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Objectives: To compare the effect of the use of custom and prefabricated insoles on the behavior of plantar weight load and musculoskeletal symptoms in assembly line workers. Methods; A randomized trial was carried out with 27 women who worked in a static standing position and had musculoskeletal symptoms. The mean age was 30.3 ± 7.09 years and the weight 64.85 ± 13.65 Kg. The Nordic Musculoskeletal Questionnaire was administered, and plantar pressure was determined using a computerized baropodometric system (FootWork). The sample was then divided into control group, which wore pre-fabricated insoles, and intervention group, which wore ethylvinylacetate insoles for eight weeks. Baropodometric data were collected and the questionnaire was administered once again. Results: There was no statistically significant difference in the comparison between groups and baropodometric data. However, a change was noted in the behavior of the load variables between evaluations, with an increase in mean load pressure and maximal plantar pressure (p<0.05). No statistically significant difference was found between groups for any anatomical site in the different evaluations. Within each group, there was a reduction in foot pain and back pain between evaluations (p<0.05). Conclusions: Both types of insole reduced pain symptoms in the lumbar region and feet. After eight weeks of use, there was an increase in maximal and mean plantar pressure and a reduction in plantar surface area with both types of insole. Article registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) under the number ACTRN 12609000922279. [ABSTRACT FROM AUTHOR]

Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival. Blood samples were collected from 55 STS patients and age-matched healthy donors (HD) controls. Deep immunophenotyping and gene expression analysis of whole blood was analyzed using multiparametric flow cytometry and real-time RT-qPCR, respectively. Using xMAP technology, proteomic analysis was also carried out on plasma samples. Unsupervised clustering analysis was used to classify patients based on their immune profiles to further analyze the impact of peripheral immunotypes on patient survival. Significant differences were found between STS patients and HD controls. It was found a contraction of B cells and CD4 T cells compartment, along with decreased expression levels of ICOSLG and CD40LG; a major contribution of suppressor factors, as increased frequency of M-MDSC and memory Tregs, increased expression levels of ARG1, and increased plasma levels of IL-10, soluble VISTA and soluble TIMD-4; and a compromised cytotoxic potential associated with NK and CD8 T cells, namely decreased frequency of CD56 dim NK cells, and decreased levels of PRF1, GZMB, and KLRK1. In addition, the patients were classified into three peripheral immunotype groups: "immune-high," "immune-intermediate," and "immune-low." Furthermore, it was found a correlation between these immunotypes and patient survival. Patients classified as "immune-high" exhibited higher levels of immune-related factors linked to cytotoxic/effector activity and longer survival times, whereas patients classified as "immune-low" displayed higher levels of immune factors associated with immunosuppression and shorter survival times. In conclusion, it can be suggested that STS patients have a compromised systemic immunity, and the correlation between immunotypes and survival emphasizes the importance of studying peripheral blood samples in STS. Assessing the peripheral immune response holds promise as a useful method for monitoring and forecasting outcomes in STS., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Almeida, Sousa, Couceiro, Andrade, Alves, Martinho, Rodrigues, Fonseca, Freitas-Tavares, Santos-Rosa, Casanova and Rodrigues-Santos.)

Background: Few studies have found long-term effects of early musical environmental enrichment in the NICU on preterm infant's development. This study examines how early music enrichment affects emotional development and effortful control abilities in 12- and 24-month-old very preterm (VPT) infants., Methods: One hundred nineteen newborns were recruited, including 83 VPTs and 36 full-term (FT) infants. The VPT infants were randomly assigned to the music intervention (44 VPT-Music) or control (39 VPT-control) groups. VPT-Music infants listened specifically designed music intervention from the 33rd week of gestation until hospital discharge. At 12 and 24 months, children were clinically evaluated using the Bayley-III Scales of Infant and Toddler Development and the Laboratory Temperament Assessment Battery, and at 24 months, with 3 additional episodes of the Effortful Control Battery., Results and Discussion: Our analysis showed that during a fear eliciting task, the VPT-Music group expressed lower level of fear reactivity and higher positive motor actions than VPT-controls and FT infants. At 24 months, the VPT-music group had lower scores for negative motor actions in the joy task, compared to both VPT-control and FT groups. In addition, both FT and VPT-music had higher scores of sustained attention compared to VPT-controls, but the contrasts were not significant. No significant effects on mental, language and motor outcomes were identified and for all three dimensions of the ECBQ., Conclusion: The present study suggests that an early music intervention in the NICU might influence preterm children's emotional processing at 12 and 24 months. Limitations and suggestions for future research are highlighted., 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 Filippa, Lordier, Lejeune, De Almeida, Hüppi, Barcos-Munoz, Monaci and Borradori-Tolsa.)

Spinal cord injury (SCI) is one of the most serious conditions of the central nervous system, causing motor and sensory deficits that lead to a significant impairment in the quality of life. Previous studies have indicated that inosine can promote regeneration after SCI. Here we investigated the effects of inosine on the behavioral and morphological recovery after a compressive injury. Adult female C57BL/6 mice were subjected to laminectomy and spinal cord compression using a vascular clip. Inosine or saline injections were administered intraperitoneally, with the first dose performed 24 h after injury and daily for 7 days after injury. The mice were evaluated using Basso Mouse Scale (BMS), locomotor rating scale, and pinprick test for 8 weeks. At the end, the animals were anesthetized and euthanized, and the spinal cords were collected for morphological evaluation. Inosine-treated animals presented better results in the immunostaining for oligodendrocytes and in the number of myelinated fibers through semithin sections compared to saline-treated animals, showing that there was a greater preservation of the white matter. Analysis of the immunoreactivity of astrocytes and evaluation of the inflammatory profile with macrophage labeling revealed that the animals of the inosine group had a lower immunoreactivity when compared to control, which suggests a reduction of the glial scar and less inflammation, respectively, leading to a more favorable microenvironment for spinal cord regeneration. Indeed, inosine-treated animals scored higher on the BMS scale and presented better results on the pinprick test, indicating that the treatment contributed to motor and sensory recovery. After the animals were sacrificed, we obtained the electroneuromyography, where the inosine group showed a greater amplitude of the compound muscle action potential. These results indicate that inosine contributed to the regeneration process in the spinal cord of mice submitted to compressive injury and should be further investigated as a candidate for SCI therapy., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Music is ubiquitous, both in its instrumental and vocal forms. While speech perception at birth has been at the core of an extensive corpus of research, the origins of the ability to discriminate instrumental or vocal melodies is still not well investigated. In previous studies comparing vocal and musical perception, the vocal stimuli were mainly related to speaking, including language, and not to the non-language singing voice. In the present study, to better compare a melodic instrumental line with the voice, we used singing as a comparison stimulus, to reduce the dissimilarities between the two stimuli as much as possible, separating language perception from vocal musical perception. In the present study, 45 newborns were scanned, 10 full-term born infants and 35 preterm infants at term-equivalent age (mean gestational age at test = 40.17 weeks, SD = 0.44) using functional magnetic resonance imaging while listening to five melodies played by a musical instrument (flute) or sung by a female voice. To examine the dynamic task-based effective connectivity, we employed a psychophysiological interaction of co-activation patterns (PPI-CAPs) analysis, using the auditory cortices as seed region, to investigate moment-to-moment changes in task-driven modulation of cortical activity during an fMRI task. Our findings reveal condition-specific, dynamically occurring patterns of co-activation (PPI-CAPs). During the vocal condition, the auditory cortex co-activates with the sensorimotor and salience networks, while during the instrumental condition, it co-activates with the visual cortex and the superior frontal cortex. Our results show that the vocal stimulus elicits sensorimotor aspects of the auditory perception and is processed as a more salient stimulus while the instrumental condition activated higher-order cognitive and visuo-spatial networks. Common neural signatures for both auditory stimuli were found in the precuneus and posterior cingulate gyrus. Finally, this study adds knowledge on the dynamic brain connectivity underlying the newborns capability of early and specialized auditory processing, highlighting the relevance of dynamic approaches to study brain function in newborn populations., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Objectives: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face limitations in portability and privacy due to their need for circulating user data in remote servers for operation. We overcome this by porting iCARE to the web platform., Materials and Methods: We refactored R-iCARE into a Python package (Py-iCARE) and then compiled it to WebAssembly (Wasm-iCARE)-a portable web module, which operates within the privacy of the user's device., Results: We showcase the portability and privacy of Wasm-iCARE through 2 applications: for researchers to statistically validate risk models and to deliver them to end-users. Both applications run entirely on the client side, requiring no downloads or installations, and keep user data on-device during risk calculation., Conclusions: Wasm-iCARE fosters accessible and privacy-preserving risk tools, accelerating their validation and delivery., Competing Interests: None declared., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)

Motivation : The proliferation of genetic testing and consumer genomics represents a logistic challenge to the personalized use of GWAS data in VCF format. Specifically, the challenge of retrieving target genetic variation from large compressed files filled with unrelated variation information. Compounding the data traversal challenge, privacy-sensitive VCF files are typically managed as large stand-alone single files (no companion index file) composed of variable-sized compressed chunks, hosted in consumer-facing environments with no native support for hosted execution. Results : A portable JavaScript module was developed to support in-browser fetching of partial content using byte-range requests. This includes on-the-fly decompressing irregularly positioned compressed chunks, coupled with a binary search algorithm iteratively identifying chromosome-position ranges. The in-browser zero-footprint solution (no downloads, no installations) enables the interoperability, reusability, and user-facing governance advanced by the FAIR principles for stewardship of scientific data. Availability - https://episphere.github.io/vcf, including supplementary material., (©2024 AMIA - All rights reserved.)

Whole Slide Images (WSI), obtained by high-resolution digital scanning of microscope slides at multiple scales, are the cornerstone of modern Digital Pathology. However, they represent a particular challenge to AI-based/AI-mediated analysis because pathology labeling is typically done at slide-level, instead of tile-level. It is not just that medical diagnostics is recorded at the specimen level, the detection of oncogene mutation is also experimentally obtained, and recorded by initiatives like The Cancer Genome Atlas (TCGA), at the slide level. This configures a dual challenge: a) accurately predicting the overall cancer phenotype and b) finding out what cellular morphologies are associated with it at the tile level. To address these challenges, a weakly supervised Multiple Instance Learning (MIL) approach was explored for two prevalent cancer types, Invasive Breast Carcinoma (TCGA-BRCA) and Lung Squamous Cell Carcinoma (TCGA-LUSC). This approach was explored for tumor detection at low magnification levels and TP53 mutations at various levels. Our results show that a novel additive implementation of MIL matched the performance of reference implementation (AUC 0.96), and was only slightly outperformed by Attention MIL (AUC 0.97). More interestingly from the perspective of the molecular pathologist, these different AI architectures identify distinct sensitivities to morphological features (through the detection of Regions of Interest, RoI) at different amplification levels. Tellingly, TP53 mutation was most sensitive to features at the higher applications where cellular morphology is resolved., Competing Interests: 7.Author Declaration There is no conflict of interest to report.

The African buffalo, Syncerus caffer, is a key species in African ecosystems. Like other large herbivores, it plays a fundamental role in its habitat acting as an ecosystem engineer. Over the last few centuries, African buffalo populations have declined because of range contraction and demographic decline caused by direct or indirect human activities. In Mozambique, historically home to large buffalo herds, the combined effect of colonialism and subsequent civil wars has created a critical situation that urgently needs to be addressed. In this study, we focused on the analysis of genetic diversity of Syncerus caffer caffer populations from six areas of Mozambique. Using genome-wide SNPs obtained from ddRAD sequencing, we examined the population structure across the country, estimated gene flow between areas under conservation management, including national reserves, and assessed the inbreeding coefficients. Our results indicate that all studied populations of Syncerus caffer caffer are genetically depauperate, with a high level of inbreeding. Moreover, buffaloes in Mozambique present a significant population differentiation between southern and central areas. We found an unexpected genotype in the Gorongosa National Park, where buffaloes experienced a dramatic population size reduction, that shares a common ancestry with southern populations of Catuane and Namaacha. This could suggest the past occurrence of a connection between southern and central Mozambique and that the observed population structuring could reflect recent events of anthropogenic origin. All the populations analysed showed high levels of homozygosity, likely due to extensive inbreeding over the last few decades, which could have increased the frequency of recessive deleterious alleles. Improving the resilience of Syncerus caffer caffer in Mozambique is essential for preserving the ecosystem integrity. The most viable approach appears to be facilitating translocations and re-establishing connectivity between isolated herds. However, our results also highlight the importance of assessing intraspecific genetic diversity when considering interventions aimed at enhancing population viability such as selecting suitable source populations., (© 2024. The Author(s).)

Objective: to understand feelings about birth among a group of high-risk pregnant women., Method: a descriptive and qualitative study, using Alfred Schütz's social phenomenology as a philosophical theoretical framework. The study included 25 pregnant women undergoing high-risk prenatal care. The interview had the following guiding questions: tell me about your feelings regarding the moment of birth/childbirth; How do you deal with the high-risk diagnosis? What are your expectations for birth/childbirth?, Results: five categories emerged: Fear of obstetric care; Fear of complications with the baby; Fear of cesarean section; Resilience in the face of high-risk pregnancy; and Expectations for birth., Considerations: high-risk pregnant women are afraid of the care they will receive, the risks and concern about the baby's vitality at birth. The importance of care is emphasized, with a welcoming environment, bonding and communication between health team and pregnant woman.

The analysis of data over space and time is a core part of descriptive epidemiology, but the complexity of spatiotemporal data makes this challenging. There is a need for methods that simplify the exploration of such data for tasks such as surveillance and hypothesis generation. In this paper, we use combined clustering and dimensionality reduction methods (hereafter referred to as 'cluster embedding' methods) to spatially visualize patterns in epidemiological time-series data. We compare several cluster embedding techniques to see which performs best along a variety of internal cluster validation metrics. We find that methods based on k-means clustering generally perform better than self-organizing maps on real world epidemiological data, with some minor exceptions. We also introduce EpiVECS, a tool which allows the user to perform cluster embedding and explore the results using interactive visualization. EpiVECS is available as a privacy preserving, in-browser open source web application at https://episphere.github.io/epivecs ., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Motivation: As prescription drug prices have drastically risen over the past decade, so has the need for real-time drug tracking resources. In spite of increased public availability to raw data sources, individual drug metrics remain concealed behind intricate nomenclature and complex data models. Some web applications, such as GoodRX, provide insight into real-time drug prices but offer limited interoperability. To overcome both obstacles we pursued the direct programmatic operation of the stateless Application Programming interfaces (HTTP REST APIs) maintained by the Food and Drug Administration (FDA), Medicaid, and National Library of Medicine. These data-intensive resources represent an opportunity to develop Software Development Kits (SDK) to streamline drug metrics without downloads or installations, in a manner that addresses the FAIR principles for stewardship in scientific data-Findability, Accessibility, Interoperability, and Reusability. These principles provide a guideline for continual stewardship of scientific data., Results: MedicaidJS SDK was developed to orchestrate API calls to three complementary data resources: Medicaid (data.medicaid.gov), Food and Drug Administration (open.fda.gov), and the National Library of Medicine RxNorm (lhncbc.nlm.nih.gov/RxNav). MedicaidJS synthesizes response data from each platform into a zero-footprint JavaScript modular library that provides data wrangling, analysis, and generation of embeddable interactive visualizations. The SDK is served on github with live examples on observableHQ notebooks. It is freely available and can be embedded into web applications as modules returning structured JSON data with standardized identifiers., Availability and Implementation: Open source code publicly available at https://github.com/episphere/medicaid, live at episphere.github.io/medicaid, supplementary interactive Observable Notebooks at observablehq.com/@medicaidsdk/medicaidsdk., Competing Interests: None declared., (Published by Oxford University Press 2023.)

Background: Online questionnaires are commonly used to collect information from participants in epidemiological studies. This requires building questionnaires using machine-readable formats that can be delivered to study participants using web-based technologies such as progressive web applications. However, the paucity of open-source markup standards with support for complex logic make collaborative development of web-based questionnaire modules difficult. This often prevents interoperability and reusability of questionnaire modules across epidemiological studies., Results: We developed an open-source markup language for presentation of questionnaire content and logic, Quest, within a real-time renderer that enables the user to test logic (e.g., skip patterns) and view the structure of data collection. We provide the Quest markup language, an in-browser markup rendering tool, questionnaire development tool and an example web application that embeds the renderer, developed for The Connect for Cancer Prevention Study., Conclusion: A markup language can specify both the content and logic of a questionnaire as plain text. Questionnaire markup, such as Quest, can become a standard format for storing questionnaires or sharing questionnaires across the web. Quest is a step towards generation of FAIR data in epidemiological studies by facilitating reusability of questionnaires and data interoperability using open-source tools., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Motivation: Currently, the Polygenic Score (PGS) Catalog curates over 400 publications on over 500 traits corresponding to over 3000 polygenic risk scores (PRSs). To assess the feasibility of privately calculating the underlying multivariate relative risk for individuals with consumer genomics data, we developed an in-browserPRS calculator for genomic data that does not circulate any data or engage in any computation outside of the user's personal device., Results: A prototype personal risk score calculator, created for research purposes, was developed to demonstrate how the PGS Catalog can be privately and readily applied to readily available direct-to-consumer genetic testing services, such as 23andMe. No software download, installation, or configuration is needed. The PRS web calculator matches individual PGS catalog entries with an individual's 23andMe genome data composed of 600k to 1.4 M single-nucleotide polymorphisms (SNPs). Beta coefficients provide researchers with a convenient assessment of risk associated with matched SNPs. This in-browser application was tested in a variety of personal devices, including smartphones, establishing the feasibility of privately calculating personal risk scores with up to a few thousand reference genetic variations and from the full 23andMe SNP data file (compressed or not)., Availability and Implementation: The PRScalc web application is developed in JavaScript, HTML, and CSS and is available at GitHub repository (https://episphere.github.io/prs) under an MIT license. The datasets were derived from sources in the public domain: [PGS Catalog, Personal Genome Project]., Competing Interests: None declared., (Published by Oxford University Press 2023.)

Starch's crystalline structure and gelatinization temperature might facilitate or hinder its use. Ball milling has frequently been mentioned in the literature as a method for reducing starch size and as a more environmentally friendly way to change starch, such as by increasing surface area and reactivity, which has an impact on other starch properties. In this study, starch samples were milled for varying durations (1, 5, 10, 20, and 30 h) and at different starch-to-ball mass ratios (1:6 and 1:20). Microscopy and XRD revealed that prolonged milling resulted in effective fragmentation and a decrease in crystallinity of the starch granules. Increasing milling times resulted in an increase in amylose content. Rheology and thermal studies revealed that gelatinization temperatures dropped with milling duration and that viscosity and thixotropy were directly influenced. The samples milled for 10, 20, and 30 h at a ratio of 1:20 were the most fragmented and upon drying formed a transparent film at ambient temperature, because of the lower gelatinization temperature. Starch ball milling could lead to the use of this material in thermosensitive systems., Competing Interests: The authors declare no conflicts of interest.

Motivation: Epidemiological studies face two important challenges: the need to ingest ever more complex data types, and mounting concerns about participant privacy and data governance. These two challenges are compounded by the expectation that data infrastructure will eventually need to facilitate cross-registration of participants by multiple epidemiological studies. Implementation: The portable web-service epiDonate was developed using the serverless model known as FaaS (Function-as-a-Service). The reference implementation uses nodejs. The implementation relies on a simple tokenization scheme, mediated by a public API, that a) distinguishes admin from participant roles, with b) extensible permission configuration operating a read/write structure. General Features: The critical design feature of epiDonate is the absence of business logic on the server-side (the web service). The simplicity removes the need to customize virtual machines and enables ecosystems of multiple web Applications backed by one or more data donation deployments. Availability: https://episphere.github.io/donate., (©2023 AMIA - All rights reserved.)

Data sharing is essential for reproducibility of epidemiologic research, replication of findings, pooled analyses in consortia efforts, and maximizing study value to address multiple research questions. However, barriers related to confidentiality, costs, and incentives often limit the extent and speed of data sharing. Epidemiological practices that follow Findable, Accessible, Interoperable, Reusable (FAIR) principles can address these barriers by making data resources findable with the necessary metadata, accessible to authorized users, and interoperable with other data, to optimize the reuse of resources with appropriate credit to its creators. We provide an overview of these principles and describe approaches for implementation in epidemiology. Increasing degrees of FAIRness can be achieved by moving data and code from on-site locations to remote, accessible ("Cloud") data servers, using machine-readable and nonproprietary files, and developing open-source code. Adoption of these practices will improve daily work and collaborative analyses and facilitate compliance with data sharing policies from funders and scientific journals. Achieving a high degree of FAIRness will require funding, training, organizational support, recognition, and incentives for sharing research resources, both data and code. However, these costs are outweighed by the benefits of making research more reproducible, impactful, and equitable by facilitating the reuse of precious research resources by the scientific community., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023.)

Forecasting methods are notoriously difficult to interpret, particularly when the relationship between the data and the resulting forecasts is not obvious. Interpretability is an important property of a forecasting method because it allows the user to complement the forecasts with their own knowledge, a process which leads to more applicable results. In general, mechanistic methods are more interpretable than non-mechanistic methods, but they require explicit knowledge of the underlying dynamics. In this paper, we introduce EpiForecast, a tool which performs interpretable, non-mechanistic forecasts using interactive visualization and a simple, data-focused forecasting technique based on empirical dynamic modelling. EpiForecast's primary feature is a four-plot interactive dashboard which displays a variety of information to help the user understand how the forecasts are generated. In addition to point forecasts, the tool produces distributional forecasts using a kernel density estimation method-these are visualized using color gradients to produce a quick, intuitive visual summary of the estimated future. To ensure the work is FAIR and privacy is ensured, we have released the tool as an entirely in-browser web-application., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with "CD1d-independent" antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings.

Motivation: The Division of Cancer Epidemiology and Genetics (DCEG) and the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI) have recently generated genome-wide association study (GWAS) data for multiple traits in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Genomic Atlas project. The GWAS included 110 000 participants. The dissemination of the genetic association data through a data portal called GWAS Explorer, in a manner that addresses the modern expectations of FAIR reusability by data scientists and engineers, is the main motivation for the development of the open-source JavaScript software development kit (SDK) reported here., Results: The PLCO GWAS Explorer resource relies on a public stateless HTTP application programming interface (API) deployed as the sole backend service for both the landing page's web application and third-party analytical workflows. The core PLCOjs SDK is mapped to each of the API methods, and also to each of the reference graphic visualizations in the GWAS Explorer. A few additional visualization methods extend it. As is the norm with web SDKs, no download or installation is needed and modularization supports targeted code injection for web applications, reactive notebooks (Observable) and node-based web services., Availability and Implementation: code at https://github.com/episphere/plco; project page at https://episphere.github.io/plco., (Published by Oxford University Press 2022.)

Social isolation is necessary during the COVID-19 pandemic but can be harmful to mental health, especially in people with neurocognitive disorders. Although physical exercise can alleviate neuropsychiatric symptoms and improve quality of life (QoL), sedentary behavior increased during the pandemic. Online interventions can contribute to improving physical activity and mental health., Objective: The objective of this study was to compare the neuropsychiatric symptoms and QoL of older adults with neurocognitive disorders who participated in an online physical exercise program with sedentary patients during the COVID-19 pandemic., Methods: In this cross-sectional study, 25 older patients with neurocognitive disorders (control group=11; online exercise group=14) were evaluated based on Neuropsychiatric Inventory (NPI) and the Quality of Life in Alzheimer's Disease (QoL-AD) scale., Results: There were differences between the two groups in the total NPI (U=36.50, p=0.025) and the nighttime behavior disturbances item (U=38.00, p=0.033), both with large effect sizes (ES=-1.03, 95% confidence interval [CI]:-1.83 to -0.16 and ES=-1.06, 95%CI -1.86 to -0.19, respectively). In terms of QoL-AD, a difference was identified only in the memory subitem (U=20.00, p=0.005), with a large ES (1.59, 95%CI 0.59-2.48)., Conclusions: Older adults with neurocognitive disorders who participated in an online physical exercise program, during the COVID-19 pandemic, showed fewer neuropsychiatric total symptoms, fewer nighttime disturbances episodes, and better subjective memory, compared to their physically inactive counterparts. Randomized controlled trials should be performed to better understand the effect of physical exercise in neuropsychiatric symptoms in dementia patients during periods of social isolation., Competing Interests: Disclosure: The authors report no conflicts of interest.

The role of the immune system, and hence inflammation, in the pathophysiology of hypertensive patients is not clear. Until now, most clinical and biochemical parameters have failed to predict a positive response to renal denervation (RDN). Our aim was to evaluate the immune response in a cohort of patients treated by RDN, through the analysis of cytokine, chemokine, and growth factor behavior. A population of 21 resistant hypertension patients, treated by RDN, was evaluated at six months and one year. Response was defined as a drop of ≥5 mmHg in ambulatory blood pressure monitoring. Sixty-seven percent and 81% of patients clinically responded after six months and one year, respectively. There were no complications or safety issues. Plasmatic levels of 45 cytokine, chemokine, and growth factors were quantified at four different times, pre- and post-procedure. Baseline characteristics were similar between groups, except that active smoking was more frequent in non-responders at one year. Regulated on activation, normal T cell expressed, and secreted (RANTES/CCL5) levels were significantly lower in responders, both at baseline and at 30 days ( p = 0.037), and a level ≤15,496 pg/mL was the optimal cutoff, for prediction of a response. IL-15, IL-17A, IL-27, and leukemia inhibitory factor varied significantly in time, with an acute rise being observed 24 h after RDN. Our group has previously showed that HLA-DR+ double-negative (DN) T cells were significantly lower in responders. There was a positive correlation between IL-13, -27, and -4, and DN T cells, and a negative correlation between the latter and SDF-1α and TNF-α, at baseline. Low plasmatic levels of the chemokine RANTES/CCL5 was the most significant result associated with RDN response and may help to identify the best candidates among patients with true resistant hypertension. Pro-inflammatory cytokines correlated negatively with DN T cells in responders, a finding compatible with an enhanced inflammatory milieu present in this extremely high cardiovascular risk cohort.

One-third of all Neotropical forests are secondary forests that regrow naturally after agricultural use through secondary succession. We need to understand better how and why succession varies across environmental gradients and broad geographic scales. Here, we analyze functional recovery using community data on seven plant characteristics (traits) of 1,016 forest plots from 30 chronosequence sites across the Neotropics. By analyzing communities in terms of their traits, we enhance understanding of the mechanisms of succession, assess ecosystem recovery, and use these insights to propose successful forest restoration strategies. Wet and dry forests diverged markedly for several traits that increase growth rate in wet forests but come at the expense of reduced drought tolerance, delay, or avoidance, which is important in seasonally dry forests. Dry and wet forests showed different successional pathways for several traits. In dry forests, species turnover is driven by drought tolerance traits that are important early in succession and in wet forests by shade tolerance traits that are important later in succession. In both forests, deciduous and compound-leaved trees decreased with forest age, probably because microclimatic conditions became less hot and dry. Our results suggest that climatic water availability drives functional recovery by influencing the start and trajectory of succession, resulting in a convergence of community trait values with forest age when vegetation cover builds up. Within plots, the range in functional trait values increased with age. Based on the observed successional trait changes, we indicate the consequences for carbon and nutrient cycling and propose an ecologically sound strategy to improve forest restoration success., Competing Interests: The authors declare no competing interest.