bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals
Authors: Andraos Rama , Ahmad Awais , Wirestam Lina , Dahle Charlotte , Frodlund Martina , Rönnelid Johan , Kastbom Alf , Sjöwall Christopher 
Published: August 2024

BackgroundAnti-nuclear antibodies (ANA) assessed by immunofluorescence (IF) microscopy are associated with systemic autoimmune rheumatic diseases (SARD) and can be detected years before onset of clinical symptoms. Recent data indicate dysregulation of the immune system with increased levels of proinflammatory cytokines, including type I interferons (IFN), in ANA-positive versus ANA-negative individuals. Herein, the aims were to investigate IF-ANA, ANA fine specificities, and IFN-α protein levels in relation to self-reported symptoms, as well as clinical signs, of SARD in a large group of healthy blood donors (HBD).MethodsSera from 825 HBD (48.8% females) were included. IF-ANA was assessed, using HEp-2 cells, according to the routine at the accredited laboratory of Clinical Immunology, Linköping University Hospital. All samples were analyzed for IgG-ANA fine specificities using addressable laser bead assay (ALBIA) at the same laboratory. IFN-α was determined using ELISA. Antibody-positive individuals, and their sex- and age-matched antibody-negative controls, were asked to fill a questionnaire regarding symptoms associated with SARD.ResultsIn total, 130 HBD (15.8%) were positive with IF-ANA and/or ALBIA. Anti-U1RNP was significantly more common among women. Generally, self-reported symptoms correlated poorly with IF-ANA and/or ALBIA results. Two females with high levels of Ro60/SSA, Ro52/SSA and IFN-α reported mild sicca symptoms and were diagnosed with Sjögren’s disease after clinical evaluation.ConclusionA considerable proportion of apparently HBD are autoantibody positive, but without clear association to self-reported symptoms. Nevertheless, the combination of autoantibodies, relevant symptoms and high IFN-α levels identified the small proportion of individuals with SARD in the study population.
Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability
Authors: Zhai Sophia R. , Sarma Sridevi V. , Gunnarsdottir Kristin , Crone Nathan E. , Rouse Adam G. , Cheng Jennifer J. , Kinsman Michael J. , Landazuri Patrick , Uysal Utku , Ulloa Carol M. , Cameron Nathaniel , Inati Sara , Zaghloul Kareem A. , Boerwinkle Varina L. , Wyckoff Sarah , Barot Niravkumar , González-Martínez Jorge A. , Kang Joon Y. , Smith Rachel June 
Published: August 2024

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain.Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome.Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%.Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG.
Brain-consistent architecture for imagination
Authors: Yamakawa Hiroshi , Fukawa Ayako , Yairi Ikuko Eguchi , Matsuo Yutaka 
Published: August 2024

BackgroundImagination represents a pivotal capability of human intelligence. To develop human-like artificial intelligence, uncovering the computational architecture pertinent to imaginative capabilities through reverse engineering the brain's computational functions is essential. The existing Structure-Constrained Interface Decomposition (SCID) method, leverages the anatomical structure of the brain to extract computational architecture. However, its efficacy is limited to narrow brain regions, making it unsuitable for realizing the function of imagination, which involves diverse brain areas such as the neocortex, basal ganglia, thalamus, and hippocampus.ObjectiveIn this study, we proposed the Function-Oriented SCID method, an advancement over the existing SCID method, comprising four steps designed for reverse engineering broader brain areas. This method was applied to the brain's imaginative capabilities to design a hypothetical computational architecture. The implementation began with defining the human imaginative ability that we aspire to simulate. Subsequently, six critical requirements necessary for actualizing the defined imagination were identified. Constraints were established considering the unique representational capacity and the singularity of the neocortex's modes, a distributed memory structure responsible for executing imaginative functions. In line with these constraints, we developed five distinct functions to fulfill the requirements. We allocated specific components for each function, followed by an architectural proposal aligning each component with a corresponding brain organ.ResultsIn the proposed architecture, the distributed memory component, associated with the neocortex, realizes the representation and execution function; the imaginary zone maker component, associated with the claustrum, accomplishes the dynamic-zone partitioning function; the routing conductor component, linked with the complex of thalamus and basal ganglia, performs the manipulation function; the mode memory component, related to the specific agranular neocortical area executes the mode maintenance function; and the recorder component, affiliated with the hippocampal formation, handles the history management function. Thus, we have provided a fundamental cognitive architecture of the brain that comprehensively covers the brain's imaginative capacities.
Dietary patterns in mild cognitive impairment and dementia in older adults from Yucatan, Mexico
Authors: Garrido-Dzib Angel Gabriel , Palacios-González Berenice , Ávila-Escalante María Luisa , Bravo-Armenta Erandi , Avila-Nava Azalia , Gutiérrez-Solis Ana Ligia 
Published: August 2024

BackgroundSome dietary patterns and dietary components have an important role in preventing and helping to improve patients’ quality of life of individuals with Mild Cognitive Impairment (MCI) and dementia. In Mexico, it is unknown what the dietary patterns are among older adults with MCI and dementia. We aimed to identify the dietary patterns of older adults with MCI and dementia living in Yucatan, Mexico.MethodsA cross-sectional study was carried out among 39 patients as controls and 34 individuals as cases (MCI and dementia). A food frequency questionnaire collected diet information, anthropometric and clinical parameters, and lifestyle characteristics. The dietary patterns were evaluated through Partial Least-Squares Discriminant Analysis (PLS-DA).ResultsThe food groups that showed discrimination between groups and were classified into the dietary patterns of MCI and dementia individuals were “pastries and cookies,” “soups,” and “legumes.” The dietary pattern of older adults without cognitive impairment was characterized by “nuts and seeds,” “candies,” “vegetables,” “coffee and tea,” and “water.” The consumption of “pastries and cookies” showed an increasing correlation with serum insulin levels (r = 0.36, p = 0.01), and “soups” showed an inverse correlation with total cholesterol levels (r = −0.36, p = 0.02) in patients with MCI and dementia. In controls, there is a positive correlation between the consumption of “nuts and seeds” (r = 0.333, p = 0.01) and “vegetables” (r = 0.32, p = 0.02) with levels of urea; “coffee and tea” showed a positive association with levels of insulin (r = 0.378, p = 0.05).ConclusionThe dietary pattern of individuals with MCI and dementia has some nutritional deficiencies. Including an adequate intake of vegetables, fruits, and protein could improve the quality of life of subjects living with these conditions in Yucatan, Mexico.
Proteomic analysis of serum small extracellular vesicles identifies diagnostic biomarkers for neuroblastoma
Authors: Cheng Juan , Ji Dongrui , Ma Jing , Zhang Qinghua , Zhang Wanglin , Yang Lin 
Published: August 2024

BackgroundNeuroblastoma (NB) primarily arises in children who are &lt;10 years of age, and originates from developing sympathetic nervous system, which results in tumors in adrenal glands and/or sympathetic ganglia. The diagnosis of NB involves a combination of laboratory and imaging tests, and biopsies. Small extracellular vesicles (sEVs) have gained attention as potential biomarkers for various types of tumors. Here, we performed proteomic analysis of serum sEVs and identified potential biomarkers for NB.MethodsLabel-free proteomics of serum sEVs were performed in the discovery phase. A bulk RNA-seq dataset of NB tissues was used to analyze the association between genes encoding sEVs proteins and prognosis. Potential biomarkers were validated via multiple reaction monitoring (MRM) or western blot analysis in the validation phase. A public single-cell RNA-seq (scRNA-seq) dataset was integrated to analyze the tissue origin of sEVs harboring biomarkers.ResultsA total of 104 differentially expressed proteins were identified in NB patients with label-free proteomics, and 26 potential biomarkers were validated with MRM analysis. Seven proteins BSG, HSP90AB1, SLC44A1, CHGA, ATP6V0A1, ITGAL and SELL showed the strong ability to distinguish NB patients from healthy controls and non-NB patients as well. Integrated analysis of scRNA-seq and sEVs proteomics revealed that these sEVs-derived biomarkers originated from different cell populations in tumor tissues.ConclusionsEVs-based biomarkers may aid the molecular diagnosis of NB, representing an innovative strategy to improve NB detection and management.
Efficacy of PD-1 or PD-L1 inhibitors for the therapy of cervical cancer with varying PD-L1 expression levels: a single-arm meta-analysis
Authors: Yang Jie , Yu Haizan , Zhang Yilei , Zhu Mingli , Zhang Mengyu , Wang Qiming 
Published: August 2024

ObjectiveTo assess the effectiveness and tolerability of both PD-1 and PD-L1 inhibitors in advanced cervical cancer (CC), focusing on varying PD-L1 levels.MethodsA comprehensive exploration was carried out on EMBASE, PubMed, Cochrane Library databases as well as Web of Science up to May 25, 2024, for studies involving advanced CC patients receiving PD-1/PD-L1 inhibitors. Inclusion criteria were studies reporting objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), as well as median overall survival (OS). Data extraction and quality assessment were performed by two reviewers using the JBI Case Series Critical Appraisal Checklist, followed by a meta-analysis via STATA/MP 16.0.ResultsFive eligible studies comprising 223 patients were chosen. ORR and DCR were 42% (95% CI: 17%-66%, P = 0.00) and 70% (95% CI: 22%-117%, P = 0.00), respectively, in the PD-L1 positive patients and were 36% (95% CI: 17%-54%, P = 0.00) and 47% (95% CI: 30%-63%, P = 0.00), respectively, in patients with PD-L1 negativity. For patients exhibiting PD-L1 positivity, median PFS and median OS were 3.98 months (95% CI: 0.80–7.16, P = 0.01) and 11.26 months (95% CI: 3.01–12.58, P = 0.00), respectively.ConclusionWith PD-1/PD-L1 inhibitors, PD-L1 positive CC patients demonstrate superior ORR, DCR, median PFS, and median OS, underscoring PD-L1 as one biomarker for immunotherapy response.
Feasibility and acceptability of remote administration of the cold pressor test
Authors: Salwen-Deremer Jessica K. , Horrigan Jamie M. , Westvold Sarah J. , Haythornthwaite Jennifer A. 
Published: August 2024

ObjectiveQuantitative sensory testing is often used to investigate pain in the context of experimental and clinical research studies. However, many of the devices used for QST protocols are only available in resource rich environments, thereby inadvertently limiting the possible pool of participants. Development of remote protocols for appropriate QST measures has the potential to reduce barriers to participation in research.MethodsParticipants with insomnia and Crohn's disease were recruited as part of a clinical trial. We adapted a remote version of the cold pressor test for use during telehealth-based study assessments. Herein, we present data from the baseline assessments including an assessment of feasibility and acceptability of the task.Results100% of participants (N = 28) were able to complete the remote cold pressor test using a combination of materials from their homes and mailed by the study team. Temperature changes during the test were minimal and fairly evenly balanced between increases and decreases. Correlations between submersion time and both general and disease specific pain trended toward significance.ConclusionsWe demonstrated that a remote version of the cold pressor test is feasible and acceptable in a clinical population and provided a step-by-step protocol for administration to facilitate use in other studies.
Discovery of new antimicrobial thiophene derivatives with activity against drug-resistant Gram negative-bacteria
Authors: Molina-Panadero Irene , Morales-Tenorio Marcos , García-Rubia Alfonso , Ginex Tiziana , Eskandari Khalil , Martinez Ana , Gil Carmen , Smani Younes 
Published: August 2024

Our aim is to identify new small molecules with antimicrobial potential, especially against colistin-resistant (Col-R) Acinetobacter baumannii and Escherichia coli. After initial hits identification by fingerprint similarity, MIC of 24 heterocyclic derivatives for A. baumannii and E. coli reference strains, and bactericidal activity of selected thiophenes against Col-R strains were determined. We analyzed changes in bacterial membrane permeability and the OMPs profile. Additionally, we determined bacterial adherence to host cells and performed molecular docking studies to assess their binding to bacterial targets. The compounds’ MICs ranged from 4 to &gt;64 mg/L. Thiophene derivatives 4, 5 and 8 exhibited MIC50 values between 16 and 32 mg/L for Col-R A. baumannii and 8 and 32 mg/L for Col-R E. coli. The time-kill curve assay demonstrated that thiophenes 4 and 8 had bactericidal effects against Col-R A. baumannii and E. coli. Furthermore, treatment with them resulted in increased membrane permeabilization and reduced adherence of these isolates to host cells. Finally, the docking studies showed a stronger binding affinity to CarO1 and Omp33 of A. baumannii and OmpW and OmpC of E. coli. These findings indicate that thiophene derivatives possess antibacterial activity against Col-R A. baumannii and E. coli, suggesting that they may enhance the repertoire of drug treatments against bacteria.
In vitro evidence of antioxidant and anti-inflammatory effects of a new nutraceutical formulation explains benefits in a clinical setting of COPD patients
Authors: Lazzara Valentina , Pinto Paola , Di Vincenzo Serena , Ferraro Maria , Catalano Filippo , Provinzano Pietro , Pace Elisabetta , Bonsignore Maria Rosaria 
Published: August 2024

Background and Aim:Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC).Methods:PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated.Results:CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life.Conclusion:The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.
The role of GZMA as a target of cysteine and biomarker in Alzheimer’s disease, pelvic organ prolapse, and tumor progression
Authors: Li Yan , Wang Zhuo , Kong Min , Yong Yuanyuan , Yang Xin , Liu Chongdong 
Published: August 2024

Objective: This study aims to investigate how changes in peripheral blood metabolites in Alzheimer’s Disease (AD) patients affect the development of Pelvic Organ Prolapse (POP) using a multi-omics approach. We specifically explore the interactions of signaling pathways, gene expression, and protein-metabolite interactions, with a focus on GZMA and cysteine in age-related diseases.Methods: This study utilized multi-omics analysis, including metabolomics and transcriptomics, to evaluate the perturbations in peripheral blood metabolites and their effect on POP in AD patients. Additionally, a comprehensive pan-cancer and immune infiltration analysis was performed on the core targets of AD combined with POP, exploring their potential roles in tumor progression and elucidating their pharmacological relevance to solid tumors.Results: We identified 47 differential metabolites linked to 9 significant signaling pathways, such as unsaturated fatty acid biosynthesis and amino acid metabolism. A thorough gene expression analysis revealed numerous differentially expressed genes (DEGs), with Gene Set Enrichment Analysis (GSEA) showing significant changes in gene profiles of AD and POP. Network topology analysis highlighted central nodes in the AD-POP co-expressed genes network. Functional analyses indicated involvement in critical biological processes and pathways. Molecular docking studies showed strong interactions between cysteine and proteins PTGS2 and GZMA, and molecular dynamics simulations confirmed the stability of these complexes. In vitro validation demonstrated that cysteine reduced ROS levels and protected cell viability. GZMA was widely expressed in various cancers, associated with immune cells, and correlated with patient survival prognosis.Conclusion: Multi-omics analysis revealed the role of peripheral blood metabolites in the molecular dynamics of AD and their interactions with POP. This study identified potential biomarkers and therapeutic targets, emphasizing the effectiveness of integrative approaches in treating AD and POP concurrently. The findings highlight the need for in-depth research on novel targets and biomarkers to advance therapeutic strategies.
Central and peripheral neuromuscular fatigue following ramp and rapid maximal voluntary isometric contractions
Authors: Dalton Benjamin , Hester Garrett , Alesi Michaela , McDougle Jacob , Cooper Michael , VanDusseldorp Trisha , Buresh Robert , Feito Yuri 
Published: August 2024

IntroductionMaximal voluntary isometric contractions (MVICs) as a fatiguing modality have been widely studied, but little attention has been given to the influence of the rate of torque development. Given the established differences in motor command and neuromuscular activation between ramp and rapid MIVCs, it is likely performance fatigue differs as well as the underlying physiological mechanisms.PurposeTo compare responses for rapid and maximal torque following ramp and rapid MVICs, and the corresponding neuromuscular and corticospinal alterations.MethodsOn separate visits, twelve healthy males (22.8 ± 2.5 years) performed fatiguing intermittent MVICs of the knee extensors with either 2 s (RAMP) or explosive (RAPID) ramp-ups until a 50% reduction in peak torque was achieved. Before and after each condition, maximal and rapid torque measures were determined from an MVIC. Additionally, peripheral (twitch parameters) and central (voluntary activation) fatigue, as well as rapid muscle activation, and cortical-evoked twitch and electromyographic responses were recorded.ResultsMaximal and late-phase rapid torque measures (p ≤ 0.001; ηp 2 = 0.635–0.904) were reduced similarly, but early rapid torque capacity (0–50 ms) (p = 0.003; d = 1.11 vs. p = 0.054; d = 0.62) and rapid muscle activation (p = 0.008; d = 1.07 vs. p = 0.875; d = 0.06) decreased more after RAMP. Changes in peripheral fatigue, as indicated by singlet and doublet contractile parameters (p &lt; 0.001 for all; ηp 2 = 0.752–0.859), and nerve-evoked voluntary activation (p &lt; 0.001; ηp 2= 0.660) were similar between conditions. Corticospinal inhibition (via silent period) was only increased after RAPID (p = 0.007; d = 0.94 vs. p = 0.753; d = 0.09), whereas corticospinal voluntary activation and excitability were unchanged.ConclusionRamp, fatiguing MVICs impaired early rapid torque capacity more than rapid MVICs, and this was accompanied by decrements in rapid muscle activation. Responses for peripheral and central fatigue (nerve and cortical stimulation) were largely similar between conditions, except that rapid MVICs increased corticospinal inhibition.
Allocation of nitrogen and phosphorus in the leaves, stems, and roots of Artemisia: a case study in phylogenetic control
Authors: Jiang Dechun , Gong Haiyang , Niklas Karl J. , Wang Zhiqiang 
Published: August 2024

IntroductionThe allocation of nitrogen (N) and phosphorus (P) among plant organs is an important strategy affecting growth and development as well as ecological processes in terrestrial ecosystems. However, due to lack of systematic investigation data, the allocation strategies of N and P in the three primary plant organs (e.g., leaves, stems and roots) are still unclear.MethodsA total of 912 individuals of 62 Artemisia species were examined across a broad environmental expanse in China, and the N and P concentrations of leaves, stems and roots were measured to explore the allocation strategies in different subgenera, ecosystem types, and local sites.Results and discussionAcross all 62 species, the N vs. P scaling exponents for leaves, stems and roots were 0.67, 0.59 and 0.67, respectively. However, these numerical values differed among subgenera, ecosystem types, and local sites. Overall, the numerical values of N vs. P scaling exponents comply with a 2/3-power function for each Artemisia organ-type reflecting a phylogenetically conserved allocation strategy that has nevertheless diversified with respect to local environmental conditions. These results inform our understanding of N and P stoichiometric patterns and responses to abiotic factors in an ecologically broadly distributed angiosperm genus.