Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Bayesian Markov Chain Monte Carlo Methods to Estimate EQ-5D Utility Scores from EORTC QLQ Data in Myeloma for Use in Cost-Effectiveness Analysis

Background. Patient-reported outcome measures are an important component of the evidence for health technology appraisal. Their incorporation into cost-effectiveness analyses (CEAs) requires conversion of descriptive information into utilities. This can be done by using bespoke utility algorithms. Otherwise, investigators will often estimate indirect utility models for the patient-reported outcome measures using off-the-shelf utility data such as the EQ-5D or SF-6D. Numerous modeling strategies are reported; however, to date, there has been limited utilization of Bayesian methods in this context. In this article, we examine the relative advantage of the Bayesian methods in relation to dealing with missing data, relaxing the assumption of equal variances and characterizing the uncertainty in the model predictions. Methods. Data from a large myeloma trial were used to examine the relationship between scores in each of the 19 domains of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/QLQ-MY20 and the EQ-5D utility. Data from 1839 patients were divided 75%/25% between derivation and validation sets. A conventional ordinary least squares model assuming equal variance and a Bayesian model allowing unequal variance were estimated on complete cases. Two further models were estimated using conventional and Bayesian multiple imputation, respectively, using the full data set. Models were compared in terms of data fit, accuracy in model prediction, and characterization of uncertainty in model predictions. Conclusions. Mean EQ-5D utility weights can be estimated from the EORTC QLQ-C30/QLQ-MY20 for use in CEAs. Frequentist and Bayesian methods produced effectively identical models. However, the Bayesian models provide distributions describing the uncertainty surrounding the estimated utility values and are thus more suited informing analyses for probabilistic CEAs.
Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma: Adding Ultrasound in Clinically Lymph Node Negative Patients May Improve Diagnostic Work-Up

Introduction Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US) is a non-expensive, accessible and non-ionising imaging modality this method is not consistently used. This study aimed to investigate if addition of US of patients classified as clinically LN negative (cN0) by CT and/or MRI, increases the detection of LN metastases. Also, we aimed to identify which of the sonographic characteristics: echogenicity, border, shape, appearance of hilum and nodal blood-flow pattern best detect metastases in this patient group. Method Fifty-one patients with OSCC classified as cN0 by CT/MRI were consecutively included and prospectively examined with US prior to sentinel node biopsy or selective neck dissection. Localisation, size and sonographic characteristics were registered for each LN and compared with the pathological findings. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different size measurements and sonographic characteristics. Results We found that short axial diameter was the best size criterion for detection of metastases. However, the sonographic characteristics were better predictors than size and the presence at least four of the sonographic characteristics: hypo-echoic or heterogeneous appearance; irregular border; spherical shape; absence of nodal hilum; and peripheral nodal blood-flow resulted in a sensitivity of 43.8; specificity 91.4; PPV 70.0; and NPV 78.0. The number of patients with occult metastases decreased from 16 out of 51 (31%) to nine out of 51 (18%). Three patients (6%) were over-staged by US. Conclusion The addition of US to the clinical work-up of patients with cN0 OSCC increases the detection of metastases, thus US potentially reduces the number of patients requiring a secondary neck surgery after sentinel node biopsy.
Internet of things: Survey on security

ABSTRACT The Internet of things (IoT) is intended for ubiquitous connectivity among different entities or “things”. While it provides effective and efficient solutions to many real world challenges, the security aspect of it has always been questioned. The situation is further exacerbated by the number of connected devices growing exponentially. As a result, security and privacy has emerged as a significant challenge for the IoT. In this paper, we aim to provide a thorough survey on IoT security and privacy challenges from the perspective of technologies and architecture used. This work focuses on IoT intrinsic vulnerabilities and their implications to the fundamental information security challenges in confidentiality, integrity, and availability. The approach of this survey is to summarize and synthesize published work in IoT; relate it to the security conjuncture of the field; and project future research directions.
Physiological Characterisation of Human iPS-Derived Dopaminergic Neurons

Human induced pluripotent stem cells (hiPSCs) offer the potential to study otherwise inaccessible cell types. Critical to this is the directed differentiation of hiPSCs into functional cell lineages. This is of particular relevance to research into neurological disease, such as Parkinson’s disease (PD), in which midbrain dopaminergic neurons degenerate during disease progression but are unobtainable until post-mortem. Here we report a detailed study into the physiological maturation over time of human dopaminergic neurons in vitro. We first generated and differentiated hiPSC lines into midbrain dopaminergic neurons and performed a comprehensive characterisation to confirm dopaminergic functionality by demonstrating dopamine synthesis, release, and re-uptake. The neuronal cultures include cells positive for both tyrosine hydroxylase (TH) and G protein-activated inward rectifier potassium channel 2 (Kir3.2, henceforth referred to as GIRK2), representative of the A9 population of substantia nigra pars compacta (SNc) neurons vulnerable in PD. We observed for the first time the maturation of the slow autonomous pace-making (<10 Hz) and spontaneous synaptic activity typical of mature SNc dopaminergic neurons using a combination of calcium imaging and electrophysiology. hiPSC-derived neurons exhibited inositol tri-phosphate (IP3) receptor-dependent release of intracellular calcium from the endoplasmic reticulum in neuronal processes as calcium waves propagating from apical and distal dendrites, and in the soma. Finally, neurons were susceptible to the dopamine neuron-specific toxin 1-methyl-4-phenylpyridinium (MPP+) which reduced mitochondrial membrane potential and altered mitochondrial morphology. Mature hiPSC-derived dopaminergic neurons provide a neurophysiologically-defined model of previously inaccessible vulnerable SNc dopaminergic neurons to bridge the gap between clinical PD and animal models.
KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques

Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues. NK cell responses in blood were broadly stimulated, as indicated by rapid increases in the CD16+ population during acute infection and sustained increases in the CD16+ and CD16-CD56- populations during chronic infection. Markers of proliferation (Ki-67), activation (CD69 & HLA-DR) and antiviral activity (CD107a & TNFα) were also widely expressed, but began to diverge during chronic infection, as reflected by sustained CD107a and TNFα upregulation by KIR3DL01+, but not by KIR3DL05+ NK cells. Significant increases in the frequency of KIR3DL01+ (but not KIR3DL05+) NK cells were also observed in tissues, particularly in the gut-associated lymphoid tissues, where this receptor was preferentially upregulated on CD56+ and CD16-CD56- subsets. These results reveal broad NK cell activation and dynamic changes in the phenotypic properties of NK cells in response to SIV infection, including the enrichment of KIR3DL01+ NK cells in tissues that support high levels of virus replication.
Molecular analysis and genetic diversity of Aedes albopictus (Diptera, Culicidae) from China

Abstract Aedes albopictus is one of the most invasive species, which can carry Dengue virus, Yellow fever virus and more than twenty arboviruses. Based on mitochondrial gene cytochrome c oxidase I (COI) and samples collected from 17 populations, we investigated the molecular character and genetic diversity of Ae. albopictus from China. Altogether, 25 haplotypes were detected, including 10 shared haplotypes and 15 private haplotypes. H1 was the dominant haplotype, which is widely distributed in 13 populations. Tajima’D value of most populations was significantly negative, demonstrating that populations experienced rapid range expansion recently. Most haplotypes clustered together both in phylogenetic and median-joining network analysis without clear phylogeographic patterns. However, neutrality tests revealed shallow divergences among Hainan and Guangxi with other populations (0.15599 ≤ FST ≤ 0.75858), which probably due to interrupted gene flow, caused by geographical isolations. In conclusion, Ae. albopictus populations showed low genetic diversity in China.
Systematic identification of feature combinations for predicting drug response with Bayesian multi-view multi-task linear regression

Motivation: A prime challenge in precision cancer medicine is to identify genomic and molecular features that are predictive of drug treatment responses in cancer cells. Although there are several computational models for accurate drug response prediction, these often lack the ability to infer which feature combinations are the most predictive, particularly for high‐dimensional molecular datasets. As increasing amounts of diverse genome‐wide data sources are becoming available, there is a need to build new computational models that can effectively combine these data sources and identify maximally predictive feature combinations. Results: We present a novel approach that leverages on systematic integration of data sources to identify response predictive features of multiple drugs. To solve the modeling task we implement a Bayesian linear regression method. To further improve the usefulness of the proposed model, we exploit the known human cancer kinome for identifying biologically relevant feature combinations. In case studies with a synthetic dataset and two publicly available cancer cell line datasets, we demonstrate the improved accuracy of our method compared to the widely used approaches in drug response analysis. As key examples, our model identifies meaningful combinations of features for the well known EGFR, ALK, PLK and PDGFR inhibitors. Availability and Implementation: The source code of the method is available at https://github.com/suleimank/mvlr. Contact: muhammad.ammad‐ud‐din@helsinki.fi or suleiman.khan@helsinki.fi Supplementary information: Supplementary data are available at Bioinformatics online.
Cxcl8b and Cxcr2 Regulate Neutrophil Migration through Bloodstream in Zebrafish

Neutrophils play an essential role during an inflammatory response, which is dependent on their rapid recruitment from the bone marrow to the vasculature. However, there is no information about the molecular signals that regulate neutrophil entry to circulation during an inflammatory process in humans. This is mainly due to the lack of a suitable model of study that contains similar set of molecules and that allows in vivo analyses. In this study, we used the zebrafish to assess the role of Cxcl8a, Cxcl8b, and Cxcr2 in neutrophil migration to blood circulation after injury. Using Tg(BACmpx:GFP)i114 transgenic embryos and two damage models (severe and mild), we developed in vivo lack of function assays. We found that the transcription levels of cxcl8a, cxcl8b, and cxcr2 were upregulated in the severe damage model. In contrast, only cxcr2 and cxcl8a mRNA levels were increased during mild damage. After knocking down Cxcl8a, neutrophil quantity decreased at the injury site, while Cxcl8b decreased neutrophils in circulation. When inhibiting Cxcr2, we observed a decrease in neutrophil entry to the bloodstream. In conclusion, we identified different functions for both Cxcl8 paralogues, being the Cxcl8b/Cxcr2 axis that regulates neutrophil entry to the bloodstream, while Cxcl8a/Cxcr2 regulates the migration to the affected area.
The Effects of Prediction on the Perception for Own-Race and Other-Race Faces

Human beings do not passively perceive important social features about others such as race and age in social interactions. Instead, it is proposed that humans might continuously generate predictions about these social features based on prior similar experiences. Pre-awareness of racial information conveyed by others' faces enables individuals to act in “culturally appropriate” ways, which is useful for interpersonal relations in different ethnicity groups. However, little is known about the effects of prediction on the perception for own-race and other-race faces. Here, we addressed this issue using high temporal resolution event-related potential techniques. In total, data from 24 participants (13 women and 11 men) were analyzed. It was found that the N170 amplitudes elicited by other-race faces, but not own-race faces, were significantly smaller in the predictable condition compared to the unpredictable condition, reflecting a switch to holistic processing of other-race faces when those faces were predictable. In this respect, top-down prediction about face race might contribute to the elimination of the other-race effect (one face recognition impairment). Furthermore, smaller P300 amplitudes were observed for the predictable than for unpredictable conditions, which suggested that the prediction of race reduced the neural responses of human brains.
CsPbX3 Quantum Dots for Lighting and Displays: Room‐Temperature Synthesis, Photoluminescence Superiorities, Underlying Origins and White Light‐Emitting Diodes

Recently, Kovalenko and co‐workers and Li and co‐workers developed CsPbX3 (X = Cl, Br, I) inorganic perovskite quantum dots (IPQDs), which exhibited ultrahigh photoluminescence (PL) quantum yields (QYs), low‐threshold lasing, and multicolor electroluminescence. However, the usual synthesis needs high temperature, inert gas protection, and localized injection operation, which are severely against applications. Moreover, the so unexpectedly high QYs are very confusing. Here, for the first time, the IPQDs' room‐temperature (RT) synthesis, superior PL, underlying origins and potentials in lighting and displays are reported. The synthesis is designed according to supersaturated recrystallization (SR), which is operated at RT, within few seconds, free from inert gas and injection operation. Although formed at RT, IPQDs' PLs have QYs of 80%, 95%, 70%, and FWHMs of 35, 20, and 18 nm for red, green, and blue emissions. As to the origins, the observed 40 meV exciton binding energy, halogen self‐passivation effect, and CsPbX3@X quantum‐well band alignment are proposed to guarantee the excitons generation and high‐rate radiative recombination at RT. Moreover, such superior optical merits endow them with promising potentials in lighting and displays, which are primarily demonstrated by the white light‐emitting diodes with tunable color temperature and wide color gamut.
Neuroanatomical changes in people with high schizotypy: relationship to glutamate levels

Background Cortical glutamatergic dysfunction is thought to be fundamental for psychosis development, and may lead to structural degeneration through excitotoxicity. Glutamate levels have been related to gray matter volume (GMV) alterations in people at ultra-high risk of psychosis, and we previously reported GMV changes in individuals with high schizotypy (HS), which refers to the expression of schizophrenia-like characteristics in healthy people. This study sought to examine whether GMV changes in HS subjects are related to glutamate levels. Methods We selected 22 healthy subjects with HS and 23 healthy subjects with low schizotypy (LS) based on their rating on a self-report questionnaire for psychotic-like experiences. Glutamate levels were measured in the bilateral anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, and GMV was assessed using voxel-based morphometry. Results Subjects with HS showed GMV decreases in the rolandic operculum/superior temporal gyrus (pFWE = 0.045). Significant increases in GMV were also detected in HS, in the precuneus (pFWE = 0.043), thereby replicating our previous finding in a separate cohort, as well as in the ACC (pFWE = 0.041). While the HS and LS groups did not differ in ACC glutamate levels, in HS subjects ACC glutamate was negatively correlated with ACC GMV (pFWE = 0.026). Such association was absent in LS. Conclusions Our study shows that GMV findings in schizotypy are related to glutamate levels, supporting the hypothesis that glutamatergic function may lead to structural changes associated with the expression of psychotic-like experiences.
In vitro antibiofilm and anti‐adhesion effects of magnesium oxide nanoparticles against antibiotic resistant bacteria

The aim of the current investigation was to determine the antibacterial and antibiofilm potential of MgO nanoparticles (NPs) against antibiotic‐resistant clinical strains of bacteria. MgO NPs were synthesized by a wet chemical method and further characterized by scanning electron microscopy and energy dispersive X‐ray. Antibacterial activity was determined by broth microdilution and agar diffusion methods. The Bradford method was used to assess cellular protein leakage as a result of loss of membrane integrity. Microtiter plate assay following crystal violet staining was employed to determine the effect of MgO NPs on biofilm formation and removal of established biofilms. MIC values ranged between 125 and 500 μg/mL. Moreover, treatment with MgO NPs accelerated rate of membrane disruption, measured as a function of leakage of cellular proteins. Leakage of cellular protein content was greater among gram‐negative bacteria. Cell adherence assay indicated 25.3–49.8% inhibition of bacterial attachment to plastic surfaces. According to a static biofilm method, MgO NPs reduced biofilm formation potential from 31% to 82.9% in a time‐dependent manner. Moreover, NPs also significantly reduced the biomass of 48, 72, 96 and 120 hr old biofilms (P < 0.05). Cytotoxicity experiments using a neutral red assay revealed that MgO NPs are non‐toxic to HeLa cells at concentrations of 15–120 μg/mL. These data provide in vitro scientific evidence that MgO NPs are effective and safe antibiofilm agents that inhibit adhesion, biofilm formation and removal of established biofilms of multidrug‐resistant bacteria.
Rational design for cervical cancer therapeutics: cellular and non-cellular based strategies on the horizon for recurrent, metastatic or refractory cervical cancer

ABSTRACT Introduction: Though cervical cytology, HPV DNA testing, and pre-invasive disease management has significantly reduced the number of new diagnoses of cervical cancer, women with persistent oncogenic HPV infection are at significant risk for developing invasive cervical cancer. Early stage and locally advanced disease can be cured, but women with advanced or recurrent disease have a very poor prognosis. This underscores the need for different treatment strategies for advanced cervical cancer, the most promising of which are novel therapeutics that target the ability of HPV to overcome host immune tolerance. Areas covered: This review includes new therapies being investigated for the treatment of recurrent, metastatic or refractory cervical cancer, separated into broad categories of cellular and non-cellular based strategies. Expert opinion: Advanced and recurrent cervical cancer has a poor prognosis, prompting investigations into the development of strategies that will eradicate tumor and/or overcome host immunologic tolerance of disease. It is unknown whether it will be these strategies alone or a combination of treatment modalities that will ultimately provide the best outcomes; nevertheless, the new data are promising.
Degradation law of municipal solid waste and settlement calculation of landfills

Based on organic matter degradation experiments performed on solid waste,a calculation formula to obtain the law of organic matter degradation in solid waste and method for parameter determination were proposed,and a settlement calculation model for solid waste was deduced.With the Xiaping Municipal Solid Waste Landfill taken as an example,laws of the rate and quantity of solid waste degradation varying with time were obtained by means of experimental data of amounts of organic matter and residue of degradation in test materials and the characteristic time of degradation.Analysis shows that the deformation calculation model is capable of reflecting the deformation characteristics of solid waste induced by compression and degradation.
Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells

Cells use multiple feedback controls to regulate metabolism in response to nutrient and signaling inputs. However, feedback creates the potential for unstable network responses. We examined how concentrations of key metabolites and signaling pathways interact to maintain homeostasis in proliferating human cells, using fluorescent reporters for AMPK activity, Akt activity, and cytosolic NADH/NAD+ redox. Across various conditions including metabolic (glycolytic or mitochondrial) inhibition or cell proliferation, we observed distinct patterns of AMPK activity, including stable adaptation and highly dynamic behaviors such as periodic oscillations and irregular fluctuations, indicating a failure to reach a steady state. Fluctuations in AMPK activity, Akt activity, and cytosolic NADH/NAD+redox state were temporally linked in individual cells adapting to metabolic perturbations. By monitoring single-cell dynamics in each of these contexts, we identified PI3K/Akt regulation of glycolysis as a multifaceted modulator of single-cell metabolic dynamics that is required to maintain metabolic stability in proliferating cells.