bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of end-of-outbreak probabilities in the presence of delayed and incomplete case reporting
Authors: Plank M. J. , Hart W. S. , Polonsky J. , Keita M. , Ahuka-Mundeke S. , Thompson R. N.
Published: January 2025

Towards the end of an infectious disease outbreak, when a period has elapsed without new case notifications, a key question for public health policymakers is whether the outbreak can be declared over. This requires the benefits of a declaration (e.g. relaxation of outbreak control measures) to be balanced against the risk of a resurgence in cases. To support this decision-making, mathematical methods have been developed to quantify the end-of-outbreak probability. Here, we propose a new approach to this problem that accounts for a range of features of real-world outbreaks, specifically: (i) incomplete case ascertainment, (ii) reporting delays, (iii) individual heterogeneity in transmissibility and (iv) whether cases were imported or infected locally. We showcase our approach using two case studies: Covid-19 in New Zealand in 2020 and Ebola virus disease in the Democratic Republic of the Congo in 2018. In these examples, we found that the date when the estimated probability of no future infections reached 95% was relatively consistent across a range of modelling assumptions. This suggests that our modelling framework can generate robust quantitative estimates that can be used by policy advisors, alongside other sources of evidence, to inform end-of-outbreak declarations.
Preparing the 2025 revision of the International Code of Nomenclature of Prokaryotes
Authors: Oren Aharon , Arahal David R. , Christensen Henrik , Göker Markus , Manaia Célia M. , Moore Edward R.B.
Published: January 2025

The editorial Board of the International Code of Nomenclature of Prokaryotes (ICNP) – the Prokaryotic Code – has compiled already ratified proposed emendations of the ICNP, together with additional editorial changes and clarifications. These were implemented in a draft 2025 revision of the Prokaryotic Code. To comply with Articles 13(b)(4) and 4(d) of the statutes of the International Committee on Systematics of Prokaryotes (ICSP), a public discussion of the document will start on 1 January (or later if required) 2025, to last for 6 months. Here, we present the basis for the revision and the procedure for the discussion. The discussion will be followed by the balloting of the ICSP members.
An ecological-evolutionary perspective on the genomic diversity and habitat preferences of the Acidobacteriota
Authors: McReynolds Ella , Elshahed Mostafa S. , Youssef Noha H.
Published: January 2025

Members of the phylum Acidobacteriota inhabit a wide range of ecosystems including soils. We analysed the global patterns of distribution and habitat preferences of various Acidobacteriota lineages across major ecosystems (soil, engineered, host-associated, marine, non-marine saline and alkaline and terrestrial non-soil ecosystems) in 248 559 publicly available metagenomic datasets. Classes Terriglobia, Vicinamibacteria, Blastocatellia and Thermoanaerobaculia were highly ubiquitous and showed a clear preference to soil over non-soil habitats, while classes Aminicenantia and Holophagae showed preferences to non-soil habitats. However, while specific preferences were observed, most Acidobacteriota lineages were habitat generalists rather than specialists, with genomic and/or metagenomic fragments recovered from soil and non-soil habitats at various levels of taxonomic resolution. Comparative analysis of 1930 genomes strongly indicates that phylogenetic affiliation plays a more important role than the habitat from which the genome was recovered in shaping the genomic characteristics and metabolic capacities of the Acidobacteriota. The observed lack of strong habitat specialization and habitat-transition-driven lineage evolution in the Acidobacteriota suggest ready cross-colonization between soil and non-soil habitats. We posit that such capacity is key to the successful establishment of Acidobacteriota as a major component in soil microbiomes post-ecosystem disturbance events or during pedogenesis.
Sagittal balance of the spine - a geometric force-line model
Authors: Song Kai , Wang Yu , Yang Qiang , Yang Cao , Wang Bing , Li Fangcai , Zhu Zezhang , Li Weishi , Zhang Jianguo , Wang Zheng
Published: January 2025

Objective

To introduce a new geometric force-line model to assess the sagittal spinal-pelvic alignments and statistically analyze the main parameters of the model, offering a novel perspective for understanding the sagittal balance.

Methods

A total of 388 healthy adults aged 18 - 35 years were recruited. To designate the mid-point of the anterior edge of the S2 vertebral body as the imaging marker point of the sagittal sacroiliac joint (SIJ). Parameters were measured included lines’ inclinations and angles related to T1, S2, HA (hip axis) and Co1(the first coccygeal).

Results

The S2-T1 inclination angle was 89.5° ± 2.8°, close to perpendicular (90°), and it means the spinal axis (S2-T1) of the population is approximately perpendicular to the ground. In addition, spinal axis (S2-T1) crossed T11-L1 segments, which means spinal S curve is basically distributed on both sides of the axis. Angles ∠Co1-S2-HA, ∠HA-Co1-S2, and ∠S2-HA-Co1 were approximate 60°, forming a horizontal stable equilateral triangle. The anterior edge of S2 was nearly perpendicular to the pelvic force line (∠S2, HA-S2 ≈ 90°).

Conclusion

The geometric performance of the proposed model is concise, clear, and logical. It provides a new perspective on the sagittal balance. This framework might help us better understand spinal-pelvic alignments and its clinical significance.
Bone Densitometry Dataset for Computer Aided Osteoporosis Disease Detection
Authors: Masnabadi Negin , Sadeghi-Niaraki Abolghasem , Karimi Mohammad , AbuHmed Tamer , Azarbani Nasrin , Choi Soo-Mi
Published: January 2025

Recently, automatic disease diagnosis based on medical images has become an integral part of digital pathology packages. To create, develop, evaluate, and compare these systems, we need diverse data sets. One of the key features in the diagnosis of bone diseases is measuring bone mineral density (BMD). Most research in this field uses manual methods to directly extract bone image features despite the underlying correlation between diseased and healthy bones, which explains the limited results. Detection of significant changes in bone mineral density (BMD) relies on minimally invasive dual energy x-ray absorptiometry (DXA) scanners. This article presents a collection of bone density test results along with a patient profile called Arak Bone Densitometry Center data. The patient profile includes height and weight and information about the patient, along with photos of the imaging areas. The number of these patients is 3,643, with about 4,020 photos stored next to them. Which can be used to develop automatic disease diagnosis methods and software.

Dataset

https://drive.google.com/drive/folders/1HmLTG4GFgB2s4D0×7TTRx8vV_VWY3sW3?usp=sharing
Risk Assessment ofEscherichia coliO157:H7 along the Farm-to-Fork Fresh-Cut Romaine Lettuce Supply Chain
Authors: Bulut Ece , Murphy Sarah I. , Strawn Laura K. , Danyluk Michelle D. , Wiedmann Martin , Ivanek Renata
Published: January 2025

Outbreaks ofEscherichia coliO157:H7 (ECO157) in romaine lettuce remain an ongoing public health concern. Quantitative microbial risk assessment (QMRA) models are key tools for identifying control measures to mitigate foodborne diseases. Here, we introduce a comprehensive QMRA framework along the farm-to-fork fresh-cut romaine lettuce chain, including a novel preharvest difference equation model, to predict annual ECO157 illness cases in the United States and evaluate control strategies. We demonstrated the importance of managing irrigation contamination at preharvest to control illness cases. Wildlife intrusions pose lower health risk, followed by runoffs and biological soil amendments of animal origin. When preharvest contamination persists and combines with time-temperature abuses at postharvest, the predicted ECO157 illness cases rise considerably. We showed a broad range of interventions targeting both preharvest and postharvest stages can effectively improve the microbial safety of fresh-cut romaine. The comprehensive practices and interventions explored in this study will aid decision-makers in establishing/enhancing food safety best management practices.
The link between motor disorders and executive or attentional cognitive disorders in people with cerebral palsy: Scoping review
Authors: Martinet Melinda , Reichert Kathrin , Schneider Juliane , Matusz Pawel J.
Published: January 2025

Introduction

Cerebral palsy (CP) causes motor deficits, which are sometimes accompanied by cognitive impairment. There are models that suggest interactions between these two domains in various populations. However, for CP, there seems to be a lack of empirical research on the subject. This scoping review aims to synthesize the literature on the specific relationships between motor and executive/attentional functions in people with CP. In addition, it seeks to identify current gaps to guide future research.

Method

A systematic search of three databases was conducted. Articles were selected on a double-blind basis according to predefined eligibility criteria. Finally, the results were presented in the form of tables and a narrative synthesis. This scoping review was written in accordance with the JBI manual for evidence synthesis.

Results

Eleven studies with different methodologies were included in this review. Relationships were investigated in different ways in each of the included studies. Some articles assessed executive functions and attention in parallel, while others focused on the individual domains. Five of the included studies found significant links between motor and executive functions. Likewise, five studies reported significant relationships between motor skills and attention. However, three of the included studies found no evidence of links between certain of these domains.

Discussion

This work provides empirical evidence of the links between motor and executive/attentional functions in CP. For the future, there remains a need for more high-quality empirical studies to clarify and quantify the specific relationships of motor and executive/attentional abilities.
Joint association of genetic risk and accelerometer-based step count with cardiovascular disease: a UK-Biobank cohort study
Authors: Birmpili Panagiota , Portas Laura , Littlejohns Thomas J. , Doherty Aiden
Published: January 2025

Background

This population-based prospective cohort study aimed to investigate whether accelerometer-measured step count is associated with incident cardiovascular disease (CVD), independently from genetic risk.

Methods

The study included participants in the UK Biobank with valid accelerometer and genetic data and without prevalent CVD at baseline. Genetic risk for CVD was categorised as low (1stfifth), moderate (2nd-4thfifths), and high (5thfifth). Median daily step count was categorised as low (<6,500), moderate (6,500-12,499), and high (≥12,500). The association of genetic risk and step count with incident CVD, defined as a composite of coronary artery disease and ischaemic stroke, was examined using adjusted Cox proportional hazards models.

Results

Of 84,286 participants, 4,847 were diagnosed with CVD during follow-up (median 7.9 years). High genetic risk and low daily step count had a log-additive association with incident CVD. In low genetic risk individuals, step count was not associated with incident CVD. However, in the moderate and high genetic risk groups, those with low step counts had 24% (HR 1.24; 95% Confidence Interval [CI] 1.10-1.40) and 37% (HR 1.37; 95% CI 1.14-1.65) higher risk of incident CVD compared to those with high step counts. There was an inverse dose-response association between the hazard of CVD and step counts up to 10,000 steps/day, which then plateaued in moderate and high genetic risk groups.

Conclusions

High daily step count was associated with lower CVD risk in individuals with moderate and high genetic risk, indicating that walking should be encouraged for all, especially those predisposed to CVD.
Surface Electromyographic Assessment of Pelvic Floor Muscles Protocol Tested by a Novel Airbag-type Stretchable Electrode Array (ASEA) Device in Stress Urinary Incontinence in Postmenopausal Women
Authors: Zhang Zujuan , Chen Qian , He Suyun , Li Wenjuan , Wang Shengming , Xie Zhenwei
Published: January 2025

Electromyography (EMG) is a well-established method to quantify the PFM activity. The purpose of this study was to investigate the PFM of US and LAMs EMG variables separately by ASEA device and determine the predict value of sEMG for ASEA assessing the PFM in postmenopausal women with SUI. We obtained the EMG of US and LAMs separately by ASEA device consisted of following elements: ARP, MVC, TCP, ECP and PRP. We performed ROC curve analysis for optimal cutoff level for sEMG activation of the PFM. For 65 healthy and 67 with SUI, muscle strength was lower in SUI group according to the modified Oxford grading system by bidigital palpation. The sEMG of PFM activities were significantly lower in SUI group tested by ASEA device, especially in the MVC, TCP and ECP activities in US and LAMs. According to ROC curves, US and LAMs, especially PR and PC, except IC, have optimum predict cutoff amplitude for SUI. Our study proved that US defect and dysfunctional LAMs play an important role in the pathogenesis of SUI and separation of specific regions of US and LAMs can provide a reliable and optimized treatment strategy for the precise rehabilitation of pelvic floor muscles.
The Advanced Organ Support (ADVOS) hemodialysis system fulfills its intended purpose: Analysis of data from 282 patients from the Registry on Extracorporeal Multiple Organ Support (EMOS)
Authors: Fuhrmann Valentin , Tyczynski Bartosz , Perez Ruiz de Garibay Aritz , Bingold Tobias Michael , Weinmann-Menke Julia , Faltlhauser Andreas , Jarczak Dominik , Lutz Jens , Sander Michael , Klimpke Pascal , Koch Christian , Kribben Andreas , Boenisch Olaf , Kluge Stefan
Published: January 2025

Background

Several case series have highlighted the ADVOS hemodialysis system’s efficacy in eliminating water-soluble and protein-bound substances across diverse patient populations, such as multiorgan failure, acute-on-chronic liver failure (ACLF), acidosis, and even COVID-19. The EMOS-Registry, a non-interventional, multi-center patient registry, amassed real-world evidence, culminating in the largest patient cohort treated with ADVOS to date. This study aims to present and analyze the final performance and safety outcomes from the entire dataset comprising 282 participants.

Methods

Data spanning from January 18, 2017, to August 31, 2020, were collected from five German hospitals, encompassing subsets of patients with acidosis and ACLF grade 3. Performance and safety were assessed through vital signs, clinical laboratory parameters and blood gas analyses. The SOFA Score-Standardized Mortality Ratio (SMR) served to evaluate patient outcomes in the absence of a control group.

Results

Participants, with a median age of 58 years, predominantly male (64%), exhibited a high requirement for mechanical ventilation (68%) and vasopressors (82%) with a median SOFA Score of 15. Notably, a median of 3 (IQR 2, 5) ADVOS sessions per patient were administered.

Following the initial treatment, significant reductions were observed in bilirubin (–1.9 [CI 95% –1.3, – 2.5]), creatinine (–0.5 [-0.4, –0.6]), and blood urea nitrogen (–13.1 mg/dL [-10.3, –16.0]) levels. Moreover, there were marked improvements in blood pH (7.34 vs. 7.41, p<0.001), HCO3-(19.4 vs. 24.6 mmol/l, p<0.001) and base excess (–5.6 vs. 0.2 mmol/l, p<0.001). The observed mortality rate (66%) was notably lower than the expected rate based on SOFA Score (84%), resulting in a SMR of 0.79 (95% CI: 0.66-0.93), with a calculated number needed to treat (NNT) of 5.8.

Conclusions

This study emphasizes the ADVOS system’s efficacy in eliminating water-soluble and protein-bound substances and correcting acid-base imbalances across a diverse cohort with multiorgan failure. However, further validation through randomized controlled trials is warranted to solidify these findings.

Trial registration: DRKS00017068. Registered 29 April 2019 – Retrospectively registered,https://drks.de/search/en/trial/DRKS00017068
The current landscape of lifestyle and other non-pharmaceutical interventions in oncology in Africa: A review of registered clinical trials
Authors: Wangari Monica , Njoroge Eunice , Mburu Grace , Mogeni Brenda , Ouma Luke
Published: January 2025

Cancer is a significant public health issue in low—and middle-income countries, especially in Africa. While lifestyle and/or behavioral interventions such as exercise and dietary modifications are known to improve patient outcomes and quality of life, critical evidence from resource-limited settings like Africa is scanty. Here, we present a review of clinical trials on the current landscape of cancer associated lifestyle interventions in oncology in Africa. We comprehensively reviewed non-pharmacological/ lifestyle cancer-related clinical trials in Africa onClinicalTrials.govand ICTRP trial registries from 01 July 2005 to 30 October 2024. We employed descriptive analyses, primarily frequency and percentage, to analyze and report the data. Overall, 53 trials matching the criteria were identified. Most of the trials were in Egypt (38/53, 97.4%), Kenya (4/53,10.3%), and Nigeria (5/53, 12.9%). The top cancer types for the trials in Africa were breast 24/62, 45.3%), colorectal (6/62, 11.3%) and acute lymphoblastic leukemia (4/62, 7.5%). Concerning sponsorship, most trials were universities/academia-sponsored trials (45/53, 84.9%), locally sponsored (37/53, 69.8%), conducted among patients (88.7%), and 84.9% cancer survivors. Most trials involved physical activity interventions (25/53, 47.2%) and psychological and psychological interventions (10/53, 18.9%), with (32/53, 60.4%) trials completed and (13/53, 24.5%) trials ongoing. Non-pharmacological interventions for the management of cancer appear to be nascent in Africa. Oncology trials are needed to ensure the effectiveness of non-pharmaceutical/lifestyle interventions in Africa, especially sub-Saharan Africa (SSA). In the current era of precision medicine, pharmacological, and lifestyle interventions, it no longer suffices to assume that interventions in high—and upper-middle-income countries will be effective in low-middle-income countries, especially Africa.
Multimodal associations between posterior hippocampus glutamate metabolism, visual cortex connectivity, and intrusive trauma reexperiencing symptoms
Authors: Clancy Kevin J. , Chen Xi , Song Xiaopeng , Song Tao , Zhou Shuqin , Akman Eylül , Ostrand Caroline , Ren Boyu , Du Fei , Rosso Isabelle M.
Published: January 2025

Objective

Hippocampal dysfunction is implicated in posttraumatic stress disorder (PTSD), particularly intrusive reexperiencing symptoms, and may be mediated by glutamatergic excitotoxicity. Markers of glutamate dysfunction (higher glutamate to N-acetyl aspartate levels; Glu/NAA) in the hippocampus (HPC) have been linked to reexperiencing symptoms. However, the HPC demonstrates heterogeneity along its anterior-posterior axis, with different functional connectivity patterns and PTSD symptom associations, motivating investigations into glutamate metabolism in anterior and posterior HPC subregions (a/pHPC).

Methods

121 symptomatic trauma-exposed adults (93 female) with current trauma reexperiencing symptoms completed magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the regional specificity of HPC Glu/NAA associations with reexperiencing, and the link to a/pHPC functional connectivity. PTSD symptoms were assessed with the Clinician-Administered PTSD Scale for DSM-5.

Results

Reexperiencing symptom severity was associated with greater Glu/NAA in the pHPC, but not aHPC. pHPC Glu/NAA was further linked to stronger functional connectivity between the pHPC and visual cortex (VC), which in turn correlated with more severe reexperiencing symptoms. This strengthened pHPC-VC connectivity explained the shared variance between pHPC Glu/NAA and reexperiencing severity, suggesting dysregulated glutamate metabolism in the pHPC may contribute to reexperiencing symptoms through functional connectivity with the VC.

Conclusions

These findings replicate prior work linking HPC Glu/NAA to trauma reexperiencing symptoms and provide novel evidence this association may be specific to the pHPC and mediated by its functional connectivity with the VC. This multimodal investigation supports translational models of glutamatergic dysfunction in trauma-related disorders and highlights new targets for pharmacological and neuromodulatory interventions.
Cellular, Connectomic, and Cognitive Impact of Glioma and its Surgical Resection
Authors: Poologaindran A , Luppi AI , Hart MG , Santarius T , Price S , Sughrue ME , Seidlitz J , Bethlehem RAI , Assem M , Erez Y , Duncan J , Bullmore ET , Suckling J , Romero-Garcia R
Published: January 2025

Awake surgery with intraoperative direct electrical stimulation (DES) is the gold-standard to maximize the extent of resection in diffuse cerebral gliomas (Duffau et al. 2023). While this approach is effective in testing for simple motor and language functions, it is inadequate for mapping higher-order cognitive functions such as attention, working memory, and cognitive control. Given that systems neuroscience is moving away from a localizationist to a connectomic perspective of human brain function, ideally, we could better understand how gliomas integrate within the connectome and how performing surgery on the brain’s mesoscale hub architecture affects long-term cognitive outcomes. To address problem, we combined cellular, connectomic, and cognitive data from healthy individuals (n=629) across the lifespan, cross-sectional glioma imaging (n=98), the Allan Human Brain Atlas (n=6), and a rare cohort of diffuse glioma patients (n=17) followed longitudinally as they underwent neurosurgery. First, we validate that meta-analytic cognitive activation maps co-localize with the Multiple Demand (MD) system and show that diffuse gliomas preferentially localize to the ‘core’ of this brain network. Second, cellular decoding of the MD core network reveals that it is uniquely enriched with oligodendrocyte precursor cells, glioma proto-oncogenes, and 5HT2-serotonergic neurotransmission. Third, the MD system is preferentially enriched for connector hubs to scaffolding the brain’s mesoscale hub architecture and that diffuse gliomas induce reorganization in this architecture thereby minimizing cognitive deficits. Lastly, surgical resection of connector, rather than provincial, hubs leads to long-term cognitive deficits while maintenance or dissolution of interhemispheric modularity predicted long-term cognitive outcomes. With the recent demonstration of the high concordance between DES and functional brain mapping (Saurrubo et al. 2024), this study provides new insight into how gliomas integrate within the connectome and that mapping the mesoscale hub architecture in each patient may improve presurgical mapping and postsurgical rehabilitation. Given the small but deeply sampled neurosurgical cohort, additional studies are now warranted to assess the value of mapping mesoscale connectivity for presurgical mapping and ‘interventional neurorehabilitation’ (Poologaindran et al. 2022).
Leveraging Longitudinal Patient-Reported Outcomes Trajectories to Predict Survival in Non-Small-Cell Lung Cancer
Authors: Zhou Jiawei , Muluneh Benyam , Wang Zhaoyang , Yao Huaxiu , Hughes Jim H.
Published: January 2025

Purpose

Despite their potential, patient-reported outcomes (PROs) are often underutilized in clinical decision-making, especially when improvements in PROs do not align with clinical outcomes. This misalignment may result from insufficient analytical methods that overlook the temporal dynamics and substantial variability of PROs data. To address these gaps, we developed a novel approach to investigate the prognostic value of longitudinal PRO dynamics in non-small-cell lung cancer (NSCLC) using Lung Cancer Symptom Scale (LCSS) data.

Methods

Longitudinal patient-reported LCSS data from 481 NSCLC participants in the placebo arm of a Phase III trial were analyzed. A population modeling approach was applied to describe PRO progression trajectories while accounting for substantial variability in the data. Associations between PRO model parameters and survival outcomes were assessed using Cox proportional hazards models. Model-informed PRO parameters were further used to predict survival via machine learning.

Results

A PRO progression model described LCSS dynamics and predicted a median time to symptom progression of 229 days (95% CI: 15-583). Faster PRO progression rates were significantly associated with poorer survival (HR 1.13, 95% CI: 1.076-1.18), while greater placebo/prior treatment effects correlated with improved survival (HR 0.93, 95% CI: 0.883-0.99). A machine learning model using PRO parameters achieved an AUC-ROC of 0.78, demonstrating their potential to predict overall survival.

Conclusions

This study demonstrates that longitudinal PRO data can provide prognostic insights into survival in NSCLC. The findings support the use of PRO dynamics to improve clinical decision-making and optimize patient-centered treatment strategies.

Translational Relevance

Patient-reported outcomes (PROs) offer a patient-centered, non-invasive approach to assessing health status and symptoms, making them a valuable tool for understanding the patient experience. However, PROs are often underutilized in clinical decision-making, especially when improvements in PROs do not align with clinical outcomes. This misalignment is often driven by analytical methods that fail to account for the temporal dynamics and inherent variability of PROs data. To address these limitations, we have developed a novel computational framework that integrates population modeling with machine learning to leverage longitudinal PRO dynamics for predicting survival in non-small-cell lung cancer patients. This innovative approach can be generalized to other PRO datasets, providing personalized insights into PRO trajectories for each patient. By enhancing the utility of PROs data, our framework holds the potential to significantly improve clinical decision-making, refine patient care strategies, and optimize the design and evaluation of clinical trials, ultimately advancing precision oncology.
Association of Oral Triptans and Other Oral Migraine Treatments With Cardiovascular Outcomes in Patients With a History of Cardiovascular Conditions
Authors: Dodick David W. , Fisher Matt , DerSarkissian Maral , Murphy Shawn N. , Duh Mei Sheng , Gao Chi , Weiner Rory B. , Yu Louise H. , Herrick Christopher , Hsieh Yichuan Grace , Wang Travis , Belsky Greg , Banatwala Azeem , Boyle-Kelly Janet , Costello Jennifer , Murphy Marykate , Wong Amy K. , Ailani Jessica
Published: January 2025

OBJECTIVE

To assess risk of major adverse cardiovascular events associated with acute antimigraine treatments in patients with preexisting cardiovascular conditions.

PATIENTS AND METHODS

In this retrospective, longitudinal, observational cohort study, we examined data from the Mass General Brigham Research Patient Data Registry on adults who received one or more prescriptions for acute migraine (index date) between January 2006 and December 2020 and who had one or more diagnoses of a cardiovascular condition during 12 months prior to index date. Study endpoints were nonfatal myocardial infarction, nonfatal stroke, and in-facility all-cause mortality, assessed separately and together as a composite major adverse cardiovascular events–proxy endpoint.

RESULTS

Prescriptions were identified for 4016 oral triptans, 6084 opioids/butalbital, and 2021 NSAIDs. Hazard ratios (HRs) for major adverse cardiovascular events were 0.38 (95% CI: 0.22, 0.67;P=.001) comparing oral triptans with opioids/butalbital and 0.46 (95% CI: 0.29, 0.71;P<.001) with NSAIDs. There was no increased risk of nonfatal stroke comparing oral triptans with opioids/butalbital (HR 0.39; 95% CI 0.22, 0.69;P=.001) and with NSAIDs (HR 0.44; 95% CI 0.26, 0.76;P=.003). In a subgroup analysis of patients taking sumatriptan, HRs for major adverse cardiovascular events were 0.34 (95% CI: 0.21, 0.56;P<.001) when comparing oral sumatriptan with opioids/butalbital and 0.47 (95% CI: 0.28, 0.79;P=.004) with NSAIDs.

CONCLUSIONS

The risk of adverse cardiovascular events observed with oral triptans is not greater than opioids/butalbital and NSAIDs in patients with migraine and preexisting cardiovascular conditions.
[Re] Deep Learning for ECG Analysis: Benchmarks and Insights from PTB-XL
Authors: Gitau Antony M. , Adeyemi Ayoade , Tavashi Belal , Singstad Bjørn-Jostein
Published: January 2025

Reproducibility Summary

Scope of Reproducibility

The authors of the original paper present six benchmark tasks on the previously published PTB-XL dataset, containing, 21837 12-lead ECGs from 18885 patients. They evaluate seven different neural network architectures on the six bench-mark tasks. The authors have published all code and claim full reproducibility. In addition, they published code for easy implementation of new models. To validate the claim of reproducibility we implemented a new model and tested it, and the seven models presented by the authors of the original paper, on the six benchmark tasks.

Methodology

We used the publicly available code, published by the authors of the original paper, as a starting point for our experiment. Furthermore, we modified the code slightly in order to make it compatible with a cloud-hosted Jupyter Notebook, Google Colab. We ran the experiments using Google Colab Pro, using 32 GB RAM and either 1 x NVIDIA P100 or 1 x NVIDIA T4 GPU.

Results

We successfully managed to reproduce the original work and also verified the validity of the main claims of the original paper. In addition, we showed how robust the models were to noise and finally implemented a new model that showed comparable performance with the models proposed in the original paper.

What was easy

The publicly available code published by the authors made it easy to reproduce and obtain the same results as reported in their paper.

What was difficult

We faced two main issues in this work. (1) running the code in a cloudhosted jupyter notebook. This was done in order to get access to free or cheap GPUs. (2) Implement own models using the provided template. The description on how to use the base class and the configuration file could have been more detailed.

Communication with original authors

Communication with the authors of the original paper was established early in the project and helped us by clarifying some aspects of the work. In the final stage of this project the authors of the original paper were given this manuscript in order to read it and provide feedback.
Cingulate and Frontopolar Cortical Projections to the Cerebellar Vermis Support Prolonged Reaction Time in Identifying Negative Emotional Scenes in Women
Authors: Wong Hak Kei , Chaudhary Shefali , Chen Yu , Ide Jaime S. , Zhang Sheng , Li Chiang-Shan R.
Published: January 2025

We previously observed sex differences in the association of individual anxiety and reaction time (RT) during identification of negative emotional scenes in a Hariri task. Prolonged RT in identifying negative (vs. neutral) images represents a behavioral marker of individual anxiety in women but not in men. However, the neural circuit that supports this behavioral observation remains unclear. Here, with a larger sample (64 men and 62 women), we employed whole-brain regression on individual differences in RT during matching negative vs. neutral images or RT (negative – neutral) and evaluated the results at a corrected threshold. Women but not men showed a significant correlation between individual anxiety and RT (negative – neutral), with a slope test confirming the sex difference. In women alone the cerebellar vermis showed activity in positive correlation with RT (negative – neutral). Further, Granger causality mapping (GCM) showed multiple brain regions, including the anterior cingulate cortex/frontopolar cortex (ACC/FPC), that provide inputs to the cerebellar vermis in women. Amongst these regions, only the ACC/FPC cluster showed activity (β) in significant correlation with both STAI State score and RT (negative – neutral) in women. GCM also identified a small cluster in the pons, suggesting that the cortical pontine cerebellar circuit may support prolonged RT during identification of negative emotions. Path analyses further characterized the inter-relationships amongst the neural markers, RT, and anxiety. These findings highlight a behavioral and circuit marker of anxiety state in neurotypical women. Studies with different behavioral paradigms are needed to characterize the behavioral and neural mechanisms of male anxiety.
Impact of Electronic Immunization Registries and Electronic Logistics Management Information Systems in four Low-and Middle-Income Countries: Guinea, Honduras, Rwanda, and Tanzania
Authors: Mantel C , Hugo C , Federici C , Sano N , Camara S , Rodriguez E , Castillo L , Condo J , Irakiza P , Sabi I , Nyanda E , Olomi W , Cavazza M , Mangiaterra V , Verykiou M , Ferenchick E , Torbica A , Cherian T , Malvolti S
Published: January 2025

Background

There is increasing interest in low-and middle-income countries (LMICs) to introduce and scale-up digital health tools like electronic immunization registries (eIR), and electronic logistics management information systems (eLMIS) to support immunization services. An evaluation of the use of these tools was conducted in four countries to inform decisions about their further expansion and investments.

Methods

Purposive sampling of regions, districts, and health facilities was done in each country based on predefined criteria. Primary data were collected between October 2021 and September 2022 in 50 health facilities in Guinea, 88 in Honduras, 36 in Rwanda, and 101 in Tanzania using semi- structured questionnaires, standardized competency assessments and data accuracy checks. Data focused on electronic tool usage, user experience, infrastructure, workforce needs, and decision- making, as well as immunization data quality and perceptions of health workers and vaccine recipients. Data analysis combined both quantitative and qualitative methods.

Findings

The implementation of eIR and eLMIS was associated with improvements in National Immunization Programme (NIP) processes and outcomes. Users were satisfied with the tools (87% satisfaction rate), and 95% of users in Africa valued the accessibility of information, with 91% finding it accurate and complete. Some caregivers reported better organization and shorter waiting times in health facilities using the tools. Most eIR users noted improvements in process efficiencies (81%) and immunization service delivery (89%). In Rwanda and Tanzania data accuracy was higher in exclusively paper or electronic settings (60%) compared to dual paper-electronic systems (45%). eLMIS use was associated with improvements in vaccine stock data quality and reduced stock-outs. While 77% of health workers were digitally literate, inadequate digital infrastructure was a key barrier to tool use. Interoperability with the Civil Registration and Vital Statistics system (CRVS) was limited, hindering the tracking of unimmunized children.

Conclusions

To fully realize the potential of electronic tools in LMICs, full government ownership, targeted infrastructure investments, migration to fully electronic systems, and integration of eIR with the CRVS are essential.
Methylphenidate stabilizes dynamic brain network organization during tasks probing attention and reward processing in stimulant-naïve children with ADHD
Authors: Nugiel Tehila , Fogleman Nicholas D. , Sheridan Margaret A. , Cohen Jessica R.
Published: January 2025

Children with ADHD often exhibit fluctuations in attention and heightened reward sensitivity. Psychostimulants, such as methylphenidate (MPH), improve these behaviors in many, but not all, children with ADHD. Given the extent to which psychostimulants are prescribed for children, coupled with variable efficacy on an individual level, a better understanding of the mechanisms through which MPH changes brain function and behavior is necessary. MPH’s primary action is on catecholamines, including dopamine and norepinephrine. Catecholaminergic signaling can influence the tradeoff between flexibility and stability of brain function, which is one candidate mechanism through which MPH may alter brain function and behavior. Time-varying functional connectivity, which models how functional brain networks reconfigure on short timescales, can be used to examine brain flexibility versus stability, and is thus well-suited to test how MPH impacts brain function. Here, we scanned stimulant-naïve children with ADHD (8-12 years) on and off a single dose of MPH. In the MRI machine, participants completed two attention-demanding tasks: 1) a standard go/no-go task and 2) a rewarded go/no-go task. For both tasks, using a within-subjects design, we compared the degree to which brain organization changed throughout the course of the MRI scan, termed whole brain flexibility, on and off MPH. We found that whole brain flexibility decreased on MPH. Further, individuals with greater decreases in whole brain flexibility on MPH exhibited greater improvements in task performance. Together, these results provide novel insights into the neurobiological mechanisms underlying the effectiveness of MPH administration for children with ADHD.
The Association of Demographic Factors to Health Policy Subscriptions in Saudi Arabia: insight from National Survey
Authors: Alasiri Ahmed Ali , Zhang Qi , Sahabi Mohammed
Published: January 2025

Background

Saudi approaches to delivering health services seem not sustainable, and it may limit access to the necessary healthcare services. Therefore, the health system is undergoing several paradigms shifts with the investment of the private sector and insurance. The subscriptions to the health policy are affected by several variables, while demographic indicators of Health policy subscription among Saudi and expatriate populations remain underexplored.

Aim

The study aims to test the association of the age, gender and nationality on the subscription of health policy by utilizing national data.

Method

The study retrieved secondary data from Saudi Data & AI Authority (SDAIA), collected between 2021 -2022 with a nationality sample that cover all Saudi regions (n=14.780). The project utilized descriptive and inferential statistical tests to analyze the data and understand the relationship between the demographic variables and how they affect the subscription to health insurance.

Result

While age, gender, and nationality have impacted the subscription of insurance to varying degrees, however, these factors revealed a small effect on the policy subscription, indicating that other social-economic variables may have a stronger prediction of the subscription rate.
Exploring booster session attendance, prescription, and outcomes in adults with chronic low back pain: Secondary analysis of a randomized clinical trial
Authors: Lanier Vanessa M. , Lohse Keith R. , Hooker Quenten L. , Civello Jesse M. , van Dillen Linda R.
Published: January 2025

Introduction

Booster sessions are a potential method for maintaining self-management behaviors and treatment effects in people with chronic low back pain (LBP). However, few studies have examined booster prescription or outcomes in people with LBP.

Objective

(1) Compare booster prescription for two exercise-based treatments for low back pain (LBP) in a randomized clinical trial (RCT) where the number of boosters prescribed was based on self-management program independence, (2) Determine if there are variables that predict who will require >1 booster, (3) Explore the effects of boosters on pain and function in people who required >1 booster.

Design

Secondary analysis of a RCT in which participants were randomized to motor skill training (MST), MST+Boosters (MST+B), strength and flexibility exercise (SFE), or SFE+B.

Setting

Academic research setting.

Participants

76 participants with chronic LBP assigned to receive boosters.

Interventions

This secondary analysis focuses only on the MST+B and SFE+B groups. Both groups received 6 visits of MST or SFE and six months later received up to 3 boosters. The number of boosters was based on self-management program independence at the first booster. Those who required >1 booster were not able to independently perform their program at the first booster.

Main Outcome Measures

Booster attendance and prescription, pain (Numeric Pain Rating Scale), function (modified Oswestry Disability Questionnaire)

Results

There was not a significant difference between MST+B and SFE+B in returning for the initial booster, χ2(1)=1.76, p=0.185. SFE+B were more likely to require >1 booster than MST+B;β=2.39,p<0.001. No participant-specific factors we examined were statistically related to needing >1 booster.

Conclusion

MST+B participants were less likely to require additional boosters. No additional participant-specific factors we examined were associated with needing additional boosters. Qualitatively, attending additional booster sessions did not appear to change pain or function in the current sample.
Examining the cognitive phenotype in Neurofibromatosis 1: a systematic review of functional imaging studies
Authors: Wild Anna , Tziraki Maria , Lea-Carnall Caroline , Garg Shruti
Published: January 2025

Neurofibromatosis 1 (NF1) is a rare genetic condition, frequently associated with learning difficulties. Functional neuroimaging techniques have been used to investigate brain mechanisms underlying learning difficulties in NF1, but these remain poorly understood. We conducted a systematic review of functional neuroimaging studies in NF1 from 2000-2024 aiming to develop a neurobiological framework for understanding the NF1 cognitive phenotype. A total of 44 studies were identified as relevant across functional magnetic resonance imaging (fMRI), electroencephalography (EEG), magnetic resonance spectroscopy (MRS), positron emission topography (PET), transcranial magnetic stimulation (TMS) and arterial spin labelling (ASL) techniques. Findings suggest mechanisms underlying learning in NF1 may be characterised as excitation/ inhibition imbalance, dysconnectivity between brain regions and perturbations in neural activation patterns. We suggest, disruptions in GABAergic signalling, beginning in early development, may alter the whole brain function, explaining the differential patterns of brain activity, connectivity, and brain chemistry. As most of the reviewed studies were cross-sectional in nature, future research should focus on longitudinal designs to better understand developmental changes in brain mechanisms and how these processes evolve over time. Finally, it is essential to explore environmental modifiers in shaping the cognitive phenotypes associated with NF1.
Immediate postoperative minimal residual disease detection with MAESTRO predicts recurrence and survival in head and neck cancer patients treated with surgery
Authors: Sim Edward S. , Rhoades Justin , Xiong Kan , Walsh Laurel , Crnjac Andjela , Blewett Timothy , Al-Inaya Yana , Mendel Julia , Ruiz-Torres Daniel A. , Efthymiou Vasileios , Lumaj Gjystina , Benjamin William J. , Makrigiorgos G. Mike , Tabrizi Shervin , Adalsteinsson Viktor A. , Faden Daniel L.
Published: January 2025

Purpose

While circulating tumor DNA (ctDNA) is a promising biomarker for minimal residual disease (MRD) detection in head and neck squamous cell carcinoma (HNSCC), more sensitive assays are needed for accurate MRD detection at clinically-relevant timepoints. Ultrasensitive MRD detection immediately after surgery could guide adjuvant therapy decisions, but early ctDNA dynamics are poorly understood.

Experimental Design

We applied MAESTRO, a whole-genome, tumor-informed, mutation-enrichment sequencing assay, in a pooled testing format called MAESTRO-Pool, to plasma samples from HNSCC patients collected immediately after surgery and during surveillance. We evaluated whether early MRD detection could predict outcomes.

Results

Among 24 predominantly HPV-independent (95.8%) HNSCC patients, rapid ctDNA clearance occurred by the first postoperative sample (1-3 days postoperatively) in 9 patients without an event (recurrence or death). 13/15 patients with an event were MRD+ (PPV = 92.9%; NPV = 80%) with a median tumor fraction (TFx) of 54 ppm (range 6-1,177 ppm). In the first and last sample of the immediate postoperative window, 8/13 and 10/13 patients had TFx below 100 ppm, respectively, the detection limit of leading commercial assays. Early MRD detection correlated with worse overall survival (HR = 8.3; 95% CI: 1.1-66.1;P= 0.02) and event-free survival (HR = 27.4; 95% CI: 3.5-214.5;P< 0.0001) independent of high-risk pathology.

Conclusions

Immediate postoperative MRD detection by MAESTRO was predictive of recurrence and death. Given the ultralow TFxs observed, ultrasensitive assays will be essential for reliable MRD detection during early postoperative timepoints to enable personalized adjuvant therapy decision-making in HNSCC.
Transformers Enhance the Predictive Power of Network Medicine
Authors: Spector Jonah , Aldana Andrés , Sebek Michael , Ehlert Joseph , DeFrondeville Christian , Ghiassian Susan Dina , Barabási Albert-László
Published: January 2025

Background

Self-attention mechanisms and token embeddings behind transformers allow the extraction of complex patterns from large datasets, and enhance the predictive power over traditional machine learning models. Yet, being trained to make predictions about individual cells or genes, it is not clear if transformers can learn the inherent interaction patterns between genes, ultimately responsible for their mechanism of action. We use Geneformer, pretrained on single-cell transcriptomes, to ask if transformers can implicitly capture molecular dependencies, including protein-protein interactions (PPIs), allowing us to explore the use of transformers to improve network medicine tasks such as disease gene identification and drug repurposing.

Methods

We extracted the cosine similarity of gene embeddings and the attention weights contained in Geneformer, allowing us to test if these weights capture experimentally validated protein interactions. Using dilated cardiomyopathy as a case study, we evaluated the effectiveness of the resulting weighted networks in disease module detection and drug repurposing.

Results

We found that Geneformer displays awareness of experimentally documented Protein-Protein Interactions, exhibiting higher cosine similarity and attention weights for gene pairs with physical interactions. Weighting PPI networks with the cosine similarity and attention weights improved the detection of disease-associated genes and the accuracy of drug repurposing predictions for dilated cardiomyopathy, surpassing the accuracy of unweighted networks. Finally, we find that combining attention weights and cosine similarities with ranking methods enhances drug candidate prioritization for drug repurposing.

Conclusions

We find that transformers, by implicitly learning the interactions between genes, offer a promising pathway for advancing medicine and drug discovery when integrated with the graph theoretic algorithms used in network medicine.