Miracle-dz/UniFAR-FTUs huggingface dataset:
Multifaceted tannin crosslinked bioinspired dECM decorated nanofibers modulating cell–scaffold biointerface for tympanic membrane perforation bioengineering

Tympanic membrane (TM) perforation leads to persistent otitis media, conductive deafness, and affects life quality. Ointment medication may not be sufficient to treat TM perforation (TMP) due to the lack of an underlying tissue matrix and thus requiring a scaffold-based application. The engineering of scaffold biointerface close to the matrix via tissue-specific decellularized extracellular matrix (dECM) is crucial in instructing cell behaviour and regulating cell-material interaction in the bioengineering domain. Herein, polycaprolactone (PCL) and TM-dECM (from Sprague–Dawley rats) were combined in a different ratio in nanofibrous form using an electrospinning process and crosslinked via tannic acid. The histological and biochemical assays demonstrated that chemical and enzymatic decellularization steps removed cellular/immunogenic contents while retaining collagen and glycosaminoglycan. The morphological, physicochemical, thermomechanical, contact angle, and surface chemical studies demonstrated that the tannin crosslinked PCL/dECM nanofibers fine-tune biophysical and biochemical properties. The multifaceted crosslinked nanofibers hold the tunable distribution of dECM moieties, assembled into a spool-shaped membrane, and could easily insert into perforated sites. The dECM decorated fibers provide a preferable biomimetic matrix for L929 fibroblast adhesion, proliferation, matrix adsorption, and f-actin saturation, which could be crucial for bioengineering. Overall, dECM patterning, surface hydrophilicity, interconnected microporosities, and multifaceted nanofibrous biosystem modulate cell–scaffold performance and could open opportunities to reconstruct TMP in a biomimetic fashion.
Down-regulation of the bacterial protein biosynthesis machinery in response to weeks, years, and decades of soil warming

How soil microorganisms respond to global warming is key to infer future soil-climate feedbacks, yet poorly understood. Here, we applied metatranscriptomics to investigate microbial physiological responses to medium-term (8 years) and long-term (>50 years) subarctic grassland soil warming of +6°C. Besides indications for a community-wide up-regulation of centralmetabolic pathways and cell replication, we observed a down-regulation of the bacterial protein biosynthesis machinery in the warmed soils, coinciding with a lower microbial biomass, RNA, and soil substrate content. We conclude that permanently accelerated reaction rates at higher temperatures and reduced substrate concentrations result in cellular reduction of ribosomes, the macromolecular complexes carrying out protein biosynthesis. Later efforts to test this, including a short-term warming experiment (6 weeks, +6°C), further supported our conclusion. Down-regulating the protein biosynthesis machinery liberates energy and matter, allowing soil bacteria to maintain high metabolic activities and cell division rates even after decades of warming.
Serine hydroxymethyltransferase 2 (SHMT2) potentiates the aggressive process of oral squamous cell carcinoma by binding to interleukin enhancer-binding factor 2 (ILF2)

ABSTRACT Oral squamous cell carcinoma (OSCC) is a frequent threatening head and neck malignancy. Serine hydroxymethyltransferase 2 (SHMT2) was identified to be upregulated in OSCC and its high expression was associated with poor patient prognosis. This paper set out to assess the influence of SHMT2 on OSCC progression and the potential mechanisms related to interleukin enhancer-binding factor 2 (ILF2). First of all, reverse transcription-quantitative PCR (RT-qPCR) and western blot examined the expression of SHMT2 and ILF2 in OSCC cells. Cell Counting Kit-8 (CCK-8) and colony formation assays appraised cell proliferation. Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) staining was to estimate the apoptotic rate of cells. Further, wound healing and transwell assays verified the migration and invasion of cells. Western blot was adopted to detect the expression of factors related to apoptosis, migration, and epithelial–mesenchymal transition (EMT). The possible interaction of SHMT2 and ILF2 was predicted by a Molecular INTeraction (MINT) and BioGRID databases and determined using co-immunoprecipitation (IP) assay. Subsequently, ILF2 was overexpressed to investigate whether SHMT2 regulated OSCC progression by binding to ILF2. Results implied that SHMT2 possessed increased expression in OSCC cells, and OSCC cell viability, migration, invasion, EMT were inhibited and apoptosis was potentiated after its silencing. ILF2 bound to SHMT2 and ILF2 expression was downregulated after SHMT2 silencing in OSCC cells. Importantly, ILF2 overexpression abolished the suppressive role of SHMT2 interference in the progression of OSCC. Collectively, SHMT2 could promote the progression of OSCC by binding to ILF2. Graphical abstract
Deciphering the role of specialist and generalist plant-microbial interactions as drivers of plant-soil feedback.

Feedback between plants and soil microbial communities can be a powerful driver of vegetation dynamics. Plants elicit changes in the soil microbiome that either promote or suppress conspecifics at the same location, thereby regulating population density-dependence and species coexistence. Such effects are often attributed to the accumulation of host-specific antagonistic or beneficial microbiota in the rhizosphere. However, the identity and host-specificity of the microbial taxa involved are rarely empirically assessed. Here we review the evidence for host-specificity in plant-associated microbes and propose that specific plant-soil feedbacks can also be driven by generalists. We outline the potential mechanisms by which generalist microbial pathogens, mutualists and decomposers can generate differential effects on plant hosts and synthesise existing evidence to predict these effects as a function of plant investments into defence, microbial mutualists and dispersal. Importantly, the capacity of generalist microbiota to drive plant-soil feedbacks depends not only on the traits of individual plants but also on the phylogenetic and functional diversity of plant communities. Identifying factors that promote specialisation or generalism in plant-microbial interactions and thereby modulate the impact of microbiota on plant performance will advance our understanding of the mechanisms underlying plant-soil feedback and the ways it contributes to plant coexistence.
MTA1-mediated RNA m6 A modification regulates autophagy and is required for infection of the rice blast fungus.

In eukaryotes, N6 -methyladenosine (m6 A) is abundant on mRNA, which plays key roles in the regulation of RNA function. However, the roles and regulatory mechanisms of m6 A in phytopathogenic fungi are still largely unknown. Combing with biochemical analysis, MeRIP-seq and RNAseq methods, as well as biological analysis, we showed Magnaporthe oryzae MTA1 gene is an ortholog of human METTL4, which is involved in m6 A modification and plays a critical role in autophagy for fungal infection. The Δmta1 mutant showed reduced virulence due to blockage of appressorial penetration and invasive growth. Moreover, the autophagy process was severely disordered in the mutant. MeRIP-seq identified 659 hypomethylated m6 A peaks covering 595 mRNAs in Δmta1 appressorium, 114 m6 A peaks was negatively related to mRNA abundance, including several ATG gene's transcripts. Typically, the mRNA abundance of MoATG8 was also increased in the single m6 A site mutant ∆atg8/MoATG8A982C , leading to an autophagy disorder. Our findings reveal the functional importance of the m6 A methylation in infection of M. oryzae and provide novel insight into regulatory mechanism of plant pathogenic fungi.
Development of the Bicycle Compatibility Evaluator (BCE) for the city of Cincinnati, OH

ii Acknowledgement. vi List of Tables . ix List of Figures . x 1. Introduction . 11 Background 11 Problem Identification 12 Thesis structure 13 Scope of study 14 Hypothesis 14 Objectives 15 2. Related works and literature review . 16 The impact of urban distribution (land use) in biking and multimodal transportation systems 17 Bicycle infrastructure studies and evaluation 21 Transportation demand forecasting methods 28 Bicycle travel demand forecasting 30 Household travel surveys 31 Cincinnati household travel survey 32 3. Methodology . 34 Preliminary data 34 Mode-based household data selection 41 Mapping GoogleEarth data 43 Finding HTS segments on the full street network 45 Demographic data coding and incorporation 47 Incorporation and recoding of land use data 49 “Predisposition to biking” analysis and mapping 49 Spatial correlation analysis 52 Ordinary least squares 56 Variable selection and filtering 59 Final results 59 Methodology schematics 60 4. Data Preparation . 61 Collected data 61 Bicycle-only data 65 Visible bicycle routes 65 Segments to be evaluated 67 HTS information incorporated into full OKI street network 69
New artificial intelligence index based on Scheimpflug corneal tomography to distinguish subclinical keratoconus from healthy corneas

The index derived from Scheimpflug tomography demonstrated good accuracy to discriminate keratoconus and normal cornea and aided in early detection of ectasia in healthy corneas. Purpose: To assess the efficiency of an index derived from multiple logistic regression analysis (MLRA) to measure differences in corneal tomography findings between subclinical keratoconus (KC) in 1 eye, corneal ectasia, and healthy corneas. Setting: 2 private Brazilian ophthalmological centers. Design: Multicenter case–control study. Methods: This study included 187 eyes with very asymmetric ectasia and with normal corneal topography and tomography (VAE-NTT) in the VAE-NTT group, 2296 eyes with healthy corneas in the control group (CG), and 410 eyes with ectasia in the ectasia group. An index, termed as Boosted Ectasia Susceptibility Tomography Index (BESTi), was derived using MLRA to identify a cutoff point to distinguish patients in the 3 groups. The groups were divided into 2 subgroups with an equal number of patients: validation set and external validation (EV) set. Results: 2893 patients with 2893 eyes were included. BESTi had an area under the curve (AUC) of 0.91 with 86.02% sensitivity (Se) and 83.97% specificity (Sp) between CG and the VAE-NTT group in the EV set, which was significantly greater than those of the Belin-Ambrósio Deviation Index (BAD-D) (AUC: 0.81; Se: 66.67%; Sp: 82.67%; P < .0001) and Pentacam random forest index (PRFI) (AUC: 0.87; Se: 78.49%; Sp: 79.88%; P = .021). Conclusions: BESTi facilitated early detection of ectasia in subclinical KC and demonstrated higher Se and Sp than PRFI and BAD-D for detecting subclinical KC.
Inkjet Printing and 3D Printing Strategies for Biosensing, Analytical, and Diagnostic Applications

Inkjet printing and 3D inkjet printing have found many applications in the fabrication of a great variety of devices, which have been developed with the aim to improve and simplify the design, fabrication, and performance of sensors and analytical platforms. Here, developments of these printing technologies reported during the last 10 years are reviewed and their versatile applicability for the fabrication of improved sensing platforms and analytical and diagnostic sensor systems is demonstrated. Illustrative examples are reviewed in the context of particular advantages provided by inkjet printing technologies. Next to aspects of device printing and fabrication strategies, the utilization of inkjet dispensing, which can be implemented into common analytical tools utilizing customized inkjet printing equipment as well as state‐of‐the‐art consumer inkjet printing devices, is highlighted. This review aims to providing a comprehensive overview of examples integrating inkjet and 3D inkjet printing technologies into device layout fabrication, dosing, and analytical applications to demonstrate the versatile applicability of these technologies, and furthermore, to inspire the utilization of inkjet printing for future developments.
Efficient silencing of hepatitis B virus S gene through CRISPR‐mediated base editing

Hepatitis B virus (HBV) infection is a major risk factor of liver cirrhosis and hepatocellular carcinoma. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) has been used to precisely edit the HBV genome and eliminate HBV through non‐homologous end‐joining repair of double‐stranded break (DSB). However, the CRISPR/Cas9‐mediated DSB triggers instability of host genome and exhibits low efficiency to edit genome, limiting its application. CRISPR cytidine base editors (CBEs) could silence genes by generating a premature stop codon. Here we developed a CRISPR base editor approach to precisely edit single nucleotide within the HBV genome to impair HBV gene expression. Specifically, a single‐guide RNA (sgRNA) was designed to edit the 30th codon of HBV S gene, which encodes HBV surface antigen (HBsAg), from CAG (glutamine) to stop codon TAG. We next used human hepatoma PLC/PRF/5 cells carrying the HBV genome to establish a cell line that expresses a CBE (PLC/PRF/5‐CBE). Lentivirus was used to introduce sgRNA into PLC/PRF/5‐CBE cells. Phenotypically, 71% of PLC/PRF/5‐CBE cells developed a premature stop codon within the S gene. Levels of HBs messenger RNA were significantly decreased. A 92% reduction of HBsAg secretion was observed in PLC/PRF/5‐CBE cells. The intracellular HBsAg was also reduced by 84% after treatment of gRNA_S. Furthermore, no off‐target effect was detected in predicted off‐target loci within the HBV genome. Sequencing confirmed that 95%, 93%, 93%, 9%, and 72% S gene sequences of HBV genotypes B, C, F, G, and H had the binding site of sgRNA. Conclusion: Our findings indicate that CRISPR‐mediated base editing is an efficient approach to silence the HBV S gene, suggesting its therapeutic potential to eliminate HBV.
Targeted Delivery of Endosomal Escape Peptides to Enhance Immunotoxin Potency and Anti-cancer Efficacy

This work describes use of anti-carcinoembryonic antigen antibodies (10H6, T84.66) for targeted delivery of an endosomal escape peptide (H6CM18) and gelonin, a type I ribosome inactivating protein. The viability of colorectal cancer cells (LS174T, LoVo) was assessed following treatment with gelonin or gelonin immunotoxins, with or without co-treatment with T84.66-H6CM18. Fluorescent microscopy was used to visualize the escape of immunoconjugates from endosomes of treated cells, and efficacy and toxicity were assessed invivo in xenograft tumor-bearing mice following single- and multiple-dose regimens. Application of 25 pM T84.66-H6CM18 combined with T84.66-gelonin increased gelonin potency by ~ 1,000-fold and by ~ 6,000-fold in LS174T and LoVo cells. Intravenous 10H6-gelonin at 1.0 mg/kg was well tolerated by LS174T tumor-bearing mice, while 10 and 25 mg/kg doses led to signs of toxicity. Single-dose administration of PBS, gelonin conjugated to T84.66 or 10H6, T84.66-H6CM18, or gelonin immunotoxins co-administered with T84.66-H6CM18 were evaluated. The combinations of T84.66-gelonin + 1.0 mg/kg T84.66-H6CM18 and 10H6-gelonin + 0.1 mg/kg T84.66-H6CM18 led to significant delays in LS174T growth. Use of a multiple-dose regimen allowed further anti-tumor effects, significantly extending median survival time by 33% and by 69%, for mice receiving 1 mg/kg 10H6-gelonin + 0.1 mg/kg T84.66-H6CM18 (p = 0.0072) and 1 mg/kg 10H6-gelonin + 1 mg/kg T84.66-H6CM18 (p = 0.0017). Combined administration of gelonin immunoconjugates with antibody-targeted endosomal escape peptides increased the delivery of gelonin to the cytoplasm of targeted cells, increased gelonin cell killing invitro by 1,000–6,000 fold, and significantly increased invivo efficacy.
Evaluation of the design, conduct and reporting of randomised controlled trials in the haemodialysis population: a scoping review and interview study

Background Fewer trials are conducted in nephrology than any other specialty, often failing to recruit to target, resulting in unclear evidence affecting translation to clinical practice. This mixed-methods study aims to provide guidance for designing and reporting future randomised controlled trials (RCTs) in the haemodialysis population. Method A scoping review was conducted. Five databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched for RCTs published between 2013 and 2019 involving prevalent adult haemodialysis patients. Reporting of sample size, recruitment, retention and statistical significance of primary outcome were assessed. Face-to-face semistructured interviews were conducted with individuals from a single centre during dialysis sessions. Interviews were analysed thematically. Results Of 786 RCTs identified, 636 (80.9%) were parallel-group, 139 (17.7%) were crossover and 11 (1.4%) were cluster (including one stepped-wedge) design. Sample size justification was reported in 73.1%, 53.8% and 45.5% of parallel-group, crossover and cluster trials, respectively. Target recruitment was achieved by 45.5% of cluster, 53.8% of crossover and 57.7% of parallel-group trials with patient retention at 75.6%, 83.1% and 87.8%, respectively. Primary outcome reached statistical significance in 81.8% of cluster trials, 69.2% of parallel-group and 38.5% of crossover trials. Themes identified from individual interviews: perceptions of the convenience of trial participation; group allocation; perceptions of the benefits and adverse effects of taking part in clinical trials. Conclusion The recruitment and reporting of RCTs involving people on haemodialysis could be improved. Involvement of all stakeholders and especially participants in the trial design process may address issues around participant burden and ultimately improve the evidence base for clinical practice.
Backstepping Technology-Based Adaptive Boundary ILC for an Input–Output-Constrained Flexible Beam

This article focuses on vibration suppression of an Euler–Bernoulli beam which is subject to external disturbance. By integrating backstepping technique, an adaptive boundary iterative learning control (ABILC) is put forward to suppressing vibration. The adaptive law is proposed for handing the parameter uncertainty and the iterative learning term is designed to deal with periodic disturbance. An auxiliary system is utilized to compensate the effect of input nonlinearity. In addition, a barrier Lyapunov function is adopted to deal with asymmetric output constraint. With the proposed control strategy, the stability of the closed-loop system is proven based on rigorous Lyapunov analysis. In the end, the effectiveness of the proposed control is illustrated through numerical simulation results.
Frontline nurses' caring experiences in COVID‐19 units: A qualitative study

Abstract Aim Exploring nurses' caring and communication experiences in COVID‐19 units. Background Frontline nurses play a critical role in providing 24‐h bedside nursing care to COVID‐19 patients. An in‐depth understanding of frontline nurses' lived experiences is necessary to establish appropriate nursing strategies during crises, such as the COVID‐19 pandemic. Methods Qualitative descriptive design with content analysis. Results Fifteen nurses were interviewed, and three themes were identified: central role of therapeutic communication, compassion that deepens naturally and expansion of professionalism in nursing. Conclusion The nurses proactively provided care for COVID‐19 patients, and they acknowledged and accepted their roles in protecting the lives and ensuring the health of their patients daily. The nurses' experiences in COVID‐19 units served as an opportunity for ruminating and rediscovering the meaning of nursing. Implications for Nursing Management Hospital policymakers and nurse managers should strive to resolve the communication‐related challenges faced by nurses. Standardizing and implementing effective communication strategies should be considered in nursing management.
Clustering high‐dimensional data via feature selection

High‐dimensional clustering analysis is a challenging problem in statistics and machine learning, with broad applications such as the analysis of microarray data and RNA‐seq data. In this paper, we propose a new clustering procedure called spectral clustering with feature selection (SC‐FS), where we first obtain an initial estimate of labels via spectral clustering, then select a small fraction of features with the largest R‐squared with these labels, that is, the proportion of variation explained by group labels, and conduct clustering again using selected features. Under mild conditions, we prove that the proposed method identifies all informative features with high probability and achieves the minimax optimal clustering error rate for the sparse Gaussian mixture model. Applications of SC‐FS to four real‐world datasets demonstrate its usefulness in clustering high‐dimensional data.
Development and validation of the Iris Glare, Appearance, and Photophobia questionnaire for patients with iris defects

Iris GAP is a patient-reported outcome measure validated to assess the quality of life in patients with iris defects. Scores correspond to severity of defect and are responsive to therapeutic interventions. Purpose: To validate the Iris Glare, Appearance, and Photophobia (Iris GAP) questionnaire, a new symptom-based and appearance-based quality-of-life measure for patients with iris defects. Setting: Single tertiary glaucoma clinic in Toronto, Ontario, Canada. Design: Prospective cohort study. Methods: Patients with varying degrees of iris defects were enrolled. Patients completed the Iris GAP questionnaire and the glare and driving subscales of the Refractive Status and Vision Profile (RSVP) questionnaire. Test–retest reliability, defined by Cronbach α and intraclass correlation coefficients (ICCs), was evaluated with repeat testing 2 weeks later. Results: The study included 73 patients with iris defects, 68 controls with no iris defects, 77 patients with peripheral iridotomies (PIs) or transillumination defects (TIDs), and 22 patientswith surgically repaired irides (n = 22). Iris GAP scores ranged from 0 to 32 with a 97% completion rate. Iris GAP had high test–retest reliability (Cronbach α = 0.866, ICC = 0.953, P < .0005). Iris GAP scores were reliably distinguishable between patients with iris defects, repaired iris defects, and PIs and TIDs and controls (1-way analysis of variance, P < .0005). In pairwise comparisons, the major defect group had statistically significant higher scores than any of the other groups (P < .005 for each). The control and repaired groups had the lowest scores, whereas the PI/TID group had intermediate scores. 9 patients underwent iris repair between tests and had a mean difference of 8.2 ± 6.2 points between their preoperative and postoperative scores (P = .004). Iris GAP scores positively correlated with RSVP scores (R2 = 0.73). Conclusions: Iris GAP can reliably evaluate symptomatology and patient-reported appearance in patients with iris defects.