Miracle-dz/UniFAR-FTUs huggingface dataset:
SLUG‐related partial epithelial‐to‐mesenchymal transition is a transcriptomic prognosticator of head and neck cancer survival

Partial epithelial‐to‐mesenchymal transition (pEMT) contributes to cellular heterogeneity that is associated with nodal metastases and unfavorable clinical parameters in head and neck squamous cell carcinomas (HNSCCs). We developed a single‐cell RNA sequencing signature‐based pEMT quantification through cell type‐dependent deconvolution of bulk RNA sequencing and microarray data combined with single‐sample scoring of molecular phenotypes (Singscoring). Clinical pEMT‐Singscores served as molecular classifiers in multivariable Cox proportional hazard models and high scores prognosticated poor overall survival and reduced response to irradiation as independent parameters in large HNSCC cohorts [The Cancer Genome Atlas (TCGA), MD Anderson Cancer Centre (MDACC), Fred Hutchinson Cancer Research Center (FHCRC)]. Differentially expressed genes confirmed enhanced cell motility and reduced oxidative phosphorylation and epithelial differentiation in pEMThigh patients. In patients and cell lines, the EMT transcription factor SLUG correlated most strongly with pEMT‐Singscores and promoted pEMT, enhanced invasion, and resistance to irradiation in vitro. SLUG protein levels in HNSCC predicted disease‐free survival, and its peripheral expression at the interphase to the tumor microenvironment was significantly increased in relapsing patients. Hence, pEMT‐Singscores represent a novel risk predictor for HNSCC stratification regarding clinical outcome and therapy response that is partly controlled by SLUG.
MiR‐149‐3p can improve the osteogenic differentiation of human adipose‐derived stem cells via targeting AKT1

The study aims to investigate the role of microRNA‐149‐3p (miR‐149‐3p) in regulating osteogenic differentiation of human adipose‐derived stem cells (hADSCs) by targeting v‐akt murine thymoma viral oncogene homolog 1 (AKT1). Bioinformatics websites and a dual luciferase reporter assay were used to predict and verify the targeting relationship between miR‐149‐3p and AKT1. The hADSCs were divided into the blank, negative control (NC), mimic, control siRNA, AKT1 siRNA, and miR‐149‐3p inhibitors + AKT1 siRNA groups and then subjected to Alizarin Red staining, Alkaline phosphatase (ALP) staining, ALP activity detections, MTT assay, and EdU cell proliferation assay. Gene or protein expression was quantified using quantitative real‐time PCR (qRT‐PCR) or Western blotting, respectively. The miR‐149‐3p expression increased gradually and AKT1 expression decreased gradually during osteogenic differentiation of hADSCs. The prediction of bioinformatics websites miRTarBase and TargetScan and the dual luciferase reporter assay indicated that miR‐149‐3p can directly target AKT1. After hADSCs were transfected with miR‐149‐3p mimic, AKT1 expression was significantly downregulated. However, transfection with AKT1 siRNA did not have an impact on miR‐149‐3p in hADSCs. In comparison with the AKT1 siRNA group, the miR‐149‐3p inhibitors + AKT1 siRNA group showed decreased miR‐149‐3p expression but increased AKT1 expression. In addition, AKT1 siRNA enhanced the cell viability and proliferation of hADSCs and increased mineral calcium deposition and ALP activity, resulting in higher expression of osteogenic differentiation‐related genes, which was reversed by miR‐149‐3p inhibition. The miR‐149‐3p can increase the expression of osteogenic differentiation‐related genes by targeting AKT1 and thereby enhance the osteogenic differentiation of hADSCs.
Our contemporary understanding of the aetiology of pressure ulcers/pressure injuries

In 2019, the third and updated edition of the Clinical Practice Guideline (CPG) on Prevention and Treatment of Pressure Ulcers/Injuries has been published. In addition to this most up‐to‐date evidence‐based guidance for clinicians, related topics such as pressure ulcers (PUs)/pressure injuries (PIs) aetiology, classification, and future research needs were considered by the teams of experts. To elaborate on these topics, this is the third paper of a series of the CPG articles, which summarises the latest understanding of the aetiology of PUs/PIs with a special focus on the effects of soft tissue deformation. Sustained deformations of soft tissues cause initial cell death and tissue damage that ultimately may result in the formation of PUs/PIs. High tissue deformations result in cell damage on a microscopic level within just a few minutes, although it may take hours of sustained loading for the damage to become clinically visible. Superficial skin damage seems to be primarily caused by excessive shear strain/stress exposures, deeper PUs/PIs predominantly result from high pressures in combination with shear at the surface over bony prominences, or under stiff medical devices. Therefore, primary PU/PI prevention should aim for minimising deformations by either reducing the peak strain/stress values in tissues or decreasing the exposure time.
Effects of 7-week Resistance Training on Handcycle Performance in Able-bodied Males

Abstract The effect of an upper body resistance training program on maximal and submaximal handcycling performance in able-bodied males was explored. Eighteen able-bodied men were randomly assigned to a training group (TG: n=10) and a control group (CG: n=8). TG received 7 weeks of upper body resistance training (60% of 1 repetition maximum (1RM), 3×10 repetitions, 6 exercise stations, 2 times per week). CG received no training. Peak values for oxygen uptake (V˙O2peak), power output (POpeak), heart rate (HRpeak), minute ventilation (V˙OEpeak) and respiratory exchange ratio (RERpeak), submaximal values (HR, V˙O2, RER, PO, and gross mechanical efficiency (GE)), and time to exhaustion (TTE) were determined in an incremental test pre- and post-training. Maximal isokinetic arm strength and 1RM tests were conducted. Ratings of perceived exertion (RPE) were assessed. A two-way repeated measures ANOVA and post-hoc comparisons were performed to examine the effect of time, group and its interaction (p<0.05). TG improved on POpeak (8.55%), TTE (10.73%), and 1RM (12.28–38.98%). RPE at the same stage during pre- and post-test was lower during the post-test (8.17%). Despite no improvements in V˙O2peak, training improved POpeak, muscular strength, and TTE. Upper body resistance training has the potential to improve handcycling performance.
The beginning and the end: flanking nucleotides induce a parallel G-quadruplex topology

Abstract Genomic sequences susceptible to form G-quadruplexes (G4s) are always flanked by other nucleotides, but G4 formation in vitro is generally studied with short synthetic DNA or RNA oligonucleotides, for which bases adjacent to the G4 core are often omitted. Herein, we systematically studied the effects of flanking nucleotides on structural polymorphism of 371 different oligodeoxynucleotides that adopt intramolecular G4 structures. We found out that the addition of nucleotides favors the formation of a parallel fold, defined as the ‘flanking effect’ in this work. This ‘flanking effect’ was more pronounced when nucleotides were added at the 5′-end, and depended on loop arrangement. NMR experiments and molecular dynamics simulations revealed that flanking sequences at the 5′-end abolish a strong syn-specific hydrogen bond commonly found in non-parallel conformations, thus favoring a parallel topology. These analyses pave a new way for more accurate prediction of DNA G4 folding in a physiological context.
Combined Neurophysiologic and Neuroimaging Approach to Reveal the Structure-Function Paradox in Cervical Myelopathy

Background and Objectives To explore the so-called structure-function paradox in individuals with focal spinal lesions by means of tract-specific MRI coupled with multimodal evoked potentials and quantitative sensory testing. Methods Individuals with signs and symptoms attributable to cervical myelopathy (i.e., no evidence of competing neurologic diagnoses) were recruited at the Balgrist University Hospital, Zurich, Switzerland, between February 2018 and March 2019. We evaluated the relationship between the extent of structural damage within spinal nociceptive pathways (i.e., dorsal horn, spinothalamic tract, anterior commissure) assessed with atlas-based MRI and (1) the functional integrity of spinal nociceptive pathways measured with contact heat–, cold-, and pinprick-evoked potentials and (2) clinical somatosensory phenotypes assessed with quantitative sensory testing. Results Sixteen individuals (mean age 61 years) with either degenerative (n = 13) or posttraumatic (n = 3) cervical myelopathy participated in the study. Most individuals presented with mild myelopathy (modified Japanese Orthopaedic Association score >15; n = 13). A total of 71% of individuals presented with structural damage within spinal nociceptive pathways on MRI. However, 50% of these individuals presented with complete functional sparing (i.e., normal contact heat–, cold-, and pinprick-evoked potentials). The extent of structural damage within spinal nociceptive pathways was not associated with functional integrity of thermal (heat: p = 0.57; cold: p = 0.49) and mechano-nociceptive pathways (p = 0.83) or with the clinical somatosensory phenotype (heat: p = 0.16; cold: p = 0.37; mechanical: p = 0.73). The amount of structural damage to the spinothalamic tract did not correlate with spinothalamic conduction velocity (p > 0.05; ρ = −0.11). Discussion Our findings provide neurophysiologic evidence to substantiate that structural damage in the spinal cord does not equate to functional somatosensory deficits. This study recognizes the pronounced structure-function paradox in cervical myelopathies and underlines the inevitable need for a multimodal phenotyping approach to reveal the eloquence of lesions within somatosensory pathways.
Culprit-only versus multivessel percutaneous coronary intervention among STEMI patients complicated by cardiogenic shock in real-world practice: an updated systematic review and meta-analysis.

BACKGROUND The recent randomized trials demonstrated that culprit-only percutaneous coronary intervention (CO-PCI) was superior to multivessel PCI (MV-PCI) among ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) complicated by cardiogenic shock, yet the realworld scenario remains to be determined. METHODS Studies that compared CO-PCI versus MV-PCI in STEMI patients with MVD complicated by cardiogenic shock were identified by a systematic search of published articles. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated by using random-effects models. RESULTS Eventually, 18 observational studies involving 73,528 patients were included. The results showed that CO-PCI was associated with lower risks of short-term renal failure (OR: 0.75; 95% CI: 0.64 to 0.88; I 2 =14.7%) and short-term stroke (OR: 0.86; 95% CI: 0.77 to 0.96; I2 =0.0%) compared with immediate MV-PCI. But the risk of short-term myocardial infarction (OR: 1.12; 95% CI: 1.03 to 1.22; I2 =0.0%) was increased. There was no significant difference during long-term follow-up. The results remained consistent after adding the only randomized trial. CONCLUSIONS Based on real-world analyses, our meta-analysis suggested that CO-PCI decreased the risks of renal failure and stroke but increased the risk of myocardial infarction relative to immediate MV-PCI during short-term follow-up in STEMI patients with MVD complicated by cardiogenic shock. If possible in clinical practice, staged MV-PCI can be given a try to decrease the risks of renal failure and stroke associated with immediate MV-PCI and myocardial infarction associated with CO-PCI. However, the conclusions need to be confirmed by further large-scale studies.
Macro-vasculature and positron emission tomography (PET) standardized uptake value in lung cancer patients.

PURPOSE To investigate the relationship between macro-vasculature features and the standardized uptake value (SUV) of positron emission tomography (PET), which is a surrogate for the metabolic activity of a lung tumor. METHODS We retrospectively analyzed a cohort of 90 lung cancer patients who had both chest CT and PET-CT examinations before receiving cancer treatment. The SUVs in the medical reports were used. We quantified three macro-vasculature features depicted on CT images (i.e., vessel number, vessel volume, and vessel tortuosity) and several tumor features (i.e., volume, maximum diameter, mean diameter, surface area, and density). Tumor size (e.g., volume) was used as a covariate to adjust for possible confounding factors. Backward stepwise multiple regression analysis was performed to develop a model for predicting PET SUV from the relevant image features. The Bonferroni correction was used for multiple comparisons. RESULTS PET SUV was positively correlated with vessel volume (R = 0.44, p<0.001) and vessel number (R = 0.44, p<0.001) but not with vessel tortuosity (R = 0.124, p >0.05). After adjusting for tumor size, PET SUV was significantly correlated with vessel tortuosity (R = 0.299, p = 0.004) and vessel number (R = 0.224, p = 0.035), but only marginally correlated with vessel volume (R = 0.187, p = 0.079). The multiple regression model showed a performance with an R-Squared of 0.391 and an adjusted R-Squared of 0.355 (p<0.001). CONCLUSIONS Our investigations demonstrate the potential relationship between macro-vasculature and PET SUV and suggest the possibility of inferring the metabolic activity of a lung tumor from chest CT images. This article is protected by copyright. All rights reserved.
LncRNA-ENST00000421645 promotes T cells to secrete IFN-γ by sponging PCM-1 in neurosyphilis.

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA-ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA-ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA-ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA-ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.
NAD+ supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells.

Although tumor-infiltrating lymphocytes (TILs) maintain their ability to proliferate, persist, and eradicate tumors, they are frequently dysfunctional in situ. By performing both whole-genome CRISPR and metabolic inhibitor screens, we identify that nicotinamide phosphoribosyltransferase (NAMPT) is required for T cell activation. NAMPT is low in TILs, and its expression is controlled by the transcriptional factor Tubby (TUB), whose activity depends on the T cell receptor-phospholipase C gamma (TCR-PLCγ) signaling axis. The intracellular level of NAD+, whose synthesis is dependent on the NAMPT-mediated salvage pathway, is also decreased in TILs. Liquid chromatography-mass spectrometry (LC-MS) and isotopic labeling studies confirm that NAD+ depletion led to suppressed glycolysis, disrupted mitochondrial function, and dampened ATP synthesis. Excitingly, both adoptive CAR-T and anti-PD1 immune checkpoint blockade mouse models demonstrate that NAD+ supplementation enhanced the tumor-killing efficacy of T cells. Collectively, this study reveals that an impaired TCR-TUB-NAMPT-NAD+ axis leads to T cell dysfunction in the tumor microenvironment, and an over-the-counter nutrient supplement of NAD+ could boost T-cell-based immunotherapy.
Metastatic Medullary Thyroid Cancer: The Role of 68Gallium-DOTA-Somatostatin Analogue PET/CT and Peptide Receptor Radionuclide Therapy.

CONTEXT Metastatic medullary thyroid cancer (MTC) is a rare malignancy with minimal treatment options. Many, but not all, MTCs express somatostatin receptors. OBJECTIVE Our aim was to explore the role of 68Ga-DOTA-somatostatin analogue (SSA) PET/CT in patients with metastatic MTC, and to determine their eligibility for peptide receptor radionuclide therapy (PRRT). METHODS We retrospectively identified patients with metastatic MTC who had 68Ga-DOTA-SSA PET/CT at five centers. We collected characteristics on contrast-enhanced CT, 68Ga-DOTA-SSA and 18F-FDG PET/CT. The efficacy of PRRT was explored in a subgroup of patients. Kaplan-Meier analysis was used to estimate time to treatment failure (TTF) and overall survival (OS). RESULTS Seventy-one patients were included (10 local recurrence, 61 distant disease). Of the patients with distant disease, 16 (26%) had ≥50% of disease sites with tracer avidity greater than background liver, including 10 (10/61, 16%) with >90%. In 19 patients with contemporaneous contrast-enhanced CT, no disease regions were independently identified on 68Ga-DOTA-SSA PET/CT. Thirty-five patients had an 18F-FDG PET/CT, with 18F-FDG positive/ 68Ga-DOTA-SSA negative metastases identified in 15 (43%). Twenty-one patients had PRRT with a median TTF of 14 months (95%CI 8-25) and a median OS of 63 months (95%CI 21-not reached). Of the entire cohort, the median OS was 323 months (95%CI 152-not reached). Predictors of poorer overall survival included a short calcitonin doubling-time (≤24 months), strong 18F-FDG avidity and age ≥60 years. CONCLUSIONS The prevalence of high tumour avidity on 68Ga-DOTA-SSA PET/CT is low in the setting of metastatic MTC; nevertheless, PRRT may still be a viable treatment option in select patients.
NbPsbO1 Interacts Specifically with the Bamboo Mosaic Virus (BaMV) Subgenomic RNA (sgRNA) Promoter and Is Required for Efficient BaMV sgRNA Transcription

Production of subgenomic RNAs (sgRNAs) for efficient translation of downstream viral proteins is one of the major strategies adapted for viruses that contain a multicistronic RNA genome. Both viral genomic RNA (gRNA) replication and sgRNA transcription rely on the combined activities of viral replicase and host proteins, which recognize promoter regions for the initiation of RNA synthesis. ABSTRACT Many positive-strand (+) RNA viruses produce subgenomic RNAs (sgRNAs) in the infection cycle through the combined activities of viral replicase and host proteins. However, knowledge about host proteins involved in direct sgRNA promoter recognition is limited. Here, in the partially purified replicase complexes from Bamboo mosaic virus (BaMV)-infected tissue, we have identified the Nicotiana benthamiana photosystem II oxygen-evolving complex protein, NbPsbO1, which specifically interacted with the promoter of sgRNA but not that of genomic RNA (gRNA). Silencing of NbPsbO1 expression suppressed BaMV accumulation in N. benthamiana protoplasts without affecting viral gRNA replication. Overexpression of wild-type NbPsbO1 stimulated BaMV sgRNA accumulation. Fluorescent microscopy examination revealed that the fluorescence associated with NbPsbO1 was redistributed from chloroplast granal thylakoids to stroma in BaMV-infected cells. Overexpression of a mislocalized mutant of NbPsbO1, dTPPsbO1-T7, inhibited BaMV RNA accumulation in N. benthamiana, whereas overexpression of an NbPsbO1 derivative, sPsbO1-T7, designed to be targeted to chloroplast stroma, upregulated the sgRNA level. Furthermore, depletion of NbPsbO1 in BaMV RdRp preparation significantly inhibited sgRNA synthesis in vitro but exerted no effect on (+) or (−) gRNA synthesis, which indicates that NbPsbO1 is required for efficient sgRNA synthesis. These results reveal a novel role for NbPsbO1 in the selective enhancement of BaMV sgRNA transcription, most likely via direct interaction with the sgRNA promoter. IMPORTANCE Production of subgenomic RNAs (sgRNAs) for efficient translation of downstream viral proteins is one of the major strategies adapted for viruses that contain a multicistronic RNA genome. Both viral genomic RNA (gRNA) replication and sgRNA transcription rely on the combined activities of viral replicase and host proteins, which recognize promoter regions for the initiation of RNA synthesis. However, compared to the cis-acting elements involved in the regulation of sgRNA synthesis, the host factors involved in sgRNA promoter recognition mostly remain to be elucidated. Here, we found a chloroplast protein, NbPsbO1, which specifically interacts with Bamboo mosaic virus (BaMV) sgRNA promoter. We showed that NbPsbO1 is relocated to the BaMV replication site in BaMV-infected cells and demonstrated that NbPsbO1 is required for efficient BaMV sgRNA transcription but exerts no effect on gRNA replication. This study provides a new insight into the regulating mechanism of viral gRNA and sgRNA synthesis.
A Preliminary Study of Short-Term Sexual Function and Satisfaction Among Men Post-Myocardial Infarction

Sexuality is an important component of holistic quality of life, and myocardial infarction (MI) negatively influences many aspects of sexuality, including sexual function. However, there is limited literature that examines sexuality beyond the most basic physical components. This pilot study aimed to describe the relationships between the physical, psychologic, and social domains of holistic sexuality at an early timepoint post-MI. Adult men post-MI were mailed self-report surveys at 2 weeks post discharge. Physical domains of sexuality were measured with the arousal, orgasm, erection, lubrication, and pain subscales of the Male Sexual Function Index (MSFI). The social domain utilized the sexual satisfaction subscale of the MSFI. The psychologic domain included the desire subscale of the MSFI and sexual fear (Multidimensional Sexuality Questionnaire). Spearman correlations were estimated to examine associations among the different measurement subscales. Twenty-four men post-MI were analyzed. Average scores on the MSFI were 9.2 (SD 7.7). Desire and satisfaction were the highest scoring subscales among men when compared with other subscales (i.e. erection, lubrication). There was minimal evidence supporting a relationship between sexual fear and function. Additional research is also needed with larger samples, and among women post-MI.
Milk metabolites, proteins and oxidative stress markers in dairy cows suffering from Staphylococcus aureus subclinical mastitis with or without spontaneous cure

Abstract Our objective was to evaluate relationships between milk components (acute phase proteins, enzymes, metabolic parameters and oxidative indices) and the spontaneous cure outcome of Staphylococcus aureus subclinical mastitis in dairy cows. The values of haptoglobin, serum amyloid A (SAA), malondialdehyde (MDA), total antioxidant capacity, milk urea nitrogen (MUN), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), electrolytes (Cl and K), total protein, albumin, α-lactalbumin, β-lactoglobulin, and immunoglobulin were measured in milk samples of S. aureus subclinical mastitis cows with spontaneous cure (n = 23), S. aureus subclinical mastitis cows without spontaneous cure (n = 29) and healthy cows (n = 23). The comparison of measured parameters revealed that subclinical mastitis cows with spontaneous cure had lower ALP and haptoglobin concentrations both at diagnosis and after cure (P < 0.05). In contrast, total antioxidant capacity and MDA concentration in subclinical mastitis cows without spontaneous cure significantly increased with time (P < 0.05). We can suggest that elevated haptoglobin concentration and higher ALP activity indicative of enhanced oxidative stress could potentially serve as early diagnostic indicators of chronic disease and the persistence of S. aureus subclinical mastitis in dairy cows.