julilili42/papers huggingface dataset:
Persistent immune abnormalities discriminate post-COVID syndrome from convalescence
2023-05-05

Abstract Innate lymphoid cells (ILCs) are key organizers of tissue immune responses and regulate tissue development, repair, and pathology. Persistent clinical sequelae beyond 12 weeks following acute COVID-19 disease, named post-COVID syndrome (PCS), are increasingly recognized in convalescent individuals. ILCs have been associated with the severity of COVID-19 symptoms but their role in the development of PCS remains poorly defined. Here we used multiparametric immune phenotyping, finding expanded circulating ILC precursors (ILCPs) and concurrent decreased group 2 innate lymphoid cells (ILC2s) in PCS patients compared to well-matched convalescent control groups at &gt; 3 months after infection. Patients with PCS showed elevated expression of chemokines and cytokines associated with trafficking of immune cells (CCL19/MIP-3b, FLT3-ligand), endothelial inflammation and repair (CXCL1, EGF, RANTES, IL1RA, PDGF-AA). These results define immunological parameters associated with PCS and might help find biomarkers and disease-relevant therapeutic strategies.
Dark-Blood Late Gadolinium Enhancement MRI Is Noninferior to Bright-Blood LGE in Non-Ischemic Cardiomyopathies
2023-05-05

(1) Background and Objectives: Dark-blood late gadolinium enhancement has been shown to be a reliable cardiac magnetic resonance (CMR) method for assessing viability and depicting myocardial scarring in ischemic cardiomyopathy. The aim of this study was to evaluate dark-blood LGE imaging compared with conventional bright-blood LGE for the detection of myocardial scarring in non-ischemic cardiomyopathies. (2) Materials and Methods: Patients with suspected non-ischemic cardiomyopathy were prospectively enrolled in this single-centre study from January 2020 to March 2023. All patients underwent 1.5 T CMR with both dark-blood and conventional bright-blood LGE imaging. Corresponding short-axis stacks of both techniques were analysed for the presence, distribution, pattern, and localisation of LGE, as well as the quantitative scar size (%). (3) Results: 343 patients (age 44 ± 17 years; 124 women) with suspected non-ischemic cardiomyopathy were examined. LGE was detected in 123 of 343 cases (36%) with excellent inter-reader agreement (κ 0.97–0.99) for both LGE techniques. Dark-blood LGE showed a sensitivity of 99% (CI 98–100), specificity of 99% (CI 98–100), and an accuracy of 99% (CI 99–100) for the detection of non-ischemic scarring. No significant difference in total scar size (%) was observed. Dark-blood imaging with mean 5.35 ± 4.32% enhanced volume of total myocardial volume, bright-blood with 5.24 ± 4.28%, p = 0.84. (4) Conclusions: Dark-blood LGE imaging is non-inferior to conventional bright-blood LGE imaging in detecting non-ischemic scarring. Therefore, dark-blood LGE imaging may become an equivalent method for the detection of both ischemic and non-ischemic scars.
Aconitum carmichaelii triggers neurotoxicity and Parkinson‐like symptoms through initiation of ROS‐mitochondrial apoptosis and the Nox5/DJ‐1 signaling pathway
2023-05-06

Abstract Background Aconitum carmichaelii , the mother root of Aconitum , has a long‐applied history for treating many diseases in China. Increased use of it has prompted significant concerns regarding its extensive cardiotoxicity and neurotoxicity. The molecular mechanisms underlying A. carmichaelii ‐induced neurotoxicity are poorly understood. Methods We took advantage of the zebrafish model to investigate the neurotoxic mechanism of A. carmichaelii . In addition to the behavior and neuronal activity testing, gene expression of neuronal oxidative stress, and apoptosis levels were also analyzed. Results In contrast to the excitatory effect of low‐dose A. carmichaelii decoction, hypoactivity of locomotor behavior, and neural activity, especially telencephalon, were detected in the 20 mg/mL group. High doses of A. carmichaelii induced excessive ROS by downregulating DJ‐1 and activating Nox5 , and further triggered cell apoptosis through the bax/bcl2a‐caspase‐9 pathway in zebrafish larva. Mitochondrial protection‐related genes PinK1 and Parkin were upregulated to protect against mitochondrial dysfunction during cellular stress. The ROS scavenger‐NAC significantly alleviated neurotoxicity in the 20 mg/mL group. Conclusion The study reveals the potential mechanism of A. carmichaelii ‐induced neurotoxicity and provides new insights into a significant risk marker of A. carmichaelii poisoning.
Machine learning identifies multi-parametric functional PET/MR imaging cluster to predict radiation resistance in preclinical head and neck cancer models
2023-05-06

Abstract Purpose Tumor hypoxia and other microenvironmental factors are key determinants of treatment resistance. Hypoxia positron emission tomography (PET) and functional magnetic resonance imaging (MRI) are established prognostic imaging modalities to identify radiation resistance in head-and-neck cancer (HNC). The aim of this preclinical study was to develop a multi-parametric imaging parameter specifically for focal radiotherapy (RT) dose escalation using HNC xenografts of different radiation sensitivities. Methods A total of eight human HNC xenograft models were implanted into 68 immunodeficient mice. Combined PET/MRI using dynamic [18F]-fluoromisonidazole (FMISO) hypoxia PET, diffusion-weighted (DW), and dynamic contrast-enhanced MRI was carried out before and after fractionated RT (10 × 2 Gy). Imaging data were analyzed on voxel-basis using principal component (PC) analysis for dynamic data and apparent diffusion coefficients (ADCs) for DW-MRI. A data- and hypothesis-driven machine learning model was trained to identify clusters of high-risk subvolumes (HRSs) from multi-dimensional (1-5D) pre-clinical imaging data before and after RT. The stratification potential of each 1D to 5D model with respect to radiation sensitivity was evaluated using Cohen’s d -score and compared to classical features such as mean/peak/maximum standardized uptake values (SUV mean/peak/max ) and tumor-to-muscle-ratios (TMR peak/max ) as well as minimum/valley/maximum/mean ADC. Results Complete 5D imaging data were available for 42 animals. The final preclinical model for HRS identification at baseline yielding the highest stratification potential was defined in 3D imaging space based on ADC and two FMISO PCs ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>&lt;</mml:mo> <mml:mn>0.001</mml:mn> </mml:mrow> </mml:math> ). In 1D imaging space, only clusters of ADC revealed significant stratification potential ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>=</mml:mo> <mml:mn>0.002</mml:mn> </mml:mrow> </mml:math> ). Among all classical features, only ADC valley showed significant correlation to radiation resistance ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>=</mml:mo> <mml:mn>0.006</mml:mn> </mml:mrow> </mml:math> ). After 2 weeks of RT, FMISO_c1 showed significant correlation to radiation resistance ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>=</mml:mo> <mml:mn>0.04</mml:mn> </mml:mrow> </mml:math> ). Conclusion A quantitative imaging metric was described in a preclinical study indicating that radiation-resistant subvolumes in HNC may be detected by clusters of ADC and FMISO using combined PET/MRI which are potential targets for future functional image-guided RT dose-painting approaches and require clinical validation.
In vitro and in vivo effects of zoledronic acid on senescence and senescence-associated secretory phenotype markers
2023-05-07

In addition to reducing fracture risk, zoledronic acid has been found in some studies to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple co-morbidities, the non-skeletal actions of zoledronic acid could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype [SASP]) actions. To test this, we first performed <i>in vitro</i> senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronic acid killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronic acid or vehicle for 8 weeks, zoledronic acid significantly reduced circulating SASP factors, including CCL7, IL-1β, TNFRSF1A, and TGFβ1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronic acid demonstrated a significant downregulation of senescence/SASP genes (SenMayo). To establish that these cells are potential senolytic/senomorphic targets of zoledronic acid, we used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronic acid significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. Collectively, our findings demonstrate that zoledronic acid has senolytic effects <i>in vitro</i> and modulates senescence/SASP biomarkers <i>in vivo</i>. These data point to the need for additional studies testing zoledronic acid and/or other bisphosphonate derivatives for senotherapeutic efficacy.
In closed wedge distal femur osteotomies for correction of valgus malalignment overcorrection of mLDFA should be avoided
2023-05-07

Abstract Purpose The purpose of the study was to investigate the influence of the mLDFA (mechanical lateral distal femur angle) as a parameter in varus realignment osteotomies for valgus deformities of the knee. We hypothesized that joint line obliquity with mLDFA &gt; 90° after distal femur osteotomy (DFO) is associated with inferior clinical outcome. Methods In a retrospective study, a total of 52 patients with isolated femoral valgus deformities were included in the study. The mean postoperative follow‐up was 70.5 (SD 33.3) months (standard deviation SD±33.3). In all patients, a distal femur osteotomy was performed. A clinical examination and survey of questionnaires was conducted with the HSS (Hospital for Special Surgery), LG (Lysholm‐Gilquist), and KOOS (Knee Injury and Osteoarthritis Outcome Score) scores. Several radiological parameters were assessed on long‐standing x‐rays: mechanical tibio‐femoral angle (mTFA), mLDFA, mechanical medial proximal tibia angle (mMPTA), joint‐line convergence angle (JLCA). The t test was used for normally distributed data. The Mann‐Whitney U test was performed in non‐normally distributed data. Results The mLDFA was 84.9° (SD±2.3) preop and changed to 91.9° (SD±3, 22.9) postop. The mTFA (mechanical tibio‐femoral angle) was 5.2° (SD±2.9°) preop and − 1.8° (SD±2.9) postop demonstrating a difference of 6.7°. For analysis, the data was divided into two groups based on postop mLDFA. Group 1: mLDFA ≤ 90°; Group 2: &gt; 90°. Postoperatively, a mean mLDFA of 88.6° (SD±1.4°) was measured in group 1 and 93.9° (SD±2.1) in group 2. The change in mLDFA was 4.7° (SD±1.6) in group 1 and 8.4° (SD±2.8) in group 2. Preoperatively, the mTFA was 4.8° (SD±1.9) in group 1 and 5.5° (SD±3.3) in group 2. Postoperatively, the mTFA decreased in group 1 by 4.8° (SD±2.3) to − 0.1° (SD±2.1). In group 2, the mTFA decreased by 8.2° (SD±3.8) to − 2.8° (SD±2.9). Regarding the HSS, group 1 showed a 10.4 points better score than group 2 ( p &lt;0.01). Also, regarding the Lysholm, a significant difference of 16.9 points was found ( p &lt;0.01). Conclusion Correction of valgus knees using closed wedge DFO leads to good clinical results. A postoperative mLDFA of 85–90° results in superior clinical outcome compared to mLDFA &gt; 90°. Joint‐line obliquity should be avoided using double level osteotomy, if needed. Level of evidence III.
Robot‐assisted stereoencephalography vs subdural electrodes in the evaluation of temporal lobe epilepsy
2023-05-07

Abstract Objective Invasive video‐electroencephalography (iVEEG) is the gold standard for evaluation of refractory temporal lobe epilepsy before second stage resective surgery (SSRS). Traditionally, the presumed seizure onset zone (SOZ) has been covered with subdural electrodes (SDE), a very invasive procedure prone to complications. Temporal stereoelectroencephalography (SEEG) with conventional frame‐based stereotaxy is time‐consuming and impeded by the geometry of the frame. The introduction of robotic assistance promised a simplification of temporal SEEG implantation. However, the efficacy of temporal SEEG in iVEEG remains unclear. The aim of this study was therefore to describe the efficiency and efficacy of SEEG in iVEEG of temporal lobe epilepsy. Methods This retrospective study enrolled 60 consecutive patients with medically intractable epilepsy who underwent iVEEG of a potential temporal SOZ by SDE (n = 40) or SEEG (n = 20). Surgical time efficiency was analyzed by the skin‐to‐skin time (STS) and the total procedure time (TPT) and compared between groups (SDE vs SEEG). Surgical risk was depicted by the 90‐day complication rate. Temporal SOZ were treated by SSRS. Favorable outcome (Engel°1) was assessed after 1 year of follow‐up. Results Robot‐assisted SEEG significantly reduced the duration of surgery (STS and TPT) compared to SDE implantations. There was no significant difference in complication rates. Notably, all surgical revisions in this study were attributed to SDE. Unilateral temporal SOZ was detected in 34/60 cases. Of the 34 patients, 30 underwent second stage SSRS. Both SDE and SEEG had a good predictive value for the outcome of temporal SSRS with no significant group difference. Significance Robot‐assisted SEEG improves the accessibility of the temporal lobe for iVEEG by increasing surgical time efficiency and by simplifying trajectory selection without losing its predictive value for SSRS.
Taking Another Look at Intelligence and Personality: An Eye-Tracking Approach
2023-05-07

Intelligence and personality are both key drivers of learning. This study extends prior research on intelligence and personality by adopting a behavioral-process-related eye-tracking approach. We tested 182 adults on fluid intelligence and the Big Five personality traits. Eye-tracking information (gaze patterns) was recorded while participants completed the intelligence test. Machine learning models showed that personality explained 3.18% of the variance in intelligence test scores, with Openness and, surprisingly, Agreeableness most meaningfully contributing to the prediction. Facet-level measures of personality explained a larger amount of variance (7.67%) in intelligence test scores than the trait-level measures, with the largest coefficients obtained for Ideas and Values (Openness) and Compliance and Trust (Agreeableness). Gaze patterns explained a substantial amount of variance in intelligence test performance (35.91%). Gaze patterns were unrelated to the Big Five personality traits, but some of the facets (especially Self-Consciousness from Neuroticism and Assertiveness from Extraversion) were related to gaze. Gaze patterns reflected the test-solving strategies described in the literature (constructive matching, response elimination) to some extent. A combined feature vector consisting of gaze-based predictions and personality traits explained 37.50% of the variance in intelligence test performance, with significant unique contributions from both personality and gaze patterns. A model that included personality facets and gaze explained 38.02% of the variance in intelligence test performance. Although behavioral data thus clearly outperformed “traditional” psychological measures (Big Five personality) in predicting intelligence test performance, our results also underscore the independent contributions of personality and gaze patterns in predicting intelligence test performance.
Inferring secretory and metabolic pathway activity from omic data with secCellFie
2023-05-07

Abstract Understanding protein secretion has considerable importance in the biotechnology industry and important implications in a broad range of normal and pathological conditions including development, immunology, and tissue function. While great progress has been made in studying individual proteins in the secretory pathway, measuring and quantifying mechanistic changes in the pathway’s activity remains challenging due to the complexity of the biomolecular systems involved. Systems biology has begun to address this issue with the development of algorithmic tools for analyzing biological pathways; however most of these tools remain accessible only to experts in systems biology with extensive computational experience. Here, we expand upon the user-friendly CellFie tool which quantifies metabolic activity from omic data to include secretory pathway functions, allowing any scientist to infer protein secretion capabilities from omic data. We demonstrate how the secretory expansion of CellFie (secCellFie) can be used to predict metabolic and secretory functions across diverse immune cells, hepatokine secretion in a cell model of NAFLD, and antibody production in Chinese Hamster Ovary cells.
Making cyber security more resilient: adding social considerations to technological fixes
2023-05-08

How can a focus on socio-technical vulnerability and uncertainty make cyber security more resilient? In this article, we provide a conceptual discussion of how to increase cyber resilience. First, we show how cyber security and resilience thinking co-evolved through their connection to critical infrastructures, and how the ensuing dominant technical focus inevitably always falls short due to the diverse societal values that underpin their critical social functions. We argue that a sole focus on aggregate systems neglects the important differences in how cyber threats are experienced and dealt with by individuals. Second, we draw on insights from social resilience and disaster management literature to establish a better link between individuals and cyber systems. We focus on two key aspects of cyber security that highlight its social nature: vulnerability and uncertainty. Instead of thinking of cyber security as a “technical problem + humans,” we suggest cyber security should be conceptualized as a “social problem + technology.” We conclude by highlighting three ways forward for researchers, policymakers, and practitioners: interdisciplinary research, public debate about a set of normative questions, and the need for an uncertainty discourse in politics and policymaking.
Plants cultivated for ecosystem restoration can evolve toward a domestication syndrome
2023-05-08

The UN Decade on Ecosystem Restoration calls for upscaling restoration efforts, but many terrestrial restoration projects are constrained by seed availability. To overcome these constraints, wild plants are increasingly propagated on farms to produce seeds for restoration projects. During on-farm propagation, the plants face non-natural conditions with different selection pressures, and they might evolve adaptations to cultivation that parallel those of agricultural crops, which could be detrimental to restoration success. To test this, we compared traits of 19 species grown from wild-collected seeds to those from their farm-propagated offspring of up to four cultivation generations, produced by two European seed growers, in a common garden experiment. We found that some plants rapidly evolved across cultivated generations towards increased size and reproduction, lower within-species variability, and more synchronized flowering. In one species, we found evolution towards less seed shattering. These trait changes are typical signs of the crop domestication syndrome, and our study demonstrates that it can also occur during cultivation of wild plants, within only few cultivated generations. However, there was large variability between cultivation lineages, and the observed effect sizes were generally rather moderate, which suggests that the detected evolutionary changes are unlikely to compromise farm-propagated seeds for ecosystem restoration. To mitigate the potential negative effects of unintended selection, we recommend to limit the maximum number of generations the plants can be cultivated without replenishing the seed stock from new wild collections.
Self-regulated and externally regulated learning in adolescence: Developmental trajectories and relations with teacher behavior, parent behavior, and academic achievement.
2023-05-08

Both self-regulation and external regulation are key to understanding adolescents' learning and positive development at school. However, evidence on the joint development of self-regulated learning and externally regulated learning during adolescence is lacking. In addition, the current knowledge on interrelations between the development of adolescents' self-regulated learning, externally regulated learning, behaviors of teachers and parents in terms of autonomy support and achievement pressure, and academic achievement is very limited. The present multilevel longitudinal analysis focusing on the domain of mathematics (<i>N</i> = 1,542 German adolescents; annual assessments from Grades 5 to 9; mean age at Grade 5 = 11.79 years, <i>SD</i> = 0.71, 51.75% female) addressed these gaps. Results from multilevel latent basic growth curve models showed that self- and externally regulated learning decreased over the 5 years at both the individual student and the class level. Changes in self- and externally regulated learning were linked: Classes with higher levels of self-regulated learning at Grade 5 showed a stronger decrease in externally regulated learning over time. Initial levels of and changes in student-reported teacher and parental autonomy support and achievement pressure were associated with self- and externally regulated learning at the individual student level; student-reported teacher autonomy support and self-regulated learning were also linked at the class level. Self-regulated learning related positively to standardized achievement test scores but not to adolescents' grades. This study adds to the scarce evidence base on different regulatory forms of adolescents' learning and can inform future research on adolescents' positive development and educational practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Exosomal non-coding RNAs’ role in immune regulation and potential therapeutic applications
2023-05-08

Exosomes are now significant players in both healthy and unhealthy cell-to-cell communication. Exosomes can mediate immune activation or immunosuppression, which can influence the growth of tumors. Exosomes affect the immune responses to malignancies in various ways by interacting with tumor cells and the environment around them. Exosomes made by immune cells can control the growth, metastasis, and even chemosensitivity of tumor cells. In contrast, exosomes produced by cancer cells can encourage immune responses that support the tumor. Exosomes carry circular RNAs, long non-coding RNAs, and microRNAs (miRNAs), all involved in cell-to-cell communication. In this review, we focus on the most recent findings concerning the role of exosomal miRNAs, lncRNAs, and circRNAs in immune modulation and the potential therapeutic implications of these discoveries.