bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease
Authors: Horie Kanta , Salvadó Gemma , Barthélemy Nicolas R. , Janelidze Shorena , Li Yan , He Yingxin , Saef Benjamin , Chen Charles D. , Jiang Hong , Strandberg Olof , Pichet Binette Alexa , Palmqvist Sebastian , Sato Chihiro , Sachdev Pallavi , Koyama Akihiko , Gordon Brian A. , Benzinger Tammie L. S. , Holtzman David M. , Morris John C. , Mattsson-Carlgren Niklas , Stomrud Erik , Ossenkoppele Rik , Schindler Suzanne E. , Hansson Oskar , Bateman Randall J. 
Published: July 2023

AbstractAggregated insoluble tau is one of two defining features of Alzheimer’s disease. Because clinical symptoms are strongly correlated with tau aggregates, drug development and clinical diagnosis need cost-effective and accessible specific fluid biomarkers of tau aggregates; however, recent studies suggest that the fluid biomarkers currently available cannot specifically track tau aggregates. We show that the microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is a new cerebrospinal fluid (CSF) biomarker specific for insoluble tau aggregates and compared it to multiple other phosphorylated tau measures (p-tau181, p-tau205, p-tau217 and p-tau231) in two independent cohorts (BioFINDER-2, n = 448; and Knight Alzheimer Disease Research Center, n = 219). MTBR-tau243 was most strongly associated with tau-positron emission tomography (PET) and cognition, whereas showing the lowest association with amyloid-PET. In combination with p-tau205, MTBR-tau243 explained most of the total variance in tau-PET burden (0.58 ≤ R2 ≤ 0.75) and the performance in predicting cognitive measures (0.34 ≤ R2 ≤ 0.48) approached that of tau-PET (0.44 ≤ R2 ≤ 0.52). MTBR-tau243 levels longitudinally increased with insoluble tau aggregates, unlike CSF p-tau species. CSF MTBR-tau243 is a specific biomarker of tau aggregate pathology, which may be utilized in interventional trials and in the diagnosis of patients. Based on these findings, we propose to revise the A/T/(N) criteria to include MTBR-tau243 as representing insoluble tau aggregates (‘T’).
GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis
Authors: Qu Guoxin , Liu Hui , Li Jin , Huang Siyuan , Zhao Nannan , Zeng Ling , Deng Jin 
Published: July 2023

AbstractSepsis is the uncontrolled reaction of the body to infection-induced inflammation, which results in life-threatening multiple-organ dysfunction (MODS). Although the research on sepsis has advanced significantly in recent years, its pathophysiology remains entirely unknown. Ferroptosis is a new-fashioned type of programmed cell death that may have an impact on sepsis development. However, the precise mechanism still needs to be explored. In this paper, Four pediatric sepsis datasets [training datasets (GSE26378 and GSE26440) and validation datasets (GSE11755 and GSE11281)] were chosen through the GEO (Gene Expression Omnibus) database, and 63 differentially expressions of ferroptosis-relation-genes (DE-FRGs) were eventually discovered using bioinformatics investigation. Functional annotation was performed using GO and KEGG pathway enrichment analysis. Then, four Core-FRGs (FTH1, GPX4, ACSL1, and ACSL6) were extracted after the construction of the protein–protein interaction (PPI) network and the research of the MCODE module. Consequently, Hub-FRG (GPX4) was found using the validation datasets, and correlation exploration of immunity populations (neutrophils, r =  − 0.52; CD8 T-cells, r = 0.43) and immunity checkpoints (CD274, r =  − 0.42) was implemented. The usefulness of GPX4 as a marker in sepsis was assessed in a mouse model of sepsis. The findings demonstrate that GPX4 is a crucial biomarker and a new latent immunotherapy target for the prediction and therapy of pediatric sepsis.
Automated F18-FDG PET/CT image quality assessment using deep neural networks on a latest 6-ring digital detector system
Authors: Schwyzer Moritz , Skawran Stephan , Gennari Antonio G. , Waelti Stephan L. , Walter Joan Elias , Curioni-Fontecedro Alessandra , Hofbauer Marlena , Maurer Alexander , Huellner Martin W. , Messerli Michael 
Published: July 2023

AbstractTo evaluate whether a machine learning classifier can evaluate image quality of maximum intensity projection (MIP) images from F18-FDG-PET scans. A total of 400 MIP images from F18-FDG-PET with simulated decreasing acquisition time (120 s, 90 s, 60 s, 30 s and 15 s per bed-position) using block sequential regularized expectation maximization (BSREM) with a beta-value of 450 and 600 were created. A machine learning classifier was fed with 283 images rated “sufficient image quality” and 117 images rated “insufficient image quality”. The classification performance of the machine learning classifier was assessed by calculating sensitivity, specificity, and area under the receiver operating characteristics curve (AUC) using reader-based classification as the target. Classification performance of the machine learning classifier was AUC 0.978 for BSREM beta 450 and 0.967 for BSREM beta 600. The algorithm showed a sensitivity of 89% and 94% and a specificity of 94% and 94% for the reconstruction BSREM 450 and 600, respectively. Automated assessment of image quality from F18-FDG-PET images using a machine learning classifier provides equivalent performance to manual assessment by experienced radiologists.
The kynurenic acid analog SZR104 induces cytomorphological changes associated with the anti-inflammatory phenotype in cultured microglia
Authors: Szabo Melinda , Lajkó Noémi , Dulka Karolina , Barczánfalvi Gábor , Lőrinczi Bálint , Szatmári István , Mihály András , Vécsei László , Gulya Karoly 
Published: July 2023

AbstractWe previously showed the anti-inflammatory effects of kynurenic acid (KYNA) and its brain-penetrable analog N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-hydroxyquinoline-2-carboxamide (SZR104) both in vivo and in vitro. Here, we identified the cytomorphological effects of KYNA and SZR104 in secondary microglial cultures established from newborn rat forebrains. We quantitatively analyzed selected morphological aspects of microglia in control (unchallenged), lipopolysaccharide (LPS)-treated (challenged), KYNA- or SZR104-treated, and LPS + KYNA or LPS + SZR104-treated cultures. Multicolor immunofluorescence labeling followed by morphometric analysis (area, perimeter, transformation index, lacunarity, density, span ratio, maximum span across the convex hull, hull circularity, hull area, hull perimeter, max/min radii, mean radius, diameter of bounding circle, fractal dimension, roughness, circularity) on binary (digital) silhouettes of the microglia revealed their morphological plasticity under experimental conditions. SZR104 and, to a lesser degree, KYNA inhibited proinflammatory phenotypic changes. For example, SZR104 treatment resulted in hypertrophied microglia characterized by a swollen cell body, enlarged perimeter, increased transformation index/decreased circularity, increased convex hull values (area, perimeter, mean radius, maximum span, diameter of the bounding circle and hull circularity), altered box-counting parameters (such as fractal dimension), and increased roughness/decreased density. Taken together, analysis of cytomorphological features could contribute to the characterization of the anti-inflammatory activity of SZR104 on cultured microglia.
Initial motor skill performance predicts future performance, but not learning
Authors: Abeles Dekel , Herszage Jasmine , Shahar Moni , Censor Nitzan 
Published: July 2023

AbstractPeople show vast variability in skill performance and learning. What determines a person's individual performance and learning ability? In this study we explored the possibility to predict participants’ future performance and learning, based on their behavior during initial skill acquisition. We recruited a large online multi-session sample of participants performing a sequential tapping skill learning task. We used machine learning to predict future performance and learning from raw data acquired during initial skill acquisition, and from engineered features calculated from the raw data. Strong correlations were observed between initial and final performance, and individual learning was not predicted. While canonical experimental tasks developed and selected to detect average effects may constrain insights regarding individual variability, development of novel tasks may shed light on the underlying mechanism of individual skill learning, relevant for real-life scenarios.
Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets
Authors: Kiczak Liliana , Pasławska Urszula , Goździk Waldemar , Adamik Barbara , Zielińska Marzena , Zieliński Stanisław , Nowak Kacper , Płóciennik Michał , Bania Jacek , Tabiś Aleksandra , Nowak Marcin , Pasławski Robert , Frostell Claes 
Published: July 2023

AbstractHospital mortality in sepsis varies between 30–45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1β maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1β. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1β form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1β processing.
Interpretable deep learning for improving cancer patient survival based on personal transcriptomes
Authors: Sun Bo , Chen Liang 
Published: July 2023

AbstractPrecision medicine chooses the optimal drug for a patient by considering individual differences. With the tremendous amount of data accumulated for cancers, we develop an interpretable neural network to predict cancer patient survival based on drug prescriptions and personal transcriptomes (CancerIDP). The deep learning model achieves 96% classification accuracy in distinguishing short-lived from long-lived patients. The Pearson correlation between predicted and actual months-to-death values is as high as 0.937. About 27.4% of patients may survive longer with an alternative medicine chosen by our deep learning model. The median survival time of all patients can increase by 3.9 months. Our interpretable neural network model reveals the most discriminating pathways in the decision-making process, which will further facilitate mechanistic studies of drug development for cancers.
Salivary ultrasonography and histopathologic evaluation of secondary Sjögren’s syndrome in rheumatoid arthritis patients
Authors: Park Youngjae , Oh Minae , Lee Youn Soo , Kim Wan-Uk 
Published: July 2023

AbstractNovel modalities, such as salivary ultrasonography (SGUS) and shear wave elastography (SWE), have previously been introduced to evaluate Sjögren’s syndrome (SS). However, in secondary SS (sSS), the diagnostic performance of SGUS and its relationship with clinicopathological characteristics have not yet been clearly defined. In this study, we aimed to investigate sSS in RA patients using SGUS and SWE and sought to determine its pathological correlations. Thirty-one RA patients who presented with sicca symptoms were included to be evaluated on SS, and were compared with 18 primary SS (pSS) patients. All subjects were assessed through SGUS, SWE, and conventional diagnostic approaches for SS, including minor salivary gland biopsy (MSGB). In SGUS evaluation, two separate scoring systems, suggested by Hocevar and OMERACT, were used. Among 31 RA patients with sicca symptoms, 19 (61.2%) were diagnosed as sSS. Similar to pSS, SGUS showed good diagnostic performance (sensitivity 68.4% and 78.9%, and specificity 91.7% and 75.0% for Hocever and OMERACT, respectively) in differentiating sSS from RA patients with simple sicca symptoms. The sSS and pSS patients exhibited significantly higher lymphoid infiltration areas in MSGB than RA patients without SS. Focus score and lymphoid infiltration areas correlated well with sonographic severity. Severity of fibrosis in MSGB showed better positive correlation with SWE than with SGUS. Similar to pSS, SGUS shows good diagnostic performance for sSS in RA patients. SWE reflects histopathologic chronicity of MSGB well in both pSS and sSS.
Pulmonary rehabilitation improves sleep efficiency measured by actigraphy in poorly sleeping COPD patients
Authors: Gabrovska Maria , Herpeux Audrey , Bruyneel Anne-Violette , Bruyneel Marie 
Published: July 2023

AbstractChronic insomnia is reported by up to 50% of chronic obstructive pulmonary disease (COPD) patients. This may be attributable to several factors including nocturnal dyspnea, reduced physical activity, and less time outside. Pulmonary rehabilitation (PR) is recommended in COPD to improve both physical and psychological conditioning. The aim of this study was to assess the effect of PR on sleep efficiency (SE, measured by actigraphy) in COPD patients. COPD eligible for PR were prospectively included. Baseline and post PR (30 sessions) assessments included incremental and maximal exercise testing, 6-min walking distance test (6MWT), actigraphy, and questionnaires [Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety Depression scale, St George Respiratory, and modified Medical Research Council dyspnea scale]. Sixty-one patients were included, and 31 patients completed the study protocol (68% of males, age 63 ± 9 y, FEV1 44.2 ± 12.3%). After PR, SE remained unchanged, p = 0.07, as well as PSQI score (p = 0.22), despite improvements in exercise capacity (incremental exercise test, 6MWT) and dyspnea. However, SE improved significantly in the poor sleeper subgroup (SE < 85%, n = 24, p = 0.02), whereas the PSQI remained unchanged. The present study shows, in COPD patients included in a PR program, that improvement in exercise capacity was disappointingly not associated with a better SE assessed by actigraphy. Subjective sleep quality was also unchanged at the end of PR program. However, SE improved significantly in the poor sleeper subgroup (SE < 85%). Further studies are required to better characterize the origin of sleep disturbances in COPD and the potential benefit of some (non-)pharmacologic interventions.
Contrast-free ultrasound imaging for blood flow assessment of the lower limb in patients with peripheral arterial disease: a feasibility study
Authors: Sabeti Soroosh , Nayak Rohit , McBane Robert D. , Fatemi Mostafa , Alizad Azra 
Published: July 2023

AbstractWhile being a relatively prevalent condition particularly among aging patients, peripheral arterial disease (PAD) of lower extremities commonly goes undetected or misdiagnosed due to its symptoms being nonspecific. Additionally, progression of PAD in the absence of timely intervention can lead to dire consequences. Therefore, development of non-invasive and affordable diagnostic approaches can be highly beneficial in detection and treatment planning for PAD patients. In this study, we present a contrast-free ultrasound-based quantitative blood flow imaging technique for PAD diagnosis. The method involves monitoring the variations of blood flow in the calf muscle in response to thigh-pressure-cuff-induced occlusion. Four quantitative metrics are introduced for analysis of these variations. These metrics include post-occlusion to baseline flow intensity variation (PBFIV), total response region (TRR), Lag0 response region (L0RR), and Lag4 (and more) response region (L4 + RR). We examine the feasibility of this method through an in vivo study consisting of 14 PAD patients with abnormal ankle-brachial index (ABI) and 8 healthy volunteers. Ultrasound data acquired from 13 legs in the patient group and 13 legs in the healthy group are analyzed. Out of the four utilized metrics, three exhibited significantly different distributions between the two groups (p-value < 0.05). More specifically, p-values of 0.0015 for PBFIV, 0.0183 for TRR, and 0.0048 for L0RR were obtained. The results of this feasibility study indicate the diagnostic potential of the proposed method for the detection of PAD.
Trends in tropical forest loss and the social value of emission reductions
Authors: Knoke Thomas , Hanley Nick , Roman-Cuesta Rosa Maria , Groom Ben , Venmans Frank , Paul Carola 
Published: July 2023

AbstractReducing global forest losses is essential to mitigate climate change and its associated social costs. Multiple market and non-market factors can enhance or reduce forest loss. Here, to understand the role of non-market factors (for example, policies, climate anomalies or conflicts), we can compare observed trends to a reference (expected) scenario that excludes non-market factors. We define an expected scenario by simulating land-use decisions solely driven by market prices, productivities and presumably plausible decision-making. The land-use allocation model considers economic profits and uncertainties as incentives for forest conversion. We compare reference forest losses in Brazil, the Democratic Republic of Congo and Indonesia (2000–2019) with observed forest losses and assign differences from non-market factors. Our results suggest that non-market factors temporarily lead to lower-than-expected forest losses summing to 11.1 million hectares, but also to phases with higher-than-expected forest losses of 11.3 million hectares. Phases with lower-than-expected forest losses occurred earlier than those with higher-than-expected forest losses. The damages avoided by delaying emissions that would otherwise have occurred represent a social value of US$61.6 billion (as of the year 2000). This result shows the economic importance of forest conservation efforts in the tropics, even if reduced forest loss might be temporary and reverse over time.
Soil moisture−atmosphere feedbacks have triggered the shifts from drought to pluvial conditions since 1980
Authors: Qing Yamin , Wang Shuo , Yang Zong-Liang , Gentine Pierre 
Published: July 2023

AbstractDrought and pluvial transitions have attracted widespread attention. However, the dynamic evolution and underlying mechanisms of drought and pluvial transitions remain poorly understood. Here, we demonstrate that there is a significant increase in the occurrence of drought and pluvial transitions (0.24−1.03% per year) globally during 1980−2020. We use convergent cross mapping to detect causal relationships between time series variables in the climate system and find that drought and pluvial transitions can be explained by an indirect transitive causal chain. Specifically, the soil moisture−latent heat flux−precipitation causal chain is likely to trigger the rainfall following the dryness in humid regions where enhanced evaporation increases the actual atmospheric moisture favoring the pluvial occurrence. By contrast, the soil moisture−moisture convergence−precipitation causal chain enhances the post-drought rainfall in arid regions due to atmospheric circulation dynamics. Our results indicate that land−atmosphere feedbacks play an important role in triggering the drought-pluvial shift in a changing climate.
Outlining cardiac ion channel protein interactors and their signature in the human electrocardiogram
Authors: Maurya Svetlana , Mills Robert W. , Kahnert Konstantin , Chiang David Y. , Bertoli Giorgia , Lundegaard Pia R. , Duran Marta Perez-Hernandez , Zhang Mingliang , Rothenberg Eli , George Alfred L. , MacRae Calum A. , Delmar Mario , Lundby Alicia 
Published: July 2023

AbstractProtein–protein interactions are essential for normal cellular processes and signaling events. Defining these interaction networks is therefore crucial for understanding complex cellular functions and interpretation of disease-associated gene variants. We need to build a comprehensive picture of the interactions, their affinities and interdependencies in the specific organ to decipher hitherto poorly understood signaling mechanisms through ion channels. Here we report the experimental identification of the ensemble of protein interactors for 13 types of ion channels in murine cardiac tissue. Of these, we validated the functional importance of ten interactors on cardiac electrophysiology through genetic knockouts in zebrafish, gene silencing in mice, super-resolution microscopy and patch clamp experiments. Furthermore, we establish a computational framework to reconstruct human cardiomyocyte ion channel networks from deep proteome mapping of human heart tissue and human heart single-cell gene expression data. Finally, we integrate the ion channel interactome with human population genetics data to identify proteins that influence the electrocardiogram (ECG). We demonstrate that the combined channel network is enriched for proteins influencing the ECG, with 44% of the network proteins significantly associated with an ECG phenotype. Altogether, we define interactomes of 13 major cardiac ion channels, contextualize their relevance to human electrophysiology and validate functional roles of ten interactors, including two regulators of the sodium current (epsin-2 and gelsolin). Overall, our data provide a roadmap for our understanding of the molecular machinery that regulates cardiac electrophysiology.
Impact of chemicals and physical stressors on horizontal gene transfer via natural transformation
Authors: Al-Gashgari Bothayna , Mantilla-Calderon David , Wang Tiannyu , de los Angeles Gomez Maria , Baasher Fras , Daffonchio Daniele , Laleg-Kirati Taous-Meriem , Hong Pei-Ying 
Published: July 2023

AbstractContaminants in the environment can increase natural transformation rates in bacteria. However, the co-occurrence of a large suite of contaminants may result in final transformation rates that are not based on the geometric addition of individual responses. Here we show that the combination of different chemicals and physical stressors results in natural transformation that do not always follow geometric additive responses. Specifically, some combinations increased transformation rates synergistically, while others decreased rates antagonistically. Unpredictability in the natural transformation outcome was also observed when Acinetobacter baylyi ADP1 was exposed to chlorinated reclaimed water. We determined that the stimulatory effect of contaminants on natural transformation can be compensated when extracellular DNA concentrations fall below 0.1 ng l−1 per 2 × 107 cells. Thus, wastewater treatment process that can minimize concentrations of extracellular DNA and cell load would be a key intervention strategy to minimize natural transformation frequency arising from the use of treated wastewater.