commercial Cu2O showed MO adsorption and high electron mobility but it was completely inactive. These results were explained in terms of the crystalline defects that influence both, the adsorption capacity and the photocatalytic activity. Keywords: Cu2O, Morphology, Photocatalysis, Photoluminescence, TRMC

Introduction: The addition of durvalumab after chemoradiation therapy (CRT) in unresectable stage III NSCLC significantly improves survival. The benefit of this approach in elderly patients is controversial given the toxicity associated with CRT and, thus, may be underutilized. We sought to investigate the outcomes of elderly patients treated with CRT without or without durvalumab at our center. Methods: We reviewed all stage III patients with NSCLC treated with CRT between 2018 and 2020. Patients were analyzed on the basis of age: less than 70 years and 70 years and older. The end points evaluated were treatment patterns, toxicity, progression-free survival, and overall survival. Results: The baseline characteristics including Eastern Cooperative Oncology Group performance status and comorbidities were similar among the 115 patients (44 elderly, 71 young). Completion rates of CRT (100%, 97%) and chemotherapy dose intensity (97%, 97%) were high in elderly and young patients, respectively. There was a trend toward increased hospitalizations in elderly patients because of infections (27% versus 13%, p = 0.08). Of those who did not have primary progression after CRT, 78% of eldery and 81% of young patients received durvalumab. The incidence of grade 3 or higher immune-related adverse events was 9% in elderly and 6% in young patients (p = 0.67). The median progression-free survival was similar (15.6 versus 10.5 mo, p = 0.10), even after adjusting for comorbidities (hazard ratio = 0.6, p = 0.09). The 12-month overall survival rates were 78% in the elderly and 76% in young patients (p = 0.98). Conclusions: Well-selected elderly patients can be treated safely with CRT followed by durvalumab with similar survival benefits compared with their younger counterparts. We would advocate for the referral of all elderly patients for oncologic assessment to avoid undertreatment.