Miracle-dz/UniFAR-FTUs huggingface dataset:
Design and Implementation of NK Cell-Based Immunotherapy to Overcome the Solid Tumor Microenvironment

Simple Summary Cell therapy over the last few years has revolutionized the treatment of blood cancers. However, efficacy against cancers of solid organs remains limited. These cancers pose a major challenge to the success of cell therapy by generating a suppressive environment that inhibits immunity. We review current efforts to improve the potency of natural killer (NK) cell therapy in the tumor microenvironment. The successful application of these approaches will lead to more effective treatment options and improve clinical outcomes for patients with solid cancers. Abstract Natural killer (NK) cells are innate immune effectors capable of broad cytotoxicity via germline-encoded receptors and can have conferred cytotoxic potential via the addition of chimeric antigen receptors. Combined with their reduced risk of graft-versus-host disease (GvHD) and cytokine release syndrome (CRS), NK cells are an attractive therapeutic platform. While significant progress has been made in treating hematological malignancies, challenges remain in using NK cell-based therapy to combat solid tumors due to their immunosuppressive tumor microenvironments (TMEs). The development of novel strategies enabling NK cells to resist the deleterious effects of the TME is critical to their therapeutic success against solid tumors. In this review, we discuss strategies that apply various genetic and non-genetic engineering approaches to enhance receptor-mediated NK cell cytotoxicity, improve NK cell resistance to TME effects, and enhance persistence in the TME. The successful design and application of these strategies will ultimately lead to more efficacious NK cell therapies to treat patients with solid tumors. This review outlines the mechanisms by which TME components suppress the anti-tumor activity of endogenous and adoptively transferred NK cells while also describing various approaches whose implementation in NK cells may lead to a more robust therapeutic platform against solid tumors.
Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State

Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, with its paracellular tight junctions, to maintain the balance, tolerance, and resistance to foreign/neo-antigens. The physiological regulator of paracellular tight junctions plays a vital role in transferring macromolecules across the intestinal barrier and thereby maintains immune response equilibrium. A new paradigm has explained the intricacies of disease development and proposed that the processes can be prevented if the interaction between the genetic factor and environmental causes is barred by re-instituting the intestinal wall function. The latest clinical evidence and animal models reinforce this current thought and offer the basis for innovative methodologies to thwart and treat autoimmune syndromes.
Adaptive Anomaly Detection Framework Model Objects in Cyberspace

Telecommunication has registered strong and rapid growth in the past decade. Accordingly, the monitoring of computers and networks is too complicated for network administrators. Hence, network security represents one of the biggest serious challenges that can be faced by network security communities. Taking into consideration the fact that e-banking, e-commerce, and business data will be shared on the computer network, these data may face a threat from intrusion. The purpose of this research is to propose a methodology that will lead to a high level and sustainable protection against cyberattacks. In particular, an adaptive anomaly detection framework model was developed using deep and machine learning algorithms to manage automatically-configured application-level firewalls. The standard network datasets were used to evaluate the proposed model which is designed for improving the cybersecurity system. The deep learning based on Long-Short Term Memory Recurrent Neural Network (LSTM-RNN) and machine learning algorithms namely Support Vector Machine (SVM), K-Nearest Neighbor (K-NN) algorithms were implemented to classify the Denial-of-Service attack (DoS) and Distributed Denial-of-Service (DDoS) attacks. The information gain method was applied to select the relevant features from the network dataset. These network features were significant to improve the classification algorithm. The system was used to classify DoS and DDoS attacks in four stand datasets namely KDD cup 199, NSL-KDD, ISCX, and ICI-ID2017. The empirical results indicate that the deep learning based on the LSTM-RNN algorithm has obtained the highest accuracy. The proposed system based on the LSTM-RNN algorithm produced the highest testing accuracy rate of 99.51% and 99.91% with respect to KDD Cup'99, NSL-KDD, ISCX, and ICI-Id2017 datasets, respectively. A comparative result analysis between the machine learning algorithms, namely SVM and KNN, and the deep learning algorithms based on the LSTM-RNN model is presented. Finally, it is concluded that the LSTM-RNN model is efficient and effective to improve the cybersecurity system for detecting anomaly-based cybersecurity.
Phenolic Constituents of Lamium album L. subsp. album Flowers: Anatomical, Histochemical, and Phytochemical Study

Flos Lamii albi has a high biological activity and is widely used in herbal medicine. The aim of the study was to characterize the secretory structures present in Lamium album subsp. album corolla and the location of phenolic compounds. Additionally, we carried out qualitative phytochemical analyses of flavonoids and phenolic acids. Light, fluorescence, and scanning electron microscopy were used to analyze the structure of the floral organs. The main classes of phenolic compounds and their localization were determined histochemically. Phytochemical analyses were performed with high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC). Six types of glandular trichomes were found which contained flavonoids, phenolic acids, and tannins. The phytochemical studies demonstrated the presence of caffeic, chlorogenic, ferulic, gallic, p-coumaric, protocatechuic, syringic, gentisic, and vanillic phenolic acids as well as rutoside, isoquercetin, and quercetin flavonoids. The corolla in L. album subsp. album has antioxidant properties due to the presence of various polyphenols, as shown by the histo- and phytochemical analyses. The distribution and morphology of trichomes and the content of phenolic compounds in the corolla have taxonomic, pharmacognostic, and practical importance, facilitating the identification of the raw material.
Epidemiologic Analysis of Taiwanese Patients with Idiopathic Pulmonary Fibrosis

Several databases of epidemiologic studies in patients with idiopathic pulmonary fibrosis (IPF) have been analyzed in the Western community. However, few studies have been reported in Asia. The objective of this study was to investigate the epidemiology of IPF in Taiwan. We collected and analyzed patients with IPF from the Taiwan National Health Insurance Research Database from 2001 to 2011. We estimated the annual incidence and cumulative prevalence of IPF and mean survival time of patients and determined the causes of death. The annual incidence rates of IPF remained stable after 2005, ranging from 0.7 to 1.3 cases per 100,000 people per year, whereas the cumulative prevalence rates increased steadily from 3.1 to 6.4 cases per 100,000 people per year during 2006–2011 based on a narrow case definition. Men older than 75 years had higher incidence compared with other age groups. The mean survival after diagnosis was 6.9 years. Old age, male sex, and respiratory hospitalization were associated with shorter survival time after diagnosis. Both the incidence and prevalence rates of IPF were lower in Taiwanese patients than Western ones. Moreover, the survival time was higher in the Asian population compared with the Western population. These results may suggest the heterogeneity of the IPF definition in different study populations and geographic locations.
SELECTIVE CHEMISORPTION OF CARBON-MONOXIDE AND HYDROGEN OVER SUPPORTED MOLYBDENUM CARBIDE CATALYSTS

Molybdenum carbides is being considered as a potential replacement for noble metals in some catalytic processes. Such catalysts have demonstrated performance in hydrocarbon synthesis from CO and H{sub 2}, hydrogenation of benzene, alcohol synthesis, etc. This paper reports work to measure the intrinsic activity of this material in comparison with known catalysts. The work is done by studying selective chemisorption of CO and H{sub 2} in much more detail than was done in earlier preliminary work.
An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

Simple Summary Prostate cancer is the second most common cancer in men. In many cases, prostate cancer grows very slowly and remains confined to the prostate. These localized cancers can usually be cured. However, prostate cancer can also metastasize to other organs of the body, which often results in death of the patient. We found that a cluster of genes involved in accumulation and utilization of fats exists in multiple copies and is expressed at much higher levels in metastatic prostate cancer compared to localized disease. These genes, called fatty acid-binding protein (or FABP) genes, individually and collectively, promote properties associated with prostate cancer metastasis. We propose that levels of these FABP genes may serve as an indicator of prostate cancer aggressiveness, and that inhibiting the action of FABP genes may provide a new approach to prevent and/or treat metastatic prostate cancer. Abstract Treatment for early stage and localized prostate cancer (PCa) is highly effective. Patient survival, however, drops dramatically upon metastasis due to drug resistance and cancer recurrence. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. It is therefore crucial to decipher the key genetic alterations and relevant molecular pathways driving PCa metastatic progression so that predictive biomarkers and precise therapeutic targets can be developed. Through PCa cohort analysis, we found that a fatty acid-binding protein (FABP) gene cluster (containing five FABP family members) is preferentially amplified and overexpressed in metastatic PCa. All five FABP genes reside on chromosome 8 at 8q21.13, a chromosomal region frequently amplified in PCa. There is emerging evidence that these FABPs promote metastasis through distinct biological actions and molecular pathways. In this review, we discuss how these FABPs may serve as drivers/promoters for PCa metastatic transformation using patient cohort analysis combined with a review of the literature.
PAFway: pairwise associations between functional annotations in biological networks and pathways

Abstract Motivation Large gene networks can be dense and difficult to interpret in a biologically meaningful way. Results Here, we introduce PAFway, which estimates pairwise associations between functional annotations in biological networks and pathways. It answers the biological question: do genes that have a specific function tend to regulate genes that have a different specific function? The results can be visualized as a heatmap or a network of biological functions. We apply this package to reveal associations between functional annotations in an Arabidopsis thaliana gene network. Availability and implementation PAFway is submitted to CRAN. Currently available here: https://github.com/ezer/PAFway. Supplementary information Supplementary data are available at Bioinformatics online.
Dynamic Fault Interaction during a Fluid-Injection-Induced Earthquake: The 2017 Mw 5.5 Pohang Event

The November 15th, 2017 Mw 5.5 Pohang earthquake (South Korea) has been linked to hydraulic stimulation and fluid injections, making this the largest induced seismic event associated with an Enhanced Geothermal System (EGS). To understand its source dynamics and fault interactions, we conduct the first 3D high-resolution spontaneous dynamic rupture simulations of an induced earthquake. We account for topography, off-fault plastic deformation under depth-dependent bulk cohesion, rapid velocity weakening friction and 1D subsurface structure. A guided fault reconstruction approach that clusters spatio-temporal aftershock locations (including their uncertainties) is used to identify a main and a secondary fault plane that intersects under a shallow angle of 15°. Based on simple Mohr-Coulomb failure analysis and 180 dynamic rupture experiments in which we vary local stress loading conditions, fluid pressure, and relative fault strength, we identify preferred two fault plane scenarios that well reproduce observations. We find that the regional far-field tectonic stress regime promotes pure strike-slip faulting, while local stress conditions constrained by borehole logging generate the observed thrust faulting component. Our preferred model is characterized by overpressurized pore fluids, non-optimally oriented but dynamically weak faults and a close to critical local stress state. In our model, earthquake rupture “jumps” to the secondary fault by dynamic triggering, generating a measurable non-double couple component. Our simulations suggest that complex dynamic fault interaction may occur during fluid-injection induced earthquakes and that local stress perturbations dominate over the regional stress conditions. These findings, therefore, have important implications for seismic hazard in active geo-reservoir.
Ta‐based barrier layer of ohmic interconnects for highly reliable GaN HEMTs

In this paper, we demonstrated a highly reliable Ta-based barrier metal between Al-based ohmic electrodes and Au interconnects for GaN-based high electron mobility transistors (HEMTs). The thermal stability of various barrier metals including conventional Pt, Ta, TaN, bi-layer Ta(lower layer)/TaN(upper layer) and bi-layer TaN(lower layer)/Ta(upper layer) was investigated. After annealing at ambient temperature (Ta) of 450 °C in a nitrogen atmosphere, it was found that bi-layer Ta/TaN barrier metal showed superior thermal stability of surface morphology and stack layer structure compared to other barrier metals. Furthermore, the reliability of the Ta/TaN applied GaN HEMT and the Pt applied one were investigated at Tj of 315 °C in the pinch-off state (Vgs = -5 V, Vds = 50 V). Though the device with Pt barrier metal showed a nearly 50% reduction in maximum saturation drain current (Imax) within 34 hours, no reduction in Imax was observed for 482 hours in the device with the Ta/TaN barrier met al. Based on TEM-EDX analysis, it was found that Au and Al inter-diffusion could be completely suppressed by the Ta/TaN barrier metal (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Exploring Hedging Strategies Identified by Fractal Dimensions

A hedging strategy is designed to increase the likelihood of desired financial out-comes. Market speculators hedge investment positions if they are worth protecting against potential negative outcomes on the underlying investment. Such negative outcomes cannot be avoided altogether, but effective hedging can reduce impact severity. The investment strategy includes an index held by investors (long position) and uses a fractal dimension indicator to warn when liquidity or sentiment changes are imminent. When the named indicator breaches a certain threshold, a hedging position is taken. This sequence of events triggers the implementation of a hedging strategy by entering a buy put-option position. The daily cumulative returns on using the fractal dimension indicators were 83% more profitable on average when applied to each chosen index respectively.
Legislation Related to E-Cigarettes in The Gulf Cooperation Council Countries

Even though 90% of the world’s population is covered by the World Health Organization’s Framework Convention on Tobacco Control, it is estimated that only one-fifth (21%) and half (49%) of the countries that ratified this convention will achieve the target of reducing tobacco use by 30 % among men and women respectively in 2025. Over the past decade, there has been an increasing trend in the use of electronic cigarettes or e-cigarettes for recreational use as well as smoking cessation. In concurrence with the increasing use of e-cigarettes among smokers of different age groups, nations have developed relevant national regulations on its sale, advertisement, packaging, product regulation, taxation, and surveillance. The countries of the Gulf Cooperation Council (GCC) region have also witnessed several legislations, at varying extent, related to the use of electronic cigarettes. However, the evidence on the use of electronic nicotine delivery systems remains scarce in the GCC region. Thus, further research on this emerging public health issue is warranted to generate the evidence necessary for the formulation of comprehensive tobacco control laws and effective prevention strategies.
Modeling by disruption and a selected‐for partner for the nude locus

A long‐standing problem in biology is how to dissect traits for which no tractable model exists. Here, we screen for genes like the nude locus (Foxn1)—genes central to mammalian hair and thymus development—using animals that never evolved hair, thymi, or Foxn1. Fruit flies are morphologically disrupted by the FOXN1 transcription factor and rescued by weak reductions in fly gene function, revealing molecules that potently synergize with FOXN1 to effect dramatic, chaotic change. Strong synergy/effectivity in flies is expected to reflect strong selection/functionality (purpose) in mammals; the more disruptive a molecular interaction is in alien contexts (flies), the more beneficial it will be in its natural, formative contexts (mammals). The approach identifies Aff4 as the first nude‐like locus, as murine AFF4 and FOXN1 cooperatively induce similar cutaneous/thymic phenotypes, similar gene expression programs, and the same step of transcription, pre‐initiation complex formation. These AFF4 functions are unexpected, as AFF4 also serves as a scaffold in common transcriptional‐elongation complexes. Most likely, the approach works because an interaction's power to disrupt is the inevitable consequence of its selected‐for power to benefit.
Synthesis, inhibitory activity and oral dosing formulation of AV5124, the structural analogue of influenza virus endonuclease inhibitor baloxavir.

BACKGROUND The development and clinical implementation of the cap-dependent endonuclease (CEN) inhibitor baloxavir marboxil was a breakthrough in influenza therapy, but it was associated with the emergence of drug-resistant variants. OBJECTIVES To design and synthesize structural analogues of CEN inhibitors and evaluate their safety, pharmacokinetics and antiviral potency in vitro and in vivo. METHODS The drug candidate AV5124 and its active metabolite AV5116 were synthesized based on pharmacophore modelling. Stability in plasma and microsomes, plasma protein binding, cytotoxicity and antiviral activities were assessed in vitro. Pharmacokinetics after IV or oral administration were analysed in CD-1 mice. Acute toxicity and protective efficacy against lethal A(H1N1)pdm09 influenza virus challenge were examined in BALB/c mice. RESULTS Pharmacophore model-assisted, 3D molecular docking predicted key supramolecular interactions of the metal-binding group and bulky hydrophobic group of AV5116 with the CEN binding site (Protein Data Bank code: 6FS6) that are essential for high antiviral activity. AV5116 inhibited influenza virus polymerase complexes in cell-free assays and replication of oseltamivir-susceptible and -resistant influenza A and B viruses at nanomolar concentrations. Notably, AV5116 was equipotent or more potent than baloxavir acid (BXA) against WT (I38-WT) viruses and viruses with reduced BXA susceptibility carrying an I38T polymerase acidic (PA) substitution. AV5116 exhibited low cytotoxicity in Madin-Darby canine kidney cells and lacked mitochondrial toxicity, resulting in favourable selective indices. Treatment with 20 or 50 mg/kg AV5124 prevented death in 60% and 100% of animals, respectively. CONCLUSIONS Overall, AV5124 and A5116 are promising inhibitors of the influenza virus CEN and warrant further development as potent anti-influenza agents.
Trematode parasites exceed aquatic insect biomass in Oregon stream food webs.

1) Although parasites are increasingly recognized for their ecosystem roles, it is often assumed that free-living organisms dominate animal biomass in most ecosystems and therefore provide the primary pathways for energy transfer. 2) To examine the contributions of parasites to ecosystem energetics in freshwater streams, we quantified the standing biomass of trematodes and free-living organisms at nine sites in three streams in western Oregon, USA. We then compared rates of biomass flow from snails (Juga plicifera) into trematode parasites relative to aquatic vertebrate predators (sculpin, cutthroat trout, and Pacific giant salamanders). 3) The trematode parasite community had the fifth highest dry biomass density among stream organisms (0.40 g m-2 ) and exceeded the combined biomass of aquatic insects. Only host snails (3.88 g m-2 ), sculpin (1.11 g m-2 ), trout (0.73 g m-2 ), and crayfish (0.43 g m-2 ) had a greater biomass. The parasite 'extended phenotype', consisting of trematode plus castrated host biomass, exceeded the individual biomass of every taxonomic group other than snails. The substantial parasite biomass stemmed from the high snail density and infection prevalence, and the large proportional mass of infected hosts that consisted of trematode tissue (mean = 31% per snail). 4) Estimates of yearly biomass transfer from snails into trematodes were slightly higher than the combined estimate of snail biomass transfer into the three vertebrate predators. Pacific giant salamanders accounted for 90% of the snail biomass consumed by predators. 5) These results demonstrate that trematode parasites play underappreciated roles in the ecosystem energetics of some freshwater streams.
Socio-demographic predictors of uptake of a virtual group weight management program during the COVID-19 pandemic.

BACKGROUND The COVID-19 pandemic has had a significant adverse impact on the delivery of weight management programmes (WMPs), in order to ensure the safety of patients and healthcare professionals. Videoconferencing could provide safe remote access to group WMPs during the COVID-19 pandemic. The objectives of this study were to determine the uptake of a virtual group WMP and its predictors. METHODS All patients enrolled on a face-to-face group WMP, which constitutes part of a Tier 3 WMP delivered by the NHS, at the time of the COVID-19 pandemic lockdown were invited to transfer to a virtual format of the group WMP. Baseline data included weight, BMI, age, gender, ethnicity and Index of Multiple Deprivation (IMD) quintile score. The outcomes were accept/decline transfer to the virtual group WMP. Logistic regression was performed to assess for predictors of uptake. RESULTS The 315 participants were included, of which 72.1% (n = 227) accepted. After adjusting for gender, deprivation and BMI; older patients (OR 0.966, [95% CI 0.944, 0.989]; p = 0.003) and Black, Asian and Minority Ethnicity (BAME) patients (OR 0.460 [95% 0.248, 0.851]; p = 0.023) were less likely to accept the virtual group WMP. CONCLUSION Strategies aimed at improving uptake of group WMP among BAME and older adult groups are needed, particularly considering the increased risk of severe COVID-19 in these two groups, and the links between obesity and poor COVID-19 outcomes.