Miracle-dz/UniFAR-FTUs huggingface dataset:
Automated Lung Nodule Detection and Classification Using Deep Learning Combined with Multiple Strategies

Lung cancer is one of the major causes of cancer-related deaths due to its aggressive nature and delayed detections at advanced stages. Early detection of lung cancer is very important for the survival of an individual, and is a significant challenging problem. Generally, chest radiographs (X-ray) and computed tomography (CT) scans are used initially for the diagnosis of the malignant nodules; however, the possible existence of benign nodules leads to erroneous decisions. At early stages, the benign and the malignant nodules show very close resemblance to each other. In this paper, a novel deep learning-based model with multiple strategies is proposed for the precise diagnosis of the malignant nodules. Due to the recent achievements of deep convolutional neural networks (CNN) in image analysis, we have used two deep three-dimensional (3D) customized mixed link network (CMixNet) architectures for lung nodule detection and classification, respectively. Nodule detections were performed through faster R-CNN on efficiently-learned features from CMixNet and U-Net like encoder–decoder architecture. Classification of the nodules was performed through a gradient boosting machine (GBM) on the learned features from the designed 3D CMixNet structure. To reduce false positives and misdiagnosis results due to different types of errors, the final decision was performed in connection with physiological symptoms and clinical biomarkers. With the advent of the internet of things (IoT) and electro-medical technology, wireless body area networks (WBANs) provide continuous monitoring of patients, which helps in diagnosis of chronic diseases—especially metastatic cancers. The deep learning model for nodules’ detection and classification, combined with clinical factors, helps in the reduction of misdiagnosis and false positive (FP) results in early-stage lung cancer diagnosis. The proposed system was evaluated on LIDC-IDRI datasets in the form of sensitivity (94%) and specificity (91%), and better results were obatined compared to the existing methods.
Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance

ABSTRACT Hypothalamic glial cells named tanycytes, which line the 3rd ventricle (3V), are components of the hypothalamic network that regulates a diverse array of metabolic functions for energy homeostasis. Herein, we report that TSPO (translocator protein), an outer mitochondrial protein, is highly enriched in tanycytes and regulates homeostatic responses to nutrient excess as a potential target for an effective intervention in obesity. Administration of a TSPO ligand, PK11195, into the 3V, and tanycyte-specific deletion of Tspo reduced food intake and elevated energy expenditure, leading to negative energy balance in a high-fat diet challenge. Ablation of tanycytic Tspo elicited AMPK-dependent lipophagy, breaking down lipid droplets into free fatty acids, thereby elevating ATP in a lipid stimulus. Our findings suggest that tanycytic TSPO affects systemic energy balance through macroautophagy/autophagy-regulated lipid metabolism, and highlight the physiological significance of TSPO in hypothalamic lipid sensing and bioenergetics in response to overnutrition. Abbreviations 3V: 3rd ventricle; ACAC: acetyl-Coenzyme A carboxylase; AGRP: agouti related neuropeptide; AIF1/IBA1: allograft inflammatory factor 1; AMPK: AMP-activated protein kinase; ARC: arcuate nucleus; Atg: autophagy related; Bafilo: bafilomycin A1; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CNS: central nervous system; COX4I1: cytochrome c oxidase subunit 4I1; FFA: free fatty acid; GFAP: glial fibrillary acidic protein; HFD: high-fat diet; ICV: intracerebroventricular; LAMP2: lysosomal-associated membrane protein 2; LD: lipid droplet; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MBH: mediobasal hypothalamus; ME: median eminence; MEF: mouse embryonic fibroblast; NCD: normal chow diet; NEFM/NFM: neurofilament medium; NPY: neuropeptide Y; OL: oleic acid; POMC: pro-opiomelanocortin-alpha; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; Rax: retina and anterior neural fold homeobox; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; RER: respiratory exchange ratio; siRNA: small interfering RNA; SQSTM1: sequestosome 1; TG: triglyceride; TSPO: translocator protein; ULK1: unc-51 like kinase 1; VCO2: carbon dioxide production; VMH: ventromedial hypothalamus; VO2: oxygen consumption
High Prevalence of Sticky Platelet Syndrome in Patients with Infertility and Pregnancy Loss

Platelet hyperaggregability, known as sticky platelet syndrome (SPS), is a prothrombotic disorder that has been increasingly associated with pregnancy loss. In this retrospective study, we aimed to investigate the clinical and diagnostic relevance of SPS in 208 patients with infertility and unexplained pregnancy loss history. We studied 208 patients that had been referred to undergo a dose-dependent platelet aggregation response to adenosine diphosphate and epinephrine using light transmission aggregometry modified by Mammen during an 11-year period. Patients’ platelet aggregation response was compared with platelet function in 29 female healthy controls of fertile age with no previous history of pregnancy loss. We found a prevalence of SPS type II (33.2%) in 208 female patients with infertility and pregnancy loss. ∆-epinephrine-induced platelet aggregation in patients with SPS was significantly decreased (median 7% and range −21 to 43%) compared to patients without SPS (median 59%, range 7–88% and p < 0.0001) and healthy controls (median 57%, range 8–106% and p < 0.0001). The optimum SPS-diagnostic cutoff value for ∆-epinephrine aggregation was ≤32% (sensitivity 95.7%, specificity 95.2%). SPS patients with low-dose acetylsalicylic acid (ASA) therapy (n = 56) showed improved pregnancy outcome (32 pregnancies; live births n = 18 (56%)) compared to SPS patients without low-dose ASA (n = 13) (3 pregnancies; live births n = 1 (33%)). Our study demonstrates the clinical and diagnostic relevance of platelet hyperaggregation in women with infertility and pregnancy loss history. Further studies should investigate the potential of SPS as a novel decisional tool with both diagnostic and clinical implications in infertility and pregnancy loss.
Situation Awareness and Transitions in Highly Automated Driving:A Framework and Mini Review

The human factors of transition in highly automated driving is becoming crucial, because transitions between the driver and the automation will remain a key element of automated driving until fully automated driving replace manual operation. This paper aims to suggest the framework to investigate human factors in transition of highly automated driving. The framework classifies transitions according to the transition initiator, control after transition, and situation awareness. Based on the framework, we retrieved previous studies and categorized their experimental designs. The inclusion criteria for the review were transitions which involved SAE level 3 automated driving and the research topics on driver behavior and/or performance during a transition. Finally, we interpreted the empirical studies on transitions using the proposed framework, and suggested areas for future research.
Targeting of CD133+ Cancer Stem Cells by Mesenchymal Stem Cell Expressing TRAIL Reveals a Prospective Role of Apoptotic Gene Regulation in Non-Small Cell Lung Cancer

Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.
Viral Metagenomics in the Clinical Realm: Lessons Learned from a Swiss-Wide Ring Trial

Shotgun metagenomics using next generation sequencing (NGS) is a promising technique to analyze both DNA and RNA microbial material from patient samples. Mostly used in a research setting, it is now increasingly being used in the clinical realm as well, notably to support diagnosis of viral infections, thereby calling for quality control and the implementation of ring trials (RT) to benchmark pipelines and ensure comparable results. The Swiss NGS clinical virology community therefore decided to conduct a RT in 2018, in order to benchmark current metagenomic workflows used at Swiss clinical virology laboratories, and thereby contribute to the definition of common best practices. The RT consisted of two parts (increments), in order to disentangle the variability arising from the experimental compared to the bioinformatics parts of the laboratory pipeline. In addition, the RT was also designed to assess the impact of databases compared to bioinformatics algorithms on the final results, by asking participants to perform the bioinformatics analysis with a common database, in addition to using their own in-house database. Five laboratories participated in the RT (seven pipelines were tested). We observed that the algorithms had a stronger impact on the overall performance than the choice of the reference database. Our results also suggest that differences in sample preparation can lead to significant differences in the performance, and that laboratories should aim for at least 5–10 Mio reads per sample and use depth of coverage in addition to other interpretation metrics such as the percent of coverage. Performance was generally lower when increasing the number of viruses per sample. The lessons learned from this pilot study will be useful for the development of larger-scale RTs to serve as regular quality control tests for laboratories performing NGS analyses of viruses in a clinical setting.
Avoidance of carnivore carcasses by vertebrate scavengers enables colonization by a diverse community of carrion insects

Carrion resources sustain a complex and diverse community of both vertebrate and invertebrate scavengers, either obligate or facultative. However, although carrion ecology has received increasing scientific attention in recent years, our understanding of carrion partitioning in natural conditions is severely limited as most studies are restricted either to the vertebrate or the insect scavenger communities. Moreover, carnivore carcasses have been traditionally neglected as study model. Here, we provide the first data on the partitioning between vertebrate and invertebrate scavengers of medium-sized carnivore carcasses, red fox (Vulpes vulpes (Linnaeus)), in two mountainous Mediterranean areas of south-eastern Spain. Carcasses were visited by several mammalian and avian scavengers, but only one carcass was partially consumed by golden eagle Aquila chrysaetos (Linnaeus). These results provide additional support to the carnivore carrion-avoidance hypothesis, which suggests that mammalian carnivores avoid the consumption of carnivore carcasses to prevent disease transmission risk. In turn, the absence of vertebrate scavengers at carnivore carcasses enabled a diverse and well-structured successional community of insects to colonise the carcasses. The observed richness and abundance of the most frequent families was more influenced by the decomposition time than by the study area. Overall, our study encourages further research on carrion resource partitioning in natural conditions.
The Human Ovary and Future of Fertility Assessment in the Post-Genome Era

Proteomics has opened up new avenues in the field of gynecology in the post-genome era, making it possible to meet patient needs more effectively and improve their care. This mini-review aims to reveal the scope of proteomic applications through an overview of the technique and its applications in assisted procreation. Some of the latest technologies in this field are described in order to better understand the perspectives of its clinical applications. Proteomics seems destined for a promising future in gynecology, more particularly in relation to the ovary. Nevertheless, we know that reproductive biology proteomics is still in its infancy and major technical and ethical challenges must first be overcome.
Probiotics for the treatment of type 2 diabetes: A review of randomized controlled trials

With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is increased interest in probiotic supplementation for improving glycaemic control. This review evaluates nine randomized controlled trials that tested the effects of probiotics on glycaemic outcomes including fasting plasma glucose, fasting plasma insulin, haemoglobin A1c, and homeostatic model assessment of insulin resistance among adults with T2DM. Based on the evidence reviewed, multistrain probiotics that contain seven million to 100 billion colony forming units of Lactobacillus acidophilus, Streptococcus thermophilus, Lactobacillus bulgaricus, and/or Bifidobacterium lactis administered for 6 to 12 weeks may be efficacious for improving glycaemic control in adults with T2DM. Further research is needed to understand the role of the gut microbiota and the probiotic dose, medium, and duration of exposure that is most effective for disease management.
Electrocardiographic and echocardiographic evaluation in dogs with hypothyroidism before and after levothyroxine supplementation: A prospective controlled study

Abstract Background Improvement in cardiac function has been demonstrated after thyroxine treatment in humans with hypothyroidism using the myocardial performance index (MPI). Cardiac changes after thyroxine supplementation are poorly documented in dogs with spontaneous hypothyroidism and comparison with clinically healthy dogs is lacking. Objectives To evaluate the electrical activity and mechanical function of the heart in dogs with primary hypothyroidism at baseline (T0) and after thyroxine supplementation (T60). Animals Forty client‐owned dogs with hypothyroidism and 20 clinically healthy dogs. Methods Prospective cohort study. Selected electrocardiographic and echocardiographic variables, including the MPI, were measured in all dogs at T0 and in 30 hypothyroid dogs at T60. Results Hypothyroid dogs had significantly decreased median or mean heart rate (HR), P wave amplitude, and R wave amplitude (P = .04, P = .002, and P = .003, respectively) and E‐point‐to‐septal separation normalized to body weight (EPSSn) and trans‐mitral E wave velocity (E max; P < .001 and P = .025, respectively) at T0 compared to control dogs. At T60, significantly increased median or mean HR, P wave amplitude, fractional shortening, and E max (P < .001, P = .004, P = .002, and P = .009, respectively) and significantly decreased left ventricular end‐diastolic volume index, and normalized systolic diameter and EPSSn (P = .03, P = .03, and P = .001, respectively) were found. Conclusions and Clinical Importance Hypothyroidism in dogs induces mild and reversible changes of electromechanical cardiac function. The MPI does not have clinical importance in identifying cardiac dysfunction in affected dogs.
Evaluating imprecision in engineering design

Imprecision is uncertainty that arises because of vague or incomplete information. Preliminary design information is characteristically imprecise: specifications and requirements are subject to change, and the design description is vague and incomplete. Yet many powerful evaluation tools, including finite element models, expect precisely specified data. Thus it is common for engineers to evaluate promising designs one by one. Alternatively, optimization may be used to search for the single "best" design. These approaches focus on individual, precisely specified points in the design space and provide limited information about the full range of acceptable designs. An alternative approach would be to evaluate sets of designs. The method of imprecision uses the mathematics of fuzzy sets in order to represent imprecision as preferences among designs: • Functional requirements model the customer's direct preference on performance variables based on performance considerations: the quantified aspects of design performance represented by performance variables. • Design preferences model the customer's anticipated preference on design variables based on design considerations: the unquantified aspects of design performance not represented by performance variables. Design preferences provide a formal structure for representing "soft" issues such as aesthetics and manufacturability and quantifying their consequences. This thesis describes continuing work in bringing the method of imprecision closer to implementation as a decision-making methodology for engineering design. The two principal contributions of this work are a clearer interpretation of the elements that comprise the method and a more efficient computational implementation. The proposed method for modeling design decisions in the presence of imprecision is defined in detail. The decision-maker is modeled as a hierarchy of preference aggregation operations. Axioms for rational design decision-making are used to define aggregation operations that are suitable for design. An electric vehicle design example illustrates the method. In particular, the process of determining preferences and a preference aggregation hierarchy is shown to be both feasible and informative. Efficient computational methods for performing preference calculations are introduced. These methods use experiment design to explore the design space and optimization assisted by linear approximation to map preferences. A user-specified fractional precision allows the number of function evaluations to be traded-off against the quality of the answer obtained. The computational methods developed are verified on design problems from aircraft engine development and automobile body design. Procedures for specifying preferences and group decisionmaking are described. These procedures provide not only a pragmatic interpretation of the method, but also an informal solution to the problem of bargaining: prerequisites for bringing the method to design problems in the real world.
Composition and structure of synaptic ectosomes exporting antigen receptor linked to functional CD40 ligand from helper T cells

Cell communication through extracellular vesicles is an emerging topic in biology, including communication between cells of the immune system. Planar supported lipid bilayers (PSLBs) presenting T cell receptor (TCR) ligands and intercellular adhesion molecule-1 (ICAM-1) induce budding of extracellular microvesicles enriched in functional TCR, defined here as synaptic ectosomes (SE), from helper T cells. SE bind peptide-MHC directly exporting TCR into the synaptic cleft, but their ability to incorporate other effectors is unknown. Here, we utilized bead supported lipid bilayers (BSLB) to capture SE from single immunological synapses (IS), determined SE composition by immunofluorescence flow cytometry and enriched SE for proteomic analysis by particle sorting. Our results demonstrate selective enrichment of CD40 ligand (CD40L) and inducible T-cell costimulator (ICOS) in SE in response to addition of CD40 and ICOS ligand (ICOSL), respectively, to SLB presenting TCR ligands and ICAM-1. TCR triggering mobilized intracellular CD40L to the T cells surface at the IS, where it engaged CD40 to enable sorting into SE. SEs were enriched in tetraspanins and bone marrow stromal cell antigen 2 (BST-2) by immunofluorescence and TCR signalling and endosomal sorting complexes required for transport by proteomics. Super-resolution microscopy demonstrated that CD40L is present in microclusters within CD81 defined SE that are spatially segregated from TCR/ICOS/BST-2 microclusters. CD40L in SE retains the capacity to induce dendritic cell (DC) maturation and cytokine production. SE enabled helper T cells to release effectors physically linked to TCR. One Sentence Summary TCR and CD40L microclusters can be linked in synaptic ectosomes (extracellular vesicles) that are released in the immunological synapse by helper T cells and induce dendritic cell maturation and cytokine production.
The Effect of Carbonic Maceration during Winemaking on the Color, Aroma and Sensory Properties of ‘Muscat Hamburg’ Wine

This is the first study on the effect of carbonic maceration on the quality (color, aroma profile and sensory properties) of Muscat Hamburg, contrasting two winemaking procedures used in Tianjin (classical white and red-winemaking techniques). The values of C* (psychometric chroma), a* (measure of redness) and b* (measure of yellowness) were significantly higher (p < 0.01) in the carbonic macerated wine than in red wine. However, there were no visual differences in color, and classical red wine and carbonic macerated wine had similar h (hue angle) values and located in the red region. Thirty-two aromatic compounds were identified and quantified in Muscat Hamburg wines. The content of volatile compounds (6384.97 μg/L) was significantly higher (p < 0.001) in the carbonic macerated Muscat Hamburg wine than in the other kinds of wine. This result led to the carbonic macerated wine having the highest odor activity values (OAVs) and sensory evaluation scores (86.8 points), which correlates with an “excellent” sensory perception. This study demonstrated that carbonic maceration significantly improved the quality of Muscat Hamburg wine based on volatile analysis and sensory evaluation compared with other conventional methods. Therefore, carbonic maceration could be well suited for making Muscat Hamburg wine.