Miracle-dz/UniFAR-FTUs huggingface dataset:
Low Serum Magnesium Levels Are Associated With Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke

Background: In patients with acute ischemic stroke, hemorrhagic transformation is a major complication after intravenous thrombolysis. This study aimed to investigate the relationship between serum magnesium levels and hemorrhagic transformation (HT) after thrombolytic therapy. Methods: We retrospectively analyzed data from 242 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China. Baseline serum magnesium levels were measured before intravenous thrombolysis, and the occurrence of HT was evaluated using computed tomography images reviewed within 24–36 h after therapy. The relationship between serum magnesium levels and HT was examined using multivariate logistic regression, subgroup analysis, and restricted cubic spline models. Results: Of the 242 included patients, 43 (17.8%) developed HT. Patients with HT had significant lower serum magnesium levels than those without HT (0.81 ± 0.08 vs. 0.85 ± 0.08 mmol/L, p = 0.007). Multivariable logistic regression analysis indicated that patients with higher serum magnesium levels had lower risk of HT (OR per 0.1-mmol/L increase 0.43, 95% CI 0.27–0.73, p = 0.002). However, this association did not persist when baseline levels of serum magnesium were higher than the median value (0.85 mmol/L) in subgroup analysis (OR per 0.1-mmol/L increase 0.58, 95% CI 0.14–2.51, p = 0.47). This threshold effect was also observed in the restricted cubic spline model when serum magnesium levels were above 0.88 mmol/L. No association between symptomatic HT and serum magnesium levels was observed in our study (OR per 0.1-mmol/L increase 0.52, 95% CI 0.25–1.11, p = 0.092). Conclusions: Lower serum magnesium levels in patients with ischemic stroke are associated with an increased risk of HT after intravenous thrombolysis, but perhaps only when serum magnesium is below a certain minimal concentration.
IGF2BP3 May Contributes to Lung Tumorigenesis by Regulating the Alternative Splicing of PKM

RNA binding proteins (RBPs) play a key role in genome regulation. Here we report the post-transcript regulation of IGF2BP3, which belongs to the insulin-like growth factor 2 mRNA binding protein family. We used iRIP-seq and RNA-seq to analyze the transcript regulation and alternative splicing on IGF2BP3 treated with overexpression cells and control. Overexpressed IGF2BP3 has broadly increased genes expression which involved in G-protein coupled receptor signaling pathway, positive regulation of cell proliferation, and signal transduction. IGF2BP3 regulated alternative splicing of multiple genes mainly clustered at response to hypoxia, negative regulation of transcription, and embryonic development. This study first provides alternative splicing analysis on transcription level of IGF2BP3 regulation, which laid the foundation for later research on IGF2BP3 critical functions.
Integrating Invasive and Non-invasive Monitoring Sensors to Detect Field-Scale Soil Hydrological Behavior

In recent decades, while great emphasis has been given to the monitoring of point-scale soil moisture patterns and field-scale integrated soil moisture, the measurement of matric potential has attracted little attention. Information on the soil matric potential is available in point-scale measurements but is still missing at field-scale. This state variable is necessary to understand hydrological fluxes and to determine the soil water retention function (WRF) for field-scale applications. In this study, we combine data from cosmic-ray neutron probes (CRNP, non-invasive proximal soil moisture sensors) and SoilNet wireless sensor networks (invasive ground-based soil moisture and matric potential sensors) installed in two sub-catchments with contrasting land-use (agroforestry vs. near-natural forest) to derive a field-scale WRF. We investigate the hypothesis that both sensor types provide effective measurements that are representative for the entire sub-catchment, as well as the drawbacks of integrating the different measurement scales of the sensor types (i.e., spatial-mean of distributed point-scale data vs. an integrated field-scale measurement). We found discrepancies in the data of the two sensor types related to the effects of the time-varying vertical measurement footprint of the CRNP, which induces a scale mismatch between CRNP-based soil moisture (referring mostly to near-surface depths) and the spatially averaged soil matric potential data measured at soil depths of 0.15 and 0.30 m. To remove the offsets, we opted to use the soil moisture index (SMI) based on the estimation of field capacity and wilting point, retrieved from the knowledge of the field-scale WRF. We found that the bimodality of SMI calculated with SoilNet-based soil moisture induced by Mediterranean rainfall seasonal behavior is not well-captured by CRNP-based soil moisture, except in a particularly dry year like 2017. The contrasts in SMI values between the two test sites were associated with differences in the spatial variability of soil moisture patterns explained by soil texture or terrain characteristics. We argue that field-scale WRFs are useful for the analysis of hydrological processes at the sub-catchment (field) scale and the application of distributed models.
Consensus-Based Core Set of Outcome Measures for Clinical Motor Rehabilitation After Stroke—A Delphi Study

Introduction: Outcome measures are key to tailor rehabilitation goals to the stroke patient's individual needs and to monitor poststroke recovery. The large number of available outcome measures leads to high variability in clinical use. Currently, an internationally agreed core set of motor outcome measures for clinical application is lacking. Therefore, the goal was to develop such a set to serve as a quality standard in clinical motor rehabilitation poststroke. Methods: Outcome measures for the upper and lower extremities, and activities of daily living (ADL)/stroke-specific outcomes were identified and presented to stroke rehabilitation experts in an electronic Delphi study. In round 1, clinical feasibility and relevance of the outcome measures were rated on a 7-point Likert scale. In round 2, those rated at least as “relevant” and “feasible” were ranked within the body functions, activities, and participation domains of the International Classification of Functioning, Disability, and Health (ICF). Furthermore, measurement time points poststroke were indicated. In round 3, answers were reviewed in reference to overall results to reach final consensus. Results: In total, 119 outcome measures were presented to 33 experts from 18 countries. The recommended core set includes the Fugl–Meyer Motor Assessment and Action Research Arm Test for the upper extremity section; the Fugl–Meyer Motor Assessment, 10-m Walk Test, Timed-Up-and-Go, and Berg Balance Scale for the lower extremity section; and the National Institutes of Health Stroke Scale, and Barthel Index or Functional Independence Measure for the ADL/stroke-specific section. The Stroke Impact Scale was recommended spanning all ICF domains. Recommended measurement time points are days 2 ± 1 and 7; weeks 2, 4, and 12; 6 months poststroke and every following 6th month. Discussion and Conclusion: Agreement was found upon a set of nine outcome measures for application in clinical motor rehabilitation poststroke, with seven measurement time points following the stages of poststroke recovery. This core set was specifically developed for clinical practice and distinguishes itself from initiatives for stroke rehabilitation research. The next challenge is to implement this clinical core set across the full stroke care continuum with the aim to improve the transparency, comparability, and quality of stroke rehabilitation at a regional, national, and international level.
Antibacterial Fusion Proteins Enhance Moraxella catarrhalis Killing

Moraxella catarrhalis is a human-specific commensal of the respiratory tract and an opportunistic pathogen. It is one of the leading cause of otitis media in children and of acute exacerbations in patients with chronic obstructive pulmonary disease, resulting in significant morbidity and economic burden. Vaccines and new immunotherapeutic strategies to treat this emerging pathogen are needed. Complement is a key component of innate immunity that mediates the detection, response, and subsequent elimination of invading pathogens. Many pathogens including M. catarrhalis have evolved complement evasion mechanisms, which include the binding of human complement inhibitors such as C4b-binding protein (C4BP) and Factor H (FH). Inhibiting C4BP and FH acquisition by M. catarrhalis may provide a novel therapeutic avenue to treat infections. To achieve this, we created two chimeric proteins that combined the Moraxella-binding domains of C4BP and FH fused to human immunoglobulin Fcs: C4BP domains 1 and 2 and FH domains 6 and 7 fused to IgM and IgG Fc, respectively. As expected, FH6-7/IgG displaced FH from the bacterial surface while simultaneously activating complement via Fc-C1q interactions, together increasing pathogen elimination. C4BP1-2/IgM also increased serum killing of the bacteria through enhanced complement deposition, but did not displace C4BP from the surface of M. catarrhalis. These Fc fusion proteins could act as anti-infective immunotherapies. Many microbes bind the complement inhibitors C4BP and FH through the same domains as M. catarrhalis, therefore these Fc fusion proteins may be promising candidates as adjunctive therapy against many different drug-resistant pathogens.
RvE1 Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction and Enhances Bacterial Clearance

The development of cardiac dysfunction caused by microbial infection predicts high mortality in sepsis patients. Specialized pro-resolving mediators (SPMs) mediate resolution of inflammation in many inflammatory diseases, and are differentially expressed in plasma of sepsis patients. Here, we investigated whether the levels of SPMs are altered in the murine septic heart following polymicrobial sepsis-induced cardiac dysfunction. Ten weeks-old male C57BL/6 mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP), which is a clinically relevant sepsis model receiving analgesics, antibiotics, and fluid resuscitation. CLP caused a significant systolic dysfunction assessed by echocardiography. The hearts were subjected to LC-MS/MS based lipid mediator profiling. Many SPMs were significantly reduced in septic hearts, among which RvE1 had a ~93-fold reduction. Treatment of CLP mice with synthetic RvE1 (1 μg/mouse i.v.) at 1 h after CLP increased peritoneal macrophages number, particularly MHC II− macrophages. RvE1 reduced pro-inflammatory gene expression (interleukin-1β, interleukin-6, and CCL2) in lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDMs) in vitro. RvE1 attenuated cardiac dysfunction in septic mice and increased cardiac phosphorylated Akt; decreased cardiac phosphorylated IκB kinase α/β, nuclear translocation of the NF-κB subunit p65, extracellular signal–regulated kinase 1/2, and c-Jun amino-terminal kinases 1/2. Most notably, RvE1 treatment reduced peritoneal bacterial load and promoted phagocytosis activity of BMDMs. In conclusion, cardiac SPMs, particularly RvE1, are substantially reduced in mice with polymicrobial sepsis. Delayed therapeutic administration of RvE1 to mice with polymicrobial sepsis attenuates the cardiac dysfunction through modulating immuno-inflammatory responses. In addition to the above effects, the ability to enhance bacterial clearance makes RvE1 an ideal therapeutic to reduce the sequalae of polymicrobial sepsis.
Silencing of LncRNA C1RL-AS1 Suppresses the Malignant Phenotype in Gastric Cancer Cells via the AKT/β-Catenin/c-Myc Pathway

Purpose: Numerous studies have shown that lncRNAs play vital roles in the development and progression of cancer. However, investigations of lncRNAs in gastric cancer are limited and need to be further pursued. Materials and Methods: According to RNA-seq results of gastric cancer (GC) tissues, we identified a novel lncRNA, C1RL-AS1. qRT-PCR was used to detect the expression level of C1RL-AS1 in paired GC and normal tissues. Nuclear/cytoplasmic fractionation was applied to evaluate the distribution of C1RL-AS1 in GC cells. For functional evaluation, CCK-8, colony formation, transwell, and apoptosis assays were used to determine the oncogenic role of C1RL-AS1. Results: C1RL-AS1 was upregulated in GC tissues, and high expression levels of C1RL-AS1 were associated with poor prognosis. Further in vitro functional assays revealed that silencing C1RL-AS1 attenuated the proliferation rate and migration ability and enhanced the apoptotic rate and the senescence of GC cells. The subsequent underlying mechanistic investigation revealed that Wnt/β-catenin was involved in C1RL-AS1-mediated signaling. Rescue experiments suggested that C1RL-AS1 probably promoted the malignant phenotype via the AKT/β-catenin pathway by downregulating c-Myc. Conclusions: C1RL-AS1 probably exerts its biological function by mediating the AKT/β-catenin/c-Myc pathway, indicating a novel therapeutic target in GC.
Obesity Accelerates Age Defects in Mouse and Human B Cells

Obesity, similar to aging, is associated with chronic low-grade systemic inflammation, known as inflammaging, and represents a significantly higher risk for developing chronic diseases typical of old age. Immune cells are recruited to the obese adipose tissue (AT) by chemotactic molecules secreted by non-immune and immune cells in the AT, both contributing to the release of several pro-inflammatory mediators that fuel local and systemic inflammation, to the refractory response of immune cells to further in vivo and in vitro stimulation and to the induction of autoimmune B cells with potentially pathogenic repertoires. In terms of molecular mechanisms involved, leptin, an adipokine secreted primarily by adipocytes, has been proposed to be involved in the reduced generation of protective antibodies, and in the increased generation of autoimmune antibodies, further supporting the concept that obesity accelerates age defects. Leptin has also been shown to induce intrinsic B cell inflammation and B cell immunosenescence. The results presented in this review highlight the importance of weight reduction programs to improve immunity and reduce the risk for developing chronic diseases in obese and older individuals.
Bridging the Gap Between Fluid Biomarkers for Alzheimer’s Disease, Model Systems, and Patients

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of two proteins in fibrillar form: amyloid-β (Aβ) and tau. Despite decades of intensive research, we cannot yet pinpoint the exact cause of the disease or unequivocally determine the exact mechanism(s) underlying its progression. This confounds early diagnosis and treatment of the disease. Cerebrospinal fluid (CSF) biomarkers, which can reveal ongoing biochemical changes in the brain, can help monitor developing AD pathology prior to clinical diagnosis. Here we review preclinical and clinical investigations of commonly used biomarkers in animals and patients with AD, which can bridge translation from model systems into the clinic. The core AD biomarkers have been found to translate well across species, whereas biomarkers of neuroinflammation translate to a lesser extent. Nevertheless, there is no absolute equivalence between biomarkers in human AD patients and those examined in preclinical models in terms of revealing key pathological hallmarks of the disease. In this review, we provide an overview of current but also novel AD biomarkers and how they relate to key constituents of the pathological cascade, highlighting confounding factors and pitfalls in interpretation, and also provide recommendations for standardized procedures during sample collection to enhance the translational validity of preclinical AD models.
Calibrating the Test of Relational Reasoning: New Information From Oblique Bifactor Models

Relational reasoning (RR) is believed to be an essential construct for studying higher education learning. Relational reasoning is defined as an ability to discern meaningful patterns within any stream of information. Nonetheless, studies of RR are limited by the psychometric structure of the construct. For many instances, the composite nature of RR has been described as a bifactor structure. Bifactor models limit possibilities for studying the inner structure of composite constructs by demanding orthogonality of latent dimensions. Such assumption severely limits the interpretation of the results when it is applied to psychological constructs. However, over the last 10 years, advances in the fields of Rasch measurement led to the development of the oblique bifactor models, which relax the constraints of the orthogonal bifactor models. We show that the oblique bifactor models exhibit model fit, which is superior compared to the orthogonal bifactor model. Then, we discuss their interpretation and demonstrate the advantages of these models for investigating the inner structure of the test of RR. The data are a nationally representative sample of Russian engineering students (N = 2,036).
Directed Evolution of Pseudomonas fluorescens Lipase Variants With Improved Thermostability Using Error-Prone PCR

Lipases catalyze the hydrolysis of fats and oils, and have been widely used in various industrial fields. However, bacterial lipases have a lower thermostability in industrial processes, which was a limiting factor in their industrial application. In this study, we obtained an improve variant of Pseudomonas fluorescens lipase (PFL) with enhanced thermostability using classical error-prone PCR. Wild-type PFL showed an optimal temperature and pH of 50°C and pH 7.5, respectively. Due to the low thermostability of PFL, a library containing over 3000 individual mutants as constructed using error-prone PCR. Screening for thermotolerance yielded the mutants L218P and P184C/M243C with Tm values of 62.5 and 66.0°C, which was 2.5 and 6°C higher than that of the WT, respectively. The combination of the two mutants (P184C/M243C/L218P) resulted in an approximately additive effect with a Tm value of 68.0°C. Although the increase of Tm was not substantial, the mutant also had dramatically increased methanol tolerance. Structural analysis revealed that the introduction of a disulfide bond between P184C and M243C and the substitution of Pro to reduce the flexibility of a loop increased the thermostability of PFL, which provides a theoretical foundation for improving the thermostability and methanol tolerance of lipase family I.1 to resist the harsh conditions of industrial processes.
Functional Outcomes and Complications After Salvage Total Laryngectomy for Residual, Recurrent, and Second Primary Squamous Cell Carcinoma of the Larynx and Hypopharynx: A Multicenter Retrospective Cohort Study

Background/Purpose: We analyzed complications and functional outcomes and aimed at identifying prognostic factors for functional outcomes and complications in patients who underwent salvage total laryngectomy (STL) for residual, recurrent, and second primary squamous cell carcinoma (SCC) of the larynx and hypopharynx after initial (chemo)radiation. Methods: Retrospective cohort study of patients who underwent STL in four major Belgian reference hospitals between 2002 and 2018. Prognostic factors for functional outcomes and complications were identified with uni- and multivariable analysis. Results: A total of 405 patients were included in the final analysis. STL was performed for residual tumor (40.2%), local recurrence (40.5%), or second primary laryngeal or hypopharyngeal SCC (19.4%). Early postoperative complications were experienced by 34.2% of patients: postoperative hemorrhage occurred in 5.4%, wound infection in 16.2%, and clinical pharyngocutaneous fistula (PCF) in 25.5% of patients. Early readmission proved necessary in 15.1% of cases, most often due to late PCF development (72.2%). Patients achieved total peroral intake in 94.2% of cases. However, subjective dysphagia was reported by 31.3% of patients during follow-up. Functional speech, defined as functional communication by speech without additional aids, was reported in 86.7% of cases and was most often achieved by tracheo-esophageal puncture (TEP) (94.1%). In a multivariable model, lower preoperative hemoglobin (<12.5 g/dl) was identified as an independent prognostic factor for higher overall complication rate. No risk factors were found significant for clinical fistula formation. Vascularized tissue augmentation did not significantly prevent clinical PCF. Patients with positive section margins, patients initially treated with surgery combined with adjuvant RT (vs. radiotherapy alone), and those developing PCF after STL were less likely to achieve total peroral intake. Postoperative dysphagia proved more likely in patients who developed a PCF postoperatively, and less likely in patients who underwent STL without partial pharyngectomy and in patients with myocutaneous pectoralis major (PM) flap reconstruction, compared to muscle onlay PM flap. Achieving postoperative functional speech proved most likely in patients with smaller tumors (lower pT classification) and free section margins. Conclusion: Substantial complication rates and favorable functional outcomes are reported after STL.
Structural Neural Correlates of Double Decision Performance in Older Adults

Speed of processing is a cognitive domain that encompasses the speed at which an individual can perceive a given stimulus, interpret the information, and produce a correct response. Speed of processing has been shown to decline more rapidly than other cognitive domains in an aging population, suggesting that this domain is particularly vulnerable to cognitive aging (Chee et al., 2009). However, given the heterogeneity of neuropsychological measures used to assess the domains underpinning speed of processing, a diffuse pattern of brain regions has been implicated. The current study aims to investigate the structural neural correlates of speed of processing by assessing cortical volume and speed of processing scores on the POSIT Double Decision task within a healthy older adult population (N = 186; mean age = 71.70 ± 5.32 years). T1-weighted structural images were collected via a 3T Siemens scanner. The current study shows that less cortical thickness in right temporal, posterior frontal, parietal and occipital lobe structures were significantly associated with poorer Double Decision scores. Notably, these include the lateral orbitofrontal gyrus, precentral gyrus, superior, transverse, and inferior temporal gyrus, temporal pole, insula, parahippocampal gyrus, fusiform gyrus, lingual gyrus, superior and inferior parietal gyrus and lateral occipital gyrus. Such findings suggest that speed of processing performance is associated with a wide array of cortical regions that provide unique contributions to performance on the Double Decision task.