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Dietary proteins are taken up by intestinal dendritic cells (DCs), cleaved into peptides, loaded to major histocompatibility complexes, and presented to T cells to generate an immune response. Amino acid (AA)-diets do not have the same effects because AAs cannot bind to major histocompatibility complex to activate T cells. Here, we show that impairment in regulatory T cell generation and loss of tolerance in mice fed a diet lacking whole protein is associated with major transcriptional changes in intestinal DCs including downregulation of genes related to DC maturation, activation and decreased gene expression of immune checkpoint molecules. Moreover, the AA-diet had a profound effect on microbiome composition, including an increase in Akkermansia muciniphilia and Oscillibacter and a decrease in Lactococcus lactis and Bifidobacterium. Although microbiome transfer experiments showed that AA-driven microbiome modulates intestinal DC gene expression, most of the unique transcriptional change in DC was linked to the absence of whole protein in the diet. Our findings highlight the importance of dietary proteins for intestinal DC function and mucosal tolerance., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Heat can vary spatially within an urban area. Individual-level heat exposure may thus depend on an individual's day-to-day travel patterns (also called mobility patterns or activity space), yet heat exposure is commonly measured based on place of residence., Objective: In this study, we compared measures assessing exposure to two heat indicators using place of residence with those defined considering participants' day-to-day mobility patterns., Methods: Participants (n = 599; aged 35-80 years old [mean =59 years]) from San Diego County, California wore a GPS device to measure their day-to-day travel over 14-day intervals between 2014-10-17 and 2017-10-06. We measured exposure to two heat indicators (land-surface temperature [LST] and air temperature) using an approach considering their mobility patterns and an approach considering only their place of residence. We compared participant mean and maximum exposure values from each method for each indicator., Results: The overall mobility-based mean LST exposure (34.7 °C) was almost equivalent to the corresponding residence-based mean (34.8 °C; mean difference in means = -0.09 °C). Similarly, the mean difference between the overall mobility-based mean air temperature exposure (19.2 °C) and the corresponding residence-based mean (19.2 °C) was negligible (-0.02 °C). Meaningful differences emerged, however, when comparing maximums, particularly for LST. The mean mobility-based maximum LST was 40.3 °C compared with a mean residence-based maximum of 35.8 °C, a difference of 4.51 °C. The difference in maximums was considerably smaller for air temperature (mean = 0.40 °C; SD = 1.41 °C) but nevertheless greater than the corresponding difference in means., Impact: As the climate warms, assessment of heat exposure both at and away from home is important for understanding its health impacts. We compared two approaches to estimate exposure to two heat measures (land surface temperature and air temperature). The first approach only considered exposure at home, and the second considered day-to-day travel. Considering the average exposure estimated by each approach, the results were almost identical. Considering the maximum exposure experienced (specific definition in text), the differences between the two approaches were more considerable, especially for land surface temperature., (© 2024. The Author(s).)

In retinopathy of prematurity (ROP) type I, the use of intravitreal bevacizumab (IVB), which is an inhibitor of endothelial growth factor (VEGF), has become popular despite not being a therapy approved by regulatory agencies. However, IVB has shown positive effects in halting disease progression at lower costs compared to other anti-VEGF therapies (ranibizumab or aflibercept). In this report, we present the experience during the treatment with IVB of 102 Colombian children with ROP type I, with a success rate of 98% (100). Complications occurred in 3.9% (4). Finally, we conclude that a single dose of IVB is an effective therapy for the management of ROP type I, with a lower risk of complications and retreatment., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cunningham, Kirk, Hong, Yang, Howard, Brearley, Sáenz-Trevizo, Krawchuck, Watt, Henderson, Dokladny, DeAguero, Escobar and Wagner.)

Background: Precipitation could affect the transmission of diarrheal diseases. The diverse precipitation patterns across different climates might influence the degree of diarrheal risk from precipitation. This study determined the associations between precipitation and diarrheal mortality in tropical, temperate, and arid climate regions., Methods: Daily counts of diarrheal mortality and 28-day cumulative precipitation from 1997 to 2019 were analyzed across 29 locations in eight middle-income countries (Argentina, Brazil, Costa Rica, India, Peru, the Philippines, South Africa, and Thailand). A two-stage approach was employed: the first stage is conditional Poisson regression models for each location, and the second stage is meta-analysis for pooling location-specific coefficients by climate zone., Results: In tropical climates, higher precipitation increases the risk of diarrheal mortality. Under extremely wet conditions (95th percentile of 28-day cumulative precipitation), diarrheal mortality increased by 17.8% (95% confidence interval [CI] = 10.4%, 25.7%) compared with minimum-risk precipitation. For temperate and arid climates, diarrheal mortality increases in both dry and wet conditions. In extremely dry conditions (fifth percentile of 28-day cumulative precipitation), diarrheal mortality risk increases by 3.8% (95% CI = 1.2%, 6.5%) for temperate and 5.5% (95% CI = 1.0%, 10.2%) for arid climates. Similarly, under extremely wet conditions, diarrheal mortality risk increases by 2.5% (95% CI = -0.1%, 5.1%) for temperate and 4.1% (95% CI = 1.1%, 7.3%) for arid climates., Conclusions: Associations between precipitation and diarrheal mortality exhibit variations across different climate zones. It is crucial to consider climate-specific variations when generating global projections of future precipitation-related diarrheal mortality., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

CD8 + T cells must persist and function in diverse tumor microenvironments to exert their effects. Thus, understanding common underlying expression programs could better inform the next generation of immunotherapies. We apply a generalizable matrix factorization algorithm that recovers both shared and context-specific expression programs from diverse datasets to a single-cell RNA sequencing (scRNA-seq) compendium of 33,161 CD8 + T cells from 132 patients with seven human cancers. Our meta-single-cell analyses uncover a pan-cancer T cell dysfunction program that predicts clinical non-response to checkpoint blockade in melanoma and highlights CXCR6 as a pan-cancer marker of chronically activated T cells. Cxcr6 is trans-activated by AP-1 and repressed by TCF1. Using mouse models, we show that Cxcr6 deletion in CD8 + T cells increases apoptosis of PD1 + TIM3 + cells, dampens CD28 signaling, and compromises tumor growth control. Our study uncovers a TCF1:CXCR6 axis that counterbalances PD1-mediated suppression of CD8 + cell responses and is essential for effective anti-tumor immunity., Competing Interests: Declaration of interests A.C.A. is a member of the SAB for Tizona Therapeutics, Trishula Therapeutics, Compass Therapeutics, ExcepGen, and Zumutor Biologics, which have interests in cancer immunotherapy. A.C.A. is also a paid consultant for iTeos Therapeutics and Larkspur Biosciences. A.C.A.’s interests were reviewed and managed by the Brigham and Women’s Hospital and Partners Healthcare in accordance with their conflict-of-interest policies. O.R.-R. is an employee of Genentech. A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was an SAB member of Thermo Fisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov. From August 1, 2020, A.R. is an employee of Genentech and has equity in Roche. When at the Broad, A.R.’s interests were reviewed and managed by the Broad Institute, MIT and HHMI in accordance with their conflict-of-interest policies. A provisional patent application was filed including work in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: fast peritoneal transport (FT) has been associated with peritoneal albumin loss and protein energy wasting (PEW); however, this relationship has not been fully studied., Aim: the aim of this study was to analyze the differences in nutritional parameters between fast-transport peritoneal membrane (FT-PET) and slow-transport peritoneal membrane (ST-PET), and analyze the association between FT-PET and PEW in peritoneal dialysis (PD) patients., Methods: a cross-sectional study of patients on PD. Peritoneal transport characteristics were assessed using the peritoneal equilibration test (PET). Malnutrition inflammation score (MIS) was used for PEW identification. Clinical and biochemical characteristics between patients with and without PEW were assessed. Association between FT-PET status and PEW were evaluated using univariate and multivariate logistic regression., Results: a total of 143 patients were included. FT-PET group showed a higher prevalence of hypoalbuminemia, edema, lower phase angle, lower energy intake, and higher values of MIS score. FT-PET was significantly associated with PEW on univariate (OR: 3.5, 95 % CI: 1.56-7.83, p = 0.002) and multivariate models (OR: 2.6, 95 % CI: 1.02-6.6, p = 0.04). This association was maintained in patients where baseline PET was performed after initiating PD therapy (OR: 6.2, 95 % CI: 1.01-38.6, p = 0.04)., Conclusion: FT-PET is associated with PEW evaluated by MIS score. Clinical trials to study nutritional interventions personalized to peritoneal-membrane transport characteristics should be designed.

Background: Climate change is expected to greatly increase exposure to flooding, particularly in urban populations in low- and middle-income countries. We examined within-city social disparities in exposure to flooding in 276 Latin American cities and associated features of the neighborhood urban environment., Methods: We used a spatially granular dataset of historical flood events from 2000 to 2018 to describe neighborhood flooding within cities across eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala, Mexico, and Panama). We estimated the percentage of the population living in flooded neighborhoods, described social disparities in flooding based on neighborhood educational attainment, and compared the magnitude of disparities across and within cities. We used multilevel models to examine how city- and neighborhood-level factors are related to neighborhood flooding., Results: We examined 44,698 neighborhoods in 276 cities from eight countries with a total of 223 million residents and 117 distinct flood events from 2000-2018. One in four residents in neighborhoods in the lowest education quintile lived in neighborhoods with flooding, compared to one in 20 residents of the highest neighborhood education quintile. Greater neighborhood flooding was associated with lower neighborhood-level educational attainment and with neighborhoods that were coastal, less dense (population or intersection), further from the city center, greener, and had steeper slopes. There was no association between city-level educational attainment and flooding., Conclusion: There are large social disparities in neighborhood flooding within Latin American cities. Residents of areas with lower education attainment face substantially higher risks of flooding. Policymakers must prioritize flood adaptation and recovery efforts in neighborhoods with lower socioeconomic position.

We present the design, fabrication, and testing of a low-cost, miniaturized detection system that utilizes chemiluminescence to measure the presence of adenosine triphosphate (ATP), the energy unit in biological systems, in water samples. The ATP-luciferin chemiluminescent solution was faced to a silicon photomultiplier (SiPM) for highly sensitive real-time detection. This system can detect ATP concentrations as low as 0.2 nM, with a sensitivity of 79.5 A/M. Additionally, it offers rapid response times and can measure the characteristic time required for reactant diffusion and mixing within the reaction volume, determined to be 0.3 ± 0.1 s. This corresponds to a diffusion velocity of approximately 44 ± 14 mm 2 /s.

Objectives: This study aims to estimate the short-term preventable mortality and associated economic costs of complying with the World Health Organization (WHO) air quality guidelines (AQGs) limit values for PM 10 and PM 2.5 in nine major Latin American cities., Methods: We estimated city-specific PM-mortality associations using time-series regression models and calculated the attributable mortality fraction. Next, we used the value of statistical life to calculate the economic benefits of complying with the WHO AQGs limit values., Results: In most cities, PM concentrations exceeded the WHO AQGs limit values more than 90% of the days. PM 10 was found to be associated with an average excess mortality of 1.88% with concentrations above WHO AQGs limit values, while for PM 2.5 it was 1.05%. The associated annual economic costs varied widely, between US$ 19.5 million to 3,386.9 million for PM 10 , and US$ 196.3 million to 2,209.6 million for PM 2.5 ., Conclusion: Our findings suggest that there is an urgent need for policymakers to develop interventions to achieve sustainable air quality improvements in Latin America. Complying with the WHO AQGs limit values for PM 10 and PM 2.5 in Latin American cities would substantially benefits for urban populations., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Madaniyazi, Alpízar, Cifuentes, Riojas-Rodríguez, Hurtado Díaz, de Sousa Zanotti Stagliorio Coelho, Abrutzky, Osorio, Carrasco Escobar, Valdés Ortega, Colistro, Roye and Tobías.)

Background: In the near future, the incidence of mosquito-borne diseases may expand to new sites due to changes in temperature and rainfall patterns caused by climate change. Therefore, there is a need to use recent technological advances to improve vector surveillance methodologies. Unoccupied Aerial Vehicles (UAVs), often called drones, have been used to collect high-resolution imagery to map detailed information on mosquito habitats and direct control measures to specific areas. Supervised classification approaches have been largely used to automatically detect vector habitats. However, manual data labelling for model training limits their use for rapid responses. Open-source foundation models such as the Meta AI Segment Anything Model (SAM) can facilitate the manual digitalization of high-resolution images. This pre-trained model can assist in extracting features of interest in a diverse range of images. Here, we evaluated the performance of SAM through the Samgeo package, a Python-based wrapper for geospatial data, as it has not been applied to analyse remote sensing images for epidemiological studies., Results: We tested the identification of two land cover classes of interest: water bodies and human settlements, using different UAV acquired imagery across five malaria-endemic areas in Africa, South America, and Southeast Asia. We employed manually placed point prompts and text prompts associated with specific classes of interest to guide the image segmentation and assessed the performance in the different geographic contexts. An average Dice coefficient value of 0.67 was obtained for buildings segmentation and 0.73 for water bodies using point prompts. Regarding the use of text prompts, the highest Dice coefficient value reached 0.72 for buildings and 0.70 for water bodies. Nevertheless, the performance was closely dependent on each object, landscape characteristics and selected words, resulting in varying performance., Conclusions: Recent models such as SAM can potentially assist manual digitalization of imagery by vector control programs, quickly identifying key features when surveying an area of interest. However, accurate segmentation still requires user-provided manual prompts and corrections to obtain precise segmentation. Further evaluations are necessary, especially for applications in rural areas., (© 2024. The Author(s).)

Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects., Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality., Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates., Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV 0-7 (0.9 °C). An IQR increase in inter-day TV 0-7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV 0-7 and inter-day TV 0-7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type., Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies., (© 2024. The Author(s).)

Objective: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project., Methods: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (< 50 and ≥ 50 years)., Results: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (< 50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥ 50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable., Conclusion: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Introduction: Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project., Methods: The sample included 308 cognitively unimpaired individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years)., Results: Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better., Conclusions: These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Chronic kidney disease (CKD) disproportionately affects minorities in the United States, including the Hispanic/Latine population, and is a public health concern in Latin American countries. An emphasis on healthy dietary patterns, including the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, has been suggested as they are associated with a lower incidence of CKD, slower CKD progression, and lower mortality in kidney failure. However, their applicability may be limited in people from Latin America. The Dieta de la Milpa (Diet of the Cornfield) was recently described as the dietary pattern of choice for people from Mesoamerica (Central Mexico and Central America). This dietary pattern highlights the intake of four plant-based staple foods from this geographical region, corn/maize, common beans, pumpkins/squashes, and chilies, complemented with seasonal and local intake of plant-based foods and a lower intake of animal-based foods, collectively classified into ten food groups. Limited preclinical and clinical studies suggest several health benefits, including cardiometabolic health, but there is currently no data concerning CKD. In this narrative review, we describe and highlight the potential benefits of the Dieta de la Milpa in CKD, including acid-base balance, protein source, potassium and phosphorus management, impact on the gut microbiota, inflammation, and cultural appropriateness. Despite these potential benefits, this dietary pattern has not been tested in people with CKD. Therefore, we suggest key research questions targeting measurement of adherence, feasibility, and effectiveness of the Dieta de la Milpa in people with CKD.

Background: Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission., Methods: We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome., Results: In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37-120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with >0.16% predicted probabilities [lower quartile for eligible infants])., Conclusions: We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis., Competing Interests: Potential conflicts of interest. T.V.H. serves on vaccine DSMBs for Pfizer and has served as a consultant to Sanofi. L.J.B. has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. University Medical Centre Utrecht has received major funding (>€100 000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD, and MeMed Diagnostics; has received major funding for the RSV GOLD study from the Bill and Melinda Gates Foundation; has received major funding as part of the public private partnership IMI-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi; has received major funding by Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer; and has received minor funding (€1000-25 000 per industrial partner) for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, Astrazeneca, MSD, Sanofi, and Janssen. L.J.B. is the founding chairman of the ReSViNET Foundation. All other authors (B.M.S., N.B.A., T.G., P.W., E.F.M., G.E.) report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Despite progress towards malaria reduction in Peru, measuring exposure in low transmission areas is crucial for achieving elimination. This study focuses on two very low transmission areas in Loreto (Peruvian Amazon) and aims to determine the relationship between malaria exposure and proximity to health facilities. Individual data was collected from 38 villages in Indiana and Belen, including geo-referenced households and blood samples for microscopy, PCR and serological analysis. A segmented linear regression model identified significant changes in seropositivity trends among different age groups. Local Getis-Ord Gi* statistic revealed clusters of households with high (hotspots) or low (coldspots) seropositivity rates. Findings from 4000 individuals showed a seropositivity level of 2.5% (95%CI: 2.0%-3.0%) for P. falciparum and 7.8% (95%CI: 7.0%-8.7%) for P. vivax, indicating recent or historical exposure. The segmented regression showed exposure reductions in the 40-50 age group (β1 = 0.043, p = 0.003) for P. vivax and the 50-60 age group (β1 = 0.005, p = 0.010) for P. falciparum. Long and extreme distance villages from Regional Hospital of Loreto exhibited higher malaria exposure compared to proximate and medium distance villages (p < 0.001). This study showed the seropositivity of malaria in two very low transmission areas and confirmed the spatial pattern of hotspots as villages become more distant., (© 2024. The Author(s).)

Introduction: The use of drones in environment and health research is a relatively new phenomenon. A principal research activity drones are used for is environmental monitoring, which can raise concerns in local communities. Existing ethical guidance for researchers is often not specific to drone technology and practices vary between research settings. Therefore, this scoping review aims to gather the evidence available on ethical considerations surrounding drone use as perceived by local communities, ethical considerations reported on by researchers implementing drone research, and published ethical guidance related to drone deployment., Methods and Analysis: This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and the Joanna Briggs Institute (JBI) guidelines. The literature search will be conducted using academic databases and grey literature sources. After pilot testing the inclusion criteria and data extraction tool, two researchers will double-screen and then chart available evidence independently. A content analysis will be carried out to identify patterns of categories or terms used to describe ethical considerations related to drone usage for environmental monitoring in the literature using the R Package RQDA. Discrepancies in any phase of the project will be solved through consensus between the two reviewers. If consensus cannot be reached, a third arbitrator will be consulted., Ethics and Dissemination: Ethical approval is not required; only secondary data will be used. This protocol is registered on the Open Science Framework (osf.io/a78et). The results will be disseminated through publication in a scientific journal and will be used to inform drone field campaigns in the Wellcome Trust funded HARMONIZE project. HARMONIZE aims to develop cost-effective and reproducible digital infrastructure for stakeholders in climate change hotspots in Latin America & the Caribbean and will use drone technology to collect data on fine scale landscape changes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hoek Spaans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent advances in blood-based biomarkers of Alzheimer's Disease (AD) show great promise for clinical applications, offering a less invasive alternative to current cerebrospinal fluid (CSF) measures. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations of amyloid-β (Aβ), Total Tau (t-Tau), Phosphorylated Tau (p-Tau), Neurofilament Light (NfL), and Glial Fibrillary Acidic Protein (GFAP) with cognitive measures. The reviewed studies are heterogeneous, varying in design and population (cognitively unimpaired, cognitively impaired, or mixed populations), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ 42 /Aβ 40 ratio. In contrast, t-Tau, p-Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-Tau measures generally exhibit stronger associations with cognitive functions compared to other biomarkers, no single blood marker has emerged as being predominantly linked to a specific cognitive domain. These findings contribute to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical assessments of cognition.

Introduction: This study examined the relationship between blood-brain-barrier permeability (BBBp), measured by cerebrospinal fluid/serum albumin ratio (QAlb), and cognitive decline progression in a clinical cohort., Methods: This prospective observational study included 334 participants from the BIODEGMAR cohort. Cognitive decline progression was defined as an increase in Global Deterioration Scale and/or Clinical Dementia Rating scores. Associations between BBBp, demographics, and clinical factors were explored., Results: Male sex, diabetes mellitus, and cerebrovascular burden were associated with increased log-QAlb. Vascular cognitive impairment patients had the highest log-QAlb levels. Among the 273 participants with valid follow-up data, 154 (56.4%) showed cognitive decline progression. An 8% increase in the hazard of clinical worsening was observed for each 10% increase in log-QAlb., Discussion: These results suggest that increased BBBp in individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: We aim to explore spatial variations in socioeconomic inequalities in HIV testing uptake in sub-Saharan Africa (SSA) at different geographical scales to identify potential geographical hotspots of inequalities. Additionally, to evaluate the potential benefits of HIV testing programmes, we assess whether local levels of HIV testing match the local levels of HIV prevalence., Design: A multi-country analysis of population-based cross-sectional surveys in SSA., Setting: We analysed data from 25 SSA countries with Demographic and Health Surveys between 2011 and 2019., Participants: Country-level analysis included 473 775 participants (312 104 women and 161 671 men) and cluster-level analysis included 328 283 individuals (241 084 women and 87 199 men). Women aged 15-49 years and men aged 15-54/59 years in selected households who were tested for HIV in the last 12 months were eligible. We quantified inequalities in self-reported recent HIV testing with the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII) across geographical scales to capture sex-specific within-country spatial variations. We also conducted local Getis-Ord Gi* statistics to consider the autocorrelation in fine-scale SII and RII across countries. To assess the efficiency of HIV testing programmes, we measured the correlation between recent HIV testing and HIV prevalence through Spearman correlation across geographical scales., Results: We observed varying inequalities in recent HIV testing in magnitude and spatial distribution on both absolute and relative scales in many countries for both sexes at national and subnational levels. Hotspots of absolute and relative inequalities were mostly observed in Western and Central Africa with a few regions in Eastern and Southern Africa. Despite significant sex-specific correlations between testing and prevalence in all countries when assessed at the national level, we report an absence of such a correlation at fine scale in 17 of 50 sex-country combinations., Conclusions: We highlight the importance of investigating the spatial variability of various HIV indicators and related inequalities across different geographical levels. Results may help inform an equitable distribution of HIV testing services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Evidence linking traffic noise to insulin resistance and diabetes is limited and unanswered questions remain regarding the potential effect modification by neighborhood socioeconomic status (nSES). We aimed to assess socioeconomic inequalities in noise exposure, whether road and aircraft noise exposures were associated with insulin resistance or diabetes, and whether nSES modified these relationships. Among the Community of Mine Study in San Diego County, road and aircraft noise exposure at enrollment was calculated based on the static (participant's administrative boundary, and circular buffer around participant homes), and dynamic (mobility data by global positioning system, GPS) spatio-temporal aggregation methods. Associations of noise with insulin resistance (HOMA-IR) or type 2 diabetes (T2DM) were quantified using generalized estimating equation models adjusted for sex, age, ethnicity, individual income, and air pollution (nitrogen dioxide) exposure. Additive interaction between noise and nSES was assessed. Among 573 participants (mean age 58.7 y), participants living in low nSES were exposed to higher levels of aircraft and road noise using noise level at the census tract, circular buffer, or Kernel Density Estimation (KDE) of GPS data. Participants exposed to road noise greater or equal to the median (53 dB(A)) at the census tract and living in low nSES had an increased level of insulin resistance (β = 0.15, 95%CI: -0.04, 0.34) and higher odds of T2DM (Odds Ratio = 2.34, 95%CI: 1.12, 4.90). A positive additive interaction was found as participants living in low nSES had higher odds of T2DM. The impact of noise exposure on insulin resistance and T2DM differs substantially by nSES. Public health benefits of reducing exposure to road or aircraft noise would be larger in individuals living in low nSES., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Stem-like CD8 + T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1 + CD8 + T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for optimal priming of tumor antigen-specific CD8 + T cells and ICB response in poorly immunogenic tumors that accumulate TOX + dysfunctional T cells, but is dispensable for T cell priming and therapy response in highly immunogenic tumors that efficiently expand transitory effectors. Importantly, improving T cell priming by vaccination or by enhancing antigen presentation on tumors rescues the defective responses of TCF1-deficient CD8 + T cells upon ICB in poorly immunogenic tumors. Our study highlights TCF1's role during the early stages of anti-tumor CD8 + T cell responses with important implications for guiding optimal therapeutic interventions in cancers with low TCF1 + CD8 + T cells and low-neo-antigen expression., Competing Interests: Declaration of interests A.C.A. is a member of the SAB for Tizona Therapeutics, Trishula Therapeutics, Compass Therapeutics, Zumutor Biologics, ImmuneOncia, and Excepgen, which have interests in cancer immunotherapy. A.C.A. is a paid consultant for iTeos Therapeutics and Larkspur Biosciences. A.C.A.’s interests were reviewed and managed by the Brigham and Women’s Hospital. C.M.J. is an employee of the VA Maryland Health Care System. The views reported here do not reflect the views of the VA or United States Government. C.M.J. has an equity position with Cartesian Therapeutics. L.B. is also an employee of SANA Biotechnology, Inc. Neither SANA Biotechnology nor its subsidiaries have conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Amyloid-β (Aβ) and tau can be quantified in blood. However, biological factors can influence the levels of brain-derived proteins in the blood. The blood-brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers., Methods: We assessed 224 participants in research (TRIAD, n = 96) and clinical (BIODEGMAR, n = 128) cohorts with plasma and CSF/positron emission tomography Aβ, p-tau, and albumin measures., Results: Plasma Aβ 42/40 better identified CSF Aβ 42/40 and Aβ-PET positivity in individuals with high BBB permeability. An interaction between plasma Aβ 42/40 and BBB permeability on CSF Aβ 42/40 was observed. Voxel-wise models estimated that the association of positron emission tomography (PET), with plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p-tau levels., Discussion: These findings suggest that BBB integrity may influence the performance of plasma Aβ, but not p-tau, biomarkers in research and clinical settings., Highlights: BBB permeability affects the association between brain and plasma Aβ levels. BBB integrity does not affect the association between brain and plasma p-tau levels. Plasma Aβ was most affected by BBB permeability in AD-related brain regions. BBB permeability increases with age but not according to cognitive status., (© 2023 the Alzheimer's Association.)

Objetivo: Presentar la metodología de elaboración del Plan para la Implementación y Monitoreo de la Política Nacional de Recursos Humanos en Salud (PNRHS) del Ministerio de Salud Pública y Bienestar Social (MSPBS) del Paraguay y los resultados de su aplicación. Material y métodos. La PNRHS abarca seis estrategias y 25 líneas de acción cuya ejecución es preciso monitorear y evaluar. La metodología, dividida en siete fases y cuatro instrumentos, implicó un principio de co-construcción que involucra, a través de la Dirección Nacional Estratégica de Recursos Humanos en Salud (DNERHS) del MSPBS, a los actores relacionados con los recursos humanos en salud (RHS). Se realizó un análisis de los factores facilitadores y obstaculizadores que se podrían potenciar o mitigar., Resultados: Para cada estrategia se definieron indicadores, actividades, metas y medios de verificación y se ordenaron las líneas de acción para programar la ejecución. Se creó un Comité Nacional para la implementación y monitoreo de la PNRHS, entre cuyas funciones se incluyen la integración en mesas intersectoriales temáticas y procesos de validación. Conclusión. Los desafíos principales radican en la capacidad de aminorar los obstáculos y en la continuidad de las acciones, lo que requiere la permanencia de un respaldo político en cada institución representada en el Comité y una fuerte capacidad de convocatoria y coordinación por parte del MSPBS.

Lactoferrin (LF) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to determine the effect of bovine lactoferrin (bLF) in the prevention of SARS-CoV-2 infection in health care personnel. A randomized, double-blinded, placebo-controlled clinical trial was conducted in two tertiary hospitals that provide care to patients with SARS-CoV-2 infection in Lima, Peru. Daily supplementation with 600 mg of enteral bLF versus placebo for 90 days was compared. Participants were weekly screened for symptoms suggestive of SARS-CoV-2 infection and molecular testing was performed on suspected episodes. A serological test was obtained from all participants at the end of the intervention. The main outcome included symptomatic and asymptomatic cases. A sub-analysis explored the time to symptomatic infection. Secondary outcomes were the severity, frequency, and duration of symptomatic infection. The study was prematurely cancelled due to the availability of vaccines against SARS-CoV-2 in Peru. 209 participants were enrolled and randomized, 104 received bLF and 105 placebo. SARS-CoV-2 infection occurred in 11 (10.6%) participants assigned to bLF and in 9 (8.6%) participants assigned to placebo without significant differences (Incidence Rate Ratio = 1.23, 95%CI 0.51-3.06, p-value = 0.64). There was no significant effect of bLF on time to symptomatic infection (Hazard Ratio = 1.61, 95%CI 0.62-4.19, p-value = 0.3). There were no significant differences in secondary outcomes. A significant effect of bLF in preventing SARS-CoV-2 infection was not proven. Further studies are needed to assess the effect of bLF supplementation on SARS-CoV-2 infection.Clinical trial registration ClinicalTrials.gov Identifier: NCT04526821, https://clinicaltrials.gov/ct2/show/NCT04526821?term=LACTOFERRIN&cond=COVID-19&cntry=PE&city=Lima&draw=2&rank=1 ., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Disease control programs are needed to identify the breeding sites of mosquitoes, which transmit malaria and other diseases, in order to target interventions and identify environmental risk factors. The increasing availability of very-high-resolution drone data provides new opportunities to find and characterize these vector breeding sites. Within this study, drone images from two malaria-endemic regions in Burkina Faso and Côte d'Ivoire were assembled and labeled using open-source tools. We developed and applied a workflow using region-of-interest-based and deep learning methods to identify land cover types associated with vector breeding sites from very-high-resolution natural color imagery. Analysis methods were assessed using cross-validation and achieved maximum Dice coefficients of 0.68 and 0.75 for vegetated and non-vegetated water bodies, respectively. This classifier consistently identified the presence of other land cover types associated with the breeding sites, obtaining Dice coefficients of 0.88 for tillage and crops, 0.87 for buildings and 0.71 for roads. This study establishes a framework for developing deep learning approaches to identify vector breeding sites and highlights the need to evaluate how results will be used by control programs., Competing Interests: Conflicts of interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Sciatic nerve entrapment is an entity that generates disabling pain, mainly when the patient is sitting on the involved side. According to some studies, the presence of fibrovascular bands has been described as the main cause of this pathology, and the sciatic nerve's decompression by endoscopic release has been described as an effective treatment generally associated with a piriformis tenotomy. The aim of this study was to present the medium-term functional results of endoscopic release of the sciatic nerve without resection of the piriformis tendon., Methods: This prospective, observational study included 57 patients who underwent an endoscopic operation for sciatic nerve entrapment between January 2014 and January 2019. In all cases, a detailed medical history was obtained and a physical examination and a functional evaluation were performed using the modified Harris hip score (mHHS), the 12-item International Hip Outcome Tool (iHOT-12), and the visual analog scale (VAS) for pain. All patients had pelvic radiographs and magnetic resonance imaging (MRI) scans of the hip on the involved side and underwent a prior evaluation by a spine surgeon., Results: This study included 20 male and 37 female patients with a mean age of 43.6 years (range, 24 to 88 years) and a mean follow-up of 22.7 months. The median mHHS improved from 59 to 85 points. The median iHOT-12 improved from 60 to 85 points. The median VAS decreased from 7 to 2. Postoperative complications occurred in 12% of patients: 1 patient with extensive symptomatic hematoma, 3 patients with hypoesthesia, and 3 patients with dysesthesia., Conclusions: Endoscopic release of the sciatic nerve by resection of fibrovascular bands without piriformis tenotomy is a technique with good to excellent functional results comparable with those of techniques in the literature incorporating piriformis tenotomy., Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H470 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: acute pulmonary embolism (APE) is a complex and potentially deadly entity, with a variable clinical course, considered the third cardiovascular cause of death. Its management varies according to the stratified risk from anticoagulation to reperfusion therapy, suggesting systemic thrombolysis as a first-choice strategy; however, in a large group of patients their use will be contraindicated, discouraged or will have failed, thus recommending as options in such cases endovascular therapies or surgical embolectomy. With the presentation of 3 clinical cases and a review of the literature, we seek to communicate our initial experience in the use of ultrasound-accelerated thrombolysis with the EKOS system and to investigate key elements for its understanding and application., Clinical Cases: the cases of 3 patients with APE of high and intermediate risk with contraindications for systemic thrombolysis taken to accelerated thrombolysis therapy by ultrasound are discussed. They presented adequate clinical and hemodynamic evolution in the short term, achieving a rapid decrease in thrombolysis, systolic and mean pulmonary arterial pressure, improvement of right ventricular function and reduction of thrombotic burden., Conclusion: Ultrasound-accelerated thrombolysis is a novel pharmaco-mechanical therapy that combines the emission of ultrasonic waves with the infusion of a local thrombolytic agent, a strategy that, according to different trials and clinical registries, has a high success rate and a good safety profile., (© 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Introduction: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences., Methods: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio., Results: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94)., Discussion: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD., Highlights: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Children's ability to learn new words during their preschool years is crucial for further academic success. Previous research suggests that children rely on different learning mechanisms to acquire new words depending on the available context and linguistic information. To date, there is limited research integrating different paradigms to provide a cohesive view of the mechanisms and processes involved in preschool children's word learning. We presented 4 year-old children ( n = 47) with one of three different novel word-learning scenarios to test their ability to connect novel words to their correspondent referents without explicit instruction to do so. The scenarios were tested with three exposure conditions of different nature: (i) mutual exclusivity-target novel word-referent pair presented with a familiar referent, prompting fast-mapping via disambiguation, (ii) cross-situational-target novel word-referent pair presented next to an unfamiliar referent prompting statistically tracking the target pairs across trials, and (iii) eBook - target word-referent pairs presented within an audio-visual electronic storybook (eBook), prompting inferring meaning incidentally. Results show children succeed at learning the new words above chance in all three scenarios, with higher performance in eBook and mutual exclusivity than in cross-situational word learning. This illustrates children's astounding ability to learn while coping with uncertainty and varying degrees of ambiguity, which are common in real-world situations. Findings extend our understanding of how preschoolers learn new words more or less successfully depending on specific word learning scenarios, which should be taken into account when working on vocabulary development for school readiness in the preschool years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pino Escobar, Tuninetti, Antoniou and Escudero.)

Background: Cerebrospinal fluid (CSF) p-tau235 is a novel biomarker highly specific of Alzheimer's disease (AD). However, CSF p-tau235 has only been studied in well-characterized research cohorts, which do not fully reflect the patient landscape found in clinical settings. Therefore, in this multicentre study, we investigated the performance of CSF p-tau235 to detect symptomatic AD in clinical settings and compared it with CSF p-tau181, p-tau217 and p-tau231., Methods: CSF p-tau235 was measured using an in-house single molecule array (Simoa) assay in two independent memory clinic cohorts: Paris cohort (Lariboisière Fernand-Widal University Hospital Paris, France; n=212) and BIODEGMAR cohort (Hospital del Mar, Barcelona, Spain; n=175). Patients were classified by the syndromic diagnosis (cognitively unimpaired [CU], mild cognitive impairment [MCI] or dementia) and their biological diagnosis (amyloid-beta [Aβ]+ or Aβ -). Both cohorts included detailed cognitive assessments and CSF biomarker measurements (clinically validated core AD biomarkers [Lumipulse CSF Aβ 1-42/40 ratio, p-tau181 and t-tau] and in-house developed Simoa CSF p-tau181, p-tau217 and p-tau231)., Results: High CSF p-tau235 levels were strongly associated with CSF amyloidosis regardless of the clinical diagnosis, being significantly increased in MCI Aβ+ and dementia Aβ+ when compared with all other Aβ- groups (Paris cohort: P ˂0.0001 for all; BIODEGMAR cohort: P ˂0.05 for all). CSF p-tau235 was pronouncedly increased in the A+T+ profile group compared with A-T- and A+T- groups (P ˂0.0001 for all). Moreover, CSF p-tau235 demonstrated high diagnostic accuracies identifying CSF amyloidosis in symptomatic cases (AUCs=0.86 to 0.96) and discriminating AT groups (AUCs=0.79 to 0.98). Overall, CSF p-tau235 showed similar performances to CSF p-tau181 and CSF p-tau231 when discriminating CSF amyloidosis in various scenarios, but lower than CSF p-tau217. Finally, CSF p-tau235 associated with global cognition and memory domain in both cohorts., Conclusions: CSF p-tau235 was increased with the presence of CSF amyloidosis in two independent memory clinic cohorts. CSF p-tau235 accurately identified AD in both MCI and dementia patients. Overall, the diagnostic performance of CSF p-tau235 was comparable to that of other CSF p-tau measurements, indicating its suitability to support a biomarker-based AD diagnosis in clinical settings., (© 2023. The Author(s).)

The COVID-19 pandemic highlighted the importance of global genomic surveillance to monitor the emergence and spread of SARS-CoV-2 variants and inform public health decision-making. Until December 2020 there was minimal capacity for viral genomic surveillance in most Caribbean countries. To overcome this constraint, the COVID-19: Infectious disease Molecular epidemiology for PAthogen Control & Tracking (COVID-19 IMPACT) project was implemented to establish rapid SARS-CoV-2 whole genome nanopore sequencing at The University of the West Indies (UWI) in Trinidad and Tobago (T&T) and provide needed SARS-CoV-2 sequencing services for T&T and other Caribbean Public Health Agency Member States (CMS). Using the Oxford Nanopore Technologies MinION sequencing platform and ARTIC network sequencing protocols and bioinformatics pipeline, a total of 3610 SARS-CoV-2 positive RNA samples, received from 17 CMS, were sequenced in-situ during the period December 5th 2020 to December 31st 2021. Ninety-one Pango lineages, including those of five variants of concern (VOC), were identified. Genetic analysis revealed at least 260 introductions to the CMS from other global regions. For each of the 17 CMS, the percentage of reported COVID-19 cases sequenced by the COVID-19 IMPACT laboratory ranged from 0·02% to 3·80% (median = 1·12%). Sequences submitted to GISAID by our study represented 73·3% of all SARS-CoV-2 sequences from the 17 CMS available on the database up to December 31st 2021. Increased staffing, process and infrastructural improvement over the course of the project helped reduce turnaround times for reporting to originating institutions and sequence uploads to GISAID. Insights from our genomic surveillance network in the Caribbean region directly influenced non-pharmaceutical countermeasures in the CMS countries. However, limited availability of associated surveillance and clinical data made it challenging to contextualise the observed SARS-CoV-2 diversity and evolution, highlighting the need for development of infrastructure for collecting and integrating genomic sequencing data and sample-associated metadata., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sahadeo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal-ligand complexes, especially with repeated use, should be studied further., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To assess the legislative frameworks concerning childhood vaccination in the English- and Dutch-speaking Caribbean and propose a model legislative framework for Caribbean countries., Methods: This study included a survey of 22 countries and territories in the Caribbean regarding legal vaccination mandates for school entry, budget allocations, sanctions, or exemptions. A legal consultant conducted a comprehensive search and analysis of legislation regarding vaccination among 13 Caribbean countries/territories. A comparative analysis of the legislation under five themes-legislative structure, mandatory vaccination, national immunization schedule, sanctions, and exemptions-formed the basis for the proposed model legislation., Results: Among the 22 Caribbean countries/territories, 17 (77%) had legislation mandating vaccination, 16 (94%) mandated vaccination for school entry, 8 (47%) had a dedicated budget for immunization programs, and 13 (76%) had no legislated national schedules. The source of legislation includes six (35%) using the Education Act, eight (47%) the Public Health Act, and five (29%) a free-standing Vaccination Act. Three countries/territories-Jamaica, Montserrat, and Saint Lucia-had immunization regulations. In 12 (71%) of the 17 countries with legislation, sanctions were included, and 10 (59%) permitted exemptions for medical or religious/philosophical beliefs., Conclusions: Several countries in the Caribbean have made failure to vaccinate a child an offense. By summarizing the existing legislative frameworks and approaches to immunization in the Caribbean, the analysis guides policymakers in making effective changes to immunization legislation in their own countries.

Background: Globally, access to life-saving vaccines has improved considerably in the past 5 decades. However, progress has started to slow down and even reverse in recent years. Understanding subnational heterogeneities in essential child immunization will be critical for closing the global vaccination gap., Methods and Findings: We use vaccination information for over 220,000 children across 1,366 administrative regions in 43 low- and middle-income countries (LMICs) from the most recent Demographic and Health Surveys. We estimate essential immunization coverage at the national and subnational levels and quantify socioeconomic inequalities in such coverage using adjusted concentration indices. Within- and between-country variations are summarized via the Theil index. We use local indicator of spatial association (LISA) statistics to identify clusters of administrative regions with high or low values. Finally, we estimate the number of missed vaccinations among children aged 15 to 35 months across all 43 countries and the types of vaccines most often missed. We show that national-level vaccination rates can conceal wide subnational heterogeneities. Large gaps in child immunization are found across West and Central Africa and in South Asia, particularly in regions of Angola, Chad, Nigeria, Guinea, and Afghanistan, where less than 10% of children are fully immunized. Furthermore, children living in these countries consistently lack all 4 basic vaccines included in the WHO's recommended schedule for young children. Across most countries, children from poorer households are less likely to be fully immunized. The main limitations include subnational estimates based on large administrative divisions for some countries and different periods of survey data collection., Conclusions: The identified heterogeneities in essential childhood immunization, especially given that some regions consistently are underserved for all basic vaccines, can be used to inform the design and implementation of localized intervention programs aimed at eliminating child suffering and deaths from existing and novel vaccine-preventable diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dimitrova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Neuropsychological assessments are essential to define the cognitive profile and contribute to the diagnosis of Alzheimer's disease (AD). The progress in knowledge about the pathophysiological process of the disease has allowed conceptualizing AD through biomarkers as a biological continuum that encompasses different clinical stages., Objective: To explore the association between cerebrospinal fluid (CSF) biomarkers of AD and cognition using the NEURONORMA battery, in a sample of cognitively unimpaired (CU), mild cognitive impaired (MCI), and mild dementia of the Alzheimer type (DAT) subjects, and to characterize the cognitive profiles in MCI subjects classified by A/T/N system., Methods: 42 CU, 35 MCI, and 35 mild DAT were assessed using the NEURONORMA battery. Core AD biomarkers [amyloid-β42 (Aβ42) peptide, total tau (t-tau), and phosphorylated tau 181 (p-tau181)] proteins were measured in CSF. Correlation coefficients, multivariate regression, and effect sizes were calculated. We explored the age- and education-adjusted cognitive profiles by A/T/N variants within the MCI group., Results: Cognitive outcomes were directly associated with CSF Aβ42 and inversely with CSF tau measures. We found differences in both biomarkers and cognitive outcomes comparing all pairs except for CSF measures between cognitively impaired groups. The highest effect size was in memory tasks and biomarkers ratios. Lower performances were in memory and executive domains in MCI subjects with AD pathology (A+T+N±) compared to those with normal levels of AD biomarkers (A- T- N)., Conclusion: This study provides further evidence of the validity of Spanish NEURONORMA cognitive battery to characterize cognitive impairment in the AD pathological continuum.

Background and Aim: The associations between COVID-19 transmission and meteorological factors are scientifically debated. Several studies have been conducted worldwide, with inconsistent findings. However, often these studies had methodological issues, e.g., did not exclude important confounding factors, or had limited geographic or temporal resolution. Our aim was to quantify associations between temporal variations in COVID-19 incidence and meteorological variables globally., Methods: We analysed data from 455 cities across 20 countries from 3 February to 31 October 2020. We used a time-series analysis that assumes a quasi-Poisson distribution of the cases and incorporates distributed lag non-linear modelling for the exposure associations at the city-level while considering effects of autocorrelation, long-term trends, and day of the week. The confounding by governmental measures was accounted for by incorporating the Oxford Governmental Stringency Index. The effects of daily mean air temperature, relative and absolute humidity, and UV radiation were estimated by applying a meta-regression of local estimates with multi-level random effects for location, country, and climatic zone., Results: We found that air temperature and absolute humidity influenced the spread of COVID-19 over a lag period of 15 days. Pooling the estimates globally showed that overall low temperatures (7.5 °C compared to 17.0 °C) and low absolute humidity (6.0 g/m 3 compared to 11.0 g/m 3 ) were associated with higher COVID-19 incidence (RR temp =1.33 with 95%CI: 1.08; 1.64 and RR AH =1.33 with 95%CI: 1.12; 1.57). RH revealed no significant trend and for UV some evidence of a positive association was found. These results were robust to sensitivity analysis. However, the study results also emphasise the heterogeneity of these associations in different countries., Conclusion: Globally, our results suggest that comparatively low temperatures and low absolute humidity were associated with increased risks of COVID-19 incidence. However, this study underlines regional heterogeneity of weather-related effects on COVID-19 transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In recent years, global health security has been threatened by the geographical expansion of vector-borne infectious diseases such as malaria, dengue, yellow fever, Zika and chikungunya. For a range of these vector-borne diseases, an increase in residual (exophagic) transmission together with ecological heterogeneity in everything from weather to local human migration and housing to mosquito species' behaviours presents many challenges to effective mosquito control. The novel use of drones (or uncrewed aerial vehicles) may play a major role in the success of mosquito surveillance and control programmes in the coming decades since the global landscape of mosquito-borne diseases and disease dynamics fluctuates frequently and there could be serious public health consequences if the issues of insecticide resistance and outdoor transmission are not adequately addressed. For controlling both aquatic and adult stages, for several years now remote sensing data have been used together with predictive modelling for risk, incidence and detection of transmission hot spots and landscape profiles in relation to mosquito-borne pathogens. The field of drone-based remote sensing is under continuous change due to new technology development, operation regulations and innovative applications. In this review we outline the opportunities and challenges for integrating drones into vector surveillance (i.e. identification of breeding sites or mapping micro-environmental composition) and control strategies (i.e. applying larval source management activities or deploying genetically modified agents) across the mosquito life-cycle. We present a five-step systematic environmental mapping strategy that we recommend be undertaken in locations where a drone is expected to be used, outline the key considerations for incorporating drone or other Earth Observation data into vector surveillance and provide two case studies of the advantages of using drones equipped with multispectral cameras. In conclusion, recent developments mean that drones can be effective for accurately conducting surveillance, assessing habitat suitability for larval and/or adult mosquitoes and implementing interventions. In addition, we briefly discuss the need to consider permissions, costs, safety/privacy perceptions and community acceptance for deploying drone activities., (© 2022. The Author(s).)

Transition metal oxide nanostructures are promising materials for energy storage devices, exploiting electrochemical reactions at nanometer solid-liquid interface. Herein, WO 3 nanorods and hierarchical urchin-like nanostructures were obtained by hydrothermal method and calcination processes. The morphology and crystal phase of WO 3 nanostructures were investigated by scanning and transmission electron microscopy (SEM and TEM) and X-ray diffraction (XRD), while energy storage performances of WO 3 nanostructures-based electrodes were evaluated by cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) tests. Promising values of specific capacitance (632 F/g at 5 mV/s and 466 F/g at 0.5 A/g) are obtained when pure hexagonal crystal phase WO 3 hierarchical urchin-like nanostructures are used. A detailed modeling is given of surface and diffusion-controlled mechanisms in the energy storage process. An asymmetric supercapacitor has also been realized by using WO 3 urchin-like nanostructures and a graphene paper electrode, revealing the highest energy density (90 W × h/kg) at a power density of 90 W × kg -1 and the highest power density (9000 W/kg) at an energy density of 18 W × h/kg. The presented correlation among physical features and electrochemical performances of WO 3 nanostructures provides a solid base for further developing energy storage devices based on transition metal oxides.

In the Amazon Region of Peru, occupational activities are important drivers of human mobility and may increase the individual risk of being infected while contributing to increasing malaria community-level transmission. Even though out-of-village working activities and other mobility patterns have been identified as determinants of malaria transmission, no studies have quantified the effect of out-of-village working activities on recent malaria exposure and proposed plausible intervention scenarios. Using two population-based cross-sectional studies in the Loreto Department in Peru, and the parametric g-formula method, we simulated various hypothetical scenarios intervening in out-of-village working activities to reflect their potential health benefits. This study estimated that the standardized mean outcome (malaria seroprevalence) in the unexposed population (no out-of-village workers) was 44.6% (95% CI: 41.7%-47.5%) and 66.7% (95% CI: 61.6%-71.8%) in the exposed population resulting in a risk difference of 22.1% (95% CI: 16.3%-27.9%). However, heterogeneous patterns in the effects of interest were observed between peri-urban and rural areas (Cochran's Q test = 15.5, p < 0.001). Heterogeneous patterns were also observed in scenarios of increased prevalence of out-of-village working activities and restriction scenarios by gender (male vs. female) and age (18 and under vs. 19 and older) that inform possible occupational interventions targetting population subgroups. The findings of this study support the hypothesis that targeting out-of-village workers will considerably benefit current malaria elimination strategies in the Amazon Region. Particularly, males and adult populations that carried out out-of-village working activities in rural areas contribute the most to the malaria seropositivity (recent exposure to the parasite) in the Peruvian Amazon., (© 2022. The Author(s).)

Introduction: The analysis of the core biomarkers of Alzheimer's Disease (AD) in the cerebrospinal fluid (CSF) is recommended in the clinical units where it is available. Because of the absence of universal validated values, the determination of specific cut-off points for each center and its population is recommended. The main objective of the CORCOBIA study was to determine the cut-off points of core AD CSF biomarkers for several centers (Parc de Salut Mar, Barcelona and Hospital General de Granollers), which work with the same reference laboratory (Laboratori de Referència de Catalunya)., Methods: Prospective study including cognitively unimpaired individuals (CU, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer's Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyse amyloid beta peptides (Aβ42, Aβ40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of sensitivity (SE), specificity (SP), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the CU and AD groups., Results: The resulting cut-offs and their AUC were the following: Aβ42 750 pg/mL (AUC 0.809); Aβ42/Aβ40 0.062 (AUC 0.78); pTau181 69.85 pg/mL (AUC 0.81); tTau 522.0 pg/mL (AUC 0.79); Aβ42/tTau 1.76 (AUC 0.86); Aβ42/pTau181 10.25 (AUC 0.86)., Conclusions: The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aβ42/pTau181 shows the highest AUC and better balance between sensitivity and specificity., (Copyright © 2022 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Uncovering the mechanisms that control CD8 + T cell function is a major focus of cancer research. Advances in flow cytometry and single-cell transcriptomics have provided unprecedented in-depth resolution of CD8 + T cell states in cancer. However, these technologies fail to capture important spatial information, including cell-cell interactions and tissue localization. The discovery that intra-tumoral immune niches, tertiary lymphoid structures, and the tumor-draining lymph node are key sites of inter-cellular communication has evoked interest in understanding the spatial determinants that regulate CD8 + T cell functions at these sites. We focus on the cellular, as well as the soluble and surface-bound signals that regulate CD8 + T cell phenotypes and functions in a topologically-regulated manner, highlighting where new spatial transcriptomics and imaging technologies can uncover mechanistic insights., Competing Interests: Declaration of interests A.C.A. is a member of the SAB for Tizona Therapeutics, Trishula Therapeutics, Compass Therapeutics, Zumutor Biologics, ImmuneOncia, and is a paid consultant for iTeos Therapeutics and Larkspur Biosciences, which have interests in cancer immunotherapy. A.C.A.’s interests were reviewed and managed by the Brigham and Women’s Hospital and Partners Healthcare in accordance with their conflict-of-interest policies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The impact of human population movement (HPM) on the epidemiology of vector-borne diseases, such as malaria, has been described. However, there are limited data on the use of new technologies for the study of HPM in endemic areas with difficult access such as the Amazon. In this study conducted in rural Peruvian Amazon, we used self-reported travel surveys and GPS trackers coupled with a Bayesian spatial model to quantify the role of HPM on malaria risk. By using a densely sampled population cohort, this study highlighted the elevated malaria transmission in a riverine community of the Peruvian Amazon. We also found that the high connectivity between Amazon communities for reasons such as work, trading or family plausibly sustains such transmission levels. Finally, by using multiple human mobility metrics including GPS trackers, and adapted causal inference methods we identified for the first time the effect of human mobility patterns on malaria risk in rural Peruvian Amazon. This study provides evidence of the causal effect of HPM on malaria that may help to adapt current malaria control programmes in the Amazon., (© 2022 The Authors.)