Miracle-dz/UniFAR-FTUs huggingface dataset:
Childhood asthma in the new omics era: challenges and perspectives

Purpose of review Childhood asthma is a heterogeneous inflammatory disease comprising different phenotypes and endotypes and, particularly in its severe forms, has a large impact on the quality-of-life of patients and caregivers. The application of advanced omics technologies provides useful insights into underlying asthma endotypes and may provide potential clinical biomarkers to guide treatment and move towards a precision medicine approach. Recent findings The current article addresses how novel omics approaches have shaped our current understanding of childhood asthma and highlights recent findings from (pharmaco)genomics, epigenomics, transcriptomics, and metabolomics studies on childhood asthma and their potential clinical implications to guide treatment in severe asthmatics. Summary Until now, omics studies have largely expanded our view on asthma heterogeneity, helped understand cellular processes underlying asthma, and brought us closer towards identifying (bio)markers that will allow the prediction of treatment responsiveness and disease progression. There is a clinical need for biomarkers that will guide treatment at the individual level, particularly in the field of biologicals. The integration of multiomics data together with clinical data could be the next promising step towards development individual risk prediction models to guide treatment. However, this requires large-scale collaboration in a multidisciplinary setting.
Murrayanine exerts antiproliferative effects on human oral cancer cells through inhibition of AKT/mTOR and Raf/MEK/ERK signalling pathways in vitro and inhibits tumor growth in vivo.

PURPOSE Oral cancer ranks as the 6th most prevalent type of cancer accounting for significant mortality around the world and studies are being directed to develop efficient chemotherapy for oral cancer. In this study the anticancer effects of a carbazole alkaloid Murrayanine were investigated in vitro and in vivo. METHODS Cell counting assay and colony formation assay were used to examine cell viability. DAPI and propidium iodide (PI) staining were used to detect apoptosis. Western blotting was used to examine protein expression. Xenografted mice were used for in vivo study. RESULTS The results showed that Murrayanine decreased the viability of the oral cancer SCC-25 cells and exhibited an IC50 of 15 µM. The cytotoxicity of Murrayanine was also investigated on the normal hTERT-OME cells and it was found that this molecule exerted very low toxic effects on these cells exhibiting an IC50 of 92 µM. Murrayanine also caused considerable changes in the morphology of the SCC-25 cells and inhibited their colony forming potential. PI and DAPI staining revealed that Murrayanine prompted apoptosis of the SCC-25 cells. The apoptotic cells from 2.2% in the control increased to around 35% at 30 µM concentration. Moreover, Murrayanine caused increase in the Bax/Bcl-2 ratio and also increased the expression of Caspase-3. Murrayanine also deactivated the AKT/mTOR and Raf/MEK/ERK signalling pathways and suppressed the growth of the xenografted tumors in vivo. CONCLUSION The findings of the present investigation suggest that Murrayanine may prove essential in the development of systemic therapy for oral cancers.
Using Deep Learning in Ultrasound Imaging of Bicipital Peritendinous Effusion to Grade Inflammation Severity

Inflammation of the long head of the biceps tendon is a common cause of shoulder pain. Bicipital peritendinous effusion (BPE) is the most common biceps tendon abnormality and is related to various shoulder injuries. Physicians usually use ultrasound imaging to grade the inflammation severity of the long head of the biceps tendon. However, obtaining a clear and accurate ultrasound image is difficult for inexperienced attending physicians. To reduce physicians’ workload and avoid errors, an automated BPE recognition system was developed in this article for classifying inflammation into the following categories—normal and mild, moderate, and severe. An ultrasound image serves as the input in the proposed system; the system determines whether the ultrasound image contains biceps. If the image depicts biceps, then the system predicts BPE severity. In this study, two crucial methods were used for solving problems associated with computer-aided detection. First, the faster regions with convolutional neural network (faster R-CNN) used to extract the region of interest (ROI) area identification to evaluate the influence of dataset scale and spatial image context on performance. Second, various CNN architectures were evaluated and explored. Model performance was analyzed by using various network configurations, parameters, and training sample sizes. The proposed system was used for three-class BPE classification and achieved 75% accuracy. The results obtained for the proposed system were determined to be comparable to those of other related state-of-the-art methods.
Reactive Extrusion of Nonmigratory Antioxidant Poly(lactic Acid) Packaging.

Reactive extrusion of bio-derived active packaging offers a new approach to address converging concerns over environmental contamination and food waste. Herein, metal chelating nitrilotriacetic acid (NTA) ligands were grafted onto poly(lactic acid) (PLA) by reactive extrusion to produce metal chelating PLA (PLA-g-NTA). Radical grafting was confirmed by ATR-FTIR with introduction of secondary alkyl stretches (2919 cm-1 and 2860 cm-1) and by XPS with increase in atomic percentage of nitrogen. Compared to films prepared from native, granular PLA (gPLA), PLA-g-NTA films had lower contact angle and hysteresis values (86.35o±2.49 and 31.89o±2.27 to 79.91o±1.58 and 21.79o±1.72 respectively) supporting the surface orientation of the NTA ligands. The PLA-g-NTA films exhibited significant antioxidant character with a radical scavenging capacity of 0.675±0.026 nmol Trolox(eq)/cm2 and an iron chelation capacity of 54.09±9.36 nmol/cm2. PLA-g¬-NTA films delayed ascorbic acid degradation, retaining ~45% ascorbic acid over the 9-day study compared to <20% for control PLA. This research makes significant advances in translating active packaging technologies to bio-derived materials using scalable, commercially translatable synthesis methods.
Pollen on stigmas as proxies of pollinator competition and facilitation: complexities, caveats, and future directions.

BACKGROUND Pollen transfer via animals is necessary for reproduction by ~80% of flowering plants, and most of these plants live in multispecies communities where they can share pollinators. While diffuse plant-pollinator interactions are increasingly recognized as the rule rather than the exception, their fitness consequences cannot be deduced from flower visitation alone, so other proxies, functionally closer to seed production and amenable for use in a broad variety of diverse communities, are necessary. SCOPE We conceptually summarize how the study of pollen on stigmas of spent flowers can reflect key drivers and functional aspects of the plant-pollinator interaction (e.g. competition, facilitation, or commensalism). We critically evaluate how variable visitation rates and other factors (pollinator pool and floral avoidance) can give rise to different relationships between heterospecific pollen and 1) conspecific pollen on the stigma, and 2) conspecific tubes/grain in the style, revealing the complexity of potential interpretations. We advise on best practices for using these proxies, noting the assumptions and caveats involved in their use, and explicate what additional data is required to verify interpretation of given patterns. CONCLUSIONS We conclude that characterizing pollen on stigmas of spent flowers provides an attainable indirect measure of pollination interactions, but given the complex processes of pollen transfer that generate patterns of conspecific-heterospecific pollen on stigmas these cannot alone determine whether competition or facilitation are the underlying drivers. Thus, functional tests are also needed to validate these hypotheses.
An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome

Supplemental Digital Content is available in the text. Background: Long QT syndrome (LQTS) is the first described and most common inherited arrhythmia. Over the last 25 years, multiple genes have been reported to cause this condition and are routinely tested in patients. Because of dramatic changes in our understanding of human genetic variation, reappraisal of reported genetic causes for LQTS is required. Methods: Utilizing an evidence-based framework, 3 gene curation teams blinded to each other’s work scored the level of evidence for 17 genes reported to cause LQTS. A Clinical Domain Channelopathy Working Group provided a final classification of these genes for causation of LQTS after assessment of the evidence scored by the independent curation teams. Results: Of 17 genes reported as being causative for LQTS, 9 (AKAP9, ANK2, CAV3, KCNE1, KCNE2, KCNJ2, KCNJ5, SCN4B, SNTA1) were classified as having limited or disputed evidence as LQTS-causative genes. Only 3 genes (KCNQ1, KCNH2, SCN5A) were curated as definitive genes for typical LQTS. Another 4 genes (CALM1, CALM2, CALM3, TRDN) were found to have strong or definitive evidence for causality in LQTS with atypical features, including neonatal atrioventricular block. The remaining gene (CACNA1C) had moderate level evidence for causing LQTS. Conclusions: More than half of the genes reported as causing LQTS have limited or disputed evidence to support their disease causation. Genetic variants in these genes should not be used for clinical decision-making, unless accompanied by new and sufficient genetic evidence. The findings of insufficient evidence to support gene-disease associations may extend to other disciplines of medicine and warrants a contemporary evidence-based evaluation for previously reported disease-causing genes to ensure their appropriate use in precision medicine.
Deep Neural Networks With Region-Based Pooling Structures for Mammographic Image Classification

Breast cancer is one of the most frequently diagnosed solid cancers. Mammography is the most commonly used screening technology for detecting breast cancer. Traditional machine learning methods of mammographic image classification or segmentation using manual features require a great quantity of manual segmentation annotation data to train the model and test the results. But manual labeling is expensive, time-consuming, and laborious, and greatly increases the cost of system construction. To reduce this cost and the workload of radiologists, an end-to-end full-image mammogram classification method based on deep neural networks was proposed for classifier building, which can be constructed without bounding boxes or mask ground truth label of training data. The only label required in this method is the classification of mammographic images, which can be relatively easy to collect from diagnostic reports. Because breast lesions usually take up a fraction of the total area visualized in the mammographic image, we propose different pooling structures for convolutional neural networks(CNNs) instead of the common pooling methods, which divide the image into regions and select the few with high probability of malignancy as the representation of the whole mammographic image. The proposed pooling structures can be applied on most CNN-based models, which may greatly improve the models’ performance on mammographic image data with the same input. Experimental results on the publicly available INbreast dataset and CBIS dataset indicate that the proposed pooling structures perform satisfactorily on mammographic image data compared with previous state-of-the-art mammographic image classifiers and detection algorithm using segmentation annotations.
Salicylic acid receptor NPR1 is involved in guard cell chitosan signaling

ABSTRACT Chitosan (CHT) induces stomatal closure and thus plays a crucial role in plants to adapt to the adverse environments. Our previous results of a SA-deficient mutant nahG suggest that endogenous salicylic acid (SA) is involved in the CHT signaling in guard cells. Here in order to make the involvement definite, we examined stomatal responses to CHT of another SA-deficient mutant, sid2, and an SA receptor mutant, npr1-3. The sid2 mutation impaired CHT-induced stomatal closure and reactive oxygen species production and both impairments were complemented with exogenous SA application. Moreover, the CHT-induced stomatal closure is disrupted in the npr1-3 mutant. These results suggest that endogenous SA is involved in the CHT-induced stomatal closure via the SA receptor, NPR1. Abbreviations SA: salicylic acid; ABA: abscisic acid; ROS: reactive oxygen species; NPR1: nonexpresser of pathogenesis-related genes1; CHT: chitosan; DAB: 3,3′-diaminobenzidine Graphical abstract Impairment of chitosan-induced stomatal closure in SA-deficient mutant, sid2, and an SA receptor mutant, npr1, and the complementation of the impairment with exogenous SA application.
Perceived social norms and concussion-disclosure behaviours among first-year NCAA student-athletes: implications for concussion prevention and education

ABSTRACT Timely disclosure and identification of concussion symptoms are essential to proper care. Perceived social norms are a potential driving factor in many health-related decisions. The study purpose was to describe concussion disclosure behaviours and identify the association between perceived social norms and these disclosure behaviours. First-year student-athletes (n = 391) at two NCAA institutions completed a cross-sectional survey about concussion disclosure and disclosure determinants. Log-binomial regression models identified factors associated with concussion disclosure behaviour prevalence for: higher intention to disclose symptoms, disclosed all at time of injury, eventually disclosed all, and never participated with concussion symptoms. More favourable perceived social norms were associated with higher prevalence of intention to disclose (PR = 1.34; 95%CI: 1.18, 1.53) and higher prevalence of never participating in sports with concussion symptoms (PR = 1.50; 95%CI: 1.07, 2.10). Clinicians, coaches, sports administrators, and healthcare practitioners should be mindful of the need to create supportive social environments to improve concussion symptom disclosure.
PROSPECT guideline for oncological breast surgery: a systematic review and procedure‐specific postoperative pain management recommendations

Analgesic protocols used to treat pain after breast surgery vary significantly. The aim of this systematic review was to evaluate the available literature on this topic and develop recommendations for optimal pain management after oncological breast surgery. A systematic review using preferred reporting items for systematic reviews and meta‐analysis guidance with procedure‐specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials assessing postoperative pain using analgesic, anaesthetic or surgical interventions were identified. Seven hundred and forty‐nine studies were found, of which 53 randomised controlled trials and nine meta‐analyses met the inclusion criteria and were included in this review. Quantitative analysis suggests that dexamethasone and gabapentin reduced postoperative pain. The use of paravertebral blocks also reduced postoperative pain scores, analgesia consumption and the incidence of postoperative nausea and vomiting. Intra‐operative opioid requirements were documented to be lower when a pectoral nerves block was performed, which also reduced postoperative pain scores and opioid consumption. We recommend basic analgesics (i.e. paracetamol and non‐steroidal anti‐inflammatory drugs) administered pre‐operatively or intra‐operatively and continued postoperatively. In addition, pre‐operative gabapentin and dexamethasone are also recommended. In major breast surgery, a regional anaesthetic technique such as paravertebral block or pectoral nerves block and/or local anaesthetic wound infiltration may be considered for additional pain relief. Paravertebral block may be continued postoperatively using catheter techniques. Opioids should be reserved as rescue analgesics in the postoperative period. Research is needed to evaluate the role of novel regional analgesic techniques such as erector spinae plane or retrolaminar plane blocks combined with basic analgesics in an enhanced recovery setting.
LncRNA-ATB promotes apoptosis of non-small cell lung cancer cells through MiR-200a/β-Catenin.

PURPOSE Long non-coding RNAs (lncRNAs) play important roles in cancer, but the effects of lncRNA-ATB on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells remain unclear. Therefore, the present study was conducted to explore the role of this lnc-RNA in NSCLC. METHODS The NSCLC NCI-H838 cell line cultured in vitro were used as the objects of study. First, the expressions of lncRNA-ATB, miR-200a and β-catenin in cells were detected. Then, the expression of lncRNA-ATB was knocked down using siRNA, and the effects of low expression of lncRNA-ATB on miR-200a/β-catenin pathway and apoptosis were studied. RESULTS Compared with normal lung epithelial cells BEAS-2B, NCI-H838 cells had a significantly increased level of lncRNA-ATB (p<0.01), a significantly decreased level of miR-200a (p<0.01) and also a significantly increased level of β-catenin (p<0.01). After knockdown of lncRNA-ATB using si-ATB, the expression level of miR-200a was significantly increased, while that of β-catenin was significantly decreased. Besides, si-ATB remarkably increased the expression of Bcl-2 (p<0.01), and reduced the expressions of cleaved-caspase3 and Cytochrome C (p<0.01) and the apoptosis. In addition, the miR-200a mimic lowered obviously the expression of β-catenin (p<0.05) and reduced apoptosis. CONCLUSIONS This study suggests that lncRNA-ATB promotes the apoptosis of NSCLC cells through inhibiting the expression of miR-200a and reversely promoting the expression of β-catenin.
Upregulation of Hallmark Muscle Genes Protects GneM743T/M743T Mutated Knock-In Mice From Kidney and Muscle Phenotype

Background: Mutations in GNE cause a recessive, adult onset myopathy characterized by slowly progressive distal and proximal muscle weakness. Knock-in mice carrying the most frequent mutation in GNE myopathy patients, GneM743T/M743T, usually die few days after birth from severe renal failure, with no muscle phenotype. However, a spontaneous sub-colony remains healthy throughout a normal lifespan without any kidney or muscle pathology. Objective: We attempted to decipher the molecular mechanisms behind these phenotypic differences and to determine the mechanisms preventing the kidney and muscles from disease. Methods: We analyzed the transcriptome and proteome of kidneys and muscles of sick and healthy GneM743T/M743T mice. Results: The sick GneM743T/M743T kidney was characterized by up-regulation of extra-cellular matrix degradation related processes and by down-regulation of oxidative phosphorylation and respiratory electron chain pathway, that was also observed in the asymptomatic muscles. Surprisingly, the healthy kidneys of the GneM743T/M743T mice were characterized by up-regulation of hallmark muscle genes. In addition the asymptomatic muscles of the sick GneM743T/M743T mice showed upregulation of transcription and translation processes. Conclusions: Overexpression of muscle physiology genes in healthy GneM743T/M743T mice seems to define the protecting mechanism in these mice. Furthermore, the strong involvement of muscle related genes in kidney may bridge the apparent phenotypic gap between GNE myopathy and the knock-in GneM743T/M743T mouse model and provide new directions in the study of GNE function in health and disease.
Autophagy-mediated compartmental cytoplasmic deletion is essential for tobacco pollen germination and male fertility

ABSTRACT In plants, macroautophagy/autophagy has mainly been associated with stress-related processes but how it impacts normal physiological and developmental processes remains largely unexplored. Pollen germination is the critical first step toward fertilization in flowering plants. It is metabolically demanding and relies on high levels of cytoplasmic reorganization activities to support a dramatic morphological transformation that underlies the development of a pollen tube as the conduit to deliver sperm for fertilization. The role of autophagy in this process remains unclear. Here we provide evidence that pollen germination is accompanied by elevated autophagic activity and successful pollen tube emergence depends on autophagy-mediated cytoplasmic deletion. Genetic and cytological experiments demonstrate that inhibition of autophagy prevents pollen germination while induces the persistence of a layer of undegraded cytoplasm at the germination aperture. Together, these results unveil a novel compartmentalized autophagy. Furthermore, high-throughput comparative lipidomic analyses show that suppressed autophagy-induced inhibition of pollen germination is accompanied by altered profiles of stored and signaling lipids. Proteomic analyses reveal that autophagy likely exert its role in pollen germination via downstream mitochondria-related pathways. These findings reveal a critical role for autophagy in initiating pollen germination and provide evidences for compartmental cytoplasmic deletion being crucial for male fertility. Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy-related gene; Cer: ceramide; CL: cardiolipin; Con A: concanamycin A; DAG: diradylglycerol; GO: gene ontology; HAG: hour after germination; LC-MS: liquid chromatography-mass spectrometry; MAG: min after germination; MDC: monodansylcadaverine; PE: phosphatidylethanolamine; PI: phosphatidylinositol; PLD: phospholipase D; PtdIns3K: phosphatidylinositol 3-kinase; RT-qPCR: quantitative real-time reverse transcription PCR; TAG: triradylglycerol; TEM: transmission electron microscopy; TMT: tandem mass tagging.