Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Analysis and Whole Genome Mapping of a New Type of Plant Virus Subviral RNA: Umbravirus-Like Associated RNAs

We report the biological and structural characterization of umbravirus-like associated RNAs (ulaRNAs), a new category of coat-protein dependent subviral RNA replicons that infect plants. These RNAs encode an RNA-dependent RNA polymerase (RdRp) following a −1 ribosomal frameshift event, are 2.7–4.6 kb in length, and are related to umbraviruses, unlike similar RNA replicons that are related to tombusviruses. Three classes of ulaRNAs are proposed, with citrus yellow vein associated virus (CYVaV) placed in Class 2. With the exception of CYVaV, Class 2 and Class 3 ulaRNAs encode an additional open reading frame (ORF) with movement protein-like motifs made possible by additional sequences just past the RdRp termination codon. The full-length secondary structure of CYVaV was determined using Selective 2’ Hydroxyl Acylation analyzed by Primer Extension (SHAPE) structure probing and phylogenic comparisons, which was used as a template for determining the putative structures of the other Class 2 ulaRNAs, revealing a number of distinctive structural features. The ribosome recoding sites of nearly all ulaRNAs, which differ significantly from those of umbraviruses, may exist in two conformations and are highly efficient. The 3′ regions of Class 2 and Class 3 ulaRNAs have structural elements similar to those of nearly all umbraviruses, and all Class 2 ulaRNAs have a unique, conserved 3′ cap-independent translation enhancer. CYVaV replicates independently in protoplasts, demonstrating that the reported sequence is full-length. Additionally, CYVaV contains a sequence in its 3′ UTR that confers protection to nonsense mediated decay (NMD), thus likely obviating the need for umbravirus ORF3, a known suppressor of NMD. This initial characterization lays down a road map for future investigations into these novel virus-like RNAs.
Development of a Questionnaire for the Search for Occupational Causes in Patients with Non-Hodgkin Lymphoma: The RHELYPRO Study

Non-Hodgkin lymphoma (NHL), multiple myeloma and chronic lymphocytic leukemia are possibly related to environmental and/or occupational exposure. The primary objective of this study was to develop a questionnaire for screening patients with these blood disorders who might benefit from a specialized consultation for possible recognition of the disease as an occupational disease. The study included 205 subjects (male gender, 67.3%; mean age, 60 years; NHL, 78.5%). The questionnaire performed very satisfactorily in identifying the exposures most frequently retained by experts for their potential involvement in the occurrence of NHL. Its sensitivity and specificity in relation to the final expertise were 96% and 96% for trichloroethylene, 85% and 82% for benzene, 78% and 87% for solvents other than trichloroethylene and dichloromethane, 87% and 95% for pesticides, respectively. Overall, 15% of the subjects were invited to ask National Social Insurance for compensation as occupational disease. These declarations concerned exposure to pesticides (64%), solvents (trichloroethylene: 29%; benzene: 18%; other than chlorinated solvents: 18%) and sometimes multiple exposures. In conclusion, this questionnaire appears as a useful tool to identify NHL patients for a specialized consultation, in order to ask for compensation for occupational disease.
Generation of a Novel Transgenic Zebrafish for Studying Adipocyte Development and Metabolic Control

Zebrafish have become a popular animal model for studying various biological processes and human diseases. The metabolic pathways and players conserved among zebrafish and mammals facilitate the use of zebrafish to understand the pathological mechanisms underlying various metabolic disorders in humans. Adipocytes play an important role in metabolic homeostasis, and zebrafish adipocytes have been characterized. However, a versatile and reliable zebrafish model for long-term monitoring of adipose tissues has not been reported. In this study, we generated stable transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) in adipocytes. The transgenic zebrafish harbored adipose tissues that could be detected using GFP fluorescence and the morphology of single adipocyte could be investigated in vivo. In addition, we demonstrated the applicability of this model to the long-term in vivo imaging of adipose tissue development and regulation based on nutrition. The transgenic zebrafish established in this study may serve as an excellent tool to advance the characterization of white adipose tissue in zebrafish, thereby aiding the development of therapeutic interventions to treat metabolic diseases in humans.
Electromyographic Assessment of the Lower Leg Muscles during Concentric and Eccentric Phases of Standing Heel Raise

Only a small number of muscle activation patterns from lower limbs have been reported and simultaneous muscle activation from several lower limb muscles have not yet been investigated. The purpose of this study was to examine any gender differences in surface electromyography (EMG) activity from six recorded lower limb muscles of the dominant limb at baseline (i.e., with the foot placed flat on the floor and in the neutral position), and during concentric and eccentric phases when performing a heel raise task. In total, 10 females and 10 males performed a standing heel raise task comprising of three continuous phases: baseline, unloading (concentric muscle action), and loading (eccentric muscle action) phases. Muscle activation from six muscles (gastrocnemius medialis, gastrocnemius lateralis, soleus, tibialis anterior, peroneus longus, and peroneus brevis) were measured using the Myon 320 EMG System. Root mean squared values of each muscle were calculated for each phase. Descriptive and inferential statistics were incorporated into the study. Statistically significant p values were set at 0.05. The results showed no significant differences between baseline, concentric, and eccentric phases with respect to each of the muscles investigated. Except for the gastrocnemius medialis at baseline and concentric phases, no significant differences were observed between genders or contractions. The data suggests that gender does not significantly influence the eccentric phase during the standing heel raise task.
Cell Force-Driven Basement Membrane Disruption Fuels EGF- and Stiffness-Induced Invasive Cell Dissemination from Benign Breast Gland Acini

Local basement membrane (BM) disruption marks the initial step of breast cancer invasion. The activation mechanisms of force-driven BM-weakening remain elusive. We studied the mechanical response of MCF10A-derived human breast cell acini with BMs of tuneable maturation to physical and soluble tumour-like extracellular matrix (ECM) cues. Traction force microscopy (TFM) and elastic resonator interference stress microscopy (ERISM) were used to quantify pro-invasive BM stress and protrusive forces. Substrate stiffening and mechanically impaired BM scaffolds induced the invasive transition of benign acini synergistically. Robust BM scaffolds attenuated this invasive response. Additional oncogenic EGFR activation compromised the BMs’ barrier function, fuelling invasion speed and incidence. Mechanistically, EGFR-PI3-Kinase downstream signalling modulated both MMP- and force-driven BM-weakening processes. We show that breast acini form non-proteolytic and BM-piercing filopodia for continuous matrix mechanosensation, which significantly push and pull on the BM and ECM under pro-invasive conditions. Invasion-triggered acini further shear and compress their BM by contractility-based stresses that were significantly increased (3.7-fold) compared to non-invasive conditions. Overall, the highest amplitudes of protrusive and contractile forces accompanied the highest invasiveness. This work provides a mechanistic concept for tumour ECM-induced mechanically misbalanced breast glands fuelling force-driven BM disruption. Finally, this could facilitate early cell dissemination from pre-invasive lesions to metastasize eventually.
Hypoxic Conditions Promote the Angiogenic Potential of Human Induced Pluripotent Stem Cell-Derived Extracellular Vesicles

Stem cells secrete paracrine factors including extracellular vesicles (EVs) which can mediate cellular communication and support the regeneration of injured tissues. Reduced oxygen (hypoxia) as a key regulator in development and regeneration may influence cellular communication via EVs. We asked whether hypoxic conditioning during human induced pluripotent stem cell (iPSC) culture effects their EV quantity, quality or EV-based angiogenic potential. We produced iPSC-EVs from large-scale culture-conditioned media at 1%, 5% and 18% air oxygen using tangential flow filtration (TFF), with or without subsequent concentration by ultracentrifugation (TUCF). EVs were quantified by tunable resistive pulse sensing (TRPS), characterized according to MISEV2018 guidelines, and analyzed for angiogenic potential. We observed superior EV recovery by TFF compared to TUCF. We confirmed hypoxia efficacy by HIF-1α stabilization and pimonidazole hypoxyprobe. EV quantity did not differ significantly at different oxygen conditions. Significantly elevated angiogenic potential was observed for iPSC-EVs derived from 1% oxygen culture by TFF or TUCF as compared to EVs obtained at higher oxygen or the corresponding EV-depleted soluble factor fractions. Data thus demonstrate that cell-culture oxygen conditions and mode of EV preparation affect iPSC-EV function. We conclude that selecting appropriate protocols will further improve production of particularly potent iPSC-EV-based therapeutics.
Sleep Disorders and Psychological Profile in Oral Cancer Survivors: A Case-Control Clinical Study

Simple Summary Sleep disorders have been increasingly investigated in several medical illnesses as their presence may affect patients’ quality of life. However, the research examining sleep disorders in oral cancer is relatively weak. Indeed, the majority of the available studies present a cross-sectional or retrospective designs. Moreover, very few of them have evaluated quality of sleep in oral cancer survivors (OC survivors). We aimed to carry out a case-control study with the purpose to investigate sleep disorders and mood impairment in 50 OC survivors. Our research has shown that quality of sleep is significantly affected in OC survivors compared to a healthy population and that OC survivors suffers from higher levels of anxiety and depression. Our results may suggest that an appropriate assessment of quality of sleep and psychological profile should be performed in OC survivors as a prompt treatment for both sleep and mood disorders is crucial for the overall improvement of patients’ quality of life. Abstract Quality of sleep (QoS) and mood may impair oral cancer survivors’ wellbeing, however few evidences are currently available. Therefore, we aimed to assess the prevalence of sleep disorders, anxiety and depression among five-year oral cancer survivors (OC survivors). 50 OC survivors were compared with 50 healthy subjects matched for age and sex. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hamilton Rating Scales for Depression and Anxiety (HAM-D, HAM-A), the Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI) were administered. The global score of the PSQI, ESS, HAM-A, HAM-D, NRS, T-PRI, was statistically higher in the OC survivors than the controls (p-value: <0.001). QoS of OC survivors was significantly impaired, especially with regard to some PSQI sub-items as the subjective sleep quality, sleep latency and daytime dysfunction (p-value: 0.001, 0.029, 0.004). Moreover, poor QoS was negatively correlated with years of education (p-value: 0.042 *) and positively correlated with alcohol consumption (p-value: 0.049 *) and with the use of systemic medications (p-value: 0.044 *). Sleep disorders and mood disorders are common comorbidities in OC survivors; therefore, early assessment and management before, during and after treatment should be performed in order to improve the quality of life of OC survivors.
Ischemia-Reperfusion under Hyperthermia Increases Heme Oxygenase-1 in Pyramidal Neurons and Astrocytes with Accelerating Neuronal Loss in Gerbil Hippocampus

It has been studied that the damage or death of neurons in the hippocampus is different according to hippocampal subregions, cornu ammonis 1–3 (CA1–3), after transient ischemia in the forebrain, showing that pyramidal neurons located in the subfield CA1 (CA1) are most vulnerable to this ischemia. Hyperthermia is a proven risk factor for brain ischemia and can develop more severe and extensive brain damage related with mortality rate. It is well known that heme oxygenase-1 (HO-1) activity and expression is increased by various stimuli in the brain, including hyperthermia. HO-1 can be either protective or deleterious in the central nervous system, and its roles depend on the expression levels of enzymes. In this study, we investigated the effects of hyperthermia during ischemia on HO-1 expression and neuronal damage/death in the hippocampus to examine the relationship between HO-1 and neuronal damage/death following 5-min transient ischemia in the forebrain using gerbils. Gerbils were assigned to four groups: (1) sham-operated gerbils with normothermia (Normo + sham group); (2) ischemia-operated gerbils with normothermia (Normo + ischemia group); (3) sham-operated gerbils with hyperthermia (39.5 ± 0.2 °C) during ischemia (Hyper + sham group); and (4) ischemia-operated gerbils with hyperthermia during ischemia (Hyper + ischemia group). HO-1 expression levels in CA1–3 of the Hyper + ischemia group were significantly higher than those in the Normo + ischemia group. HO-1 immunoreactivity in the Hyper + ischemia group was significantly increased in pyramidal neurons and astrocytes with time after ischemia, and the immunoreactivity was significantly higher than that in the Normo + ischemia group. In the Normo + Ischemia group, neuronal death was shown in pyramidal neurons located only in CA1 at 5 days after ischemia. However, in the Hyper + ischemia group, pyramidal neuronal death occurred in CA1–3 at 2 days after ischemia. Taken together, our findings showed that brain ischemic insult during hyperthermic condition brings up earlier and severer neuronal damage/death in the hippocampus, showing that HO-1 expression in neurons and astrocytes is different according to brain subregions and temperature condition. Based on these findings, we suggest that hyperthermia in patients with ischemic stroke must be taken into the consideration in the therapy.
To Adapt or Not to Adapt: The Association between Implementation Fidelity and the Effectiveness of Diabetes Self-Management Education

Self-management education (SME) is a key determinant of diabetes treatment outcomes. While SME programs are often adapted for implementation, the impact of adaptations on diabetes SME effectiveness is not well documented. This study evaluated the impact of the implementation fidelity of diabetes SME programs on program effectiveness, exploring which factors influence implementation fidelity. Data from 33 type 2 diabetes SME program providers and 166 patients were collected in 8 countries (Austria, Belgium, Germany, Ireland, UK, Israel, Taiwan and USA). Program providers completed a questionnaire assessing their adherence to the program protocol and factors that influenced the implementation. Patients answered a pre–post questionnaire assessing their diabetes-related health literacy, self-care behavior, general health and well-being. Associations between implementation fidelity and outcomes were estimated through logistic regressions and repeated measures MANOVA, controlling for potential confounders. Adaptations of the program protocol regarding content, duration, frequency and/or coverage were reported by 39% of the providers and were associated with better, not worse, outcomes than strict adherence. None of the factors related to the participants, facilitating strategies, provider or context systematically influenced the implementation fidelity. Future research should focus on individual and contextual factors that may influence decisions to adapt SME programs for diabetes.
Complement Inactivation Strategy of Staphylococcus aureus Using Decay-Accelerating Factor and the Response of Infected HaCaT Cells

Staphylococcus aureus is a species of Gram-positive staphylococcus. It can cause sinusitis, respiratory infections, skin infections, and food poisoning. Recently, it was discovered that S. aureus infects epithelial cells, but the interaction between S. aureus and the host is not well known. In this study, we confirmed S. aureus to be internalized by HaCaT cells using the ESAT-6-like protein EsxB and amplified within the host over time by escaping host immunity. S. aureus increases the expression of decay-accelerating factor (CD55) on the surfaces of host cells, which inhibits the activation of the complement system. This mechanism makes it possible for S. aureus to survive in host cells. S. aureus, sufficiently amplified within the host, is released through the initiation of cell death. On the other hand, the infected host cells increase their surface expression of UL16 binding protein 1 to inform immune cells that they are infected and try to be eliminated. These host defense systems seem to involve the alteration of tight junctions and the induction of ligand expression to activate immune cells. Taken together, our study elucidates a novel aspect of the mechanisms of infection and immune system evasion for S. aureus.
Urinary Metabolomic Profiling after Administration of Corydalis Tuber and Pharbitis Seed Extract in Healthy Korean Volunteers

Pharmacometabolomics is a useful tool to identify biomarkers that can assess and predict response after drug administration. The primary purpose of pharmacometabolomics is to better understand the mechanisms and pathways of a drug by searching endogenous metabolites that have significantly changed after drug administration. DA-9701, a prokinetic agent, consists of Pharbitis seed and Corydalis tube extract and it is known to improve the gastrointestinal motility. Although the overall mechanism of action of DA-9701 remains unclear, its active ingredients, corydaline and chlorogenic acid, act as a 5-HT3 and D2 receptor antagonist and 5-HT4 receptor agonist. To determine the significant metabolites after the administration of DA-9701, a qualitative analysis was carried out using ultra-high performance liquid chromatography coupled with orbitrap mass spectrometer followed by a multivariate analysis. Seven candidates were selected and a statistical analysis of fold change was performed over time. Our study concluded that all the seven selected metabolites were commonly involved in lipid metabolism and purine metabolism.
Urinary Peptides as Potential Non-Invasive Biomarkers for Lupus Nephritis: Results of the Peptidu-LUP Study

Background: Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design: Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery (n = 42) and an independent validation (n = 51) cohort. Clinical characteristics were collected at inclusion and prospectively for 24 months. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. The value of previously validated prognostic (CKD273) and differential diagnostic (LN172) signatures was evaluated. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Tubulo-interstitial fibrosis was correlated to the CKD273. The LN172 score identified 92.5% of samples as LN. Few patients developed new-onset CKD. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated.
Reliable Service Function Chain Deployment Method Based on Deep Reinforcement Learning

Network function virtualization (NFV) is a key technology to decouple hardware device and software function. Several virtual network functions (VNFs) combine into a function sequence in a certain order, that is defined as service function chain (SFC). A significant challenge is guaranteeing reliability. First, deployment server is selected to place VNF, then, backup server is determined to place the VNF as a backup which is running when deployment server is failed. Moreover, how to determine the accurate locations dynamically with machine learning is challenging. This paper focuses on resource requirements of SFC to measure its priority meanwhile calculates node priority by current resource capacity and node degree, then, a novel priority-awareness deep reinforcement learning (PA-DRL) algorithm is proposed to implement reliable SFC dynamically. PA-DRL determines the backup scheme of each VNF, then, the model jointly utilizes delay, load balancing of network as feedback factors to optimize the quality of service. In the experimental results, resource efficient utilization, survival rate, and load balancing of PA-DRL were improved by 36.7%, 35.1%, and 78.9% on average compared with benchmark algorithm respectively, average delay was reduced by 14.9%. Therefore, PA-DRL can effectively improve reliability and optimization targets compared with other benchmark methods.
Combination Therapy of Novel Oncolytic Adenovirus with Anti-PD1 Resulted in Enhanced Anti-Cancer Effect in Syngeneic Immunocompetent Melanoma Mouse Model

Malignant melanoma, an aggressive form of skin cancer, has a low five-year survival rate in patients with advanced disease. Immunotherapy represents a promising approach to improve survival rates among patients at advanced stage. Herein, the aim of the study was to design and produce, by using engineering tools, a novel oncolytic adenovirus AdV-D24- inducible co-stimulator ligand (ICOSL)-CD40L expressing potent co-stimulatory molecules enhancing clinical efficacy through the modulation of anti-cancer immune responses. Firstly, we demonstrated the vector’s identity and genetic stability by restriction enzyme assay and sequencing, then, by performing in vitro and in vivo pre-clinical studies we explored the anti-cancer efficacy of the virus alone or in combination with anti PD-1 inhibitor in human melanoma cell lines, i.e., MUG Mel-1 and MUG Mel-2, and in immunocompetent C57BL/6 melanoma B16V mouse model. We showed that both monotherapy and combination approaches exhibit enhanced anti-cancer ability and immunogenic cell death in in vitro settings. Furthermore, AdV-D24-ICOSL-CD40L combined with anti PD-1 revealed a fall in tumor volume and 100% survival in in vivo context, thus suggesting enhanced efficacy and survival via complementary anti-cancer properties of those agents in melanoma therapy. Collectively, the novel oncolytic vector AdV-D24-ICOSL-CD40L alone or in combination with anticancer drugs, such as check point inhibitors, may open novel therapeutic perspectives for the treatment of melanoma.
Polyacetylenes as Colorimetric and Fluorescent Chemosensor for Anions

ABSTRACT This review describes the recent progress in the design and fabrication of polyacetylene-based chemosensors applicable to colorimetric and fluorescence anion sensing that has been increasingly demanded in diverse fields. The validity of polyacetylene derivatives as an anion sensor material has been demonstrated based on the evaluation of the anion-induced optical responses for various types of polyacetylenes with different binding sites and pendant structures. Suitable molecular designs of the polyacetylene have been found to exert a beneficial influence on the anion detection abilities, which are specifically highlighted in this review article.