bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the care of children with GENetic Rare disease: Observational Cohort study (GenROC): a study protocol
Authors: Low KJ , Watford A , Blair PS , Nabney I , Powell J , Wynn SL , Foreman J , Firth HV , Ingram JC. 
Published: December 2024

AbstractAround 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality(1). Often little is known about expected growth and phenotypes in these children. Parents have responded by setting up social media groups to generate data themselves. Given the significant clinical evidence gaps, this research will attempt to identify growth patterns, developmental profiles and phenotypes, providing data on long-term medical and educational outcomes. This will guide clinicians when to investigate, monitor or treat symptoms and when to search for additional or alternative diagnoses.Methods and analysisThis is an observational, multicentre cohort study recruiting between March 2023 and February 2026. Children aged 6 months up to 16 years with a pathogenic or likely pathogenic variant in a specified gene will be eligible. Children will be identified through the NHS and via self-recruitment. Parents or carers will complete a questionnaire at baseline and again one year after recruitment. The named clinician (in most cases a clinical geneticist) will complete a clinical proforma which will provide data from their most recent clinical assessment. Qualitative interviews will be undertaken with a subset of parents partway through the study. Growth and developmental milestone curves will be generated through the DECIPHER website (https://deciphergenomics.org) where 5 or more children have the same genetic syndrome (at least ten groups expected).The results will be presented at national and international conferences concerning the care of children with genetic syndromes. Results will also be submitted for peer review and publication.Article SummaryStrengths and Limitations of this studyThis study is a collaborative effort which combines previous data with that of a large cohort to maximise possible outputs through the DECIPHER database.The study is the first of its kind to acquire natural history clinical data from a large cohort across the UK to ascertain both gene specific data but also cross syndrome cohort metrics.The study utilises the Musketeers Memorandum to facilitate recruitment from genetics centres across the UK and also empowers families to volunteer directly which will be supported by a national patient support charity.This study does not recruit individuals over the age of 15 and so longer-term outcomes will not be evaluated. Further studies of older individuals will be required to gather their data and we hope that a follow-on study would be possible to enable this.Data are largely gathered through online questionnaires completed by both parent and clinician. The quality of data received will vary depending on the user. This method of data collection may result in selection bias against certain demographic groups which will need to be accounted for in any discussion regarding the generalisability of the results.
A Protocol for a Scoping Study of Economic and Data System Considerations for Climate Change and Pandemic Preparedness in Africa
Authors: Brunn Ariel , Ruiz Francis , Falconer Jane , Delight Ellie , Gerard Jessica , Lui Yang , Bett Bernard , Bah Bubacarr , Uzochukwu Benjamin , Murray Kris 
Published: December 2024

AbstractBackgroundAfrica’s changing climate heightens risk of disease outbreaks with impacts on vulnerable demographics already encumbered by health and socioeconomic burdens. Health preparedness policies to address disease outbreaks rely on integrated information systems and value-for-cost analysis to facilitate sound decision-making during a public health emergency. This rapid scoping review protocol describes thea prioriobjectives and methods to conduct a synthesis of the evidence on economic evaluation and data system capacity at the intersection of pandemic preparedness and climate change.MethodsA search of six bibliographic databases will be conducted by a library information professional spanning the period 2010 – 2023, focused on literature published about pandemic preparedness in Africa in the context of climate change. Studies will be screened in a three-stage process by independent reviewers using Covidence software, with a proportion of excluded articles crosschecked by a reviewer not involved in screening. All articles included in the final study set will need to have a positive response to at least three out of foura prioriscreening questions. Data extraction will follow established frameworks for pandemic preparedness, a list of 14 target climate-sensitive infectious diseases with pandemic potential declared as Public Health Emergencies of International Concern and listed on the WHO’s R&D Blueprint Pathogens, and economic evaluation or data systems domains. Evidence synthesis will include article bibliometric analysis as well as thematic topic categorisation. Gap analysis will be conducted through topic mapping.DiscussionThis protocol lists the methods and analysis that will be followed to survey the literature on the linkages between climate change and pandemic preparedness relating to economic evaluation and data systems structures and needs.
A systematic scoping review of studies describing human factors, human-centered design, and usability of sensor-based digital health technologies
Authors: Tandon Animesh , Cobb Bryan R , Centra Jacob , Izmailova Elena , Manyakov Nikolay V. , McClenahan Samantha , Patel Smit , Sezgin Emre , Vairavan Srinivasan , Vrijens Bernard , Bakker Jessie P 
Published: December 2024

AbstractBackgroundIncreasing adoption of sensor-based digital health technologies (sDHTs) in recent years has cast light on the many challenges in implementing these tools into clinical trials and patient care at scale across diverse patient populations; however, the methodological approaches taken towards sDHT usability evaluation have varied markedly.ObjectiveTo elucidate the current landscape of studies reporting data related to sDHT human factors, human-centered design, and/or usability.MethodsWe conducted a systematic scoping review of studies published between 2013 and 2023 and indexed in PubMed, in which data related to sDHT human factors, human-centered design, and/or usability were reported. Following a systematic screening process, we extracted the study design; participant sample; the sDHT(s) used; the method(s) of data capture; and the type(s) of usability-related data captured.ResultsOur literature search returned 442 papers, of which 85 were found to be eligible and 83 were available for data extraction and not under embargo. In total, 164 sDHTs were evaluated; 141 were wearable tools while the remaining 23 were ambient tools. The majority of studies (n=55; 66%) reported summative evaluations of final-design sDHTs. Almost all studies (n=82; 98%) captured data from targeted end-users, but only 18 (22%) captured data from additional users such as carepartners or clinicians. User satisfaction and ease of use were evaluated for >80% of sDHTs; however, learnability, eficiency, and memorability were reported for only 11 (13%), 4 (5%), and 2 sDHTs (2%), respectively. Fourteen sDHTs (17%) were evaluated according to the extent to which users were able to understand the clinical data or other information presented to them (understandability) and/or the actions or tasks they should complete in response (actionability). Notable gaps in reporting included the absence of a sample size rationale (reported for 25% of all studies and 31% of summative studies) and incomplete sociodemographic descriptive data (complete age, sex/gender, and race/ethnicity reported for 17% of studies).ConclusionsBased on our findings, we suggest four actionable recommendations for future studies that will help to advance the implementation of sDHTs: 1) Consider in-depth assessment of technology usability beyond user satisfaction and ease of use; 2) Expand recruitment to include important user groups such as clinicians and carepartners; 3) Report the rationale for key study design considerations including the sample size; and 4) Provide rich descriptive statistics regarding the study sample to allow a complete understanding of generalizability to other patient populations and contexts of use.
Development and exploratory analysis of a multi-dimensional metric of adherence for digital health interventions
Authors: Mason Harry T. , O’Connor Siobhán , Wong David , Stanmore Emma 
Published: December 2024

AbstractIntroductionAdherence is often cited as an important metric to demonstrate sustained engagement of an individual or population with a health technology, but its definition is often ill-defined. Any adherence definition made for digital health interventions must be clearly defined to ensure a consistent approach to measuring sustained use as an indicator of impact.MethodsThis study followed mathematically-defined definitions of distinct aspects of adherence: initial adoption, consistency, duration, and dropout. These were then applied to a digital physiotherapy dataset of older adults (N=56). Participants were assigned 3 sessions a week of exergames (exercise-based videogames) for 12 weeks using MIRA rehab software platform.ResultsThe following adherence characteristics emerged: an initial dropout of 3% (completed ≤3 sessions), 20% of participants achieving the desired consistency (≥3 sessions a week for 12 weeks), 39% of participants passing a duration threshold (completing ≥20 minutes a week for 12 weeks), and an average dropout at 72.3% (when judged by percentage of sessions completed at dropout).ConclusionThe approach used for measuring and reporting adherence metrics allows readers to draw clear conclusions about the different aspects of engagement that users displayed with the digital health programme. This type of reporting is recommended for all future digital health studies reporting adherence measures to ensure a consistent approach to reporting and comparing digital health interventions and their impact.
Global patterns of rebound to normal RSV dynamics following COVID-19 suppression
Authors: Thindwa Deus , Li Ke , Cooper-Wootton Dominic , Zheng Zhe , Pitzer Virginia E , Weinberger Daniel M 
Published: December 2024

AbstractIntroductionAnnual epidemics of respiratory synctial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting in April 2020, RSV seasonal activity declined due to COVID-19 non-pharmaceutical interventions (NPIs) before re-emerging after relaxation of NPIs. We described the unusual patterns of RSV epidemics that occurred in multiple subsequent waves following COVID-19 in different countries and explored factors associated with these patterns.MethodsWeekly cases of RSV from twenty-eight countries were obtained from the World Health Organisation and combined with data on country-level characteristics and the stringency of the COVID-19 response. Dynamic time warping and regression were used to describe epidemic characteristics, cluster time series patterns, and identify related factors.ResultsWhile the first wave of RSV epidemics following pandemic suppression exhibited unusual patterns, the second and third waves more closely resembled typical RSV patterns in many countries. Post-pandemic RSV patterns differed in their intensity and/or timing, with several broad patterns across the countries. The onset and peak timings of the first and second waves of RSV epidemics following COVID-19 suppression were earlier in the Southern Hemisphere. The second wave of RSV epidemics was also earlier with higher population density, and delayed if the intensity of the first wave was higher. More stringent NPIs were associated with lower RSV growth rate and intensity and a shorter gap between the first and second waves.ConclusionPatterns of RSV activity have largely returned to normal following successive waves in the post-pandemic era. Onset and peak timings of future epidemics following disruption of normal RSV dynamics need close monitoring to inform the delivery of preventive and control measures.
Risk Assessment and Mapping in a Space Analog Station: Collaborations to Ensure Safety and Minimize Failures
Authors: Cabral Iris Campanella , de Oliveira Santana Ana Carolina Seixas , de Rezende Júlio Francisco Dantas , Chucair Soraya , Santos Gabriel Matheus Dutra , Fürstenau Cristina Ribas 
Published: December 2024

AbstractThe development of Map Assessments, especially in analog space missions, plays a fundamental role in identifying, assessing, and mitigating potential threats and challenges that may arise during space operations in extraterrestrial environments. These missions are designed to simulate real space flight conditions, allowing space agencies and exploration teams to test and refine procedures, technologies, and protocols before implementing them in actual space missions. During the risk analysis, various factors are considered, including: i) Environmental Risks: the context in which the mission will occur, as extreme weather conditions; ii) Health and Safety Risks: health and safety of the team members, as exposure to radiation; iii) Operational Risks: associated with operational procedures, communications, resource management, team coordination, and decision-making during the mission; iv) Psychosocial Risks: interpersonal conflicts, and emotion management along with the crew. Based on the analysis of these risks, strategies and mitigation measures are developed to minimize the likelihood of adverse events and their potential consequences. This study aims to analyze occupation risks, divided into physical, chemical, ergonomic, biological, and mechanical, at the analog space station Habitat Marte, located in Rio Grande do Norte, Brazil. As a result, various sources of danger and vulnerabilities in analog space operations were identified, which include: a. identification of the biological risk group, which includes symptoms associated with transmitted diseases or infections, the possibilities of contamination and spread of transmissible diseases; b. identification of the chemical risk group, which includes the presence of harmful gases, such as carbon dioxide and methane, symptoms of exposure, such as breathing difficulties; c. Identification of the mechanical risk group, where insect bites, possible fires, structural collapses, d. Identification of the physical risk group, which includes exposure to extreme temperatures, dehydration, fatigue and falls, e. Identification of the ergonomic risk group, strongly present in issues such as work in confined spaces and repetitive movements, f. Identification of the psychological risk group, which ultimately encompasses stress due to confinement, lack of rest, and fear of incidents during the journey. By conducting this comprehensive and multidisciplinary risk analysis, space agencies and exploration teams can significantly increase the safety, efficacy, and success of their future missions in space. These results provide a solid foundation for the continuous development of risk management strategies and safety measures for long-duration space missions, contributing to the viability and success of future human expeditions to Mars and beyond.
Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation
Authors: Missey Florian , Acerbo Emma , Dickey Adam S. , Trajlinek Jan , Studnička Ondřej , Lubrano Claudia , de Araújo e Silva Mariane , Brady Evan , Všianský Vit , Szabo Johanna , Dolezalova Irena , Fabo Daniel , Pail Martin , Gutekunst Claire-Anne , Migliore Rosanna , Migliore Michele , Lagarde Stanislas , Carron Romain , Karimi Fariba , Astorga Raul Castillo , Cassara Antonino M. , Kuster Niels , Neufeld Esra , Bartolomei Fabrice , Pedersen Nigel P. , Gross Robert E. , Jirsa Viktor , Drane Daniel L. , Brázdil Milan , Williamson Adam 
Published: December 2024

AbstractMedication-refractory focal epilepsy creates a significant challenge, with approximately 30% of patients ineligible for surgery due to the involvement of eloquent cortex in the epileptogenic network. For such patients with limited surgical options, electrical neuromodulation represents a promising alternative therapy. In this study, we investigate the potential of non-invasive temporal interference (TI) electrical stimulation to reduce epileptic biomarkers in patients with epilepsy by comparing intracerebral recordings obtained before, during, and after TI stimulation, to recordings during low and high kHz frequency (HF) sham stimulation. Thirteen patients with symptoms of mesiotemporal epilepsy (MTLE) and implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130Hz (Δf), where the AM was delivered with lower frequency kHz carriers (1kHz + 1.13kHz), or higher frequency carriers (9kHz + 9.13kHz), targeting the hippocampus – a common epileptic focus and consequently stimulation target in MTLE. Our results show that TI stimulation yields a statistically significant decrease in interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs) – specifically fast-ripples (FR) –, where the suppression is apparent in the hippocampal focus and propagation from the focus is reduced brain-wide. HF sham stimulation at 1kHz frequency also impacted the IED rate in the cortex, but without reaching the hippocampal focus. The HF sham effect diminished with increasing frequencies (2, 5, and 9kHz, respectively), specifically as a function of depth into the cortex. This depth dependence was not observed with the TI, independent of the employed carrier frequency (low or high kHz). Furthermore, a strong carry-over effect, i.e., suppression of epileptic biomarkers for a period of time after the end of stimulation, was observed for TI but not for kHz. Our findings underscore the possible application of TI in epilepsy, as an additional non-invasive brain stimulation tool, potentially offering opportunities to assess brain region response to electrical neuromodulation before committing to a deep brain stimulation (DBS) or responsive neurostimulation (RNS) implants. Our results further demonstrate distinct biophysical differences between kHz and focal AM stimulation.Graphical Abstract
Impact of disease-associated chromatin accessibility QTLs across immune cell types and contexts
Authors: Mu Zepeng , Randolph Haley E. , Aguirre-Gamboa Raúl , Ketter Ellen , Dumaine Anne , Locher Veronica , Brandolino Cary , Liu Xuanyao , Kaufmann Daniel E. , Barreiro Luis B. , Li Yang I. 
Published: December 2024

AbstractOnly a third of immune-associated loci from genome-wide association studies (GWAS) colocalize with expression quantitative trait loci (eQTLs). To learn about causal genes and mechanisms at the remaining loci, we created a unified single-cell chromatin accessibility (scATAC-seq) map in peripheral blood comprising a total of 282,424 cells from 48 individuals. Clustering and topic modeling of scATAC data identified discrete cell-types and continuous cell states, which helped reveal disease-relevant cellular contexts, and allowed mapping of genetic effects on chromatin accessibility across these contexts. We identified 37,390 chromatin accessibility QTLs (caQTL) at 10% FDR across eight cell groups and observed extensive sharing of caQTLs across immune cell contexts, finding that fewer than 20% of caQTLs are specific to a single cell type. Notably, caQTLs colocalized with ∼50% more GWAS loci compared to eQTLs, helping to nominate putative causal genes for many unexplained loci. However, most GWAS-caQTL colocalizations had no detectable downstream regulatory effects on gene expression levels in the same cell type. We find evidence that the higher rates of colocalization between caQTLs and GWAS signals reflect missing disease-relevant cellular contexts among existing eQTL studies. Thus, there remains a pressing need for identifying disease-causing cellular contexts and for mapping gene regulatory variation in these cells.
Enzyme-Regulated Non-Thermal Fluctuations Enhance Ligand Diffusion and Receptor-Mediated Endocytosis
Authors: Nividha  , Maiti Arnab , Parihar Kshitiz , Chakraborty Rik , Agarwala Pratibha , Sasmal Dibyendu K. , Radhakrishnan Ravi , Bhatia Dhiraj , Dey Krishna Kanti 
Published: December 2024

AbstractActive enzymes during catalyzing chemical reactions, have been found to generate significant mechanical fluctuations, which can influence the dynamics of their surroundings. These phenomena open new avenues for controlling mass transport in complex and dynamically inhomogeneous environments through localized chemical reactions. To explore this potential, we studied the uptake of transferrin molecules in retinal pigment epithelium (RPE) cells via clathrin-mediated endocytosis. In the presence of enzyme catalysis in the extracellular matrix, we observed a significant enhancement in the transport of fluorophore-tagged transferrin inside the cells. Fluorescence correlation spectroscopy measurements showed substantial increase in transferrin diffusion in the presence of active fluctuations. This study sheds light on the possibility that enzyme-substrate reactions within the extracellular matrix may induce long-range mechanical influences, facilitating targeted material delivery within intracellular milieu more efficiently than passive diffusion. These insights are expected to contribute to the development of better therapeutic strategies by overcoming limitations imposed by slow molecular diffusion under complex environments.
Eukaryotic Translation Initiation Factor Loaded Extracellular Vesicles Promotes Macrophage Cholesterol Metabolism in ovarian cancer
Authors: Mittal Sonam , Nenwani Minal , Kadamberi Ishaque Pulikkal , Kumar Sudhir , Animasahun Olamide , George Jasmine , Tsaih Shirng-Wern , Gupta Prachi , Singh Mona , Geethadevi Anjali , Dey Chandrima , Meurs Noah , Shankaran Ajay , Chaluvally Raghavan Pradeep , Nagrath Deepak , Pradeep Sunila 
Published: December 2024

SummaryTumor-driven immune suppression poses a significant impediment to the success of immunotherapy in ovarian cancer. Among the various mechanisms contributing to immune suppression, intracellular communication facilitated by tumor-derived extracellular vesicles (EVs) within the tumor microenvironment (TME) emerges as a pivotal factor influencing tumor growth.We discovered that EVs from both ovarian tumor cell lines and the plasma of ovarian cancer patients are encapsulated with eukaryotic translation initiation factor 4E (eIF4E). Our study revealed a new mechanism showing how these EVs are loaded with eIF4E and its impact on ovarian cancer progression. We also demonstrated that eIF4E-containing EVs (eIF4E-EVs) alter protein translation in macrophages, contributing to anti-tumor immune response.Treatment of macrophages with eIF4E-EVs induces an immunosuppressive phenotype marked by the release of cytokines such as IL-6 and an elevated expression of Programmed death-ligand 1 (PD-L1). Notably, eIF4E-packaged EVs enhance the expression of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) a pivotal enzyme in cholesterol biosynthesis, resulting in increased cholesterol levels within macrophages. Inhibition of HMGCR or reduction of cholesterol in macrophages effectively restores their antitumor activity by decreasing PD-L1 on macrophages.Analysis of tumor tissue from ovarian cancer patients revealed a positive correlation between HMGCR and TAM in ovarian cancer. In summary, we have characterized the mechanism of how eIF4E loaded EVs induced cholesterol synthesis, creating an immunosuppressive environment by upregulating PD-L1 expression in macrophages.