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MethodsX

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match MethodsX's content profile, based on 14 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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CT Attenuation Map Derived Body Composition Is Associated with Cardiorespiratory Fitness in Multicenter External Validation

Miller, R. J.; Yi, J.; Shanbhag, A.; Patel, K. K.; Ruddy, T. D.; Einstein, A. J.; Feher, A.; Miller, E. J.; Liang, J. X.; Ramirez, G.; Slipczuk, L.; Travin, M. I.; Alexanderson, E.; Carvajal-Juarez, I.; Packard, R. R. S.; Al-Mallah, M.; Acampa, W.; Knight, S.; Le, V. T.; Mason, S.; Wopperer, S.; Chareonthaitawee, P.; Buechel, R. R.; Rosamond, T. L.; Berman, D. S.; Dey, D.; Di Carli, M. F.; Slomka, P.

2026-05-08 cardiovascular medicine 10.64898/2026.05.07.26352573 medRxiv
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AimsExercise capacity is a powerful predictor of cardiovascular risk. In patients unable to exercise, body composition analysis can potentially be used to estimate cardiorespiratory fitness. We developed a body composition "fitness" score, then validated its utility in two external populations. Methods and ResultsWe included patients from four sites undergoing single photon emission computed tomography (SPECT) and twelve sites undergoing positron emission tomography (PET). We quantified body composition using deep learning. We evaluated associations between body composition and good exercise capacity (defined as completing [&ge;]7 minutes on a Bruce protocol) then developed a body composition "fitness" score. We then assessed the associations of "fitness" score with exercise capacity and all-cause mortality in external populations. In total, 36471 patients were included with median age 67 (interquartile range 58 - 74). Median skeletal muscle density was higher among patients with good exercise capacity. In the external SPECT population, the body composition "fitness" score had higher prediction performance for good exercise capacity (AUC 0.771, 95% CI 0.752 - 0.789) than age (AUC 0.717, p<0.01). In the external PET population, high body composition "fitness" score was associated with lower cardiovascular death (adjusted hazard ratio 0.70, 95% CI 0.62 - 0.79, p<0.001). ConclusionsWe demonstrated that a comprehensive body composition "fitness" score could identify patients with good cardiorespiratory fitness. This approach transforms routinely acquired CT data into a surrogate marker of fitness which can be applied in patients undergoing PET, or other CT imaging, where exercise testing is not performed. Graphical AbstractOverview of study design. The overall population (n=36471) was split as outlined above. Body composition was analyzed from available computed tomography imaging. The distribution of body composition measures were analyzed in the combined single photon emission computed tomography (SPECT) populations. A body composition "fitness" score was derived to predict good exercise capacity in the internal population, with associations assessed in the two external testing populations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/26352573v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1b98c3eorg.highwire.dtl.DTLVardef@a64282org.highwire.dtl.DTLVardef@1589559org.highwire.dtl.DTLVardef@b5423f_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Sustainable Health Innovation for Global Health Equity: Solar-Powered MRI for Affordable Healthcare in Resource-Limited Settings

Papasavva, M.; Abate, G. B.; Piper, J.; Kahari, C.; Tavengwa, N. V. B.; Mazhanga, C.; Chidhanguro, D.; Mutero, A.; Musiiwa, L.; Giampietro, V.; Twumasi, R.; Clemensson, P.; Bennallick, C.; Deoni, S.; Nyachowe, C.; Ntozini, R.; Williams, S. C. R.; Prendergast, A. J.; Bourke, N. J.

2026-05-10 neurology 10.64898/2026.05.07.26352684 medRxiv
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IntroductionMagnetic resonance imaging (MRI) is central to neurological care, yet access remains profoundly inequitable in low- and middle-income countries, especially in rural health facilities where high costs and fragile electricity supply limit services. Ultra-low-field (ULF) portable MRI offers a way to expand access, but deployment in weak-grid settings requires robust affordable power. We characterized the power needs of a 0.064T portable ULF MRI system and assessed the feasibility of a solar-powered MRI-capable facility in a rural Zimbabwean clinic, which we believe to be the first of its kind in the world. MethodsWe measured the power draw of an ultra-low-field MRI session from a portable photovoltaic (PV) battery kit in the UK, quantifying scan, standby and energy use. We then monitored a PV-battery micro-grid supplying a protected circuit at an MRI-capable clinic in Shurugwi, Zimbabwe. Inverter telemetry was used to derive PV generation, load, battery state of charge (SoC) and grid import for working days in October-November 2025, spanning the end of the dry season and onset of the rainy season. ResultsIn the portable configuration, a 64-minute MRI session consumed [~]0.21 kWh, with standby demand of [~]1.44 kWh per 24 hours. In clinic, mean PV generation was 9.10 kWh (SD=1.34) and load 9.91 kWh, with zero recorded grid import and minimum daily SoC typically [&ge;]60%, including during the early rainy season. ConclusionAn affordable PV-battery micro-grid can reliably support ULF MRI and associated research power loads in a rural, weak-grid clinic, offering a reproducible blueprint to narrow diagnostic equity gaps in resource-limited settings.

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Development and Validation of an LC-MS Method for Quantification of Sex Steroid Hormones in Skeletal Muscle

Engman, V.; Lamon, S.; Mason, S.

2026-05-15 biochemistry 10.64898/2026.05.12.724720 medRxiv
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1Sex steroid hormones are not exclusively localised in the circulation and can be found in numerous extragonadal tissues, in concentrations unrelated to the circulating fraction. Existing methodology to measure intramuscular steroid hormone concentrations includes both immune-based assays and liquid chromatography-mass spectrometry (LC-MS), the gold standard for hormone measurements. To date, no LC-MS based methods validation has been published on the measurement of intramuscular sex steroid hormones, despite clear biological relevance. Here, we describe the development and validation of a simple, high-throughput LC-MS Orbitrap method for the measurement of 10 intramuscular sex steroid hormones, including pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, epitestosterone, dihydrotestosterone, oestrone, oestradiol, and oestriol. In brief, isotope labelled standards were added to 5-6 milligrams of lyophilised muscle tissue, homogenised and extracted with ethyl acetate. The extracts were dried down and sequentially derivatised with 1-methylimidazole-2-sulfonyl chloride and hydroxylamine hydrochloride to target both the phenolic hydroxyl groups and ketone groups. The limit of detection was 1.0 {+/-} 1.0 pg/mg (range 0.36 - 3.26 pg/mg), with a R2 > 0.99 for all analytes. Matrix effects were 90-110% for all analytes except for dihydrotestosterone (143.6%), and precision was <10 CV% for all analytes in the presence of a muscle matrix. Our method allows for 20-40 samples to be prepared in [~]4 h, with a sample data acquisition time of 13 minutes. Moreover, our method provides the opportunity for specific analysis of steroid hormone concentrations in skeletal muscle, allowing target tissue specificity instead of relying on proxy measures from the circulation.

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Protocol for measuring endocrine disruptive effects on transcriptional bursting using single-molecule imaging in human breast cancer cells

Yasar, P.; Day, C. R.; Rodriguez, J.

2026-05-05 cell biology 10.64898/2026.05.01.722245 medRxiv
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Transcriptional bursts regulate gene expression by altering burst size or burst frequency. Here, we present a protocol that integrates fixed-cell smFISH and live-cell single-molecule imaging to analyze estrogen-responsive transcriptional bursting of the TFF1 gene in human breast cancer cell lines. This workflow enables measurement of burst size, burst initiation, and active allele frequency to determine how endocrine disruptor chemicals modulate transcriptional bursting dynamics. For complete details on the use and execution of this protocol, please refer to Day, Yasar et al.1

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Report on pre-validation of an animal-free alternative method (NAM) for regulatory safety testing: InfiniteLungDT, an in-vitro-learned digital twin for the prediction of material-triggered chronic neutrophilic lung inflammation

Urbancic, I.; Koklic, T.; Kokot, H.; Kokot, B.; Kozoderec, N.; Kolodziej, T.; Licina, T.; Ma-Hock, L.; Hogh Danielsen, P.; Alstrup Jensen, K.; Cubej Gasparin, M.; Pahor, T.; Cosnier, F.; Valentino, S.; Seidel, C.; Isaxon, C.; Vuk, T.; Gate, L.; Landsiedel, R.; Stöger, T.; Vogel, U. B.; Strancar, J.

2026-05-17 pharmacology and toxicology 10.64898/2026.05.12.723437 medRxiv
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Until now, there has been no animal-free alternative method for predicting chronic inflammation and delivering the associated dose responses, the timing of onset, and the duration of inflammation, as required by regulatory agencies. We present the results of pre-validation of an in-vitro-learned digital twin (InFiniteLungDT) capable of predicting chronic neutrophilic lung inflammation for regulatory use. The method is based on measuring the dynamics of early biological effects in vitro induced by respirable materials or their mixtures, without the need to know their intrinsic properties. We constructed the digital twin(s) for each of the material, for which we have in vivo exposure data. The instillation data set, comprising 49 different nanomaterials, was used as the primary anchor to calibrate the model. Inhalation data set, comprising 7 different nanomaterials, compliant with OECD TG 412, was used to show the general applicability of the method across species and for different exposure scenaria. In total, about 3094 single mouse exposures and 364 rat exposures (and approx. 775/225 non-exposed mouse/rat controls) were used to predict concentration-dependent time-evolved neutrophil influx into the lung. The accuracy (predictive capacity) of LOAEL determination is 93% for instillation and 84% for inhalation exposure. Taking into account the time-to-deliver-result being less than 1 week, this proves that the effect of inhaled material from acute to chronic conditions can be assessed orders of magnitude faster and cheaper than in a reference animal study.

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A quantitative proteomics dataset for assessment and prediction of low dose X-ray radiation exposure in mice.

Zelter, A.; Riffle, M.; Merrihew, G. E.; Mutawe, B.; Shulman, N.; Sanders, J. A.; Noble, W. S.; Johnson Erickson, D. P.; Morimoto, A.; Shaver, B. A.; Steins, T. N.; Cao, N.; Ford, E. C.; Rudnick, P. A.; Chelsky, D.; Wan, K. H.; Inman, J. L.; Chang, H.; Snijders, A. M.; Mao, J.-H.; Celniker, S. E.; De Chant, J.; Obst-Huebl, L.; Nakamura, K.; Wu, C. C.; MacCoss, M. J.

2026-05-19 biochemistry 10.64898/2026.05.18.725951 medRxiv
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Ionizing radiation induces molecular responses that may be used to estimate exposure when physical dosimeters are unavailable. Here we present two large-scale proteomics datasets generated from mouse dorsal skin punch samples collected following controlled X-ray exposures spanning multiple doses, dose rates, and post-exposure time points. Experiment 1 comprised 96 samples (including 16 reference samples) collected 6 days after exposure to 0-75 cGy delivered at either 30 or 300 cGy/min. Experiment 2 comprised 936 samples (including 236 reference samples) exposed to 0-100 cGy at either 3 or 28 cGy/min dose rates and harvested between 7 and 150 days post-exposure. All samples were processed using a standardized workflow involving automated bead-based digestion and data-independent acquisition mass spectrometry. The datasets include multiple pooled reference sample types, process controls, and system suitability standards ensuring high quality data. All data presented are available via ProteomeXchange at several levels of processing, from raw files through normalized peptide- and protein-level abundance matrices suitable for biomarker discovery and machine learning applications. This dataset will facilitate generation of new insights into the biological changes and molecular signatures resulting from X-ray exposure in mice and may also help inform future studies in humans.

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Model-supported patient stratification using multi-objective synergy optimization in combination therapy

Gevertz, J. L.; Kareva, I.

2026-05-07 pharmacology and toxicology 10.64898/2026.05.04.722754 medRxiv
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The challenge of stratifying patients for combination therapy is both technically demanding and clinically crucial. In previous work, we introduced a multi-objective optimization framework for identifying optimally synergistic combination protocols that are robust to competing definitions of additivity. This manuscript extends this methodology to quantify how inter-individual variability in drug sensitivity influences the combination doses that optimally balance the competing objectives of synergy of efficacy and synergy of potency (a proxy measure of toxicity). For this methodology, we introduce a voxel-based stratification approach to characterize individuals (model parameterizations) into subgroups based on sensitivity to each drug as a monotherapy and in combination. As a case study, we apply the method to a preclinical dataset of murine response to the combination of an immune checkpoint inhibitor and an antiangiogenic agent. We demonstrate that the algorithm can quantify how the robustly optimal combination therapies vary across different treatment response subgroups and how the algorithm can identify subpopulations for which no meaningfully efficacious combination exists. As applying the methodology requires knowledge of specific parameter values for which measurable biomarkers may be unavailable, we also propose an initiation protocol that permits identification of the parameters necessary to place an individual in a subgroup. This methodology is a step in the direction of determining the right combination therapy for a subgroup and finding the right subgroup for an existing therapy.

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Reliability and Concurrent Validity of a Computer Vision-Based Tool for Quantitative Finger Movement Analysis

Maharshi, A.; Ladha, B.; Malani, R.; Palaskar, P.

2026-06-01 rehabilitation medicine and physical therapy 10.64898/2026.05.21.26353446 medRxiv
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Background: Accurate evaluation of fine motor abilities is a key aspect of neurological rehabilitation. However, conventional approaches like goniometry are limited by variations among raters and their difficulty in detecting active movement. On the other hand, computer vision-based software delivers non-invasive and quantitative analysis of hand movements. An innovative computer-vision-based software tool, F.A.I.R. Chance(C), was developed to track and analyze individual finger joint movements on a camera-equipped laptop and give real-time numerical feedback. However, its metrics require validation in a healthy population before the tool can be used for clinical purposes. Objective: To assess the reliability and validity of finger movement assessment by the F.A.I.R. Chance computer vision-based tool in healthy adult participants. Methods: An observational cross-sectional study was done at MGM School of Physiotherapy, comprising 30 healthy participants between 18 and 60 years of age. Finger movements like flexion, extension, abduction, and adduction were measured with a standard handheld goniometer. These same finger movements were then measured with the tool at two time points separated by a 30-minute interval to determine the test-retest reliability. The tool's measurements were compared with the goniometric measurements to determine its concurrent validity. Test retest reliability was checked by the Intra-class Correlation Coefficient ICC (2,1), while concurrent validity was tested through Pearson's correlation coefficients. Results: Metacarpophalangeal and proximal interphalangeal joint motions demonstrated moderate to good test-retest reliability (ICC: 0.716-0.953) for the F.A.I.R. Chance tool. However, distal interphalangeal joint movements had lower consistency. Good reliability (ICC: 0.754-0.908) was seen for movements of abduction and adduction in the fingers. Strong concurrent validity for extension movements of the metacarpophalangeal joints (r=0.760-0.914) and moderate concurrent validity for flexion movements of the metacarpophalangeal joints (r=0.427-0.604) was demonstrated for all fingers for the F.A.I.R. Chance tool. Concurrent validity for adduction and abduction movements demonstrated a low to fair correlation with goniometric measurements (r=0.210-0.440). This is consistent with previous research showing poor agreement between goniometry and adduction-abduction movements of the fingers. Conclusion: The F.A.I.R. Chance tool shows good reliability and acceptable concurrent validity to assess fine motor movements in the healthy adult population. This sets a basis for further clinical study of the tool in the target population with fine motor impairments. Keywords: artificial intelligence; assistive technology; computer vision; fine motor evaluation; hand function;

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A Cardiac Contouring Atlas of the Left Ventricle Myocardial Walls on CT

Wei, J.; Abdollahi, A.; Knoll, M.; Furkel, J.

2026-05-07 cardiovascular medicine 10.64898/2026.05.06.26352374 medRxiv
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Background and purposePrecise manual annotation of the left ventricular myocardial (LVM) wall is essential for cardiac substructure research, wall-specific radiation dosimetry, and segmentation model development. However, existing radiotherapy-oriented atlases and conventional CT viewing planes lack an explicit framework for reproducible, wall-level LVM delineation. To address this gap, we developed an anatomy-guided manual segmentation protocol for delineating the five LVM walls on non-contrast-enhanced CT (NECT) or contrast-enhanced CT (CECT) scans. Materials and methodsThis protocol was developed using 60 chest CT scans from two prospective cohorts at Heidelberg University Hospital, including 50 CECTs from IMRT-MC2 cohort and 10 NECTs from MAGELLAN cohort. Manual contouring was performed in 3D Slicer. Segmentation rules were established through review by a radiation oncologist and a cardiology expert, based on the American Heart Association 17-segment model, and were tested on additional CT scans before final protocol definition. ResultsThe protocol centers on three geometric steps: (1) defining the LV long axis using the endocardial apex and the center of the mitral annulus; (2) constructing an apical delimitation plane based on LV geometry; and (3) partitioning wall regions via intersections of the right ventricular and LV cavity centers in the short-axis view. This workflow enables structured segmentation of the anterior, septal, lateral, inferior, and apical LVM walls, supporting anatomically coherent 3D reconstruction. ConclusionThis study provides contouring steps and a representative atlas as a methodological basis for standardized annotation, with potential applications in dose-mapping cardiotoxicity analysis and deep-learning modeling for radiotherapy.

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InSleep46: Deployment of a remote monitoring device for the detection and monitoring dementia risk in older adult populations: a feasibility study

King-Robson, J.; Cartlidge, M. R. E.; Soreq, E.; Murray-Smith, H.; Harrison, M.; Horrocks, S.; Aimola, L.; Poole, M.; Mc Ardle, R.; Robinson, L.; Sharp, D. J.; Schott, J. M.

2026-05-24 neurology 10.64898/2026.05.22.26353861 medRxiv
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Background: Improvements in health technology offer opportunities for remote disease screening, diagnosis and monitoring. The Withings Sleep Analyzer (WSA), an under mattress ballistocardiograph sensor able to detect body movement, breathing, and cardiac ejection is a promising technology for the non-invasive detection and monitoring of neurodegenerative diseases. InSleep46 aims to evaluate whether the WSA is able to detect preclinical Alzheimer's disease in members of the 1946 British Birth cohort, now in their late 70s. Objectives: To assess feasibility of deployment of a remote sleep, circadian and physiological monitoring device in a population of older adults. Participants: 356 participants from the Insight 46 neuroimaging sub-study (1946 British Birth Cohort), all born in one week in March 1946. Methods: We describe remote recruitment, device installation, and troubleshooting protocols. Feasibility analysis examined participant characteristics associated with recruitment and successful device set-up using logistic regression. Troubleshooting events for device installation and maintenance were recorded over a mean 14-month follow-up period. Results: During the feasibility analysis period, 263 (74%) participants, mean (SD) age 77 years (0.47) agreed to take part, of whom 245 (93%) successfully set up the WSA. Recruitment and successful set up of the WSA were not dependent on cognitive ability, socioeconomic position, or educational attainment. 162 (62%) of recruited individuals required [&ge;]1 troubleshooting call (mean 2.3 per participant, range 0-16). 603 calls were required in total. Conclusion: Deployment of a remote sleep and physiological monitoring device in an older adult population is feasible. Most participants required individualised assistance to set up the device. For the technology to be widely implemented, the set up must be accessible, with dedicated support available.

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A Supervised Learning Framework for Stroke Hospitalization Factors Selection Using the Lasso-MIDAS Model

Li, Q.; Wang, L.

2026-05-20 cardiovascular medicine 10.64898/2026.05.15.26353365 medRxiv
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Stroke, as an acute cerebrovascular disease with significant public health implications, is influenced by a complex interplay of meteorological conditions, air quality, and socioeconomic factors. However, the inherent challenges of mixed-frequency data from diverse sources and high-dimensional variable spaces limit the effectiveness of traditional regression models. This study develops a Lasso-MIDAS model framework to identify the key multidimensional drivers of stroke admissions. Using this approach, 21 candidate variables encompassing meteorological, environmental, and economic indicators were screened. The empirical results identified 11 core influencing factors. In the meteorological and environmental dimensions, Wind Speed, Carbon Monoxide (CO), and Sulfur Dioxide (SO2) were identified as significant positive drivers, with Temperature Difference also positively correlating with admission risks. Conversely, Nitrogen Dioxide (NO2) exhibited a negative correlation, potentially reflecting behavioral adaptation and exposure reduction during peak pollution periods. In the socioeconomic dimension, the Consumer Price Index (CPI) for Food, Tobacco, and Alcohol emerged as a major risk factor, highlighting the impact of living cost pressures on public health. The findings demonstrate the superiority of the Lasso-MIDAS model in handling large-scale healthcare data. It effectively addresses the frequency mismatch problem while enhancing the robustness of causal identification through variable shrinkage. These conclusions provide a scientific basis for health authorities to establish early warning systems and optimize public health policy interventions.

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Addressing Data Fragmentation in Biodiversity: A Workflow for integrated Species Distribution Models

Perrin, S. W.; Adjei, K. P.; Mostert, P.; Togunov, R. R.; Herfindal, I.; Topper, J. P.; Grytnes, J.-A.; Chipperfield, J.; O'Hara, R. B.; Finstad, A. G.

2026-05-21 ecology 10.64898/2026.05.19.721053 medRxiv
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AimA comprehensive understanding of the spatial distribution of biodiversity is hindered by fragmented datasets, sampling biases, and inconsistent observation protocols. Here, we present a workflow that integrates disparate datasets to produce large scale maps of biodiversity metrics as a basis for management-relevant information tools. We use integrated species distribution modeling (iSDM) to account for sampling biases and disparate data collection techniques, taking advantage of the vast numbers of open datasets available in data aggregators like GBIF. LocationNorway (excluding Svalbard and Jan Mayen) TaxonVascular plants MethodsThe workflow consists of four main steps: data acquisition, data integration, integrated species distribution modelling (iSDM), and the production of derived outputs. Input data include structured surveys, opportunistic observations, and environmental covariates. These are standardised and integrated into a point-processed based iSDM framework to produce species richness maps, associated uncertainties, and sampling effort maps. The outputs are further processed to identify biodiversity hotspots or to summarise species-environment relationships. The workflow used vascular plant data from Norway, combining occurrence-only and presence-absence datasets with environmental covariates. Outputs were generated at a spatial resolution of 500 x 500 meters, balancing accuracy, computational feasibility and relevance for management decisions. High-performance computing resources were utilized for model fitting and predictions. A subset of available data was used to validate the species richness maps. ResultsWe produced detailed maps of species richness, uncertainties and sampling intensity across Norways heterogeneous landscape, incorporating 1218 species in our final results. The species richness patterns highlight patterns consistent with previous mapping efforts. Validation showed an increase in model accuracy when compared to models which did not use an iSDM framework. The workflow highlights limitations in the infrastructure of the currently openly accessible data, particularly the need for more structured presence-absence datasets and standardized metadata. Main conclusionsThis study underscores the potential of workflows that integrate disparate datasets for biodiversity modeling. To maximize accuracy and utility, future efforts should focus on improving data standardization, the publication and collection of more structured data, and fostering data-sharing collaborations. Advances in the workflow itself, including optimising modelling covariates and integrating more comprehensive spatio-temporal aspects, will also increase the relevance of the outputs. These advances will increase our ability to estimate species richness with a precision and accuracy that can reliably inform conservation and management decisions.

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When advantage turns into risk: disentangling landscape and behavioural drivers of socioeconomic inequality in Lyme disease risk, Glasgow as a case study

Gandy, S. L.; Plahe, G.; Hall, J.; Watkinson, K.; Guntupalli, S.; Johnson, D.; Birtles, R.; Mavin, S.; Gilbert, L.

2026-05-21 public and global health 10.64898/2026.05.18.26353476 medRxiv
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Introduction: Socioeconomic deprivation is often associated with poorer health outcomes, but some studies suggest the opposite for Lyme disease. Here we test two hypotheses to explain this: differences in (i) local landcover of high risk habitats such as woodlands (landscape hypothesis) and (ii) outdoor recreation in such habitats (behaviour hypothesis). Methods: We analysed reported Lyme disease incidence data for 824 data zones in the city of Glasgow, UK, against deprivation rank (based on indicators relating to income, employment, health, education, crime and housing). We then tested how these relate to woodland cover and indices of urban greenspace usage (per capita and per ha of greenspace). Additionally, we measured Lyme disease hazard (density of infected ticks) in 32 greenspaces and tested relationships with deprivation, woodland and greenspace usage. Results: More advantaged data zones (data zones with low deprivation rank) had higher Lyme disease incidence. These areas had more woodland and woodland cover was positively correlated with both Lyme disease incidence and hazard. Deprivation did not correlate with greenspace usage, nor did greenspace usage correlate with Lyme disease incidence. Intensely used greenspaces had lower infected tick densities, consistent with a human disturbance effect on wildlife that carry ticks. Conclusions: Differences in woodland cover, but not outdoor recreation behaviour, can help explain our finding of higher Lyme disease incidence in more advantaged areas. However, to further test the behaviour hypothesis, we need more detailed data on outdoor recreation activity per capita both locally and in rural areas, as well data on mitigation behaviours.

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Homologous recombination delayed repair in oocytes in the bdelloid rotifer Adineta vaga post radiation

Moris, V. C.; Philippart, A.; Husson, C.; Hallet, B.; Hespeels, B.; Van Doninck, K.

2026-05-05 molecular biology 10.64898/2026.04.30.722046 medRxiv
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Bdelloid rotifers are known to survive desiccation and high doses of ionizing radiation. This extreme resistance is notably due to their capacity to cope with numerous DNA double-strand breaks (DSBs). Genes encoding key components of the non-homologous end joining (NHEJ) DNA repair pathway are strongly upregulated in the bdelloid rotifer Adineta vaga following exposure to ionizing radiation. Considering the notably high doses tolerated by these organisms, their capacity to efficiently restore genome integrity is particularly striking. Although NHEJ is generally regarded as less accurate than homologous recombination (HR), the absence of major genomic rearrangements in the descendants of irradiated rotifers suggests that DNA repair occurs with high fidelity. Terwagne et al. recently reported a delayed repair in germline nuclei, occurring during oocyte development when homologous chromosomes pair, thereby enabling template-based repair through HR. In this study, we established an in situ hybridization approach on A. vaga cryosections to investigate the spatial and temporal expression of key actors involved in NHEJ, HR, and Base excision repair (BER) pathways in somatic and germline tissues. We show that NHEJ (KU80) and BER-related genes (PARPs) as well as A. vaga Ligase E (putatively involved in DNA repair) are expressed early after radiation exposure in the somatic syncytium. In contrast, HR-related genes (Rad51: two paralogs, Rad54), as well as PCNA (involved in DNA replication, NER, BER, HR) are expressed later in maturing oocytes, indicating the activation of a delayed homologous recombination repair pathway in germline nuclei. Nurse cells, which express genes associated with both HR and NHEJ pathways, may rely on both mechanisms for their own DNA repair while also supplying mRNAs to the maturing oocyte. Our results provide new evidence for a differential regulation of DNA DSB repair pathways between soma and germline in bdelloids, with NHEJ predominating in somatic tissues and HR in the germline of A. vaga. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/722046v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@3b1f3borg.highwire.dtl.DTLVardef@17f5eb5org.highwire.dtl.DTLVardef@122ef14org.highwire.dtl.DTLVardef@7e4413_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOAbstract Figure:C_FLOATNO Summary of in situ hybridization results: genes coding for actors of NHEJ are expressed in the somatic nuclei and in the nurse nuclei of Adineta vaga individuals 2.5 hours post X-rays radiation, while genes coding for HR actors and PCNA (involved in multiple pathways including DNA replication and DNA repair: NER, BER, MR, HR) are expressed in the nurse nuclei 2.5 hours post radiation, and later in the maturing oocyte during oogenesis and in the laid eggs. Genes coding for actors highly expressed post-radiation, involved in the BER pathway appear to be only expressed in the somatic syncytium 2.5 hours post radiation, as well as the gene coding for the Ligase E, likely involved in DNA repair. C_FIG

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Exploring Auditory Biofeedback Paradigms for Gait Training in Children with Cerebral Palsy: A User-Centered Design Study

Kantan, P. R.; Hansen, M. B.; Foldager, J. J.; Fjeldgaard, F. S.; Dahl, S.; Spaich, E. G.

2026-05-29 rehabilitation medicine and physical therapy 10.64898/2026.05.29.26353852 medRxiv
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Purpose: To identify, through iterative user-centered design, the auditory biofeedback requirements and sound preferences supporting gait training in children with cerebral palsy (CP), and to determine which feedback variables, sound mappings, and sound types yield clinically viable and movement-interpretable paradigms. Methods: The iterative process spanned two prototype phases. Prototype A comprised seven paradigms demonstrated to two experienced physiotherapists (Workshop 1A). Two of these were subsequently discarded owing to poor sound-movement interpretability and two were modified. Six paradigms were added to Prototype B, demonstrated to four children, five parents, and one therapist (Workshop 1B) and two therapists (Workshop 2B). Data were analyzed using systematic text condensation. Results: Within-child sound preferences varied with energy level and sensory state on a given day. Sound-movement interpretability tended to suffer for paradigms with greater acoustic complexity (e.g. computer-generated music). Therapists endorsed a repertoire spanning both movement quality and movement quantity targets. Participants independently proposed paradigms rewarding restrained and controlled movement, a feedback category absent from the current prototype. Conclusions: Session-level calibration is preferable to fixed sound profiles, requiring real-time interface support for paradigm adjustment. Acoustic complexity must remain subordinate to movement-sound interpretability. Paradigms targeting movement restraint are a development priority unaddressed in the literature.

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Integration of Deep-Learning and Species Distribution Models for Classification of Animal Species of the Brazilian Fauna

Oliveira, M. B.; Bernardino, H. S.; Vieira, A. B.; Barroso, A. A.; Augusto, D. A.

2026-05-08 ecology 10.64898/2026.05.06.723365 medRxiv
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The automated classification of animals from photos is important in ecology and conservation biology for organizing and understanding the immense diversity of species, as well as facilitating effective conservation and management practices. It is equally important for disease surveillance systems, allowing prompt detection of anomalies in species distributions and boosting citizen-scientist platforms by making user-reported data more accurate and convenient. Image classification uses photos and can also rely on the geographical locations of animals to improve performance. While image classification models have difficulties in classifying low-quality images, unbalanced datasets, and with a small number of images, species distribution models have difficulty in classifying species that coexist in a given region. We propose here strategies for combining image classification models based on deep neural networks with species distribution models using genetic algorithms. The proposal is applied to a real-world dataset comprising fifteen classes of animals from the Brazilian fauna obtained from Fiocruzs citizen-scientist Wildlife Health Information System (SISS-Geo). The SISS-Geo photos portray the reality of animals in their environments, with varying quality, and pose numerous difficulties for classification. Experimental results demonstrate that the proposed integration consistently outperforms standalone models. While individual SDMs achieve Top-1 accuracies of 27.79% (MaxEnt) and 31.76% (Bioclim), and CNN-based classifiers reach 58.17% with ResNet50 and 64.13% with ResNet-152, the hybrid strategies yield substantial improvements. The genetic algorithm-based integration with a single global weight achieves up to 67.96% Top-1 accuracy, whereas the class-specific integration using fifteen parameters attains the best overall performance, reaching 69.03%.

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Landscape heterogeneity as a main driver of avian population dynamics

Malinowska, K.; Chodkiewicz, T.; Kuczynski, L.

2026-05-21 ecology 10.64898/2026.05.19.726359 medRxiv
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The ongoing decline in biodiversity highlights the need for understanding the causes of population changes. This study uses 25-year, large-scale monitoring dataset to investigate the influence of climate and landscape structure on the annual population growth rates of 84 bird species across Poland. Our methodological framework involves the spatiotemporal decomposition of these environmental drivers to decouple demographic effects of long-term carrying capacities from the short-term effects of environmental perturbations. Using species-specific demographic models followed by a community-wide meta-analysis, we evaluated how individual species responses scale up to shape community-level dynamics. The results reveal significant variation in species-specific responses to individual drivers. At the community level, our findings suggest that bird populations are mainly regulated by the long-term spatial constraints rather than short-term disturbances. Persistent environmental heterogeneity had the strongest positive demographic effect on birds, followed by temperature, forest dominance over croplands, and precipitation. In contrast, rapid temporal shifts in environmental heterogeneity and precipitation anomalies negatively affected population growth, whereas urbanisation consistently exerted a negative effect across both spatiotemporal dimensions. Our results highlight the significance of protecting existing heterogeneous and ecotonal habitats, as well as the need to incorporate features that enhance habitat heterogeneity into urban development. Article impact statementPreserving heterogeneous habitats is essential for the conservation of bird populations.

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Analytical Validation of Minimally Invasive Capillary Blood Microsampling using Tasso+ for Multiplexed Neurological Biomarkers

Swann, O.; Hicks, S.; Lynch, C.; Wallman-Jones, A.; Shoai, M.; Mulvaney, R.; Fernandes Gomes, B.; Kodosaki, E.; Tecilla, M.; Ghajari, M.; Jones, B.; Kemp, S.; TBI-REPORTER Biomarker group, ; Sylvester, R.; Cross, M.; Stokes, K.; Wilson, M. G.; Menon, D. K.; Heslegrave, A.; Zetterberg, H.; Sharp, D. J.; Parker, T. D.

2026-05-15 neurology 10.64898/2026.05.15.26353201 medRxiv
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Blood-based biomarkers are increasingly used to investigate brain health, but collecting venous blood is difficult in remote and field settings. Capillary microsampling offers a practical alternative, although the ability to delay processing and its agreement with gold-standard venous blood require validation. We evaluated Tasso+, a minimally invasive upper-arm capillary blood collection system, for measuring neurological and host-response biomarkers in plasma and serum during an exercise-based protocol. Sampling occurred before, immediately after, and approximately 24-to-36 hours after exercise; Tasso+ samples were processed with or without a 72-hour room-temperature delay. Tasso+ samples were compared with matched venous blood, and Capitainer SEP10 dried plasma spots were also evaluated, using Quanterix Simoa and Alamar Biosciences NULISAseq CNS panel. Tasso+ enabled reliable measurement of several key biomarkers, including GFAP and NfL, even after delayed processing. These findings support capillary microsampling for neurological biomarker studies where venepuncture is challenging, including field-based research and participant-led remote sampling.

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Left Ventricular Volume and Function Assessment Using a Reduced-Slice Approach in Cardiovascular Magnetic Resonance

Tejaswi, A.; Fyrdahl, A.; Sigfridsson, A.

2026-06-01 cardiovascular medicine 10.64898/2026.05.29.26354413 medRxiv
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Background: Cardiovascular magnetic resonance (CMR) quantification of the left ventricular (LV) volumes and ejection fraction (EF) typically involves manual segmentation of many short axis (SAx) and long axis (LAx) slices of the left ventricle. The scan time and the number of breath holds is proportional to the number of slices. We aimed to evaluate a geometric model of the left ventricle that could enable planimetry from a reduced number of slices. We sought to determine whether acceptable accuracy was retained for evaluating the End Diastolic Volume (EDV), End Systolic Volume (ESV), Stroke Volume (SV), and EF to provide a rapid and reliable clinical alternative. Methods: A cohort of 342 patients, median age: 54 (40 - 65) years, with full-stack CMR examinations was used. Nine geometrical combinations were evaluated: 3, 4 or 5 short axis slices and one of three LAx orientations (2-chamber, 3-chamber or 4-chamber) by retrospectively decimating the full-stack acquisition. LV volumes were calculated as a sum of trapezoidal approximations for apical and mid-cavity slices and a generalized prismoidal model at the base. The accuracy of the volume calculations was quantified against the full-stack reference for the EDV, ESV, SV, and EF using concordance correlation coefficient (CCC), two-way repeated measures ANOVA, pairwise tests, and Bayes factor log10(BF10) analysis. Results: The choice of the long axis (LAx) view was the most influential driver of accuracy (g2 = 0.104, for EDV), approximately 50 times more impactful than the number of SAx slices (g2 = 0.002, for EDV). Volumes calculated using the combination of 2-chamber LAx view and 5 SAx slices had the highest concordance with the full stack (CCC>0.90). While the estimated absolute volumes displayed a systematic negative bias, EF and SV remained highly robust due to bias cancellation. For a 2ch + 5 SAx protocol, EF bias was just 0.83% (LoA: -6.18 to 7.84%), with a minimum detectable change (MDC) of 7.01%, compared to 8.7% reported for expert human readers, suggesting strong concordance. Bayesian paired-samples t-tests yielded log10(BF10) = 6.42 in favor of 5 SAx over 3 SAx, constituting decisive evidence on the Jeffreys scale. The bias and limits of agreement (LoA) for stroke volume and ejection fraction were found to be lower than scan-rescan reproducibility in literature. Conclusion: This reduced-slice geometric model allows for reduced number of breath holds compared to a conventional full-stack CMR acquisition and provides an acceptable accuracy with bias less than scan-rescan variability.

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The dangers of data double dipping in assessing the classification accuracies of blood biomarkers in Alzheimer's disease and related disorder research

Liu, T.; Zeng, X.; Snitz, B. E.; Karikari, T. K.; Deek, R. A.

2026-06-01 neurology 10.64898/2026.05.22.26353848 medRxiv
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Blood biomarker models are increasingly used in Alzheimer's disease and related dementia translational research, but predictive performance can be inflated when the same dataset is used for both model development and evaluation. We assess the effect of data double dipping using simulations and NULISA proteomic data from the MYHAT-NI community-based cohort to predict brain amyloid-beta neuroimaging status. In both settings, training AUC increased as more biomarkers were added, while testing AUC peaked earlier and then declined. These findings show that data double dipping can inflate model performance and highlight the need for external validation or internal validation with data partitioning.