Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Fat and Fatty Acids on the Formation of Autolysosomes in the Livers from Yellow Catfish Pelteobagrus Fulvidraco

The autophagy-lysosome pathway, which involves many crucial genes and proteins, plays crucial roles in the maintenance of intracellular homeostasis by the degradation of damaged components. At present, some of these genes and proteins have been identified but their specific functions are largely unknown. This study was performed to clone and characterize the full-length cDNA sequences of nine key autolysosome-related genes (vps11, vps16, vps18, vps33b, vps41, lamp1, mcoln1, ctsd1 and tfeb) from yellow catfish Pelteobagrus fulvidraco. The expression of these genes and the transcriptional responses to a high-fat diet and fatty acids (FAs) (palmitic acid (PA) and oleic acid (OA)) were investigated. The mRNAs of these genes could be detected in heart, liver, muscle, spleen, brain, mesenteric adipose tissue, intestine, kidney and ovary, but varied with the tissues. In the liver, the mRNA levels of the nine autolysosome-related genes were lower in fish fed a high-fat diet than those fed the control, indicating that a high-fat diet inhibited formation of autolysosomes. Palmitic acid (a saturated FA) significantly inhibited the formation of autolysosomes at 12 h, 24 h and 48 h incubation. In contrast, oleic acid (an unsaturated FA) significantly induced the formation of autolysosomes at 12 h, but inhibited them at 24 h. At 48 h, the effects of OA incubation on autolysosomes were OA concentration-dependent in primary hepatocytes of P. fulvidraco. The results of flow cytometry and laser confocal observations confirmed these results. PA and OA incubation also increased intracellular non-esterified fatty acid (NEFA) concentration at 12 h, 24 h and 48 h, and influenced mRNA levels of fatty acid binding protein (fabp) and fatty acid transport protein 4 (fatp4) which facilitate FA transport in primary hepatocytes of P. fulvidraco. The present study demonstrated the molecular characterization of the nine autolysosome-related genes and their transcriptional responses to fat and FAs in fish, which provides the basis for further exploring their regulatory mechanism in vertebrates.
Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures

ABSTRACT The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response to assaults. In chronic airway diseases, defective repair leads to tissue remodeling. Delineating key drivers of differentiation dynamics can help understand how normal or pathological regeneration occurs. Using single-cell transcriptomics and lineage inference, we have unraveled trajectories from basal to luminal cells, providing novel markers for specific populations. We report that: (1) a precursor subgroup of multiciliated cells, which we have entitled deuterosomal cells, is defined by specific markers, such as DEUP1, FOXN4, YPEL1, HES6 and CDC20B; (2) goblet cells can be precursors of multiciliated cells, thus explaining the presence of hybrid cells that co-express markers of goblet and multiciliated cells; and (3) a repertoire of molecules involved in the regeneration process, such as keratins or components of the Notch, Wnt or BMP/TGFβ pathways, can be identified. Confirmation of our results on fresh human and pig airway samples, and on mouse tracheal cells, extend and confirm our conclusions regarding the molecular and cellular choreography at work during mucociliary epithelial differentiation. Highlighted Article: Single-cell RNAseq data in fresh human airway epithelial tissues and air liquid cultures identifies novel cell populations and offers new insights into the molecular mechanisms occurring during mucociliary epithelium regeneration.
Evaluation of student use of videos to support learning in a simulation laboratory course: A perception and analytics approach.

AIM This paper evaluates the use of online video learning materials used for a simulation laboratory course for 2 consecutive cohorts of students using an evaluation and analytics approach. METHODS 100 online video clips were created to support students' learning before, during and after the scheduled simulation laboratory teaching sessions in a fixed prosthodontics course. Videoed online presentations included screen-captured PowerPoint presentations, simulation laboratory psychomotor and clinical skills demonstrations, individual student case consultations and whole-class worksheet debriefings. Data files and access data were analyzed for 2 consecutive cohorts of 4th year students. An evaluation questionnaire was administered on the 2015 cohort. RESULTS Feedback on learning resources were strongly positive. 100% of students reported that the videos helped in their learning, preparation for simulation laboratory classes, to refresh their memory prior to clinical care, prepare for the clinical competency test and prepare for examinations. In total, 4689 videos were accessed, 35% by class 2015 and 65% by 2016. 73% of these were watched during the simulation laboratory course, 13% were watched 2-3 weeks before examinations and 14% during the remainder of the year. CONCLUSION Videos were reported to support student learning and were valued for a range of learning needs. However, significant differences between student consumption and strategies need to be designed to engage low consumers.
γ-secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma.

B cell maturation antigen (BCMA) is a validated target for chimeric antigen receptor (CAR) T cell therapy in multiple myeloma (MM). Despite promising objective response rates, most patients relapse and low levels of BCMA on a subset of tumor cells has been suggested as a probable escape mechanism. BCMA is actively cleaved from the tumor cell surface by the ubiquitous multisubunit γ-secretase complex, which reduces ligand density on tumor cells for CAR-T cell recognition and releases a soluble BCMA (sBCMA) fragment capable of inhibiting CAR-T cell function. Sufficient sBCMA can accumulate in the bone marrow of MM patients to inhibit CAR-T cell recognition of tumor cells, and potentially limit efficacy of BCMA directed adoptive T cell therapy. We investigated whether blocking BCMA cleavage by small molecule γ-secretase inhibitors (GSIs) could augment BCMA-targeted CAR-T cell therapy. We found that exposure of myeloma cell lines and patient tumor samples to GSIs markedly increased surface BCMA levels in a dose-dependent fashion, concurrently decreased sBCMA concentrations, and improved tumor recognition by CAR-T cells in vitro GSI treatment of MM tumor bearing NOD/SCID/γc-/- mice increased BCMA expression on tumor cells, decreased sBCMA in peripheral blood, and improved antitumor efficacy of BCMA-targeted CAR-T cell therapy. Importantly, short term GSI administration to MM patients markedly increases the percentage of BCMA+tumor cells, and the levels of BCMA surface expression in vivo Based on these data, an FDA-approved clinical trial (NCT03502577) has been initiated, combining GSI with concurrent BCMA CAR-T cell therapy.
Estimation of Danger Signs in Regional Complaint Data

Government 2.0 activities have become very attractive and popular. Using the platforms to support the activities, anyone can anytime report issues in a city on the Web and share the reports with other people. Since a variety of reports are posted, officials in the city management section have to give priorities to the reports. However, it is not easy task for the officials to judge the importance of the reports because importance judgments vary depending on the officials, and consequently the agreement rate becomes low. To remedy the low agreement rate problem of human judgment, it is necessary to create an intelligent agent which supports finding reports with high priorities. Hirokawa et al. employed the Support Vector Machine (SVM) with a word Feature Selection method (SVM+FS) to detect signs of danger from posted reports because the signs of danger is one of high priority issues to be dealt with. However they did not compare the SVM+FS method with other conventional machine learning methods and it is not clear if the SVM+FS method has better performance than the other methods. This paper explores methods for detecting the signs of danger through comprehensive experiments to develop an intelligent agent which supports officials in the city management sections. We explores conventional machine learning methods: SVM, Random Forest, Naïve Bayse using conventional word vectors, an LDA-based document vector, and word embedding by Word2Vec and compared the best method with SVM+FS. Experimental results illustrate the superiority of SVM+FS and invoke the importance of using multiple data sets when evaluating the methods of detecting signs of danger.
A carbohydrate-binding family 48 module enables feruloyl esterase action on polymeric arabinoxylan

Feruloyl esterases (EC 3.1.1.73), belonging to carbohydrate esterase family 1 (CE1), hydrolyze ester bonds between ferulic acid (FA) and arabinose moieties in arabinoxylans. Recently, some CE1 enzymes identified in metagenomics studies have been predicted to contain a family 48 carbohydrate-binding module (CBM48), a CBM family associated with starch binding. Two of these CE1s, wastewater treatment sludge (wts) Fae1A and wtsFae1B isolated from wastewater treatment surplus sludge, have a cognate CBM48 domain and are feruloyl esterases, and wtsFae1A binds arabinoxylan. Here, we show that wtsFae1B also binds to arabinoxylan and that neither binds starch. Surface plasmon resonance analysis revealed that wtsFae1B's Kd for xylohexaose is 14.8 μm and that it does not bind to starch mimics, β-cyclodextrin, or maltohexaose. Interestingly, in the absence of CBM48 domains, the CE1 regions from wtsFae1A and wtsFae1B did not bind arabinoxylan and were also unable to catalyze FA release from arabinoxylan. Pretreatment with a β-d-1,4-xylanase did enable CE1 domain-mediated FA release from arabinoxylan in the absence of CBM48, indicating that CBM48 is essential for the CE1 activity on the polysaccharide. Crystal structures of wtsFae1A (at 1.63 Å resolution) and wtsFae1B (1.98 Å) revealed that both are folded proteins comprising structurally-conserved hydrogen bonds that lock the CBM48 position relative to that of the CE1 domain. wtsFae1A docking indicated that both enzymes accommodate the arabinoxylan backbone in a cleft at the CE1–CBM48 domain interface. Binding at this cleft appears to enable CE1 activities on polymeric arabinoxylan, illustrating an unexpected and crucial role of CBM48 domains for accommodating arabinoxylan.
Comprehensive Transcriptomic Profiling Identifies Breast Cancer Patients Who May Be Spared Adjuvant Systemic Therapy

Purpose: There is currently no molecular signature in clinical use for adjuvant endocrine therapy omission in breast cancer. Given the unique trial design of SweBCG91-RT, where adjuvant endocrine and chemotherapy were largely unadministered, we sought to evaluate the potential of transcriptomic profiling for identifying patients who may be spared adjuvant endocrine therapy. Experimental Design: We performed a whole-transcriptome analysis of SweBCG91-RT, a randomized phase III trial of ± radiotherapy after breast-conserving surgery for node-negative stage I–IIA breast cancer. Ninety-two percent of patients were untreated by both adjuvant endocrine therapy and chemotherapy. We calculated 15 transcriptomic signatures from the literature and combined them into an average genomic risk, which was further used to derive a novel 141-gene signature (MET141). All signatures were then independently examined in SweBCG91-RT and in the publicly available METABRIC cohort. Results: In SweBCG91-RT, 454 patients were node-negative, postmenopausal, and systemically untreated with ER-positive, HER2-negative cancers, which constitutes a low-risk subgroup and potential candidates for therapy omission. Most transcriptomic signatures were highly prognostic for distant metastasis, but considerable discordance was observed on the individual patient level. Within the MET141 low-risk subgroup (lowest 25th percentile of scores), 95% of patients were free of metastasis at 15 years, even in the absence of adjuvant endocrine therapy. In a clinically low-risk subgroup of the METABRIC cohort not treated with systemic therapy, no breast cancer death occurred among the MET141 low-risk patients. Conclusions: Transcriptomic profiling identifies patients with an excellent outcome without any systemic adjuvant therapy in clinically low-risk patients of the SweBCG91-RT and METABRIC cohorts.
Effect of Gypsum on Hydration and Hardening Properties of Alite Modified Calcium Sulfoaluminate Cement

Calcium sulphoaluminate cement (CSA) has the characteristics of quick hardening, high early strength and high impermeability, however its strength growth persistence in the middle and late stages (after the age of 3 days) is poor. In order to improve this disadvantage, the pilot production of alite (C3S) modified CSA (AMCSA) clinker was carried out by liquid phase manipulation and barium ion doping technology. The effects of different dosages of gypsum on the hydration and hardening properties of AMCSA, such as setting time, hydration rate, compressive strength and hydration products, were studied. The results show that the mineral content of ye’elimite, C2S, C3S and iron phase in the calcined AMCSA clinker are 48.5 wt. %, 32.6 wt. %, 11.7 wt. % and 7.2 wt. % respectively, which are close to the designed mineral composition. The stable coexistence of ye’elimite and C3S in the same clinker system is realized. The initial and final setting time of AMCSA are retarded with the increasing gypsum dosage. When the gypsum dosage is 15 wt. % under the experimental conditions in this study, the AMCSA mortar reaches the highest compressive strength at every age. The strength of AMCSA mortar at 28 days is still significantly improved compared with that at 3 days, which indicates that the shortcoming of the low strength growth persistence of CSA in the middle and late stages is improved.
The Bactericidal Activity of Temporin Analogues Against Methicillin Resistant Staphylococcus aureus

Staphylococcus aureus is a major infectious agent responsible for a plethora of superficial skin infections and systemic diseases, including endocarditis and septic arthritis. Recent epidemiological data revealed the emergence of resistance to commonly used antibiotics, including increased numbers of both hospital- and community-acquired methicillin-resistant S. aureus (MRSA). Due to their potent antimicrobial functions, low potential to develop resistance, and immunogenicity, antimicrobial peptides (AMPs) are a promising alternative treatment for multidrug-resistant strains. Here, we examined the activity of a lysine-rich derivative of amphibian temporin-1CEb (DK5) conjugated to peptides that exert pro-proliferative and/or cytoprotective activity. Analysis of a library of synthetic peptides to identify those with antibacterial potential revealed that the most potent agent against multidrug-resistant S. aureus was a conjugate of a temporin analogue with the synthetic Leu-enkephalin analogue dalargin (DAL). DAL-PEG-DK5 exerted direct bactericidal effects via bacterial membrane disruption, leading to eradication of both planktonic and biofilm-associated staphylococci. Finally, we showed that accumulation of the peptide in the cytoplasm of human keratinocytes led to a marked clearance of intracellular MRSA, resulting in cytoprotection against invading bacteria. Collectively, the data showed that DAL-PEG-DK5 might be a potent antimicrobial agent for treatment of staphylococcal skin infections.
Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.
Preoperative Anemia and Postoperative Mortality in Patients with Aortic Stenosis Treated with Transcatheter Aortic Valve Implantation (TAVI): A Systematic Review and Meta-Analysis

Background Patients with severe aortic stenosis who have comorbidities that prevent general anesthesia and open cardiothoracic surgery are candidates for transcatheter aortic valve implantation (TAVI). However, TAVI can result in patient mortality following the procedure. This systematic review of the literature and meta-analysis aimed to determine the relationship between preoperative anemia and postoperative mortality in patients following TAVI. Material/Methods PubMed, EMBASE, the Cochrane Library, and the Web of Science were systematically searched from their inception to February 2019 for relevant published studies that included patients with bicuspid aortic valve stenosis and tricuspid aortic valve stenosis who underwent TAVI and who had preoperative data on hemoglobin levels. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated using a random-effects generic inverse variance method. Results Six published studies that involved 6,406 patients with aortic stenosis were included in the meta-analysis. There was no significant difference observed for the final pooled result for patients with and without anemia for the short-term 30-day postoperative mortality (OR, 1.34; 95% CI, 0.77–2.35). However, long-term mortality rates were significantly worse in patients with preoperative anemia compared with those without anemia (OR, 1.77; 95% CI, 1.34–2.35). Conclusions Systematic review of the literature and meta-analysis showed that pre-procedural anemia reduced long-term mortality following TAVI. This finding supports the need to correct preoperative anemia in patients with aortic stenosis to improve patient outcome following TAVI.
A Critical Look Into Stapedotomy Learning Curve: Influence of Patient Characteristics and Different Criteria Defining Success

Purpose: To evaluate stapedotomy learning curve with cumulative summation methodology using different success criteria (ie, air-bone gap [ABG] ≤10 dB, ABG ≤15 dB, restoration of interaural symmetry, or hearing threshold gain >20 dB), and to assess patient characteristics influencing or modifying the learning curve. Methods: Retrospective chart review of primary and revision stapedotomy cases performed by surgeon 1 (S1, n = 78) and surgeon 2 (S2, n = 85). Results: Using the classic criterion for a successful stapedotomy (ABG ≤10 dB), patients with preoperative ABG >34 dB were associated with unsuccessful procedures (S1 P = .02; S2 P = .07). Revision surgery was associated with unsuccessful outcomes (S1 P = .005; S2 P = .0012). Cumulative summation plots using different criteria did not show a linear trend of association between stapedotomy success and number of operations, but preoperative characteristics of the patients who underwent stapedotomy significantly influenced the plots. Cumulative summation plots showed an initial increasing tendency with improving results, but when ear surgeons got more skilled, they operated on more complex cases (ie, patients with higher preoperative ABG or revision stapedotomy) and they could not meet the success criteria. Conclusions: Cumulative summation plots do not seem useful to evaluate the stapedotomy learning curve, as they do not correctly deal with heterogeneous case series. The increasing complexity of the stapedotomy patients during the surgeons’ career impacts on the outcome of stapedotomy and confounds the evaluation of the growing skills of the surgeon. Stapedotomy audiological success rates are strongly influenced by the success criteria used.
Does the physical and mental health of veterans differ by military branch?

Abstract The purpose of this study was to examine the relationship between health behaviors and their levels of positive and negative affect and determine the overall level of physical health and mental health among members of the armed forces. Overall, the results showed that veterans in the Army, Navy and Marines are more often than members who are in the Air Force to be deployed. Members in the Army, Navy and Marines also experience higher levels of reported cases of PTSD, higher levels of negative affect (i.e. anxiety), a lower health composite score and report poorer perception of their own health. This study also showed that veterans of the Air Force had a stronger emphasis on their physical health which resulted in higher levels of positive affect (excited about life). Limitations and future directions of this research are discussed.
A review: Issues and Challenges in Big Data from Analytic and Storage perspectives

There is an up-and-coming topic in the field of computer science and technology that is getting a lot of publications these days and that is Big Data. The term Big data is referring for a collection of large and complex data sets which is very hard to process by database management tools or data processing applications. The volumes are in the range of Exabyte and above. Most of companies and government agencies are dealing with it in this current speedy moving technology environment. Stand -alone applications as well as today’s newer web-based processes are generating large amount of data. This raise some issues that has to be considered when dealing with big data. Some of the issues are storage, management and processing. This data also creates new challenges which make the framework based developers to come up with solutions to the problems. They introduced different frameworks for the storage, management and processing of big data that are scalable and portable with fault tolerance capabilities. Newer technologies for the analysis of such large amount data that is complex to handle are also introduced. These challenges include Privacy and Security, Scale, and Heterogeneity to mention a few. This paper reviews the Issues and Challenges of Big Data from Data Analytic and Storage Perspectives. We also briefly discussed about the frameworks and databases that can be used to tackle the challenges that is facing Big Data world.