Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.

TAPSE/sPAP prognostic value for In-Hospital Adverse Events in Patients Hospitalized for Acute Coronary Syndrome.

AIMS: Although several studies have shown that the right ventricular to pulmonary artery (RV-PA) coupling, assessed by the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) using echocardiography, is strongly associated with cardiovascular events, its prognostic value is not established in acute coronary syndrome (ACS). We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for ACS in a retrospective analysis from the prospective ADDICT-ICCU study. METHODS AND RESULTS: 481 consecutive patients hospitalized in intensive cardiac care unit (mean age 65±13 years, 73% of male, 46% STEMI) for ACS (either ST-elevation [STEMI] or non-ST-elevation [NSTEMI] myocardial infarction) with TAPSE/sPAP available were included in this prospective French multicentric study (39 centers). The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 33 (7%) patients. ROC-curve analysis identified 0.55 mm/mmHg as the best TAPSE/sPAP cut-off to predict in-hospital MACEs. TAPSE/sPAP <0.55 was associated with in-hospital MACEs, even after adjustment with comorbidities (OR:19.1, 95%CI[7.78-54.8]), clinical severity including left ventricular ejection fraction (OR:14.4, 95%CI[5.70-41.7]) and propensity-matched population analysis (OR:22.8, 95%CI[7.83-97.2], all p<0.001). After adjustment, TAPSE/sPAP <0.55 showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.16; global chi-square improvement: 52.8; LR-test p<0.001) with similar results for both STEMI and NSTEMI subgroups. CONCLUSION: A low RV-PA coupling defined as TAPSE/sPAP ratio <0.55 was independently associated with in-hospital MACEs and provided incremental prognostic value over traditional prognosticators in patients hospitalized for ACS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

Mapping of susceptibility loci for Ebola virus pathogenesis in mice.

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.

An interplay between Ni and Brønsted and Lewis acid sites in the hydrodesulfurization of dibenzothiophene.

NiMo-S2/γ-Al2O3 catalysts are commonly used in hydrotreating to enhance fossil fuel quality. The extensive research on these catalysts reveals a gap in understanding the role of Ni, often underestimated as an inactive sulfide phase or just a MoS2 promoter. In this work, we focused on analyzing whether well-dispersed supported nickel nanoparticles can be active in the hydrodesulfurization of dibenzothiophene. We dispersed Ni by the Strong Electrostatic Adsorption (SEA) method over four supports with different types of acidity: silica (~ neutral acidity), γ-Al2O3 (Lewis acidity), H+-Y zeolite, and microporous-mesoporous H+-Y zeolite (both with Brønsted-Lewis acidity). Our findings reveal that Ni is indeed active in dibenzothiophene hydrodesulfurization, even with alumina and silica as supports, although their catalytic activity declines abruptly in the first hours. Contrastingly, the acid nature of zeolites imparts sustained stability and performance, attributed to robust metal-support interactions. The efficacy of the SEA method and the added mesoporosity in zeolites further amplify catalytic efficiency. Overall, we demonstrate that Ni nanoparticles may perform as a hydrogenating metal in the same manner as noble metals such as Pt and Pd perform in hydrodesulfurization. We discuss some of the probable reasons for such performance and remark on the role of Ni in hydrotreatment.

Innovative Metaheuristic Optimization Approach with a Bi-Triad for Rehabilitation Exoskeletons.

The present work proposes a comprehensive metaheuristic methodology for the development of a medical robot for the upper limb rehabilitation, which includes the topological optimization of the device, kinematic models (5 DOF), human-robot interface, control and experimental tests. This methodology applies two cutting-edge triads: (1) the three points of view in engineering design (client, designer and community) and (2) the triad formed by three pillars of Industry 4.0 (autonomous machines and systems, additive manufacturing and simulation of virtual environments). By applying the proposed procedure, a robotic mechanism was obtained with a reduction of more than 40% of its initial weight and a human-robot interface with three modes of operation and a biomechanically viable kinematic model for humans. The digital twin instance and its evaluation through therapeutic routines with and without disturbances was assessed; the average RMSEs obtained were 0.08 rad and 0.11 rad, respectively. The proposed methodology is applicable to any medical robot, providing a versatile and effective solution for optimizing the design and development of healthcare devices. It adopts an innovative and scalable approach to enhance their processes.

Profiling wastewater characteristics in intra-urban catchments using online monitoring stations.

This study aims to investigate the differences in intra-urban catchments with different characteristics through real-time wastewater monitoring. Monitoring stations were installed in three neighbourhoods of Barcelona to measure flow, total chemical oxygen demand (COD), pH, conductivity, temperature, and bisulfide (HS-) for 1 year. Typical wastewater profiles were obtained for weekdays, weekends, and holidays in the summer and winter seasons. The results reveal differences in waking up times and evening routines, commuting behaviour during weekends and holidays, and water consumption. The pollutant profiles contribute to a better understanding of pollution generation in households and catchment activities. Flows and COD correlate well at all stations, but there are differences in conductivity and HS- at the station level. The article concludes by discussing the operational experience of the monitoring stations.

Mutations spike in a reservoir of compromised immunity.

The hierarchy of immunosuppression predicts SARS-CoV-2 time to clearance and intrahost viral evolution.

Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis.

INTRODUCTION: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer. METHODS AND ANALYSIS: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis. ETHICS AND DISCLOSURE: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235163.

[Androgenetic alopecia: where do we stand in 2024?] / Alopécie androgénétique : où en est-on en 2024 ?

Androgenetic alopecia, the most prevalent type of hair loss, is characterized by a receding hairline in men and diffuse thinning of hair in women. Despite being considered a benign condition, it can exert a considerable psychological toll, especially on women and young men. Despite its high prevalence, only a limited number of medications have received approval for its treatment. In this article, we review the available treatment options, assessing their efficacy and potential side effects. Additionally, we explore minimally-invasive strategies such as photobiomodulation, micro-needling and platelet-rich plasma therapy. Furthermore, we delve into discussions on hair transplantation and camouflage methods.

L'alopécie androgénétique (AAG) est la forme la plus fréquente de perte de cheveux, caractérisée par le recul de la ligne frontale des cheveux chez les hommes et l'élargissement des lignes de partage des cheveux chez les femmes avec épargne de la ligne frontale. L'AAG, considérée comme une pathologie bénigne, a toutefois un impact psychologique pouvant être très important, notamment chez les femmes et les jeunes hommes. Bien qu'il s'agisse d'une entité très répandue, peu de médicaments sont approuvés pour son traitement. Dans cet article, nous parcourons les différentes options thérapeutiques disponibles, leurs efficacités et effets secondaires ainsi que les traitements minimalement invasifs tels que la photobiomodulation, aiguilletage de la peau ou encore le plasma riche en plaquettes. Nous discutons également de la greffe capillaire et des méthodes de camouflages.

mRNA-LNP vaccine-induced CD8+ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies.

The role of CD8+ T cells in SARS-CoV-2 pathogenesis or mRNA-LNP vaccine-induced protection from lethal COVID-19 is unclear. Using mouse-adapted SARS-CoV-2 virus (MA30) in C57BL/6 mice, we show that CD8+ T cells are unnecessary for the intrinsic resistance of female or the susceptibility of male mice to lethal SARS-CoV-2 infection. Also, mice immunized with a di-proline prefusion-stabilized full-length SARS-CoV-2 Spike (S-2P) mRNA-LNP vaccine, which induces Spike-specific antibodies and CD8+ T cells specific for the Spike-derived VNFNFNGL peptide, are protected from SARS-CoV-2 infection-induced lethality and weight loss, while mice vaccinated with mRNA-LNPs encoding only VNFNFNGL are protected from lethality but not weight loss. CD8+ T cell depletion ablates protection in VNFNFNGL but not in S-2P mRNA-LNP-vaccinated mice. Therefore, mRNA-LNP vaccine-induced CD8+ T cells are dispensable when protective antibodies are present but essential for survival in their absence. Hence, vaccine-induced CD8+ T cells may be critical to protect against SARS-CoV-2 variants that mutate epitopes targeted by protective antibodies.

Systematic research is needed on the potential effects of lifelong technology experience on cognition: a mini-review and recommendations.

Digital technology now occupies a fundamental space in human life. Increasingly sophisticated access to information and social interactions has enabled a sort of offloading of many aspects of cognition, and for many people, this technology use has been lifelong. While the global development of technologies advances exponentially as part of the Fourth Industrial Revolution, researchers have not yet fully characterized the human effects of this technology-centric revolution at the same pace. In this mini-review, we consider three important higher-level cognitive functions: creativity, adaptability, and decision-making, and discuss their potential relationship to lifelong digital technology experience, which here includes both passive exposure and active use of electronic devices. We then articulate the gaps in related literature and knowledge, and outline general considerations, suggestions, and challenges for future research avenues. In general, we found that prior research has investigated uses of specific technology products on lower-level cognition (e.g., how does the use of online search engines affect memory?), but there is a lack of research assessing the overall effects of technology experience on cognitive functioning, particularly complex cognition.

Cryo-EM structures of type IV pili complexed with nanobodies reveal immune escape mechanisms.

Type IV pili (T4P) are prevalent, polymeric surface structures in pathogenic bacteria, making them ideal targets for effective vaccines. However, bacteria have evolved efficient strategies to evade type IV pili-directed antibody responses. Neisseria meningitidis are prototypical type IV pili-expressing Gram-negative bacteria responsible for life threatening sepsis and meningitis. This species has evolved several genetic strategies to modify the surface of its type IV pili, changing pilin subunit amino acid sequence, nature of glycosylation and phosphoforms, but how these modifications affect antibody binding at the structural level is still unknown. Here, to explore this question, we determine cryo-electron microscopy (cryo-EM) structures of pili of different sequence types with sufficiently high resolution to visualize posttranslational modifications. We then generate nanobodies directed against type IV pili which alter pilus function in vitro and in vivo. Cyro-EM in combination with molecular dynamics simulation of the nanobody-pilus complexes reveals how the different types of pili surface modifications alter nanobody binding. Our findings shed light on the impressive complementarity between the different strategies used by bacteria to avoid antibody binding. Importantly, we also show that structural information can be used to make informed modifications in nanobodies as countermeasures to these immune evasion mechanisms.

Excess Mortality During 2020 in Spain: The Most Affected Population, Age, and Educational Group by the COVID-19 Pandemic.

OBJECTIVE: The objective of this work was to study mortality increase in Spain during the first and second academic semesters of 2020, coinciding with the first 2 waves of the Covid-19 pandemic; by sex, age, and education. METHODS: An observational study was carried out, using linked populations and deaths' data from 2017 to 2020. The mortality rates from all causes and leading causes other than Covid-19 during each semester of 2020, compared to the 2017-2019 averages for the same semester, was also estimated. Mortality rate ratios (MRR) and differences were used for comparison. RESULTS: All-cause mortality rates increased in 2020 compared to pre-covid, except among working-age, (25-64 years) highly-educated women. Such increases were larger in lower-educated people between the working age range, in both 2020 semesters, but not at other ages. In the elderly, the MMR in the first semester in women and men were respectively, 1.14, and 1.25 among lower-educated people, and 1.28 and 1.23 among highly-educated people. In the second semester, the MMR were 1.12 in both sexes among lower-educated people and 1.13 in women and 1.16 in men among highly-educated people. CONCLUSION: Lower-educated people within working age and highly-educated people at older ages showed the greatest increase in all-cause mortality in 2020, compared to the pre-pandemic period.

Combination of different noninvasive brain stimulation treatments for upper limb recovery in stroke patients: A systematic review.

We report a review of Pubmed (Medline), CENTRAL, Web of Science, and Scopus to test the effectiveness of the combined application of repetitive transcranial magnetic stimulation and transcranial direct current stimulation in the improvement of different functional variables of the upper limb in people with stroke. Two independent reviewers assessed eligibility and evaluated the quality of the studies. Five articles were included in the final review according to the inclusion criteria: Most show statistically significant differences in motor function improvement in favor of the experimental group, but not in activity. Due to the heterogeneity of the observed studies, the results should be interpreted with caution-more high-quality studies are needed to investigate the effectiveness of these interventions in different stages of stroke patients.

Thiourea-Based Receptors for Anion Recognition and Signaling.

This work reports on two thiourea-based receptors with pyridine and amine units including 1-naphthyl (MT1N) and 4-nytrophenyl (MT4N) as signaling units. For both compounds, their affinity and signaling ability toward various anions of different geometry and basicity in DMSO were studied using UV-vis, fluorescence, and 1H NMR techniques. Anion recognition studies revealed that both MT1N and MT4N have, in general, high affinities toward basic anions. In this regard, a higher acidity of the MT4N receptor was demonstrated. Furthermore, MT4N has a higher affinity for fluoride (log K1 = 5.98) than for the other anions and can effectively detect it through colorimetric changes that can be monitored by the UV-vis technique. The interaction between receptors and anions mainly involves the hydrogens of the amino and thiourea groups of the former. Complementary single-crystal X-ray diffraction studies and molecular modeling at the DFT level were also performed.

Assessment of asbestos-cement roof distribution and prioritized intervention approaches through hyperspectral imaging.

The discernment of asbestos-cement (AC) roofs within urban areas stands as a pivotal concern pertinent to communal well-being and ecological oversight, particularly in emerging nations where asbestos continues to be extensively employed. Conventional methodologies entailing the recognition of asbestos-cement roofs and the characterization of their degradation status, such as tangible examinations and laboratory assays, prove to be temporally protracted, financially demanding, and arduous to extrapolate comprehensively across expansive urban domains. In this paper, it is presented a novel approach for identifying asbestos-cement roofs in urban areas using hyperspectral airborne acquisition and carry out a diagnosis that allows to identify the state of asbestos-cement roofs and thus provide a tool for the competent authorities to develop and prioritize intervention strategies to mitigate the problem. Four different methodologies were implemented and compared, three of which are new in the literature, to identify the deterioration of asbestos-cement (AC) roof state in large urban areas. This, in turn, furnishes a tool for competent authorities to identify the state of AC roofs, develop and prioritize intervention strategies to mitigate the problem. The control points in field allowed validating the classification and the proposed methodology for the prioritization of intervention in AC roofs. Some neighborhoods in the city showed peaks in the area of asbestos-cement roofs of 47% of the total area of the neighborhood, representing practically all of the roofs present in the neighborhood. On average around 20% of the total area of a neighborhood in Cartagena is covered by AC. Furthermore, it was found a total area of AC roofs throughout the city of more than 9 km2 (9 million square meters). On the other hand, two of the 4 methods used showed encouraging results that demonstrate their ability to identify covers in poor and good condition at a large scale from hyperspectral images. This academic novelty suggests that there is a possibility of practical application of these methods in other urban contexts with high concentrations of AC roofs, helping in the planning and optimization of intervention strategies to mitigate the risk in public and environmental health due to the presence of asbestos.

Simple visualization of submicroscopic protein clusters with a phase-separation-based fluorescent reporter.

Protein clustering plays numerous roles in cell physiology and disease. However, protein oligomers can be difficult to detect because they are often too small to appear as puncta in conventional fluorescence microscopy. Here, we describe a fluorescent reporter strategy that detects protein clusters with high sensitivity called CluMPS (clusters magnified by phase separation). A CluMPS reporter detects and visually amplifies even small clusters of a binding partner, generating large, quantifiable fluorescence condensates. We use computational modeling and optogenetic clustering to demonstrate that CluMPS can detect small oligomers and behaves rationally according to key system parameters. CluMPS detected small aggregates of pathological proteins where the corresponding GFP fusions appeared diffuse. CluMPS also detected and tracked clusters of unmodified and tagged endogenous proteins, and orthogonal CluMPS probes could be multiplexed in cells. CluMPS provides a powerful yet straightforward approach to observe higher-order protein assembly in its native cellular context. A record of this paper's transparent peer review process is included in the supplemental information.