bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual reliability of a composite material subjected to buckling and post-buckling tests: the case of reinforced concrete
Authors: Ngnassi Djami Aslain Brisco , Nguelcheu Ulrich Ngnassi , Offole Florence
Published: December 2024

This article examines the residual reliability of composite materials, focusing on reinforced concrete subjected to buckling and post-buckling tests, a crucial topic in civil engineering. The main aim of the study is to assess how these loads affect mechanical properties, including compressive strength and elongation at break, while identifying associated failure mechanisms. A rigorous methodology was adopted, involving experimental tests on reinforced concrete samples, followed by microscopic analysis and comparison with literature data. The results reveal a significant decrease in compressive strength and modulus of elasticity with increasing loads and loading cycles. In addition, the study highlights a reduction in elongation at break, indicating a loss of ductility and stiffness of the material. Failure mechanisms observed include cracking and delamination, suggesting that the residual reliability of reinforced concrete is inferior to that of advanced composites. These findings underline the importance of appropriate design to ensure the durability of reinforced concrete structures, taking into account the impact of extreme loads and environmental conditions. This research contributes to a better understanding of the behavior of composite materials under critical conditions, providing recommendations for improving design and construction practices in civil engineering.
Primary perianal alveolar rhabdomyosarcoma with uncommon metastatic sites: a case report and follow-up using 18F-FDG PET/CT
Authors: Yang Yihan , Chen Zhao , Qiu Yongkang , Cheng Jia , Na Ritai , Liu Min , Kang Lei
Published: December 2024

Background

Rhabdomyosarcoma (RMS), a rare pediatric soft tissue neoplasm, predominantly develops in late childhood and adolescence with no discernible gender bias. Alveolar rhabdomyosarcoma (ARMS) stems from mesenchymal cells and may develop most frequently in the trunk, extremities, and head/neck areas, while occurrences in the pelvic cavity are less frequent. The manifestation is typically characterized by a high rate of aggressive metastasis and a poor overall survival prognosis.

Case report

We present the case of an 11-year-old girl with ARMS initially presenting with a perianal mass. The diagnostic workup included MRI and PET/CT, which highlighted the tumor’s aggressive nature and metastatic potential. Subsequent metastases to the pleura, lymph nodes, and, less frequently, to the bone were detected using 2-deoxy-2-[fluorine-18]-fluoro-D-glucose positron emission tomography combined with computed tomography (18F-FDG PET/CT) imaging. The patient underwent a multi-regimen chemotherapy protocol but showed an incomplete response, indicating a poor prognosis.

Conclusion

This report presents a rare case of ARMS primarily located in the perianal region with multiple metastases, including the uncommon occurrence of bone metastasis, which illustrates the challenges in diagnosing and treating ARMS, emphasizing the need for accurate and early diagnosis, advanced imaging for disease assessment, and more effective treatment strategies. 18F-FDG PET/CT imaging highlights its preeminence in detecting multiple rare metastatic lesions. However, the persistent disease activity despite treatment highlights the need for further research into the biology of ARMS and the development of novel therapeutics to improve patient outcomes.
Evaluation of post-COVID mortality risk in cases classified as severe acute respiratory syndrome in Brazil: a longitudinal study for medium and long term
Authors: Rodrigues Nádia Cristina Pinheiro , Andrade Mônica Kramer de Noronha
Published: December 2024

Background

There are few studies in the literature evaluating post-COVID mortality in Brazil, along medium and long term, especially in those who presented severe clinical disease.

Objective

This study aims to investigate the factors associated with post-COVID mortality of severe acute respiratory syndrome (SARS) cases from 2020 to 2023 in Brazil, along medium and long term.

Methods

Retrospective cohort study using notification data of SARS classified as COVID-19 from the Brazilian National Information System, “Sistema de Vigilância Epidemiológica (SIVEP),” during the period 2020 to 2023. Data included demographics, comorbidities, vaccination status, number of COVID-19 vaccine doses, city of residence, and survival outcomes. Classic Cox, Cox mixed effects, and Cox fragility models were used to assess medium and long-term risks of dying post-COVID.

Results

In the medium and long-term periods studied, 5,157 deaths were recorded out of 15,147 reported SARS/COVID-19 cases. Of these deaths, 91.5% (N = 4,720) occurred within the first year, while 8,5% (N = 437) after the first year. People without formal education, the older adult, had higher percentages of deaths in both periods. In the medium-term post-COVID period, the risk of death was reduced by 8% for those who had been vaccinated while in the long-term post-COVID period, the risk of death almost doubled for those who had been vaccinated. While in the medium term, there was a reduction in mortality risk for those who took two or three doses, in the long term the risk of death was greater for those who took one or two doses.

Conclusion

The protective effect of COVID-19 immunization was observed up to one year after the first symptoms. After one year, the effect was reversed, showing an increased risk of death for those vaccinated. These results highlight the need for further research to elucidate the factors that contribute to these findings.
Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes
Authors: Diehl Kyra , Stoos Elizabeth , Becker Alyssa , Orfaly Victoria E. , Nelson Jacob , Gillespie Jordan , Ng Justin , Tobey Tayler , Latour Emile , Ludzik Joanna , Berry Elizabeth G. , Geller Alan C. , Jacobe Heidi , Leitenberger Justin , McClanahan Danielle , Tran Jessica , Prasad Smriti , Mengden-Koon Stephanie , Nelson Kelly C. , Petering Ryan , Verdieck Alex , Savory Stephanie , Smith Emily H. , Tofte Susan , Weinstock Martin A. , White Kevin , Wisco Oliver , Curiel-Lewandrowski Clara , Swetter Susan M. , Witkowski Alexander M. , Ferris Laura , Black Samantha , Xu Rebecca , Xu Shuai , Leachman Sancy
Published: December 2024

Introduction

Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.

Methods

We have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.) that suits their learning style and time availability. Here we present the toolkit, the development and validation of the curriculum, and report on 1-year outcomes of a nested survey study. Because the goal of the program is to maximize participation by allowing PCPs to tailor their experience to their own needs and interests, the majority of participants did not complete every element of the program.

Results

A total of 8,683 PCPs have accessed at least one element of the toolkit from 2019–2024. Participants completed a pre-survey, online training module, and post-survey that included self-reported screening behaviors, changes in confidence, and malignant and benign lesion categorization based on clinical images. A total of 139 pre-surveys and 92 post-surveys were completed, including 55 matched participants that completed both the pre- and post-training surveys. There were significant improvements in PCP confidence (P < 0.001) and malignant (P < 0.001) and benign image (P = 0.029) identification respectively.

Discussion

PCPs may serve as a valuable aid in skin cancer screening efforts, but additional studies are needed to evaluate the impact of these curricula in clinical practice.
Association between red cell distribution width and 30-day mortality in patients with sepsis-associated liver injury: a retrospective cohort study
Authors: Ao Ting , Huang Yingxiu , Zhen Peng , Hu Ming
Published: December 2024

Background

Sepsis-associated liver injury (SALI) is a critical component of sepsis-induced multiple organ dysfunction with high mortality. Identifying biomarkers for risk stratification is essential. Red cell distribution width (RDW), indicating variation in red blood cell volume, has been linked to adverse outcomes in various diseases. This study aimed to evaluate the association between RDW and 30-day mortality in SALI patients.

Methods

A retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care-IV database. Patients admitted to the intensive care unit (ICU) with SALI were included. RDW was recorded within the initial 24 h. The primary outcome was 30-day mortality. A multivariable Cox regression analysis was performed to examine the relationship between RDW and mortality.

Results

Among 529 SALI patients (mean age 68.7 years, 61.8% male), 46.1% had RDW > 15.5%. The 30-day mortality rate was 35.5%. RDW was significantly higher in non-survivors compared to survivors (17.2 ± 3.0 vs. 15.4 ± 2.3, P < 0.001). Cox regression identified RDW as an independent risk factor for 30-day mortality (HR 1.14, 95% CI 1.09 to 1.19, P < 0.001). Subgroup analyses demonstrated that the findings were consistent across the various groups.

Conclusion

Elevated RDW is independently associated with higher 30-day mortality in patients with SALI, suggesting its potential role in risk stratification and clinical management.
Semiquantitative 2-[18F]FDG PET/CT-based parameters role in lymphoma
Authors: Albano Domenico , Ravanelli Marco , Durmo Rexhep , Versari Annibale , Filice Angelina , Rizzo Alessio , Racca Manuela , Pizzuto Daniele Antonio , Bertagna Francesco , Annunziata Salvatore
Published: December 2024

2-deoxy-2-[18F]-fluoro-D-glucose (2-[18F]FDG) positron emission tomography/computed tomography (PET/CT) plays a crucial role in the management of lymphoma in different settings, such as staging disease, assessing response to therapy, predicting prognosis, and planning RT. Beside visual analysis, several semiquantitative parameters were introduced to study lymphoma with promising results. These parameters can represent different disease characteristics, like body composition (such as sarcopenic index), dissemination of disease (Dmax), tumor burden (including metabolic tumor volume) and texture features. All these parameters showed promising results, especially in terms of prognosis (progression free survival and overall survival), but lack of standardization and shared methodology remains a big issue. Advances in PET-based biomarkers are on the horizon, yet their integration into clinical decision-making is currently hindered by methodological limitations that require resolution through confirmatory prospective validation in specific patient groups. This review highlights studies demonstrating the prognostic and predictive value of these semiquantitative parameters in lymphoma, while also discussing their potential applicability in clinical practice.
The application of ChatGPT in nursing: a bibliometric and visualized analysis
Authors: Wang Peng , Zhang Qian , Zhang Wenyu , Sun Jing
Published: December 2024

Objective

With the development of ChatGPT, the number of studies within the nursing field has increased. The sophisticated language capabilities of ChatGPT, coupled with its exceptional precision, offer significant support within the nursing field, which includes clinical nursing, nursing education, and the clinical decision-making process. Preliminary findings suggest positive outcomes, underscoring its potential as a valuable resource for enhancing clinical care. However, a comprehensive analysis of this domain is lacking, and the application of bibliometric methods remains rare. This study aims to describe and predict the developmental trajectory of the discipline, identify research hotspots and trends, and provide a comprehensive framework for the integration of ChatGPT in nursing.

Methods

Following the development of a search strategy in collaboration with librarians, the implementation of this strategy occurred in the Web of Science Core Collection (WoSCC) on June 30, 2024. For bibliometric and visual analyses—including evaluations of sources, institutions, countries, author collaboration networks, and keywords—Bibliometrix (version 4.4.2) and CiteSpace (version 6.2.R2 Basic) were employed.

Results

A total of 81 articles published by 67 authors were retrieved from the Web of Science Core Collection database, covering the period of June 30, 2024. The number of published studies has exhibited an increasing trend. The “European Journal of Cardiovascular Nursing” emerged as the most productive journals, while the USA, the UK, and China were identified as the leading countries in terms of publication output. The top 10 keywords identified in this study include artificial intelligence, nursing education, large language models, ChatGPT, natural language processing, generative artificial intelligence, care, nursing practice, clinical decision-making, and deep learning.

Conclusion

ChatGPT is an emerging tool in the nursing field, currently in the foundational research phase. While there is significant international collaboration, cooperation among author groups remains somewhat limited. Studies focusing on ChatGPT in nursing primarily concentrate on two key themes: (1) the deep learning of ChatGPT in nursing and (2) the feasibility of its application. It is essential for nurses across various specialties to collaborate in exploring the diverse applications of ChatGPT within their domains, thereby fostering the ongoing development and enhancement of this technology.
Diurnal temperature variation in surface soils: an underappreciated control on microbial processes
Authors: Sanford Robert A. , Chee-Sanford Joanne C. , Yang Wendy H.
Published: December 2024

Large diurnal temperature changes (ΔT) (or the diurnal temperature range (DTR)) in surface soils, ranging from 5°C to often greater than 20°C, are generally acknowledged to occur yet largely disregarded in studies that seek to understand how temperature affects microbially-mediated carbon and nitrogen cycling processes. The soil DTR is globally significant at depths of 30 cm or less, occurring from spring through summer in temperate biomes, during summer periods in the arctic, and year-round in the tropics. Thus, although temperature has long been considered an important factor in controlling microbial processes, our understanding of its effects remains incomplete when considering natural soil temperature cycles. Here we show: (1) documented impacts of diurnal temperature changes on microbial respiration rates; (2) documented observations of surface soils with large DTR (>5°C) that affect soil microbial mineralization rates and redox potentials of important biogeochemical reactions; and (3) direct evidence that the constant temperature regime typically used in laboratory soil incubation studies may therefore lead to mischaracterization of in situ temperature controls on microbially influenced processes in the environment. The overall effect is that the DTR yields process rates that are often higher than what has been observed under experimental mean temperature incubation. We suggest that overlooked genetic mechanisms, such as the presence of a circadian clock or thermophilic activity during summer months, are likely contributing to the observed effects of the DTR. To improve our understanding of climate change effects on soil greenhouse gas emissions, nutrient cycling, and other biogeochemical soil processes, we propose a paradigm shift in approach to temperature-inclusive process modeling and laboratory incubation studies that accounts for the important role of natural diurnal temperature fluctuations.
Comparative analyses of persistence traits in Escherichia coli O157:H7 strains belonging to different clades including REPEXH01 and REPEXH02 strains
Authors: Carter Michelle Qiu , Carychao Diana , Bono James L.
Published: December 2024

Recent application of whole genome sequencing in the investigation of foodborne illness outbreaks has facilitated the identification of Reoccurring, Emerging, or Persistent (REP) bacterial strains that have caused illnesses over extended periods of time. Here, the complete genomes of two Escherichia coli O157:H7 (EcO157) outbreak strains belonging to REPEXH01 and REPEXH02, respectively, were sequenced and annotated. Comparative genomics and phenotypic analyses were carried out to identify REP-associated traits. The REPEXH01 strain PNUSAE013245 belonged to clade 8 and shared >96% CDSs with the 2006 spinach-associated outbreak strain EC4115. A 79-Kb genomic island was identified only in PNUSAE013245, and encoded functions related to heavy metals and antibiotic resistances. The REPEXH02 strain PNUSAE043864 belonged to clade 2, like the 2006 Taco John’s restaurants-associated outbreak strain TW14588 and the REPEXH02 strain 2019C-3201. These three strains differed mainly in plasmids and prophages repertoire. Unlike 2019C-3201, PNUSAE043864 carried only the virulence plasmid pO157; unlike TW14588, PNUSAE043864 carried one Stx2a-encoding prophage. Phenotypic assays revealed that all clade 2 strains produced greater amounts of biofilms than the clade 8 strains, although there were no significant differences in adhesion of EcO157 to romaine lettuce. The persistence of EcO157 was further evaluated by quantifying populations of culturable cells, persisters, and Viable But Not Culturable (VBNC) cells for strains inoculated in river water and incubated at 15°C for 14 weeks. The fractions of culturable cells were comparable among the strains tested until 10 weeks post inoculation, when the three clade 2 strains exhibited significantly greater survival than strain PNUSAE013245. The population of persisters for all strains except PNUSAE013245 increased when the incubation time increased and reached up to 24–30% of the total culturable cells. The population of VBNC increased for all strains during the incubation and reached up to 65–80% of the total population. Both persisters and VBNC cells represent the dormancy state of pathogen cells that have increased tolerance to antibiotics and sanitizers. Presence of high portions of persisters and VBNC cells in agricultural environments highlights the need to understand the physiology of bacterial pathogens in leafy greens production environments and the challenges in developing effective control strategies.
The synthesis of the novel Escherichia coli toxin—colibactin and its mechanisms of tumorigenesis of colorectal cancer
Authors: Zhang Guojing , Sun Daqing
Published: December 2024

Escherichia coli is part of the normal flora of the human gut and performs vital functions; however, certain strains can cause disease in the host, impairing gut function and adversely affecting overall health. The pks gene cluster in the E. coli B2 serogroup encodes colibactin, a secondary metabolite and a potential gut toxin. However, the mechanism underlying colibactin production in E. coli is complex, and the function of the pks gene cluster is not fully understood. This review explores the complex mechanisms and processes by which the pks island in E. coli produces colibactin, clarifying the specific role played by the clbA-S genes within it. It also reveals the toxic effects of colibactin on the host cell’s DNA and elaborates the mechanisms that may be important in inducing the development of colorectal cancer, such as single-base substitution (SBS), small insertion/deletion (small indel) features (ID-pks), inter-chromosomal linkages (ICLs), and DNA double-strand breaks (DSBs). The elucidation of these mechanisms is of great significance for the further exploration and development of related drugs.
Biomarker discovery and development of prognostic prediction model using metabolomic panel in breast cancer patients: a hybrid methodology integrating machine learning and explainable artificial intelligence
Authors: Yagin Fatma Hilal , Gormez Yasin , Al-Hashem Fahaid , Ahmad Irshad , Ahmad Fuzail , Ardigò Luca Paolo
Published: December 2024

Background

Breast cancer (BC) is a significant cause of morbidity and mortality in women. Although the important role of metabolism in the molecular pathogenesis of BC is known, there is still a need for robust metabolomic biomarkers and predictive models that will enable the detection and prognosis of BC. This study aims to identify targeted metabolomic biomarker candidates based on explainable artificial intelligence (XAI) for the specific detection of BC.

Methods

Data obtained after targeted metabolomics analyses using plasma samples from BC patients (n = 102) and healthy controls (n = 99) were used. Machine learning (ML) models based on raw data were developed, then feature selection methods were applied, and the results were compared. SHapley Additive exPlanations (SHAP), an XAI method, was used to clinically explain the decisions of the optimal model in BC prediction.

Results

The results revealed that variable selection increased the performance of ML models in BC classification, and the optimal model was obtained with the logistic regression (LR) classifier after support vector machine (SVM)-SHAP-based feature selection. SHAP annotations of the LR model revealed that Leucine, isoleucine, L-alloisoleucine, norleucine, and homoserine acids were the most important potential BC diagnostic biomarkers. Combining the identified metabolite markers provided robust BC classification measures with precision, recall, and specificity of 89.50%, 88.38%, and 83.67%, respectively.

Conclusion

In conclusion, this study adds valuable information to the discovery of BC biomarkers and underscores the potential of targeted metabolomics-based diagnostic advances in the management of BC.
Hippocampal SIRT1 signaling mediates the ameliorative effect of treadmill exercise on anxiety- and depression-like behavior in APP/PS1 mice
Authors: Wang Yarong , Zhang Rongxing , Jiang Yumin , Liao Jingwen , Mu Lianwei , Hu Min
Published: December 2024

Objective

Anxiety and depression-like symptoms occur in the early stages of Alzheimer’s disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic restraint stress model, rat model of posttraumatic stress disorder, and rat model of fetal alcohol spectrum disorders. Here, we aimed to investigate whether exercise ameliorates anxiety- and depression like behaviors in APP/PS1 mice and explore the potential mechanisms.

Methods

After eight weeks of exercise intervention, we assessed anxiety- and depression-like behaviors in Alzheimer’s disease (AD) model mice. We then measured the levels of SIRT1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial biogenesis (CO2, ATP6, and mitochondrial content) using immunofluorescence, reverse transcription-quantitative real-time PCR, and transmission electron microscopy. Finally, we investigated the effects of pharmacological activation of SIRT1 on anxiety- and depression-like behaviors, the SIRT1/PGC-1α/NRF1/TFAM signaling axis, and mitochondrial biogenesis.

Results

We first observed that treadmill exercise improved anxiety- and depression-like behaviors in six-month-old APP/PS1 mice and increased SIRT1 levels in the hippocampus. Pharmacological activation of hippocampal SIRT1 function also reduced anxiety and depression-like behaviors in APP/PS1 mice. Meanwhile, both treadmill exercise and pharmacological activation of hippocampal SIRT1 increased the levels of PGC1α, NRF1, TFAM, and enhanced mitochondrial biogenesis (CO2, ATP6, or mitochondrial content) in the hippocampus of APP/PS1 mice.

Conclusion

These findings reveal that treadmill exercise reduces anxiety- and depression-like behaviors in six-month-old APP/PS1 mice by enhancing the SIRT1-dependent PGC-1α/NRF1/TFAM axis, promoting mitochondrial biogenesis in the hippocampus.
Apolipoprotein E dysfunction in Alzheimer’s disease: a study on miRNA regulation, glial markers, and amyloid pathology
Authors: Wijesinghe Printha , Li Hao Ran , Ai Zhengyuan , Campbell Matthew , Chen Si Xuan , Xi Jeanne , Pham Wellington , Matsubara Joanne A.
Published: December 2024

Introduction

Apolipoprotein E (ApoE) plays a crucial role in lipid homeostasis, predominantly expressed in astrocytes and to a lesser extent in microglia within the central nervous system (CNS). While the APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD), its precise role in AD pathogenesis remains elusive. Apoe-knockout (Apoe-ko) mice, mice expressing human APOE4, and human APOE4 carriers exhibit similar deficits in lipid metabolism, cognitive and behavioral functions, and neurodegeneration. The retina, as part of the CNS, has been studied to investigate the underlying mechanisms of AD, including neuroinflammation, amyloid aggregation, and neurodegeneration. This study explores ApoE’s role in AD by analyzing brain and eye samples from Apoe-ko mice, focusing on identifying potential retinal biomarkers associated with ApoE dysfunction.

Methods

We compared female Apoe-ko mice on a regular diet to age-matched C57BL/6J controls at 3 and 9 months. Our investigations included microRNAs (miRNAs), their target messenger RNAs (mRNAs), and selected protein markers, including astroglial (Gfap), microglial/macrophage (Iba1 and Trem2) markers, and amyloid precursor protein (APP)/amyloid-β (Aβ) peptides implicated in AD pathogenesis. We also examined female Apoe-ko mice on a high-fat diet versus a regular diet at 9 months for differential miRNA and mRNA expressions.

Results

Our findings demonstrated that miRNA levels were generally lower in 3-month-old Apoe-ko mice but increased in 9-month-old mice across five distinct brain regions, as well as in eye tissue and tear fluid. A high-fat diet further enhanced miRNA dysregulation in brain and eye tissues, but not in tear fluid. Target mRNAs were generally higher in the neocortex-hippocampus and eye tissue of 3-month-old Apoe-ko mice but decreased with age, except for glial cell mRNAs like Gfap and Aif1. Protein analysis revealed elevated Gfap expression, and increased APP/Aβ peptide accumulation in the neocortex-hippocampus, including brain endothelial cells at the meninges, as well as in the retina of 9-month-old Apoe-ko mice. These findings highlight ApoE’s pivotal role in AD, demonstrating its impact on inflammatory and amyloidogenic/angiogenic miRNA expression, glial homeostasis, and APP/Aβ peptide clearance. The observed upregulation of proinflammatory miR-146a and anti-amyloidogenic/angiogenic miR-15a in 9-month-old Apoe-ko mice suggests their potential as tear-based biomarkers for ApoE dysfunction.
Targeted plasma metabolomics reveals potential biomarkers of the elderly with mild cognitive impairment in Qingdao rural area
Authors: Meng Yuchi , Cheng Murong , Qu Hongyan , Song Zhenxue , Zhang Ling , Zeng Yuanjun , Zhang Dongfeng , Li Suyun
Published: December 2024

Introduction

Previous research has suggested a link between the onset of Alzheimer’s disease (AD) and metabolic disorder; however, the findings have been inconsistent. To date, the majority of metabolomics studies have focused on AD, resulting in a relative paucity of research on early-stage conditions such as mild cognitive impairment (MCI) underexplored. In this study, we employed a comprehensive platform for the early screening of individuals with MCI using high-throughput targeted metabolomics.

Method

We included 171 participants including 124 individuals with MCI and 47 healthy subjects. Univariate statistical analysis was conducted using t-tests or Wilcoxon rank-sum tests, with p-values corrected by the Benjamini-Hochberg method. The screening criteria were set at FDR < 0.05 and fold change (FC) > 1.5 or < 0.67. Multivariate analysis was performed using orthogonal partial least squares discriminant analysis (OPLS-DA), where differential metabolites were identified based on variable influence on projection (VIP) scores (VIP > 1 and FDR < 0.05). Random forest analysis was used to further evaluate the ability of the metabolic data to distinguish effectively between the two groups.

Results

A total of 14 differential metabolites were identified, leading to the discovery of a biomarker panel consisting of three plasma metabolites including uric acid, pyruvic acid and isolithocholic acid that effectively distinguished MCI patients from healthy subjects.

Discussion

These findings have provided a comprehensive metabolic profile, offering valuable insights into the early prediction and understanding of the pathogenic processes underlying MCI. This study holds the potential for advancing early detection and intervention strategies for MCI.
The constrained-disorder principle defines the functions of systems in nature
Authors: Ilan Yaron
Published: December 2024

The Constrained Disorder Principle (CDP) defines all systems in nature by their degree of inherent variability. Per the CDP, the intrinsic variability is mandatory for their proper function and is dynamically changed based on pressures. The CDP defines the boundaries of inherent variability as a mechanism for continuous adaptation to internal and external perturbations, enabling survival and function under dynamic conditions. The laws of nature govern the world’s natural phenomena and underlie the function of all systems. Nevertheless, the laws of physics do not entirely explain systems’ functionality under pressure, which is essential for determining the correct operation of complex systems in nature. Variability and noise are two broad sources of inherent unpredictability in biology and technology. This paper explores how the CDP defines the function of systems and provides examples from various areas in nature where the CDP applies, including climate, genetic, biology, and human behavioral variabilities. According to the CDP, system malfunction results from inappropriate performance of the boundaries of inherent variability. The environment influences the physiological variability, and species interactions influence eco-evolutionary outcomes. The CDP defines human behavior as being driven by randomness and accounts for malfunctions and their corrections. The paper reviews variability-based CDP algorithms and CDP-based second-generation artificial intelligence systems and their potential for improving systems’ prediction and efficiency by using variability.
Establishment and evaluation of a carotid artery dissection model in rats
Authors: Zhang Shufan , Han Zhenxiang , Cao Ying , Wu Weicheng , Liu Yuanzeng , Yang Shilin , Feng Xiaochao , Yu Chun , Zhu Zhu , Dong Qiang , Han Xiang
Published: December 2024

Background

Given the lack of models for carotid artery dissections (CAD), we aim to investigate effects of beta-aminopropionitrile (BAPN) combined with physical damage on the arterial walls of rats, and to establish a high-incidence and low-mortality CAD model.

Methods

Sixteen SPF SD rats (3-week-old) were divided into two groups. Group B was given 0.25% BAPN solution and group W was given water. Then we established an animal model of CAD by carotid artery torsion. One of the two carotid arteries in each rat was randomly selected for torsion. We got four groups of blood vessels following above-mentioned methods: BAPN plus torsion group (group Bt), BAPN plus non-torsion group (group Bn), water plus torsion group (group Wt), and water plus non-torsion group (group Wn). The hematoxylin and eosin (HE) staining and Verhoeff’s Van Gieson (EVG) staining were performed to observe structures of arteries. Immunofluorescence staining was used to detect structural proteins in vessels. We used triphenyltetrazolium chloride (TTC) staining and neurological function assessment to detect the infarct area of brain and neurological deficits in rats with carotid dissection to verify the validity of the rat model.

Results

BAPN treatment significantly affected the weight gain of rats, but had little effect on survival during the first 5 weeks. The group Bt had the highest incidence of CAD among all groups (p = 0.014). HE staining of carotid artery tissue sections showed that the vascular walls were the thickest in group Bt (p < 0.001). EVG staining showed the arrangement of elastic fibers was the most irregular in group Bt. Immunofluorescence staining revealed that the expression of a-SMA and SM22a were decreased remarkably in group Bt (p < 0.001). Both motor and sensory deficits were more severe in CAD group than control group (p = 0.0004; p = 0.0036). The relative infarction volumes of CAD group rats were significantly larger than control group (p < 0.001).

Conclusion

The animal model of CAD can be feasible to establish by mechanical torsion combined with BAPN free drinking. With this method, the animal mortality was low and the model formation rate was high. This model will enable further studies on CAD.
Toward the Bayesian brain: a generative model of information transmission by vestibular sensory neurons
Authors: Paulin Michael G. , Pullar Kiri F. , Hoffman Larry F.
Published: December 2024

The relative accessibility and simplicity of vestibular sensing and vestibular-driven control of head and eye movements has made the vestibular system an attractive subject to experimenters and theoreticians interested in developing realistic quantitative models of how brains gather and interpret sense data and use it to guide behavior. Head stabilization and eye counter-rotation driven by vestibular sensory input in response to rotational perturbations represent natural, ecologically important behaviors that can be reproduced in the laboratory and analyzed using relatively simple mathematical models. Models drawn from dynamical systems and control theory have previously been used to analyze the behavior of vestibular sensory neurons. In the Bayesian framework, which is becoming widely used in cognitive science, vestibular sense data must be modeled as random samples drawn from probability distributions whose parameters are kinematic state variables of the head. We show that Exwald distributions are accurate models of spontaneous interspike interval distributions in spike trains recoded from chinchilla semicircular canal afferent neurons. Each interval in an Exwald distribution is the sum of an interval drawn from an Exponential distribution and a Wald or Inverse Gaussian distribution. We show that this abstract model can be realized using simple physical mechanisms and re-parameterized in terms of the relevant kinematic state variables of the head. This model predicts and explains statistical and dynamical properties of semicircular canal afferent neurons in a novel way. It provides an empirical foundation for realistic Bayesian models of neural computation in the brain that underlie the perception of head motion and the control of head and eye movements.
Changes in serum concentration of perioperative inflammatory cytokines following the timing of surgery among mild–moderate traumatic brain injury patients and factors associated
Authors: Lekuya Hervé Monka , Cose Stephen , Nakibuule Marjorie , Ahimbisibwe Gift , Fuller Anthony , Kamabu Larrey Kasereka , Biryabarema Emmanuel , Olweny Geoffrey , Kateete David Patrick , Kirabira Anthony , Makumbi Fredrick , Vandersteene Jelle , Baert Edward , Galukande Moses , Kalala Jean-Pierre Okito
Published: December 2024

Background

The safe timing window for surgery during the acute phase of inflammation due to traumatic brain injury (TBI) has not been studied extensively. We aimed to elucidate the relationship between the timing of surgery and changes in perioperative serum levels of inflammatory cytokines and factors associated to optimize TBI management in low-middle-income countries.

Methods

A prospective cohort study was conducted among TBI Patients with depressed skull fractures with a GCS > 8 operated at different timing from injury and followed up peri-operatively. We collected the clinical-radiological data, as well as pre-and postoperative venous samples from participants; we then did Luminex Assay to quantify the serum levels of pro/anti-inflammatory cytokines using the kits of 96-well human cytokine “27-Plex-Assay (#M500KCAF0Y®).” We performed the analysis with STATA version 17 and R_studio applying both descriptive and inferential methods.

Results

We enrolled 82 TBI patients with a median (IQR) age of 25.5 (20–34) years, and the majority were male (85.4%). There were 48.8% victims of assaults, and 73.2% had a post-resuscitation admission GCS of 14–15. There were 38 (46.3%) who were operated within 48 h of injury versus 44 (53.7%) after 48 h. Serum levels of TNF-α were significantly higher after surgeries done >48 h compared to those done ≤48 h (p = 0.0327); whereas, the difference in post-operative mean serum levels of IL-10 was significantly increased in patients who developed later SSI compared to those who did not (11.56 versus −0.58 pg./mL, p = 0.0489). In multivariate analysis, the history of post-traumatic seizure (PTS) was associated with a postoperative increase in TNF-α (p = 0.01), the hemoglobin of 10–12 with a postoperative decrease of IL-4 (p = 0.05); the presence of focal neurological deficit was associated with a significant postoperative increased of TNF-α, IL-6, and IL-4 (p = 0.05). The presence of extra-axial hemorrhage was associated with a postoperative increase of IL-10 (p = 0.05).

Conclusion

Delayed surgical intervention beyond 48 h post-injury in mild–moderate TBI patients results in a significantly increased postoperative inflammatory response, as evidenced by elevated serum levels of TNF-α and IL-6. Neurological deficits, PTS, reduced hemoglobin rate, and extra-axial intracranial hemorrhage are factors associated with this heightened response.
Remotely induced electrical modulation of deep brain circuits in non-human primates
Authors: Lybbert Carter , Webb Taylor , Wilson Matthew G. , Tsunoda Keisuke , Kubanek Jan
Published: December 2024

Introduction

The combination of magnetic and focused ultrasonic fields generates focused electric fields at depth entirely noninvasively. This noninvasive method may find particularly important applications in targeted treatments of the deep brain circuits involved in mental and neurological disorders. Due to the novelty of this method, it is nonetheless unknown which parameters modulate neural activity effectively.

Methods

We have investigated this issue by applying the combination of magnetic and focused ultrasonic fields to deep brain visual circuits in two non-human primates, quantifying the electroencephalographic gamma activity evoked in the visual cortex. We hypothesized that the pulse repetition frequency of the ultrasonic stimulation should be a key factor in modulating the responses, predicting that lower frequencies should elicit inhibitory effects and higher frequencies excitatory effects.

Results

We replicated the results of a previous study, finding an inhibition of the evoked gamma responses by a strong magnetic field. This inhibition was only observed for the lowest frequency tested (5 Hz), and not for the higher frequencies (10 kHz and 50 kHz). These neuromodulatory effects were transient and no safety issues were noted.

Discussion

We conclude that this new method can be used to transiently inhibit evoked neural activity in deep brain regions of primates, and that delivering the ultrasonic pulses at low pulse repetition frequencies maximizes the effect.
Normative data for instrumented posturography: a systematic review and meta-analysis
Authors: Julienne Angela , Verbecque Evi , Besnard Stéphane
Published: December 2024

Postural control is a multisensory adaptive system performing predictive (anticipatory) and/or reactive (compensatory) actions, with varying degrees of accuracy, to maintain balance in a changing environmental context. Common instrumentation to evaluate balance includes static and dynamic force platforms; added sway-referenced perturbations on the dynamic platform constitute its main advantage. Clinical applications notwithstanding, normative data are needed for interpretation in clinical settings. Posturography norms are used to compare a reference group (healthy individuals) and a specific patient population. This work, to the best of our knowledge, represents the first attempt to synthesize the literature on normative data for computerized posturography using a combined mixed method. The search strategy resulted in the retrieval of 1,244 articles from PubMed, Web of Science, and Science Direct. After deduplication, 689 articles were screened based on title and abstract. One hundred and seven articles met the criteria after the first screening. In-depth, full-text screening resulted in the inclusion of 44 studies for the systematic review and 17 studies for the meta-analyses. The main findings of the systematic review are (1) extensive heterogeneity was found in methodological characteristics, (2) there was insufficient risk of bias mitigation, (3) the majority of tasks evaluated less than four components of the systems framework for postural control (SFPC), and (4) studies mostly used distance domain sway parameters and did not report the influence of other variables on postural sway. Based on the multilevel meta-analyses, females appeared to outperform males in eyes closed (EC) conditions significantly. Based on the network meta-analyses, we found that younger children swayed more than those aged between 8 and 14 years both in eyes open (EO) conditions and EC conditions significantly. The results also revealed a significant difference in sway between individuals of age range between 50 and 79 years old and younger individuals, with more instability observed in older participants both in EO conditions and in EC conditions. Thus, future studies need to ensure that enough information about participants is provided. Standardization of experimental conditions and sway parameters harmonization are still needed to ensure high-quality assessment (QA). Finally, evidence-based postural impairment management requires both age- and sex-related normative data.

Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023378144, identifier PROSPERO 2023 CRD42023378144.
Waist-to-height ratio and body roundness index: superior predictors of insulin resistance in Chinese adults and take gender and age into consideration
Authors: Li Anxiang , Liu Yunwei , Liu Qi , Peng You , Liang Qingshun , Tao Yiming , Liu Yunyi , Cui Chongsong , Ren Qiqi , Zhou Yingling , Long Jieer , Fan Guanjie , Lu Qiyun , Liu Zhenjie
Published: December 2024

Background and objectives

Metabolic disease has become a global health concern, and insulin resistance (IR) is a crucial underlying mechanism in various metabolic diseases. This study aims to compare the ability of seven anthropometric indicators in predicting IR in the Chinese population, and to find more sensitive and simple anthropometric indicator for early identification of IR.

Methods

This prospective cross-sectional study obtained participants’ medical history, anthropometric indicators, and serum samples from three hospitals in China. Various anthropometric indicators were calculated, including body mass index (BMI), Waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), conicity index (CI), A Body Shape Index (ABSI), body roundness index (BRI), abdominal volume index (AVI). The evaluation of IR is performed using the homeostasis model assessment-insulin resistance (HOMA-IR). Logistic regression analysis examined the relationship between indicators and HOMA-IR. The ability of the anthropometric indicators to predict IR was analyzed using the receiver operating characteristic (ROC) curve. Additionally, a stratified analysis was performed to evaluate the ability of the indicators in different age and gender groups.

Results

The study included 1,592 adult subjects, with 531 in the non-IR group and 1,061 in the IR group. After adjusting for confounding factors, the anthropometric indicators showed a positive correlation with IR in the general population and across different genders and age groups (OR > 1, p < 0.05), except for ABSI. In the ROC curve analysis, WtHR and BRI had the highest AUC values of 0.711 for detecting IR. The optimal cut-off value for WtHR to diagnose IR was 0.53, while for BRI, it was 4.00. In the gender-stratified and age-stratified analysis, BMI, WtHR, BRI, and AVI all had AUC values >0.700 in females and individuals below 60.

Conclusion

WtHR and BRI demonstrated a better ability to predict IR in the overall study population, making them preferred indicators for screening IR, and gender and age are important considerations. In the stratified analysis of different genders or age, BMI, WtHR, BRI, and AVI are also suitable for detecting IR in women or individuals under 60 years old in this study.

Clinical trial registration

www.chictr.org.cn, ChiCTR2100054654.
The mediating role of vitamin D in the relationship between triglyceride glucose index and mortality in patients with diabetes mellitus: a causal mediation analysis
Authors: Zhang Fan , Li Wenjian
Published: December 2024

Objective

This study investigated the effects of triglyceride glucose index (TyG) and vitamin D levels on all-cause and cardiovascular mortality in diabetic patients and assessed the potential mediating role of vitamin D in the relationship between TyG and mortality.

Methods

The study was based on data from the National Health and Nutrition Examination Survey (NHANES) database from 2001 to 2018, which included 6,318 patients with diabetes. Multivariable Cox proportional risk regression models were employed to assess the association between TyG and vitamin D levels and the risk of death in diabetic patients. The interaction between TyG and vitamin D and its effect on mortality was explored through restricted cubic spline analysis and causal mediation analysis.

Results

The results demonstrated that the TyG index was positively associated with all-cause and cardiovascular mortality in diabetic patients, whereas vitamin D levels were negatively associated with mortality, exhibiting an overall U-shaped association. The results indicated that vitamin D partially mediated the association between TyG and all-cause mortality. Further analysis revealed a significant mediation between vitamin D and TyG, whereby alterations in vitamin D levels influenced the impact of TyG on mortality. Subgroup analyses demonstrated that the correlation between TyG and mortality was more pronounced in diabetic patients with vitamin D insufficiency.

Conclusion

The study demonstrates the mediating influence of vitamin D on the relationship between TyG and mortality in diabetic patients. This finding underscores the necessity of evaluating the influence of vitamin D on survival outcomes in individuals with disparate levels of the TyG index.