bluuebunny/crossref_metadata_2025 huggingface dataset:
Agroecological transition: towards a better understanding of the impact of ecology-based farming practices on soil microbial ecotoxicology
Authors: Vermeire Marie-Liesse , Thiour-Mauprivez Clémence , De Clerck Caroline
Published: March 2024

Alternative farming systems have developed since the beginning of industrial agriculture. Organic, biodynamic, conservation farming, agroecology and permaculture, all share a grounding in ecological concepts and a belief that farmers should work with nature rather than damage it. As ecology-based agricultures rely greatly on soil organisms to perform the functions necessary for agricultural production, it is thus important to evaluate the performance of these systems through the lens of soil organisms, especially soil microbes. They provide numerous services to plants, including growth promotion, nutrient supply, tolerance to environmental stresses and protection against pathogens. An overwhelming majority of studies confirm that ecology-based agricultures are beneficial for soil microorganisms. However, three practices were identified as posing potential ecotoxicological risks: the recycling of organic waste products, plastic mulching, and pest and disease management with biopesticides. The first two because they can be a source of contaminants; the third because of potential impacts on non-target microorganisms. Consequently, developing strategies to allow a safe recycling of the increasingly growing organic matter stocks produced in cities and factories, and the assessment of the ecotoxicological impact of biopesticides on non-target soil microorganisms, represent two challenges that ecology-based agricultural systems will have to face in the future.
Fuzzy controller system utilization to increase the hydrogen production bioreactor capacity: toward sustainability and low carbon technology
Authors: Kuterbekov Kairat A , Bekmyrza Kenzhebatyr Zh , Kabyshev Asset M , Kubenova Marzhan M , Shokatian-Beiragh Mehrdad
Published: March 2024

The utilization of bio-hydrogen as a fuel source holds immense promise as a renewable energy option, offering compelling economic and environmental advantages. This study investigates the economic and environmental advantages of bio-hydrogen as a renewable energy source compared to fossil fuels, focusing on the reduction of greenhouse gas emissions such as carbon dioxide and carbon monoxide. The enhancement of anaerobic hydrogen production reactor capacity is explored through the application of a fuzzy controller system. Numerical simulations demonstrate that the fuzzy controller outperforms other methods in augmenting biological hydrogen production, effectively addressing the inherent non-linear characteristics of the system. In contrast, limitations in robustness against system uncertainty are observed with the non-linear controller. Exceptional tracking of desired values by the fuzzy controller, even in the presence of model uncertainty, results in a lower integral of time multiplied by squared error (ITSE) performance index compared to non-linear and proportional–integral controllers. Emphasizing the viability of the fuzzy method for regulating hydrogen production processes, potential gains of up to 95% in biological hydrogen production are indicated compared to open-loop configurations. This clean-burning fuel holds promise for industrial applications, contributing to the reduction of harmful gas emissions. The findings underscore the transformative potential of the fuzzy controller system in advancing sustainable hydrogen production and its significant role in addressing environmental concerns.
Significant association of HLA-A26 with uveitis and gastrointestinal involvement in patients with Behçet’s disease in a multicentre study
Authors: Nakajima Tomoya , Tsuji Hideaki , Inaba Ryuta , Saito Rintaro , Nishimura Keisuke , Morinobu Akio
Published: March 2024

Objectives

Specific human leukocyte antigen (HLA) haplotypes are associated with Behçet’s disease. Because the effects of HLA-A26 and its combination with HLA-B51 on organ involvement in Behçet’s disease have not been well demonstrated, we aimed to examine them.

Methods

This multicentre, cross-sectional, observational study enrolled patients with Behçet’s disease who visited Kyoto University Hospital between 2018 and 2021 or Kurashiki Central Hospital between 2006 and 2016 (n = 200). Disease severity was evaluated using the Krause score.

Results

Uveitis and gastrointestinal involvement were observed in 95/196 and 57/167 patients, respectively. The HLA alleles identified were HLA-B51 (n = 52/106), HLA-A26 (n = 25/88), and HLA-B51 and HLA-A26 (n = 6/88). In patients harbouring HLA-B51, the presence of HLA-A26 was associated with higher frequencies of uveitis (P = .03) and coexistence of uveitis and gastrointestinal involvement (P = .002) and higher Krause scores (P = .02). Furthermore, the presence of HLA-A26 was associated with a higher frequency of uveitis in patients with gastrointestinal involvement (P = .001) and gastrointestinal involvement in patients with uveitis (P = .001).

Conclusions

Since specific HLA haplotypes and their combinations are associated with organ involvement, both HLA-A and HLA-B haplotypes should be confirmed when screening for affected organs.
Genetic causes of lymphatic disorders: recent updates on the clinical and molecular aspects of lymphatic disease
Authors: Bowman Catharine , Rockson Stanley G.
Published: March 2024

Purpose of review

The lymphatic system facilitates several key functions that limit significant morbidity and mortality. Despite the impact and burden of lymphatic disorders, there are many remaining disorders whose genetic substrate remains unknown. The purpose of this review is to provide an update on the genetic causes of lymphatic disorders, while reporting on newly proposed clinical classifications of lymphatic disease.

Recent findings

We reviewed several new mutations in genes that have been identified as potential causes of lymphatic disorders including: MDFIC, EPHB4, and ANGPT2. Furthermore, the traditional St. George's Classification system for primary lymphatic anomalies has been updated to reflect the use of genetic testing, both as a tool for the clinical identification of lymphatic disease and as a method through which new sub-classifications of lymphatic disorders have been established within this framework. Finally, we highlighted recent clinical studies that have explored the impact of therapies such as sirolimus, ketoprofen, and acebilustat on lymphatic disorders.

Despite a growing body of evidence, current literature demonstrates a persistent gap in the number of known genes responsible for lymphatic disease entities. Recent clinical classification tools have been introduced in order to integrate traditional symptom- and time-based diagnostic approaches with modern genetic classifications, as highlighted in the updated St. George's classification system. With the introduction of this novel approach, clinicians may be better equipped to recognize established disease and, potentially, to identify novel causal mutations. Further research is needed to identify additional genetic causes of disease and to optimize current clinical tools for diagnosis and treatment.
Implementation of remote monitoring strategies to improve chronic heart failure management
Authors: Chau Vinh Q. , Imamura Teruhiko , Narang Nikhil
Published: March 2024

Purpose of review

The goal of this review is to describe the current evidence available for remote monitoring devices available for patients with chronic heart failure, and also detail practical clinical recommendations for implementing these tools in daily clinical practice.

Recent findings

Several devices ranging from sophisticated multiparametric algorithms in defibrillators, implantable pulmonary artery pressure sensors, and wearable devices to measure thoracic impedance can be utilized as important adjunctive tools to reduce the risk of heart failure hospitalization in patients with chronic heart failure. Pulmonary artery pressure sensors provide the most granular data regarding hemodynamic status, while alerts from wearable devices for thoracic impedance and defibrillator-based algorithms increase the likelihood of worsening clinical status while also having high negative predictive value when values are within normal range.

Multiple device-based monitoring strategies are available to reduce longitudinal risk in patients with chronic heart failure. Further studies are needed to best understand a practical pathway to integrate multiple signals of data for early clinical decompensation risk prediction

Video abstract: http://links.lww.com/HCO/A95.
Potassium-competitive acid blockers and acid-related disorders
Authors: Huang Kevin Z. , Weber H. Christian
Published: March 2024

Purpose of review

Potassium-competitive acid blockers (PCABs) represent a new class of compounds for the treatment of acid-related disorders. Recent FDA approval of the PCAB vonoprazan for erosive esophagitis has started an important new approach to acid-related disorders.

Recent findings

Compared to conventional proton pump inhibitors (PPIs), PCABs provide more rapid, potent, and sustained suppression of gastric acid with faster and more durable symptom relief. Studies have demonstrated the efficacy of PCABs for erosive esophagitis, nonerosive reflux disease, and peptic ulcer disease including H. pylori. However, the PCAB vonoprazan was only approved in the US as part of combination therapy for eradication of H. pylori. Clinical trials have now demonstrated noninferiority of vonoprazan to lansoprazole for treatment of erosive esophagitis, particularly noting superiority of vonoprazan in patients with severe esophagitis resulting in FDA approval of vonoprazan for treatment of erosive esophagitis. Emerging data suggests a possible utility of vonoprazan for PPI-resistant gastroesophageal reflux disease (GERD) and on-demand therapy for nonerosive reflux disease. Vonoprazan is generally well tolerated but long-term safety data is not well established.

The PCAB vonoprazan is a newly FDA approved treatment option for erosive esophagitis. Its possible role in PPI-resistant GERD and nonerosive reflux disease warrants further investigation.
Biomechanics of fracture healing: how best to optimize your construct in the OR
Authors: Hast Michael , Glatt Vaida , Archdeacon Michael , Ledet Eric , Lewis Gregory , Ahn Jaimo , Haller Justin
Published: March 2024

Orthopaedic surgeons routinely assess the biomechanical environment of a fracture to create a fixation construct that provides the appropriate amount of stability in efforts to optimize fracture healing. Emerging concepts and technologies including reverse dynamization, “smart plates” that measure construct strain, and FractSim software that models fracture strain represent recent developments in optimizing construct biomechanics to accelerate bone healing and minimize construct failure.
Distal femur fractures: basic science and international perspectives
Authors: Nauth Aaron , Haller Justin , Augat Peter , Anderson Donald D. , McKee Michael D. , Shearer David , Jenkinson Richard , Pape Hans-Christoph
Published: March 2024

Distal femur fractures are challenging injuries to manage, and complication rates remain high. This article summarizes the international and basic science perspectives regarding distal femoral fractures that were presented at the 2022 Orthopaedic Trauma Association Annual Meeting. We review a number of critical concepts that can be considered to optimize the treatment of these difficult fractures. These include biomechanical considerations for distal femur fixation constructs, emerging treatments to prevent post-traumatic arthritis, both systemic and local biologic treatments to optimize nonunion management, the relative advantages and disadvantages of plate versus nail versus dual-implant constructs, and finally important factors which determine outcomes. A robust understanding of these principles can significantly improve success rates and minimize complications in the treatment of these challenging injuries.
Geriatric trauma: there is more to it than just the implant!
Authors: Lee Christopher , Kates Stephen L. , Graves Matthew L. , Jeray Kyle J. , Javedan Houman , Firoozabadi Reza , Schemitsch Emil
Published: March 2024

Geriatric trauma continues to rise, corresponding with the continuing growth of the older population. These fractures continue to expand, demonstrated by the incidence of hip fractures having grown to 1.5 million adults worldwide per year. This patient population and their associated fracture patterns present unique challenges to the surgeon, as well as having a profound economic impact on the health care system. Pharmacologic treatment has focused on prevention, with aging adults having impaired fracture healing in addition to diminished bone mineral density. Intraoperatively, novel ideas to assess fracture reduction to facilitate decreased fracture collapse have recently been explored. Postoperatively, pharmacologic avenues have focused on future fracture prevention, while shared care models between geriatrics and orthopaedics have shown promise regarding decreasing mortality and length of stay. As geriatric trauma continues to grow, it is imperative that we look to optimize all phases of care, from preoperative to postoperative.
Epidemiology of Craniofacial Injuries from Exercise and Weightlifting: A 10-Year Analysis
Authors: Mangal Rohan , Treger Dylan , Daniel Anjali , Prasad Soumil , Gompels Matthew T. , Thaller Seth R.
Published: March 2024

Introduction:

Exercise is the cornerstone of a healthy lifestyle. It is recognized for enhancing cardiovascular health and bolstering mental well-being. While the fitness industry grows, the incidence of exercise-related injuries continues to rise. This study examines craniofacial injuries resulting from exercise and weightlifting over the past decade. The goal is to uncover trends, demographics, diagnoses, and patient dispositions.

Methods and Materials:

A retrospective review was conducted using the National Electronic Injury Surveillance System database. Emergency department visits for craniofacial injuries associated with exercise and weightlifting between 2013 and 2022 were analyzed. One-sample t-tests and the Mann-Kendall test were used to evaluate injury prevalence and significant trends.

Results:

Over the past decade, 582,972 craniofacial injuries related to exercise and weightlifting were documented. Men accounted for 55.7% of cases. Annual incidence increased by 32.7% between 2013 and 2022. It was statistically significant. Adolescents aged 15 to 19 displayed the highest injury rate. Head injuries were most common (45%), followed by face (26%), neck (21%), mouth (4%), eye (3%), and ear (1%). Diagnoses included internal injury (25.2%), laceration (24.8%), contusions/abrasions (12.9%), and strain/sprain (11.9%). Hospitalization was required for only 8.5% of patients.

Discussion:

This study elucidates the need for injury prevention strategies. Vulnerable subgroups such as males, adolescents, and the elderly demand targeted prevention efforts. Future research should explore specific mechanisms of injury to identify high-risk exercise. This study promotes the need for safe exercise practices and increases awareness of craniofacial injury risks associated with physical activity.
Pilot Randomised Controlled Trial - Nurture Early for Optimal Nutrition (NEON) Study: Community facilitator-led participatory learning and action (PLA) women’s groups to improve infant feeding, care and dental hygiene practices in South Asian infants aged < 2 years in East London
Authors: Manikam Logan , Patil Priyanka , El Khatib Tala , Chakraborty Subarna , Hiley Delaney Douglas- , Fujita Sumire , Dwardzweska Joanna , Oyebode Oyinlola , Llewellyn Clare H. , Webb-Martin Kelley , Irish Carol , Archibong Mfon , Gilmour Jenny , Kalungi Phoebe , Batura Neha , Shringarpure Kalpita , Lakhanpaul Monica , Heys Michelle
Published: March 2024

Background

The first 1000-days of life are a critical window and can result in adverse-health consequences due to inadequate nutrition. South-Asian (SA) communities face significant health-disparities, particularly in maternal and child-health. Community-based-interventions, often employing Participatory-Learning-and-Action (PLA) approaches, have effectively addressed health-inequalities in lower-income-nations. The aim of this study was to assess the feasibility of implementing a PLA-intervention to improve infant-feeding and care-practices in SA communities in London.

Methods

Comprehensive-analyses were conducted to assess the feasibility/fidelity of this pilot-randomised-controlled-trial. Summary-statistics were computed to compare key-metrics (participant consent-rates, attendance, retention, intervention-support, perceived-effectiveness) against predefined-progression-rules guiding towards a definitive-trial. Secondary-outcomes were analysed, drawing insights from sources, such as The-Children’s-Eating-Behaviour-Questionnaire (CEBQ), Parental-Feeding-Style-Questionnaires (PFSQ), 4-Day-Food-diary, and the Equality-Impact-Assessment (EIA) tool. Video-analysis of children’s mealtime behaviour trends was conducted. Feedback-interviews were collected from participants.

Results

Process-outcome measures met predefined-progression-rules for a definitive-trial which deemed the intervention as feasible. The secondary-outcomes analysis revealed no significant changes in children’s BMI z-scores. This could be attributed to the abbreviated follow-up period of 6-months, reduced from 12-months, due to COVID-19-related delays. CEBQ analysis showed increased food-responsiveness, along with decreased emotional-over/undereating. A similar trend was observed in PFSQ. The EIA-tool found no potential discrimination areas, and video-analysis revealed a decrease in force-feeding-practices. Participant-feedbacks revealed improved awareness and knowledge-sharing.

Conclusion

The study validates the feasibility of a community-oriented, co-adapted Participatory-Learning-and-Action approach for optimising infant-care among South-Asians in high-income countries. It underscores the potential of such interventions in promoting health-equity and improving health-outcomes. Further research is required to evaluate their wider impact.
Sex disparities in in-hospital outcomes after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction and a history of coronary artery bypass grafting (CABG): A nationwide inpatient sample-matched analysis (2016–2019)
Authors: Yan Rui , Ma Xueping , Shi Bo , Ye Congyan , Fu Shizhe , Wang Kairu , Qi Haohong , Cui Mingzhi , Yan Ru , Jia Shaobin , Cong Guangzhi
Published: March 2024

Background

The role of sex disparities in in-hospital outcomes after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in patients with a history of coronary artery bypass grafting (CABG) remains underexplored. This study aimed to identify sex disparities in in-hospital outcomes after PCI in patients with AMI and a history of CABG.

Methods

Using the National Inpatient Sample database, we identified patients hospitalized for AMI with a history of CABG who underwent PCI between 2016 and 2019. The primary outcome was in--hospital mortality, and the secondary outcomes were the length of hospital stay and hospitalization costs. 1:1 propensity score matching was used to minimize standardized mean differences of baseline variables and compare in--hospital outcomes.

Results

In total, 75,185 weighted hospitalizations of patients who underwent PCI were identified, with 25.2% being female patients. Compared with male patients, female patients exhibited elevated risks of in-hospital mortality (3.72% vs. 2.85%, p = 0.0095), longer length of stay (4.64 days vs. 3.96 days, p < 0.001), and higher hospitalization costs ($112,594.43 vs. $107,020.54, p = 0.0019). After propensity score matching, female patients had higher in-hospital mortality rates than male patients (3.81% vs. 2.89%, p = 0.028). Multivariable logistic regression (adjusted odds ratio [aOR]: 1.48; 95% confidence interval [CI]: 1.14–1.92) and propensity score matching (aOR: 1.34; 95% CI: 1.03–1.73) showed a consistently higher risk of in-hospital mortality among female patients than among male patients. Female patients aged >60 years were more vulnerable to in-hospital mortality than were their male counterparts (3.06% vs. 4.15%, p = 0.0003, aOR: 1.55; 95% CI: 1.18–2.04).

Conclusions

Female patients who underwent PCI for AMI with a history of CABG had a higher in-hospital mortality rate, which was particularly evident among older patients aged >60 years. Therefore, sex- and age-specific investigations and interventions are required to reduce disparities within this high-risk population.
RevGraphVAMP: A protein molecular simulation analysis model combining graph convolutional neural networks and physical constraints
Authors: Huang Ying , Zhang Huiling , Lin Zhenli , Wei Yanjie , Xi Wenhui
Published: March 2024

Molecular simulation (MD) is an important research area in the field of life sciences, focusing on understanding the mechanisms of biomolecular interactions at atomic scales. Protein simulation, as a critical subfield of life science, has frequently adopted MD for implementation, where the trajectory data play an important role in drug discovery. With the advancement of high-performance computing and deep learning technology, machine-prediction of protein properties from enormous trajectory data becomes popular and critical, which puts challenges on how to extract useful data features from the complicated simulation data and reasonably reduce the dimensionality. At the same time, in order to better study the Protein system, it is necessary to provide a meaningful explanation of biological mechanism for dimensionality reduction. In order to address this issue, a new unsupervised model RevGraphVAMP is proposed to intelligently analyze the simulation trajectory. RevGraphVAMP is based on the Markov variation method (VAMP) and innovatively integrates graph convolutional neural networks and physical constraint optimization to improve the learning performance of the model. Besides, the attention mechanism is introduced to calculate the importance of protein molecules, leading to interpretation of molecular mechanism. Compared with other VAMPNets models, the new model presented in this paper has achieved the highest VAMP scores and better state transition prediction accuracy in two public datasets. Additionally, it has higher dimensionality reduction discrimination ability for different substates and provides interpretable results for protein structural characterization.
Emotion arousal but not valence is strongly represented in aperiodic EEG activity stemming from thalamocortical interactions
Authors: Borah Ritu M , Pathak Anagh , Banerjee Arpan
Published: March 2024

Oscillatory EEG signals contain both periodic and aperiodic (1/f components), segregating which is important for gaining insights into the underlying neural computations. Several studies have explored the periodic features underlying neural basis of emotion processing, while 1/f component is less explored. Hence, the present study sought to determine whether seeing emotionally laden music video clips have an impact on aperiodic components along with the periodic components and their underlying basis by conceptualizing a biophysically realistic computational model. Using the publicly available Data for Emotional Analysis using Physiological Signals (DEAP) dataset we elucidate that there is a significant increase in exponent and offset of aperiodic background during high arousal compared to low arousal trials. In contrast, there were no discernible variations between the aperiodic components during the high and low valence categories. In high arousal, we also discovered reduction in alpha power in line with previous studies. Finally, to elucidate the underlying mechanisms, we employed a biophysically realistic and previously established thalamo-cortical model of neural field activity, which which allowed us to characterize that heightened emotional arousal appears emerge from an increased cooperation in information communication between neuronal populations in reticular and relay nuclei of thalamus.

Significance statement

Dissociation of emotion and valence and arousal is an established theory in affective neuroscience. Are these dimensions represented in aperiodic background of macrocscopic electrophysiological scales of EEG? We sought to ask this question in the publicly available DEAP data. Our findings of increased aperiodic components during high arousal in contrast to low arousal suggest heightened neural activity alongside an inhibitory influence. Using a neural field model of thalamo-cortical interactions reveals a mechanistic approach that suggests heightened arousal corresponds to an enhanced inhibitory coupling between thalamic reticular and relay neuronal populations. In essence, this study advances our understanding of the intricate relationship between electrophysiological signals and emotion dimensions, shedding light on the mechanisms underlying arousal-related emotional responses.
Differentiation marker-negative CD4+T cells persist after yellow fever virus vaccination and contribute to durable memory
Authors: Pan Yi-Gen , Bartolo Laurent , Xu Ruozhang , Patel Bijal , Zarnitsyna Veronika , Su Laura
Published: March 2024

Factors that contribute to durable immunological memory remain incompletely understood. In our longitudinal analyses of CD4+T cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found naïve phenotype virus-specific CD4+T cells that persisted months to years after immunization. These Marker negative T cells (TMN) lacked CD95, CXCR3, CD11a, and CD49d surface protein expression, distinguishing them from previously discovered stem-cell memory T cells. Functionally, they resembled genuine naïve T cells uponin vitrostimulation. Single-cell TCR sequencing detected expanded clonotypes within the TMNsubset and identified a shared repertoire with memory and effector T cells. T cells expressing TMN-associated TCRs were rare before vaccination, suggesting their expansion following vaccination. Longitudinal tracking of YFV-specific responses over the subsequent years revealed superior stability of the TMNsubset and their association with the longevity of the overall population. The identification of these long-lived, antigen-experienced T cells may inform the design of durable T cell-based vaccines and engineered T cell therapies.
Influence of a Large Language Model on Diagnostic Reasoning: A Randomized Clinical Vignette Study
Authors: Goh Ethan , Gallo Robert , Hom Jason , Strong Eric , Weng Yingjie , Kerman Hannah , Cool Josephine , Kanjee Zahir , Parsons Andrew S. , Ahuja Neera , Horvitz Eric , Yang Daniel , Milstein Arnold , Olson Andrew P.J , Rodman Adam , Chen Jonathan H
Published: March 2024

Importance

Diagnostic errors are common and cause significant morbidity. Large language models (LLMs) have shown promise in their performance on both multiple-choice and open-ended medical reasoning examinations, but it remains unknown whether the use of such tools improves diagnostic reasoning.

Objective

To assess the impact of the GPT-4 LLM on physicians’ diagnostic reasoning compared to conventional resources.

Design

Multi-center, randomized clinical vignette study.

Setting

The study was conducted using remote video conferencing with physicians across the country and in-person participation across multiple academic medical institutions.

Participants

Resident and attending physicians with training in family medicine, internal medicine, or emergency medicine.

Intervention(s)

Participants were randomized to access GPT-4 in addition to conventional diagnostic resources or to just conventional resources. They were allocated 60 minutes to review up to six clinical vignettes adapted from established diagnostic reasoning exams.

Main Outcome(s) and Measure(s)

The primary outcome was diagnostic performance based on differential diagnosis accuracy, appropriateness of supporting and opposing factors, and next diagnostic evaluation steps. Secondary outcomes included time spent per case and final diagnosis.

Results

50 physicians (26 attendings, 24 residents) participated, with an average of 5.2 cases completed per participant. The median diagnostic reasoning score per case was 76.3 percent (IQR 65.8 to 86.8) for the GPT-4 group and 73.7 percent (IQR 63.2 to 84.2) for the conventional resources group, with an adjusted difference of 1.6 percentage points (95% CI -4.4 to 7.6; p=0.60). The median time spent on cases for the GPT-4 group was 519 seconds (IQR 371 to 668 seconds), compared to 565 seconds (IQR 456 to 788 seconds) for the conventional resources group, with a time difference of -82 seconds (95% CI -195 to 31; p=0.20). GPT-4 alone scored 15.5 percentage points (95% CI 1.5 to 29, p=0.03) higher than the conventional resources group.

Conclusions and Relevance

In a clinical vignette-based study, the availability of GPT-4 to physicians as a diagnostic aid did not significantly improve clinical reasoning compared to conventional resources, although it may improve components of clinical reasoning such as efficiency. GPT-4 alone demonstrated higher performance than both physician groups, suggesting opportunities for further improvement in physician-AI collaboration in clinical practice.
Advanced ECG heart age estimation applicable to both sinus and non-sinus rhythm associates with cardiovascular risk, cardiovascular morbidity, and survival
Authors: Al-Falahi Zaidon , Schlegel Todd T , Lamela-Palencia Israel , Li Annie , Schelbert Erik B , Niklasson Louise , Maanja Maren , Lindow Thomas , Ugander Martin
Published: March 2024

Background

An explainable advanced electrocardiography (A-ECG) heart age gap is the difference between A-ECG heart age and chronological age. This gap is an estimate of accelerated cardiovascular ageing expressed in years of healthy human aging, and can intuitively communicate cardiovascular risk to the general population. However, existing A-ECG heart age measures require discernible P waves on the ECG.

Aims

To develop and prognostically validate a revised, explainable A-ECG heart age gap without incorporating P-wave measures.

Methods

An A-ECG heart age without P-wave measures (non-P) was derived from the 10-second 12-lead ECG in a derivation cohort using multivariable regression using an existing Bayesian 5-minute 12-lead A-ECG heart age as reference. The non-P heart age was externally validated in a separate cohort of patients referred for cardiovascular magnetic resonance imaging by describing its association with heart failure hospitalization or death using Cox regression, and its association with comorbidities.

Results

In the derivation cohort (n=2771), A-ECG non-P heart age agreed with the 5-min heart age (R2=0.91, bias 0.0±6.7 years), and increased with increasing co-morbidity. In the validation cohort (n=731, mean age 54±15 years, 43% female, n=139 events over 5.7 [4.8–6.7] years follow-up), increased A-ECG non-P heart age gap (≥10 years) associated with events (hazard ratio [95% confidence interval] 2.04 [1.38–3.00], C-statistic 0.58 [0.54–0.62], and the presence of hypertension, diabetes mellitus, hypercholesterolemia, and heart failure (p≤0.009 for all).

Conclusions

An explainable A-ECG non-P heart age gap applicable to both sinus and non-sinus rhythm associates with cardiovascular risk, cardiovascular morbidity, and survival.
Predictive Modeling to Uncover Parkinson’s Disease Characteristics That Delay Diagnosis
Authors: Hähnel Tom , Raschka Tamara , Klucken Jochen , Glaab Enrico , Corvol Jean-Christophe , Falkenburger Björn H. , Fröhlich Holger
Published: March 2024

Background

People with Parkinson’s disease (PwPD) present with a variety of motor and non-motor symptoms, and a more biological definition of PD is poised to expand the diagnostic spectrum beyond the stereotypical “elderly male with tremor”. This heterogeneity can potentially pose a challenge for an accurate and early diagnosis.

Objectives

To determine whether demographic or clinical characteristics systematically affect the time till diagnosis, by modeling large-scale longitudinal data.

Methods

Using longitudinal data from three large PD cohorts and a latent time joint mixed-effects model (LTJMM), we aligned the disease courses of individual PwPD and estimated whether individual PD diagnosis was early or late compared to the average time of PD diagnosis in each cohort. Initial clinical manifestations at the typical time of PD diagnosis were estimated using mixed-effects models.

Results

We included 1,124 PwPD in our analysis. Several clinical and demographic factors were associated with a later-than-average diagnosis of PD: higher age, tremor dominance, rapid progression, anxiety, autonomic symptoms, depression, fatigue, pain, sleep problems, and in general more non-motor symptoms. In contrast, postural and gait disturbance was associated with an earlier-than-average PD diagnosis. Sex, family history of PD and predominantly affected side did not impact the time of PD diagnosis.

Conclusions

Using statistical modeling, we were able to study initial clinical characteristics of PwPD even in the absence of directly observable clinical data at the time when PD is diagnosed typically. Our findings are consistent with a biological definition of PD that includes patients who present initially with non-motor symptoms.
Detection and quantification of human immunodeficiency virus-1 (HIV-1) total nucleic acids in wastewater settled solids from two California communities
Authors: Wolfe Marlene K. , Shelden Bridgette , Duong Dorothea , Varkila Meri R.J. , White Bradley J. , Parsonnet Julie , Boehm Alexandria B.
Published: March 2024

Wastewater surveillance for infectious agents has proved useful in identifying circulation of viruses within populations. We investigated the presence and concentration of human immunodeficiency virus (HIV)-1 total nucleic acids (including both viral RNA and proviral DNA) in wastewater solids. We retrospectively measured HIV-1 nucleic-acids in two samples per week for 26 months at two wastewater treatment plants serving populations with different prevalences of HIV infections in San Francisco and Santa Clara County, California, USA. We detected HIV nucleic-acids in a majority of samples with concentrations ranging from non-detect to 3.9×105cp/g (N=459 samples total). Concentrations of HIV-1 were significantly higher in samples from the wastewater treatment plant serving a population with a higher prevalence of people living with HIV than in the plant serving a population with lower prevalence. The HIV-1 nucleic-acids amplified were primarily DNA and thus represented proviral DNA shedding into wastewater. Additionally, we found that HIV-1 nucleic-acid concentrations in wastewater solids were orders of magnitude higher than those in liquid wastewater indicating that the HIV-1 target preferentially sorbs to solids. Whether concentrations of HIV-1 in wastewater solids can be used to identify numbers of incident cases remains unknown. Additional work on HIV-1 shedding from individuals with viremia and people living with HIV is needed to translate wastewater measurements to quantitative information on infections.
Aligning visual prosthetic development with implantee needs
Authors: Nadolskis Lucas G. , Turkstra Lily M. , Larnyo Ebenezer , Beyeler Michael
Published: March 2024

Purpose

Visual prosthetics are a promising assistive technology for vision loss, yet research often overlooks the human aspects of this technology. While previous studies focus on the perceptual experiences or attitudes of implant recipients (implantees),a systematic account of how current implants are being used in everyday life is still lacking.

Methods

We interviewed six recipients of the most widely used visual implants (Argus II and Orion) and six leading researchers in the field. Through thematic analyses, we explored the daily usage of these implants by implantees and compared their responses to the expectations of researchers. We also sought implantees’ input on desired features for future versions, aiming to inform the development of the next generation of implants.

Results

Although implants are designed to facilitate various daily activities, we found that implantees use them less frequently than researchers expect. This discrepancy primarily stems from issues with usability and reliability, with implantees finding alternative methods to accomplish tasks, reducing the need to rely on the implant. For future implants, implantees emphasized the desire for improved vision, smart integration, and increased independence.

Conclusions

Our study reveals a significant gap between researcher expectations and implantee experiences with visual prostheses. Although limited by access to a small population of implantees, this study highlights the importance of focusing future research on usability and real-world applications.

Translational relevance

This retrospective qualitative study advocates for a better alignment between technology development and implantee needs to enhance clinical relevance and practical utility of visual prosthetics.
ExploringWNT2Polymorphisms in Comitant Strabismus: A Genetic Association Study
Authors: Zehra Zainab , von Bartheld Christopher S. , Agarwal Andrea B. , Vasquez-Gross Hans , Siddiqui Sorath Noorani , Azam Maleeha , Qamar Raheel
Published: March 2024

Background

Strabismus is a complex oculomotor condition characterized by a misalignment of the visual axis. The genetics of strabismus are poorly defined although a few candidate genes have been identified, among which is the WNT2 gene. Our study was designed to assess the association of single nucleotide polymorphisms (SNPs) ofWNT2in Pakistani strabismus patients.

Methods

A total of six SNPs, three intronic and three in the 3’ untranslated region, were screened in the current study. Logistic regression was performed using a dominant, recessive and additive model to determine the association of SNPs with strabismus and its clinical subtypes: esotropia and exotropia. Furthermore, haplotype analysis was performed.

Results

Regression analysis revealed an association of rs2896218, rs3779550, rs2285544 and rs4730775 with strabismus under the dominant model. When analyzed separately, rs2896218 and rs2285544 were found to be associated with both esotropia and exotropia, while rs4730775 was significantly associated only with exotropia under the dominant model. Based on clinical parameters, rs2896218, rs2285544 and rs4730775 were also found to be associated with the group of strabismus patients who were diagnosed at birth, but not in the group of patients who were diagnosed later in life. Haplotype analysis revealed that the haplotype A T T (corresponding to rs2896218, rs3779550 and rs2285544) was significantly more prevalent in the strabismus group.

Conclusion

Overall, the results of the present study suggests an association ofWNT2polymorphisms with strabismus and its subtypes in the Pakistani population, though further studies are needed to elucidate their role in strabismus etiology.

What is already known on this topic

Strabismus is a common oculomotor condition with a genetic component.

WNT2has been identified as a candidate gene for comitant strabismus.

What this study adds

TwoWNT2polymorphisms not previously reported have been found to be associated with strabismus.

There are genetic variations between clinical subtypes of strabismus (esotropia and exotropia).

WNT2polymorphisms are associated with age at the time of diagnosis and family history.

Combinations of different alleles (haplotypes) are associated with the disease.

How this study might affect research, practice or policy

Our study adds to the limited genetic data for strabismus and suggests further studies on the role ofWNT2in strabismus causation.
Small animal brain surgery with neither a brain atlas nor a stereotaxic frame
Authors: Ron Shaked , Beeri Hadar , Shinover Ori , Tur Noam M , Brokman Jonathan , Engelhard Ben , Gutfreund Yoram
Published: March 2024

Stereotaxic surgery is a cornerstone in brain research for the precise positioning of electrodes and probes, but its application is limited to species with available brain atlases and tailored stereotaxic frames. Addressing this limitation, we introduce an alternative technique for small animal brain surgery that requires neither an aligned brain atlas nor a standard stereotaxic frame. This method requires a high-contrast MRI scan of a specimen and access to a microCT scanner. The process involves attaching miniature markers to the skull, followed by CT scanning of the head. Subsequently, MRI and CT images are co-registered using standard image processing software and the targets for recordings in the brain are marked in the MRI image. During surgery, the animal's head is stabilized in any convenient orientation, and the probe's 3D position and angle are tracked using a multi-camera system. We have developed a software that utilizes the on-skull markers as fiducial points to align the CT/MRI 3D model with the surgical positioning system, and in turn instructs the surgeon how to move the probe to reach the targets within the brain. Our technique allows the execution of insertion tracks connecting two points in the brain. We successfully applied this method for neuropixels probe positioning in owls, quails, and mice, demonstrating its versatility and its potential to open new avenues for research in non-standard and novel animal models.
Behavior can be decoded across the cortex when individual differences are considered
Authors: Nakuci Johan , Yeon Jiwon , Kim Ji-Hyun , Kim Sung-Phil , Rahnev Dobromir
Published: March 2024

Group-level analyses have typically associated behavioral signatures with a constrained set of brain areas. Here we show that two behavioral metrics - reaction time (RT) and confidence - can be decoded across the cortex when each individual is considered separately. Subjects (N=50) completed a perceptual decision-making task with confidence. We built models decoding trial-level RT and confidence separately for each subject using the activation patterns in one brain area at a time after splitting the entire cortex into 200 regions of interest (ROIs). At the group level, we replicated previous results by showing that both RT and confidence could be decoded from a small number of ROIs (12.0% and 3.5%, respectively). Critically, at the level of the individual, both RT and confidence could be decoded from most brain regions even after Bonferroni correction (90.0% and 72.5%, respectively). Surprisingly, we observed that many brain regions exhibited opposite brain-behavior relationships across individuals, such that, for example, higher activations predicted fast RTs in some subjects but slow RTs in others. These results were further replicated in a second dataset. Lastly, we developed a simple test to determine the robustness of decoding performance, which showed that several hundred trials per subject are required for robust decoding. These results show that behavioral signatures can be decoded from a much broader range of cortical areas than previously recognized and suggest the need to study the brain-behavior relationship at both the group and the individual level.
Potential associations of selected polymorphic genetic variants with COVID-19 disease susceptibility and severity
Authors: Mózner Orsolya , Szabó Edit , Kulin Anna , Várady György , Moldvay Judit , Vass Vivien , Szentesi Andrea , Jánosi Ágoston , Hegyi Péter , Sarkadi Balázs
Published: March 2024

In this study, we analyzed the potential associations of selected laboratory and anamnestic parameters, as well as 12 genetic polymorphisms (SNPs), with clinical COVID-19 occurrence and severity in 869 hospitalized patients. The SNPs analyzed by qPCR were selected based on population-wide genetic (GWAS) data previously indicating association with the severity of COVID-19. We confirmed the associations of disease with several clinical laboratory and anamnestic parameters and found an unexpected association between less severe disease and the loss of smell and taste. In most cases, selected SNP analysis supported earlier results by indicating genetic associations with hospitalization and disease severity, while the potential role of some previously unrecognized polymorphisms has also been observed. A genetic association was indicated between the presence of a reduced-function ABCG2 transporter variant and a less severe disease, which was also observed in diabetic patients. Our current results, which should be reinforced by larger studies, indicate that together with laboratory and anamnestic parameters, genetic polymorphisms may have predictive value for the clinical occurrence and severity of COVID-19.
Ant queens cannibalise infected brood to contain disease spread and recycle nutrients
Authors: Bizzell Flynn , Pull Christopher D.
Published: March 2024

Filial cannibalism, where parents eat their own offspring, is a taxonomically widespread behaviour with a multitude of potential adaptive explanations. Of these, the impact of parasites on the expression of filial cannibalism is particularly poorly understood. On one hand, cannibalising young with low survival probability may enable parents to reinvest valuable resources into future reproduction; on the other, cannibalising offspring harbouring parasites that can potentially also infect the parents may select against this behaviour. Although disease-induced cannibalism of eggs has been reported in fish, the benefits of consuming infected brood to contain infections – as an explanation for the evolution of filial cannibalism – remains largely unexplored. Here, we demonstrate that solitarily founding ant queens cannibalise all sick larvae in their nests before they become contagious, showing clearly that filial cannibalism both (i) contains an otherwise lethal infection without any long-term consequences on queen survival and (ii) enables the reinvestment of recouped energy into additional egg production.
Sulfite oxidase deficiency causes persulfidation loss and H2S release
Authors: Fu Chun-Yu , Kohl Joshua B. , Liebsch Filip , D’Andrea Davide , Mai Max , Mellis Anna T. , Kouroussis Emilia , Ditrói Tamás , Santamaria-Araujo José Angel , Yeo Sin Yuin , Endepols Heike , Křížková Michaela , Kozich Viktor , Barayeu Uladzimir , Akaike Takaaki , Hennermann Julia B. , Nagy Peter , Filipovic Milos , Schwarz Guenter
Published: March 2024

Sulfite oxidase (SOX) deficiency is a rare inborn error of cysteine metabolism resulting in severe neurological damage. In patients, sulfite accumulates to toxic levels causing a raise in downstream productsS-sulfocysteine (SSC), mediating excitotoxicity, and thiosulfate, a catabolic intermediate/product of H2S metabolism. Here, we report a full-body knock-out mouse model for SOX deficiency (SOXD) with a severely impaired phenotype. Amongst the urinary biomarkers, thiosulfate showed a 45-fold accumulation in SOXD mice representing the major excreted S-metabolite. Consistently, we found increased plasma H2S, which was derived from sulfite-induced release from persulfides as demonstratedin vitroandin vivo. Mass spectrometric analysis of total protein persulfidome identified a major loss of persulfidation in 20% of the proteome affecting enzymes in amino acids and fatty acid metabolism. Urinary amino acid profiles indicate metabolic rewiring suggesting partial reversal of the TCA cycle thus identifying a novel contribution of H2S metabolism and persulfidation in SOXD.