Search Results (283)

Highly pathogenic avian influenza (HPAI) represents an enormous pandemic risk amid the ongoing H5N1 panzootic. HPAI, defined by its high lethality in domestic poultry, includes the influenza A virus (IAV) H5N1 and H7N9 subtypes and has a 40–50% case fatality rate in humans. To facilitate the development of efficacious HPAI vaccination regimens and isolation of HPAI-neutralizing monoclonal antibodies (nmAbs) for prophylactic and therapeutic use, we performed a proof-of-concept pilot study wherein we developed an array of mRNA and adenovirus-vectored vaccines encoding HPAI hemagglutinins (HAs) and then assessed their immunogenicity in IAV-naïve Indian rhesus macaques (RMs). All RMs developed binding IgG recognizing both HPAI HAs. HPAI-nAbs were detected in RMs vaccinated with full-length HAs, but not in RMs vaccinated with HA stems alone. Potent HPAI neutralization activity was observed in two animals with serum ID₅₀ titers of ~1:100,000 against H5N1 and ~1:50,000 against H7N9. Most RMs developed cross-reactive IgG recognizing the HAs of additional IAV subtypes, and HA-specific B cells were readily identifiable in vaccinee PBMCs by flow cytometric analysis. The results of our pilot study suggest that elicitation of potent HPAI-nAb responses is enhanced by vaccination with the HA head domain and that vaccination with the HA stem alone tends to elicit binding non-nAbs. Furthermore, use of our fluorophore-conjugated HA probes to identify HA-specific B cells could enable HPAI-nmAb isolation. Collectively, our findings could facilitate the development of novel vaccines and nmAb therapeutics leveraging the superior neutralization potency of HA head-specific Abs to prevent and treat HPAI infections in humans. Full article

Measurements are presented from a purpose-built outdoor test facility for the assurance of situational awareness sensors for Autonomous Vehicles (AVs). The testbed included meteorological instrumentation for an accurate high-resolution picture of weather traversing the site. Static targets at ranges up to 250 m were observed simultaneously with multiple radar, LiDAR and camera systems exposed to the natural weather events over a two-year period. The aim of the testbed was to collect data over a prolonged period of time to ensure the maximum amount of variation in weather was encountered. Uniquely, the testbed treats the measurement of weather as an equal metrology challenge to that of measuring the CAV sensor response with the aim of understanding the extent to which it is possible to quantitatively correlate sensor performance degradation with weather parameters. In this paper case study examples of the testbed data for rainfall, fog and ‘ideal’ neutral conditions have been analysed. Correlations between sensor performance degradation and weather parameters were observed in several cases, including comparisons with rain rate and MOR (visibility). However, large uncertainties and complex interactions between weather-related performance reduction and secondary weather effects, like sensor window and target surface wetting, make an explicit determination of the severity at which a weather condition causes a sensor to become untrustworthy, problematic. Full article

In 1980, the UNEP, IUCN, and WWF published the World Conservation Strategy (WCS). This was the first time that the United Nations, alongside an intergovernmental organization (IUCN) and NGO (WWF), identified a comprehensive set of global conservation priorities. An evaluation of the WCS after 45 years provides insights into global progress in conservation implementation and its intellectual contribution to international strategies, including the Kunming–Montreal Global Biodiversity Framework. We assess progress on the 13 priority requirements and 14 priority international actions identified in the WCS by evaluating achievements to date, persistent knowledge gaps, and how priorities have shifted over time. Whilst many of the policy and institutional frameworks identified in the WCS have been achieved, most of the key priorities remain, at best, only partially achieved, having progressed more slowly than hoped. In several cases, the situation has worsened. The only clear exception to this trend is the case of protected areas, which, although beset with imperfections that limit their effectiveness, have a coverage far larger than that envisaged in 1980. We explore why some actions have shown progress while others did not and reflect on lessons for future conservation strategies. Full article

Introduction: Community engagement offers an approach to improve our understanding of vaccine hesitancy, yet some worry that public engagement centered around controversial and politicized topics such as COVID-19 vaccines carries a risk of increasing concerns. Methods: Respondents who reported hesitance to vaccinate against COVID-19 in a December 2020 national panel survey were recruited to participate in three interactive and respectful virtual community engagement meetings. A second survey in September 2021 resampled respondents to ascertain changes over time. Of the 291 respondents to both survey waves who had been willing to participate in community meetings, 94 (32%) participated. Multivariate linear and logistic regressions were used to assess the potential impact of meeting participation on outcomes of interest. Results: At follow-up, participants had nearly double the odds of vaccinating against COVID-19 (adjusted Odds Ratio: 1.88; 95% Confidence Interval: 1.06–3.34), about one-third the odds of contracting COVID-19 disease (aOR: 0.37; 95% CI: 0.14–0.96), and increased trust in the Centers for Disease Control and Prevention (CDC) (adjusted Regression Coefficient: 4.16; 95% CI: 0.37–7.94), compared to non-participants. Most participants found the meetings unbiased (89%) and trustworthy (90%). Conclusions: The design of our community meetings to focus on learning from and supporting the decision-maker (versus only promoting “shots in arms”) improved health outcomes and increased trust. Similar meetings could improve how public health engages communities. Full article

Patients with multiple myeloma (MM) exhibit profound immune dysregulation, predisposing them to severe outcomes following SARS-CoV-2 infection. Current evidence highlights shared immunopathological mechanisms linking MM and COVID-19, with particular emphasis on the interleukin-6 (IL-6) axis as a shared amplifier of inflammation rather than the sole driver of disease. MM is characterized by a baseline pro-inflammatory milieu, in part mediated by IL-6, which is further amplified during SARS-CoV-2 infection, resulting in cytokine escalation, complement activation, coagulopathy, and multi-organ injury. This amplification operates within a broader, redundant network that also includes T-cell exhaustion, NK-cell dysfunction, checkpoint signaling, complement and endothelial injury, and treatment-induced immune defects. This overlap provides a mechanistic basis for the disproportionately high morbidity and mortality observed in this population. Even with advancements in vaccination, antiviral therapy, and clinical practice, patients with MM who exhibit impaired vaccine responses, active disease, or treatment-related immune dysfunction continue to experience considerable vulnerability to COVID-19. In addition, MM patients demonstrate suboptimal vaccine-induced immune responses, contributing to persistent vulnerability to severe and breakthrough infections. Modern MM therapies, including anti-CD38 antibodies, BCMA-directed agents, and bispecific T-cell redirecting antibodies, further reshape antiviral immunity by reducing NK cells, inducing plasma cell aplasia, causing hypogammaglobulinemia, and impairing T-cell function. Emerging treatment approaches targeting this shared pathway have been explored, with a focus on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). EVs exhibit multimodal properties, including suppression of pro-inflammatory cytokines, restoration of immune homeostasis, inhibition of viral entry, and promotion of tissue repair and regeneration. Early clinical experience in severe COVID-19 populations suggests a favorable short-term safety profile; reported efficacy, however, derives from small, largely uncontrolled or early-phase studies, and the single randomized trial reporting a mortality benefit did so only in an exploratory post hoc subgroup, with its pre-specified primary endpoint not met. Overall, EVs constitute a biologically plausible but as yet unproven adjunctive strategy that warrants further investigation. Critically, no MM patient has ever been enrolled in an EV trial; current rationale for EV use in MM is therefore extrapolated entirely from non-MM populations, and no MM-specific data exist. Difficulties such as EV heterogeneity, manufacturing variability, uncertain pharmacokinetics, limited targeting efficiency, and potential prothrombotic effects must be resolved before their application in MM-specific clinical settings. Full article

Background/Objectives: Current trends show a significant increase in Alzheimer’s disease and related dementias (ADRD) rates, reflecting a growing need for interventions. Recently, non-pharmacological interventions have received increased recognition as a viable option for ADRD prevention and disease modification. The current study focuses on a music-based community engagement program, titled B Sharp, to investigate the effects of music experiences on domain- and subtest-specific cognitive processing in ADRD. Methods: Participants were provided season tickets (six performances over ten months) to a local MasterWorks Symphony. Across the program’s three seasons (18 individual musical performances), a total of 55 individuals with ADRD participated. Subtest- and domain-specific changes in cognition were assessed before and after each individual symphony performance of 1.5–3 h duration. Variables of interest include auditory-verbal (N = 67) and visuospatial (N = 49) cognitive subtests. Results: In a comparison of pre- and post-symphony performance scores, results indicate statistically significant improvements on a visuospatial working memory task (Coding) (p = 0.021) and statistically significant decline on verbal working memory/immediate memory (List Learning/Story Memory) (p = 0.045). Significant differences were not observed on the remaining subtests. Discussion: Results suggest that even brief exposure to music results in cognitive benefits on visuospatial working memory and contribute to a body of findings which suggest that non-pharmacological arts-based programs may be beneficial for adults with ADRD for specific types of cognition, even for single or sporadic attendance. As research in arts programming increases, it is hoped that findings will guide how to apply various types of programs for specific cognitive deficits accompanying ADRD. Full article

Quintero is a Chilean coastal city located 40 km north of Valparaiso. In the surroundings of Quintero, there are a number of industries that generate high levels of atmospheric pollutants such as sulfur dioxide (SO₂), nitrogen oxides (NO_x), carbon monoxide (CO) and non-methane hydrocarbons (NMHCs). These compounds may also be generated during oil handling in storage facilities in this area. Quintero Bay has a port that is being used mainly for oil and copper transportation. Since 2010, there have been reports of events producing nausea, vomiting and abdominal pain in the residents of Quintero, and some previous studies have correlated these medical events with high concentrations of SO₂ and NMHCs. One of the main sources of SO₂ in the area was identified to be the Ventanas copper foundry. Following public pressure, the government stopped the operation of the foundry by mid-2023, which led to a significant decrease in SO₂ levels. However, reports of health problems persisted to some extent. In this work, delayed cross-correlation, trajectory and dispersion analyses indicate that an upwind source of air pollution impacting Quintero originates near the oil refinery in Concón, located 20 km to the south. This source of air pollution could provide a background of NMHCs, over which local emissions add up to attain very high concentrations in Quintero. Our analysis shows that there is evidence of the transport of NMHCs from the Concón refinery to the Quintero area. In 2022, of the 20 days with NMHC concentrations greater than 200 ppvb, 50% of them were associated with prevalent southwest winds. Using trajectory and dispersion analyses for eight episodes in Quintero, it has been found that an approximate fraction of pollution generated in Concón that could arrive in Quintero is between 2 and 24%. Full article

Staphylococcus aureus is a major bacterial pathogen that can cause clinical infections and foodborne illnesses through the production of 25 exotoxin types. The most frequently implicated toxins in food poisoning outbreaks are Staphylococcal enterotoxins type A–E (SEA-SEE), which are the first enterotoxins discovered. While in vitro detection methods are available to identify the presence of enterotoxins, they cannot distinguish between biologically active and inactive forms of the toxins. Detection of biologically active enterotoxins currently relies on in vivo testing, using the emetic response in kittens or monkeys. Here, we show the development of an in vitro assay to detect the active forms of SEB, a potential biological warfare agent and leading cause of food poisoning, and SEC1, a frequent cause of staphylococcal food poisoning. The novel assay involves the implementation of a genetically engineered Jurkat T-cell line expressing TCR Vβ3, resulting in a dose response of IL-2 production when exposed to active toxin. We also show that at a concentration of 100 ng/mL, the biological activity of SEB is significantly decreased at temperatures over 70 °C, while pasteurization at 63 °C only slightly reduces the biological activity of the toxin. Our studies provide an alternative method to animal testing to determine the presence of active toxins and provide possible inactivation methods of the toxins. Full article

Ribosome-inactivating proteins are a class of toxins that target eukaryotic ribosomes, inhibit protein synthesis, and ultimately induce cell death. Several of these toxins pose significant clinical and public health threats. Among these, ricin, derived from the castor bean plant (Ricinus communis), is a highly potent biotoxin with recognized bioterrorism potential. Other ribosome-inactivating proteins, including Shiga toxin produced by pathogenic Shigella and Escherichia coli, as well as mucoricin from Mucorales fungi, contribute to disease severity and can lead to life-threatening complications. Despite these risks, no approved therapeutics are currently available. The development of effective inhibitors depends on robust and well-defined strategies to identify and validate small molecules that disrupt toxin–ribosome interactions. Efforts to target the catalytic active site have met with limited success, largely due to its broad, shallow, and highly polar architecture, which is not conducive to high-affinity binding by drug-like molecules. In contrast, the ribosome-binding interface represents a more tractable target, as it is essential for toxin recruitment and offers more structurally defined and druggable features. Inhibitors targeting this interface can also exert allosteric effects by disrupting long-range conformational coupling between the ribosome-binding region and the active site, thereby attenuating catalytic activity without directly engaging the catalytic pocket. In this review, we compile and evaluate biophysical and biochemical assays for the discovery and characterization of small-molecule inhibitors that target toxin–ribosome interactions. We examine in vitro binding approaches, including surface plasmon resonance-based fragment screening and fluorescence anisotropy assays for ranking inhibitory activity. We further review biochemical and molecular assays that assess ribosome protection from toxin-mediated depurination, along with complementary cell-based assays that evaluate functional rescue in cellular systems. Collectively, this review consolidates current screening methodologies and highlights opportunities to refine assay strategies, thereby supporting the advancement of targeted therapeutics. Full article

Objective: Traumatic brain injury (TBI) is disproportionately prevalent in incarcerated populations, yet the potential impact on cognitive functioning remains underexplored. This study examined the relationship between TBI history and cognitive performance in a male prison population. Method: Sixty-three participants from Tongariro Prison completed a comprehensive neuropsychological assessment including measures of executive function, memory, processing speed, and perceptual reasoning, with embedded performance validity metrics. TBI history was assessed using the Ohio State University TBI Identification Method (OSU-TBI ID), premorbid function was assessed using the Speed and Capacity of Language Processing (SCOLP) Spot-the-Word task, mood was assessed using the Depression, Anxiety and Stress Scales (DASS-21), and alcohol and substance use were measured using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Regression analyses explored the relationship between TBI history and cognitive functioning, controlling for premorbid function, mood, alcohol and substance use, and ethnicity. Results: Contrary to hypotheses, TBI frequency and severity were not associated with poorer cognitive performance in this population. However, a self-reported history of pervasive TBI—defined as repeated head impacts over a narrow time frame—was significantly associated with reduced performance on the Color–Word Interference Test (CWIT) inhibition task, indicating links to greater cognitive disinhibition. Conclusions: Findings suggest that experiencing at least one period of pervasive TBI may be associated with an impact on inhibition (but not other aspects of executive functioning) in men in prison. These results underscore the importance of nuanced TBI history assessment and highlight inhibition as a potential target for rehabilitation in incarcerated individuals exposed to repetitive head trauma. Full article

Urban air quality management has been playing a significant role due to its effects on public health and pollution characteristics of countries with constantly changing policies. Traditional approaches capture how much pollution is present but are unable to detect changes in the chemical character of the atmosphere, the relationships between co-emitted species, the balance of photochemical processing, and the combustion fingerprint of emission sources. This study introduces a framework that identifies and diagnoses such evolutions within the pollutants of the atmosphere. A chemistry-aware Variational Autoencoder is trained on 19 multivariate pollution features (7 raw concentrations, 5 chemical ratios, 7 temporal gradients) at London Marylebone Road (urban roadside) and North Kensington (urban background) from 2015 to 2019, and tested on 2022–2025. A four-method ensemble framework (VAE reconstruction error, reconstruction probability, Isolation Forest, and statistical Z-score) requires ≥3 agreement to identify high-confidence departed pollution states. Per-feature decomposition of the reconstruction probability diagnoses the chemical character of each departure. At the roadside site, 14.5% of post-COVID hours fall within departed states, dominated by the CO/NO_x combustion ratio (513.2) and the photostationary state proxy (391.4), chemical relationships rather than individual concentrations. This indicates that at the point of emission, London’s fleet modernisation and Ultra Low Emission Zone (ULEZ) have changed the combustion fingerprint and photochemical equilibrium. The same structural indicators are carried over during the COVID-19 lockdown; however, O₃ rises 3.2× during the pandemic period, reflecting suppressed NO titration. Conversely, at the urban background site, where the departures are driven by concentrations and boundary-layer trapping ($r=-0.659$), the combustion fingerprint of the atmosphere is invisible to detect (CO/NO_x$=-45.0$). These findings indicate that London’s emission landscape has undergone fundamental transformations over the past decade, and the consequences of ULEZ and similar interventions or greater impacts of pandemic-related events are non-homogeneously distributed across the relevant region. Full article

Arthritis (RA) is characterized by immune-mediated chronic inflammation and endothelial dysfunction, ultimately resulting in clinically overt cardiovascular complications. As a prototypical disease of microvascular dysfunction, RA represents an ideal model to study microvascular alterations. The dermal capillary network offers an easily accessible window to the peripheral microcirculation, whose function can be easily assessed using Nailfold videocapillaroscopy (NVC) or laser techniques. Whereas the clinical significance of structural alterations is not always clear, functional abnormalities may provide more direct insight into the dynamic status of the microvasculature and endothelial integrity. The present narrative review aims to provide an integrative overview of available studies evaluating functional abnormalities of the dermal microcirculation in RA, with particular emphasis on the emerging role of NVC as a dynamic vascular assessment tool. Several studies in RA have assessed the structure and morphology of the peripheral microvasculature using NVC, but far fewer data exist on functional alterations assessed with this method. The study of functional alterations of the dermal microvascular network in RA has largely been based on laser techniques, which consistently point towards altered microvascular reactivity. By contrast, functional NVC-related approaches remain limited, despite their potential ability to simultaneously assess structural and dynamic capillary abnormalities in vivo. Available evidence supports that NVC may be reframed as a promising functional vascular biomarker in RA. However, the available literature is characterized by small sample sizes, predominantly cross-sectional designs, and methodological heterogeneity, highlighting the need for standardized prospective studies. Full article

Annually, there are more than two million deaths from liver disease. This is driven by organ inflammation and scarring, leading to a decline in function and regeneration. Frequently, this can develop into decompensated liver disease, resulting in the loss of physiological balance and toxin build-up within the body, with an increased risk of patient mortality. Currently, there are no approved medicines for the long-term treatment of liver cirrhosis. The only successful treatment option for end-stage liver disease patients is donor organ transplantation. However, patient requirement outstrips the number of donated organs. To address this bottleneck, researchers around the world have developed cell-based prototype systems to restore failing liver function, with some in clinical trials. Although significant progress has been made, no mainstream commercial liver assist products are available for routine clinical use. In this study we developed a stem cell-derived vascularized liver tissue implant prototype from pluripotent cells. The liver tissue was produced from a stem cell line that is banked at clinical grade, and displayed stable and mature liver function over a 6-week period in vitro. This included decreasing levels of the fetal marker, alpha-fetoprotein, when the serum albumin increased. This was further supported by stable alpha-1-antitrypsin secretion and cytochrome P450 function. Following the establishment of stable liver tissue, it was delivered as a cell product or attached to an electrospun polycaprolactone scaffold, to form a tissue implant. Next, cellular material was quality-controlled, and subsequently shipped to a contract research organization for external in vivo validation. The transplanted liver tissue functioned when implanted into the kidney capsule and subcutaneously, remaining functional for up to two weeks in vivo. Full article

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Epidemiologic evidence increasingly indicates that women with PCOS exhibit elevated risk of ischaemic stroke. Unlike prior reviews that have focused predominantly on general cardiovascular risk in PCOS, this review specifically examines ischaemic stroke risk, its mechanistic links, and the extent to which current stroke and cardiovascular frameworks fail to account for PCOS. We conducted a narrative review examining the association of PCOS on ischaemic stroke and cardiovascular disease (CVD). Large-scale cohort studies and meta-analyses from 2000 to 2025 were identified from Medline, Embase, PubMed, and Google Scholar, with specific emphasis on ischaemic stroke in women with PCOS. Case reports and case series were excluded. There is substantial evidence supporting the relationship between PCOS and increased vascular risk. Large-scale cohort studies and meta-analyses report higher rates of cerebrovascular events among women with PCOS. A recent 2025 meta-analysis pooling 11 studies reported a statistically significantly increased risk of stroke in women with PCOS (OR = 1.89, 95% CI = 1.22–2.55), although heterogeneity was high (I² = 97.7%), indicating important variation in study design, populations, and confounder adjustment. Other meta-analyses report more modest associations, and some studies did not demonstrate significant associations with myocardial infarction or all-cause mortality. Several analyses also showed attenuation of risk following adjustment for body mass index and metabolic factors. The observed association between PCOS and vascular risk should be interpreted with caution, given substantial heterogeneity and potential confounding by cardiometabolic factors. These findings raise the possibility that increased risk may be mediated through established pathways such as obesity, insulin resistance, and dyslipidaemia rather than representing a consistently independent effect. Despite this, PCOS remains inconsistently recognised within clinical frameworks. Current stroke guidelines and widely used risk prediction tools, including QRISK3 and the Essen Stroke Risk Score, do not incorporate PCOS, highlighting a potential gap in sex-specific risk assessment. Evidence demonstrating that inclusion of PCOS improves risk prediction or clinical outcomes remains limited. However, under-recognition of vascular risk in women with PCOS may limit timely risk assessment and intervention. This review highlights a number of implementation gaps globally, including gaps in research and inter-disciplinary communication. Priority next steps include prospective studies to clarify whether PCOS independently contributes to vascular risk, and predictive modelling studies to determine whether including PCOS improves risk stratification. In parallel, multidisciplinary care pathways may support earlier identification and prevention in higher-risk women. Full article

Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs—including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)—emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks. Full article