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Abstract The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023–24. However, this surge in infections was not accompanied by COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86 lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86 lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86 lineages experienced greater numbers of documented prior SARS-CoV-2 infections. Cases infected with BA.2.86 lineages also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.

The use of aquaponic systems has grown in recent years, but few of these systems have integrated the production of prawns and short-cycle vegetables. This study evaluated the potential for producing microgreens (beet, amaranth, arugula, and red cabbage) integrated with Amazon River prawns (Macrobrachium amazonicum) in an aquaponic system. Four seeding densities (5, 10, 15, or 20 seeds/cell) were assessed in two treatments: one using prawn wastewater and the other using plain dechlorinated water (control). Water quality, prawn growth performance, and microgreen productivity were monitored over 13 days, revealing optimal conditions for both prawns and microgreens in the aquaponic system. Amaranthus paniculatus yielded 374.00 g/m2 in prawn wastewater compared to 231.34 g/m2 in the control, while Beta vulgaris produced 1734.39 g/m2 in wastewater versus 1127.69 g/m2 in the control. Similarly, Brassica oleracea (2180.69 g/m2) and Eruca sativa (2109.46 g/m2) had higher yields in the prawn aquaponics system. These findings demonstrate that integrating prawn cultivation in aquaponic systems significantly enhances microgreen production compared to traditional methods. This integrated approach not only improves yields but also offers a more sustainable production model. Significant variation in productivity and growth metrics among species treatments underscores the viability and need for more systematic aquaponic procedures.

Abstract COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02–1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86–0.95), circulatory (RR: 0.88, 0.83–0.94), blood and hematologic (RR: 0.79, 0.71–0.89), skin and subcutaneous (RR: 0.69, 0.66–0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51–0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1–2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.

Abstract Background During the coronavirus disease 2019 (COVID-19) pandemic, the use of information and communication technologies (ICTs) to support care management exponentially increased. Governments around the world adapted existing programs to meet the needs of patients. The reactivity of governments, however, led to changes that were inequitable, undermining groups such as older adults living with chronic diseases and disability. Policies that align with recent developments in ICTs can promote better health outcomes and innovation in care management. A framework for policymaking presents potential for overcoming barriers and gaps that exist in current policies. Objective The goal of this study was to examine how well a provisional framework for policymaking represented the interactions between various components of government policymaking on older adults’ self-management of chronic disease and disability using ICTs. Methods Through an online survey, the study engaged policymakers from various ministries of the government of Ontario in the evaluation and revision of the framework. The data were analyzed using simple statistics and by interpreting written comments. Results Nine participants from three ministries in the government of Ontario responded to the questionnaire. Overall, participants described the framework as useful and identified areas for improvement and further clarification. A revised version of the framework is presented. Conclusions Through the revision exercise, our study confirmed the relevance and usefulness for a policymaking framework on the self-management of disease and disability of older adults’ using ICTs. Further inquiries should examine the application of the framework to jurisdictions other than Ontario considering the dissociated nature of Canadian provincial healthcare systems.

BackgroundThe potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far. ObjectiveThis study aimed to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination during the 2022-2023 season. MethodsA self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022, and March 31, 2023, in a large health care system. Ischemic strokes were identified using International Classification of Diseases, Tenth Revision codes in emergency departments and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were prespecified as 1-21 days and 1-42 days after bivalent vaccination; all non–risk-interval person-time served as the control interval. The incidence of ischemic stroke was compared in the risk interval and control interval using conditional Poisson regression. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and coadministration of influenza vaccine. When an elevated risk was detected, we performed a chart review of ischemic strokes and analyzed the risk of chart-confirmed ischemic stroke. ResultsWith 4933 ischemic stroke events, we found no increased risk within the 21-day risk interval for the 2 vaccines and by subgroups. However, risk of ischemic stroke was elevated within the 42-day risk interval among individuals aged younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day; the relative incidence (RI) was 2.13 (95% CI 1.01-4.46). Among those who also had a history of SARS-CoV-2 infection, the RI was 3.94 (95% CI 1.10-14.16). After chart review, the RIs were 2.34 (95% CI 0.97-5.65) and 4.27 (95% CI 0.97-18.85), respectively. Among individuals aged younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the RI was 2.62 (95% CI 1.13-6.03) before chart review and 2.24 (95% CI 0.78-6.47) after chart review. Stratified analyses by sex did not show a significantly increased risk of ischemic stroke after bivalent vaccination. ConclusionsWhile the point estimate for the risk of chart-confirmed ischemic stroke was elevated in a risk interval of 1-42 days among individuals younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day and among individuals younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the risk was not statistically significant. The potential association between bivalent vaccination and ischemic stroke in the 1-42–day analysis warrants further investigation among individuals younger than 65 years with influenza vaccine coadministration and prior SARS-CoV-2 infection. Furthermore, the findings on ischemic stroke risk after bivalent COVID-19 vaccination underscore the need to evaluate monovalent COVID-19 vaccine safety during the 2023-2024 season.

Abstract We explore the construction of four-dimensional thick branes supported by massless 3-forms in a five-dimensional bulk space. The required residual Poincaré symmetry on the brane is realised as a combination of the bulk symmetries and the internal gauge symmetry of the 3-form. We show the presence of a gradient instability for the perturbations orthogonal to the brane when its profile decays slowly in the asymptotic regions. In particular, we ascertain that the prevailing profiles found in the literature are susceptible to such instabilities. We confirm our results by transitioning to the dual formulation in terms of a shift-symmetric scalar. In this formulation, the residual Poincaré group is trivially realised without internal symmetries, and there is a diagonal translational invariance in the fifth dimension reminiscent of the invariance under translations orthogonal to the brane of the dual 3-form. We demonstrate the extension of our results to the cases of de Sitter and Anti de Sitter branes where the gradient instabilities of asymptotically slowly decaying branes persist. Finally, we briefly comment on the construction of thick branes with massive 3-forms and their 1-form duals.

Analog computing is based upon using physical processes to solve formal mathematical problems. In the past, it was the predominant instrument of scientific calculations. Now, as the physical limits imposed on digital devices compel research into alternate computing paradigms, a reexamination of the potentialities of analog computing is warranted. This work studies the application of analog CMOS cells toward the simulation of dynamical systems, and, more generally, solving sets of coupled time-dependent ordinary differential equations. Following a brief review of the fundamentals of systems theory and analog computing, the main set of computing elements is introduced, each comprising analog cells designed in a 130 nm process. These are subsequently applied to the realization of practical, special-purpose analog computing modules. Illustrative systems from various fields are selected for simulation. Though by no means comprehensive, these case studies highlight the capabilities of contemporary analog computing, especially in solving nonlinear problems. Circuit simulations show good agreement with solutions obtained from high-order numerical methods, at least over a limited range of system parameters. The article concludes with a brief discussion of broader analog computing applications, offering future prospects toward further exploration of its potentialities and limitations in a wide range of domains.

Cancer resistance to chemotherapy and radiation therapies presents significant challenges, necessitating the exploration of alternative approaches. Targeting specific proteins at the molecular level, particularly their active sites, holds promise in addressing this issue. We investigated the potential of 4′-methoxy-2-nitrochalcone (MNC) as an MCL-1 inhibitor, examining its chemical and structural characteristics to elucidate its biological activity and guide the selection of potential candidates. We conducted a docking study, followed by synthesis, structural characterization, theoretical calculations, and in vitro experiments to comprehensively evaluate MNC. The docking results revealed MNC’s excellent binding within the active site of MCL-1. At 50 µM, MNC demonstrated 99% inhibition of HCT116 cell proliferation, with an IC50 value of 15.18 µM after 24 h. Treatment with MNC at 30.36 and 15.18 µM resulted in reduced cell density. Notably, MNC exhibited marked cytotoxicity at concentrations of 15.58 µM and 7.79 µM, inducing high frequencies of plasma membrane rupture and apoptosis, respectively. Our findings highlight the significant biological potential of MNC as an MCL-1 inhibitor. Furthermore, we propose exploring chalcones with hydrogen bond acceptor substituents as promising candidates for studying inhibitors targeting this protein. In conclusion, our study addresses the challenge of cancer resistance by investigating MNC as an MCL-1 inhibitor. Through detailed characterization and experimental validation, we establish the efficacof MNC in inhibiting cell proliferation and inducing cytotoxic effects. These results underscore the potential of MNC as a valuable therapeutic agent and suggest the use of chalcones with hydrogen bond acceptor substituents as a basis for developing novel MCL-1 inhibitors.

Abstract Background Policies that support health self-management are malleable and highly dependent on various factors that influence governments. Within a world that is shifting toward digitalization due to pressures such as the COVID-19 pandemic and labor shortages, policymaking on older adults’ self-management of chronic diseases and disability using information and communication technologies (ICTs) needs to be better understood. Using the province of Ontario, in Canada, as a case study, the research question was What is the environment that policymakers must navigate through in development and implementation of policies related to older adults’ self-management of disease and disability using information and communication technologies (ICTs)? Methods This study used a qualitative approach where public servants from 4 ministries within the government of Ontario were invited to participate in a 1-h, one-on-one, semi-structured interview. The audio-recorded interviews were based on an adapted model of the policy triangle, where the researcher asked questions about the influences from the different sources identified in the model. The interviews were later transcribed and analyzed using a deductive-inductive coding approach. Results Ten participants across 4 different Ministries participated in the interviews. Participants shared insights on various aspects of context, process and actors that help shape the current content of policies. The analysis revealed that policies, in the form of programs, services, legislation and regulations, are the result of collaborations and dialogue between different actors and get developed and implemented via a set of complex government processes. In addition, policy actions come from a plethora of sectors which all get influenced by several predictable and unpredictable external pressures. Conclusions The environment for policymaking in the government of Ontario regarding older adults’ self-management of disease and disability using ICTs is one that is mostly reactive to external pressures, while organized within a set of complex processes and multi-sectoral collaborations. The present research helped us to understand the complexity of policymaking on the topic and highlights the need for increased foresight and proactive policymaking, regardless of which governments are in-place.

Recent data showed that prenatal alcohol exposure (PAE) impairs the “placenta–brain” axis controlling fetal brain angiogenesis in human and preclinical models. Placental growth factor (PlGF) has been identified as a proangiogenic messenger between these two organs. CD146, a partner of the VEGFR-1/2 signalosome, is involved in placental angiogenesis and exists as a soluble circulating form. The aim of the present study was to investigate whether placental CD146 may contribute to brain vascular defects described in fetal alcohol spectrum disorder. At a physiological level, quantitative reverse transcription polymerase chain reaction experiments performed in human placenta showed that CD146 is expressed in developing villi and that membrane and soluble forms of CD146 are differentially expressed from the first trimester to term. In the mouse placenta, a similar expression pattern of CD146 was found. CD146 immunoreactivity was detected in the labyrinth zone and colocalized with CD31-positive endothelial cells. Significant amounts of soluble CD146 were quantified by ELISA in fetal blood, and the levels decreased after birth. In the fetal brain, the membrane form of CD146 was the majority and colocalized with microvessels. At a pathophysiological level, PAE induced marked dysregulation of CD146 expression. The soluble form of CD146 decreased in both placenta and fetal blood, whereas it increased in the fetal brain. Similarly, the expression of several members of the CD146 signalosome, such as VEGFR2 and PSEN, was differentially impaired between the two organs by PAE. At a functional level, targeted repression of placental CD146 by in utero electroporation (IUE) of CRISPR/Cas9 lentiviral plasmids resulted in (i) a decrease in cortical vessel density, (ii) a loss of radial vascular organization, and (iii) a reduced density of oligodendrocytes. Statistical analysis showed that the more the vasculature was impaired, the more the cortical oligodendrocyte density was reduced. Altogether, these data support that placental CD146 contributes to the proangiogenic “placenta–brain” axis and that placental CD146 dysfunction contributes to the cortical oligo-vascular development. Soluble CD146 would represent a promising placental biomarker candidate representative of alcohol-induced neurovascular defects in neonates, as recently suggested by PlGF (patents WO2016207253 and WO2018100143).

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

IntroductionThe COVID-19 pandemic has highlighted the need to identify mechanisms of antiviral host defense against SARS-CoV-2. One such mediator is interferon-g (IFN-γ), which, when administered to infected patients, is reported to result in viral clearance and resolution of pulmonary symptoms. IFN-γ treatment of a human lung epithelial cell line triggered an antiviral activity against SARS-CoV-2, yet the mechanism for this antiviral response was not identified.MethodsGiven that IFN-γ has been shown to trigger antiviral activity via the generation of nitric oxide (NO), we investigated whether IFN-γ induction of antiviral activity against SARS-CoV-2 infection is dependent upon the generation of NO in human pulmonary epithelial cells. We treated the simian epithelial cell line Vero E6 and human pulmonary epithelial cell lines, including A549-ACE2, and Calu-3, with IFN-γ and observed the resulting induction of NO and its effects on SARS-CoV-2 replication. Pharmacological inhibition of inducible nitric oxide synthase (iNOS) was employed to assess the dependency on NO production. Additionally, the study examined the effect of interleukin-1b (IL-1β) on the IFN-g-induced NO production and its antiviral efficacy.ResultsTreatment of Vero E6 cells with IFN-γ resulted in a dose-responsive induction of NO and an inhibitory effect on SARS-CoV-2 replication. This antiviral activity was blocked by pharmacologic inhibition of iNOS. IFN-γ also triggered a NO-mediated antiviral activity in SARS-CoV-2 infected human lung epithelial cell lines A549-ACE2 and Calu-3. IL-1β enhanced IFN-γ induction of NO, but it had little effect on antiviral activity.DiscussionGiven that IFN-g has been shown to be produced by CD8+ T cells in the early response to SARS-CoV-2, our findings in human lung epithelial cell lines, of an IFN-γ-triggered, NO-dependent, links the adaptive immune response to an innate antiviral pathway in host defense against SARS-CoV-2. These results underscore the importance of IFN-γ and NO in the antiviral response and provide insights into potential therapeutic strategies for COVID-19.

Abstract Background As people live longer, they are at increased risk for chronic diseases and disability. Self-management is a strategy to improve health outcomes and quality of life of those who engage in it. This study sought to gain a better understanding of the factors, including digital technology, that affect public health policy on self-management through an analysis of government policy in the most populous and multicultural province in Canada: Ontario. The overarching question guiding the study was: What factors have influenced the development of healthcare self-management policies over time? Methods Archival research methods, combining document review and evaluation, were used to collect data from policy documents published in Ontario. The documents were analyzed using the READ approach, evaluated using a data extraction table, and synthesized into themes using the model for health policy analysis. Results Between January 1, 1985, and May 5, 2022, 72 policy documents on self-management of health were retrieved from databases, archives, and grey literature. Their contents largely focussed on self-management of general chronic conditions, while 47% (n = 18/72) mention diabetes, and 3% (n = 2/72) focussed solely on older adults. Digital technologies were mentioned and were viewed as tools to support self-management in the context of healthcare delivery and enhancing healthcare infrastructure (i.e., telehealth or software in healthcare settings). The actors involved in the policy document creation included mostly Ontario government agencies and departments, and sometimes expert organizations, community groups and engaged stakeholders. The results suggest that several factors including pressures on the healthcare system, hybrid top-down and bottom-up policymaking, and political context have influenced the nature and implementation timing of self-management policy in Ontario. Conclusions The policy documents on self-management of health reveal a positive evolution of the content discussed over time. The changes were shaped by an evolving context, both from a health and political perspective, within a dynamic system of interactions between actors. This research helps understand the factors that have shaped changes and suggests that a critical evidence-based approach on public health policy is needed in understanding processes involved in the development of healthcare self-management policies from the perspective of a democratic governing system.

This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction–precipitation (MR/P) and co-precipitation at controlled pH (MpH), were explored, including the assessment of the coating’s influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from MR/P consist of approximately 11–13% of Fe present in magnetite, while samples obtained from MpH have higher contents of 33–45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SPpH-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.

Abstract Solute exchange between the sediment and the water column strongly influences water quality in aquatic ecosystems. Among the techniques available for in situ observation, only aquatic eddy covariance (AEC) can resolve the hourly dynamics of benthic fluxes, but only for few substances like oxygen. In micrometeorology, relaxed eddy accumulation (REA), a technique based on high‐frequency sampling conditioned by current direction, overcomes this limitation. We developed a portable prototype instrumentation platform to transfer REA to the sediment‐water interface of shallow aquatic ecosystems. In order to evaluate the sampling system, we configured the prototype for measuring oxygen fluxes and comparing them to simultaneous AEC measurements. In a river and two artificial lakes, at depths 1–3 m and 0.2 m above the sediment, we measured 15 oxygen flux pairs in fully developed turbulence during 8–15 min periods, ranging from −150 to 50 mmol m−2 day−1. The good agreement between REA and AEC fluxes (R2 = 0.94) shows the reliability of the conditional sampling system. REA represents a promising technique for exploring the sediment contribution to biogeochemical cycles in aquatic ecosystems.

The literature on the crosstalk between the brain and the gut has increased considerably in recent years. It is widely accepted now that the microbiome plays a significant role in several brain disorders, neurodevelopment, neurocognitive stages, and physiological functions. However, the mechanisms that influence such crosstalk are still not well elucidated. In this sense, one of the possible mechanisms by which the microbiome could influence brain function is through gut hormones released by enteroendocrine cells: ghrelin, cholecystokinin (CCK), peptide YY (PYY), vasoactive intestinal polypeptide (VIP), glucagon-like peptide (GLP1-2), corticotropin-releasing factor (CRF), glucose-dependent insulinotropic polypeptide (GIP), secretin, serotonin (5-HT), and oxytocin. Especially when one considers that the brain expresses receptors for these hormones in areas important to the neurobiology of brain disorders (e.g., depression), such as the hippocampus, amygdala, hypothalamus, and suprachiasmatic nucleus. To strengthen this hypothesis, gastrointestinal dysfunction (such as altered motility or pain) is relatively common in depressive patients, and changes in diet (low-carbohydrate diets, for example) positively affect mood. Additionally, alterations in the gut microbiome are relatively common in depressive patients and are related to the levels of Akkermansia, Lactobacillus, Bifidobacteria, Faecalibacterium, Roseburia and Clostridium. Finally, concerning the gut-released hormones, the literature reports that ghrelin can be a peripheral marker for the antidepressant treatment success rate and has elevated levels during depression. GLP-1 is tightly correlated with HPA axis activity being decreased by high cortisol levels. CCK seems to be altered in depression due to increased inflammation and activation of Toll-like receptor 4. Such finds allow the postulation that hormones, the microbiome and mood are intertwined and co-dependent. VIP is correlated with circadian rhythms. There is a bidirectional connection of the circadian rhythms between the host and the microbiota. Circadian rhythm disruption is associated with both poor outcomes in mental health and alterations in the microbiota composition. In sum, in the past year, more and more research has been published showing the tight connection between gut and brain health and trying to decipher the feedback in play. Here, we focus on depression.

Commodity price forecasting is an essential task for the definition of economic strategies to reduce the impact of inflation in several countries. During the covid-19 pandemic, commodity prices have increased due to external factors such as the influence of brokers, traders, policymakers, and investors. Accurate forecasts are important to increase the quality of the decision making processes of governments in order to alleviate negative economic impacts such as inflation. The forecasting of commodity prices is a challenging task due to the dynamic characteristics of commodity prices and external influences. In this work, we presented a hybrid swarm-based system combining the Autoregressive Integrated Moving Average with exogenous variables (ARIMAX) model and a Support Vector Regression (SVR) model optimized by the Particle Swarm Optimization (PSO). In the proposed method the PSO algorithm selects the most relevant variables for the ARIMAX model and optimizes SVR parameters. The experiments were conducted on various time series of commodity prices and exogenous variables, with single models and hybrid methods in the literature. The proposed method significantly reduced MSE and MAPE metrics compared to other approaches. The most selected features were the new cases, cumulative deaths, and the dollar exchange rate.

Equatorial plasma bubbles are depleted plasma structures aligned to the geomagnetic field lines that are generated in the nighttime ionosphere bottomside and rise to the topside extending to increasingly higher latitudes. These structures induce fluctuations in the transionospheric radio signals causing the phenomenon known as ionospheric scintillation. Ionospheric scintillation is one of the main concerns for safety critical applications that rely on Global Navigation Satellite System information, therefore, the understanding about the occurrence and severity of scintillation is necessary. In this work, an analysis considering aspects of the orientation of the propagation of the radio signals through the plasma bubbles structures is performed to evaluate how this geometry can affect the scintillation profile. The dataset covers five months of records from three stations over the Brazilian region during the last solar cycle maximum. The initial results indicate that propagation paths fully aligned are consistently related to larger values of $S_{4}$ and more severe scintillation. The statistical evaluations with the $\alpha - \mu $ model show that during such cases stronger fading events are expected. According to the field measurements, fading events deeper than −15 dB are 73% more likely to occur under some aligned environments when compared to other propagation paths.

We describe six datasets that contain GPS and accelerometer data of 202 Eurasian oystercatchers (Haematopus ostralegus) spanning the period 2008–2021. Birds were equipped with GPS trackers in breeding and wintering areas in the Netherlands and Belgium. We used GPS trackers from the University of Amsterdam Bird Tracking System (UvA-BiTS) for several study purposes, including the study of space use during the breeding season, habitat use and foraging behaviour in the winter season, and impacts of human disturbance. To enable broader usage, all data have now been made open access. Combined, the datasets contain 6.0 million GPS positions, 164 million acceleration measurements and 7.0 million classified behaviour events (i.e., flying, walking, foraging, preening, and inactive). The datasets are deposited on the research repository Zenodo, but are also accessible on Movebank and as down-sampled occurrence datasets on the Global Biodiversity Information Facility (GBIF) and Ocean Biodiversity Information System (OBIS).

BackgroundVirtual reality (VR) based meditation has been shown to help increase relaxation and decrease anxiety and depression in younger adults. However, this has not been studied in Randomized Controlled Trials (RCT) in the older adult population. The aim of this RCT is to assess the feasibility and acceptability of a VR-guided meditation intervention for community-dwelling older adults and its effect on stress and mental health.MethodsWe will recruit 30 participants aged ≥ 60 years, whose perceived stress score (PSS) is > 14 (moderate stress), and randomize them 1:1 to the intervention or control waitlist group. The intervention will involve exposure to eight 15-min VR-guided meditation sessions distributed twice weekly for 4-weeks. Two modalities will be offered: in-home and at the hospital.Data analysisBaseline and post-intervention assessments will evaluate perceived stress, anxiety, depression, sleep quality, quality of life, and mindfulness skills. Analyses will employ mixed methods repeated ANOVA tests. Qualitative analyses through semi-structured interviews and participant observation will be used to assess participants’ experiences. Study outcomes include: (A) feasibility and acceptability compared to a waitlist control (B) stress, using the Perceived Stress Scale (PSS); (C) anxiety, and depression, using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9); (D) insomnia, quality of life and mindfulness skills, using the Athens Insomnia Scale (AIS), Quality of Life Questionnaire (EQ-5D-5L) and Five Facets Mindfulness Questionnaire Short Forms (FFMQ-SF), respectively. We will also measure immersive tendencies, sickness and sense of presence using the Simulator Sickness Questionnaire (SSQ) and the Presence Questionnaire (PQ).DiscussionVirtual reality-guided meditation could be an acceptable, feasible, safe, and cost-effective novel alternative health intervention for improving older adults’ mental health.Clinical trial registration: NCT05315609 at https://clinicaltrials.gov.

Abstract Prenatal alcohol exposure is a major cause of neurobehavioral disabilities. MRI studies in humans have shown that alcohol is associated with white matter microstructural anomalies but these studies focused on myelin abnormalities only after birth. Only one of these studies evaluated oligodendrocyte lineage, but only for a short period during human foetal life. As data are lacking in humans and alcohol is known to impair oligodendrocyte differentiation in rodents, the present study aimed to compare by immunohistochemistry the oligodendrocyte precursor cells expressing PDGFR-α and immature premyelinating/mature oligodendrocytes expressing Olig2 in the ganglionic eminences and the frontal cortex of 14 human foetuses exposed to alcohol from 15 to 37 weeks’ gestation with age-matched controls. The human brains used in this study were obtained at the time of foetal autopsies for medical termination of pregnancy, in utero or post-natal early death. Before birth, PDGFR-α expression was strongly increased in the ganglionic eminences and the cortex of all foetuses exposed to alcohol except at the earliest stage. No massive generation of Olig2 immunoreactive cells was identified in the ganglionic eminences until the end of pregnancy and the density of Olig2-positive cells within the cortex was consistently lower in foetuses exposed to alcohol than in controls. These antenatal data from humans provides further evidence of major oligodendrocyte lineage impairment at specific and key stages of brain development upon prenatal alcohol exposure including defective or delayed generation and maturation of oligodendrocyte precursors.

Abstract Saliva is an attractive sample for coronavirus disease 2019 testing due its ease of collection and amenability to detect viral RNA with minimal processing. Using a direct-to-RT-PCR method with saliva self-collected from confirmed COVID-19 positive volunteers, we observed 32% false negative results. Confirmed negative and healthy volunteer samples spiked with 106 genome copies/mL of heat-inactivated severe acute respiratory syndrome coronavirus 2 showed false negative results of 10% and 13%, respectively. Additional sample heating or dilution of the false negative samples conferred only modest improvements. These results highlight the potential to significantly underdiagnose COVID-19 infections when testing directly from minimally processed heterogeneous saliva samples.

Citizen scientists around the world are collecting data with their smartphones, performing scientific calculations on their home computers, and analyzing images on online platforms. These online citizen science projects are frequently lauded for their potential to revolutionize the scope and scale of data collection and analysis, improve scientific literacy, and democratize science. Yet, despite the attention online citizen science has attracted, it remains unclear how widespread public participation is, how it has changed over time, and how it is geographically distributed. Importantly, the demographic profile of citizen science participants remains uncertain, and thus to what extent their contributions are helping to democratize science. Here, we present the largest quantitative study of participation in citizen science based on online accounts of more than 14 million participants over two decades. We find that the trend of broad rapid growth in online citizen science participation observed in the early 2000s has since diverged by mode of participation, with consistent growth observed in nature sensing, but a decline seen in crowdsourcing and distributed computing. Most citizen science projects, except for nature sensing, are heavily dominated by men, and the vast majority of participants, male and female, have a background in science. The analysis we present here provides, for the first time, a robust 'baseline' to describe global trends in online citizen science participation. These results highlight current challenges and the future potential of citizen science. Beyond presenting our analysis of the collated data, our work identifies multiple metrics for robust examination of public participation in science and, more generally, online crowds. It also points to the limits of quantitative studies in capturing the personal, societal, and historical significance of citizen science.

Category: Arthroscopy; Midfoot/Forefoot Introduction/Purpose: Hallux rigidus is a common pathological condition of the foot, responsible for a great functional limitation. Metatarsophalangeal arthrodesis is an excellent therapeutic alternative for advanced stages of the disease, usually performed using an open technique. Forefoot arthroscopy has been developed in the last decade, with progressive expansion of indications, bringing encouraging results. Our objective is present the clinical-radiographic results of patients undergoing arthroscopic metatarsophalangeal arthrodesis of the hallux, showing the technique and reporting complications. Methods: This study involves a series of 9 patients (10 feet), all with advanced hallux rigidus (Coughlin-Shurnas grades 3 and 4). All patients underwent an arthroscopic procedure through two dorsal portals with small-joint instruments. Outcomes were assessed using the AOFAS functional score and a visual analogue scale of pain. The radiographic parameters of interest were metatarsal-phalangeal angulation in the anteroposterior (pre- and postoperative) and lateral (post-operative) views, as well as ray shortening. Results: All patients evolved with consolidation in radiographic control at 6 weeks postoperatively and showed a marked improvement in functional scores. We observed a reduction in the metatarsophalangeal angle, without shortening of the radius and of the finger. No patient had transfer metatarsalgia or complaints of cosmetic problems. Conclusion: Arthroscopic metatarsophalangeal arthrodesis is a very relevant therapeutic option for managing advanced stages of hallux rigidus, with minimal aggression and providing excellent results, in addition to a low incidence of complications.

Category: Basic Sciences/Biologics; Ankle; Sports Introduction/Purpose: The best alternative for treating calcaneal tendon rupture is still controversial. The treatment can be conservative or surgical; the latter is better indicated in high-performance athletes. The pursue of faster recovery, reductions in skin complications and re-ruptures have brought about improvements to the tendon repair technique and to early assisted rehabilitation programs. Our goal was to check whether or not the adjuvant use of 2-octyl cyanoacrylate provides additional mechanical resistance to the calcaneal tenorraphy, when compared to suture alone, using the same tenorraphy technique. Methods: We used 45 three-month-old New Zealand rabbits, distributed into three groups of 15 animals each. The rabbits underwent two surgical procedures at a 30-day interval. In the first procedure, we performed the complete calcaneal tendon section on the right side, and then we repaired it using three different techniques: suture alone in group 1, suture with 2-octyl cyanoacrylate in group 2, and 2-octyl cyanoacrylate alone in group 3. After 30 days, we slaughtered the rabbits, and resected their right-side calcaneal tendon, and sent the specimen for pathology analysis. Then, we performed a cross section of the left calcaneal tendon, and used the same three repair techniques. After 15 minutes, we subjected the repaired tendons to the linear traction mechanical strength test. Results: The results from the linear strength test showed that suture with glue outperformed suture alone (p = 0.0427), and glue alone (p

BackgroundMindfulness affects human levels of experience by facilitating the immediate and impartial perception of phenomena, including sensory stimulation, emotions, and thoughts. Mindfulness is now a focus of neuroimaging, since technical and methodological developments in magnetic resonance imaging have made it possible to observe subjects performing mindfulness tasks.ObjectiveWe set out to describe the association between mental processes and characteristics of mindfulness, including their specific cerebral patterns, as shown in structural and functional neuroimaging studies.MethodsWe searched the MEDLINE databank of references and abstracts on life sciences and biomedical topics via PubMed using the keywords: “mindfulness,” “focused attention (FA),” “open monitoring (OM),” “mind wandering,” “emotional regulation,” “magnetic resonance imaging (MRI)” and “default mode network (DMN).” This review extracted phenomenological experiences across populations with varying degrees of mindfulness training and correlated these experiences with structural and functional neuroimaging patterns. Our goal was to describe how mindful behavior was processed by the constituents of the default mode network during specific tasks.Results and conclusionsDepending on the research paradigm employed to explore mindfulness, investigations of function that used fMRI exhibited distinct activation patterns and functional connectivities. Basic to mindfulness is a long-term process of learning to use meditation techniques. Meditators progress from voluntary control of emotions and subjective preferences to emotional regulation and impartial awareness of phenomena. As their ability to monitor perception and behavior, a metacognitive skill, improves, mindfulness increases self-specifying thoughts governed by the experiential phenomenological self and reduces self-relational thoughts of the narrative self. The degree of mindfulness (ratio of self-specifying to self-relational thoughts) may affect other mental processes, e.g., awareness, working memory, mind wandering and belief formation. Mindfulness prevents habituation and the constant assumptions associated with mindlessness. Self-specifying thinking during mindfulness and self-relational thinking in the narrative self relies on the default mode network. The main constituents of this network are the dorsal and medial prefrontal cortex, and posterior cingulate cortex. These midline structures are antagonistic to self-specifying and self-relational processes, since the predominant process determines their differential involvement. Functional and brain volume changes indicate brain plasticity, mediated by mental training over the long-term.

Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician’s difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta–cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects. However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic “placenta–cortex” signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ “placenta–cortex” signature in control and PAE groups at gestational day 20. Genespring comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta–cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein–protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that “intercellular communication” was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand/receptors interactors. Protein validation experiments involving Western blot for one ligand–receptor couple (Agt/AGTR1/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta–cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.

High amounts of coal combustion products, such as fly ash and bottom ash, are generated every year; however, only 64% are used, which means that a significant part is landfilled despite containing valuable materials such as ferrospheres, which may be used as catalysts, substituting critical raw materials (e.g., platinoids). In commercial coals, pyrite contents are reduced as a pre-combustion S-emissions control measure, so low amounts of ferrospheres are expected in the respective ashes. However, given the large amounts of ash being generated from these coals, it may provide a reliable source of catalysts, with ferrospheres being easily recovered via magnetic separation. Several studies have been conducted regarding these morphotypes; however, there is a lack of investigation considering the ash derived from highly beneficiated coals and the variations with location and time. In this study, bottom ash, economizer grits, and fly ash samples from a Portuguese power plant burning Colombian commercial coal were fractionated using ferrite (Fe-MC fraction) and Nd (Nd-MC fraction) magnets, and a multi-technique approach was used to assess their properties (magnetic parameters, particle size distribution, mineralogy, particle morphology, microtexture, and chemical composition). The Fe-MC presented higher Fe concentrations (up to 44 wt.% Fe2O4) than the Nd-MC (up to 7 wt.% Fe2O4). Once it was a sequential process, Nd magnets essentially collected Fe-bearing aluminosilicate glass, and Fe-bearing minerals were residual when compared to the Fe-MC, where magnetite, magnesioferrite, hematite, and maghemite accounted for up to 30 wt.%. Among the Fe-MC, the sample collected from electrostatic precipitator fly ash (ESP FA), despite having a lower yield, presented higher Fe concentrations than the ones from bottom ash and economizer grits, which was related to the mode of occurrence of Fe-bearing phases: in the Fe-MC from ESP FA, discrete ferrospheres predominated, while in the remaining Fe-bearing phases, they were often embedded in aluminosilicate glass. All Fe-MC samples showed an increase of Fe-substituting elements (e.g., Mn and Ni) and their concentration tended to increase with decreasing particle size along with Fe. The integrated study of cross-sections enabled the identification of oxidation rims, martitization aspects, and the co-existence of hematite and magnesioferrite.

The opportunities for leveraging technology to enhance the efficiency of vessel port activities are vast. Applying video analytics to model and optimize certain processes offers a remarkable way to improve overall operations. Within the realm of vessel port activities, two crucial processes are vessel approximation and the docking process. This work specifically focuses on developing a vessel velocity estimation model and a docking mooring analytical system using a computer vision approach. The study introduces algorithms for speed estimation and mooring bitt detection, leveraging techniques such as the Structural Similarity Index (SSIM) for precise image comparison. The obtained results highlight the effectiveness of the proposed algorithms, demonstrating satisfactory speed estimation capabilities and successful identification of tied cables on the mooring bitts. These advancements pave the way for enhanced safety and efficiency in vessel docking procedures. However, further research and improvements are necessary to address challenges related to occlusions and illumination variations and explore additional techniques to enhance the models’ performance and applicability in real-world scenarios.

In Mexico, pasture degradation is associated with extensive pastures; additionally, under these conditions, livestock activities contribute considerably to greenhouse gas (GHG) emissions. Among the options to improve grazing systems and reduce GHG emissions, silvopastoral systems (SPS) have been recommended. The objectives of this work were to quantify the N outflow in a soil–plant–animal interface, as well as the CH4 emissions and milk production in an SPS with woody legumes (Leucaena leucocephala) that is associated with stargrass (Cynodon nlemfuensis). This was then compared with stargrass in a monoculture system (MS) in the seasons (dry and rainy period) over a two-year period. Dung was collected from the animals of each of the grazing systems and applied fresh to the land plots. Fresh dung and urine were collected from the cows of each grazing system and were applied to the experimental plots. In addition, the soil CH4 and N2O contents were measured to quantify the emissions. Average milk yield by seasons was similar: MS (7.1 kg per animal unit (AU)/day−1) and SPS (6.31 kg per AU/day−1). Cows in the MS had a mean N intake of 171.9 g/UA day−1 without seasonal variation, while the SPS animals’ mean N intake was 215.7 g/UA day−1 for both seasons. For the urine applied to soil, the N2O outflow was higher in the MS (peak value = 1623.9 μg N-N2O m−2 h−1). The peak value for the SPS was 755.9 μg of N-N2O m−2 h−1. The N2O emissions were higher in the rainy season (which promotes denitrification). The values for the feces treatment were 0.05% (MS) and 0.01% (SPS). The urine treatment values were 0.52% (MS) and 0.17% (SPS). The emissions of CH4 showed that the feces of the SPS systems resulted in a higher accumulation of gas in the rainy season (29.8 g C ha−1), followed by the feces of the MS system in the dry season (26.0 g C ha−1). Legumes in the SPS helped to maintain milk production, and the N2O emissions were lower than those produced by the MS (where the pastures were fertilized with N).

Abstract The prevalence of congenital hydrocephalus has been estimated at 1.1 per 1000 infants when including cases diagnosed before 1 year of age after exclusion of neural tube defects. Classification criteria are based either on CSF dynamics, pathophysiological mechanisms or associated lesions. Whereas inherited syndromic hydrocephalus has been associated with more than 100 disease-causing genes, only four genes are currently known to be linked to congenital hydrocephalus either isolated or as a major clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. In the past 10 years, pathogenic variants in CCDC88C have been documented but the neuropathology remains virtually unknown. We report the neuropathology of two foetuses from one family harbouring two novel compound heterozygous pathogenic variants in the CCDC88C gene: a maternally inherited indel in exon 22, c.3807_3809delinsACCT;p.(Gly1270Profs*53) and a paternally inherited deletion of exon 23, c.3967-?_c.4112-?;p.(Leu1323Argfs*10). Medical termination of pregnancy was performed at 18 and 23 weeks of gestation for severe bilateral ventriculomegaly. In both fetuses, brain lesions consisted of multifocal atresia-forking along the aqueduct of Sylvius and the central canal of the medulla, periventricular neuronal heterotopias and choroid plexus hydrops. The second fetus also presented lumbar myelomeningocele, left diaphragmatic hernia and bilateral renal agenesis. CCDC88C encodes the protein DAPLE which contributes to ependymal cell planar polarity by inhibiting the non-canonical Wnt signaling pathway and interacts with MPDZ and PARD3. Interestingly, heterozygous variants in PARD3 result in neural tube defects by defective tight junction formation and polarization process of the neuroepithelium. Besides, during organ formation Wnt signalling is a prerequisite for planar cell polarity pathway activation, and mutations in planar cell polarity genes lead to heart, lung and kidney malformations. Hence, candidate variants in CCDC88C should be carefully considered whether brain lesions are isolated or associated with malformations suspected to result from disorders of planar cell polarity.

Acute myeloid leukemia (AML) is a hematologic malignancy associated with high morbidity and mortality. Here we describe a case of a patient with AML who presented a partial response after utilization of the non-steroidal anti-inflammatory drug nimesulide. The response was characterized by complete clearance of peripheral blood blasts and an 82% decrease of bone marrow blasts associated with myeloblast differentiation. We have then shown that nimesulide induces in vitro cell death and cell cycle arrest in all AML cell lines (HL-60, THP-1, OCI-AML2, and OCI-AML3). Weighted Correlation Network Analysis (WGCNA) of serial whole-transcriptome data of cell lines treated with nimesulide revealed that the sets of genes upregulated after treatment with nimesulide were enriched for genes associated with autophagy and apoptosis, and on the other hand, the sets of downregulated genes were associated with cell cycle and RNA splicing. Serial transcriptome of bone marrow patient sample confirmed the upregulation of genes associated with autophagy after the response to nimesulide. Lastly, we demonstrated that nimesulide potentiates the cytotoxic in vitro effect of several Food and Drug Administration (FDA)-approved chemotherapy drugs used in AML, including cytarabine.

Abstract We consider interior static and spherically symmetric solutions in a gravity theory that extends the standard Hilbert–Einstein action with a Lagrangian constructed from a three-form field $$A_{\alpha \beta \gamma }$$ A α β γ , which generates, via the field strength and a potential term, a new component in the total energy-momentum tensor of the gravitational system. We formulate the field equations in Schwarzschild coordinates and investigate their solutions numerically for different equations of state of neutron and quark matter, by assuming that the three-field potential is either a constant or possesses a Higgs-like form. Moreover, stellar models, described by the stiff-fluid, radiation-like, bag model and the Bose–Einstein condensate equations of state are explicitly obtained in both general relativity and three-form gravity, thus allowing an in-depth comparison between the astrophysical predictions of these two gravitational theories. As a general result we find that, for all the considered equations of state, three-form field stars are more massive than their general relativistic counterparts. As a possible astrophysical application, we suggest that the 2.5 $$ M_{\odot }$$ M ⊙ mass compact object, associated with the GW190814 gravitational wave event, could be in fact a neutron or a quark star described by the three-form gravity theory.

Automatic systems to monitor people and subsequently improve people’s lives have been emerging in the last few years, and currently, they are capable of identifying many activities of daily living (ADLs). An important field of research in this context is the monitoring of health risks and the identification of falls. It is estimated that every year, one in three persons older than 65 years will fall, and fall events are associated with high mortality rates among the elderly. We propose an anomaly identification framework to detect falls, which incorporates a spatial-temporal convolutional graph network (ST-GCN) as a feature extractor and uses an encoder process to reconstruct ADLs and identify falls as anomalies. As the publicly available fall datasets are few and generally unbalanced, training a reliable model using approaches that need explicit labeling is challenging. Thus, a focus on learning without external supervision is desirable. Treating a fall as an exception of ADLs allows us to recognize falls as anomalies without explicit labels. Given its modular architecture, our framework can robustly represent visual information and use the encoder’s reconstruction error to identify falls as anomalies. We assess our framework’s ability to recognize falls by training it with only ADLs. We perform three types of experiments: single dataset training and evaluation that consists of separate 90% of the data to train the model 5% to adjust the model, and the rest to the test. A joint dataset experiment, where we combine two datasets to increase the number of samples our model is trained on, and a cross-dataset evaluation, where we train on one dataset and evaluate using another one. Besides presenting state-of-the-art results on our experiments, particularly on the cross-dataset one, the model also presents a low number of false events, which makes it an ideal candidate for real-world application.

Reinforcement learning refers to a machine learning paradigm in which an agent interacts with the environment to learn how to perform a task. The characteristics of the environment may change over time or be affected by disturbances not controlled, avoiding the agent finding a proper policy. Some approaches attempt to address these problems, as interactive reinforcement learning, where an external entity helps the agent learn through advice. Other approaches, such as robust reinforcement learning, allow the agent to learn the task, acting in a disturbed environment. In this paper, we propose an approach that addresses interactive reinforcement learning problems in a dynamic environment, where advice provides information on the task and the dynamics of the environment. Thus, an agent learns a policy in a disturbed environment while receiving advice. We implement our approach in the dynamic version of the cart-pole balancing task and a simulated robotic arm dynamic environment to organize objects. Our results show that the proposed approach allows an agent to complete the task satisfactorily in a dynamic, continuous state-action domain. Moreover, experimental results suggest agents trained with our approach are less sensitive to changes in the characteristics of the environment than interactive reinforcement learning agents.

Scholars have paid significant attention to the role of gender in social movements, especially in the women’s health and other feminist protest organizations. Gender issues have been less studied in other social movements, such as the anti-nuclear movement, and when they have, then almost always with a focus on the role of women. This paper explores the role of men and the performance of masculinities in protests against civilian nuclear energy. During the 1970s–1990s, activists performed three distinct forms of protest (sabotage, counter-information, and counter-expertise) in dissent against Superphénix, an experimental nuclear reactor built in Creys-Malville, France. This paper looks at how these different forms of protest were grounded in traditional Western views of masculinity, especially virility and paternalism. By comparing and contrasting counter-expertise in the anti-nuclear and the women’s health movement, the paper argues that anti-nuclear counter-expertise was less about providing an alternative view of nature, than personally discrediting official experts in a fight of “man against man” (Lewontin 1968, 2). Finally, it reflects on the consequences of these types of confrontational masculinity on the possibility of science-based dissent.

Abstract Alcohol affects multiple neurotransmitter systems, notably the GABAergic system and has been recognised for a long time as particularly damaging during critical stages of brain development. Nevertheless, data from the literature are most often derived from animal or in vitro models. In order to study the production, migration and cortical density disturbances of GABAergic interneurons upon prenatal alcohol exposure, we performed immunohistochemical studies by means of the proliferation marker Ki67, GABA and calretinin antibodies in the frontal cortical plate of 17 foetal and infant brains antenatally exposed to alcohol, aged 15 weeks’ gestation to 22 postnatal months and in the ganglionic eminences and the subventricular zone of the dorsal telencephalon until their regression, i.e., 34 weeks’ gestation. Results were compared with those obtained in 17 control brains aged 14 weeks of gestation to 35 postnatal months. We also focused on interneuron vascular migration along the cortical microvessels by confocal microscopy with double immunolabellings using Glut1, GABA and calretinin. Semi-quantitative and quantitative analyses of GABAergic and calretininergic interneuron density allowed us to identify an insufficient and delayed production of GABAergic interneurons in the ganglionic eminences during the two first trimesters of the pregnancy and a delayed incorporation into the laminar structures of the frontal cortex. Moreover, a mispositioning of GABAergic and calretininergic interneurons persisted throughout the foetal life, these cells being located in the deep layers instead of the superficial layers II and III. Moreover, vascular migration of calretininergic interneurons within the cortical plate was impaired, as reflected by low numbers of interneurons observed close to the cortical perforating vessel walls that may in part explain their abnormal intracortical distribution. Our results are globally concordant with those previously obtained in mouse models, in which alcohol has been shown to induce an interneuronopathy by affecting interneuron density and positioning within the cortical plate, and which could account for the neurological disabilities observed in children with foetal alcohol disorder spectrum.

Abstract Background Motor hand skill and associated dexterity is important for meeting the challenges of daily activity and an important resource post-stroke. In this context, the present study investigated the finger movements of right-handed subjects during tactile manipulation of a cuboid, a prototypical task underlying tactile exploration. During one motor act, the thumb and fingers of one hand surround the cuboid in a continuous and regular manner. While the object is moved by the guiding thumb, the opposed supporting fingers are replaced once they reach their joint limits by free fingers, a mechanism termed finger gaiting. Methods For both hands of 22 subjects, we acquired the time series of consecutive manipulations of a cuboid at a frequency of 1 Hz, using a digital data glove consisting of 29 sensors. Using principle component analysis, we decomposed the short action into motor patterns related to successive manipulations of the cuboid. The components purport to represent changing grasp configurations involving the stabilizing fingers and guiding thumb. The temporal features of the components permits testing whether the distinct configurations occur at the frequency of 1 Hz, i.e. within the time window of 1 s, and, thus, taxonomic classification of the manipulation as finger gaiting. Results The fraction of variance described by the principal components indicated that three components described the salient features of the single motor acts for each hand. Striking in the finger patterns was the prominent and varying roles of the MCP and PIP joints of the fingers, and the CMC joint of the thumb. An important aspect of the three components was their representation of distinct finger configurations within the same motor act. Principal component and graph theory analysis confirmed modular, functionally synchronous action of the involved joints. The computation of finger trajectories in one subject illustrated the workspace of the task, which differed for the right and left hands. Conclusion In this task one complex motor act of 1 s duration could be described by three elementary and hierarchically ordered grasp configurations occurring at the prescribed frequency of 1 Hz. Therefore, these configurations represent finger gaiting, described until now only in artificial systems, as the principal mechanism underlying this prototypical task. Trial registration clinicaltrials.gov, NCT02865642 , registered 12 August 2016.

The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.

Abstract We investigate static and spherically symmetric solutions in a gravity theory that extends the standard Hilbert–Einstein action with a Lagrangian constructed from a three-form field $$A_{\alpha \beta \gamma }$$ Aαβγ , which is related to the field strength and a potential term. The field equations are obtained explicitly for a static and spherically symmetric geometry in vacuum. For a vanishing three-form field potential the gravitational field equations can be solved exactly. For arbitrary potentials numerical approaches are adopted in studying the behavior of the metric functions and of the three-form field. To this effect, the field equations are reformulated in a dimensionless form and are solved numerically by introducing a suitable independent radial coordinate. We detect the formation of a black hole from the presence of a Killing horizon for the timelike Killing vector in the metric tensor components. Several models, corresponding to different functional forms of the three-field potential, namely, the Higgs and exponential type, are considered. In particular, naked singularity solutions are also obtained for the exponential potential case. Finally, the thermodynamic properties of these black hole solutions, such as the horizon temperature, specific heat, entropy and evaporation time due to the Hawking luminosity, are studied in detail.

From a cohort of 36 patients presenting apperceptive tactile agnosia after first cortical ischemic stroke, 14 showed temporary impairment at admission. A previous multi-voxel analysis of the cortical lesions, using as explanatory variable the course of tactile object recognition performance over the recovery period of 9 months, partitioned the cohort into three subgroups. Of the 14 patients constituting two of the subgroups, 7 recovered from their impairment whereas 7 did not. These two subgroups could not be distinguished at admission. The primary aim of the present study is to present two assessments that can do so.The first assessment comprises a pattern of behavioral measures, determined via principal component analysis, encoded in three tests: picking small objects, macrogeometrical discrimination and tactile object recognition. The receiver operating characteristic curve derived from permutation of the behavioral test scores yielded an 80% probability of correct identification of the patient subgroup and an 8% probability for false identification. As done with the permuted scores, the pattern could predict the persistence of affliction of new stroke patients with tactile agnosia.The second predictive assessment extends our previous evaluation of cortical MRI lesion maps to include subcortical regions. Confirming our previous study, the lesions of the persistently impaired subgroup disrupted significantly the anterior arcuatus fasciculus and associated superior longitudinal fasciculus III in the ipsilesional hemisphere, impeding reciprocal information transfer between supramarginal gyrus and both the ventral premotor cortex and Brodmann area 44. Due to the importance of interhemispheric information transfer in tactile agnosia, we performed a supplementary analysis of tactile object recognition scores. It showed that haptic information transfer from the non-affected to the affected hands in the persistent cases partly restored function during the nine months, possibly following restoration of functional interhemispheric haptic information transfer at the border of posterior corpus callosum and splenium.In conclusion, the combined findings of the cortical lesion at subarea PFt of the inferior parietal lobule and the associated subcortical tract lesions permit almost perfect prediction of persistent impairment of tactile object recognition. The study substantiates the need for combined analysis of both cortical lesions and white matter tract disconnections.

Automatized scalable healthcare support solutions allow real-time 24/7 health monitoring of patients, prioritizing medical treatment according to health conditions, reducing medical appointments in clinics and hospitals, and enabling easy exchange of information among healthcare professionals. With recent health safety guidelines due to the COVID-19 pandemic, protecting the elderly has become imperative. However, state-of-the-art health wearable device platforms present limitations in hardware, parameter estimation algorithms, and software architecture. This paper proposes a complete framework for health systems composed of multi-sensor wearable health devices (MWHD), high-resolution parameter estimation, and real-time monitoring applications. The framework is appropriate for real-time monitoring of elderly patients' health without physical contact with healthcare professionals, maintaining safety standards. The hardware includes sensors for monitoring steps, pulse oximetry, heart rate (HR), and temperature using low-power wireless communication. In terms of parameter estimation, the embedded circuit uses high-resolution signal processing algorithms that result in an improved measure of the HR. The proposed high-resolution signal processing-based approach outperforms state-of-the-art HR estimation measurements using the photoplethysmography (PPG) sensor.

The analysis and interpretation of data retrieved from Oxygen Radical Absorbance Capacity (ORAC) assays represent a challenging task. ORAC indexes originate from different mathematical approaches often lacking correct elucidation of kinetic features concerning radical scavenging reactions by antioxidant compounds. In this work, the expression of ORAC values as area under fluorescein (FL) decay curves (AUC) and lag time are critically compared. This multi-parametric analysis showed the extension of radical scavenging reactions beyond the lag time period for caffeic acid, gallic acid, reduced glutathione and quercetin, extending their antioxidant protection of FL. Ethanol delayed the reaction of both FL and antioxidant compounds with free radical species generated from 2,2′-azobis(2-amidinopropane) dihydrochloride thermolysis. Trolox equivalent values, commonly used to express ORAC values, were more affected by the differences in radical scavenging kinetics between the reference and the tested antioxidant compounds when calculated from AUC than from lag time. These findings stressed the importance of choosing calibrator compounds presenting ORAC kinetics similar to samples to prevent biased estimation of the antioxidant capacity. Additionally, the framework proposed here provides a sustainable analytical method for the evaluation of antioxidant capacity, with an AGREE score of 0.73.

Periodontitis (PDT) and type 2 diabetes (T2D) have demonstrated a bidirectional relationship and imbalanced oxidative stress linked to mitochondrial dysfunction. Therefore, we investigated mitochondrial and redox (de)regulation in peripheral blood mononuclear cells (PBMCs) in comorbid T2D-PDT, compared to PDT, T2D patients, and control individuals. PBMCs were analyzed for mitochondrial respiration, reactive oxygen species, antioxidant proteins, and expression of Nrf2-target genes. PDT and T2D-PDT patients exhibited altered periodontal clinical markers, while T2D and T2D-PDT patients displayed increased blood HbA1c. Decreased oxygen consumption and ATP production were observed in the PDT patient’s PBMCs. PDT and T2D-PDT PBMCs also evidenced increased H2O2 levels and reduced catalase levels (also detected in T2D patients), whereas a compromised glutathione cycle was observed in T2D-PDT patients. PBMCs from both T2D or T2D-PDT patients showed increased Nrf2 protein levels, enhanced GCL activity and GCL-catalytic subunit protein levels, and maintained GCLc, GST, and HO-1 mRNA levels. In contrast, the expressions of Nrf2-target genes were significantly diminished in the PDT patient’s PBMCs. Decreased SOD1 and GST mRNA levels were also observed in CD3+CD8+-lymphocytes derived from PDT and T2D-PDT patients. In conclusion, PBMCs from T2D-PDT patients showed major redox changes, while mononuclear cells from PDT patients showed mitochondrial deregulation and reduced expression of Nrf2-target genes.

Chemically induced toxicity is the leading cause of recent extinction of honey bees. In this regard, we developed an innovative artificial intelligence-based web app (BeeToxAI) for assessing the acute toxicity of chemicals to Apis mellifera. Initially, we developed and externally validated QSAR models for classification (external set accuracy ∼91%) through the combination of Random Forest and molecular fingerprints to predict the potential for chemicals to cause acute contact toxicity and acute oral toxicity to honey bees. Then, we developed and externally validated regression QSAR models (R2 = 0.75) using Feedforward Neural Networks (FNNs). Afterward, the best models were implemented in the publicly available BeeToxAI web app (http://beetoxai.labmol.com.br/). The outputs of BeeToxAI are: toxicity predictions with estimated confidence, applicability domain estimation, and color-coded maps of relative structure fragment contributions to toxicity. As an additional assessment of BeeToxAI performance, we collected an external set of pesticides with known bee toxicity that were not included in our modeling dataset. BeeToxAI classification models were able to predict four out of five pesticides correctly. The acute contact toxicity model correctly predicted all of the eight pesticides. Here we demonstrate that BeeToxAI can be used as a rapid new approach methodology for predicting acute toxicity of chemicals in honey bees.

Cerebral palsy (CP) is defined as permanent disorders of movement and posture. Prematurity and hypoxia–ischemia (HI) are risk factors of CP, and boys display a greater vulnerability to develop CP. Magnesium sulfate (MgSO4) is administered to mothers at risk of preterm delivery as a neuroprotective agent. However, its effectiveness is only partial at long term. To prolong MgSO4 effects, it was combined with 4-phenylbutyrate (4-PBA). A mouse model of neonatal HI, generating lesions similar to those reported in preterms, was realized. At short term, at the behavioral and cellular levels, and in both sexes, the MgSO4/4-PBA association did not alter the total prevention induced by MgSO4 alone. At long term, the association extended the MgSO4 preventive effects on HI-induced motor and cognitive deficits. This might be sustained by the promotion of oligodendrocyte precursor differentiation after HI at short term, which led to improvement of white matter integrity at long term. Interestingly, at long term, at a behavioral level, sex-dependent responses to HI were observed. This might partly be explained by early sex-dependent pathological processes that occur after HI. Indeed, at short term, apoptosis through mitochondrial pathways seemed to be activated in females but not in males, and only the MgSO4/4-PBA association seemed to counter this apoptotic process.

Hydrogels are smart-swelling 3D structures capable of incorporating/expelling water while maintaining their structures. When combined with electroactive materials, such as conducting polymers, the resulting composite may present tunable properties. Herein, the preparation and characterization of alginate-polypyrrole composite hydrogels is described using chemical polymerization to form polypyrrole inside and around alginate beads, employing two simple protocols. These materials were qualitatively tested as extraction phases, using the solid-phase extraction technique, for the pre-concentration of contaminants of emerging concern (atrazine, caffeine, and progesterone). Compared to alginate alone, the composite materials showed a modified extraction capacity, especially for the extraction of progesterone. It was shown that the alginate matrix also contributes to the extraction, not only acting as a support but also as an active extraction media, evidencing a good combination of materials.