bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term multichannel recordings inDrosophilaflies reveal distinct responses to deviant visual stimuli during sleep compared to wake
Authors: Van De Poll Matthew N. , van Swinderen Bruno
Published: January 2025

During sleep, behavioral responsiveness to external stimuli is decreased. This classical definition of sleep has been applied effectively across the animal kingdom to identify this common behavioral state in a growing list of creatures, from mammals to invertebrates. Yet it remains unclear whether decreased behavioral responsiveness during sleep is necessarily associated with decreased responsiveness in brain activity, especially in relative latecomers to the sleep field, such as insects. Here, we perform long-term multichannel electrophysiology in tetheredDrosophila melanogasterflies exposed continuously to flashing visual stimuli. Flies were still able to sleep under these visual stimulation conditions, as determined by traditional immobility duration criteria for the field. Interestingly, local field potentials (LFPs) recorded in a transect through the fly brain failed to show any difference in amplitude during sleep compared to wake when the visual stimuli were invariant. In contrast, LFP responses were lower when visual stimuli were variable and of lower probability, especially in the central brain. Central brain responses to ‘deviant’ stimuli were lowest during the deepest stage of sleep, characterized by more regular proboscis extensions. This shows that the sleeping fly brain processes low-probability visual stimuli in a different way than more repeated stimuli and presentsDrosophilaas a model system for studying the potential role of sleep in regulating predictive processing.

SUMMARY STATEMENT

The sleeping fly brain still responds to visual stimuli. However, response amplitudes depend on stimulus history and probability, as well as recording location.
Age-related differences in the impact of background noise on neural speech tracking
Authors: Herrmann Bjorn
Published: January 2025

Tracking the envelope of speech in the brain is important for speech comprehension. Recent research suggests that acoustic background noise can enhance neural speech tracking, enabling the auditory system to robustly encode speech even under unfavorable conditions. Aging and hearing loss are associated with internal, neural noise in the auditory system, raising the question whether additional acoustic background noise enhances neural speech tracking in older adults. In the current electroencephalography study, younger (~25.5 years) and older adults (~68.5 years) listened to spoken stories in quiet (clear) or in the presence of background noise at a wide range of different signal-to-noise ratios. In younger adults, early neural speech tracking responses (<0.15 s) were enhanced by minimal background noise, indicating response facilitation through noise. In contrast, older adults, compared to younger adults, showed enhanced neural speech tracking for clear speech and speech masked by minimal background noise, but the acoustic noise led to little enhancement of the early neural tracking response in older people. The data demonstrate different sensitivity of the auditory cortex to speech masked by noise between younger and older adults. The results are consistent with the idea that the auditory cortex of older people exhibits more internal, neural noise that enhances neural speech tracking but that additional acoustic noise does not further support speech encoding. The work points to a highly non-linear auditory system that differs between younger and older adults.
Genomes of the entomopathogenic nematodeSteinernema hermaphroditumand its associated bacteria
Authors: Schwarz Erich M. , Baniya Anil , Heppert Jennifer K. , Schwartz Hillel T. , Tan Chieh-Hsiang , Antoshechkin Igor , Sternberg Paul W. , Goodrich-Blair Heidi , Dillman Adler R.
Published: January 2025

As an entomopathogenic nematode (EPN),Steinernema hermaphroditumparasitizes insect hosts and harbors symbioticXenorhabdus griffinaebacteria. In contrast to other Steinernematids,S. hermaphroditumhas hermaphroditic genetics, offering the experimental scope found inCaenorhabditis elegans. To enable biological analysis ofS. hermaphroditum, we have assembled and analyzed its reference genome. This genome assembly has five chromosomal scaffolds and 83 unassigned scaffolds totaling 90.7 Mb, with 19,426 protein-coding genes having a BUSCO completeness of 88.0%. Its autosomes show higher densities of strongly conserved genes in their centers, as inC. elegans, but repetitive elements are evenly distributed along all chromosomes, rather than with higher arm densities as inC. elegans. Either when comparing protein motif frequencies between nematode species or when analyzing gene family expansions during nematode evolution, we observed two categories of genes preferentially associated with the origin ofSteinernemaorS. hermaphroditum: orthologs of venom genes inS. carpocapsaeorS. feltiae; and some types of chemosensory G protein-coupled receptors, despite the tendency of parasitic nematodes to have reduced numbers of chemosensory genes. Three-quarters of venom orthologs occurred in gene clusters, with the larger clusters comprising functionally diverse pathogenicity islands rather than paralogous repeats of a single venom gene. While assembling the genome ofS. hermaphroditum, we coassembled bacterial genomes, finding sequence data for not only the known symbiont,X. griffinae, but also for eight other bacterial genera. All eight genera have previously been observed to be associated withSteinernemaspecies or the EPNHeterorhabditis, and may constitute a "second bacterial circle" of EPNs. The genome assemblies ofS. hermaphroditumand its associated bacteria will enable use of these organisms as a model system for both entomopathogenicity and symbiosis.
Neural decoding of competitive decision-making in Rock-Paper-Scissors using EEG hyperscanning
Authors: Moerel Denise , Grootwagers Tijl , Chin Jessica L. L. , Ciardo Francesca , Nijhuis Patti , Quek Genevieve L. , Smit Sophie , Varlet Manuel
Published: January 2025

Social interactions are fundamental to daily life, yet social neuroscience research has often studied individuals’ brains in isolation. Hyperscanning, the simultaneous recording of neural data from multiple participants, enables real-time investigation of social processes by examining multiple brains while they interact. Previous hyperscanning research has mostly focused on cooperative tasks and remains limited in competitive contexts. Here, we obtained electroencephalography (EEG) hyperscanning data for 62 participants (31 pairs) who played a computerised version of the Rock-Paper-Scissors game, a classic paradigm for studying competitive decision-making. Although the optimal strategy is to be unpredictable and thus act randomly, participants exhibited behavioural biases, deviating from this ideal. Using multivariate decoding methods, we found that neural signals contained information about decisions made by participants during gameplay, revealing certain strategies. Notably, losers showed unique reliance on prior trials, suggesting memory-based strategies that may impair optimal performance. These results reveal how competitive decision-making is shaped by cognitive biases and memory of previous outcomes, highlighting the difficulty of achieving randomness in strategic contexts. This work advances our understanding of decision-making and cognitive dynamics in competitive interactions.
Evaluating the biomedical and behavioural drivers of HIV-1 incidence decline in adolescent girls and young women in Uganda: A mathematical modelling study
Authors: Akullian Adam , Ssempijja Victor , Bridenbecker Dan , Nalugoda Fred , Nakigozi Gertrude , Santelli John , Kreniske Philip , Chang Larry William , Reynolds Steven , Ssekubugu Robert , Gray Ronald , J. Wawer Maria , Quinn Thomas , Galiwango Ronald , Probert Will , Imai-Eaton Jeff , Ratmann Oliver , Kagaayi Joseph , Fraser Christophe , Kigozi Godfrey , Grabowski Mary Kate , Serwadda David
Published: January 2025

Background: Recent declines in HIV incidence among adolescent girls and young women (AGYW) in Africa are often attributed to the expansion of biomedical interventions such as antiretroviral therapy and voluntary medical male circumcision. However, changes in sexual behaviour may also play a critical role. Understanding the relative contributions of these factors is essential for developing strategies to sustain and further reduce HIV transmission. Methods: We conducted a mathematical modelling study of data from the Rakai Community Cohort Study (RCCS), an open, population-based cohort of 15- to 49-year-olds in 30 communities in Rakai, Uganda, to investigate the biomedical and behavioural drivers of HIV incidence decline in AGYW (15-24 years of age). We estimated changes in the HIV incidence rate between 2000-2019 using retrospective cohort data to validate our modelled incidence estimates. We ran modelled counterfactual scenarios to quantify the independent and combined effects (cumulative infections averted and difference in incidence rates) of antiretroviral therapy (ART), voluntary medical male circumcision (VMMC), and delays in age of first sex (AFS) over historical (between 2000-2020) and projected (between 2000-2050) time horizons. Findings: Incidence in women 15-24 years of age declined by 83% between 2000-2019 (from 1.72 per 100 person-years in 2000 to 0.30 per 100 person-years in 2019), the largest reduction in incidence of all age groups of women. Increasing AFS over the last two decades (by 3 years in women and 2 years in men) was the largest contributor to incidence decline in women 15-19 years of age, averting 17% of cumulative infections between 2000-2020 and 37% between 2000-2050. Incidence in 15-19-year-old women was 69% lower in 2020 and 75% lower in 2050 compared to counterfactual scenarios without changes in AFS. ART scale-up contributed the most to incidence declines among women 20-24 years of age, averting 13% of infections between 2000-2020 and 43% of infections between 2000-2050. VMMC averted < 5% of infections in 15-24-year-olds to-date, with larger reductions in incidence between 2000-2050 in both 15-19 year-olds (13% reduction in cumulative infections) and 20-24 year-olds (22% of cumulative infections). ART, VMMC, and increasing AFS acted additively to reduce HIV incidence in AGYW, with little redundancy when combined. Interpretation: Our results provide strong support for maintaining both the protective changes in sexual behaviours and effective biomedical interventions to sustain continued reductions in HIV incidence among AGYW.
Stable isotope labeling kinetics of neurofilament lightin vitroandin vivo
Authors: Leckey Claire A. , Giovannucci Tatiana A. , Coulton John B. , He Yingxin , Sato Chihiro , Ghoshal Nupur , Vignarajah Tharini , Jaunmuktane Zane , Barthélemy Nicolas R. , Zetterberg Henrik , Elbert Donald L. , Mills Kevin , Wray Selina , Bateman Randall J. , Paterson Ross W.
Published: January 2025

Importance

Neurofilament light (NfL) is elevated in CSF and blood across a range of traumatic, inflammatory and neurodegenerative diseases of the central nervous system, and has been increasingly included in clinical trials as an outcome measure of target engagement. Interpreting trajectories of NfL post-treatment has been challenging, prompting a greater need and focus on understanding its pathophysiology.

Objective

We measured NfL kinetics in the human central nervous system using stable isotope labeling kinetics (SILK).

Design

Observational study. Participants underwent SILK protocol. Infusion of 16 hours with 4mg/kg/h and follow-up lumbar punctures scheduled at 7, 14, 60 and 120 days post-labeling.

Setting

Referral center – specialist neurology clinic.

Participants

Participants with diagnosed primary tauopathies (n=10) were recruited to the Human CNS Tau Kinetics in Tauopathies (TANGLES) study. A control case was examinedpost-mortemto assess the technical background of the SILK method.

Exposure

Intravenous infusion of13C6-leucine, with rates of label incorporation representative of fractional synthesis and fractional clearance ratesin vivoandin vitro.

Main outcome and Measure

Level of incorporation of13C6-leucine tracer into newly-translated NfL divided by the pool of NfL with previously incorporated12C6-leucine, expressed as a percentage tracer-to-tracee (TTR) ratio.

Results

NfL is rapidly translated in human brain within hours but takes 53 – 162 days to appear in cerebrospinal fluid (CSF). Labeled NfL remains detectable inpost-mortembrain tissue 1.5 years post-labeling, indicating an extremely slow turnover in the human CNS. Together, these data suggest the greatest contribution of CSF NfL in neurodegeneration is from slow release of a large pool of previously translated NfL. However, release of newly translated NfL makes a significant contribution.

Conclusion and relevance

Rapid increases in CSF NfL seen within weeks of disease processes or interventions are likely to reflect release of pre-existing NfL from damaged neurons, but later increases in NfL (>3 months) may also reflect new NfL translation and release. Clinical trials using NfL as an outcome measure to track neurodegeneration would particularly benefit from substantially longer follow-up periods due to the slow turnover of the protein in the central nervous system.
RNAsum: A tool for personalised genome and transcriptome interpretation for improved cancer diagnostics
Authors: Kanwal Sehrish , Marzec Jacek , Vissers Joseph H.A. , Diakumis Peter , Varghese Leila , Tork Luke , Hofmann Oliver , Luen Stephen J. , Grimmond Sean
Published: January 2025

The integration of whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) has revolutionized cancer diagnostics, enabling comprehensive molecular profiling of tumours. While WGS uncovers genomic alterations such as single nucleotide variants (SNVs), structural variants (SVs), and copy number changes, WTS provides complementary insights into transcriptomic changes, including gene expression levels, alternative splicing, and fusion events. Together, these technologies offer unparalleled potential to guide precision oncology by identifying actionable biomarkers and stratifying patients for targeted therapies or clinical trials. However, the integration of WGS and WTS data remains a significant bioinformatics challenge due to biological variability, tumour-specific complexities, and the lack of harmonized reference datasets. To address this, we developed RNAsum, an open-source tool designed to combine and interpret WGS and WTS data from individual cancer patient samples. RNAsum compares patient data against curated cohorts from The Cancer Genome Atlas (TCGA) and integrates quantitative expression data with genomic insights to enhance diagnostic accuracy, validate genomic findings, and prioritize clinically relevant alterations. We demonstrate the utility of RNAsum through case studies, showcasing its ability to confirm clinically reportable variants, refine diagnoses, and identify novel therapeutic targets. By bridging the gap between genome and transcriptome analyses, RNAsum represents a step forward in the routine clinical application of multi-omics for personalized cancer care. The tool is freely available as an R package on GitHub, supporting accessibility and scalability for diverse research and clinical settings.
A Method for Sensitivity Analysis of Automatic Contouring Algorithms Across Different MRI Contrast Weightings Using SyntheticMR
Authors: McCullum Lucas , Belal Zayne , Floyd Warren , Ali Alaa Mohamed Shawky , West Natalie , Mulder Samuel , Ding Yao , Xu Jiaofeng , Thill Dan , O’Connell Nicolette , Stancanello Joseph , Wahid Kareem A. , Fuentes David T. , Hwang Ken-Pin , Fuller Clifton D.
Published: January 2025

Background

Currently, a majority of institution-specific automatic MRI-based contouring algorithms are trained, tested, and validated on one contrast weighting (i.e., T2-weighted), however their actual performance within this contrast weighting (i.e., across different repetition times, TR, and echo times, TE) is under-investigated and poorly understood. As a result, external institutions with different scan protocols for the same contrast weighting may experience sub-optimal performance.

Purpose

The purpose of this study was to develop a method to evaluate the robustness of automatic contouring algorithms to varying MRI contrast weightings.

Methods

One healthy volunteer and one patient was scanned using SyntheticMR on the MR-Simulation device. The parotid and submandibular glands in these subjects were contoured using an automatic contouring algorithm trained on T2-weighted MRIs. For ground truth manual contours, two radiation oncology residents and one pre-resident physician were recruited and their STAPLE consensus was determined. A total of 216 different MRI TR and TE combinations were simulated across T1-, T2-, and PD-weighted contrast ranges using SyntheticMR’s post-processing software, SyMRI. Comparisons between automatic contouring algorithm contours and the ground truth were determined using the Dice similarity coefficient (DSC) and 95thpercentile Hausdorff distance (HD95).

Results

Notable differences in the automatic contouring model’s performance were seen across the contrast-weighted range, even within the T2-weighted range. Further, some models even performed as well or better across subsets of the T1-weighted range. The PD-weighted range saw the worst performance. The range of discrepancy in DSC and HD95 exceeded 0.2 and 3.66 mm, respectively, in some structures. In the T2-weighted contrast region where the model was trained, 100%, 40%, 24%, and 57% for the DSC in the left parotid, right parotid, left submandibular, and right submandibular gland, respectively, exceeded interobserver variability.

Conclusions

This study demonstrates the variable performance of MRI-based automatic contouring algorithms across varying TR and TE combinations. This methodology could be applied in future studies as a method for evaluating model sensitivity, out of distribution detection ability, and performance drift.
Distinct temporal stages of infant brain processing associate with early versus later autism diagnosis
Authors: Bazelmans T. , Charman T. , Johnson M. H. , Jones E.J.H. ,   BASIS Team
Published: January 2025

Background

The expression of autism traits sufficient to meet criteria for a diagnosis can occur early (by 3 years) or later (from mid-childhood onwards). It remains unknown whether variation in age of onset is due to clinical recognition or whether it reflects distinct biological pathways. One way of addressing this question is by investigating biological differences very early in development associated with age of onset. We use a prospective design to look at event related potentials to faces, one of the most robust biomarkers in autism.

Methods

A sample of 102 infants (aged 6-10 months, 54% female) with an older autistic sibling had EEG recorded whilst viewing faces (faces versus noise; gaze towards versus away). Autism diagnostic assessments were conducted at three years and again in mid-childhood (aged 6-12 years), resulting in early diagnosed (at age 3; N=22), later diagnosed (at mid-childhood; N=21) and no autism (N=59) groups.

Results

While a short latency response (P1) does not associate with autism outcome, a mid-latency component (N290) associates with early onset autism only, and a later latency component (P400) associates with both early and later onset autism.

Conclusion

Temporal stages of face processing in infancy differentially associate with age of autism onset such that an earlier age of diagnosis is associated with earlier stage deviation within the event-related waveform. Early and later onset autism may represent different biological subtypes, with different early brain development, challenging the view of one etiological pathway and that variation in diagnostic age is solely due to clinical ascertainment.
The Role of Fermented Pickles in Shaping Gut Microbiota and Immune Response in Women: A Community-Based Trial in Pakistan
Authors: Hafeez Sumbal , Khalid Aqsa , Ahmed Sheraz , Umrani Fayaz , Qureshi Abdul Khaliq , Ahmed Kumail , Shaheen Fariha , Hotwani Aneeta , Kabir Furqan , Moore Sean R. , Ali Syed Asad , Iqbal Junaid , Iqbal Najeeha Talat
Published: January 2025

A gut microbiome-targeted diet can potentially mitigate chronic diseases like malnutrition. In a prospective 12-week intervention trial, we evaluated the effects of six different plant-based fermented pickles (∼50g/day) on clinical, inflammatory, and gut-microbiome parameters in women (n=230) in a rural setting with a high prevalence of undernutrition. Blood was collected at two, whereas stool was collected at three timepoints. Among fecal biomarkers, myeloperoxidase (MPO), Lipocalin-2 (LCN2), and 16S rRNA sequencing were measured at baseline, 8th,and 12thweeks. Overall compliance rate was >70%. WBC and neutrophils significantly decreased among radish (p=0.002, p=0.01) and carrot (p=0.005, p=0.006) groups compared to controls. In lemon-chili groups, platelets significantly decreased (p<0.001) while MCV increased (p=0.02). In onion and lemon-chili groups, the alpha (р=0.001 and p=0.0005, respectively) and beta diversities (p=9e-04 and p=0.0223, respectively) were significantly increased. Post-intervention linear discriminant analysis (LDA) identified 25 bacterial taxa markers at 8thand 12thweek, that includedEggerthellaceaeandOscillospiraceae, ErysipelatoclostridiaceaeandSubdoligranumlum,predominantly in lemon-chili group. Correlation analysis revealed six taxa negatively associated with inflammatory markers such as CRP, LCN2, and platelets. Our study provides preliminary information about consumption of culturally acceptable fermented pickles exerting beneficial changes in hematological and gut microbiome profiles of women, post-intervention.
Effect of Oxygen Saturation Targets on Neurologic Outcomes after Cardiac Arrest: A Secondary Analysis of the PILOT Trial
Authors: DeMasi Stephanie C. , Clark Alexander T. , Muhs Amelia L. , Han Jin H. , Shipley Kipp , McKinney Jared J. , Wang Li , Rice Todd W. , Moskowitz Ari , Prekker Matthew E. , Johnson Nicholas J , Self Wesley H. , Casey Jonathan D. , Semler Matthew W. , Seitz Kevin P. ,   Pragmatic Critical Care Research Group
Published: January 2025

Background

More than 600,000 adults in the United States experience a cardiac arrest each year. After resuscitation from cardiac arrest, most patients receive mechanical ventilation. The oxygenation target that optimizes neurologic outcomes after cardiac arrest is uncertain.

Research Question

After cardiac arrest, does a lower oxygen saturation (SpO2) target improve neurologic outcomes compared to a higher SpO2target?

Study Design and Methods

We conducted a secondary analysis of patients who experienced a cardiac arrest before enrollment in the Pragmatic Investigation of optimal Oxygen Targets (PILOT) trial. The PILOT trial assigned critically ill adults receiving mechanical ventilation to a lower (88-92%), intermediate, (92-96%), or higher (96-100%) SpO2target. This subgroup analysis compared patients randomized to a lower-or-intermediate SpO2target (88-96%) versus a higher SpO2target (96-100%) with regard to the primary outcome of survival with a favorable neurologic outcome at hospital discharge (Cerebral Performance Category 1 or 2). The secondary outcome was in-hospital death.

Results

Of 2,987 patients in the PILOT trial, 339 (11.3%) experienced a cardiac arrest before enrollment: 221 were assigned to a lower-or-intermediate SpO2target, and 118 were assigned to a higher SpO2target. Overall, the median age was 60 years, 43.5% were female, 58.7% experienced an in-hospital cardiac arrest, and 10.2% had an initial shockable rhythm. Survival with a favorable neurologic outcome occurred in 50 patients (22.6%) assigned to a lower-or-intermediate SpO2target and 15 (12.7%) patients assigned to a higher SpO2target (P=0.03). In-hospital death occurred in 146 patients (66.1%) assigned to a lower-or-intermediate SpO2target and 89 (75.4%) assigned to a higher target (P=0.08).

Interpretation

Among patients receiving mechanical ventilation after a cardiac arrest, use of a lower-or-intermediate SpO2target was associated with a higher incidence of a favorable neurologic outcome compared with a higher target. A randomized trial comparing these targets in the cardiac arrest population is needed to confirm these findings.
Development of a Research Program Focused on Non-Invasive Brain Stimulation for Peripheral Neuropathy in Minoritized Communities
Authors: Wong Marlon L. , McTeague Lisa M. , Miller Chelsea A. , Gonzalez Gabriel , Tovin Melissa M. , Penedo Frank J. , Widerstrom-Noga Eva
Published: January 2025

Black and Hispanic/Latino communities experience disproportionate chronic pain and are underrepresented in pain research. Transcutaneous auricular vagus nerve stimulation (taVNS) and transcranial magnetic stimulation (TMS) are promising tools for pain management. Therefore, it is critical to ensure that research using these tools engages underrepresented communities to make research findings more generalizable and reach all who may benefit. Lack of diversity in the research workforce itself is a key barrier to improving Black and Hispanic/Latino representation in pain research, and video-enhanced recruitment and consenting may be a useful tool to better engage minoritized communities.

Using community participatory research principles in an iterative process, we engaged key stakeholders, including neuromodulation researchers and minoritized community members, to create and test informational videos on taVNS and TMS. These videos were designed for Black English-speaking, Hispanic/Latino Spanish-speaking, and Haitian-Creole speaking people with chronic pain. Study 1 involved iterative feedback from stakeholders to develop test videos, which were then refined based on community member input. Study 2 was a pilot randomized controlled trial assessing the impact of these videos on participant expectations for pain relief with taVNS.

Results indicated that the videos were well-received, and there was no significant difference in expectancy scores between those who viewed the videos and those who received traditional brochures. This suggests that while videos may improve engagement, they do not unduly influence expectations, potentially making them valuable tools for improving research participation in underrepresented populations. These videos will be freely available to help researchers to engage people from minority communities.

PERSPECTIVE

This article presents the process of developing culturally sensitive informational videos on taVNS and TMS, and provides the field with these videos in English, Spanish, and Haitian-Creole language. These videos could potentially help researchers to engage people from minority communities to enhance the diversity and reach of research using noninvasive brain stimulation for pain.
HaptiKart: An engaging videogame reveals elevated proprioceptive vs. visual bias in individuals with autism spectrum disorder
Authors: Lidstone Daniel E. , Singhala Mohit , Wang Liam J. , Brown Jeremy D. , Mostofsky Stewart H.
Published: January 2025

An overreliance on proprioceptive (intrinsic) sensory input from the body, compared to visual (extrinsic) input from the environment, may underpin core features of autism spectrum disorder (ASD). We developed an engaging videogame (“HaptiKart”) as a tool to examine differences in proprioceptive vs. visual bias in children and adults with ASD and whether bias correlates with age, core autism features, and intellectual ability. Eighty-one participants (33 ASD, 48 typically-developing, TD) aged 8 to 31 years played “HaptiKart,” a driving videogame with a force-feedback steering wheel that provided “steering assist” during gameplay. In separate trials, proprioceptive and visual feedback were selectively delayed, and differences in driving error between the conditions were used to calculate perceptual bias scores. Effects of autism diagnosis and age on perceptual (proprioceptive vs. visual) bias scores were examined, controlling for sex, as were associations of perceptual bias with autism symptom severity (ADOS-2, SRS-2), attention-deficit symptom severity (Conners4 ADHD Total Scores) ratings, and IQ (general ability index, GAI). The ASD group exhibited significantly higher proprioceptive bias than did the TD group (p=0.002). There was a trend for decreasing proprioceptive bias with age, but no significant diagnosis-by-age interaction. Increased proprioceptive bias correlated with higher autism severity and with lower IQ, but not ADHD symptoms. HaptiKart provides a highly scalable approach for measuring sensory-motor bias, revealing that individuals with ASD show elevated proprioceptive bias, correlating with autism severity. HaptiKart’s sensory-motor bias measure may thereby serve as a digital biomarker for addressing autism heterogeneity in ways that can improve targeted intervention.

Author Summary

In this study, we explored how people with autism spectrum disorder (ASD) may rely more on body-based (proprioceptive) senses than on visual information when interacting with their surroundings. Using a custom video game,HaptiKart, we designed a fun and engaging driving task to measure this sensory preference. Players drove a virtual car using a steering wheel that could be set to delay either visual or proprioceptive feedback, allowing us to observe how each type of feedback affects driving accuracy.

Our results showed that individuals with ASD had a stronger preference for proprioceptive feedback than those without ASD. This sensory preference was linked to greater autism symptom severity and lower IQ, suggesting that heightened reliance on body-centered feedback may contribute to learning and skill differences often seen in autism. These findings support the potential ofHaptiKartas a simple, accessible tool to help clinicians better understand and address sensory biases in ASD, tailoring interventions to improve learning from visual information.
Modeling the microbial contribution to human Energy Balance using the Digestion, Absorption, and Microbial Metabolism (DAMM) model
Authors: Davis Taylor L. , Dirks Blake , Carnero Elvis A. , Corbin Karen D. , Smith Steven R. , Marcus Andrew , Krajmalnik-Brown Rosa , Rittmann Bruce E
Published: January 2025

Colonic microorganisms have been linked to human health and disease, specifically metabolic disease states such as obesity, but causal relationships remain to be established. Previous work demonstrated that interactions between the host’s diet and intestinal microbiome were associated with human energy balance by affecting the human’s energy absorption, quantified by metabolizable energy. We developed the Digestion, Absorption and Microbial Metabolism (DAMM) model, which explicitly accounts for the energy contributions of the colonic microbial community by: 1) breaking down the diet composition into the gross energy of the individual macronutrients, 2) calculating direct absorption in the upper gastrointestinal tract, 3) using microbial stoichiometry to estimate the consumption of the remaining unabsorbed nutrients by microbes in the large intestine, and 4) quantifying predicted production of microbial products (short-chain fatty acids (SCFA) and methane) in the colon and estimating absorption from the colonic tract to the host. When used to predict the results from a clinical study that compared two distinctly different diets, the DAMM model captured the directionality and magnitude of change in measured metabolizable chemical oxygen demand (which can be converted to metabolizable energy), improved on the accuracy of predictions compared to the Atwater factors by reducing systematic bias on one of the diets, and estimated substrate availability within the colon and rate of production of microbially derived short-chain fatty acids. Measured methane concentrations, combined with findings from the DAMM model, support the hypothesis that methanogens accumulated in mucosal biofilms in participants harboring methanogens. Model outputs also support that colonic transit time directly influenced SCFA absorption rates. The DAMM model now can be linked to existing human models that predict changes in body energy stores to extend our understanding of how microbial metabolic processes affect macronutrient absorption and metabolizable energy.
Social Compliance with NPIs, Mobility Patterns, and Reproduction Number: Lessons from COVID-19 in Europe
Authors: Baccega Daniele , Aguilar Jose , Baquero Carlos , Fernández Anta Antonio , Ramirez Juan Marcos
Published: January 2025

Non-pharmaceutical interventions (NPIs), including measures such as lockdowns, travel limitations, and social distancing mandates, play a critical role in shaping human mobility, which subsequently influences the spread of infectious diseases. Using COVID-19 as a case study, this research examines the relationship between restrictions, mobility patterns, and the disease’s effective reproduction number (Rt) across 13 European countries. Employing clustering techniques, we uncover distinct national patterns, highlighting differences in social compliance between Northern and Southern Europe. While restrictions strongly correlate with mobility reductions, the relationship between mobility and Rtis more nuanced, driven primarily by the nature of social interactions rather than mere compliance. Additionally, employing XGBoost regression models, we demonstrate that missing mobility data can be accurately inferred from restrictions, and missing infection rates can be predicted from mobility data. These findings provide valuable insights for tailoring public health strategies in future crisis and refining analytical approaches.
Evaluation of age groupings used for syndromic surveillance
Authors: Morbey R. A. , Todkill D. , Hughes H. E. , Charlett A. , Elliot A. J.
Published: January 2025

Public health surveillance stratifies populations into age groups to help identify threats and provide appropriate responses. However, there is considerable variation in the age groupings used for epidemiology both between and within countries.

We evaluate the age groups (under 1, 1-4, 5-14, 15-44, 45-64, over 65 years) used for syndromic surveillance in England. Comparing the existing age grouping with alternatives and using syndromic data to suggest new age groupings that maximise the homogeneity within groups and heterogeneity between groups. Data between November 2011 and March 2024 was extracted from four syndromic systems including 79 different syndromic indicators.

Correlations between time series for individual ages in years were used to calculate homogeneity of specific age groups and age groupings (collections of age groups that completely span 0 to 90 years). Young adolescents were identified as a specific age group with distinct trends different to younger children or older adolescents. The current age group of 5 to 14 years was found to be more heterogeneous that over age groups, even those with a much wider span. Also, the age group over 65 years was assessed to be too broad and would benefit from being split into those over 90 years and below. Thus, our recommendation is a new age grouping for syndromic surveillance consisting of under 1s, 1 to 4, 5 to 8, 9 to 17, 18 to 33, 34 to 50, 51 to 67, 68 to 89 and over 90 years.
Systematic Exploration of Hospital Cost Variability: A Conformal Prediction-Based Outlier Detection Method for Electronic Health Records
Authors: Grolleau François , Goh Ethan , Ma Stephen P. , Masterson Jonathan , Ross Ted , Milstein Arnold , Chen Jonathan H.
Published: January 2025

Marked variability in inpatient hospitalization costs poses significant challenges to healthcare quality, resource allocation, and patient outcomes. Traditional methods like Diagnosis-Related Groups (DRGs) aid in cost management but lack practical solutions for enhancing hospital care value. We introduce a novel methodology for outlier detection in Electronic Health Records (EHRs) using Conformal Prediction. This approach identifies and prioritizes areas for optimizing high-value care processes. Unlike conventional predictive models that neglect uncertainty, our method employs Conformal Quantile Regression (CQR) to generate robust prediction intervals, offering a comprehensive view of cost variability. By integrating Conformal Prediction with machine learning models, healthcare professionals can more accurately pinpoint opportunities for quality and efficiency improvements. Our framework systematically evaluates unexplained hospital cost variations and generates interpretable hypotheses for refining clinical practices associated with atypical costs. This data-driven approach offers a systematic method to generate clinically sound hypotheses that may inform processes to enhance care quality and optimize resource utilization.
Phase 2b clinical study evaluating efficacy of RTS,S/AS01EinPlasmodium falciparum-exposed Kenyan adults treated with antimalarial chemopreventive drugs
Authors: Copeland Nathanial K. , Otieno Lucas , Otieno June Doryne , Otieno Solomon , Chira Salome , Ivinson Karen , Onyango Irene , Wasuna Ruth , Akala Hoseah , Onditi Amos , Sifuna Peter , Andagalu Ben , Oyugi Roselyne , Omondi Mary , Amoit Stellah , Locke Emily , Gregory Scott , Bergmann-Leitner Elke S. , Pindolia Hema , Raine Mike , Gast Chris , Mercer Laina D. , Aponte John J. , Lievens Marc , Ockenhouse Christian F. , Lee Cynthia K.
Published: January 2025

Background

RTS,S/AS01 vaccine efficacy (VE) was previously shown to be lower in African adults than in malaria-naïve US adults, potentially due to concurrentPlasmodium falciparum(Pf) infections. We investigated whether treatment of infection prior to vaccination would lead to improved VE and immunogenicity.

Methods

A Phase 2b study in Kenyan adults evaluated the efficacy of RTS,S/AS01Ein conjunction with antimalarial chemopreventive drugs. Participants, grouped by baseline presence or absence ofPfinfections, were randomized to receive RTS,S/AS01Eor rabies vaccine. Four groups received antimalarial drugs prior to immunization and were followed for six months to assessPfinfection. We included an additional group of adults not treated with antimalarial drugs for immunological assessment.

Results

VE (RTS,S/AS01Eversus rabies vaccine) was 34.8% (8.9%, 53.4%) and −24.0% (−97%, 22.4%) in baselinePf-positive and baselinePf-negative participants, respectively. In RTS,S/AS01Erecipients, there were no statistical differences in anti-circumsporozoite (CS) antibody titers in baselinePf-positive orPf-negative participants, or in susceptibility to infection during the post-vaccination follow-up period. Drug treatment did not improve anti-CS antibody titers.

Conclusions

TreatingPfinfections during vaccination does not result in increased VE. Anti-CS antibody responses to vaccination do not differ with baselinePfinfection status, drug treatment, or susceptibility toPfinfections.

Clinical Trial Registration

NCT04661579; PACTR202006896481432
Impact of SGLT2 Inhibitors on Survival in Gastrointestinal Cancer Patients Undergoing Chemotherapy and/or Radiotherapy: A Real-World Data Retrospective Cohort Study
Authors: Flausino Lucas E. , Murillo Carrasco Alexis Germán , Furuya Tatiane Katsue , Tuan Wen-Jan , Chammas Roger
Published: January 2025

Background

The role of sodium-glucose co-transporter 2 inhibitor (SGLT2i) drugs in the management of diabetes and cardiovascular disease is well-established, but emerging evidence suggests potential effects on cancer outcomes, including gastrointestinal (GI) cancers. We conducted an extensive, sex-oriented, real-world data analysis to investigate whether SGLT2i can enhance GI cancer outcomes when used alongside standard therapies such as chemotherapy and radiotherapy.

Methods

The study applied a retrospective cohort design with data from the TriNetX research database (https://trinetx.com), examining GI cancer patients treated with chemotherapy and/or radiotherapy between 2013 and 2023. The intervention cohort consisted of Gl cancer patients who received SGLT2i, while the control cohort did not. A 5-year follow-up period was used, and baseline characteristics were balanced using a 1:1 propensity score matching technique. Cox proportional-hazards and logistic regression models assessed mortality and morbidity risks between the cohorts.

Results

The study included 6,389 male and 3,457 female patients with GI cancer (ICD-10: C15-C25). The use of SGLT2i was significantly associated with improved survival for both male (HR 0.568; 95% CI 0.534-0.605) and female (HR 0.561; 95% CI 0.513-0.614) patients undergoing chemotherapy and/or radiotherapy. SGLT2i use also correlated significantly with lower hospitalisation rates both in male (OR 0.684; 95% CI 0.637-0.734) and female (OR, 0.590; 95% CI 0.536-0.650) patients. The analysis of GI cancer subtypes also demonstrated similar benefits, without significant adverse effects.

Conclusions

Repurposing SGLT2 inhibitors for cancer treatment could potentially improve outcomes for GI cancer patients without causing significant side effects. Further clinical trials are needed to confirm these findings and establish the optimal condition for its application in GI cancer treatment.
The correlations of outcomes and vascular morphology with infarct patterns in middle cerebral arterial trunk occlusion
Authors: Cai ZhiRong , Chen Yuan , Pei ShaoQing , He Yue , Zhu YaNan , Zhang Rui , Lin JingWei , Yang Yi , Zhu Ying
Published: January 2025

Background and purpose

The large vessel occlusion (LVO) in middle cerebral artery (MCA) trunk (i.e., M1segment) caused by intracranial atherosclerotic disease (ICAD) could introduce with different infarct patterns. We aimed to compare the clinical outcomes among these patterns and investigate the associations between the morphological parameters of contralateral MCA (cMCA) M1segment and infarct patterns.

Methods

Patients with stroke attributed to M1-ICAD-LVO were enrolled. The infarct patterns were categorized into artery-artery embolism (AAE), large infarct, borderzone infarct (BZI) and perforating artery infarction (PAI). The morphological parameters of cMCA-M1segment consisted of proximal diameter, distal diameter, arc length and chord length were measured. The tortuosity index of cMCA-M1segment was calculated by (arc length/chord length-1) × 100%.

Results

A total of 171 subjects were enrolled. Compared to AAE, the risk of poor outcome significantly increased in BZI (odds ratio [OR]= 5.51, 95% confidence interval [CI] = 1.71–17.78,p= 0.004) and large infarct (OR= 10.92, 95% CI = 2.01–59.27,p= 0.006), and was comparable in PAI. The tortuosity index (OR= 2.85, 95% CI = 1.13–7.18,p= 0.026) and arc length (OR= 2.47, 95% CI = 1.02–5.97,p= 0.045) significantly elevated in BZI and were identical in other three patterns. Subjects other than BZI were categorized into large infarct (n = 32) and non-large-infarct (n = 46) groups, and the proximal diameter (OR= 0.22, 95% CI = 0.07–0.72,p= 0.012), arc length (OR= 0.88, 95% CI = 0.78–0.98,p= 0.018) and chord length (OR= 0.87, 95% CI = 0.77–0.995,p= 0.042) were all negatively associated with the onset of large infarct.

Conclusion

For patients with M1-ICAD-LVO, the outcomes of large infarct and BZI were poorer than AAE and PAI. The cMCA-M1segment with elevated tortuosity and arc length was associated with BZI, whereas a thin and short M1segment was correlated with large infarct in patients with a cMCA trunk of low tortuosity.
Ivabradine and Atrial Fibrillation Incidence: A Nested Matching Study
Authors: Kim Kibum , Keur Jasmeen , Anderson Halie , Radwański Przemysław B. , Munger Mark A.
Published: January 2025

Objective

The objective of this real-world study was to quantify and project the cumulative incidence of atrial fibrillation (AF) associated with exposure to ivabradine (IVB) in naïve-AF heart failure (HF) patients.

Methods

A retrospective observational comparative study was performed using a health plan claims database. The new diagnosis of AF was compared between adult HF patients receiving IVB versus no IVB controls (CTRs) over 180-day follow-up period. Eligible IVB subjects were free from AF diagnosis before the IVB index date, which should be longer than 6 months. Incidence-density sampling was performed to select matched CTRs based on clinical characteristics, AF naïve status and time to be selected as a CTRs corresponding to the time to receive IVB from the initial HF diagnosis. The measure of IVB-AF association was tested using Cox Proportional Hazards Regression model.

Results

Of the 153 IVB and 4,494,305 CTRs meeting the AF-naïve HF status, the analytic cohort of 107 IVB and 321 matched controls were created. The groups were well matched for age: 52.9±11.3 (IVB) vs. 53.5±11.8, gender: 57% male, HFrEF diagnosis: 66.4%, co-morbidities: hypertension 81.3% and coronary artery disease event 38.3%, and goal-directed medical therapy: ß-adrenergic blockers 89.7%, ACEi/ARB/sacubitril/valsartan 79.4%, mineral corticoid antagonists 39.3%. The adjusted HR [95% CI] estimates was 7.293 [4.985-10.668]. The only variable that predicted AF incidence was the IVB prescription.

Conclusions

In HF AF-naive patients, analysis of healthcare claims point to a significant risk of AF receiving IVB.
Deep Learning–Based Early Detection of Major Adverse Cerebral Injuries in Cardiothoracic and Vascular Surgery
Authors: Yoo Dongjoon , Tae Yunwon , Cho Kyungjae , Je Hyunggon , Kim Dohyung , Son Bongsoo , Ju Minho , Lee Cheehoon , Lee Sangsu , Kim Taehwa , Cho Woo Hyun , Kim Young A. , Lee Narae , Ahn Sung-Ho
Published: January 2025

Background

Despite advances in central nervous system (CNS)-protective anesthetic and surgical strategies, perioperative stroke remains a significant concern in high-risk cardiothoracic and vascular surgery (CTVS). Early detection, facilitating timely and prompt intervention, is often hindered by sedation and mechanical ventilation (MV) in the immediate postoperative period. This study aimed to develop and validate a deep learning (DL)-based artificial intelligence (AI) program for early detection of severe, surgery-related major adverse cerebral injury (sMACI), encompassing fatal CNS and systemic insults in high-risk CTVS patients.

Methods

We retrospectively analyzed data from 4,455 patients who underwent seven types of CTVS (2010–2021), requiring postoperative ICU admission and ongoing MV. Continuous vital signs (heart rate, blood pressures, respiratory rate, pulse oximetry saturation, temperature) were extracted from the operating room (OR) and intensive care unit (ICU), along with demographic and laboratory data. sMACI was defined as significant postoperative CNS injury (modified Rankin Scale ≥3 at 1 month) or 1-month mortality. Two-tier DL models were constructed: Model 1 using ICU data alone, and Model 2 integrating pre-ICU and ICU data. Performance in detecting sMACI within 24 hours of ICU admission was assessed using the area under the receiver operating characteristic curve (AUROC) and precision-recall curve (AUPRC).

Results

Among 4,455 patients, 5% experienced sMACI. Model 1 achieved an AUROC of 0.809 (95% CI: 0.759–0.858) and an AUPRC of 0.275 (0.195–0.375). Model 2 showed improved detection (AUROC 0.826 [0.781–0.871]; AUPRC 0.322 [0.233–0.423]). Both models outperformed conventional early warning scores and other machine learning algorithms, demonstrating robust performance as early as 4 hours after ICU admission. Key contributors included systolic blood pressure, heart rate, diastolic blood pressure, mean arterial pressure, and pulse oximetry saturation.

Conclusions

A DL-based AI program leveraging continuous vital signs enables effective early detection of severe surgery-related CNS and systemic injury in high-risk CTVS patients, outperforming established scoring systems and other machine learning approaches.