Systematic reanalysis of copy number losses of uncertain clinical significance.

BACKGROUND: Reanalysis of exome/genome data improves diagnostic yield. However, the value of reanalysis of clinical array comparative genomic hybridisation (aCGH) data has never been investigated. Case-by-case reanalysis can be challenging in busy diagnostic laboratories. METHODS AND RESULTS: We harmonised historical postnatal clinical aCGH results from ~16 000 patients tested via our diagnostic laboratory over ~7 years with current clinical guidance. This led to identification of 37 009 copy number losses (CNLs) including 33 857 benign, 2173 of uncertain significance and 979 pathogenic. We found benign CNLs to be significantly less likely to encompass haploinsufficient genes compared with the pathogenic or CNLs of uncertain significance in our database. Based on this observation, we developed a reanalysis pipeline using up-to-date disease association data and haploinsufficiency scores and shortlisted 207 CNLs of uncertain significance encompassing at least one autosomal dominant disease-gene associated with haploinsufficiency or loss-of-function mechanism. Clinical scientist reviews led to reclassification of 15 CNLs of uncertain significance as pathogenic or likely pathogenic. This was ~0.7% of the starting cohort of 2173 CNLs of uncertain significance and 7.2% of 207 shortlisted CNLs. The reclassified CNLs included first cases of CNV-mediated disease for some genes where all previously described cases involved only point variants. Interestingly, some CNLs could not be reclassified because the phenotypes of patients with CNLs seemed distinct from the known clinical features resulting from point variants, thus raising questions about accepted underlying disease mechanisms. CONCLUSIONS: Reanalysis of clinical aCGH data increases diagnostic yield.

Effects of Online Unfolding Case Studies on Clinical Reasoning and Academic Performance of Undergraduate Nursing Students.

ABSTRACT: A single-episode online case study increases cognitive load in contrast to an unfolding online case study, which decreases cognitive load, improves academic performance, and enhances clinical reasoning. However, online utilization of unfolding case studies is limited. A one-group pretest posttest experimental design was employed with 45 nursing students in a pathophysiology course. Data were collected using Lasater's clinical reasoning scale and quiz scores to assess academic performance. The academic performance and clinical reasoning of nursing students were significantly higher with online unfolding case studies (p < .001), providing support for the use of the online unfolding case study method.

Virtual Skills Teaching of Nursing Students during COVID-19: A Problem-Solving Approach.

The COVID-19 pandemic radically affected the whole education system including nursing education. Nursing is a practice-based profession; therefore, it is necessary to transform acquired knowledge into practice. However, in the current situation of the pandemic, the nursing students were unable to learn and practise nursing skills in the skills lab on manikins or simulation. This paper aims to give an overview and practical application of alternative solutions to overcome this situation. Alternatives like virtual skills teaching along with sign-off were sought by using problem-solving approaches to facilitate students' learning and help them to acquire necessary skills timely. Key Words: Virtual skills teaching, Nursing students, Problem-solving approach, COVID-19.

Twelve tips to organise a mock OSCE.

The objective structured clinical examination (OSCE) is central to assessing clinical competence in undergraduate and postgraduate exams for medical and allied healthcare professions. A mock OSCE on the other hand is a simulation of the OSCE and a unique learning experience for the examinee. They benefit in a variety of ways; from enhancing their time management skills to receiving feedback that can improve their clinical skills. Unfortunately, opportunities to participate in simulated OSCEs remain limited. Reasons include difficulty in fulfilling organisational requirements and equipment-related costs. Mock OSCEs can be set up by undergraduate students or junior trainees for peers, without senior supervision or direct guidance. This article will discuss 12 tips regarding the arrangement of mock OSCEs to guide organisers, including accessing resources and establishing the content of the exam.

Oxygen Generation Using Catalytic Nano/Micromotors.

Gaseous oxygen plays a vital role in driving the metabolism of living organisms and has multiple agricultural, medical, and technological applications. Different methods have been discovered to produce oxygen, including plants, oxygen concentrators and catalytic reactions. However, many such approaches are relatively expensive, involve challenges, complexities in post-production processes or generate undesired reaction products. Catalytic oxygen generation using hydrogen peroxide is one of the simplest and cleanest methods to produce oxygen in the required quantities. Chemically powered micro/nanomotors, capable of self-propulsion in liquid media, offer convenient and economic platforms for on-the-fly generation of gaseous oxygen on demand. Micromotors have opened up opportunities for controlled oxygen generation and transport under complex conditions, critical medical diagnostics and therapy. Mobile oxygen micro-carriers help better understand the energy transduction efficiencies of micro/nanoscopic active matter by careful selection of catalytic materials, fuel compositions and concentrations, catalyst surface curvatures and catalytic particle size, which opens avenues for controllable oxygen release on the level of a single catalytic microreactor. This review discusses various micro/nanomotor systems capable of functioning as mobile oxygen generators while highlighting their features, efficiencies and application potentials in different fields.

Parameters Optimization of Catalytic Tubular Nanomembrane-Based Oxygen Microbubble Generator.

A controllable generation of oxygen gas during the decomposition of hydrogen peroxide by the microreactors made of tubular catalytic nanomembranes has recently attracted considerable attention. Catalytic microtubes play simultaneous roles of the oxygen bubble producing microreactors and oxygen bubble-driven micropumps. An autonomous pumping of peroxide fuel takes place through the microtubes by the recoiling microbubbles. Due to optimal reaction-diffusion processes, gas supersaturation, leading to favorable bubble nucleation conditions, strain-engineered catalytic microtubes with longer length produce oxygen microbubbles at concentrations of hydrogen peroxide in approximately ×1000 lower in comparison to shorter tubes. Dynamic regimes of tubular nanomembrane-based oxygen microbubble generators reveal that this depends on microtubes' aspect ratio, hydrogen peroxide fuel concentration and fuel compositions. Different dynamic regimes exist, which produce specific bubble frequencies, bubble size and various amounts of oxygen. In this study, the rolled-up Ti/Cr/Pd microtubes integrated on silicon substrate are used to study oxygen evolution in different concentrations of hydrogen peroxide and surfactants. Addition of Sodium dodecyl sulfate (SDS) surfactants leads to a decrease of bubble diameter and an increase of frequencies of bubble recoil. Moreover, an increase of temperature (from 10 to 35 °C) leads to higher frequencies of oxygen bubbles and larger total volumes of produced oxygen.

Catalytic/magnetic assemblies of rolled-up tubular nanomembrane-based micromotors.

Nano/-micromotors self-assembling into static and dynamic clusters are of considerable promise to study smart, interactive, responsive, and adaptive nano/-micromaterials that can mimic spatio-temporal patterns, swarming, and collective behaviors widely observed in nature. Previously, the dynamic self-assembly of bubble-propelled catalytic micromotors initiated by capillary forces has been reported. This manuscript shows novel self-assembly modes of magnetic/catalytic Ti/FeNi/Pt tubular micromotors. When chemical fuel (hydrogen peroxide) is added it is decomposed on contact with Pt catalyst into oxygen and water. Here, the non-bubbling motion and autonomous assembly of catalytic/magnetic nanomembranes, i.e. without nucleation/generation of oxygen bubbles, are shown. Moreover, magnetic Ti/FeNi/Pt micromotors are spun using an external magnetic field and they form dynamic clusters balanced by attractive magnetic and repulsive hydrodynamic interactions. Micromotors form dynamic clusters, undergo precession and rapidly propagate through the solution.

Oxygen Microbubble Generator Enabled by Tunable Catalytic Microtubes.

Rolled-up catalytic Ti/Cr/Pt microtubes, consisting of inorganic nanomembranes integrated on-chip, are used to generate oxygen microbubbles in solutions of hydrogen peroxide. Oxygen bubble parameters (frequency, radius and volumetric flow rate) are optimized at different concentrations of hydrogen peroxide and common dish soap. Increasing the aspect ratio of the microtube (e.g., tube length/diameter) leads to the formation of smaller bubbles, but at higher frequencies. Longer tubes produce less total oxygen volume in comparison to shorter tubes. We attribute this observation to the specific dynamic behaviours of bubbles in tubes.

TiO2 Nanomembranes Fabricated by Atomic Layer Deposition for Supercapacitor Electrode with Enhanced Capacitance.

TiO2 is a promising environment friendly, low cost, and high electrochemical performance material. However, impediments like high internal ion resistance and low electrical conductivity restrict its applications as electrode for supercapacitor. In the present work, atomic layer deposition was used to fabricate TiO2 nanomembranes (NMs) with accurately controlled thicknesses. The TiO2 NMs were then used as electrodes for high-performance pseudocapacitors. Experimental results demonstrated that the TiO2 NM with 100 ALD cycles had the highest capacitance of 2332 F/g at 1 A/g with energy density of 81 Wh/kg. The enhanced performance was ascribed to the large surface area and the interconnectivity in the case of ultra-thin and flexible NMs. Increased ALD cycles led to stiffer NMs and decreased capacitance. Moreover, one series of two supercapacitors can light up one light-emitting diode with a working voltage of ~ 1.5 V, sufficiently describing its application values.

TGF-ß1 Causes EMT by Regulating N-Acetyl Glucosaminyl Transferases via Downregulation of Non Muscle Myosin II-A through JNK/P38/PI3K Pathway in Lung Cancer.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is a major determinant of cancer metastasis and is closely linked with TGF-ß1. Intracellular proteins, including E. Cadherin, N. Cadherin and Vimentin are directly related to EMT that affect cell migration and adhesion; on the other hand, non muscle myosin (NM) has a central role in cytokinesis, migration and adhesion. OBJECTIVE: We aimed to explore the association of EMT and metastasis with TGF-ß1 through regulation of non-muscle myosin II-A (NMII-A) and its interaction with Hexosamine Biosynthesis Pathway (HBP). METHOD: Protein expression changes were assessed by western blotting and immunofluorescent staining while transcription level changes were assessed by qRT-PCR. EMT was assessed by phenotypic analysis, wound healing, proliferation and transwell migration assay in vitro while in vivo studies were conducted in BALB/c nude mice for lung orthotopic and tail vein metastasis models. RESULTS: We demonstrated that regulation of JNK/ P38/PI3K by TGF-ß1 led to down expression of NMII-A which promoted EMT and lung cancer metastasis. This down expression of NMII-A conversely upregulated the expression of Core 2 N-acetyl Glucosaminyl Transferase mucin type (C2GnT-M) and further facilitated up-regulation and down-regulation of N-acetylglucosaminyltransferase (GnT) -V and -III respectively; moreover, NMII-A K.D cells showed 3 times more tendency to migrate towards brain in vivo. CONCLUSION: The study reports a novel pathway through which NMII-A negatively regulates EMT and metastasis via up regulation of C2GnT-M, GnT-V and down expression of GnT-III. These findings of lung cancer may further be required to study other cancer types.