bluuebunny/crossref_metadata_2025 huggingface dataset:
AUGMENT: a framework for robust assessment of the clinical utility of segmentation algorithms
Authors: McCague Cathal , Buddenkotte Thomas , Escudero Sanchez Lorena , Hulse David , Pintican Roxana , Rundo Leonardo ,   AUGMENT study team, Brenton James D. , Couturier Dominique-Laurent , Öktem Ozan , Woitek Ramona , Schönlieb Carola-Bibiane , Sala Evis , Crispin Ortuzar Mireia
Published: September 2024

Background

Evaluating AI-based segmentation models primarily relies on quantitative metrics, but it remains unclear if this approach leads to practical, clinically applicable tools.

Purpose

To create a systematic framework for evaluating the performance of segmentation models using clinically relevant criteria.

Materials and Methods

We developed the AUGMENT framework (Assessing Utility of seGMENtation Tools), based on a structured classification of main categories of error in segmentation tasks. To evaluate the framework, we assembled a team of 20 clinicians covering a broad range of radiological expertise and analysed the challenging task of segmenting metastatic ovarian cancer using AI. We used three evaluation methods: (i) Dice Similarity Coefficient (DSC), (ii) visual Turing test, assessing 429 segmented disease-sites on 80 CT scans from the Cancer Imaging Atlas), and (iii) AUGMENT framework, where 3 radiologists and the AI-model created segmentations of 784 separate disease sites on 27 CT scans from a multi-institution dataset.

Results

The AI model had modest technical performance (DSC=72±19 for the pelvic and ovarian disease, and 64±24 for omental disease), and it failed the visual Turing test. However, the AUGMENT framework revealed that (i) the AI model produced segmentations of the same quality as radiologists (p=.46), and (ii) it enabled radiologists to produce human+AI collaborative segmentations of significantly higher quality (p=<.001) and in significantly less time (p=<.001).

Conclusion

Quantitative performance metrics of segmentation algorithms can mask their clinical utility. The AUGMENT framework enables the systematic identification of clinically usable AI-models and highlights the importance of assessing the interaction between AI tools and radiologists.

Summary statement

Our framework, called AUGMENT, provides an objective assessment of the clinical utility of segmentation algorithms based on well-established error categories.

Key results

Combining quantitative metrics with qualitative information on performance from domain experts whose work is impacted by an algorithm’s use is a more accurate, transparent and trustworthy way of appraising an algorithm than using quantitative metrics alone.

The AUGMENT framework captures clinical utility in terms of segmentation quality and human+AI complementarity even in algorithms with modest technical segmentation performance.

AUGMENT might have utility during the development and validation process, including in segmentation challenges, for those seeking clinical translation, and to audit model performance after integration into clinical practice.
Thiamine pyrophosphokinase-1 deficiency in neurons drives Alzheimer’s multiple pathophysiological alterations
Authors: Sang Shaoming , Zhao Xiangteng , Qian Ting , Xia Yingfeng , Pan Xiaoli , Zhao Qianhua , Cai Fang , Zeng Yeting , Cai Wenwen , Jin Boru , Qiu Hongyan , Xu Yangqi , Huang Qiang , Zhang Yun , Huang Shajin , Jiang Donglang , Wu Yun , Tong Haiyang , Zhang Qing , Wang Changpeng , Cheng Xiaoqin , Zhong Kai , Guan Yihui , Zhu Michael X. , Yu Xiang , Yuan Peng , Song Weihong , Zhong Chunjiu ,   Benfotiamine Phase 2 Clinical Trial Investigators
Published: September 2024

Background

The mechanism driving multiple pathophysiological alterations in Alzheimer’s disease (AD) remains unclear. Thiamine deficiency, a well-known feature of AD, may contribute to these alterations.

Methods

The expressions of four known genes associated with thiamine metabolism were studied in brain samples from patients with AD and other neurodegenerative disorders. The results were further demonstrated in AD and diabetic mouse and cellular models. The phenotypes of mice with conditionalThiamine pyrophosphokinase-1(Tpk) knockout in brain excitatory neurons were investigated. The therapeutic effects of thiamine diphosphate supplement andTpkdelivery on cellular and mouse models were explored. Phase 2 clinical trial of benfotiamine, a thiamine derivative, plus donepezil was performed.

Results

Only TPK expression was inhibited in brain samples of AD patients, while none of thiamine-associated genes were significantly changed in other neurodegenerative disorders. TPK inhibition in the brains and neurons was verified in AD and diabetic mouse and cellular models. Mice withTpkdeletion in neurons exhibited all major pathophysiological alterations of AD, including amyloid deposition, Tau hyperphosphorylation, and brain atrophy. TPK expression restoration and thiamine diphosphate supplement ameliorated the pathophysiological and behavioral phenotypes in mouse and cell models withTpkinsufficiency. Benfotiamine delayed cognitive decline in mild-to-moderate AD patients with a dose-effect relationship, particularly with a significant attenuation of the deterioration in moderate AD patients by post hoc analysis.

Conclusions

TPK deficiency and hence thiamine diphosphate reduction in neurons are a decisive factor driving multiple pathophysiologic alterations of AD, unveiling a new direction for the disease mechanism and treatment.
Correct deconfounding enables causal machine learning for precision medicine and beyond
Authors: Komeyer Vera , Eickhoff Simon B. , Rathkopf Charles , Grefkes Christian , Patil Kaustubh R. , Raimondo Federico
Published: September 2024

Artificial intelligence holds promise for individualized medicine. Yet, predictive models in the neurobiomedical domain suffer from a lack of generalizability and replicability so that transitioning models from prototyping to clinical applications still poses challenges. Key contributors to these challenges are confounding effects; in particular the oftentimes purely statistical perspective on confounding. However, complementing these statistical considerations with causal reasoning from domain knowledge can make predictive models a tool for causal biomedical inference beyond associative insights. Such causal insights give answers to biomedical questions ofhowandwhy, arguably what most biomedical investigations ultimately seek for. Here, we suggest a 5-step approach for targeted, context-informed deconfounding. We exemplify the 5-step approach with a real-world neurobiomedical predictive task using data from the UK Biobank. The core of this approach constitutes a bottom-up causal analysis to identify a correct set of deconfounders and the appropriate deconfounding method for a given causal predictive endeavour. Using the 5-step approach to combine causal with statistical confounder considerations can make predictive models based on observational (big) data a technique comparable to Randomized Control Trials (RCTs). Through causally motivated deconfounding we aim at facilitating the development of reliable and trustworthy AI as a medical tool. In addition, we aim to foster the relevance of low performing or even null result models if they originate from a “skilful interrogation of nature”, i.e. a deconfounding strategy derived from an adequate causal and statistical analysis. Ultimately, causal predictive modelling through appropriate deconfounding can contribute to mutual recursive feedback loops of causal insights across disciplines, scales and species that enable the field to disentangle the cause-effect structure of neurobiomedical mechanisms.
Signals reported to Rucaparib: An Updated Comprehensive Disproportionality Analysis Using FDA Adverse Event Reporting System
Authors: Sharma Anshaj , Adusumilli Pramod Kumar
Published: September 2024

Ovarian cancer currently ranks as the fourth most common cancer. This cancer is metastatic in nature and making it more challenging to manage. Prostate cancer is the one of the major causes of disease and death among men. Approximately 1.6 million men are diagnosed with prostate cancer. Rucaparib, a poly-ADP ribose polymerase inhibitor has been approved by United States Food and Drug Administration for management of ovarian cancer and prostate cancer. Rucaparib was approved by US Food and Drug Administration in the year 2016 for the treatment of ovarian cancer and 2020 for the treatment of prostate cancer. To assess the potential association between rucaparib and the identified signals, a disproportionality analysis of spontaneous reports is being conducted. Reports were taken from FAERS data base and retrospective case/non case study was conducted. Reporting Odds ratio (ROR), Relative Reporting Ratio (RRR), Chi Squared Value (χ2) and Proportional Reporting Ratio (PRR) and Drug Event (DE) were used to perform disproportionality analysis. 144 signals were considered as positive adverse drug reactions using the criteria χ2>4, PRR >2, ROR >2 and DE ≥ 3. Through disproportionality analysis of the FAERS data, signal was identified between the signals-increased prostate specific antigen, decreased serum magnesium levels, decreased glomerular filtration rates, blood iron decreased and vitamin d decreased and rucaparib. The current investigation indicated that rucaparib may increase the incidence of the identified signals.
Enhancing ADHD Prediction in Adolescents through Fitbit-Derived Wearable Data
Authors: Rahman Muhammad Mahbubur
Published: September 2024

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by a complex etiology. The diagnostic process for ADHD is often time-consuming and subjective in nature. Recent advancements in machine learning offer promising avenues for improving ADHD diagnosis automatically using various data sources. In this study, we harness Fitbit-derived physical activity measurements to investigate potential associations with ADHD and evaluate machine learning classifiers for their predictive accuracy in ADHD diagnosis. Our analysis involves a sample of 450 participants from the Adolescent Brain Cognitive Development (ABCD) study data release 5.0. We conduct correlation analyses to explore the connections between ADHD diagnosis and Fitbit-derived measurements, including sedentary time, resting heart rate, and energy expenditure. Subsequently, we employ multivariable logistic regression models to assess the predictive capability of these measurements for ADHD diagnosis. Furthermore, we train machine learning classifiers to achieve a diagnosis by automatically categorizing individuals into ADHD+ and ADHD-groups. Our correlation analysis unveils statistically significant associations between ADHD diagnosis and Fitbit-derived measurements, suggesting a potential link between physical activity patterns and ADHD. Importantly, multivariable logistic regression models demonstrate that some of the Fitbit measurements significantly predict ADHD diagnosis. Notably, our Random Forest machine learning classifier outperforms other classifiers with cross-validation accuracy (0.89), AUC (0.95), precision (0.88), recall (0.90), f1-score (0.89) and test accuracy (0.88), surpassing the performance of previous ADHD classification studies. These findings not only lay the groundwork for further exploration but also offer insights into the clinical integration of wearable data for a deeper understanding and improved identification of ADHD.
Severity of lumbar spinal stenosis does not impact responsiveness to exercise-based rehabilitation
Authors: Shahidi Bahar , Zavareh Armin , Richards Connor , Taitano Lissa , Raiszadeh Kamshad
Published: September 2024

Spine pain is a prevalent and costly condition affecting up to 85% of individuals throughout their lifetime, and spinal stenosis is one of the most debilitating sources of spine pain. Although conservative management is the first line of treatment for spinal stenosis, severe cases often are directly referred to surgical intervention due to the belief that conservative strategies delay necessary treatment. However, there are no studies supporting the premise that individuals with more severe stenosis respond poorly to conservative management. The purpose of this study was to compare improvements in pain, disability, strength, medication usage, and patient goals in response to an exercise-based physical therapy program across 1,806 individuals with mild, moderate, or severe lumbar spine stenosis. Participants demonstrated significant improvements in all variables of interest (p<0.001), and 11.5% of participants reported cessation of narcotic use with treatment. There were no significant differences in treatment response across mild, moderate, or severe stenosis groups for any outcome (p>0.546). Exercise-based rehabilitation is as beneficial in the short term for individuals presenting for nonoperative care with severe stenosis compared to their milder counterparts. Future research is needed to evaluate long term durability and cost effectiveness of rehabilitation in this patient population.
Association between Neonatal Necrotizing Enterocolitis and Neurodevelopmental Outcomes: A Comprehensive Systematic Review and Meta-Analysis
Authors: Berken Jonathan A. , Ramanan Priyanka , Akel Mary J. , Miller Corinne , Nunes Denise , Aleynick Daniel N. , Wechsler Joshua B. , Wakschlag Lauren S. , Mithal Leena B.
Published: September 2024

Preterm infants are at high risk for systemic inflammatory disorders, including sepsis, meningitis, bronchopulmonary dysplasia, and necrotizing enterocolitis (NEC). The developing brain of the premature newborn is especially susceptible to the cascade of inflammatory mediators elaborated in these conditions that cross the blood-brain barrier. NEC, a severe and potentially fatal condition of the gut that occurs in premature newborns, is a prime example of how an inflammatory reaction, perhaps initially localized, can become generalized and cause systemic harm. One such result is brain injury, especially to the cerebral white matter, which may lead to neurodevelopmental abnormality and dysregulated behavior. Numerous studies have documented an association between necrotizing enterocolitis and neurodevelopmental impairment (NDI), but to date, the brain and behavioral deficits associated with neonatal NEC are not fully understood. We performed a comprehensive systematic review and meta-analysis of existing literature to characterize brain injury and behavioral alterations associated with NEC. 7153 peer-reviewed published manuscripts were screened by two independent reviewers and evidence quality was assessed using GRADE criteria. Of these papers, 62 satisfied the criteria for our review (i.e., no case reports, meta-analyses, systematic reviews, or animal studies). Data from 32 papers using Bayley Scales of Infant and Toddler Development to assess infant outcomes were included in the meta-analysis. Our findings support neonatal necrotizing enterocolitis having deleterious effects on brain and behavioral development and impact on cognitive function, risk of cerebral palsy and motor impairment, educational achievement, behavior, and neuroanatomy. We discuss herein findings of both short-term outcomes (1-3 years) and long-term outcomes (until 13 years). Our meta-analysis also indicates that NEC has a moderate effect size on infant development, with consistent impairment across mental, cognitive, language and motor domains.

WHAT DO THE FINDINGS OF THIS REVIEW MEAN?

In this review, we describe several short-term and long-term neurodevelopmental outcomes of preterm infants with NEC. These findings suggest that infants with NEC should be monitored with close developmental follow-up so that individuals can receive appropriate testing that may prompt therapies and qualify them to receive early intervention services.

HOW UP TO DATE IS THIS REVIEW?

The review authors searched for studies published up to 2021. Abstracts with no data available were excluded, so this review does not consider any new findings published from 2022-2024.
Collaborative Large Language Models for Automated Data Extraction in Living Systematic Reviews
Authors: Khan Muhammad Ali , Ayub Umair , Naqvi Syed Arsalan Ahmed , Khakwani Kaneez Zahra Rubab , Sipra Zaryab bin Riaz , Raina Ammad , Zou Sihan , He Huan , Hossein Seyyed Amir , Hasan Bashar , Rumble R. Bryan , Bitterman Danielle S. , Warner Jeremy L. , Zou Jia , Tevaarwerk Amye J. , Leventakos Konstantinos , Kehl Kenneth L. , Palmer Jeanne M. , Murad M. Hassan , Baral Chitta , Riaz Irbaz bin
Published: September 2024

Objective

Data extraction from the published literature is the most laborious step in conducting living systematic reviews (LSRs). We aim to build a generalizable, automated data extraction workflow leveraging large language models (LLMs) that mimics the real-world two-reviewer process.

Materials and Methods

A dataset of 10 clinical trials (22 publications) from a published LSR was used, focusing on 23 variables related to trial, population, and outcomes data. The dataset was split into prompt development (n=5) and held-out test sets (n=17). GPT-4-turbo and Claude-3-Opus were used for data extraction. Responses from the two LLMs were compared for concordance. In instances with discordance, original responses from each LLM were provided to the other LLM for cross-critique. Evaluation metrics, including accuracy, were used to assess performance against the manually curated gold standard.

Results

In the prompt development set, 110 (96%) responses were concordant, achieving an accuracy of 0.99 against the gold standard. In the test set, 342 (87%) responses were concordant. The accuracy of the concordant responses was 0.94. The accuracy of the discordant responses was 0.41 for GPT-4-turbo and 0.50 for Claude-3-Opus. Of the 49 discordant responses, 25 (51%) became concordant after cross-critique, with an increase in accuracy to 0.76.

Discussion

Concordant responses by the LLMs are likely to be accurate. In instances of discordant responses, cross-critique can further increase the accuracy.

Conclusion

Large language models, when simulated in a collaborative, two-reviewer workflow, can extract data with reasonable performance, enabling truly ‘living’ systematic reviews.
The evolution and developmental dynamics of histone-based chromatin regulation in Annelida
Authors: Martín-Zamora Francisco M. , Cole Joby , Donnellan Rory D. , Guynes Kero , Carrillo-Baltodano Allan M. , Dickman Mark J. , Hurd Paul J. , Martín-Durán José M.
Published: September 2024

Eukaryotic histones protect and package nuclear DNA into nucleosomes. The dynamic addition and removal of posttranslational modifications on these proteins define regulatory regions that play a central role in genome and chromatin biology. However, our understanding of these regulatory mechanisms in animals is largely based on a few model systems, which prevents a general understanding of how histone-based regulation unfolds and promotes phenotypic variation during animal embryogenesis. Here, we apply a comprehensive multi-omics approach to dissect the histone-based regulatory complement in Annelida, one of the largest invertebrate phyla. Annelids exhibit a conserved histone repertoire organised in clusters of dynamically regulated, hyperaccessible chromatin. However, unlike other animals with reduced genomes, the wormDimorphilus gyrociliatusshows a dramatically streamlined histone repertoire, revealing that genome compaction has lineage-specific effects on histone-based regulation. Notably, the annelidOwenia fusiformishas two H2A.X variants that co-occur in other animals, whose functional implications are unclear but represent a unique case of widespread parallel evolution of a histone variant in Eukarya. Histone-modifying enzyme complements are largely conserved amongst annelids. Yet, temporal differences in the expression of a reduced set of histone modifiers correlate with distinct ontogenetic traits and variation in the adult landscapes of histone modifications, as revealed by quantitative mass spectrometry inO. fusiformisandCapitella teleta. Collectively, our unparalleled analysis of histone-based epigenetics within a non-model phylum informs the evolution of histone-based regulation, presenting a framework to explore how this fundamental genome regulatory layer contributes to developmental and morphological diversification in annelids and animals generally.
Common regulatory mutation increases single-cell survival to antibiotic exposures inPseudomonas aeruginosa
Authors: Ritz David , Deng Yijie , Schultz Daniel
Published: September 2024

Typical antibiotic susceptibility testing (AST) of microbial samples is performed in homogeneous cultures in steady environments, which does not account for the highly heterogeneous and dynamic nature of antibiotic responses. The most common mutation found inP. aeruginosalineages evolved in the human lung, a loss of function of repressor MexZ, increases basal levels of multidrug efflux MexXY, but does not increase resistance by traditional MIC measures. Here, we use single cell microfluidics to show thatP. aeruginosaresponse to aminoglycosides is highly heterogeneous, with only a subpopulation of cells surviving exposure.mexZmutations then bypass the lengthy process of MexXY activation, increasing survival to sudden drug exposures and conferring a fitness advantage in fluctuating environments. We propose a simple “Response Dynamics” assay to quantify the speed of population-level recovery to drug exposures. This assay can be used alongside MIC for resistance profiling to better predict clinical outcomes.
Thalamic burst and tonic firing selectively indicate patients’ consciousness level and recovery
Authors: Wang Huan , Hu Yongxiang , Ge Qianqian , Dang Yuanyuan , Yang Yi , Xu Long , Xia Xiaoyu , Zhang Peng , He Sheng , Laureys Steven , Yang Yan , He Jianghong
Published: September 2024

Patients with disorders of consciousness exhibit severe declines in arousal and awareness, alongside anomalous functional brain connections and aberrant neuronal activities1–4. Yet, the diagnostic error of patients’ consciousness states can reach up to forty percent5,6, resulting in a worse prognosis. Neuronal mechanisms underlying the disorders are indispensable for identifying objective and intrinsic markers of consciousness. As the principal relay station between the brainstem arousal nuclei and the cerebral cortex, the thalamus has been empirically inferred to maintain consciousness and wakefulness within the brain connectome7–12. Here, we investigated thalamic spiking, brain connections, consciousness states, and outcomes following deep brain stimulation in 29 patients. Our study reveals that thalamic activities can signal their consciousness states. Patients diagnosed with vegetative state/unresponsive wakefulness syndrome exhibited less active neurons with longer and more variable burst discharges compared to those in a minimally conscious state. Furthermore, as a direct deep brain stimulation site, neuronal profiles in the centromedian/parafascicular complex of the thalamus indicated whether electrostimulation here improved outcomes. Stronger tonic firing was associated with enhanced thalamocortical connections and better recovery outcomes in patients. These findings suggest that thalamic spiking signatures, including single-neuron burst discharge and tonic firing, selectively indicate the representation and alteration of consciousness. These findings provide direct neuronal and clinical evidence for understanding of thalamic contributions to disorders of consciousness.
Genome-wide Association Study of Social Isolation in 63 497 Japanese Individuals from the General Population
Authors: Ohseto Hisashi , Inoue Kosuke , Takahashi Ippei , Obara Taku , Narita Akira , Ishikuro Mami , Orui Masatsugu , Murakami Keiko , Noda Aoi , Shinoda Genki , Takase Masato , Nakaya Naoki , Kogure Mana , Hatanaka Rieko , Nakaya Kumi , Chiba Ippei , Tokioka Sayuri , Kotozaki Yuka , Shimizu Atsushi , Tanno Kozo , Hozawa Atsushi , Tamiya Gen , Kondo Naoki , Kuriyama Shinichi
Published: September 2024

Social isolation, characterized by a lack of social connections with family, friends, and others, is associated with adverse health outcomes. However, the genetic contribution to the susceptibility to social isolation remains unclear. This study aimed to identify genetic loci associated with social isolation using the Lubben Social Network Scale (LSNS-6) in a Japanese population. The Tohoku Medical Megabank Community-Based Cohort Study was conducted between 2013 and 2016. The participants were genotyped using the Affymetrix Axiom Japonica Array. The LSNS-6 was used to assess familial and friend ties through six questions and social isolation statuses were defined as total scale, family subscale, and friend subscale. Genome-wide association studies (GWASs) were conducted using a generalized linear mixed model, adjusting for age, sex, and 10 genetic principal components. In total, 63 497 participants who completed genotyping and the LSNS-6 were included. The mean age was 59.4±11.9 years, and 41 126 (64.8%) were female. Significant genetic loci were identified in GWASs for the total scale (rs10736933 near ACADSB and HMX3) and friend subscale of LSNS-6 (rs1778366 near LINC02315 and LRFN5). This study provides the first genome-wide evidence of social isolation in the Japanese population, suggesting associations with ACADSB, HMX3, LINC02315, and LRFN5. These findings could enable personalized prevention and intervention for social isolation and related psychiatric disorders.
Bibliometric analysis of disaster nursing based on CiteSpace
Authors: Xie Haixia , Zhang Zhi , Han Ruijuan , Li Fulan , Yu Tianshuang
Published: September 2024

Background

Disaster nursing as a response to natural disasters, accidents disasters and other emergencies important areas, on a global scale in recent years received wide attention and research. This study discusses the research status and development trend of disaster nursing in the past 10 years, to provide a reference for future research and practice.

Methods

Literature in disaster nursing from 2013 to 2023 was searched using the Web of Science database, and CiteSpace 6.1.R6 software was used for visual analysis.

Results

A total of 4865 articles were retrieved, identified, and presented with a trend of steady rise. The United States has the largest number and has significant influence in the field. Disaster preparedness, disaster resilience, and disaster nursing education are the research hotspots. The combination of disaster nursing and intelligent technology will be the future research trend.

Conclusion

In the last 10 years, research on disaster nursing has shown a diversified and comprehensive development trend. In the future, with the continuous impact of global climate change and the increasing social demand for disaster nursing, the research and practice of disaster nursing will pay more attention to interdisciplinary cooperation, technological innovation, and humanistic care.
Applying item response theory to psychometrically evaluate and shorten the Negative Acts Questionnaire-Revised
Authors: Dåderman Anna M. , Kajonius Petri J. , Basinska Beata A.
Published: September 2024

Workplace bullying (WB) assessment often relies on the Negative Acts Questionnaire-Revised (NAQ-R). This study aimed to shorten and improve the NAQ-R using Item Response Theory (IRT) and address sex bias. IRT analysis from 867 Swedish employees (66% women) identified less-informative items. Based on this, a 13-item NAQ-R Short Form (NAQ-R-SF) was developed, demonstrating strong discrimination and validity. The new NAQ-R-SF showed a significant correlation with a primary WB measure (r = .57) and other relevant constructs, including individual factors like neuroticism and health quality, as well as work-related factors such as interpersonal conflicts and work performance. Sex bias was not found. IRT and validity evidence support the NAQ-R-SF as a robust tool for measuring WB, aligning with established WB constructs and individual differences.
Analysis of IL-4 Levels, IL-1α, Cortisol Hormone, and Blood Cell Number in Parkinson’s Disease Patients Undergoing Dance-based Movement Therapy: A Preliminary Study
Authors: Marques Karen Adriana Pastana , Bahia Gabriel Mesquita da Conceição , Duarte Juliana dos Santos , Pinto Denise da Silva , Martins Filho Arnaldo Jorge , de Jesus Oliveira Batista Evander , Oliveira da Silva Anderson Manoel Herculano , Matos Oliveira Karen Renata Herculano , Krejcova Lane Viana , Bahia Carlomagno Pacheco
Published: September 2024

Introduction

The interplay between neuroinflammation and Parkinson’s disease (PD) is still unclear, although several studies suggest that neuroinflammation plays an important role in the pathophysiological pathways of neurodegenerative disorders. Dance-based movement therapy has been studied as an adjuvant treatment for PD symptoms by modulating some inflammatory interleukins and improving the overall effect of pharmacological treatments.

Objective

To evaluate the levels of Interleukin 4, Interleukin 1α, cortisol hormone, and blood cell total numbers in PD subjects undergoing dance-based movement therapy.

Methods

Twenty-five participants were selected for this study. Seventeen subjects diagnosed with PD were divided into two groups: PD group (n=8) and PD+dance group (n=9). Another group was composed of age-matched healthy controls (n=8). The dance-based movement therapy was performed twice a week for 50-60 minutes/session over six months.

Results

The serum IL-4 levels were significantly lower in the PD group when compared to the healthy group, while the PD+Dance group showed similar levels to the healthy group. The levels of IL-1α, cortisol, and blood cell count showed no statistical differences between groups.

Conclusion

Our results suggest that regular practice of dance-based movement therapy may induce a neuroprotective effect by modulating the levels of IL-4 in people with PD similarly to healthy participants.

Trial registration

The study was registered in the Brazilian registry of clinical trials: RBR-3bhbrb5.
Learning geometric models for developmental dynamics
Authors: Howe Addison , Mani Madhav
Published: September 2024

Abstract

Successful development from a single cell to a complex, multicellular organism requires that cells differentiate in a coordinated and organized manner in response to a number of chemical morphogens. While the molecular underpinnings may be complex, the resulting phenomenon, in which a cell decides between one fate or another, is relatively simple. A body of work—rooted in dynamical systems theory—has formalized this notion of cellular decision making as flow in a Waddington-like landscape, in which cells evolve according to gradient-like dynamics within a potential that changes shape in response to a number of signals. We present a framework leveraging neural networks as universal function approximators to infer such a parameterized landscape from gene expression data. Inspired by the success of physics-informed machine learning in data-limited contexts, we enforce principled constraints motivated not by physical laws, but by this phenomenological understanding of differentiation. Our data-driven approach infers a governing landscape atop a manifold situated within expression space, thereby describing the dynamics of interest in a biologically meaningful context. The resulting system provides an intuitive, visualizable, and interpretable model of cellular differentiation dynamics.
The response of multi-disease and insect-resistant tomato lines to the accumulation of TYLCV, a whitefly-transmitted virus
Authors: Prabhakar Shruthi Shimoga , Hsu Yun-che , Yen Joyce , Chou Hsiu-yi , Lin Mei-ying , Priya M. Shanthi , Othim Stephen , Ramasamy Srinivasan , Eybishitz Assaf
Published: September 2024

Tomato (Solanum lycopersicum) is a major vegetable crop grown worldwide for its culinary versatility and nutritional richness. The whitefly-transmitted Tomato yellow leaf curl virus (TYLCV) poses a significant threat to its cultivation. The management strategies for this disease include controlling the virus and/or the vector. The multi-disease and insect-resistant lines developed by the World Vegetable Centre (WorldVeg) contain Ty-1/Ty-3 genes for virus resistance and WF2-10 and WF3-09 genes for whitefly resistance. This study evaluates the efficacy of suppressing virus accumulation in multi-disease and insect-resistant tomato lines compared to Ty-resistant or whitefly-resistant lines and a susceptible check. Preference bioassays, controlled inoculation with viruliferous whiteflies, and acylsugar quantification revealed that multi-disease and insect-resistant lines, developed at WorldVeg, had significantly higher acylsugar concentration and were less preferred by the whitefly adults for settling and whiteflies had high adult mortality. The multi-disease and insect-resistant lines also showed less severe disease symptoms and reduced virus accumulation over time when compared to Ty-resistant, whitefly-resistant, and susceptible check. The findings reveal that the multi-disease and insect-resistant lines are superior in mitigating the threat posed by TYLCV compared to TYLCV-resistant lines. These results underscore the potential of combined virus and vector resistance in tomatoes as a key element of Integrated Pest Management strategies against whitefly-transmitted TYLCV, offering a sustainable solution for safeguarding tomato production.
Visitor effect on the behavior of chimpanzees (pan troglodyte) at a primate rescue center
Authors: Alegre Maurer Sofia , Ross Miriam , Gil Dolz Jose
Published: September 2024

1.

The objective of this study was to examine the impact of visitors on the behavior of chimpanzees at a sanctuary. We hypothesized there wouldn’t be an increase in abnormal, agnostic, or self-directed behaviors during visits, nor a decrease in affiliative behaviors when visitors are present.

The study examined the effects of visitor presence on chimpanzee behavior at Fundació MONA, a rescue center.

Key findings include

No significant changes in abnormal or self-directed behaviors or agonistic behaviors were observed with visitor presence.

Affiliative behaviors (excluding grooming) showed a slight decrease during visits.

These results indicate that guided visitor interactions do not adversely affect chimpanzee behavior and may even enhance their welfare. The study supports the implementation of structured visitor programs for public education and funding, without compromising animal well-being. This contrasts with some previous research in zoo settings, suggesting that controlled visits can be beneficial in primate sanctuaries.
Reusable Generic Clinical Decision Support System Module for Immunization Recommendations in Resource-Constraint Settings
Authors: Orlioglu Samuil , Boobalan Akash Shanmugan , Abanyie Kojo , Boyce Richard D. , Min Hua , Gong Yang , Sittig Dean F. , Biondich Paul , Wright Adam , Nøhr Christian , Law Timothy , Robinson David , Faxvaag Arild , Hubig Nina , Gimbel Ronald , Rennert Lior , Jing Xia
Published: September 2024

Clinical decision support systems (CDSS) are routinely employed in clinical settings to improve quality of care, ensure patient safety, and deliver consistent medical care. However, rule-based CDSS, currently available, do not feature reusable rules. In this study, we present CDSS with reusable rules. Our solution includes a common CDSS module, electronic medical record (EMR) specific adapters, CDSS rules written in the clinical quality language (CQL) (derived from CDC immunization recommendations), and patient records in fast healthcare interoperability resources (FHIR) format. The proposed CDSS is entirely browser-based and reachable within the user’s EMR interface at the client-side. This helps to avoid the transmission of patient data and privacy breaches. Additionally, we propose to provide means of managing and maintaining CDSS rules to allow the end users to modify them independently. Successful implementation and deployment were achieved in OpenMRS and OpenEMR during initial testing.
Effect of different lining paper materials and infusions on oviposition preference ofAedes aegypti(Diptera: Culicidae) gravid mosquitoes
Authors: Momen Mahfuza , Seheli Kajla , Hossain Md. Aftab , Ghosh Ananna , Hossain Md. Forhad
Published: September 2024

Aedes aegypti(Linnaeus) mosquito is a vector, responsible for increasing global public health concerns due to its rapid geographical spread and increasing vectorial capacity. Understanding the breeding behavior ofAe. aegyptiis crucial to control this vector and thereby limiting the spread of diseases. To study this mosquito breeding in the laboratories and ovitraps, different types of lining-papers, surrounding inner surface of a container along with different types of added infusions, are used. Lining-papers serve as surfaces for oviposition and infusions provide the essential environment for nurturing. The types of oviposition surfaces and infusions used in laboratory rearing facilities or ovitraps influence oviposition preference, changing the breeding behavior ofAe. aegyptigravid mosquitoes. This study presents a comparative study on oviposition preferences for six different types of lining-papers and six different types of infusions in a bioassay cage. ANOVA analysis shows a significant effect on oviposition preference of different types of lining-papers that served as oviposition surfaces. The highest oviposition activity was observed for the‘agri seed germination paper-75’lining-paper when normal tap water infusion was used. Likewise, statistical analysis shows that when a‘plain printing offset paper 80 GSM’lining-paper was used, a highly statistically significant effect on oviposition preference is observed for different types of infusions used in the oviposition cups.
Selection on time to parasite transmission shapes the hostAnopheles gambiaetranscriptional response and suggests immune evasion
Authors: Silva Luís M.
Published: September 2024

Understanding host-parasite interactions is of the utmost importance for the correct disease prediction, prevention and management. Hence, this study assessed the transcriptional response of the primary malaria vector,Anopheles gambiae, to infection with several lines of the prominent vector-control parasite, the microsporidianVavraia culicis. These parasitic lines have been selected for early or late transmission within this host. Previous studies extensively described them phenotypically, differing in their virulence, infection dynamics and host exploitation. Using RNA sequencing, gene expression profiles were analyzed in mosquitoes infected with early-selected, late-selected, unselected (reference)V. culicislines and uninfected controls. The results revealed distinct transcriptional changes associated with each parasite line. Early-selected parasites induced a broader immune response than late-selected ones. Differential expression of immune-related genes, includingToll-interacting proteinandProtein ERGIC-53, suggests enhanced immune evasion in late-selected parasites. Additionally, significant changes were observed in pathways related to Golgi membrane function and oxidative stress response, particularly in response to early-selected parasites. These findings highlight the evolutionary pressures shaping host-parasite coevolution and provide insights into how parasite transmission traits can influence mosquito immune response and regulation. This work offers a foundation for future studies on mosquito-microsporidia dynamics and potential applications for vector control strategies, particularlyPlasmodium.
The HIV-1 Nuclear Export Complex Reveals the Role of RNA in Crm1 Cargo Recognition
Authors: Smith Amber M. , Li Yang , Velarde Arianna , Cheng Yifan , Frankel Alan D.
Published: September 2024

Crm1 is a highly conserved nuclear exportin that transports >1000 human proteins including ribonucleoprotein (RNP) complexes. The interface between Crm1 and RNP cargos is unknown. The HIV regulatory protein, Rev, was one of the first identified cargos for Crm1 and contains a prototypic nuclear export sequence (NES). We present the cryo-electron microscopy structure of the HIV-1 nuclear export complex (Crm1/Ran-GTP and the Rev/RRE RNP). Rev binds at a previously unseen protein-protein binding site that stabilizes a unique Crm1 dimer and positions two NESs within the Crm1 dimer. The orientation of Rev binding positions the RRE within a charged pocket on the inside of the Crm1 toroid, mediating direct RNA-Ran-GTP contacts, highlighting the significant role of the RRE in the interaction. Structure based mutations, combined with cell-based assays, show that Crm1 has multiple distinct cargo recognition sites and explains how Crm1 can recognize a diverse range of protein and RNP cargos.
Charged current weak production of
Δ(1232)
induced by electrons and positrons
Authors: Fatima A. , Athar M. Sajjad , Singh S. K.
Published: September 2024

The charged current weak production of Δ(1232) from the free proton target induced by the electron/positron in the intermediate energy range corresponding to the beam energy available at JLab and Mainz, has been studied. The results for the differential scattering cross section dσdQ2, the angular distribution dσdΩΔ, and the total scattering cross section σ(Ee) for both the electron and positron induced processes are presented, for the various energies in the range of 0.5–4 GeV. The cross section

σ

(

E

e

)

is found to be of the order of 10−39  cm2 for the electron/positron energies in the few GeV range. The availability of electron/positron beams having well-defined energy and direction with very high luminosity of the order of 1038–1039  cm−2  sec−1, makes it possible to observe the weak charged current production of Δ(1232) and determine the axial vector form factors CiA(Q2);(i=3–5). The sensitivity of the differential cross section dσdQ2 to the subdominant form factors C3A(Q2) and C4A(Q2) is found to be strong enough, especially in the low Q2 region, which can be used to determine them phenomenologically and to test the various theoretical models proposed to calculate them.

Published by the American Physical Society
2024
Gravitational form factors of pseudoscalar mesons in a contact interaction
Authors: Sultan M. Atif , Xing Zanbin , Raya Khépani , Bashir Adnan , Chang Lei
Published: September 2024

Given the unique role played by the gravitational form factors (GFFs) in unraveling the internal mechanics of hadrons, we examine the GFFs of ground state pseudoscalar mesons π, ηc, ηb and the hypothetical ηs(ss¯). We adopt the coupled framework of Dyson-Schwinger and Bethe-Salpeter equations within a contact interaction and employ a novel approach to the dressed amputated meson-meson scattering amplitude, which makes connection with the energy-momentum tensor and with the GFFs. The resulting GFFs fulfill the anticipated symmetry constraints. The corresponding charge and mass radii and the D term are also computed. We show that the D term for the pseudoscalar mesons is bounded within the (−1,−1/3) range; these bounds correspond to the massless (chiral limit) and infinitely massive cases, respectively. Considering the current interest in the GFFs, understanding the D term of pseudoscalar mesons and their GFFs can provide an important first step for future endeavors in the field.

Published by the American Physical Society
2024
Calculating the two-photon exchange contribution to
KL→μ+μ−
decay
Authors: Chao En-Hung , Christ Norman
Published: September 2024

We present a theoretical framework within which both the real and imaginary parts of the complex, two-photon exchange amplitude contributing to KL→μ+μ− decay can be calculated using lattice quantum chromodynamics. The real part of this two-photon amplitude is of approximately the same size as that coming from a second-order weak strangeness-changing neutral-current process. Thus a test of the standard model prediction for this second-order weak process depends on an accurate result of this two-photon amplitude. A limiting factor of our proposed method comes from low-energy three-particle ππγ states. The contribution from these states will be significantly distorted by the finite volume of our calculation—a distortion for which there is no available correction. However, a simple estimate of the contribution of these three-particle states suggests their contribution to be at most a few percent allowing their neglect in a lattice calculation with a 10% target accuracy.

Published by the American Physical Society
2024
Constraints on light dark sector particles from lifetime difference of heavy neutral mesons
Authors: Kumar Girish , Petrov Alexey A.
Published: September 2024

Heavy meson decays with missing energy in the final state offer interesting avenues to search for light invisible new physics such as dark matter (DM). In this context, we show that such new physics (NP) interactions also affect lifetime difference in neutral meson-antimeson mixing. We consider general dimension-six effective quark interactions involving a pair of DM particles and calculate their contributions to lifetime difference in beauty and charm meson systems. We use the latest data on mixing observables to constrain the relevant effective operators. We find that lifetime differences provide novel and complementary flavor constraints compared to those obtained from heavy meson decays.

Published by the American Physical Society
2024
Comparing advanced-era interferometric gravitational-wave detector network configurations: Sky localization and source properties
Authors: Emma Mattia , de Nobrega Tiago Fernandes , Ashton Gregory
Published: September 2024

The expansion and upgrade of the global network of ground-based gravitational-wave detectors promises to improve our capacity to infer the sky localization of transient sources, enabling more effective multimessenger follow-ups. At the same time, the increase in the signal-to-noise ratio of detected events allows for more precise estimates of the source parameters. This study aims to assess the performance of advanced-era networks of ground-based detectors, focusing on the Hanford, Livingston, Virgo, and KAGRA instruments. We use full Bayesian parameter estimation procedures to predict the scientific potential of a network. Assuming a fixed configuration of the LIGO Hanford and Livingston detectors, we find that the addition of the Virgo detector is beneficial to the sky localization starting from a binary neutron star range of 20 Mpc and improves significantly from 40 Mpc onward for both a single and double LIGO detector network, reducing the inferred mean sky area by up to 95%. Similarly, the KAGRA detector tightens the constraints, starting from a binary neutron star range of 10 Mpc. Looking at highly spinning binary black holes, we find significant improvements with increasing sensitivity in constraining the intrinsic source parameters when adding Virgo to the two LIGO detectors. Finally, we also examine the impact of the low-frequency cutoff data on the signal-to-noise ratio. We find that existing 20 Hz thresholds are sufficient and propose a metric to monitor this to study detector performance. Our findings quantify how future enhancements in detector sensitivity and network configurations will improve the localization of gravitational-wave sources and allow for more precise identification of their intrinsic properties.

Published by the American Physical Society
2024