bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Utilization of 3D Anatomy Education Content using Metaverse and XR for Remote Telemedicine Education
Authors: Choi Dong Hyeok , Choi Seo Yi , Ahn So Hyun , Lee Rena , Cho Sung Ho , Han Seung Ho
Published: June 2024

The objective of this study is to explore innovative integration within the field of anatomy education by leveraging HoloLens 2 Augmented Reality Head-Mounted Display (AR HMD) technology and real-time cloud rendering. Initial 3D datasets, comprising extensive anatomical information for each bone, were obtained through the 3D scanning of a full-body cadaver of Korean male origin. Subsequently, these datasets underwent refinement processes aimed at enhancing visual fidelity and optimizing polygon counts, utilizing Blender software. Unity was employed for the development of the Metaverse platform, incorporating tailored 3D User Experience (UX) and User Interface (UI) components to facilitate interactive anatomy education via imported cadaver models. Integration with real-time remote rendering cloud servers, such as Azure, was implemented to augment the performance and rendering capabilities of the HoloLens 2 AR HMD. The extended reality (XR) content uses the Photon Cloud network for real-time data synchronization and HoloLens 2 voice functionality. The metaverse platform supports user interaction through room creation and joining, with various tools for bone manipulation, color differentiation, and surface output. Collaboration features enable sharing and synchronization of model states. The study highlights the importance of technological innovation in anatomy education for future medical professionals. The proposed content aims to address limitations of traditional methods and enhance learning experiences. Continued efforts in developing and improving such technologies are crucial to equip learners with essential skills for adaptation in the evolving healthcare landscape. keyword: Metaverse, Anatomy, Cadaver, Extended Reality(XR), Virtual Reality(VR)
Active enhancement of synapse driven depolarization of perisynaptic astrocytic processes
Authors: Nakatani Ryo J. , De Schutter Erik
Published: June 2024

Electrophysiological properties underlie the fundamental mechanisms of the brain. Although astrocytes have typically been considered not electrically excitable, recent studies have shown depolarization of astrocytes induced by local extracellular potassium changes caused by neuronal activity. Interestingly, astro-cytic depolarization is only induced within the periphery of the astrocyte, where astrocytes contact neurons. This depolarization affects the brain’s information processing, as depolarization alters astrocyte functionality and neurotransmit-ter dynamics. However, specific mechanisms causing astrocytic depolarization have remained unknown due to the limitations of experimental techniques. Here, we construct a computational whole-cell astrocyte model containing experimen-tally verified astrocytic channels relevant to depolarization. Using our model, we suggest that previously reported potassium channels alone are insufficient for astrocyte depolarization and additional mechanisms are required. Our sim-ulations show that NMDARs contribute to this depolarization by cooperating with Kir 4.1 to actively enhance extracellular potassium concentration and, thus, sustain depolarization.
Effect of Circadian Rhythm Modulated Blood Flow on Nanoparticle based Targeted Drug Delivery in VirtualIn VivoArterial Geometries
Authors: Goraya Shoaib A. , Ding Shengzhe , Arif Mariam K. , Kong Hyunjoon , Masud Arif
Published: June 2024

Delivery of drug using nanocarriers tethered with vasculature-targeting epitopes aims to maximize the therapeutic efficacy of the drug while minimizing the drug side effects. Circadian rhythm which is governed by the central nervous system has implications for targeted drug delivery due to sleep-wake cycle changes in blood flow dynamics. This paper presents an advanced fluid dynamics modeling method that is based on viscous incompressible shear-rate fluid (blood) coupled with an advection-diffusion equation to simulate the formation of drug concentration gradients in the blood stream and buildup of concentration at the targeted site. The method is equipped with an experimentally calibrated nanoparticle-endothelial cell adhesion model that employs Robin boundary conditions to describe nanoparticle retention based on probability of adhesion, a friction model accounting for surface roughness of endothelial cell layer, and a dispersion model based on Taylor-Aris expression for effective diffusion in the boundary layer. The computational model is first experimentally validated and then tested on engineered bifurcating arterial systems where impedance boundary conditions are applied at the outflow to account for the downstream resistance at each outlet. It is then applied to a virtual geometric model of anin vivoarterial tree developed through MRI-based image processing techniques. These simulations highlight the potential of the computational model for drug transport, adhesion, and retention at multiple sites in virtualin vivomodels. The model provides a virtual platform for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing thein vivoexperimentation.

Statement of Significance

A novel integration of nanoparticle-based drug delivery framework with shear-rate dependent blood flow model is presented. The framework is comprised of a unique combination of mechanics-based dispersion model, an asperity model for endothelium surface roughness, and a stochastic nanoparticle-endothelial cell adhesion model. Simulations of MRI basedin vivocarotid artery system showcase the effects of vessel geometry on nanoparticle adhesion and retention at the targeted site. Vessel geometry and target site location impact nanoparticle adhesion; curved and bifurcating regions favor local accumulation of drug. It is also shown that aligning drug administration with circadian rhythm and sleep cycle can enhance the efficacy of drug delivery processes. These simulations highlight the potential of the computational modeling for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing thein vivoexperimentation.
Molecular modeling of Proteinase-Activated Receptor 1 in complex with Thrombin Receptor Activator Peptide 6
Authors: Reboul E , El Hamaoui D. , Pasquali S. , Gaussem P. , Rossi E. , Taly A.
Published: June 2024

The protease-activated receptor 1 (PAR1) and its activator thrombin re-ceptor activator peptide 6 (TRAP6) play crucial roles in various physiologi-cal and pathological processes, including hemostasis, thrombosis, and cancer progression. Although the interaction between PAR1 and TRAP6 has been heavily studied using experimental technique such as mutagenesis, structural data remains scarce due to the technical hardship of studying membrane pro-teins such as PAR1.

In this study, we employed an integrative modeling approach to elucidate the structure of the PAR1-TRAP6 complex. Leveraging state-of-the-art AI-based protein modeling tools, including AlphaFold2 and ESMFOLD, we in-tegrated HADDOCK, a physics-based method to refine predictions. Overall, the predicted structures are in good agreement with the experimental data available in the literature. Our model unveiled a new T-shaped pi-stacking interaction between TRAP6’s F2 and PAR1’s Y360.

The integrative modeling approach combining the predictions of the deep learning model with a physics-based method proves to be an interesting strat-egy for solving challenging membrane protein structures with high confidence. Our model of the PAR1-TRAP6 complex will be an interesting starting point for further investigation of the activation of PAR1 by TRAP6.
Assessing the impact of periodontal therapy on tooth loss: a register-based longitudinal study in Denmark
Authors: Raittio Eero , Baelum Vibeke
Published: June 2024

Abstract

Background

While regular periodontal care is advocated to reduce tooth loss considerably among periodontitis patients, evidence from observational studies is often limited to small single-center studies. This study aims to quantify the effect of periodontal care on tooth extractions using comprehensive Danish register data.

Methods

A nation-wide register-based cohort study was conducted, encompassing 40-year- old individuals with incident periodontitis in 2001, tracked through Danish registers until the end of 2021. Receiving any periodontal care was determined annually, and the number of non-surgical tooth extractions serving as the annually varying outcome. G-estimation of structural nested mean models adjusted for time-varying confounding and loss to follow-up were employed to estimate the average treatment effect of periodontal therapy on subsequent tooth extractions.

Results

The study included 1,251 40-year-olds with incident periodontitis in 2001. The average follow-up from 2002 onwards was 19.1 years and amounted to 23,878 person-years. On average, participants received periodontal care in 12.1 years (SD 6.3) and lost an average of 1.4 teeth (SD 3.0). G-estimation showed that receiving periodontal therapy in a given year reduced the number of teeth extracted in the following year by 0.03 (95% CI: -0.00; 0.05). The cumulative effect of receiving periodontal therapy for five consecutive years was associated with an average of 0.06 (95% CI: 0.03; 0.11) less extracted teeth, while on average 0.36 teeth were lost in a five-year period (0.072 per year). This protective effect was observed regardless of the baseline severity of periodontitis.

Conclusions

Periodontal therapy resulted in a modest reduction in tooth extractions. The effectiveness of periodontal therapy against tooth loss seems to be considerably smaller than indicated by earlier clinical studies.
M&M: An RNA-seq based Pan-Cancer Classifier for Pediatric Tumors
Authors: Wallis Fleur S.A. , Baker-Hernandez John L. , van Tuil Marc , van Hamersveld Claudia , Koudijs Marco J. , Verwiel Eugène T.P. , Janse Alex , Hiemcke-Jiwa Laura S. , de Krijger Ronald R. , Kranendonk Mariëtte E.G. , Vermeulen Marijn A. , Wesseling Pieter , Flucke Uta E. , de Haas Valérie , Luesink Maaike , Hoving Eelco W. , Vormoor H. Josef , van Noesel Max M. , Hehir-Kwa Jayne Y. , Tops Bastiaan B.J. , Kemmeren Patrick , Kester Lennart A.
Published: June 2024

With many rare tumor types, acquiring the correct diagnosis is a challenging but crucial process in pediatric oncology. Here, we present M&M, a pan-cancer ensemble-based machine learning algorithm tailored towards inclusion of rare tumor types. The RNA-seq based algorithm can classify 52 different tumor types (precision∼99%, recall∼80%), plus the underlying 96 tumor subtypes (precision∼96%, recall∼70%). For low-confidence classifications, a comparable precision is achieved when including the three highest-scoring labels. M&M’s pan-cancer setup allows for easy clinical implementation, requiring only one classifier for all incoming diagnostic samples, including samples from different tumor stages and treatment statuses. Simultaneously, its performance is comparable to existing tumor- and tissue-specific classifiers. The introduction of an extensive pan-cancer classifier in diagnostics has the potential to increase diagnostic accuracy for many pediatric cancer cases, thereby contributing towards optimal patient survival and quality of life.
Postoperative Acute Kidney Injury is Associated with Persistent Renal Dysfunction: A Multicenter Propensity Matched Cohort Study
Authors: Stannard Blaine , Epstein Richard H. , Gabel Eilon , Nadkarni Girish N. , Ouyang Yuxia , Lin Hung-Mo , Salari Valiollah , Hofer Ira S.
Published: June 2024

Background

The risk of developing a persistent reduction in renal function after postoperative acute kidney injury (pAKI) is not well-established.

Objective

Perform a multi-center retrospective propensity matched study evaluating whether patients that develop pAKI have a greater decline in long-term renal function than patients that did not develop postoperative AKI.

Design

Multi-center retrospective propensity matched study.

Setting

Anesthesia data warehouses at three tertiary care hospitals were queried.

Patients

Adult patients undergoing surgery with available preoperative and postoperative creatinine results and without baseline hemodialysis requirements.

Measurements

The primary outcome was a decline in follow-up glomerular filtration rate (GFR) of 40% relative to baseline, based on follow-up outpatient visits from 0-36 months after hospital discharge. A propensity score matched sample was used in Kaplan-Meier analysis and in a piecewise Cox model to compare time to first 40% decline in GFR for patients with and without pAKI.

Results

A total of 95,208 patients were included. The rate of pAKI ranged from 9.9% to 13.7%. In the piecewise Cox model, pAKI significantly increased the hazard of a 40% decline in GFR. The common effect hazard ratio was 13.35 (95% CI: 10.79 to 16.51, p<0.001) for 0-6 months, 7.07 (5.52 to 9.05, p<0.001) for 6-12 months, 6.02 (4.69 to 7.74, p<0.001) for 12-24 months, and 4.32 (2.65 to 7.05, p<0.001) for 24-36 months.

Limitations

Retrospective; Patients undergoing ambulatory surgery without postoperative lab tests drawn before discharge were not captured; certain variables like postoperative urine output were not reliably available.

Conclusion

Postoperative AKI significantly increases the risk of a 40% decline in GFR up to 36 months after the index surgery across three institutions.
Spectral Analysis Comparison of Pushbroom and Snapshot Hyperspectral Cameras forIn-VivoBrain Tissues and Chromophores Identification
Authors: Martín-Pérez Alberto , de Ternero Alejandro Martinez , Lagares Alfonso , Juarez Eduardo , Sanz César
Published: June 2024

Significance

Hyperspectral imaging sensors have rapidly advanced, aiding in tumor diagnostics forin-vivobrain tumors. Linescan cameras effectively distinguish between pathological and healthy tissue, while snapshot cameras offer a potential alternative to reduce acquisition time.

Aim

Our research compares linescan and snapshot hyperspectral cameras forin-vivobrain tissues and chromophores identification.

Approach

We compared a lines-can pushbroom camera and a snapshot camera using images from 10 patients with various pathologies. Objective comparisons were made using unnormalized and normalized data for healthy and pathological tissues. We utilized Interquartile Range (IQR) for the Spectral Angle Mapping (SAM), the Goodness-of-Fit Coefficient (GFC), and the Root Mean Square Error (RMSE) within the 659.95 to 951.42 nm range. Additionally, we assessed the ability of both cameras to capture tissue chromophores by analyzing absorbance from reflectance information.

Results

The SAM metric indicates reduced dispersion and high similarity between cameras for pathological samples, with a 9.68% IQR for normalized data compared to 2.38% for unnormalized data. This pattern is consistent across GFC and RMSE metrics, regardless of tissue type. Moreover, both cameras could identify absorption peaks of certain chromophores. For instance, using the absorbance measurements of the linescan camera we obtained SAM values below 0.235 for four peaks, regardless of the tissue and type of data under inspection. These peaks are: one for cytochrome b in its oxidised form atλ= 422 nm, two for HbO2 atλ= 542 nm andλ= 576 nm, and one for water atλ= 976 nm.

Conclusion

The spectral signatures of the cameras show more similarity with unnormalized data, likely due to snapshot sensor noise, resulting in noisier signatures post-normalization. Comparisons in this study suggest that snapshot cameras might be viable alternatives to linescan cameras for real-time brain tissues identification.
Comparison of healthcare resource use and cost between influenza and COVID-19 vaccine coadministration and influenza vaccination only
Authors: Mehta Darshan , Sun Tianyu , Wang Jane , Situ Aaron , Park Yoonyoung
Published: June 2024

Objective

To compare healthcare recourse utilizations (HCRU) and all-cause medical costs among individuals 50 years or older who received both influenza and COVID-19 vaccines on the same day and those that received influenza vaccine only

Methods

We conducted a retrospective cohort study leveraging Optum’s de-identified Clinformatics® DataMart from 8/31/2021 to 7/31/2023. Individuals 50 years or older continuously enrolled in health plans for one year prior and until 7/31/2023 were included in the study. Subjects were categorized into 2 cohorts based on their vaccination status between 8/31/2022 and 1/31/2023: receiving influenza and COVID-19 vaccine on same day (co-admin cohort) and receiving influenza vaccine only (influenza cohort). The association between vaccination status and all-cause, influenza-related, COVID-related, pneumonia-related, and cardiorespiratory-related hospitalization, as well as outpatient or emergency room visits and all-cause medical costs was estimated by weighted generalized linear models, adjusting for confounding by stabilized inverse probability of treatment weighting.

Results

613,156 (mean age: 71) and 1,340,011 (mean age: 72) individuals were included in the co-admin and influenza cohort respectively. After weighting, the baseline characteristics were balanced between cohorts. The co-admin cohort was at statistically significant lower risk of all-cause (RR: 0.95, 95%CI: 0.93-0.96), COVID-19-related (RR: 0.59, 95%CI: 0.56-0.63), cardiorespiratory-related (RR: 0.94, 95%CI: 0.93-0.96) and pneumonia-related (RR: 0.86, 95%CI: 0.83-0.90) hospitalization but not influenza-related hospitalizations (RR: 0.91, 95%CI: 0.81, 1.04) compared to influenza cohort. Co-administration was associated with 3% lower all-cause medical cost (cost ratio: 0.974, 95% CI: 0.968, 0.979) during the follow-up period compared to receiving influenza vaccine only.

Conclusion

Receiving both COVID-19 and influenza vaccines on the same day in comparison to receipt of influenza vaccine only was associated with reduced risk of HCRU, especially COVID-19 related hospitalization and all-cause medical costs. Interventions that increase vaccine coverage, particularly for COVID-19 might have public health and economic benefits.
Prognostic Significance of Left Ventricular Diastolic Dysfunction in the Community: A Project Baseline Health Study
Authors: Fahed Gracia , Santana Everton , Cauwenberghs Nicholas , Celestin Bettia , Carroll Megan K. , Short arah A. , Alexander Kevin M. , Bagherzadeh Shadi P. , Mahaffey Kenneth W. , Hernandez Adrian F. , Shah Svati H. , Salerno Michael , Douglas Pamela S. , Kusnetsova Tatiana , Daubert Melissa A. , Haddad Francois
Published: June 2024

Introduction

Left ventricular diastolic dysfunction (LVDD) is an important predictor of cardiovascular outcomes. To date, however, few studies have validated the prognostic value of the LVDD assessment guidelines in a community-based setting. This study aimed to validate the predictive significance of LVDD following recommendations from the American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI), and to explore the use of a diastolic score in characterizing LVDD, particularly in individuals who remain unclassified (indeterminate) by the guidelines.

Materials and Methods

Project Baseline Health Study (PBHS) participants were included (n=1,952). LVDD was graded using the ASE/EACVI criteria. Multivariable Cox regression estimated associations between LVDD and major adverse cardiovascular events (MACE). To gain insights into the indeterminate group, we developed a novel diastolic score (0-6 points) with minor and major criteria guided by percentile deviation from a healthy reference cohort (n=565), including early mitral annular tissue Doppler velocity (e’), the ratio of early diastolic inflow velocity to e’ (E/e’), and left atrial volume index.

Results

At enrollment, the mean age of participants was 50±16; and 56% were female. According to the ASE/EACVI guidelines, LVDD was indeterminate in 5.9% and present in 8.4% of participants, of whom 54.3% had an indeterminate LVDD grade. Age, hypertension, diabetes mellitus, and cardiovascular disease were strongly associated with LVDD. Using the PBHS diastolic score, scores ≥3 and ≥4 were observed in 14.1% and 5.8% of the population, respectively. ASE/EACVI grades 2-3 corresponded with scores ≥4, whereas indeterminate categories corresponded with scores of 1-5. After multivariable adjustment, both LVDD grading systems predicted MACE (ASE/EACVI grade indeterminate and grades 2-3: aHRs 2.49 [95%CI: 1.39-4.46] and 5.7 [95%CI: 3.01-10.7], respectively; PBHS scores 4 and 5-6: aHRs 2.3 [95%CI: 1.25-4.33] and 5.3 [95%CI: 2.44-11.56], respectively).

Conclusions

This study validated the prognostic value of the ASE/EACVI diastolic function guidelines in the community. Assessing LVDD using a diastolic score free of indeterminate classifications may be worth exploring in future studies.

ClinicalTrials.govIdentifier

NCT03154346
Acquired hypothyroidism, iodine status and hearing impairment in adults: a pilot study
Authors: Grimmichova Tereza , Verespejova Ludmila , Urbaniova Zuzana , Chovanec Martin , Hill Martin , Bilek Radovan
Published: June 2024

Objectives

Hearing impairment can have major impacts on behavior, educational attainment, social status, and quality of life. In congenital hypothyroidism, the incidence of hearing impairment reaches 35-50%, while in acquired hypothyroidism there is a reported incidence of 25%. Despite this, knowledge of the pathogenesis, incidence and severity of hearing impairment remains greatly lacking. The aim of our study was to evaluate hearing in patients with acquired hypothyroidism.

Methods

30 patients with untreated and newly diagnosed peripheral hypothyroidism (H) and a control group of 30 healthy probands (C) were enrolled in the study. Biochemical markers were measured, including median iodine urine concentrations (IUC) ⍰g/L. The hearing examination included a subjective complaint assessment, otomicroscopy, tympanometry, transitory otoacoustic emission (TOAE), tone audiometry, and brainstem auditory evoked potential (BERA) examinations. The Mann-Whitney U test, Fisher’s Exact test and multivariate regression were used for statistical analysis.

Results

The H and C groups had significantly different thyroid hormone levels (medians with 95% CI) TSH mU/L 13.3 (8.1, 19.3) vs. 1.97 (1.21, 2.25) p=0 and fT4 pmol/L 10.4 (9.51, 11.1) vs. 15 (13.8, 16.7) p=0. The groups did not significantly differ in age 39 (34, 43) vs. 41 (36,44) p=0.767 and IUC 142 (113, 159) vs. 123 (101, 157) p=0.814. None of the hearing examinations showed differences between the H and C groups: otomicroscopy (p=1), tympanometry (p=1), TOAE (p=1), audiometry (p=0.179), and BERA (p=0.505).

Conclusions

We did not observe any hearing impairment in adults with acquired hypothyroidism, and there were no associations found between hearing impairment and the severity of hypothyroidism or iodine status. However, some forms of hearing impairment, mostly mild, were very common in both studied groups.
Age-appropriate Vaccination and Associated Factors among Children Aged 12- 35 Months in Ethiopia: A Multi-Level Analysis
Authors: Worku Bekelu Teka , Wordofa Eshetu Alemayehu , Senbeto Gadisa , Zinab Beakal , Bayana Kebede Ebissa , Abamecha Fira , Debela Gurmessa Tura , Birhanu Negalign , Siraneh Yibeltal , Tamiru Dessalegn
Published: June 2024

Background

Age-appropriate vaccination is one of the key public health measures to prevent morbidity and mortality worldwide. Despite its importance, there has been insufficient emphasis on tackling this problem. Therefore, this study aimed to determine the prevalence of age-appropriate vaccination and associated factors in Ethiopia.

Method

Data of 1077 children aged 12-35months were extracted from the Ethiopian Mini Demographic and Health Survey 2019 using a prepared data extraction checklist and included in the analysis. The extracted data was analyzed using STATA version 14.0. Descriptive and inferential statistics were applied. then analysis at different levels was done using multilevel logistic regression. Significant variables were identified at p-value < 0.05 within 95% confidence level and AOR.

Result

The pooled prevalence of age-appropriate vaccination in this study was 21.17% at 95%CI (18.73-23.61). Factors like mothers aged >= 40 (AOR=4.05 at 95%CI1.03, 15.83), 35-39 years (AOR= 4.62 at 95%CI1.27,16.71), 25-29 years, (AOR =4.07 at 95%CI 1.18,14.03), Maternal secondary education (AOR=1.85 at 95% CI 1.06, 3.22), Maternal primary education (AOR= 1.60 at 95% CI1.07, 2.41) and rural residence (AOR=0.34, 95%CI 0.23,0.51) were significant predictors of age-appropriate vaccinations.

Conclusion

This study concluded that the prevalence of age-appropriate vaccination of children in Ethiopia is below the desired level. Hence, the stakeholders should give due attention to the timely vaccination of children equally as the effort being made to increase the coverage.
Refinement of efficient encodings of movement in the dorsolateral striatum throughout learning
Authors: Jáidar Omar , Albarran Eddy , Albarran Eli Nathan , Wu Yu-Wei , Ding Jun B.
Published: June 2024

The striatum is required for normal action selection, movement, and sensorimotor learning. Although action-specific striatal ensembles have been well documented, it is not well understood how these ensembles are formed and how their dynamics may evolve throughout motor learning. Here we used longitudinal 2-photon Ca2+imaging of dorsal striatal neurons in head-fixed mice as they learned to self-generate locomotion. We observed a significant activation of both direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs, respectively) during early locomotion bouts and sessions that gradually decreased over time. For dSPNs, onset- and offset-ensembles were gradually refined from active motion-nonspecific cells. iSPN ensembles emerged from neurons initially active during opponent actions before becoming onset- or offset-specific. Our results show that as striatal ensembles are progressively refined, the number of active nonspecific striatal neurons decrease and the overall efficiency of the striatum information encoding for learned actions increases.
Neural Decoding and Feature Selection Techniques for Closed-Loop Control of Defensive Behavior
Authors: Liu Jinhan , Younk Rebecca , Drahos Lauren M , Nagrale Sumedh S , Yadav Shreya , Widge Alik S , Shoaran Mahsa
Published: June 2024

Objective

Many psychiatric disorders involve excessive avoidant or defensive behavior, such as avoidance in anxiety and trauma disorders or defensive rituals in obsessive-compulsive disorders. Developing algorithms to predict these behaviors from local field potentials (LFPs) could serve as foundational technology for closed-loop control of such disorders. A significant challenge is identifying the LFP features that encode these defensive behaviors.

Approach

We analyzed LFP signals from the infralimbic cortex and basolateral amygdala of rats undergoing tone-shock conditioning and extinction, standard for investigating defensive behaviors. We utilized a comprehensive set of neuro-markers across spectral, temporal, and connectivity domains, employing SHapley Additive exPlanations for feature importance evaluation within Light Gradient-Boosting Machine models. Our goal was to decode three commonly studied avoidance/defensive behaviors: freezing, bar-press suppression, and motion (accelerometry), examining the impact of different features on decoding performance.

Main results

Band power and band power ratio between channels emerged as optimal features across sessions. High-gamma (80-150 Hz) power, power ratios, and inter-regional correlations were more informative than other bands that are more classically linked to defensive behaviors. Focusing on highly informative features enhanced performance. Across 4 recording sessions with 16 subjects, we achieved an average coefficient of determination of 0.5357 and 0.3476, and Pearson correlation coefficients of 0.7579 and 0.6092 for accelerometry jerk and bar press rate, respectively. Utilizing only the most informative features revealed differential encoding between accelerometry and bar press rate, with the former primarily through local spectral power and the latter via inter-regional connectivity. Our methodology demonstrated remarkably low time complexity, requiring<110 ms for training and<1 ms for inference.

Significance

Our results demonstrate the feasibility of accurately decoding defensive behaviors with minimal latency, using LFP features from neural circuits strongly linked to these behaviors. This methodology holds promise for real-time decoding to identify physiological targets in closed-loop psychiatric neuromodulation.
Evidence for optimal behavior of predators from parallel field investigations in two distinct wolf-prey systems
Authors: Prokopenko Christina M. , Kingdon Katrien A. , Dupont Daniel L.J. , Naaykens Taylor M. , Prokopenko John , Turner Julie W. , Zabihi-Seissan Sana , Vander Wal Eric
Published: June 2024

Animals behave ‘optimally’ when they minimize their costs while maximizing their energetic gain. Optimal foraging theory predicts that with decreasing resource abundance, animals will increase 1) niche breadth, 2) territory size and movement distance, and 3) time spent at resource patches. We test these predictions by investigating clusters from GPS collared wolves (Canis lupus) in two predator populations with marked differences in their prey composition and abundance. As expected, wolves in a less abundant system increase niche breadth, territory size, step lengths, and time spent at each kill. Our work provides evidence of optimal behavior in an apex predator which can support population resilience across changing landscapes.
Microbial interactions affect the tempo and mode of antibiotic resistance evolution
Authors: Zandbergen Laurens E. , van den Heuvel Joost , Farr Andrew D. , Zwaan Bas J. , de Visser J. Arjan G. M. , de Vos Marjon G. J.
Published: June 2024

The global rise of antibiotic resistance impedes the treatment of bacterial infections. To limit the emergence and evolution of antibiotic resistance it is important to understand how bacterial interactions in multispecies communities affect the course of evolution. We investigated how ecological interactions between microbes derived from polymicrobial urinary tract infections affect the tempo and mode of antibiotic resistance evolution. We show that for representative strains of three uropathogens,Escherichia coli, Klebsiella pneumoniaeandEnterococcus faecium,the rate and evolutionary trajectories towards antibiotic resistance differ depending on the conditioned medium mediated interactions with other microbes that alter their growth and antibiotic tolerance. Replicate lineages of the same species evolved under similar ecological conditions show parallel evolutionary trajectories, and resistance mutations and other functional targets selected differed between these conditions. Our findings demonstrate that bacterial interactions differentially affect the evolutionary potential of antibiotic resistance evolution.
ComputAgeBench: Epigenetic Aging Clocks Benchmark
Authors: Kriukov Dmitrii , Efimov Evgeniy , Kuzmina Ekaterina , Dudkovskaia Anastasiia , Khrameeva Ekaterina E. , Dylov Dmitry V.
Published: June 2024

The success of clinical trials of longevity drugs relies heavily on identifying integrative health and aging biomarkers, such as biological age. Epigenetic aging clocks predict the biological age of an individual using their DNA methylation profiles, commonly retrieved from blood samples. However, there is no standardized methodology to validate and compare epigenetic clock models as yet. We proposeComputAgeBench, a unifying framework that comprises such a methodology and a dataset for comprehensive benchmarking of different clinically relevant aging clocks. Our methodology exploits the core idea that reliable aging clocks must be able to distinguish between healthy individuals and those with aging-accelerating conditions. Specifically, we collected and harmonized 66 public datasets of blood DNA methylation, covering 19 such conditions across different ages, and tested 13 published clock models. Additionally, we compiled 46 separate datasets to facilitate the training of new aging clocks. We believe our work will bring the fields of aging biology and machine learning closer together for the research on reliable biomarkers of health and aging.

Code

https://github.com/ComputationalAgingLab/ComputAge

Dataset

https://huggingface.co/datasets/computage/computage_bench
Differentiating mechanism from outcome for ancestry-assortative mating in admixed human populations
Authors: Massey Dashiell J. , Szpiech Zachary A. , Goldberg Amy
Published: June 2024

Population genetic theory, and the empirical methods built upon it, often assume that individuals pair randomly for reproduction. However, natural populations frequently violate this assumption, which may potentially confound genome-wide association studies, selection scans, and demographic inference. Within several recently admixed human populations, empirical genetic studies have reported a correlation in global ancestry proportion between spouses, referred to as ancestry-assortative mating. Here, we use forward genomic simulations to link correlations in global ancestry proportion between mates to the underlying mechanistic mate-choice process. We consider the impacts of two types of mate-choice model, using either ancestry-based preferences or social groups as the basis for mate pairing. We find that multiple mate-choice models can produce the same correlations in global ancestry proportion between spouses; however, we also highlight alternative analytic approaches and circumstances in which these models may be distinguished. With this work, we seek to highlight potential pitfalls when interpreting correlations in empirical data as evidence for a particular model of human mating practices, as well as to offer suggestions toward development of new best practices for analysis of human ancestry-assortative mating.
Experimental evolution ofEscherichia colion semi-dry silver, copper, stainless steel, and glass surfaces
Authors: Rosenberg Merilin , Park Sandra , Umerov Sigrit , Ivask Angela
Published: June 2024

To study bacterial adaptation to antimicrobial metal surfaces in application-relevant conditions,Escherichia coliwas exposed to copper and silver surfaces for thirty exposure cycles in low-organic dry or high-organic humid conditions. The evolved populations demonstrated increased metal surface tolerance without concurrent increase in MBC and MIC values of respective metal ions or selected antibiotics. Mutation analysis did not detect increased mutation accumulation nor mutations incop, cus, cue, sil, pcoor general efflux genes known to actively maintain copper/silver homeostasis. Instead, during cyclic exposure mutations in genes related to cellular barrier functions and sulfur metabolism were enriched potentially suggesting that reducing bioavailability and passively restricting uptake of the toxic metals rather than active efflux is selected for on copper and silver surfaces. The changes detected in the evolved populations did not indicate an increased risk of antibiotic cross-resistance as a result of copper or silver surface exposure. However, rapid emergence of mutations insilSactivated the crypticsilefflux locus during silver ion challenge in liquid MBC assay with the evolved populations. ThesilSmutants showed no benefit on copper and silver surfaces but demonstrated decreased sensitivity to ampicillin and ciprofloxacin as well as copper and silver ions in liquid tests indicating that efflux might be specific to granting heavy metal tolerance in liquid but not surface exposure format. Our findings highlight the critical importance of appropriate exposure conditions not only in efficacy assessment but also risk assessment of antimicrobial surface applications.

Importance

This study examines the evolutionary adaptations ofEscherichia coliafter semi-dry exposure to copper and silver surfaces, leading to an increase in surface tolerance but no increase in mutation accumulation or substantially enhanced metal ion tolerance in standard tests. Notably, enriched mutations indicate a shift toward more energy-passive mechanisms of metal tolerance. Additionally, while enhanced silver efflux was rapidly selected for in a single round of silver exposure in liquid tests and substantially increased copper and silver ion tolerance in conventional test formats, the causal mutations did not improve viability on silver and copper surfaces, underscoring the different fitness scenarios of tolerance mechanisms dependent on exposure conditions. These findings emphasize the need for appropriate exposure conditions in evaluating of both efficacy and the potential risks of using antimicrobial surfaces, as the results from conventional liquid-based tests may not apply in solid contexts.
Landscape genomics highlights the adaptive evolution of chickpea
Authors: Rocchetti Lorenzo , Rodriguez Monica , Pieri Alice , Papalini Simone , De Antoni Luca , Vitali Erika , Vincze Astrid , Brezeanu Creola , Bellucci Elisa , Nanni Laura , Rossato Marzia , Delledonne Massimo , Bitocchi Elena , Papa Roberto
Published: June 2024

The structure of crop genetic diversity reflects spatial and ecological variations caused by population dynamics during adaptation to different agricultural environments. Landscape genomics can reveal patterns of neutral and adaptive variation related to environmental and spatial heterogeneity. We assembled a collection of 532 chickpea accessions and genotyped them by whole-genome sequencing. We then assessed their genetic diversity and population structure and coupled these data to environmental variables. We applied redundancy analysis as a multivariate landscape genomics method to describe the distribution of genetic diversity according to spatial and environmental factors. Environmental and geographic factors played a key role in the diversification of chickpea germplasm. We also identified a set of candidate adaptive loci, which were enriched for genes mainly involved in responses to abiotic stress factors such as heat and drought. Our study provides new insight into the evolution, dispersal and adaptation of chickpea to different agricultural environments, and will also facilitate the efficient use of genetic resources in gene discovery and breeding programs.
Laboratory horror stories: Poison in the agars
Authors: Davidson Mari K. , Protacio Reine U. , Helmlinger Dominique , Wahls Wayne P.
Published: June 2024

The fission yeastSchizosaccharomyces pombeis a single-celled eukaryote that can be cultured as a haploid or as a diploid. Scientists employ mating, meiosis, and the plating of ascospores and cells to generate strains with novel genotypes and to discover biological processes. Our two laboratories encountered independently sudden-onset, major impediments to such research. Spore suspensions and vegetative cells no longer plated effectively on minimal media. By systematically analyzing multiple different media components from multiple different suppliers, we identified the source of the problem. Specific lots of agar, from different suppliers, were toxic. Interestingly, the inhibitory effect was attenuated on rich media. Consequently, quality control checks that use only rich media can provide false assurances on the quality of the agar. Lastly, we describe likely sources of the toxicity and we provide specific guidance for quality control measures that should be applied by all vendors as preconditions for their sale of agar.

Graphical Abstract

Take-away

Sporadically, batches of agar from different suppliers strongly inhibit the plating efficiency ofS. pombespores and vegetative cells on minimal media.

Quality control checks that are not quantitative or that use only rich media can provide false assurances on the quality of the agar.

Vendors should conduct rigorous, thorough, organism-specific tests for potential toxicity of each lot of agar as a pre-condition for its sale.
Efficacy of Nirmatrelvir/ritonavir in reducing the risk of severe outcome in patients with SARS-CoV-2 infection: a real-life full-matched case-control study (SAVALO Study)
Authors: Gentile Ivan , Giaccone Agnese , Scirocco Maria Michela , Di Brizzi Francesco , Cuccurullo Federica , Silvitelli Maria , Ametrano Luigi , Alfè Francesco Antimo , Pietroluongo Daria , Irace Irene , Chiariello Mariarosaria , De Felice Noemi , Severino Simone , Viceconte Giulio , Schiano Moriello Nicola , Maraolo Alberto Enrico , Buonomo Antonio Riccardo , Scotto Riccardo ,   Federico II COVID team
Published: June 2024

Introduction Ritonavir-boosted nirmatrelvir (N/r) is an antiviral which targets the main viral protease, administered to prevent the progression of SARS-CoV-2 infection in patients at high risk for severe COVID-19. We present a real-life case-control study evaluating the efficacy of N/r therapy in SARS-CoV-2 omicron variants positive outpatients in Campania region, Italy, with the aim of assessing the occurrence of three outcomes (hospital admission, admission in ICU and death) in cases and controls. Methods We enrolled SARS-CoV-2 positive subjects that came to our attention in Early antiviral treatment ambulatory of Infectious Disease ward of University Federico II of Naples, Italy from January 1st, 2022, to December 31st, 2022, during the first five days from symptoms occurrence. Patients were enrolled as cases or controls if they were treated with N/r or not treated at all, respectively. Results 1064 patients were included (cases: 423, controls: 1184). Cases showed a lower mortality compared with controls while no differences were observed for other outcomes. Vaccinated patients showed a lower mortality compared with non-vaccinated ones (0.5% vs 7.8%, p<0.001). After full-matching propensity score, N/r reduced hospitalization rate only in unvaccinated patients. In contrast N/r significantly reduced mortality regardless of vaccination status. Conclusions Treatment with N/r has proven effective in reducing mortality among outpatients with SARS-CoV-2 infection during several omicron variant surges. The beneficial effect of N/r treatment in reducing progression is more pronounced in unvaccinated patients.
An AI-based approach to predict delivery outcome based on measurable factors of pregnant mothers
Authors: Owusu-Adjei Michael , Ben Hayfron-Acquah James , Gaddafi Abdul-Salaam , Frimpong Twum
Published: June 2024

The desire for safer delivery mode that preserves the lives of both mother and child with minimal or no complications before, during and after childbirth is the wish for every expectant mother and their families. However, the choice for any particular birth delivery mode is determined primarily by a number of factors that feed into the ultimate decision of choice. Some of these include maternal birth history, maternal and child health conditions prevailing before and during labor onset. Predictive modeling has been used extensively to determine important contributory factors influencing delivery choice. However, missing among a myriad of features used in various research studies for this determination is maternal history of spontaneous, threatened and inevitable abortion(s) and how its inclusion can impact delivery outcomes. This research work therefore takes measurable maternal features that include real time information on administered partographs to predict delivery type. This is achieved by adopting effective feature selection technique to estimate variable relationship with the target variable. Three supervised learning techniques are used and evaluated for performance. Prediction accuracy score of area under the curve obtained show Gradient Boosting classifier achieved 91% accuracy, Logistic Regression 93% and Random Forest 91%. Balanced accuracy score for the same learning techniques obtained were; Gradient Boosting 82.73%, Logistic Regression 84.62% and Random Forest 83.02%. Correlation statistic for variable independence among input variables showed that delivery type as an output is associated with gestational age and the progress of maternal cervix dilatation during labor onset.
Local selection shaped the diversity of European maize landraces
Authors: Takou Margarita , Schulz Kerstin , Stetter Markus G
Published: June 2024

The introduction of populations to novel environments can lead to a loss of genetic diversity and the accumulation of deleterious mutations due to selection and demographic changes. We investigate how the recent introduction of maize to Europe shaped the genetic diversity and differentiation of European traditional maize populations and quantify the impact of its recent range expansion and consecutive breeding on the accumulation of genetic load. We use genome-wide genetic markers of almost 2,000 individuals from 38 landraces, 155 elite breeding lines and a large set of doubled haploid lines derived from two landraces to find extensive population structure within European maize, with landraces being highly differentiated even over short geographic distances. Yet, diversity change does not follow the continuous pattern of range expansions. Landraces maintain high genetic diversity that is distinct between populations and does not decrease along the possible expansion routes.Signals of positive selection in European landraces that overlap with selection in Asian maize suggest convergent selection during maize introductions. At the same time, environmental factors partially explain genetic differences across Europe. Consistent with the maintenance of high diversity, we find no evidence of genetic load accumulating along the maize introduction route in European maize. However, modern breeding likely purged highly deleterious alleles but accumulated genetic load in elite germplasm. Our results reconstruct the history of maize in Europe and show that landraces have maintained high genetic diversity that could reduce genetic load in the European maize breeding pools.
DNA-m6A calling and integrated long-read epigenetic and genetic analysis withfibertools
Authors: Jha Anupama , Bohaczuk Stephanie C. , Mao Yizi , Ranchalis Jane , Mallory Benjamin J. , Min Alan T. , Hamm Morgan O. , Swanson Elliott , Dubocanin Danilo , Finkbeiner Connor , Li Tony , Whittington Dale , Noble William Stafford , Stergachis Andrew B. , Vollger Mitchell R.
Published: June 2024

Long-read DNA sequencing has recently emerged as a powerful tool for studying both genetic and epigenetic architectures at single-molecule and single-nucleotide resolution. Long-read epigenetic studies encompass both the direct identification of native cytosine methylation and the identification of exogenously placed DNAN6-methyladenine (DNA-m6A). However, detecting DNA-m6A modifications using single-molecule sequencing, as well as coprocessing single-molecule genetic and epigenetic architectures, is limited by computational demands and a lack of supporting tools. Here, we introducefibertools, a state-of-the-art toolkit that features a semisupervised convolutional neural network for fast and accurate identification of m6A-marked bases using Pacific Biosciences (PacBio) single-molecule long-read sequencing, as well as the coprocessing of long-read genetic and epigenetic data produced using either the PacBio or Oxford Nanopore Technologies (ONT) sequencing platforms. We demonstrate accurate DNA-m6A identification (>90% precision and recall) along >20 kb long DNA molecules with an ∼1000-fold improvement in speed. In addition, we demonstrate thatfibertoolscan readily integrate genetic and epigenetic data at single-molecule resolution, including the seamless conversion between molecular and reference coordinate systems, allowing for accurate genetic and epigenetic analyses of long-read data within structurally and somatically variable genomic regions.