Miracle-dz/UniFAR-FTUs huggingface dataset:
A transcriptomic study of probenecid on injured spinal cords in mice

Background Recent studies have found that probenecid has neuroprotective and reparative effects on central nervous system injuries. However, its effect on genome-wide transcription in acute spinal cord injury (SCI) remains unknown. In the present study, RNA sequencing (RNA-Seq) is used to analyze the effect of probenecid on the local expression of gene transcription 8 h after spinal injury. Methods An Infinite Horizon impactor was used to perform contusive SCI in mice. The SCI model was made by using a rod (1.3 mm diameter) with a force of 50 Kdynes. Sham-operated mice only received a laminectomy without contusive injury. The injured mice were randomly assigned into either the control (SCI_C) or probenecid injection (SCI_P) group. In the latter group, the probenecid drug was intraperitoneally injected (0.5 mg/kg) immediately following injury. Eight hours after the injury or laminectomy, the spinal cords were removed from the mice in both groups. The total RNAs were extracted and purified for library preparation and transcriptome sequencing. Differential gene expressions (DEGs) of the three groups—sham, SCI_C and SCI_P—were analyzed using a DESeq software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs were performed using a GOseq R package and KOBAS software. Real-time quantitative reverse-transcriptase polymerase chain reaction was used to validate RNA-Seq results. Results RNA-Seq showed that, compared to the SCI_C group, the number of DEGs was 641 in the SCI_P group (286 upregulated and 355 downregulated). According to GO analysis, DEGs were most enriched in extracellular matrix (ECM), collagen trimer, protein bounding and sequence specific DNA binding. KEGG analysis showed that the most enriched pathways included: cell adhesion molecules, Leukocyte transendothelial migration, ECM-receptor interactions, PI3K-Akt signaling pathways, hematopoietic cell lineages, focal adhesions, the Rap1 signaling pathway, etc. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA554464).
Development and Validation of Nomograms for Predicting the Prognosis of Triple-Negative Breast Cancer Patients Based on 379 Chinese Patients

Purpose We aimed to construct universally applicable nomograms incorporating prognostic factors to predict the prognosis of patients with triple-negative breast cancer (TNBC). Patients and methods Clinicopathological data of 379 patients with TNBC from March 2008 to June 2014 were retrospectively collected and analyzed. The endpoints were disease-free survival (DFS) and overall survival (OS). Patients were randomly divided into a training group and an independent validation group. In the training group, the prognostic factors were screened to develop nomograms. C-index and calibration curves were used to evaluate the predictive accuracy and discriminative ability of nomograms in both groups. The accuracy of the nomograms was also compared with the traditional American Joint Committee on Cancer Tumor-Node-Metastasis anatomical stage (8th edition). Results Four prognostic factors (albumin-to-globulin ratio, neutrophil-to-lymphocyte ratio, positive lymph nodes, and tumor size) were used to construct the nomogram of DFS. In addition to the aforementioned factors, age was taken into account in the construction of the OS nomogram. The C-index of the DFS nomogram in the training and validation groups was 0.71 (95% confidence interval [CI]: 0.64–0.77) and 0.69 (95% CI: 0.58–0.79), respectively; the C-index of the OS nomogram was 0.77 (95% CI: 0.70–0.84) and 0.74 (95% CI: 0.62–0.86), respectively. This suggests that the nomograms had high accuracy. Moreover, calibration curves showed good consistencies in both groups. Our models showed superiority in predicting accuracy compared with the AJCC TNM staging system. Furthermore, two web pages of the nomograms were produced: DFS: https://sh-skipper.shinyapps. io/TNBC1/; OS: https://sh-skipper.shinyapps. io/TNBC2/. Conclusion These predictive models are simple and easy to use, particularly the web versions. They have certain clinical value in predicting the prognosis of patients with TNBC. They can assist doctors in identifying patients at different prognostic risks and strengthen the treatment or follow-up accordingly.
A mixed method study of a peer support intervention for newly diagnosed primary brain tumour patients

Purpose The purpose of this pilot study was to investigate the impact of an intervention designed to enhance quality of life in newly diagnosed primary brain tumour (PBT) patients. The intervention involved a structured, one time meeting between newly diagnosed PBT patients and trained volunteer "veteran" PBT patients. Methods Two volunteers met for a single, one-on-one meeting with a total of 10 newly diagnosed PBT patients. A combination of questionnaires and interviews were used to investigate the impact of the intervention for both the new patients and the volunteers. Results The intervention appeared to be of substantial value for both groups of participants. Analysis revealed that the newly diagnosed patients experienced a range of benefits, including those related to the themes of: increased hope, valued guidance, hearing what it's really like, overcoming aloneness, and receiving a wake up call to what matters. Only relatively minor adverse effects and challenges were reported. Conclusions The findings provide initial evidence that the developed intervention has the potential to be a safe, useful means of enhancing psycho-social well-being in newly diagnosed PBT patients.Further investigation into the potential of one-to-one, peer support for brain tumour patients is an important research priority.
Exploring the clinical relevance of cough hypersensitivity syndrome

ABSTRACT Introduction: Knowledge of the pathophysiology of cough has continued to advance over recent decades. Establishing anatomic-diagnostic protocols, based on the anatomy and distribution of vagus nerve pathways regulating the cough reflex, was the first breakthrough in modern clinical medicine for chronic cough. The unmet clinical need has prompted revised thinking regarding the pathophysiology of and the clinical approach to chronic cough. Areas covered: The paradigm of cough hypersensitivity syndrome (CHS) has been recently proposed, wherein aberrant neuro-pathophysiology is a common etiology. This review covers major findings on chronic cough and cough hypersensitivity, particularly focused on recently-published studies and explores the clinical relevance and applicability of CHS based on current knowledge and discuss knowledge gaps and future research directions. Expert opinion: This paradigm has provided new opportunities in managing chronic cough and evidence is accumulating to support the validity of CHS. It also warrants the re-appraisal of existing clinical evidence and investigation of how to refine our clinical strategy. While CHS highlights the importance of clinical thinking from the viewpoint of cough, the value of anatomic-diagnostic protocols should remain. Moreover, given the considerable heterogeneity in clinical presentation, cough-associated disease conditions, and treatment responses across different patients, precise molecular endotyping remains key to making further to advancing clinical practice .
Risk and treatment of symptomatic epidural hematoma after anterior cervical spine surgery

Abstract Symptomatic epidural hematoma (SEH) after anterior cervical spine surgery is very rare, but it has disastrous consequences for the patients. Timely diagnosis and evaluation can effectively reduce the sequelae of neurological deficit in SEH. The purpose of this study was to retrospectively analyze a subset of clinical data of SEH after anterior cervical spine surgery, and to investigate the risk factors and treatment experience of this serious complication. Neurological deterioration after anterior cervical spine surgery was detected in six patients. Epidural hematoma was confirmed by emergency cervical magnetic resonance imaging (MRI). The patients included five males and one female, with an average age of 56.7 ± 13.1 years (range 42–76 years). Three patients had a history of drinking and/or smoking. All of the patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) preoperatively, but without anticoagulant drugs or pre-spinal surgery. The coagulation function was normal in all patients. Except for one patient, who had lower blood pressure (BP) during the operation and higher BP after the operation, the other patients had a normal level of BP during the pre-, intra-, and post-operation periods. The average time was 9.9 ± 6.7 hours (range, 2−19 hours) from the postoperative period to the initial neurological deficit and 6.3 ± 6.0 hours (range, 1.8−16.7 hours) from the initial deterioration to evacuation. Five patients underwent emergency evacuation, and one patient underwent conservative treatment. Four patients who underwent evacuation and one patient who received conservative treatment achieved neurological function recovery with an American Spinal Injury Association (ASIA) grade 2.4 ± 0.9 (range, 2−4 score) score at the last follow-up. One patient with confirmed arterial epidural hemorrhage during the evaluation showed no neurological function recovery at the last follow-up. Wide exposure of the epidural space and BP level during the perioperative period play an important role in the formation of SEH after anterior cervical spine surgery. Arterial epidural hematoma has serious consequences; therefore, early diagnosis and evaluation play an important role in the recovery from paralysis.
Ste20-Like Kinase (SLK) Mediated Control of Actin Polymerization is a New Mechanism for Thin Filament Associated Regulation of Airway Smooth Muscle Contraction.

It has been reported that actin polymerization is regulated by protein tyrosine phosphorylation in smooth muscle upon contractile stimulation. The role of protein serine/threonine phosphorylation in modulating actin dynamics is under-investigated. Ste20-like kinase (SLK) is a serine/threonine protein kinase that plays a role in apoptosis, cell cycle, proliferation, and migration. The function of SLK in smooth muscle is mostly unknown. Here, SLK knockdown (KD) inhibited the acetylcholine (ACh)-induced actin polymerization and contraction without affecting myosin light chain phosphorylation at Ser-19 in human airway smooth muscle. Stimulation with ACh induced paxillin phosphorylation at Ser-272, which was reduced in SLK KD cells. However, SLK did not catalyze paxillin Ser-272 phosphorylation in vitro. But, SLK KD attenuated polo-like kinase 1 (Plk1) phosphorylation at Thr-210. Plk1 mediated paxillin phosphorylation at Ser-272 in vitro. Expression of the non-phosphorylatable paxillin mutant S272A (substitution of alanine at Ser-272) attenuated the agonist-enhanced F-actin/G-actin ratios without affecting myosin light chain phosphorylation. Because neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) phosphorylation at Tyr-256 (an indication of its activation) promotes actin polymerization, we also assessed the role of paxillin phosphorylation in N-WASP activation. S272A paxillin inhibited the ACh-enhanced N-WASP phosphorylation at Tyr-256. Together, these results suggest that SLK regulates paxillin phosphorylation at Ser-272 via Plk1, which modulates N-WASP activation and actin polymerization in smooth muscle. SLK-mediated actin cytoskeletal reorganization may facilitate force transmission between the contractile units and the extracellular matrix.
Are changes in depressive symptoms, general health and residential area socio-economic status associated with trajectories of waist circumference and body mass index?

Objective This study sought to assess whether changes in depressive symptoms, general health, and area-level socio-economic status (SES) were associated to changes over time in waist circumference and body mass index (BMI). Methods A total of 2871 adults (18 years or older), living in Adelaide (South Australia), were observed across three waves of data collection spanning ten years, with clinical measures of waist circumference, height and weight. Participants completed the Centre for Epidemiologic Studies Depression (CES-D) and Short Form 36 health questionnaires (SF-36 general health domain). An area-level SES measure, relative location factor, was derived from hedonic regression models using residential property features but blind to location. Growth curve models with latent variables were fitted to data. Results Waist circumference, BMI and depressive symptoms increased over time. General health and relative location factor decreased. Worsening general health and depressive symptoms predicted worsening waist circumference and BMI trajectories in covariate-adjusted models. Diminishing relative location factor was negatively associated with waist circumference and BMI trajectories in unadjusted models only. Conclusions Worsening depressive symptoms and general health predict increasing adiposity and suggest the development of unhealthful adiposity might be prevented by attention to negative changes in mental health and overall general health.
Proposing an Endotracheal Tube Selection Tool Based on Multivariate Analysis of Airway Imaging

Objectives: We aimed to comprehensively investigate different upper airway segments in adults, determine the predictors of the size of each segment, and identify an appropriate endotracheal tube (ETT) size chart. Study Design: Retrospective chart review. Setting: Tertiary care center. Materials and Methods: The data for patients aged >18 years who underwent neck computed tomography were screened. Patients with existing tumors, trauma, or any pathology that can alter the normal airway anatomy and those with intubation, tracheostomy, or nasogastric tubes were excluded. Computed tomography software was used to measure the anteroposterior diameter (APD), transverse diameter (TD), and cross-sectional area (CSA) at the glottic, proximal subglottic, distal subglottic, and tracheal levels. Multiple regression analysis was used to identify the predictors of the airway size. Results: One hundred patients were reviewed. The TD was consistently smaller than or equal to the APD at each level in all but 3 patients. The mean CSA and TD (170 mm2 and 11.3 mm, respectively) of the glottis indicated that the glottis was most often the narrowest level, followed by the proximal subglottis where the mean CSA and TD were 192.1 mm2 and 12.7 mm, respectively. Moreover, the mean APD was the smallest at the level of the trachea (20.1 mm). Multiple regression analysis confirmed that height and sex were the predominant predictors of measurements for the 4 airway segments. In addition, age was associated with the TD and CSA of the distal subglottic and tracheal segments, respectively. Conclusion: One-third of our participants exhibited a proximal subglottic diameter that was equal to or smaller than the glottic diameter. Our findings also suggested that the height and sex of the patients are important variables for the selection of an appropriate ETT size.
Septin architecture and function in budding yeast

Abstract The septins constitute a conserved family of guanosine phosphate-binding and filament-forming proteins widespread across eukaryotic species. Septins appear to have two principal functions. One is to form a cortical diffusion barrier, like the septin collar at the bud neck of Saccharomyces cerevisiae, which prevents movement of membrane-associated proteins between the mother and daughter cells. The second is to serve as a polymeric scaffold for recruiting the proteins required for critical cellular processes to particular subcellular areas. In the last decade, structural information about the different levels of septin organization has appeared, but crucial structural determinants and factors responsible for septin assembly remain largely unknown. This review highlights recent findings on the architecture and function of septins and their remodeling with an emphasis on mitotically dividing budding yeasts.
Efficacy and safety of core stability training on gait of children with cerebral palsy

Abstract Background: Cerebral palsy (CP) is a common disability in children featured with pathological gait and limb function limitation due to muscle weakness. Improving limb function and quality of life is currently considered to be highlighted. Physiotherapy is a chief component of rehabilitation for children with CP, correcting gait and improve walking capacity through muscle strength training. Standard rehabilitation programs for CP have not been determined. Core stability training (CST), which coordinates limb balance via trunk control, is widely used in sports competition. And it is gradually introduced into the rehabilitation of children with cerebral palsy with a positive impact on the patients’ gait performance. By screening published literatures, this study aims to conduct a meta-analysis to systematically evaluate the effectiveness and safety of CST in gait of children with CP. Methods: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on CST in the treatment of children with CP were searched from 6 databases. Moreover, the reference lists of conference papers and included literatures will be manually searched to avoid omissions. Literature screening and data extraction were performed independently by 2 researchers. RCTs carry out the risk of bias analysis evaluation from seven aspects through the Cochrane Collaboration's risk of bias tool. Fixed or random effect model will be performed to analyze the outcomes. When higher heterogeneity occurs (I2 > 50%), the sensitivity or subgroup analysis will also be conducted to find potential factors. And the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is used for assessing the quality of evidence. Results: The study will evaluate the effect of CST on gait of children with CP from multiple outcomes, including walking speed, endurance, stride length, and safety. Conclusion: Based on evidence-based medicine, the conclusion of this study can demonstrate the effectiveness and safety of CST in gait correction for children with CP. PROSPERO registration number: PROSPERO CRD 42019134094.
The intuitive number sense contributes to symbolic equation error detection abilities.

Research over the past 20 years has suggested that our intuitive sense of number-the Approximate Number System (ANS)-is associated with individual differences in symbolic math performance. The mechanism supporting this relationship, however, remains unknown. Here, we test whether the ANS contributes to how well adult observers judge the direction and magnitude of symbolic math equation errors. We developed a novel task in which participants view symbolic equations with incorrect answers (e.g., 47 + 21 = 102), and indicate whether the provided answer was too high or too low. By varying the ratio between the correct and the provided answers, we measured individual differences in how well participants detect the magnitude and direction of symbolic equation errors. We find that individual differences in equation error detection were uniquely predicted by ANS acuity-that is, the precision of each participant's intuitive number representations-even when controlling for differences in surface area perception, working memory span, and operational span. This suggests that the ANS can act as a unique source of error detection variability for formal mathematics, providing a plausible mechanism for how our universally shared number sense might link with human-specific symbolic math abilities. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Succinate dehydrogenase deficiency in a chromaffin cell model retains metabolic fitness through the maintenance of mitochondrial NADH oxidoreductase function

Mutations in succinate dehydrogenase (SDH) lead to the development of tumors in a restricted subset of cell types, including chromaffin cells and paraganglia. The molecular basis for this specificity is currently unknown. We show that loss of SDH activity in a chromaffin cell model does not perturb complex I function, retaining the ability to oxidize NADH within the electron transport chain. This activity supports continued oxidation of substrates within the tricarboxylic acid (TCA) cycle. However, due to the block in the TCA cycle at SDH, the high glutamine oxidation activity is only maintained through an efflux of succinate. We also show that although the mitochondria of SDH‐deficient cells are less active per se, their higher mass per cell results in an overall respiratory rate that is comparable with wild‐type cells. Finally, we observed that when their mitochondria are uncoupled, SDH‐deficient cells are unable to preserve their viability, suggesting that the mitochondrial metabolic network is unable to compensate when exposed to additional stress. We therefore show that in contrast to models of SDH deficiency based on epithelial cells, a chromaffin cell model retains aspects of metabolic “health,” which could form the basis of cell specificity of this rare tumor type.
Midkine Inhibits Cholesterol Efflux by Decreasing ATP-Binding Membrane Cassette Transport Protein A1 via Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling in Macrophages.

BACKGROUND Midkine (MK), a heparin-binding protein, participates in multiple cellular processes, such as immunity, cellular growth and apoptosis. Overwhelming evidence indicates that MK plays an important role in various pathological processes, including chronic inflammation, autoimmunity, cancer, and infection. Recent studies demonstrated that MK may be involved in the development of atherosclerosis, yet the mechanism has not been fully explored. Therefore, this study aims to investigate the effect and mechanism of MK on macrophage cholesterol efflux.Methods and Results:Using Oil Red O staining, NBD-cholesterol fluorescence labeling and enzymatic methods, it observed that MK markedly promoted macrophage lipid accumulation. Liquid scintillation counting (LSC) showed that MK decreased cholesterol efflux. Moreover, cell immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) showed that MK downregulated ATP-binding membrane cassette transport protein A1 (ABCA1) expression. Functional promotion of ABCA1 expression attenuated the inhibitory effects of MK on cholesterol efflux, which reduced lipid accumulation. Additionally, intervention of adenosine monophosphate activated protein (AMPK)-mammalian target of rapamycin (mTOR) signaling molecule by the AMPK activator, AICAR, increased p-AMPK and ABCA1 expression, decreased p-mTOR expression and promoted cholesterol efflux, resulting in an obvious reduction in intracellular lipid content. CONCLUSIONS These data suggest that MK reduces the expression of ABCA1, inhibits the efflux of cholesterol and promotes the accumulation of lipids in RAW264.7 macrophages, and AMPK-mTOR signaling is involved in MK-mediated regulation of cholesterol metabolism in RAW264.7 macrophages.