Search

Abstract Background This systematic review investigates the relationship between malaria incidence, climate variables, and deforestation in Colombia, Latin America, and the Caribbean from 2000 to 2020. Malaria, a significant public health issue in these regions, is influenced by ecological factors including climatic conditions and environmental changes, such as deforestation. Methods The review employs a comprehensive search strategy across PubMed, Web of Science, Embase, Scopus, Cochrane, and Scielo databases. It applies strict inclusion and exclusion criteria to ensure the relevance and quality of selected studies, focusing on analysing the relationship between climate variables, deforestation, and malaria incidence. Results Twenty-four articles were included in this review, fourteen of which assessed the relationship between climatic variables and malaria and ten between deforestation and malaria. The analysis reveals a nuanced understanding of malaria dynamics. A significant finding is the seasonal effect of climatic variables on malaria incidence. The study notes that increased rainfall is positively correlated with malaria incidence. Similarly, warmer temperatures are associated with increased malaria risks, and malaria rates can change by 10% to 80% for every degree of temperature increase, after adjusting for altitude. The impact of deforestation on malaria is complex, with positive and negative correlations observed, depending on the remaining forest cover. Conclusions The review highlights the multifaceted nature of malaria transmission, emphasizing the need for integrated approaches that consider both environmental and health perspectives. It underscores the importance of understanding the complex relationships between malaria incidence, climate variables, and deforestation.

BackgroundMost longitudinal studies of COVID-19 incidence have used unlinked samples. The city of Manaus, Brazil, has a blood donation program which allows sample linkage, and was struck by two large COVID-19 epidemic waves between mid-2020 and early 2021.MethodsWe estimated the changing force of infection, i.e. incidence in susceptible individuals. Seroconversion was inferred by a mixture model for serial values from the Abbott Architect SARS-CoV-2 nucleocapsid (N) IgG assay. We estimated the number of suspected COVID-19 hospitalizations arising from each infection over calendar time.ResultsWhole blood donations between April 2020 and March 2021 were included from 6734 people, 2747 with two or more donations. The inferred criterion for seroconversion, and thus an incident infection, was a 6.07 fold increase in N IgG reactivity. The overall force of infection was 1.19 per person year (95% confidence interval 1.14-1.24) during the two main waves. The estimated number of suspected hospitalizations per infection, was approximately 4.1 times higher in the second wave than in the first.ConclusionsSerial values from this assay can be used to infer seroconversion over time, and in Manaus show a higher number of suspected COVID-19 hospitalizations per infection in the second wave relative to the first.

Increased soil nutrient availability, and associated increases in vegetation productivity, could create a negative feedback between Arctic ecosystems and the climate system, thereby reducing the contribution of Arctic ecosystems to future climate change. To predict whether this feedback will develop, it is important to understand the environmental controls over nutrient cycling in High Arctic ecosystems and their impact on carbon cycling processes. Here, we examined the environmental controls over soil nitrogen availability in a High Arctic wet sedge meadow and how abiotic factors and soil nitrogen influenced carbon dioxide exchange processes. The importance of environmental variables was consistent over the 3 years, but the magnitudes of their effect varied depending on climate conditions. Ammonium availability was higher in warmer years and wetter conditions, while drier areas within the wetland had higher nitrate availability. Carbon uptake was driven by soil moisture, active layer depth, and variability between sampling sites and years (R2 = 0.753), while ecosystem respiration was influenced by nitrogen availability, soil temperature, active layer depth, and sampling year (R2 = 0.848). Considered together, the future carbon dioxide source or sink potential of high latitude wetlands will largely depend on climate-induced changes in moisture and subsequent impacts on nutrient availability.

Abstract Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.

Barrett’s esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC), and is caused by chronic gastroesophageal reflux. BE can progress over time from metaplasia to dysplasia, and eventually to EAC. EAC is associated with a poor prognosis, often due to advanced disease at the time of diagnosis. However, if BE is diagnosed early, pharmacologic and endoscopic treatments can prevent progression to EAC. The current standard of care for BE surveillance utilizes the Seattle protocol. Unfortunately, a sizable proportion of early EAC and BE-related high-grade dysplasia (HGD) are missed due to poor adherence to the Seattle protocol and sampling errors. New modalities using artificial intelligence (AI) have been proposed to improve the detection of early EAC and BE-related HGD. This review will focus on AI technology and its application to various endoscopic modalities such as high-definition white light endoscopy, narrow-band imaging, and volumetric laser endomicroscopy.

Degraded peatlands are significant sources of carbon greenhouse gases (CGHG), and their recovery can make significant contributions to climate change mitigation as well as deliver biodiversity benefits. Sphagnum mosses are key species for northern peatland formation and re-introduction is often needed for successful ecohydrological restoration of degraded bogs, but natural sources are scarce and often protected. Micropropagated Sphagnum moss products (BeadaMoss®) were developed to alleviate this constraint. This research explored in detail, for the first time, the CGHG fluxes on a cut-over lowland peatland restoration site where micropropagated Sphagnum was introduced to an existing ‘nurse crop’ of Eriophorum angustifolium, and tested the influence of vegetation maturity. Ecosystem CGHG flux was measured using closed chambers at plot scale in areas of both mature and immature E. angustifolium with and without application of BeadaGel™ Sphagnum, with control plots on bare peat. Studies were conducted over two years of contrasting weather patterns. In Year 1, mean net (CO2e) CGHG uptake on vegetated plots was -2.33 (minimum 1.55, maximum 5.55) t ha-1 yr-1 with increasing CGHG uptake as vegetation matured. In Year 2, gross photosynthesis reduced significantly during the 2018 summer drought resulting in a small mean net CGHG emission of 0.11 (minimum 2.21 maximum -1.22) t ha-1 yr-1. Sphagnum application within immature vegetation resulted in greater CGHG uptake in both years, but was not as beneficial within mature vegetation. CGHG emission from bare peat (3.79 t ha-1 yr-1 overall) showed the magnitude of avoided losses. Methane flux contributed significantly to CGHG emission but was not closely related to water table depth. Application of Sphagnum within E. angustifolium can deliver good CGHG flux results in the early stages of degraded lowland bog recovery but cannot fully mitigate vulnerability to climate change scenarios.

BackgroundA better understanding of SARS-CoV-2 infection risk among Hispanic and Latino populations and in low-resource settings in the United States is needed to inform control efforts and strategies to improve health equity. Puerto Rico has a high poverty rate and other population characteristics associated with increased vulnerability to COVID-19, and there are limited data to date to determine community incidence. ObjectiveThis study describes the protocol and baseline seroprevalence of SARS-CoV-2 in a prospective community-based cohort study (COPA COVID-19 [COCOVID] study) to investigate SARS-CoV-2 infection incidence and morbidity in Ponce, Puerto Rico. MethodsIn June 2020, we implemented the COCOVID study within the Communities Organized to Prevent Arboviruses project platform among residents of 15 communities in Ponce, Puerto Rico, aged 1 year or older. Weekly, participants answered questionnaires on acute symptoms and preventive behaviors and provided anterior nasal swab samples for SARS-CoV-2 polymerase chain reaction testing; additional anterior nasal swabs were collected for expedited polymerase chain reaction testing from participants that reported 1 or more COVID-19–like symptoms. At enrollment and every 6 months during follow-up, participants answered more comprehensive questionnaires and provided venous blood samples for multiantigen SARS-CoV-2 immunoglobulin G antibody testing (an indicator of seroprevalence). Weekly follow-up activities concluded in April 2022 and 6-month follow-up visits concluded in August 2022. Primary study outcome measures include SARS-CoV-2 infection incidence and seroprevalence, relative risk of SARS-CoV-2 infection by participant characteristics, SARS-CoV-2 household attack rate, and COVID-19 illness characteristics and outcomes. In this study, we describe the characteristics of COCOVID participants overall and by SARS-CoV-2 seroprevalence status at baseline. ResultsWe enrolled a total of 1030 participants from 388 households. Relative to the general populations of Ponce and Puerto Rico, our cohort overrepresented middle-income households, employed and middle-aged adults, and older children (P

Abstract Tooth classes are an innovation that has contributed to the evolutionary success of mammals. However, our understanding of the mechanisms by which tooth classes diversified remain limited. We use the evolutionary radiation of noctilionoid bats to show how the tooth developmental program evolved during the adaptation to new diet types. Combining morphological, developmental and mathematical modeling approaches, we demonstrate that tooth classes develop through independent developmental cascades that deviate from classical models. We show that the diversification of tooth number and size is driven by jaw growth rate modulation, explaining the rapid gain/loss of teeth in this clade. Finally, we mathematically model the successive appearance of tooth buds, supporting the hypothesis that growth acts as a key driver of the evolution of tooth number and size. Our work reveal how growth, by tinkering with reaction/diffusion processes, drives the diversification of tooth classes and other repeated structure during adaptive radiations.

Interbody fusion is a workhorse technique in lumbar spine surgery that facilities indirect decompression, sagittal plane realignment, and successful bony fusion. The 2 most commonly employed cage materials are titanium (Ti) alloy and polyetheretherketone (PEEK). While Ti alloy implants have superior osteoinductive properties they more poorly match the biomechanical properties of cancellous bones. Newly developed 3-dimensional (3D)-printed porous titanium (3D-pTi) address this disadvantage and are proposed as a new standard for lumbar interbody fusion (LIF) devices. In the present study, the literature directly comparing 3D-pTi and PEEK interbody devices is systematically reviewed with a focus on fusion outcomes and subsidence rates reported in the in vitro, animal, and human literature. A systematic review directly comparing outcomes of PEEK and 3D-pTi interbody spinal cages was performed. PubMed, Embase, and Cochrane Library databases were searched according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Mean Newcastle-Ottawa Scale score for cohort studies was 6.4. A total of 7 eligible studies were included, comprising a combination of clinical series, ovine animal data, and in vitro biomechanical studies. There was a total population of 299 human and 59 ovine subjects, with 134 human (44.8%) and 38 (64.4%) ovine models implanted with 3D-pTi cages. Of the 7 studies, 6 reported overall outcomes in favor of 3D-pTi compared to PEEK, including subsidence and osseointegration, while 1 study reported neutral outcomes for device related revision and reoperation rate. Though limited data are available, the current literature supports 3D-pTi interbodies as offering superior fusion outcomes relative to PEEK interbodies for LIF without increasing subsidence or reoperation risk. Histologic evidence suggests 3D-Ti to have superior osteoinductive properties that may underlie these superior outcomes, but additional clinical investigation is merited.

The adultification of Black children is a form of anti-Blackness that brings Black children into adult situations. The adultification of Black children can be rooted in early 20th-century children’s books with minstrel imagery showing Black children in perilous situations for adult entertainment and for white children’s learning. This essay puts “digital blackface”—the online cross-racial memes using Black children’s reactions, emotions, and stereotypes as cross-racial humor—in conversation with historical children’s books featuring Black children. Linking digital representations and misrepresentations to children’s picture books demonstrates how Black children in both formats and social spheres are thrust into adult politics at their expense. Adultifying Black children across time in children’s books with minstrel imagery and digital blackface shows how Black children have never been exempt from the anti-Blackness and systemic white supremacy erroneously believed to be an adult issue.

Summary: The lateral root angle or gravitropic set-point angle (GSA) is an important trait for root system architecture (RSA) that determines the radial expansion of the root system. The GSA therefore plays a crucial role for the ability of plants to access nutrients and water in the soil. Only a few regulatory pathways and mechanisms that determine GSA are known. These mostly relate to auxin and cytokinin pathways. Here, we report the identification of a small molecule, mebendazole (MBZ), that modulates GSA in Arabidopsis thaliana roots and acts via the activation of ethylene signaling. MBZ directly acts on the serine/threonine protein kinase CTR1, which is a negative regulator of ethylene signaling. Our study not only shows that the ethylene signaling pathway is essential for GSA regulation but also identifies a small molecular modulator of RSA that acts downstream of ethylene receptors and that directly activates ethylene signaling.

Introduction: Stereotactic body radiation therapy (SBRT) is an emerging treatment modality for clinically localized prostate cancer (PCa). Online daily adaptive radiotherapy (ART) could potentially improve the therapeutic ratio of prostate SBRT by accounting for inter-fraction variation in target and OAR volumes. To our knowledge, no group has evaluated the clinical utility of a novel AI-augmented CT-based ART system for prostate SBRT. In this study we hypothesized that adaptive prostate SBRT plans would result in improved target coverage and lower dose to OARs in comparison to unadapted treatment plans. Methods: Seven patients with favorable intermediate to oligometastatic PCa treated with 5-fx prostate adaptive SBRT were retrospectively reviewed. Patients were treated with 3625 cGy to the prostate and seminal vesicles. 6 patients additionally received 2500 cGy to the pelvic nodes, 5 patients underwent a boost to 4000 cGy to the prostate. For each fraction, a CBCT was acquired and OARs (rectum, bladder, bowel, sigmoid, femurs) were segmented/deformed using AI. CTVs were rigidly registered. Volumes were adjusted manually and PTV expansions added. Adaptive treatment plans were developed based on the contoured targets and OARs and dose to these volumes for the adapted vs. initial plans were compared for each fraction. V100 and the D0.03 cc between scheduled and adapted treatment plans were compared using a Student’s t-test, with significance threshold of P

To address the history of unethical research and community distrust in research among Native Hawaiian and Pacific Islander communities, we developed the “Community 101 for Researchers” training program, which was launched in 2014 to enhance the capacity of researchers to engage in ethical community-engaged research. The purpose of this paper is to describe the development of this training program as well as its reach and feedback from participants. The Community 101 training program is a self-paced, 2-h online training program featuring community-engaged researchers from the University of Hawai‘i and their longstanding community partners. Throughout the five modules, we highlight the historical context of Native Hawaiians and Pacific Islander populations in Hawai‘i related to research ethics and use examples from the community as well as our own research projects that integrate community ethics, relevance, benefits, and input. To determine reach and gather participant feedback on the training, we extracted data from the user accounts. The training has been completed by 697 users to-date since its launch. Despite very little advertisement, an average of nearly 70 users have completed the Community 101 Program each year. The majority of the participants were located in Hawai‘i though participants were also from other states and territories in the US, and international locations. The majority of participants were from universities in Hawai‘i in 51 different departments demonstrating multidisciplinary relevance of the program's training. The general feedback from the 96 participants who completed an optional anonymous evaluation survey given at the end of the training was positive. The “Community 101 for Researchers” Training program is an accessible and relevant tool that can be used to advance ethical community engaged research, specifically with Native Hawaiian and Pacific Islander communities.

Background: Retesting for Human epidermal growth factor receptor-2 (HER2) in post-neoadjuvant therapy resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy. Methods: We identified 104 patients with localized HER2 IHC 3+ breast cancer who received neoadjuvant trastuzumab(T)/pertuzumab(P) containing chemotherapy at Yale Cancer Center between 2012 and 2022. Patients were divided into 3 cohorts by response and HER2 IHC in the residual disease: Cohort 1 pathologic complete response (pCR), Cohort 2 pre-treatment IHC 3+/post treatment IHC 1+/2+, and Cohort 3 pre-treatment IHC 3+/post-treatment IHC 3+. Kaplan-Meier survival analysis was performed to assess recurrence free survival at 36 months. Results: The overall pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had residual disease (RD). Among patients with RD, 58.9% (23/39) remained IHC 3+ and 41.1% (16/39) had reduced HER2 expression IHC1+ or 2+. In patients with HER2 IHC 3+ RD, 26% (6/23) developed local recurrence or distant metastasis while none of patients with post NAT HER2 IHC 1+ or 2+ RD had relapse (p = 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis revealed superior disease-free survival in patients with reduced HER2 IHC expression compared to those with remained IHC 3+ (log rank p = 0.004). Conclusion: We conclude that reduced HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates in HER2 IHC 3+ breast cancer. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to stratify patients in adjuvant trials and identify patients who may benefit from more intensive adjuvant therapy and post therapy surveillance.

Arctic warming and changing precipitation patterns are altering soil nutrient availability and other processes that control the greenhouse gas balance of high-latitude ecosystems. Changes to these biogeochemical processes will ultimately determine whether the Arctic will enhance or dampen future climate change. At the Cape Bounty Arctic Watershed Observatory, a full-factorial International Tundra Experiment site was established in 2008, allowing for the investigation of ten years of experimental warming and increased snow depth on nutrient availability and trace gas exchange in a mesic heath tundra across two growing seasons (2017 and 2018). Plots with open-top chambers (OTCs) had drier soils (p

Abstract Background Through the evolution of novel wing structures, bats (Order Chiroptera) became the only mammalian group to achieve powered flight. This achievement preceded the massive adaptive radiation of bats into diverse ecological niches. We investigate some of the developmental processes that underlie the origin and subsequent diversification of one of the novel membranes of the bat wing: the plagiopatagium, which connects the fore- and hind limb in all bat species. Results Our results suggest that the plagiopatagium initially arises through novel outgrowths from the body flank that subsequently merge with the limbs to generate the wing airfoil. Our findings further suggest that this merging process, which is highly conserved across bats, occurs through modulation of the programs controlling the development of the periderm of the epidermal epithelium. Finally, our results suggest that the shape of the plagiopatagium begins to diversify in bats only after this merging has occurred. Conclusions This study demonstrates how focusing on the evolution of cellular processes can inform an understanding of the developmental factors shaping the evolution of novel, highly adaptive structures.

Abstract Background Many pregnant women and parents have concerns about vaccines. This analysis examined the impact of MomsTalkShots, an individually tailored educational application, on vaccine attitudes of pregnant women and mothers. Methods MomsTalkShots was the patient-level component of a multi-level intervention to improve maternal and infant vaccine uptake that also included provider- and practice-level interventions. The impact of these interventions was studied using a two-by-two factorial design, randomizing at both the patient- and the practice-level. Study staff recruited pregnant women from a diverse set of prenatal care practices in Colorado and Georgia between June 2017 and July 2018. All participants (n = 2087) received a baseline survey of maternal and infant vaccine intentions and attitudes, and two follow-up surveys at least 1 month and 1 year after their infant’s birth, respectively. Half of participants (n = 1041) were randomly assigned to receive educational videos through MomsTalkShots, algorithmically tailored to their vaccine intentions, attitudes, and demographics. Since the practice/provider intervention did not appear impactful, this analysis focused on MomsTalkShots regardless of the practice/provider intervention. Results By 1 month post-birth, MomsTalkShots increased perceived risk of maternal influenza disease (61% among MomsTalkShots recipients vs 55% among controls; Odds Ratio: 1.61, 95% Confidence Interval: 1.23–2.09), confidence in influenza vaccine efficacy (73% vs 63%; OR: 1.97, 95%CI: 1.47–2.65), and perceived vaccine knowledge (55% vs 48%; OR: 1.39, 95%CI: 1.13–1.72). Among those intending not to vaccinate at baseline, MomsTalkShots increased perceived risk of maternal influenza disease (38% vs 32%; OR: 2.07, 95%CI: 1.15–3.71) and confidence in influenza vaccine efficacy (44% vs 28%; OR: 2.62, 95%CI: 1.46–4.69). By 1 year post-birth, MomsTalkShots increased perceived vaccine knowledge (62% vs 50%; OR: 1.74, 95%CI: 1.36–2.24) and trust in vaccine information from obstetricians and pediatricians (64% vs 55%; OR: 1.53, 95%CI: 1.17–2.00). Among those uncertain about vaccinating at baseline, MomsTalkShots increased perceived vaccine knowledge (47% vs 12%; OR: 6.89, 95%CI: 1.52–31.25) and reduced infant vaccine safety concerns (71% vs 91%; OR: 0.24, 95%CI: 0.06–0.98). Conclusions MomsTalkShots improved pregnant women’s and mothers’ knowledge and perceptions of maternal and infant vaccines and the diseases they prevent, and offers a scalable tool to address vaccine hesitancy. Trial registration Registered at Clinicaltrials.gov on 13/09/2016 (registration number: NCT02898688).

Purpose: Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) with optional online adaptation has shown promise in delivering ablative doses to unresectable primary liver cancer. However, there remain limited data on the indications for online adaptation as well as dosimetric and longer-term clinical outcomes following MRgSBRT Methods and Materials: Patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CCA) who completed MRgSBRT to 50 Gy in 5 fractions between June of 2015 and December of 2021 were analyzed. The necessity of adaptive techniques was evaluated. The cumulative incidence of local progression was evaluated and survival and competing risk analyses were performed. Results: Ninety-nine analyzable patients completed MRgSBRT during the study period and 54 % had planning target volumes (PTVs) within 1 cm of the duodenum, small bowel, or stomach at the time of simulation. Online adaptive RT was used in 53 % of patients to correct organ-at-risk constraint violation and/or to improve target coverage. In patients who underwent adaptive RT planning, online replanning resulted in superior target coverage when compared to projected, non-adaptive plans (median coverage ≥ 95 % at 47.5 Gy: 91 % [IQR: 82–96] before adaptation vs 95 % [IQR: 87–99] after adaptation, p

Abstract Pipe failure prediction models are essential for informing proactive management decisions. This study aims to establish a reliable prediction model returning the probability of pipe failure using a gradient boosted tree model, and a specific segmentation and grouping of pipes on a 1 km grid that associates localised characteristics. The model is applied to an extensive UK network with approximately 40,000 km of pipeline and a 14-year failure history. The model was evaluated using the Receiver Operator Curve and Area Under the Curve (0.89), briers score (0.007) and Mathews Correlation Coefficient (0.27) for accuracy, indicating acceptable predictions. A weighted risk analysis is used to identify the consequence of a pipe failure and provide a graphical representation of high-risk pipes for decision makers. The weighted risk analysis provided an important step to understanding the consequences of the predicted failure. The model can be used directly in strategic planning, which sets long-term key decisions regarding maintenance and potential replacement of pipes.

The complexity of modern biology poses challenges in fostering interdisciplinary understanding, particularly between practicing scientists and the public. Furthermore, scientists often lack formal training in science communication, despite various motivations to engage the public. The science literacy of the public in the biological sciences can also vary across socio-economic and cultural backgrounds. Leveraging popular culture and informal learning practices to promote active learning offers promising avenues to enhance public understanding of biological systems. Organized sports hold collective recognition across various communities and cultures, serving as a means to bring people together. Notably, the NCAA March Madness event holds widespread national and international popularity, presenting an opportunity to laterally apply this concept to promote science communication within STEM and biology education. An educational social media and web-based contest tool was developed integrating NCAA-inspired brackets with animal biological systems concepts. The tool featured tournament-style matchups based on animal biological systems, interesting animal facts, and a voting system, all housed within a user-friendly interface. To encourage regular user access to the tool, graphic designs were developed for all social media posts to aid in visual recruitment to the voting website. Based on online metrics, the use of social media garnered repeat users across both the public and educators. The latter noted the tool's simplicity and informative content. Application of this social media and web-based bracket contest tool, which leverages informal settings for active learning for use in biology education, can foster science communication to engage audiences, improve comprehension, and promote interdisciplinary biology education.

Abstract Introduction The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co‐occurrence of COVID‐19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia). Methods This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia. Results The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible. Conclusions Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research. Trial registration Trial registration number: ISRCTN-81915073 . Date of registration: 17/04/2020, 'Retrospectively registered'.

Background: Adverse events in COVID-19 are difficult to predict. Risk stratification is encumbered by the need to protect healthcare workers. We hypothesize that artificial intelligence (AI) can help identify subtle signs of myocardial involvement in the 12-lead electrocardiogram (ECG), which could help predict complications. Objective: Use intake ECGs from COVID-19 patients to train AI models to predict risk of mortality or major adverse cardiovascular events (MACE). Methods: We studied intake ECGs from 1448 COVID-19 patients (60.5% male, aged 63.4 ± 16.9 years). Records were labeled by mortality (death vs discharge) or MACE (no events vs arrhythmic, heart failure [HF], or thromboembolic [TE] events), then used to train AI models; these were compared to conventional regression models developed using demographic and comorbidity data. Results: A total of 245 (17.7%) patients died (67.3% male, aged 74.5 ± 14.4 years); 352 (24.4%) experienced at least 1 MACE (119 arrhythmic, 107 HF, 130 TE). AI models predicted mortality and MACE with area under the curve (AUC) values of 0.60 ± 0.05 and 0.55 ± 0.07, respectively; these were comparable to AUC values for conventional models (0.73 ± 0.07 and 0.65 ± 0.10). There were no prominent temporal trends in mortality rate or MACE incidence in our cohort; holdout testing with data from after a cutoff date (June 9, 2020) did not degrade model performance. Conclusion: Using intake ECGs alone, our AI models had limited ability to predict hospitalized COVID-19 patients’ risk of mortality or MACE. Our models’ accuracy was comparable to that of conventional models built using more in-depth information, but translation to clinical use would require higher sensitivity and positive predictive value. In the future, we hope that mixed-input AI models utilizing both ECG and clinical data may be developed to enhance predictive accuracy.

Summary: Background: Despite the importance of social determinants of health, studies on the effects of socioeconomic, sanitary, and housing conditions on Indigenous child health are scarce worldwide. This study aims to identify patterns in housing, water & sanitation, and wealth (HSW) in the first Indigenous birth cohort in Brazil–The Guarani Birth Cohort. Methods: Cross-sectional study using baseline data from The Guarani Birth Cohort. We used Multiple Correspondence Analysis and Cluster Analysis. The clusters identified were ordered in increasing degrees of access to public policies and wealth, defining the patterns of HSW. Finally, we explored the association between the patterns and one of the health outcomes, hospitalization, in the birth cohort. Findings: Three patterns were identified for housing and water & sanitation, and four for wealth status, resulting in 36 combinations of patterns (3 × 3 × 4). More than 62% of children in the cohort were found with the lowest wealth patterns. The distribution of children across patterns in one dimension was not fully determined by the other two dimensions. Statistically significant associations were found between precarious households and extreme poverty, and hospitalization. Interpretation: We observed substantial heterogeneity in the distribution of children across the 36 combinations. These findings highlight that, should the dimensions of HSW be associated with health outcomes, as seen for hospitalization, they should be considered separately in multivariable models, in order to improve the estimation of their independent effects. Funding: National Council for Scientific and Technological Development, Brazil (CNPq); Oswaldo Cruz Foundation, Brazil (Fiocruz); Research Foundation of the State of Rio de Janeiro, Brazil (FAPERJ).

BackgroundIn Latin America, cutaneous leishmaniasis primarily affects dispersed rural communities, that have limited access to the public health system and medical attention. Mobile health (mHealth) strategies have shown potential to improve clinical management and epidemiological surveillance of neglected tropical diseases, particularly those of the skin.MethodsThe Guaral +ST app for Android was designed to monitor cutaneous leishmaniasis treatment and assess therapeutic response. We carried out a randomized trial in the coastal municipality of Tumaco in southwestern Colombia, with parallel arms comparing a) follow-up aided by the app to b) standard institution-based follow-up. Treatment was prescribed according to national guidelines. Follow-up of therapeutic response was scheduled at the end of treatment and at 7, 13 and 26 weeks after the start of treatment. The primary endpoint was the proportion of participants who were monitored at or around week 26, allowing outcome and effectiveness of treatment to be determined.ResultsFollow-up of treatment and outcome assessment was achieved in significantly more patients in the intervention arm than the controls, Of the 75 participants in the two randomized arms, 74 had information on whether or not treatment was followed and outcome determined at or around week 26. Among these, 26/49 (53.1%) were evaluated in the intervention arm, and none (0/25, 0%) in the control arm (difference = 53.1%, 95% confidence interval 39.1-67.0%, pConclusionThis study provides proof of concept for mHealth to monitor treatment of CL in remote and complex settings, deliver improved care and to provide information to the health system on the effectiveness of treatment as it is delivered to affected populations.Clinical trial registrationISRCTN54865992.

Abstract Background The city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection. Methods We tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants. Results From 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0–24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3–34.2%) and 39.3% (95% CI 29.5–50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3–92.7%), decreasing to respectively 72.5% (95% CI 54.7–83.6%) and 39.5% (95% CI 14.1–57.8%) if probable and possible reinfections are included. Conclusions Reinfection by Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.

RNA Polymerase III (Pol III) transcribes non-coding RNA, including tRNAs. Applying different RNA-Seq techniques, Dremel et al. provide the Pol III transcriptional landscape of Herpes simplex virus 1 (HSV-1) infected cells. Infection leads to an increase in tRNA expression from host euchromatin and Pol II re-localization to tRNA loci. They also find that Pol III – associated factors bind to the viral genome.

Objectives To determine SARS-CoV-2 seroprevalence over time and risk factors among pregnant women at delivery in São Paulo, Brazil; and to evaluate the suitability of pregnant women as a sentinel population for SARS-CoV-2 serosurveillance. Methods Unselected consecutive pregnant women presenting at the labor ward of a single large hospital between July 20th 2020 to February 21st 2021 were enrolled and tested for SARS-CoV-2 serology using two assays: the rapid chromatic Wondfo One Step (for total IgA and IgG detection) and Roche Elecsys assay (detecting anti-nucleoprotein [N] IgG). SARS-CoV-2 seroprevalence was computed as smooth spline function over time with 95% confidence intervals (CI). Risk factors were evaluated for positivity by each assay. We compared timepoint seroprevalence by the two assays with four concomitant community household surveys (HHS), in which the Roche assay was used, to determine the sensitivity and relevance of the pregnant women population as sentinel population. Results Overall SARS-CoV-2 seroprevalence was 28.9% (221/763) by Roche and 17.9% (137/763) by Wondfo. Reported symptoms experienced during pregnancy were all significantly correlated with being SARS-CoV-2 seropositive at delivery with any assay (with odds-ratios ranging from 3.0 [95% CI: 2.1–4.3] for coryza to 22.8 [95% CI: 12.3–46.6] for ageusia). Seropositivity by either assay was high in women at delivery in the early period of the pandemic (June 2020), compared with seropositivity in women from the concomitant HHS: 44.1% (95% CI: 21.8–66.4) for Roche, 54.1% (30.9–78.5) for Wondfo, versus 11.4% (95% CI: 9.2–13.6) for HHS. For later periods (October 2020 and January 2021), the seropositivity in women at delivery measured by Roche corresponded well with the prevalence found among women in the HHS using the same assay, whilst prevalence measured by Wondfo dropped. Conclusions Women at delivery represent a highly exposed and readily accessible population for sentinel surveillance of emerging infections such as SARS-CoV-2.

Introduction There is insufficient evidence supporting the use of rapid diagnostic tests (RDTs) for syphilis in people living with HIV (PLWH). We evaluated the diagnostic performance of two commercially available RDTs (Bioline and Determine) in PLWH in Cali, Colombia. Methods A cross-sectional field validation study on consecutive adults with confirmed HIV diagnosis attending three outpatient clinics. Both RDTs were performed on capillary blood (CB), obtained by finger prick, and sera, by venipuncture. A combination of treponemal enzyme linked immunosorbent assay (ELISA) and Treponema pallidum haemagglutination assay (TPHA) on serum samples was the reference standard. Rapid plasma reagin (RPR) and clinical criteria were added to define active syphilis. Sensitivity and specificity, predictive values and likelihood ratios (LR) of RDTs were estimated with their corresponding 95% confidence interval (95% CI). Stratified analyses by sample type, patient characteristics, non-treponemal titers, operator and re-training were performed. Results 244 PLWH were enrolled, of whom 112 (46%) had positive treponemal reference tests and 26/234 (11.1%) had active syphilis. The sensitivities of Bioline on CB and sera were similar (96.4% vs 94.6%, p = 0.6). In contrast, Determine had a lower sensitivity on CB than sera (87.5% vs 99.1%, p 95% in most analyses. Predictive values were 90% or higher. For active syphilis, the RDTs showed a similar performance pattern but with decreased specificities. Conclusion The studied RDTs have an excellent performance in PLWH to screen for syphilis and potentially for active syphilis, yet Determine performs better on sera than CB. Patient characteristics and potential difficulties operators may face in acquiring enough blood volume from finger pricks should be considered for the implementation and the interpretation of RDTs.

BackgroundTreatment guidance for children and older adult patients affected by cutaneous leishmaniasis (CL) is unclear due to limited representation of these groups in clinical trials.MethodsWe conducted a collaborative retrospective study to describe the effectiveness and safety of antileishmanial treatments in children ≤ 10 and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in Latin America.Results2,037 clinical records were assessed for eligibility. Of them, the main reason for non-inclusion was lack of data on treatment follow-up and therapeutic response (182/242, 75% of children and 179/468, 38% of adults). Data on 1,325 eligible CL patients (736 children and 589 older adults) were analyzed. In both age groups, disease presentation was mild, with a median number of lesions of one (IQR: 1-2) and median lesion diameter of less than 3 cm. Less than 50% of the patients had data for two or more follow-up visits post-treatment (being only 28% in pediatric patients). Systemic antimonials were the most common monotherapy regimen in both age groups (590/736, 80.2% of children and 308/589, 52.3% of older adults) with overall cure rates of 54.6% (95% CI: 50.5-58.6%) and 68.2% (95% CI: 62.6-73.4%), respectively. Other treatments used include miltefosine, amphotericin B, intralesional antimonials, and pentamidine. Adverse reactions related to the main treatment were experienced in 11.9% (86/722) of children versus 38.4% (206/537) of older adults. Most adverse reactions were of mild intensity.ConclusionOur findings support the need for greater availability and use of alternatives to systemic antimonials, particularly local therapies, and development of strategies to improve patient follow-up across the region, with special attention to pediatric populations.

Focal cortical dysplasias (FCDs) are the most common cause of treatment-resistant epilepsy affecting the pediatric population. Most individuals with FCD have seizure onset within the first five years of life and the majority will develop epilepsy by the age of sixteen. Many cases of FCD are postulated to be the result of abnormal brain development in utero by germline or somatic gene mutations regulating neuronal growth and migration during corticogenesis. Other cases of FCD are thought to be related to infections during brain development, with other causes still not fully determined. Typical anti-seizure medications are oftentimes ineffective in FCD. In addition, surgical intervention is often unable to be successfully performed due to the involvement of eloquent areas of the brain or insufficient resection of the epileptogenic focus, posing a challenge for physicians. The genetic nature of FCDs provides an avenue for drug development with several genetic and molecular targets undergoing study over the last two decades, with the most widely studied target being mammalian target of rapamycin (mTOR). However, other molecular targets of FCD have been identified and provide a rich field of opportunity to expand current understanding and subsequentlydesign targeted molecular therapy to improve the lives of patients with FCDs. To better inform this area of ongoing research, we performed a narrative review of the molecular markers and potential therapeutic drugs for FCDs.

BackgroundImproved education on water-related diseases in schools could help to reduce disease burden. This paper presents specific results on knowledge, attitudes and practices (KAP) of a cluster-randomized controlled trial to reduce diarrheal disease and dengue entomological risk factors in rural primary schools in Colombia. The aim was to investigate whether enhanced educational interventions on dengue and diarrheal disease in schools could improve KAP scores related to these diseases in students and teachers in rural primary schools, as well as the students' parents.Methodology/principal findingsA factorial cluster-randomized controlled trial was carried out in 35 rural primary schools in two municipalities in Cundinamarca, central Colombia. Schools were randomized into four arms: interventions related to diarrheal disease (DIA), dengue (DEN), both (DIADEN), or no interventions (control, CON). Both educational and physical interventions to reduce risk factors of dengue and diarrhea were implemented. Comprehensive teachers' manuals were developed and deployed to guide the learning activities. The intervention was carried out over two school years. The knowledge scores of students receiving dengue interventions (DEN, DIADEN) increased by 1.16 point score (0.75-1.56, pConclusions/significanceThere were increases in knowledge scores among students, their teachers and their parents for both diseases. However, the attitudes and practices components were not affected to the same extent. The hypothesis that the students would disseminate knowledge acquired from the educational interventions to their parents was confirmed for dengue, but not for diarrhea.Trial registrationISRCTN40195031 The trial is registered in the Current Controlled Trials under Infections and Infestations category.

As educational justice scholarship addressing racial oppression continues to name the role of the spirit, there is a need for Black and Brown Christian educators and researchers to locate ourselves as grounded in the epistemologies and pedagogies of Christ as our spiritual home. This paper brings together eight Black and Brown Christian educators and researchers to grapple with what it means to be Christians committed to racial justice in education against the backdrop of centuries of religious corruption. Through collaborative autoethnography, we turn to our spiritual and religious lives situated within our racialized identities to challenge the disciplinary and material boundaries of what critical qualitative research counts as "knowing." In doing this, we give ourselves, and all educators and researchers, permission to make evident the unseen forces that shape our ways of being in research and teaching.

College-in-prison programs are positioned to expand substantially under the reinstatement of Pell Grant eligibility for people in prison. While this change will enable more students who have been systemically excluded from higher education to attend college, degree completion is rare during incarceration and post-release. Student perspectives can shed light on both the value of college-in-prison and the financial barriers to realizing its value. This study analyzes data from 12 focus groups with 105 total college-in-prison student participants, 114 student survey responses, and 45 stakeholder interviews. The data were collected between 2018-2022 during a process evaluation of the College-in-Prison Reentry Initiative, which provided funding to college-in-prison programs in New York State as part of the Manhattan District Attorney's Office Criminal Justice Investment Initiative. The findings demonstrate that students value college-in-prison, describing how it fostered self-reflection and personal growth and provided them with a skillset that may help them gain employment upon release. However, students also raised concerns about reenrolling and completing their degrees following release. Intentional, holistic reentry support could address the largely financial barriers to reenrollment. In so doing, students will be more likely to earn their college degrees after incarceration and experience the full value of a college education.

BACKGROUND: Hypotension is associated with organ injury and death in surgical and critically ill patients. In clinical practice, treating hypotension remains challenging because it can be caused by various underlying haemodynamic alterations. We aimed to identify and independently validate endotypes of hypotension in big datasets of surgical and critically ill patients using unsupervised deep learning. METHODS: We developed an unsupervised deep learning algorithm, specifically a deep learning autoencoder model combined with a Gaussian mixture model, to identify endotypes of hypotension based on stroke volume index, heart rate, systemic vascular resistance index, and stroke volume variation observed during episodes of hypotension. The algorithm was developed with data from 871 surgical patients who had 6962 hypotensive events and validated in two independent datasets, one including 1000 surgical patients who had 7904 hypotensive events and another including 1000 critically ill patients who had 53 821 hypotensive events. We defined hypotension as a mean arterial pressure

Background/Objectives: Health care workers are at greater risk for death by suicide compared to the general population and are less likely to seek assistance. More information about correlates of suicidality and treatment-seeking behavior are needed to reduce risk. Methods: The American Foundation for Suicide Prevention developed an Interactive Screening Program to identify and engage at-risk staff and trainees in health care settings. The study reports on the prevalence and demographic and clinical predictors of current suicidal thoughts, behaviors and mental health treatment at a single site (n = 5898) from 2009 to 2024. Results: The study found that 18.2% of respondents reported current suicidal thoughts and behaviors. These were more common among respondents who were younger, male, and who identified as a race/ethnicity other than non-Hispanic White. Suicidal thoughts and behaviors were more likely among those with higher PHQ-8 scores (OR = 1.23, p < 0.01) and those who endorsed maladaptive coping behaviors, hopelessness, loneliness, stress and nervousness (ORs 1.36-3.04, ps < 0.01). Current mental health treatment was more likely among women, non-Hispanic White respondents compared with Asian or Pacific Islander respondents, and nurses relative to physicians. Mental health treatment was also associated with higher PHQ-8 scores, lifetime suicide attempts, difficulty controlling eating and alcohol consumption, and recent feelings of anxiety, stress and nervousness. Conclusions: Findings suggest a continued need to identify and engage health care trainees and staff who are at risk for suicide and to establish new approaches to linking these individuals to resources or interventions aimed at reducing risk. The study identified male and/or Asian/Pacific Islander-identifying health care workers who reported intense loneliness and/or hopelessness, use of non-prescription drugs and recent suicidal thoughts and/or behaviors as high-risk individuals who may require enhanced methods of outreach, identification, acceptance and accessibility of treatment.