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Abstract Background Home monitoring systems utilising artificial intelligence hold promise for digitally enhanced healthcare in older adults. Their real-world use will depend on acceptability to the end user i.e. older adults and caregivers. We explored the experiences of adults over the age of 60 and their social and care networks with a home monitoring system installed on hospital discharge after sustaining a moderate/severe Traumatic Brain Injury (TBI), a growing public health concern. Methods A qualitative descriptive approach was taken to explore experiential data from older adults and their caregivers as part of a feasibility study. Semi-structured interviews were conducted with 6 patients and 6 caregivers (N = 12) at 6-month study exit. Data were analysed using Framework analysis. Potential factors affecting acceptability and barriers and facilitators to the use of home monitoring in clinical care and research were examined. Results Home monitoring was acceptable to older adults with TBI and their caregivers. Facilitators to the use of home monitoring were perceived need for greater support after hospital discharge, the absence of sound and video recording, and the peace of mind provided to care providers. Potential barriers to adoption were reliability, lack of confidence in technology and uncertainty at how data would be acted upon to improve safety at home. Conclusions Remote monitoring approaches are likely to be acceptable, especially if patients and caregivers see direct benefit to their care. We identified key barriers and facilitators to the use of home monitoring in older adults who had sustained TBI, which can inform the development of home monitoring for research and clinical use. For sustained use in this demographic the technology should be developed in conjunction with older adults and their social and care networks.

Group B Streptococcus sequence type 103 is known primarily as a bovine mastitis pathogen. In Brazil, it has circulated in cattle and humans since the 1990s. It lacks scpB and, in humans, was found only among carriage isolates. Bovine–human interspecies transmission may have contributed to its evolution and spread.

Abstract Natural aerosols are an important, yet understudied, part of the Arctic climate system. Natural marine biogenic aerosol components (e.g., methanesulfonic acid, MSA) are becoming increasingly important due to changing environmental conditions. In this study, we combine in situ aerosol observations with atmospheric transport modeling and meteorological reanalysis data in a data-driven framework with the aim to (1) identify the seasonal cycles and source regions of MSA, (2) elucidate the relationships between MSA and atmospheric variables, and (3) project the response of MSA based on trends extrapolated from reanalysis variables and determine which variables are contributing to these projected changes. We have identified the main source areas of MSA to be the Atlantic and Pacific sectors of the Arctic. Using gradient-boosted trees, we were able to explain 84% of the variance and find that the most important variables for MSA are indirectly related to either the gas- or aqueous-phase oxidation of dimethyl sulfide (DMS): shortwave and longwave downwelling radiation, temperature, and low cloud cover. We project MSA to undergo a seasonal shift, with non-monotonic decreases in April/May and increases in June-September, over the next 50 years. Different variables in different months are driving these changes, highlighting the complexity of influences on this natural aerosol component. Although the response of MSA due to changing oceanic variables (sea surface temperature, DMS emissions, and sea ice) and precipitation remains to be seen, here we are able to show that MSA will likely undergo a seasonal shift solely due to changes in atmospheric variables.

Abstract We describe a method to extract an effective Lagrangian description for open bosonic strings, at zero transcendentality. The method relies on a particular formulation of its scattering amplitudes derived from color-kinematics duality. More precisely, starting from a (DF)2 + YM quantum field theory, we integrate out all the massive degrees of freedom to generate an expansion in the inverse string tension α′. We explicitly compute the Lagrangian terms through O $$ \mathcal{O} $$ (α′4), and target the sector of operators proportional to F 4 to all orders in α′.

ABSTRACT Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV) causing hantavirus pulmonary syndrome. In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV) causing hemorrhagic fever with renal syndrome. Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from the plasma of transchromosomic bovines (TcB) vaccinated with hantavirus DNA plasmids coding for the major glycoproteins of ANDV, SNV, HTNV, and PUUV. SAB-163 has potent neutralizing antibodies (PRNT50 > 200,000) against the four targeted hantavirus and cross-neutralization against several other heterotypic hantaviruses. At a dosage of 10 mg/kg, SAB-163 is bioavailable in Syrian hamsters out to 70 days post-treatment with a half-life of 10–15 days. At this same dosage, SAB-163 administered 1 day before, or 5 days after exposure, protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial but significant protection was achieved as late as day 6. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. This pan-hantavirus therapeutic is attractive because it is fully human, multi-targeted, safe, stable at 4°C, and effective in animal models. SAB-163 was evaluated for safety in GLP human tissue binding studies and a GLP rabbit toxicity study at 365 and 730 mg/kg and is investigational new drug enabled for phase 1 clinical trial(s).IMPORTANCEThis candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world’s most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents.

ABSTRACT The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others.

Abstract Internet of things (IOT) based in‐home monitoring systems can passively collect high temporal resolution data in the community, offering valuable insight into the impact of health conditions on patients' day‐to‐day lives. We used this technology to monitor activity and sleep patterns in older adults recently discharged after traumatic brain injury (TBI). The demographics of TBI are changing, and it is now a leading cause of hospitalisation in older adults. However, research in this population is minimal. We present three cases, showcasing the potential of in‐home monitoring systems in understanding and managing early recovery in older adults following TBI.

Plant microbiomes are known to serve several important functions for their host, and it is therefore important to understand their composition as well as the factors that may influence these microbial communities. The microbiome of Thalassia testudinum has only recently been explored, and studies to-date have primarily focused on characterizing the microbiome of plants in a single region. Here, we present the first characterization of the composition of the microbial communities of T. testudinum across a wide geographical range spanning three distinct regions with varying physicochemical conditions. We collected samples of leaves, roots, sediment, and water from six sites throughout the Atlantic Ocean, Caribbean Sea, and the Gulf of Mexico. We then analyzed these samples using 16S rRNA amplicon sequencing. We found that site and region can influence the microbial communities of T. testudinum, while maintaining a plant-associated core microbiome. A comprehensive comparison of available microbial community data from T. testudinum studies determined a core microbiome composed of 14 ASVs that consisted mostly of the family Rhodobacteraceae. The most abundant genera in the microbial communities included organisms with possible plant-beneficial functions, like plant-growth promoting taxa, disease suppressing taxa, and nitrogen fixers.

Prior studies have identified various determinants of differential immune responses to COVID-19. This study focused on the Ig-G anti-RBD marker, analyzing its potential correlations with sex, vaccine type, body fat percentage, metabolic risk, perceived stress, and previous COVID-19 exposure. In this study, data (available in S1 Data) were obtained from 108 participants from the ESFUERSO cohort, who completed questionnaires detailing their COVID-19 experiences and stress levels assessed through the SISCO scale. IgG anti-RBD concentrations were quantified using an ELISA assay developed by UNAM. Multiple regression analysis was employed to control for covariates, including sex, age, body fat percentage, body mass index (BMI), and perceived stress. This sample comprised young individuals (average age of 21.4 years), primarily consisting of females (70%), with a substantial proportion reporting a family history of diabetes, hypertension, or obesity. Most students had received the Moderna or Pfizer vaccines, and 91% displayed a positive anti-RBD response. A noteworthy finding was the interaction between body fat percentage and sex. In males, increased adiposity was associated with decreased Ig-G anti-RBD concentration; in females, the response increased. Importantly, this pattern remained consistent regardless of the vaccine received. No significant associations were observed for dietary habits or perceived stress variables. This research reports the impact of sex and body fat percentage on the immune response through Ig-G anti-RBD levels to COVID-19 vaccines. The implications of these findings offer a foundation for educational initiatives and the formulation of preventive policies aimed at mitigating health disparities.

Right hemisphere stroke patients frequently present with a combination of lateralised and non-lateralised attentional deficits characteristic of the neglect syndrome. Attentional deficits are associated with poor functional outcome and are challenging to treat, with non-lateralised deficits often persisting into the chronic stage and representing a common complaint among patients and families.In this study, we investigated the effects of non-invasive brain stimulation on non-lateralised attentional deficits in right-hemispheric stroke. In a randomised double-blind sham-controlled crossover study, twenty-two patients received real and sham transcranial Direct Current Stimulation (tDCS) whilst performing a non-lateralised attentional task. A high definition tDCS montage guided by stimulation modelling was employed to maximise current delivery over the right dorsolateral prefrontal cortex, a key node in the vigilance network. In a parallel study, we examined brain network response to this tDCS montage by carrying out concurrent fMRI during stimulation in healthy participants and patients.At the group level, stimulation improved target detection in patients, reducing overall error rate when compared with sham stimulation. TDCS boosted performance throughout the duration of the task, with its effects briefly outlasting stimulation cessation. Exploratory lesion analysis indicated that response to stimulation was related to lesion location rather than volume. In particular, reduced stimulation response was associated with damage to the thalamus and postcentral gyrus. Concurrent stimulation-fMRI revealed that tDCS did not affect local connectivity but influenced functional connectivity within large-scale networks in the contralesional hemisphere.This combined behavioural and functional imaging approach shows that brain stimulation targeted to surviving tissue in the ipsilesional hemisphere improves non-lateralised attentional deficits following stroke. This effect may be exerted via contralesional network effects.

Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

BackgroundMobile e-health technologies have proven to provide tailored assessment, intervention, and coaching capabilities for various usage scenarios. Thanks to their spread and adoption, smartphones are one of the most important carriers for such applications.ProblemHowever, the process of design, realization, evaluation, and implementation of these e-health solutions is wicked and challenging, requiring multiple stakeholders and expertise.MethodHere, we present a tailorable intervention and interaction e-health solution that allows rapid prototyping, development, and evaluation of e-health interventions at scale. This platform allows researchers and clinicians to develop ecological momentary assessment, just-in-time adaptive interventions, ecological momentary intervention, cohort studies, and e-coaching and personalized interventions quickly, with no-code, and in a scalable way.ResultThe Twente Intervention and Interaction Instrument (TIIM) has been used by over 320 researchers in the last decade. We present the ecosystem and synthesize the main scientific output from clinical and research studies in different fields.DiscussionThe importance of mobile e-coaching for prediction, management, and prevention of adverse health outcomes is increasing. A profound e-health development strategyand strategic, technical, and operational investments are needed to prototype, develop, implement, and evaluate e-health solutions. TIIM ecosystem has proven to support these processes. This paper ends with the main research opportunities in mobile coaching, including intervention mechanisms, fine-grained monitoring, and inclusion of objective biomarker data.

Dreaming, a widely researched aspect of sleep, often mirrors waking-life experiences. Despite the prevalence of sensory perception during wakefulness, sensory experiences in dreams remain relatively unexplored. Free recall dream reports, where individuals describe their dreams freely, may not fully capture sensory dream experiences. In this study, we developed a dream diary with direct questions about sensory dream experiences. Participants reported sensory experiences in their dreams upon awakening, over multiple days, in a home-based setting (n = 3476 diaries). Our findings show that vision was the most common sensory dream experience, followed by audition and touch. Olfaction and gustation were reported at equally low rates. Multisensory dreams were far more prevalent than unisensory dreams. Additionally, the prevalence of sensory dream experiences varied across emotionally positive and negative dreams. A positive relationship was found between on the one hand sensory richness and, on the other emotional intensity of dreams and clarity of dream recall, for both positive and negative dreams. These results underscore the variety of dream experiences and suggest a link between sensory richness, emotional content and dream recall clarity. Systematic registration of sensory dream experiences offers valuable insights into dream manifestation, aiding the understanding of sleep-related memory consolidation and other aspects of sleep-related information processing.

The room temperature spectrum of anthracene was measured in the intermediate THz range. The anthracene measurements revealed five absorption bands which have not been previously reported. These bands appeared at 4.97 THz, 6.39 THz, 7.65 THz, 11.52 THz and 13.21 THz. There was a good correspondence between the observed experimental bands and the theoretical peaks with the maximum shift of 0.45 THz. The theoretical model discovered that the spectrum of this material in the considered frequency range is comprised of both intermolecular and intramolecular spectral features. Comparison of the spectra of anthracene, BMC biochar and TP18 highlights the availability of tricyclic aromatic compounds in biochar and TP18 soil. This work supplements the existing studies of anthracene in the intermediate THz range. Furthermore, the study hints that not all form of biochar are good fertilizers as some lack the key component attributed to fertility.

Predicative modal superlatives, such as Italian Luisa è stata il più calma possibile (‘Luisa was the most unperturbed possible’), state that the highest amount of calm that could be instantiated in the type of situation at hand, was associated with Luisa in the actual world. The semantic strategy proposed for tracking situations of the relevant type across worlds and varying individuals builds on the assumption that the modal adjective projects a predicate (Q) that captures specific circumstances affecting individuals that do not necessarily have a counterpart in all worlds, and that such circumstances cannot therefore be included in a standard modal base. The analysis verifies a relation between Luisa and a particular amount q in the real world w under some specific circumstances, and checks that for all amounts q’ and accessible worlds w’, if there is an individual holding the same relation to q’ in w’ and under the same circumstances, then q’ ≤ q.

Abstract DNA polymerase ε (Polε) is a key enzyme for DNA replication in eukaryotes. Recently it was shown that the catalytic domain of yeast Polε (PolεCD) contains a [4Fe-4S] cluster located at the base of the processivity domain (P-domain) and coordinated by four conserved cysteines. In this work, we show that human PolεCD (hPolεCD) expressed in bacterial cells also contains an iron-sulfur cluster. In comparison, recombinant hPolεCD produced in insect cells contains significantly lower level of iron. The iron content of purified hPolECD samples correlates with the level of DNA-binding molecules, which suggests an important role of the iron-sulfur cluster in hPolε interaction with DNA. Indeed, mutation of two conserved cysteines that coordinate the cluster abolished template:primer binding as well as DNA polymerase and proofreading exonuclease activities. We propose that the cluster regulates the conformation of the P-domain, which, like a gatekeeper, controls access to a DNA-binding cleft for a template:primer. The binding studies demonstrated low affinity of hPolεCD to DNA and a strong effect of salt concentration on stability of the hPolεCD/DNA complex. Pre-steady-state kinetic studies have shown a maximal polymerization rate constant of 51.5 s−1 and a relatively low affinity to incoming dNTP with an apparent K D of 105 µM.

Introduction and aims Digital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour can provide informative measures of neurological conditions and neurodegenerative decline. New digital technologies present an opportunity to provide remote, high-frequency monitoring of patients from within their homes. The purpose of the living lab study is to develop novel digital biomarkers of functional impairment in those living with neurodegenerative disease (NDD) and neurological conditions.Methods and analysis The Living Lab study is a cross-sectional observational study of cognition and behaviour in people living with NDDs and other, non-degenerative neurological conditions. Patients (n≥25 for each patient group) with dementia, Parkinson’s disease, amyotrophic lateral sclerosis, mild cognitive impairment, traumatic brain injury and stroke along with controls (n≥60) will be pragmatically recruited. Patients will carry out activities of daily living and functional assessments within the Living Lab. The Living Lab is an apartment-laboratory containing a functional kitchen, bathroom, bed and living area to provide a controlled environment to develop novel digital biomarkers. The Living Lab provides an important intermediary stage between the conventional laboratory and the home. Multiple passive environmental sensors, internet-enabled medical devices, wearables and electroencephalography (EEG) will be used to characterise functional impairments of NDDs and non-NDD conditions. We will also relate these digital technology measures to clinical and cognitive outcomes.Ethics and dissemination Ethical approvals have been granted by the Imperial College Research Ethics Committee (reference number: 21IC6992). Results from the study will be disseminated at conferences and within peer-reviewed journals.

Background: interleukin 23 (IL-23) is an important factor involved in the survival and proliferation of T helper 17 cells (Th17), known for their implication in multiple sclerosis (MS). By contrast, IL-27 regulates and modulates the function of T lymphocytes, in particular as a suppressor of Th17 differentiation. The aims of the study were i) to test the association of cytokines with the clinical and genetic characteristics in each of the multiple sclerosis groups (CIS - clinically isolated syndrome, RRMS - relapsing-remitting MS and SPMS – Secondary progressive MS) and ii) to evaluate the association between serum levels of IL-23 and IL-27 with T4730C (IL-27), A964G (IL-27) and R381Q (IL-23) gene polymorphisms in RRMS patients. Methods: Blood samples were obtained from 82 patients diagnosed with MS under treatment with glatiramer acetate (GA), interferon beta (IFN) 1 A and 1 B. IL-23 and IL-27 serum concentrations were measured by enzyme-linked immunosorbant assay (ELISA). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used in order to determine the genotypes for R381Q (IL-23) polymorphisms, T4730C (IL-27) and A964G (IL-27). Results: Patients with SPMS, RRMS and CIS respectively differed significantly regarding age distribution (p = 0.003) but the studied MS groups were similar regarding age at disease onset (p = 0.528) and treatment type (p = 0.479). A significant increase of mean serum IL-27 was noticed in cases with early onset (age at disease onset 0.05) in the CIS and SPMS group respectively but a significant correlation between IL-23 and the duration of disease-modifying treatment was noticed only in the SPMS group. Conclusions: The results of the current study suggest an association between IL-23 levels and the R381Q gene polymorphism and also a relationship between IL-27 serum levels and early age at disease onset in RRMS patients.

Abstract Background The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28–59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusion Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.

La floricultura argentina presenta un desafío que incluye el mejoramiento de la producción mediante el uso de compuestos orgánicos. Las fitohormonas, como los brasinoesteroides (BRs), son una alternativa promisoria. El objetivo de este trabajo fue evaluar la respuesta agronómica y los cambios estructurales en hoja de Petunia × hybrida frente a la aplicación de BRs. Plantines de la Serie Dreams® fueron trasplantados en macetas, a los 15 días se efectuó la aplicación de la primera dosis de los BRs EP24 y BB16. La segunda aplicación se realizó a los 20 días. Para el análisis agronómico se evaluó: índice de verdor, biomasa, área foliar y número de flores; para los cambios estructurales: cierre estomático, deposición de calosa y lignina. Los resultados evidenciaron que las plantas tratadas con BB16 y EP24, mostraron mayor producción de biomasa en relación con el testigo absoluto. Las plantas tratadas con EP24 mostraron aumento en el número de flores, menor apertura estomática, y mayor deposición de calosa y lignina en los haces vasculares del nervio principal. Los BRs podrían ser utilizados en el cultivo de Petunia × hybrida, como alternativa biotecnológica para mejorar la producción de flores, promoviendo el crecimiento de las plantas y reduciendo el uso de fertilizantes sintéticos.

Abstract DNA polymerase ε (Polε) performs bulk synthesis of DNA on the leading strand during genome replication. Polε binds two substrates, a template:primer and dNTP, and catalyzes a covalent attachment of dNMP to the 3' end of the primer. Previous studies have shown that Polε easily inserts and extends ribonucleotides, which may promote mutagenesis and genome instability. In this work, we analyzed the mechanisms of discrimination against RNA-containing primers by human Polε (hPolε), performing binding and kinetic studies at near-physiological salt concentration. Pre-steady-state kinetic studies revealed that hPolεCD extends RNA primers with approximately 3300-fold lower efficiency in comparison to DNA, and addition of one dNMP to the 3′ end of an RNA primer increases activity 36-fold. Likewise, addition of one rNMP to the 3′ end of a DNA primer reduces activity 38-fold. The binding studies conducted in the presence of 0.15 M NaCl revealed that human hPolεCD has low affinity to DNA (K D of 1.5 µM). Strikingly, a change of salt concentration from 0.1 M to 0.15 M reduces the stability of the hPolεCD/DNA complex by 25-fold. Upon template:primer binding, the incoming dNTP and magnesium ions make hPolε discriminative against RNA and chimeric RNA–DNA primers. In summary, our studies revealed that hPolε discrimination against RNA-containing primers is based on the following factors: incoming dNTP, magnesium ions, a steric gate for the primer 2′OH, and the rigid template:primer binding pocket near the catalytic site. In addition, we showed the importance of conducting functional studies at near-physiological salt concentration.

Introduction A significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn is associated with widespread neurodegeneration. We aim to evaluate systemic inflammation as a mediator of ongoing neurodegeneration after TBI.Methods and analysis TBI-braINFLAMM will combine data already collected from two large prospective TBI studies. The CREACTIVE study, a broad consortium which enrolled >8000 patients with TBI to have CT scans and blood samples in the hyperacute period, has data available from 854 patients. The BIO-AX-TBI study recruited 311 patients to have acute CT scans, longitudinal blood samples and longitudinal MRI brain scans. The BIO-AX-TBI study also has data from 102 healthy and 24 non-TBI trauma controls, comprising blood samples (both control groups) and MRI scans (healthy controls only). All blood samples from BIO-AX-TBI and CREACTIVE have already been tested for neuronal injury markers (GFAP, tau and NfL), and CREACTIVE blood samples have been tested for inflammatory cytokines. We will additionally test inflammatory cytokine levels from the already collected longitudinal blood samples in the BIO-AX-TBI study, as well as matched microdialysate and blood samples taken during the acute period from a subgroup of patients with TBI (n=18).We will use this unique dataset to characterise post-TBI systemic inflammation, and its relationships with injury severity and ongoing neurodegeneration.Ethics and dissemination Ethical approval for this study has been granted by the London—Camberwell St Giles Research Ethics Committee (17/LO/2066). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of larger observational and experimental medicine studies assessing the role and management of post-TBI systemic inflammation.

Introduction The prevalence of traumatic brain injury (TBI) among older adults is increasing exponentially. The sequelae can be severe in older adults and interact with age-related conditions such as multimorbidity. Despite this, TBI research in older adults is sparse. Minder, an in-home monitoring system developed by the UK Dementia Research Institute Centre for Care Research and Technology, uses infrared sensors and a bed mat to passively collect sleep and activity data. Similar systems have been used to monitor the health of older adults living with dementia. We will assess the feasibility of using this system to study changes in the health status of older adults in the early period post-TBI.Methods and analysis The study will recruit 15 inpatients (>60 years) with a moderate-severe TBI, who will have their daily activity and sleep patterns monitored using passive and wearable sensors over 6 months. Participants will report on their health during weekly calls, which will be used to validate sensor data. Physical, functional and cognitive assessments will be conducted across the duration of the study. Activity levels and sleep patterns derived from sensor data will be calculated and visualised using activity maps. Within-participant analysis will be performed to determine if participants are deviating from their own routines. We will apply machine learning approaches to activity and sleep data to assess whether the changes in these data can predict clinical events. Qualitative analysis of interviews conducted with participants, carers and clinical staff will assess acceptability and utility of the system.Ethics and dissemination Ethical approval for this study has been granted by the London-Camberwell St Giles Research Ethics Committee (REC) (REC number: 17/LO/2066). Results will be submitted for publication in peer-reviewed journals, presented at conferences and inform the design of a larger trial assessing recovery after TBI.

Summary: Background: Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity. Methods: This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary’s Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George’s Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients’ performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary’s Hospital TBI clinic in London (UK). Findings: The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r = 0.86, p

BackgroundInternet of Things (IoT) technology enables physiological measurements to be recorded at home from people living with dementia and monitored remotely. However, measurements from people with dementia in this context have not been previously studied. We report on the distribution of physiological measurements from 82 people with dementia over approximately 2 years. ObjectiveOur objective was to characterize the physiology of people with dementia when measured in the context of their own homes. We also wanted to explore the possible use of an alerts-based system for detecting health deterioration and discuss the potential applications and limitations of this kind of system. MethodsWe performed a longitudinal community-based cohort study of people with dementia using “Minder,” our IoT remote monitoring platform. All people with dementia received a blood pressure machine for systolic and diastolic blood pressure, a pulse oximeter measuring oxygen saturation and heart rate, body weight scales, and a thermometer, and were asked to use each device once a day at any time. Timings, distributions, and abnormalities in measurements were examined, including the rate of significant abnormalities (“alerts”) defined by various standardized criteria. We used our own study criteria for alerts and compared them with the National Early Warning Score 2 criteria. ResultsA total of 82 people with dementia, with a mean age of 80.4 (SD 7.8) years, recorded 147,203 measurements over 958,000 participant-hours. The median percentage of days when any participant took any measurements (ie, any device) was 56.2% (IQR 33.2%-83.7%, range 2.3%-100%). Reassuringly, engagement of people with dementia with the system did not wane with time, reflected in there being no change in the weekly number of measurements with respect to time (1-sample t-test on slopes of linear fit, P=.45). A total of 45% of people with dementia met criteria for hypertension. People with dementia with α-synuclein–related dementia had lower systolic blood pressure; 30% had clinically significant weight loss. Depending on the criteria used, 3.03%-9.46% of measurements generated alerts, at 0.066-0.233 per day per person with dementia. We also report 4 case studies, highlighting the potential benefits and challenges of remote physiological monitoring in people with dementia. These include case studies of people with dementia developing acute infections and one of a person with dementia developing symptomatic bradycardia while taking donepezil. ConclusionsWe present findings from a study of the physiology of people with dementia recorded remotely on a large scale. People with dementia and their carers showed acceptable compliance throughout, supporting the feasibility of the system. Our findings inform the development of technologies, care pathways, and policies for IoT-based remote monitoring. We show how IoT-based monitoring could improve the management of acute and chronic comorbidities in this clinically vulnerable group. Future randomized trials are required to establish if a system like this has measurable long-term benefits on health and quality of life outcomes.

Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines.

Background: Community health worker (CHW) programmes, when adequately integrated into mainstream health systems, can provide a viable, affordable and sustainable path to strengthened health systems that better meets demands for improved child health, especially in resource-constrained settings. However, studies that report on how CHW programmes are integrated into respective health systems in sub-Saharan Africa (SSA) are missing. Aim: This review presents evidence on CHW programmes’ integration into National Health Systems for improved health outcomes in SSA. Setting: Sub-Saharan Africa. Method: Six CHW programmes representing three sub-Saharan regions (West, East, and Southern Africa) were purposively selected based on their deemed integration into respective National Health Systems. A database search of literature limited to the identified programmes was then conducted. Screening and literature selection was guided a scoping review framework. Abstracted data were synthesised and presented in a narrative form. Results: A total of 42 publications met the inclusion criteria. Reviewed papers had an even focus on all six CHW programmes integration components. Although some similarities were observed, evidence of integration on most CHW programme integration components varied across countries. The linkage of CHW programmes to respective health systems runs across all reviewed countries. Some CHW programme components such as CHW recruitment, education and certification, service delivery, supervision, information management, and equipment and supplies are integrated into the health systems differently across the region. Conclusion: Different approaches to the integration of all the components depict complexity in the field of CHW programme integration in the region. Contribution: The study presents synthesized evidence on CHW programmes integration into national health systems in SSA.

We present a survey to evaluate crypto-political, crypto-economic, and crypto-governance sentiment in people who are part of a blockchain ecosystem. Based on 3,710 survey responses, we describe their beliefs, attitudes, and modes of participation in crypto and investigate how self-reported political affiliation and blockchain ecosystem affiliation are associated with these. We observed polarization in questions on perceptions of the distribution of economic power, personal attitudes towards crypto, normative beliefs about the distribution of power in governance, and external regulation of blockchain technologies. Differences in political self-identification correlated with opinions on economic fairness, gender equity, decision-making power and how to obtain favorable regulation, while blockchain affiliation correlated with opinions on governance and regulation of crypto and respondents’ semantic conception of crypto and personal goals for their involvement. We also find that a theory-driven constructed political axis is supported by the data and investigate the possibility of other groupings of respondents or beliefs arising from the data.

The effect of temperature and drying technologies on mucilage and cellulose (obtained by the microwave-assisted extraction technique, MAE) from Opuntia ficus-indica (OFI) and Austrocylindropuntia cylindrica (CC) was determined using a conventional oven (CO) and Refractive Window (RW). Mathematical modeling was performed from drying kinetics data using the Lewis, Henderson-Pabis, Page, and Logarithmic models. Activation Energy (Ea) and Diffusivity (D) were also determined. The model with the best fit was the logarithmic one, with a correlation coefficient (R2) greater than 0.99. The obtained activation energies were 22.81 kJ mol−1 for Refractance window (RW) and 31.44 kJ mol−1 using conventional hot air drying (CO) while a diffusivity of 2.9 ∗10−8 m2 s−1 for RW and 1.3∗10−8 m2 s−1 for CO were found as well. According to our results, a greater drying efficiency and a less chemical deterioration of the plant sample are obtained by drying with Refractance window.

Substantial evidence suggests that sleep has a role in declarative memory consolidation. An influential notion holds that such sleep-related memory consolidation is associated with a process of abstraction. The neural underpinnings of this putative process are thought to involve a hippocampo-neocortical dialogue. Specifically, the idea is that, during sleep, the statistical contingencies across episodes are re-coded to a less hippocampus-dependent format, while at the same time losing configural information. Two previous studies from our lab, however, failed to show a preferential role of sleep in either episodic memory decontextualisation or the formation of abstract knowledge across episodic exemplars. Rather these processes occurred over sleep and wake time alike. Here, we present two experiments that replicate and extend these previous studies and exclude some alternative interpretations. The combined data show that sleep has no preferential function in this respect. Rather, hippocampus-dependent memories are generalised to an equal extent across both wake and sleep time. The one point on which sleep outperforms wake is actually the preservation of episodic detail of memories stored prior to sleep.

As grandes cidades brasileiras passaram, nos últimos anos, por importantes transformações em sua estrutura social. Trata-se de um urbano marcado por disputas, lutas e conflitos que revelam a presença de formas precárias de vida, de trabalho e de habitação geradas pela lógica capitalista de produção do espaço. Nesse contexto, a pandemia da Covid-19 construiu padrões de disseminação socioterritorial que evidenciaram a presença nas cidades de grupos sociais de grande vulnerabilidade. Este texto analisa os impactos da Covid-19 sobre a desigualdade de renda e a vulnerabilidade social nas principais regiões metropolitanas brasileiras. Consideram-se como principais indicadores para a análise o Coeficiente de Gini e o percentual dos indivíduos vivendo em domicílios com rendimento per capita mensal de até ¼ de salário-mínimo. A metodologia contempla revisão bibliográfica dos conceitos e categorias analisados e levantamento estatístico de dados sociodemográficos e econômicos.

Background: Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation whose potential as a cognitive therapy is hindered by our limited understanding of how participant and experimental factors influence its effects. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. We have additionally shown, in both healthy and traumatic brain injury (TBI) populations, that the behavioral effects of tDCS are positively correlated with white matter (WM) structure. Objectives: In this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity. Methods: We applied anodal, cathodal and sham tDCS to the right inferior frontal gyrus (rIFG) of healthy (n = 22) and TBI participants (n = 34). We used the Choice Reaction Task (CRT) performance to manipulate brain state during tDCS. We acquired simultaneous fMRI to assess activity of cognitive brain networks and used Fractional Anisotropy (FA) as a measure of WM structure. Results: We find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. We then show that WM structure further modulates the brain-state dependent effects of tDCS on brain network activity. These effects are not unidirectional - in the absence of task with anodal and cathodal tDCS, FA is positively correlated with brain activity in several regions of the default mode network. Conversely, with cathodal tDCS during CRT performance, FA is negatively correlated with brain activity in a salience network region. Conclusions: Our results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the factors in isolation.

Ocean acidification (OA) threatens the persistence of reef-building corals and the habitat they provide. While species-specific effects of OA on marine organisms could have cascading effects on ecological interactions like competition, few studies have identified how benthic reef competitors respond to OA. We explored how two common Caribbean competitors, branching Porites and a colonial zoanthid (Zoanthus), respond to the factorial combination of OA and competition. In the laboratory, we exposed corals, zoanthids and interacting corals and zoanthids to ambient (8.01 ± 0.03) and OA (7.68 ± 0.07) conditions for 60 days. The OA treatment had no measured effect on zoanthids or coral calcification but decreased Porites maximum PSII efficiency. Conversely, the competitive interaction significantly decreased Porites calcification but had minimal-to-no countereffects on the zoanthid. Although this interaction was not exacerbated by the 60-day OA exposure, environmental changes that enhance zoanthid performance could add to the dominance of zoanthids over corals. The lack of effects of OA on coral calcification indicates that near-term competitive interactions may have more immediate consequences for some corals than future global change scenarios. Disparate consequences of competition have implications for community structure and should be accounted for when evaluating local coral reef trajectories.

More than 100 Russian varieties and collection samples of winter rye were studied under the conditions of the Kirov region against the natural infectious background of the development of mycoses (2019-2020). The degree of damage by powdery mildew during the years of research reached 86.3 %, septoria – 63.3 %, brown rust – 40.5 %, stem rust – 60.0 %, rhynchosporiosis – 29.3 %. During plant ontogenesis (from phases 31 to 85 Zadoks scale), the growth of fungal infection in varietal biocenoses was analyzed. When accounting for diseases, well-known methods were used. The nature of plant-microbial interactions and the parameters of resistance were assessed by indicators of ADDC (area under the curve of disease development), IR (resistance index) and LP (latency period). A close relationship was established between the duration of LP and the degree of septoria infection (r = -0.98), brown rust (r = -0.95), powdery mildew (r = -0.92), stem rust (r = -0.80), rhynchosporiosis (r = -0.67). The regression equations are linear (R2 = 0.84 ... 0.96) and indicate a daily increase in diseases (from 0.52 to 0.88 %). In the course of immunological management, there have been identified about 20 varieties of Russian selection distinguished by nonspecific resistance to two or more diseases, slow (slow rusting) growth of infection in varietal biocenoses and a long latent period of pathogenesis. Among them are the varieties of the Federal Agricultural Research Center of the North-East named N.V. Rudnitsky (Falyonskaya 4, Vyatka 2, Rushnik, Kirovskaya 89, Snezhana, Flora, Rumba), other scientific institutions of the Russian Federation (Alisa, Pamyati Bambysheva, P-01/14, GP-901 and others) and new samples from the VIR collection (Trinodis 4 Minvak – 139/09 NP, Estet NP 42/14 and others). They can be used in breeding as sources, and indicators of ADDC, IR, LP – as immunologically significant parameters of nonspecific resistance.

How acute deoxygenation events affect tropical marine ecosystems remains poorly understood. This study integrates analyses of coral reef benthic communities with microbial community sequencing to show how a deoxygenation event rapidly altered a shallow tropical coral reef ecosystem in the Caribbean.

The Zika virus is a flavivirus spread by the Aedes aegypti mosquito, which also transmits dengue and chikungunya. Current forms of control include elimination of mosquito breeding sites, use of insecticides, repellents and other means. The present study developed new adsorbent materials based on silica and biomaterials capable of releasing an Aedes aegypti mosquito repellent. The materials synthesized were characterized by Fourier-Transform Infrared, thermogravimetric analysis, Scanning Electron Microscopy and Brunauer, Emmett and Teller analysis and tested with citronella, an essential oil widely recognized as a natural insect repellent. The materials presented type IV isotherms, with type H1 hysteresis, characteristic of mesoporous materials, with pore diameters of between 50 Å and 80 Å. Materials based on silica-chitosan-glutaraldehyde dried in an oven (SCGO) and silica-chitosan-glutaraldehyde dried under a vacuum (SCGV) were found to produce more controlled release of citronella essential oil. The bioassay test was performed using a horizontal double-choice olfactometer. The adsorbent SCGO remained stable for the four hours of the bioassay, while the commercial repellent became ineffective after two hours of release. The production of a prototype in the form of bracelets, stickers releasing a volatile repellent is therefore proposed as a method for the control of the mosquito in urban areas.

Background: Streptococcus pneumoniae (S. pneumoniae) of serogroup 19 are mainly represented by serotypes 19A and 19F, which are associated with antimicrobial resistance and disease. The wzy gene, a component of the pneumococcal capsular locus, is the target to differentiate serotypes 19A and 19F by PCR-based capsular typing. In the last decade, allelic variants of the wzy19F gene have been described, leading to misinterpretation of capsular typing results. Methods: A collection of 154 serotype 19F S. pneumoniae strains recovered from carriage and disease in Brazil was evaluated to identify and characterize wzy19F variant isolates. Results: Eleven (7%) wzy19F variant isolates were detected and identified as belonging to ST810 (n = 10) or ST13673 (n = 1; single-locus variant of ST810). They were mostly recovered from diseased patients, susceptible to the antimicrobial agents tested (except for one multidrug-resistant strain) and did not harbor pili genes. Sequences of the wzy19F gene of these variants were identical to each other and to those previously described in Brazil, but slightly different from wzy19F variants identified in other countries. Conclusion: This study indicated that wzy19F variants present a geographically driven distribution and was the first to uncover phenotypic and genetic features of a wzy19F variant lineage occurring in Brazil since 1989.

(1) Background: Vascular endothelial growth factor (VEGF) is essential in vasculo- and angiogenesis due to its role in endothelial cell proliferation and migration. As a vascular proliferative factor, VEGF is one of the hallmarks of cancer and, in adult populations, the relationship between genetic polymorphism and neoplasm was widely investigated. For the neonatal population, only a few studies attempted to uncover the link between the genetic polymorphism of VEGF and neonatal pathology, especially related to late-onset complications. Our objective is to evaluate the literature surrounding VEGF genetic polymorphisms and the morbidity of the neonatal period. (2) Methods: A systematic search was initially conducted in December 2022. The PubMed platform was used to explore MEDLINE (1946 to 2022) and PubMed Central (2000 to 2022) by applying the search string ((VEGF polymorphism*) and newborn*). (3) Results: The PubMed search yielded 62 documents. A narrative synthesis of the findings was undertaken considering our predetermined subheadings (infants with low birth weight or preterm birth, heart pathologies, lung diseases, eye conditions, cerebral pathologies, and digestive pathologies). (4) Conclusion: The VEGF polymorphisms seem to be associated with neonatal pathology. The involvement of VEGF and VEGF polymorphism has been demonstrated for retinopathy of prematurity.

Breast cancer is the most common cancer in women, with a high incidence estimated to reach 2.3 million by 2030. Triple-Negative Breast Cancer (TNBC) is the greatest invasive class of breast cancer with a poor prognosis, due to the side-effects exerted by the chemotherapy used and the low effectivity of novel treatments. In this sense, copper compounds have shown to be potentially effective as antitumor agents, attracting increasing interest as alternatives to the usually employed platinum-derived drugs. Therefore, the aim of this work is to identify differentially expressed proteins in MDA-MB-231 cells exposed to two copper(II)-hydrazone complexes using label-free quantitative proteomics and functional bioinformatics strategies to identify the molecular mechanisms through which these copper complexes exert their antitumoral effect in TNBC cells. Both copper complexes increased proteins involved in endoplasmic reticulum stress and unfolded protein response, as well as the downregulation of proteins related to DNA replication and repair. One of the most relevant anticancer mechanisms of action found for CuHL1 and CuHL2 was the down-regulation of gain-of-function-mutant p53. Moreover, we found a novel and interesting effect for a copper metallodrug, which was the down-regulation of proteins related to lipid synthesis and metabolism that could lead to a beneficial decrease in lipid levels.

Abstract Background Cellular sex has rarely been considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and “omics” approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms. Methods We performed proteomic and Gene Ontology (GO) analyses of the secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and Western blot techniques and efferocytosis through the ability of the macrophage cell line RAW 264.7 to engulf apoptotic ECs. PTX3 mRNA levels were measured by RT-qPCR. Results Proteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison with female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 suggested that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis seemed to be independent on PTX3 expression. Conclusions Our results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.

Abstract A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.

Background Survivors of moderate-to-severe traumatic brain injury (msTBI) frequently experience troublesome unexplained somatic symptoms. Autonomic dysfunction may contribute to these symptoms. However, there is no previous study of clinical subjective and objective autonomic dysfunction in msTBI.Methods We present results from two groups of patients with msTBI. The first, a case–control comparative study, comprises prospectively recruited msTBI outpatients, in whom we measured burden of autonomic symptoms using the Composite Autonomic Symptom Score (COMPASS31) questionnaire. The second, a descriptive case series, comprises retrospectively identified msTBI outpatients who had formal clinical autonomic function testing at a national referral autonomics unit.Results Group 1 comprises 39 patients with msTBI (10F:20M, median age 40 years, range 19–76), median time from injury 19 months (range 6–299) and 44 controls (22F:22M, median age 45, range 25–71). Patients had significantly higher mean weighted total COMPASS-31 score than controls (p

The pathology of Dravet syndrome is of particular importance in children. In this article we analyze the involvement of the SCN1A gene in Dravet syndrome, we approach the new treatment strategies in Dravet syndrome.

We report here a new species belonging to Nephus (Nephus) Mulsant. Nephus (Nephus) apolonia sp. nov. was collected in the Reunion Island (Mascarene Archipelago, Indian Ocean). We describe this new species and redescribe and illustrate three other Nephus species already known from Reunion: Nephus (Nephus) oblongosignatus Mulsant, 1850, Nephus (Geminosipho) reunioni (Fürsch, 1974) and Nephus (Nephus) voeltzkowi Weise, 1910. Furthermore, we present a phylogenetic tree for these four species and calculate the genetic distances between them, using high-throughput DNA sequencing of the mitochondrial genome. The similar external morphology of N. apolonia sp. nov. and N. voeltzkowi very probably explains why individuals from the first species have been mistakenly identified as the latter and were not recognized as different until now. Other than external and genitalia traits, the present study provides molecular evidence confirming these are indeed two different species.

Abstract Background Neurofeedback aids volitional control of one’s own brain activity using non-invasive recordings of brain activity. The applications of neurofeedback include improvement of cognitive performance and treatment of various psychiatric and neurological disorders. During real-time magnetoencephalography (rt-MEG), sensor-level or source-localized brain activity is measured and transformed into a visual feedback cue to the subject. Recent real-time fMRI (rt-fMRI) neurofeedback studies have used pattern recognition techniques to decode and train a brain state to link brain activities and cognitive behaviors. Here, we utilize the real-time decoding technique similar to ones employed in rt-fMRI to analyze time-varying rt-MEG signals. Results We developed a novel rt-MEG method, state-based neurofeedback (sb-NFB), to decode a time-varying brain state, a state signal, from which timings are extracted for neurofeedback training. The approach is entirely data-driven: it uses sensor-level oscillatory activity to find relevant features that best separate the targeted brain states. In a psychophysical task of spatial attention switching, we trained five young, healthy subjects using the sb-NFB method to decrease the time necessary for switch spatial attention from one visual hemifield to the other (referred to as switch time). Training resulted in a decrease in switch time with training. We saw that the activity targeted by the training involved proportional changes in alpha and beta-band oscillations, in sensors at the occipital and parietal regions. We also found that the state signal that encodes whether subjects attend to the left or right visual field effectively switches consistently with the task. Conclusion We demonstrated the use of the sb-NFB method when the subject learns to increase the speed of shifting covert spatial attention from one visual field to the other. The sb-NFB method can target timing features that would otherwise also include extraneous features such as visual detection and motor response in a simple reaction time task.

Background: Earlier age at menarche (AAM), a marker of puberty timing in females, has been associated with a higher likelihood of adolescent risk-taking behaviours and variably associated with educational attainment. Aim: To examine the association between AAM and educational attainment in the Pelotas, Brazil, 1982 Birth Cohort. Subjects and methods: AAM was categorised as Early (7–11 years), Average (12–13 years), or Late (14+ years). Primary outcome: years of education (age 30). Secondary outcomes: risk-taking behaviours, adult income and school grade failure. Results: In adjusted models, compared to Average AAM, Late AAM was associated with 0.64 fewer years of education (95% CI: −1.15, −0.13). Early AAM was associated with earlier age at first sexual intercourse (−0.25 years; 95% CI: −0.39, −0.12), whereas Late AAM was associated with 17% lower adult income (0.83; 95% CI: 0.71, 0.95) and 0.31 years older age at first alcohol consumption (95% CI: 0.10, 0.52). Conclusions: Our findings confirm the association between earlier puberty timing in females and a greater likelihood of risk-taking behaviours in this setting of recent secular changes towards earlier puberty. However, the association between Late AAM and lower education was surprising and may support a psychosocial rather than biological link between puberty timing and educational outcomes.

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15μg H7N9, 1B) IB160 + 7.5μg H7N9, 1C) IB160 + 3.75μg H7N9, 2A) SE + 15μg H7N9, 2B) SE + 7.5μg H7N9, 2C) SE + 3.75μg H7N9, 3) unadjuvanted vaccine 15μg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.

Some recent uses of artificial intelligence for (for example) facial recognition, evaluating resumes, and sorting photographs by subject matter have revealed troubling disparities in performance or impact based on the demographic traits (like race and gender) of subject populations. These disparities raise pressing questions about how using artificial intelligence can work to promote justice or entrench injustice. Political theorists and philosophers have developed nuanced vocabularies and theoretical frameworks for understanding and adjudicating disputes about what justice requires and what constitutes injustice. The interdisciplinary community committed to understanding and conscientiously using big data could benefit from this work. Thus, in the spirit of encouraging cross-disciplinary dialogue and collaboration, this piece examines contemporary scholarship in political theory and philosophy to illustrate some of the vocabularies and frameworks political theorists and philosophers have developed for thinking about justice and injustice. It then draws on these frameworks to illuminate how the use of artificial intelligence can implicate questions of justice, with a focus on institutional discrimination, structural injustice, and epistemic injustice. Ultimately, the piece argues that the use of artificial intelligence—far from representing a decision to take power out of human hands—represents a novel way of harnessing human power, making questions of justice central to its conscientious undertaking.

Prior exposure to variable environmental conditions is predicted to influence the resilience of marine organisms to global change. We conducted complementary 4-month field and laboratory experiments to understand how a dynamic, and sometimes extreme, environment influences growth rates of a tropical reef-building crustose coralline alga and its responses to ocean acidification (OA). Using a reciprocal transplant design, we quantified calcification rates of the Caribbean coralline Lithophyllum sp. at sites with a history of either extreme or moderate oxygen, temperature, and pH regimes. Calcification rates of in situ corallines at the extreme site were 90% lower than those at the moderate site, regardless of origin. Negative effects of corallines originating from the extreme site persisted even after transplanting to more optimal conditions for 20 weeks. In the laboratory, we tested the separate and combined effects of stress and variability by exposing corallines from the same sites to either ambient (Amb: pH 8.04) or acidified (OA: pH 7.70) stable conditions or variable (Var: pH 7.80-8.10) or acidified variable (OA-Var: pH 7.45–7.75) conditions. There was a negative effect of all pH treatments on Lithophyllum sp. calcification rates relative to the control, with lower calcification rates in corallines from the extreme site than from the moderate site in each treatment, indicative of a legacy effect of site origin on subsequent response to laboratory treatment. Our study provides ecologically relevant context to understanding the nuanced effects of OA on crustose coralline algae, and illustrates how local environmental regimes may influence the effects of global change.