bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of immune cell profiles associated with heatstroke, sepsis, or cardiopulmonary bypass: Study protocol for an exploratory, case-control study trial
Authors: Wu Juan , Yang Sha , Wang Tingting , Wu Qinjuan , Liao Xinyi , Yao Rong , Du Lei 
Published: April 2023

IntroductionHeatstroke is a life-threatening illness involving extreme hyperthermia and multi-organ failure, and it is associated with high mortality. The immune profiles of heatstroke have not been fully elucidated, and diagnostic and prognostic biomarkers of heatstroke are lacking. This study will analyze immune profiles in heatstroke patients as they differ from profiles in patients with sepsis or aseptic inflammation patients in order to identify diagnostic and prognostic biomarkers.MethodsThis exploratory, case–control study will recruit patients with heatstroke, patients with sepsis, patients undergoing cardiopulmonary bypass as well as healthy controls at West China Hospital of Sichuan University from 1 January 2023 to 31 October 2023. The four cohorts will be profiled at one time point in terms of lymphocytes, monocytes, natural killer cells, and granulocytes using flow cytometry, and cell populations will be visualized in two dimensions using t-SNE and UMAP, then clustered using PhenoGraph and FlowSOM. Gene expression in the specific immune cell populations will also be compared across the four cohorts, as will levels of plasma cytokines using enzyme-linked immunosorbent assays. Outcomes in the cohorts will be monitored during 30-day follow-up.DiscussionThis trial is, to our knowledge, the first attempt to improve the diagnosis of heatstroke and prediction of prognosis based on immune cell profiles. The study is also likely to generate new insights into immune responses during heatstroke, which may help clarify the disease process and lay the foundation for immunotherapies.
Identification of novel pathways and immune profiles related to sarcopenia
Authors: Abdelrahman Zeinab , Wang Xiaosheng , Wang Daming , Zhang Tianfang , Zhang Yue , Wang Xuhua , Chen Zuobing 
Published: April 2023

IntroductionSarcopenia is a progressive deterioration of skeletal muscle mass strength and function.MethodsTo uncover the underlying cellular and biological mechanisms, we studied the association between sarcopenia's three stages and the patient's ethnicity, identified a gene regulatory network based on motif enrichment in the upregulated gene set of sarcopenia, and compared the immunological landscape among sarcopenia stages.ResultsWe found that sarcopenia (S) was associated with GnRH, neurotrophin, Rap1, Ras, and p53 signaling pathways. Low muscle mass (LMM) patients showed activated pathways of VEGF signaling, B-cell receptor signaling, ErbB signaling, and T-cell receptor signaling. Low muscle mass and physical performance (LMM_LP) patients showed lower enrichment scores in B-cell receptor signaling, apoptosis, HIF-1 signaling, and the adaptive immune response pathways. Five common genes among DEGs and the elastic net regression model, TTC39DP, SLURP1, LCE1C, PTCD2P1, and OR7E109P, were expressed between S patients and healthy controls. SLURP1 and LCE1C showed the highest expression levels among sarcopenic Chinese descent than Caucasians and Afro-Caribbeans. Gene regulatory analysis of top upregulated genes in S patients yielded a top-scoring regulon containing GATA1, GATA2, and GATA3 as master regulators and nine predicted direct target genes. Two genes were associated with locomotion: POSTN and SLURP1. TTC39DP upregulation was associated with a better prognosis and stronger immune profile in S patients. The upregulation of SLURP1 and LCE1C was associated with a worse prognosis and weaker immune profile.ConclusionThis study provides new insight into sarcopenia's cellular and immunological prospects and evaluates the age and sarcopenia-related modifications of skeletal muscle.
The detection and prediction of surgical site infections using multi-modal sensors and machine learning: Results in an animal model
Authors: Hughes Charmayne Mary Lee , Jeffers Andrew , Sethuraman Arun , Klum Michael , Tan Milly , Tan Valerie 
Published: April 2023

IntroductionSurgical Site Infection (SSI) is a common healthcare-associated infection that imposes a considerable clinical and economic burden on healthcare systems. Advances in wearable sensors and digital technologies have unlocked the potential for the early detection and diagnosis of SSI, which can help reduce this healthcare burden and lower SSI-associated mortality rates.MethodsIn this study, we evaluated the ability of a multi-modal bio-signal system to predict current and developing superficial incisional infection in a porcine model infected with Methicillin Susceptible Staphylococcus Aureus (MSSA) using a bagged, stacked, and balanced ensemble logistic regression machine learning model.ResultsResults demonstrated that the expression levels of individual biomarkers (i.e., peri-wound tissue oxygen saturation, temperature, and bioimpedance) differed between non-infected and infected wounds across the study period, with cross-correlation analysis indicating that a change in bio-signal expression occurred 24 to 31 hours before this change was reflected by clinical wound scoring methods employed by trained veterinarians. Moreover, the multi-modal ensemble model indicated acceptable discriminability to detect the presence of a current superficial incisional SSI (AUC = 0.77), to predict an SSI 24 hours in advance of veterinarian-based SSI diagnosis (AUC = 0.80), and to predict an SSI 48 hours in advance of veterinarian-based SSI diagnosis (AUC = 0.74).DiscussionIn sum, the results of the current study indicate that non-invasive multi-modal sensor and signal analysis systems have the potential to detect and predict superficial incisional SSIs in porcine subjects under experimental conditions.
PHT427 as an effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitor restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1
Authors: Li Xiaohui , Wang Qian , Zheng Ji , Guan Yan , Liu Chennan , Han Jiangxue , Liu Sihan , Liu Tianjun , Xiao Chunling , Wang Xiao , Liu Yishuang 
Published: April 2023

IntroductionWith the increasingly serious problem of bacterial drug resistance caused by NDM-1, it is an important strategy to find effective inhibitors to assist β-lactam antibiotic treatment against NDM-1 resistant bacteria. In this study, PHT427 (4-dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide) was identified as a novel NDM-1 inhibitor and restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1.MethodsWe used a high throughput screening model to find NDM-1 inhibitor in the library of small molecular compounds. The interaction between the hit compound PHT427 and NDM-1 was analyzed by fluorescence quenching, surface plasmon resonance (SPR) assay, and molecular docking analysis. The efficacy of the compound in combination with meropenem was evaluated by determining the FICIs of Escherichia coli BL21(DE3)/pET30a(+)-blaNDM–1 and Klebsiella pneumoniae clinical strain C1928 (producing NDM-1). In addition, the mechanism of the inhibitory effect of PHT427 on NDM-1 was studied by site mutation, SPR, and zinc supplementation assays.ResultsPHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 μmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-blaNDM–1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. The mutation of Asn220 and Gln123 abolished the affinity of NDM-1 by PHT427 via SPR assay.DiscussionThis is the first report that PHT427 is a promising lead compound against carbapenem-resistant bacteria and it merits chemical optimization for drug development.
Network analysis of the associations between personality traits, cognitive functioning, and inflammatory markers in elderly individuals without dementia
Authors: Bastelica Thomas , Lespine Louis-Ferdinand , Rouch Isabelle , Tadri Myriam , Dorey Jean-Michel , Strippoli Marie-Pierre F. , d'Amato Thierry , von Gunten Armin , Preisig Martin , Rey Romain 
Published: April 2023

IntroductionLower cognitive functioning in old age has been associated with personality traits or systemic inflammatory markers. Associations have also been found between personality traits and inflammatory markers. However, no study has explored the inter-relationships between these three components simultaneously. The present study aims to better understand the inter-relationships among personality traits, inflammatory markers, and cognitive performance in elderly individuals without dementia.MethodsThis study utilizes a network analysis approach, a statistical method that allows visualization of the data’s unique pairwise associations. We performed a cross-sectional analysis on 720 elderly individuals without dementia, using data from Colaus|PsyColaus, a population-based study conducted in Lausanne, Switzerland. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to assess personality traits, and interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were used as peripheral inflammatory markers. Cognitive domains were investigated using the Mini-Mental State Examination (MMSE), the Verbal Fluency Test, the Stroop Test, the DO40, and the Free and Cued Selective Reminding (FCSR) test.ResultsOpenness was associated with verbal fluency and Agreeableness with immediate free recall. In contrast, no association between inflammatory markers and personality traits or cognition was identified.DiscussionIn elderly individuals without dementia, a high level of Openness or Agreeableness was associated with executive functioning/semantic memory and episodic memory, respectively.
Hub structure in functional network of EEG signals supporting high cognitive functions in older individuals
Authors: Tobe Mayuna , Nobukawa Sou , Mizukami Kimiko , Kawaguchi Megumi , Higashima Masato , Tanaka Yuji , Yamanishi Teruya , Takahashi Tetsuya 
Published: April 2023

IntroductionMaintaining high cognitive functions is desirable for “wellbeing” in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the “hub” node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals.MethodTo test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score.ResultsWe found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network.DiscussionThe hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals.
Influence of goals on modular brain network organization during working memory
Authors: Gallen Courtney L. , Hwang Kai , Chen Anthony J.-W. , Jacobs Emily G. , Lee Taraz G. , D’Esposito Mark 
Published: April 2023

IntroductionTop-down control underlies our ability to attend relevant stimuli while ignoring irrelevant, distracting stimuli and is a critical process for prioritizing information in working memory (WM). Prior work has demonstrated that top-down biasing signals modulate sensory-selective cortical areas during WM, and that the large-scale organization of the brain reconfigures due to WM demands alone; however, it is not yet understood how brain networks reconfigure between the processing of relevant versus irrelevant information in the service of WM.MethodsHere, we investigated the effects of task goals on brain network organization while participants performed a WM task that required participants to detect repetitions (e.g., 0-back or 1-back) and had varying levels of visual interference (e.g., distracting, irrelevant stimuli). We quantified changes in network modularity–a measure of brain sub-network segregation–that occurred depending on overall WM task difficulty as well as trial-level task goals for each stimulus during the task conditions (e.g., relevant or irrelevant).ResultsFirst, we replicated prior work and found that whole-brain modularity was lower during the more demanding WM task conditions compared to a baseline condition. Further, during the WM conditions with varying task goals, brain modularity was selectively lower during goal-directed processing of task-relevant stimuli to be remembered for WM performance compared to processing of distracting, irrelevant stimuli. Follow-up analyses indicated that this effect of task goals was most pronounced in default mode and visual sub-networks. Finally, we examined the behavioral relevance of these changes in modularity and found that individuals with lower modularity for relevant trials had faster WM task performance.DiscussionThese results suggest that brain networks can dynamically reconfigure to adopt a more integrated organization with greater communication between sub-networks that supports the goal-directed processing of relevant information and guides WM.
Secondary hyperperfusion injury following surgical evacuation for acute isolated epidural hematoma with concurrent cerebral herniation
Authors: Huang Wei , Li Jun , Wang Wen-hao , Zhang Yuan , Luo Fei , Hu Lian-Shui , Lin Jun-Ming 
Published: April 2023

ObjectiveHemispherical cerebral swelling or even encephalocele after head trauma is a common complication and has been well elucidated previously. However, few studies have focused on the secondary brain hemorrhage or edema occurring regionally but not hemispherically in the cerebral parenchyma just underneath the surgically evacuated hematoma during or at a very early stage post-surgery.MethodsIn order to explore the characteristics, hemodynamic mechanisms, and optimized treatment of a novel peri-operative complication in patients with isolated acute epidural hematoma (EDH), clinical data of 157 patients with acute-isolated EDH who underwent surgical intervention were reviewed retrospectively. Risk factors including demographic characteristics, admission Glasgow Coma Score, preoperative hemorrhagic shock, anatomical location, and morphological parameters of epidural hematoma, as well as the extent and duration of cerebral herniation on physical examination and radiographic evaluation were considered.ResultsIt suggested that secondary intracerebral hemorrhage or edema was determined in 12 of 157 patients within 6 h after surgical hematoma evacuation. It was featured by remarkable, regional hyperperfusion on the computed tomography (CT) perfusion images and associated with a relatively poor neurological prognosis. In addition to concurrent cerebral herniation, which was found to be a prerequisite for the development of this novel complication, multivariate logistic regression further showed four independent risk factors contributing to this type of secondary hyperperfusion injury: cerebral herniation that lasted longer than 2 h, hematomas that were located in the non-temporal region, hematomas that were thicker than 40 mm, and hematomas occurring in pediatric and elderly patients.ConclusionSecondary brain hemorrhage or edema occurring within an early perioperative period of hematoma-evacuation craniotomy for acute-isolated EDH is a rarely described hyperperfusion injury. Because it plays an important prognostic influence on patients’ neurological recovery, optimized treatment should be given to block or reduce the consequent secondary brain injuries.
Incomplete spectrum QSM using support information
Authors: Fuchs Patrick , Shmueli Karin 
Published: April 2023

IntroductionReconstructing a bounded object from incomplete k-space data is a well posed problem, and it was recently shown that this incomplete spectrum approach can be used to reconstruct undersampled MRI images with similar quality to compressed sensing approaches. Here, we apply this incomplete spectrum approach to the field-to-source inverse problem encountered in quantitative magnetic susceptibility mapping (QSM). The field-to-source problem is an ill-posed problem because of conical regions in frequency space where the dipole kernel is zero or very small, which leads to the kernel's inverse being ill-defined. These “ill-posed” regions typically lead to streaking artifacts in QSM reconstructions. In contrast to compressed sensing, our approach relies on knowledge of the image-space support, more commonly referred to as the mask, of our object as well as the region in k-space with ill-defined values. In the QSM case, this mask is usually available, as it is required for most QSM background field removal and reconstruction methods.MethodsWe tuned the incomplete spectrum method (mask and band-limit) for QSM on a simulated dataset from the most recent QSM challenge and validated the QSM reconstruction results on brain images acquired in five healthy volunteers, comparing incomplete spectrum QSM to current state-of-the art-methods: FANSI, nonlinear dipole inversion, and conventional thresholded k-space division.ResultsWithout additional regularization, incomplete spectrum QSM performs slightly better than direct QSM reconstruction methods such as thresholded k-space division (PSNR of 39.9 vs. 39.4 of TKD on a simulated dataset) and provides susceptibility values in key iron-rich regions similar or slightly lower than state-of-the-art algorithms, but did not improve the PSNR in comparison to FANSI or nonlinear dipole inversion. With added (ℓ1-wavelet based) regularization the new approach produces results similar to compressed sensing based reconstructions (at sufficiently high levels of regularization).DiscussionIncomplete spectrum QSM provides a new approach to handle the “ill-posed” regions in the frequency-space data input to QSM.
Subcortical volumes in cerebral amyloid angiopathy compared with Alzheimer’s disease and controls
Authors: Chen Chih-Hao , Khnaijer Mary Klir , Beaudin Andrew E. , McCreary Cheryl R. , Gee Myrlene , Saad Feryal , Frayne Richard , Ismail Zahinoor , Pike G. Bruce , Camicioli Richard , Smith Eric E. 
Published: April 2023

BackgroundPrevious reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy.MethodsThe study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity.ResultsParticipants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups.ConclusionIn contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.
Astaxanthin From Haematococcus pluvialis Prevents High-Fat Diet-Induced Hepatic Steatosis and Oxidative Stress in Mice by Gut-Liver Axis Modulating Properties
Authors: Wang Meng , Xu Wenxin , Yu Jie , Liu Yingying , Ma Haotian , Ji Chunli , Zhang Chunhui , Xue Jinai , Li Runzhi , Cui Hongli 
Published: April 2023

Graphical AbstractAstaxanthin (ATX) preventive effects on lipid metabolic disorders, hepatic steatosis, and oxidative stress in high-fat diet-induced mice.