Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Significance of Preoperative Fibrinogen to Albumin Ratio in Patients with Glioblastoma: A Singe Center Experience

Objective To explore the prognostic value of preoperative fibrinogen to albumin ratio (FAR) in patients with glioblastoma (GBM) and its association with clinical characteristics. Patients and Methods A retrospective analysis was carried out on patients with newly diagnosed GBM who had undergone operation at the Department of Neurosurgery at West China Hospital between June 1st 2015 to June 31st 2018. Receiver operating characteristic (ROC) curves were performed to determine the optimal cut-off values for fibrinogen, albumin, neutrophil to lymphocyte ratio (NLR), and FAR by calculating the maximum Youden index. Kaplan–Meier curves and Cox regression analyses were applied to evaluate the prognostic value of FAR in GBM. Harrell concordance index (C-index) and Akaike information criterion (AIC) were calculated to compare different prognostic models. Results A total of 206 GBM patients were included in this research. The optimal cut-off value for fibrinogen, albumin, NLR, and FAR were 2.57, 42.4, 2.28, and 0.068 respectively. High FAR was significantly related to older age, KPS≤80, IDH-1 wildtype, presence of preoperative seizures, higher NLR, and tumor location. In Cox regression analyses, high FAR was significantly associated with poor prognosis. Prognostic models including FAR had the largest C-index and lowest AIC. Conclusion FAR was determined to be an independent risk factor of prognosis in patients with newly-diagnosed GBM. And the prognostic predictive ability of FAR is stronger than fibrinogen and albumin.
Acupuncture for Paclitaxel-Induced Peripheral Neuropathy: A Review of Clinical and Basic Studies

Abstract Paclitaxel-induced peripheral neuropathy (PIPN) is a common and intractable side effect of the conventional chemotherapeutic agent paclitaxel. Acupuncture has been reported as an effective alternative therapy in treatment of PIPN in both basic studies and clinical trials. However, there is a lack of comprehensive surveys to summarize the action of acupuncture in management of PIPN. In this review, we briefly demonstrate the basic pathology of PIPN, which includes the activation of ion channels, mitochondrial dysfunction, disruption of axonal transport and also neuro-inflammatory involvement. Meanwhile, we review both the clinical and basic studies as an emphasis to give a general overview of the therapeutic effect of acupuncture against PIPN. Finally, we summarize the current known mechanisms underlying the action of acupuncture against PIPN mainly at peripheral and spinal levels, which include various neurotransmitters, multiple receptors, different types of enzymes and molecules. In conclusion, acupuncture could be considered as a potential alternative therapy in treatment of PIPN, and further clinical and experimental studies are called for in the future.
Expression Analysis of MIST1 and EMT Markers in Primary Tumor Samples Points to MIST1 as a Biomarker of Cervical Cancer

Background Mist1 is a basic transcription factor, which plays an important role in the development of multiple organs, and may also regulate tumor progression by mediating epithelial-mesenchymal transformation. However, there is lack of research on its role of squamous cell carcinoma, especially in cervical squamous cell carcinoma. Methods Bioinformatic methods were used to analyze gene expression, correlation, and patient survival according to the TCGA database. Thirty pairs of cancer tissues and distal cancer tissues from cervical cancer patients who received radical surgery were enrolled in the study. The expression of Mist1 was analyzed using Western blot. Furthermore, the potential associations among Mist1 expression, EMT biomarkers and various clinicopathological characteristics were investigated. All statistical tests employed in this study were two-sided, and P values <0.05 were deemed statistically significant. Results Overall survival data were obtained from TCGA-CESC dataset, containing 3 control samples and 305 tumor samples. The expression of Mist1 was significantly higher in primary tumor than in normal tissues (P<0.001). The samples were divided into a low Mist1 expression group (n=144) and a high Mist1 expression group (n=146) according to the median expression level. Kaplan–Meier survival analysis revealed that high expression of Mist1 was significantly correlated with poor overall survival (P=0.032). We further explored the relationships between Mist1 and EMT. Among the 30 primary cervical cancer specimens investigated, the difference in Mist1 expressed statuses between cervical cancer tissues and distal noncancerous cervical tissues was significant (P=0.001). And the epithelial cell marker E-cadherin was downregulated in Mist1 overexpressed cervical cancer cells; however, the mesenchymal marker N-Cadherin and Twist was upregulated. Conclusion Our study found that Mist1 seemed to play the role of oncogene in cervical squamous cell carcinoma and could be a potential biomarker.
Immunomodulatory Effect of a New Ingredients Group Extracted from Astragalus Through Membrane Separation Technique

Introduction Astragalus is a commonly used traditional Chinese medicine in China, which has been widely applied to enhance the immunomodulatory function of the body. The main bioactive components are complicated. To explore the role of the components, various techniques have been applied in Astragalus extraction. Membrane separation technique featured with green processing condition and high efficiency is of signification interest in the application of Astragalus treatment. Methods In this study, a new ingredients group A4 was separated from Astragalus using membrane separation technique. The quantification and identification of A4 were achieved by UV-vis spectrometry and UPLC-MS measurements. Pathological approaches along with serum metabolomics were utilized to study the immunoprotective effects of the extracts and explore the underlying mechanisms on metabolic activity. Results It was observed that A4 could promote the secretion of IL-2 and IFN-γ, stimulate the activated CD4+CD25+ and CD8+ CD25+ T lymphocytes in splenocytes and protect rat spleen to some extent. Seven crucial biomarkers that related to immunity regulations were screened out and identified through serum metabonomic analysis coupled with nuclear magnetic resonance. The enrichment analysis revealed that A4 alleviated the immune dysfunction by modulating amino acid metabolism and energy metabolism for the first time. Conclusion The new ingredients group A4 isolated from the Astragalus membrane can reduce the immune dysfunction by regulating the amino acid metabolism and energy metabolism of rats.
Gas-Particle Partitioning and SOA Yields of Organonitrate Products from NO3-Initiated Oxidation of Isoprene under Varied Chemical Regimes

Alkyl nitrate (AN) and secondary organic aerosol (SOA) from the reaction of nitrate radicals (NO3) with isoprene were observed in the Simulation of Atmospheric PHotochemistry In a large Reaction (SAPHIR) chamber during the NO3Isop campaign in August 2018. Based on 15 day-long experiments under various reaction conditions, we conclude that the reaction has a nominally unity molar AN yield (observed range 90 ± 40%) and an SOA mass yield of OA + organic nitrate aerosol of 13–15% (with ∼50 μg m–3 inorganic seed aerosol and 2–5 μg m–3 total organic aerosol). Isoprene (5–25 ppb) and oxidant (typically ∼100 ppb O3 and 5–25 ppb NO2) concentrations and aerosol composition (inorganic and organic coating) were varied while remaining close to ambient conditions, producing similar AN and SOA yields under all regimes. We observe the formation of dinitrates upon oxidation of the second double bond only once the isoprene precursor is fully consumed. We determine the bulk partitioning coefficient for ANs (Kp ∼ 10–3 m3 μg–1), indicating an average volatility corresponding to a C5 hydroxy hydroperoxy nitrate.
Centrum Semiovale Perivascular Space and Amyloid Deposition in Spontaneous Intracerebral Hemorrhage

Supplemental Digital Content is available in the text. Background and Purpose: We explored whether high-degree magnetic resonance imaging–visible perivascular spaces in centrum semiovale (CSO) are more prevalent in cerebral amyloid angiopathy (CAA) than hypertensive small vessel disease and their relationship to brain amyloid retention in patients with primary intracerebral hemorrhage (ICH). Methods: One hundred and eight spontaneous ICH patients who underwent magnetic resonance imaging and Pittsburgh compound B were enrolled. Topography and severity of enlarged perivascular spaces were compared between CAA-related ICH (CAA-ICH) and hypertensive small vessel disease–related ICH (non-CAA ICH). Clinical and image characteristics associated with high-degree perivascular spaces were evaluated in univariate and multivariable analyses. Univariate and multivariable models were performed to evaluate associations between the severity of perivascular spaces in CSO and amyloid retention in CAA-ICH and non–CAA-ICH cases. Results: Patients with CAA-ICH (n=29) and non–CAA-ICH (n=79) had similar prevalence of high-degree perivascular spaces in CSO (44.8% versus 36.7%; P=0.507) and in basal ganglia (34.5% versus 51.9%; P=0.131). High-degree perivascular spaces in CSO were independently associated with the presence of lobar microbleed (odds ratio, 3.0 [95% CI, 1.1–8.0]; P=0.032). The amyloid retention was higher in those with high-degree than those with low-degree CSO-perivascular spaces in CAA-ICH (global Pittsburgh compound B standardized uptake value ratio, 1.55 [1.33–1.61] versus 1.13 [1.01–1.48]; P=0.003) but not in non–CAA-ICH. In CAA-ICH, the association between cerebral amyloid retention and the degree of perivascular spaces in CSO remained significant after adjustment for age and lobar microbleed number (P=0.004). Conclusions: Although high-degree magnetic resonance imaging–visible perivascular spaces are equally prevalent between CAA-ICH and non–CAA-ICH in the Asian cohort, the severity of magnetic resonance imaging–visible CSO-perivascular spaces may be an indicator of higher brain amyloid deposition in patients with CAA-ICH.
Kullback–Leibler Divergence-Based Optimal Stealthy Sensor Attack Against Networked Linear Quadratic Gaussian Systems

This article concentrates on designing optimal stealthy attack strategies for cyber-physical systems (CPSs) modeled by the linear quadratic Gaussian (LQG) dynamics, where the attacker aims to increase the quadratic cost maximally and keeping a certain level of stealthiness by simultaneously intercepting and modifying the transmitted measurements. In our work, a novel attack model is developed, based on which the attacker can launch strictly stealthy or <inline-formula> <tex-math notation="LaTeX">$\epsilon $ </tex-math></inline-formula>-stealthy attacks. To remain strictly stealthy, the attacker only needs to solve an off-line semidefinite program problem. In such a case, the attack performance is optimal but limited. To achieve a higher desired attack effect than that of the strictly stealthy attack, the attacker sometimes needs to sacrifice the stealthy level. Thus, the <inline-formula> <tex-math notation="LaTeX">$\epsilon $ </tex-math></inline-formula>-stealthy attack is analyzed, where an upper bound of the optimal attack performance is obtained by solving a convex optimization problem. Then, an optimal <inline-formula> <tex-math notation="LaTeX">$\epsilon $ </tex-math></inline-formula>-stealthy attack is designed to achieve the upper bound, which differs from the existing suboptimal <inline-formula> <tex-math notation="LaTeX">$\epsilon $ </tex-math></inline-formula>-stealthy attack for the considered LQG systems. Finally, the simulations are provided to verify the developed results.
Tracking Single Molecule Dynamics in the Adult Drosophila Brain

Visual Abstract Super-resolution microscopy provides valuable insight for understanding the nanoscale organization within living tissue, although this method is typically restricted to cultured or dissociated cells. Here, we develop a method to track the mobility of individual proteins in ex vivo adult Drosophila melanogaster brains, focusing on a key component of the presynaptic release machinery, syntaxin1A (Sx1a). We show that individual Sx1a dynamics can be reliably tracked within neurons in the whole fly brain, and that the mobility of Sx1a molecules increases following conditional neural stimulation. We then apply this preparation to the problem of general anesthesia, to address how different anesthetics might affect single molecule dynamics in intact brain synapses. We find that propofol, etomidate, and isoflurane significantly impair Sx1a mobility, while ketamine and sevoflurane have little effect. Resolving single molecule dynamics in intact fly brains provides a novel approach to link localized molecular effects with systems-level phenomena such as general anesthesia.
Predicting the neuro‐cardio‐haemodynamic outcomes of sepsis and its pharmacological interventions: Get to the future through numerical equations

Henry Sutanto1 and Aurore Lyon2,3 1Department of Cardiology, CARIMSchool for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands 2Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands 3Division of Heart and Lungs, Department of Medical Physiology, University Medical Centre Utrecht, Utrecht, The Netherlands
Eliminating the gap between the use of assistive technologies and the inclusion of people with intellectual disabilities in leisure activities

Information and Communication Technology (ICT) tools and Assistive Technologies (AT) can support people with Down Syndrome (PDS) and Intellectual Disabilities (PID) in increasing their self-confidence and independence, enhancing skills, and competences, participating in leisure activities. For families of PDS/PID, professionals, non-formal caregivers and volunteers, the challenge is to appreciate the benefits of ICT Tools in promoting inclusion. The aim of this study is to present the interdisciplinary and multidimensional scope of the DS Leisure project aiming at promoting the inclusion of PDS/PID through innovative ICT tools and their participation in inclusive leisure activities. Particularly, 24 individuals were asked to assess the global satisfaction and performance of PDS/PID, as well as the exploitation of ICT tools. Findings suggested that PDS/PID specific social, decision-making, and communication skills were significantly improved after their participation in the Experiential Activity and the e-Training platform was positively rated and considered a constructive learning experience.
Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800

Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non‐Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well‐characterized GRAS host.
Vitamins and Infusion of Levodopa-Carbidopa Intestinal Gel

ABSTRACT: Levodopa-carbidopa intestinal gel infusion (LCIG) is an established therapy for advanced Parkinson disease (PD), resulting in a significant improvement of quality of life. With increased LCIG adoption worldwide, potential complications due to abnormal vitamin absorption or metabolism have been reported in these patients. Neurologists are unfamiliar with vitamins physiology and pathophysiological mechanisms in case of their deficiency. Unfortunately, clinical and laboratory guidelines related to vitamin monitoring and supplementation in the context of treatment with LCIG are not available. We herein summarize the current knowledge on three vitamins that are reduced with LCIG therapy reporting on their physiology, laboratory testing, and clinical impact of their deficiency/excess. In addition, we proposed an opinion-based recommendation for clinicians treating LCIG patients. Patients and caregivers should be informed about the risk of vitamin deficiency. Vitamin B12, homocysteine, and methylmalonic acid (MMA) should be tested before starting LCIG, six months after and once/year thereafter. Vitamin B6 and folate testing is not universally available but it should be considered if homocysteine is elevated but MMA and/or total vitamin B12 are normal. Prophylaxis of vitamin deficiency should be started as soon as LCIG is implemented, possibly even before. Dietary recommendations are enough in most patients although a subgroup of patients is at higher risk and should receive Vitamin B12 regularly and cycles of B6. Finally, once diagnosed a vitamin deficiency should be readily treated and accompanied by clinical and laboratory monitoring. Resistant cases should receive non-oral routes of administration and possibly discontinue LCIG, even temporarily.
Bacterial persisters are a stochastically formed subpopulation of low-energy cells

Persisters represent a small subpopulation of non- or slow-growing bacterial cells that are tolerant to killing by antibiotics. Despite their prominent role in the recalcitrance of chronic infections to antibiotic therapy, the mechanism of their formation has remained elusive. We show that sorted cells of Escherichia coli with low levels of energy-generating enzymes are better able to survive antibiotic killing. Using microfluidics time-lapse microscopy and a fluorescent reporter for in vivo ATP measurements, we find that a subpopulation of cells with a low level of ATP survives killing by ampicillin. We propose that these low ATP cells are formed stochastically as a result of fluctuations in the abundance of energy-generating components. These findings point to a general “low energy” mechanism of persister formation.
Criteria related to precooling of tulip bulbs cv.Apeldoorn at 5°c

Based on trials in 1981, 1982 and 1983 the following tentative criteria are proposed for detecting whether dry bulbs (12–13 cm circumference) have been exposed to 5°C: the starch content of freeze-dried anthers should exceed 10% and the specific activity of -amylase in anthers extracts should be below 0.16 (arbitrary unit per mg protein). Data from a recent trial (1984) corroborated the proposed indicators. However, these critaria could not be used to determine how long the bulbs had been exposed to 5°C. During the 12 weeks of cold treatment development of anthers, expressed as fresh or dry weight, was a linear function of time; but, as the slope and Y-intercept of the lines differed from one year to another, this criterion was discarded as an indicator of the duration of cold treatment. The ratio of two bands obtained by liquid chromatography of acetone extracts from shoots shows no significant trend as a function of duration of cold treatment. The osmotic potential of shoots was not included in our model because it decreased linearly during treatment but after one week of simulated transport it increased to a level that would indicate a treatment of only 6 weeks.
Presurgical platelet–lymphocyte ratio for prognosis in advanced hypopharyngeal squamous cell carcinoma in individuals undergoing radical resection

Abstract Background Patient prognosis in hypopharyngeal carcinoma remains difficult to predict, necessitating new, readily available biomarkers. Objective Platelet–lymphocyte ratio (PLR)’s effects on recurrence-free survival (RFS) and overall survival (OS) were evaluated in individuals undergoing radical resection for advanced hypopharyngeal squamous cell carcinoma (HSCC). Methods A total of 89 patients were retrospectively assessed. PLR, and derived neutrophil–lymphocyte (dNLR) and neutrophil–lymphocyte (NLR) ratios were determined based on complete blood count. Then, the prognostic values of PLR, dNLR and NLR were assessed by univariate and multivariate Cox regression analyses adjusted for disease-specific prognostic factors. Endpoints of interest were RFS and OS. Results The optimal cutoff of PLR was 98.815, based on which individuals were categorized into the high- (PLR ≥98.815) and low- (PLR <98.815) PLR groups. High PLR (p = .022) had a significant association with reduced RFS, which still showed significance in multivariable analysis (HR = 2.020, 95%CI: 1.076–3.794, p = .029). In univariate analysis, PLR (p = .046) and positive surgical margin (p = .021) also had significant associations with OS. Conclusion Elevated PLR has associations with increased risk of recurrence and reduced survival in advanced HSCC cases undergoing radical resection. High presurgical PLR may independently predict RFS. Therefore, further multi-institutional prospective studies are needed to better characterize the role of pre-operative blood PLR as prognostic factors in HSCC.
Computational study to evaluate the potency of phytochemicals in Boerhavia diffusa and the impact of point mutation on cyclin-dependent kinase 2-associated protein 1

Abstract A protein's function is closely related to its structural properties. Mutations can affect the functionality of a protein. Different cancer tissues have found disordered expression of the cyclin-dependent kinase 2-associated Protein 1 (CDK2AP1) gene. A protein molecule's conformational flexibility affects its interaction with phytochemicals and their biological partners at various levels. Boerhavia diffusa has been investigated most extensively for its medicinal activities like anticancer properties. It contains many bioactive compounds like Boeravinone A, Boeravinone B, Boeravinone C, Boeravinone D, Boeravinone E, Boeravinone F, Boeravinone G, Boeravinone H, Boeravinone I and Boeravinone J. We have studied to analyse the binding efficacy properties as well as essential dynamic behaviour, free energy landscape of both the native and mutant protein CDK2AP1 with bioactive compounds from Boerhavia diffusa plant extracts through computational approaches by homology modelling, docking and molecular dynamics simulation. From the molecular docking study, we found that. Boeravinone J have best binding affinity (–7.9 kcal/mol) towards the native protein of CDKAP1 compared to others phytochemicals. However, we found the binding energy for H23R and C105R (mutation point) −7.8 and −7.6 kcal/mol, respectively. A single minima energy point (from 100 ns molecular dynamics simulation study) was found in the H23R mutant with Boeravinone J complex suggested that minimum structural changes with less conformational mobility compared C105A mutant model. Communicated by Ramaswamy H. Sarma