Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function

The liver is a complex organ with critical physiological functions including metabolism, glucose storage, and drug detoxification. Its unique immune profile with large numbers of cytotoxic CD8+ T cells and significant innate lymphoid population, including natural killer cells, γδ T cells, MAIT cells, and iNKTcells, suggests an important anti-tumor surveillance role. Despite significant immune surveillance in the liver, in particular large NK cell populations, hepatic cell carcinoma (HCC) is a relatively common outcome of chronic liver infection or inflammation. The liver is also the second most common site of metastatic disease. This discordance suggests immune suppression by the environments of primary and secondary liver cancers. Classic tumor microenvironments (TME) are poorly perfused, leading to accumulation of tumor cell metabolites, diminished O2, and decreased nutrient levels, all of which impact immune cell phenotype and function. Here, we focus on changes in the liver microenvironment associated with tumor presence and how they affect NK function and phenotype.
Cognitive training and neuroplasticity in mild cognitive impairment (COG-IT): protocol for a two-site, blinded, randomised, controlled treatment trial

Introduction Mild cognitive impairment (MCI) is common in older adults and represents a high-risk group for progression to Alzheimer’s disease (AD). Medication trials in MCI have generally failed, but new discoveries with brain plasticity in ageing have led to the study of cognitive training as a potential treatment to improve cognitive abilities. Computerised cognitive training (CCT) involves computerised cognitive exercises that target specific cognitive abilities and neural networks to potentially improve cognitive functioning through neuroplasticity. Methods and analysis In a two-site study (New York State Psychiatric Institute/Columbia University Medical Center and Duke University Medical Center), we will randomise 100 patients with MCI (Wechsler Memory Scale-III Logical Memory II score 0–11; Folstein Mini Mental State Examination ≥23) to home-based CCT (suite of exercises: memory, matching, spatial recognition, processing speed) or a home-based active control condition (computerised crossword puzzle training (CPT)) with 12 weeks of intensive training followed by regular booster sessions up to 78 weeks. All patients will receive standard neuropsychological and functional assessments in clinic as well as structural/functional brain MRI scans at study entry and endpoint. We will test if CCT, versus CPT, leads to improved cognitive functioning, transfers to functional ability and tasks of everyday life and impacts hippocampal volume changes and changes in the default mode network of the brain measured by resting-state functional MRI. Ethics and dissemination The study will be conducted following ethics approval and written informed consent will be obtained from all subjects. Study results will be disseminated via publication, clinicaltrials.gov, media and conference presentations. This will be the first controlled long-term trial to evaluate the effects of home-based CCT versus computerised CPT on cognitive abilities and functional measures and neural outcomes as determined by MRI indices in patients with MCI. Positive results from trial may support further development of home-based CCT. Trial registration number ClinicalTrials.gov identifier (NCT03205709).
A Quorum-Sensing Inhibitor Strain of Vibrio alginolyticus Blocks Qs-Controlled Phenotypes in Chromobacterium violaceum and Pseudomonas aeruginosa

The cell density-dependent mechanism, quorum sensing (QS), regulates the expression of virulence factors. Its inhibition has been proposed as a promising new strategy to prevent bacterial pathogenicity. In this study, 827 strains from the microbiota of sea anemones and holothurians were screened for their ability to produce quorum-sensing inhibitor (QSI) compounds. The strain M3-10, identified as Vibrio alginolyticus by 16S rRNA gene sequencing, as well as ANIb and dDDH analyses, was selected for its high QSI activity. Bioassay-guided fractionation of the cell pellet extract from a fermentation broth of strain M3-10, followed by LC–MS and NMR analyses, revealed tyramine and N-acetyltyramine as the active compounds. The QS inhibitory activity of these molecules, which was confirmed using pure commercially available standards, was found to significantly inhibit Chromobacterium violaceum ATCC 12472 violacein production and virulence factors, such as pyoverdine production, as well as swarming and twitching motilities, produced by Pseudomonas aeruginosa PAO1. This constitutes the first study to screen QSI-producing strains in the microbiota of anemones and holothurians and provides an insight into the use of naturally produced QSI as a possible strategy to combat bacterial infections.
JNK1 Induces Notch1 Expression to Regulate Genes Governing Photoreceptor Production

c-Jun N-terminal kinases (JNKs) regulate cell proliferation and differentiation via phosphorylating such transcription factors as c-Jun. The function of JNKs in retinogenesis remains to be elucidated. Here, we report that knocking out Jnk1, but not Jnk2, increased the number of photoreceptors, thus enhancing the electroretinogram (ERG) responses. Intriguingly, Notch1, a well-established negative regulator of photoreceptor genesis, was significantly attenuated in Jnk1 knockout (KO) mice compared to wild-type mice. Mechanistically, light specifically activated JNK1 to phosphorylate c-Jun, which in turn induced Notch1 transcription. The identified JNK1–c-Jun–Notch1 axis strongly inhibited photoreceptor-related transcriptional factor expression and ultimately impaired photoreceptor opsin expression. Our study uncovered an essential function of JNK1 in retinogenesis, revealing JNK1 as a potential candidate for targeting ophthalmic diseases.
Electrochemical Sensors Fabricated by Electrospinning Technology: An Overview

Nanofibers or nanofibrous membranes prepared by electrospinning possess many attractive properties, including excellent mechanical properties, high specific surface area and high porosity, making them attractive for sensor application, especially for the electrochemical sensors. Many nanomaterials are used as additives to improve the conductivity, sensitivity and selectivity of sensors. Based on the different modifiers of electrode materials, electrochemical sensors can be divided into enzyme sensors and non-enzyme sensors. In this review, we summarize the recent progress of the electrochemical sensors fabricated by electrospinning, including hydrogen peroxide (H2O2) sensors, glucose sensors and other sensors. In addition, the sensing mechanisms of various electrochemical sensors are introduced in detail. Finally, future research directions of electrochemical sensors based on electrospinning and the challenges faced by large-scale applications of electrospun electrochemical sensors are presented.
A Computational Platform for Visible Light Communications

This paper proposes a computational platform for simulations of visible light communication (VLC) systems. Special emphasis is placed on the modeling of light-emitting diode and its nonlinear aspects, optical channel, and photodiode. In addition, the equalization performance of VLC systems is assessed using adaptive filters, such as Volterra decision-feedback equalizer. Bit error rate results indicate that adaptive nonlinear techniques outperform linear-in-parameter approaches when it comes to coping with VLC nonlinearities. Keywords— Visible light communication, light-emitting diode, adaptive filters, Volterra series, decision-feedback equalizer.
Tracing genetic resurrection of pointing dog breeds: Cesky Fousek as both survivor and rescuer

Cesky Fousek is considered to be one of the oldest pointing dog breeds in Europe and has been appreciated for its versatile working skills. Because it faced extinction in the past, the Cesky Fousek was restored from German Wirehaired and Shorthaired Pointers. Additionally, the breed was recently used in the USA with the initial intent of improvement of the Wirehaired Pointing Griffon (synonymous with Korthals Griffon) by the Bohemian Wirehaired Pointing Griffon Club of America. This study evaluates genetic diversity parameters of Cesky Fousek and compares them to the other continental pointing dogs that played a role in the formation of its gene pool. DNA from buccal swab and blood samples (n = 405) were analyzed using 18 microsatellite markers. Parameters of genetic polymorphism show that the Cesky Fousek breed has a comparable rate of variation as other hunting breeds despite the low population size and severe historical bottlenecks. Clustering analyses reveal a unique genetic status as a distinct pointing dog breed and the relatedness of the breeds is in good concordance with historical data. The present study demonstrates that despite historical admixture among lineages, separate pointing breeds constitute genetically differentiated units, mirroring unique breeding stocks and pedigree isolation among specific breed clubs, reflecting differences in breeding programs under each association.
Harmony Perception in Prelingually Deaf, Juvenile Cochlear Implant Users

Prelingually deaf children listening through cochlear implants (CIs) face severe limitations on their experience of music, since the hearing device degrades relevant details of the acoustic input. An important parameter of music is harmony, which conveys emotional as well as syntactic information. The present study addresses musical harmony in three psychoacoustic experiments in young, prelingually deaf CI listeners and normal-hearing (NH) peers. The discrimination and preference of typical musical chords were studied, as well as cadence sequences conveying musical syntax. The ability to discriminate chords depended on the hearing age of the CI listeners, and was less accurate than for the NH peers. The groups did not differ with respect to the preference of certain chord types. NH listeners were able to categorize cadences, and performance improved with age at testing. In contrast, CI listeners were largely unable to categorize cadences. This dissociation is in accordance with data found in postlingually deafened adults. Consequently, while musical harmony is available to a limited degree to CI listeners, they are unable to use harmony to interpret musical syntax.
Associations between functional capacity, isokinetic leg strength, sleep quality and cognitive function in multiple sclerosis patients: a cross-sectional study

ABSTRACT Objectives: Recent evidence suggests an association between functional capacity and cognitive function, at least in older adults. The aim of this cross-sectional study was to examine the association between cognitive function, functional capacity, isokinetic leg strength, health-related quality of life (HRQOL), sleep quality, body fat, handgrip strength, and fatigue among a sample of MS patients. Methods: Fifty-one relapsing-remitting MS patients (age: 38.4 ± 7.1 yrs; 30 females) were recruited and agreed to participate in this study. Cognitive function was assessed by the Paced Auditory Serial Addition Test (PASAT). Functional capacity was examined using various functional tests commonly used in MS patients. Maximal voluntary unilateral leg strength was assessed using isokinetic dynamometer. Isometric handgrip strength was assessed by a dynamometer. Total body and visceral fat levels were assessed via bioelectrical impedance analyzers. Finally, the patients’ HRQOL, sleep quality, and fatigue levels were evaluated using specific questionnaires. Results: A significant association was found between the PASAT score and the performance score in various functional capacity tests (p < 0.050). On the other hand, a weak but statistically significant association was found between the PASAT score and isokinetic strength of knee extensors (r = 0.319, p = 0.022) and knee flexors (r = 0.354 p = 0.011). Poor sleep quality was associated with lower performance in all the functional capacity tests examined (p < 0.05) whilst was negatively associated with the PASAT score (r = −0.334, p = 0.017). The multivariate regression analysis revealed that the performance on the TUG test was a significant predictor of cognitive function. Conclusion: Based on the results of this study, functional capacity was found to be associated with both impaired cognitive performance and low HRQOL in MS patients. In addition, an association between sleep quality and cognitive performance was revealed, confirming existing literature. Functional capacity as assessed by the TUG test emerged as the best predictor of cognitive function.
Cost-analysis of virtual reality training based on the Virtual Reality for Upper Extremity in Subacute stroke (VIRTUES) trial

Abstract Objectives Stroke is a major cause of lasting disability worldwide. Virtual reality (VR) training has been introduced as a means of increasing the effectiveness of rehabilitation by providing large doses of task-related training with many repetitions and different modes of feedback. As VR is increasingly used in neurorehabilitation, cost considerations are important. Methods A cost-analysis was conducted based on the Virtual Reality for Upper Extremity in Subacute stroke (VIRTUES) trial, a recent international randomized controlled observer-blind multicenter trial. Average therapist time required per therapy session may differ between VR and conventional training (CT), leading to potential cost savings due to a therapist being able to supervise more than one patient at a time. Exploratory cost analyses are presented to explore such assumptions. Results Based on our calculations, VR incurs extra costs as compared with CT when the same amount of therapist contact is provided, as was the case in VIRTUES. However, the exploratory analyses demonstrated that these costs may be rapidly counterbalanced when time for therapist supervision can be reduced. Conclusions Extra costs for VR can be outweighed by reduced therapist time and decreasing VR system costs in the nearer future, and not least by increased patient motivation.
Autoimmune thrombocytopenia: Current treatment options in adults with a focus on novel drugs

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by platelet destruction and reduced platelet production resulting in decreased platelet level and an increased risk of bleeding. Based on the immunologic mechanism of ITP, front‐line standard therapy consists of corticosteroids and intravenous immunoglobulins (IVIG). If patients do not respond to the first‐line treatment, or if continuous therapy is required, the disorder is called refractory ITP, and second‐line therapy is indicated. This treatment may consist of rituximab, thrombopoietin receptor agonists, splenectomy, or cytotoxic drugs. Despite significant advances, many patients do not respond to any the treatments listed below, and new treatment options need to be developed for this relapsed and refractory group. Recent clinical studies have indicated promising outcomes for novel drugs, either as single agents or in combination with traditional drugs. This review discusses the latest and the most promising novel drugs for ITP in adults.
The Use of Nanotechnology to Increase Quality and Yield of Fruit Crops.

Nanotechnology is currently being widely employed in agriculture and horticulture. The most widely investigated and developed factor related to fruit trees is nanofertilizers (NFs), which play very important roles in increasing vegetative growth, improving reproductive growth and flowering, thereby increasing productivity, product quality and ultimately increasing shelf-life and decreasing fruit waste. These nanomaterials, which are generally sprayed at low concentrations on trees at different time intervals and in frequent sessions, are also considered as growth stimulants. Macro- and micro-scale NFs such as zinc, boron, chitosan, and fertilizer nanocomposites such as ZnFeMnB, NPKMg, and calcite have been shown to significantly improve the vegetative and reproductive traits of fruit trees such as pomegranate, strawberry, mango, date, coffee and grape. Knowledge on the effects of NFs on fruit trees and biological reasons for their effects on different traits is incomplete and there is an urgent need for extensive research on these topics. This article is protected by copyright. All rights reserved.
Risk stratification and avoiding overtreatment in localized prostate cancer.

PURPOSE OF REVIEW Significant morbidity is associated with overtreatment of clinically localized prostate cancer (PCa). Risk stratification tools such as novel biomarkers, MRI and risk calculators are useful in predicting which patients would benefit from active surveillance. This review examines current risk stratification tools in localized PCa and the safety of active surveillance in these patients. RECENT FINDINGS Very low risk, low-risk and favourable intermediate-risk PCa variants may benefit from treatment with active surveillance. These disease categories have been shown (with up to 10-year follow-up) to have survival and cancer-specific complication rates similar to immediate definitive treatment. Novel biomarkers sensitively predict upstaging, recurrence and metastatic progression while multiparametric MRI reliably detects clinically significant PCa and is valuable in the biopsy naïve patient considering active surveillance. Lastly, risk calculators and nomograms are being developed to combine clinical data and provide optimal individualized treatment while minimizing overtreatment in clinically localized disease. SUMMARY Although large randomized trials are needed to validate treatment pathways, current data supports active surveillance in certain clinically localized PCa. Many tools exist to define and support active surveillance in this group.
Immediate post-operative rehabilitation after decoronation. A systematic review.

BACKGROUND/AIMS Decoronation is currently considered the best treatment option for ankylosed teeth and discrepancies in the alveolar bone, particularly in childhood and adolescence. The loss of a front tooth creates aesthetic, functional and psychological distress in patients and their parents. The aim of this study was to analyze the types of restorations provided after decoronation, their suitability, durability and follow-up until insertion of the final restoration. MATERIALS AND METHODS A literature review was conducted using Ovid-Medline, Embase and Web of Science to identify eligible articles. English language publications until August 9, 2018, were searched independently and crosschecked by two researchers online, in print, and in press. RESULTS Of 618 articles screened, 10 included reports on 11 patients with detailed descriptions of 13 provisional restorations. Patients' ages at the time of decoronation were 8-15 years. Seven underwent avulsion and four intrusion. Removable partial denture (9 cases) was the most common restoration. In two cases, the restoration was provisional with a lingual bar with prosthetic crown and in two other cases with an adhesive bridge. Follow up ranged from 3 months to 5 years in 9 patients. Two cases were followed until the permanent restoration was placed. CONCLUSIONS The importance of long-term provisional restorations was disregarded by most authors. A multidisciplinary approach should take into consideration immediate, mid and long-term rehabilitation of the decoronated tooth. This article is protected by copyright. All rights reserved.
Extensive Inhibitory Gating of Viscerosensory Signals by a Sparse Network of Somatostatin Neurons

Integration and modulation of primary afferent sensory information begins at the first terminating sites within the CNS, where central inhibitory circuits play an integral role. Viscerosensory information is conveyed to the nucleus of the solitary tract (NTS) where it initiates neuroendocrine, behavioral, and autonomic reflex responses that ensure optimal internal organ function. This excitatory input is modulated by diverse, local inhibitory interneurons, whose functions are not clearly understood. Here we show that, in male rats, 65% of somatostatin-expressing (SST) NTS neurons also express GAD67, supporting their likely role as inhibitory interneurons. Using whole-cell recordings of NTS neurons, from horizontal brainstem slices of male and female SST-yellow fluorescent protein (YFP) and SST-channelrhodopsin 2 (ChR2)-YFP mice, we quantified the impact of SST-NTS neurons on viscerosensory processing. Light-evoked excitatory photocurrents were reliably obtained from SST-ChR2-YFP neurons (n = 16) and the stimulation–response characteristics determined. Most SST neurons (57%) received direct input from solitary tract (ST) afferents, indicating that they form part of a feedforward circuit. All recorded SST-negative NTS neurons (n = 72) received SST-ChR2 input. ChR2-evoked PSCs were largely inhibitory and, in contrast to previous reports, were mediated by both GABA and glycine. When timed to coincide, the ChR2-activated SST input suppressed ST-evoked action potentials at second-order NTS neurons, demonstrating strong modulation of primary viscerosensory input. These data indicate that the SST inhibitory network innervates broadly within the NTS, with the potential to gate viscerosensory input to powerfully alter autonomic reflex function and other behaviors. SIGNIFICANCE STATEMENT Sensory afferent input is modulated according to state. For example the baroreflex is altered during a stress response or exercise, but the basic mechanisms underpinning this sensory modulation are not fully understood in any sensory system. Here we demonstrate that the neuronal processing of viscerosensory information begins with synaptic gating at the first central synapse with second-order neurons in the NTS. These data reveal that the somatostatin subclass of inhibitory interneurons are driven by visceral sensory input to play a major role in gating viscerosensory signals, placing them within a feedforward circuit within the NTS.
Optimizing the Limit of Detection of Waveguide-Based Interferometric Biosensor Devices

Waveguide-based photonic sensors provide a unique combination of high sensitivity, compact size and label-free, multiplexed operation. Interferometric configurations furthermore enable a simple, fixed-wavelength read-out making them particularly suitable for low-cost diagnostic and monitoring devices. Their limit of detection, i.e., the lowest analyte concentration that can be reliably observed, mainly depends on the sensors response to small refractive index changes, and the noise in the read-out system. While enhancements in the sensors response have been extensively studied, noise optimization has received much less attention. Here we show that order-of-magnitude enhancements in the limit of detection can be achieved through systematic noise reduction, and demonstrate a limit of detection of ∼10−8RIU with a silicon nitride sensor operating at telecom wavelengths.
Lower Bound and Correctness Proofs for Consensus in the Visigoth Model

• In the definition of the actions of a process for implementing a given protocol, some of these actions can be marked by the protocol writer as “message collection steps”. These must be internal steps resulting from a condition over the state becoming true, and the condition that triggers these actions must be that the process collected in its internal state a sufficiently large threshold of messages from distinct processes that meet a certain condition. (Both the threshold and the condition are protocolspecific.) Example. For example, a message collection step can be triggered by gathering a majority (or a quorum) of messages of the same type and for the same sequence number from distinct processes.