Precise correction of a spectrum of β-thalassemia mutations in coding and non-coding regions by base editors.

β-thalassemia/HbE results from mutations in the β-globin locus that impede the production of functional adult hemoglobin. Base editors (BEs) could facilitate the correction of the point mutations with minimal or no indel creation, but its efficiency and bystander editing for the correction of β-thalassemia mutations in coding and non-coding regions remains unexplored. Here, we screened BE variants in HUDEP-2 cells for their ability to correct a spectrum of β-thalassemia mutations that were integrated into the genome as fragments of .

Macrophakia: The characterization of a novel lens condition.

Purpose: To present a novel characterization of a lens condition termed which includes large or proportionally large lenses with shallow anterior chamber dimensions that are statistically deviant of a normal population.

Observations: We identified five eyes from three cases to have significantly large lens parameters and small anterior chamber depths. In all five eyes, the anterior chamber depth was less than 2 mm and the anterior chamber depth to lens thickness ratio was two standard deviations outside the normative range of lens and chamber measurements.

Base editing of key residues in the BCL11A-XL-specific zinc finger domains derepresses fetal globin expression.

BCL11A-XL directly binds and represses the fetal globin (HBG1/2) gene promoters, using 3 zinc-finger domains (ZnF4, ZnF5, and ZnF6), and is a potential target for β-hemoglobinopathy treatments. Disrupting BCL11A-XL results in derepression of fetal globin and high HbF, but also affects hematopoietic stem and progenitor cell (HSPC) engraftment and erythroid maturation. Intriguingly, neurodevelopmental patients with ZnF domain mutations have elevated HbF with normal hematological parameters.

A transparent synthetic peptide hydrogel as a haemostatic agent in athermal nerve sparing robot-assisted radical prostatectomy: an observational study.

Background: PuraStat is a new synthetic haemostatic agent constituting peptides that self-assemble into sheets when exposed to ionic charges. The objective of this submission is to assess the perioperative, functional and user-reported outcomes of PuraStat as an athermal topical haemostatic agent for use on the neurovascular bundle (NVB) in robot-assisted radical prostatectomy (RARP), and to inform further research into this developing field.

Methods: Demographic and disease data for 29 consecutive patients undergoing RARP were recorded.

van der Waals Epitaxy, Superlubricity, and Polarization of the 2D Ferroelectric SnS.

Tin monosulfide (SnS) is a two-dimensional layered semiconductor that exhibits in-plane ferroelectric order at very small thicknesses and is of interest in highly scaled devices. Here we report the epitaxial growth of SnS on hexagonal boron nitride (hBN) using a pulsed metal-organic chemical vapor deposition process. Lattice matching is observed between the SnS(100) and hBN{11̅0} planes, with no evidence of strain.

Experimental Study on Sustainability Involving the Pugh Matrix on Emission Values of High-Temperature Air in the Premixed Charged Compression Ignition Engine.

The main aim of the study was to reduce carbon emissions in the atmosphere using a novel (AN) biofuel using higher air temperatures and reducing the consumption of conventional fossil fuel (diesel). The use of a heat exchange chamber within the air intake manifold is a popular method to reduce hydrocarbon (HC) and carbon monoxide (CO) emissions during cold starts. A premixed charged compression ignition engine in the dual-fuel mode was used in this study with raw diesel, raw AN oil, AN70+D30, AN80+D20, AN80+D20 (35 °C), AN80+D20 (40 °C), and AN80+D20 (45 °C).

Social health: rethinking the concept through social practice theory and feminist care ethics.

The social sciences have long shown that health is not born of pure biology, empirically (re)centred the social and material causes of disease, and affirmed the subjective experiences of disease. Disputed both in popular and academic discourses, social health has variously attempted to stress the social aspects of health. Existing conceptions remain analytically limited as they are predominantly used as descriptors for populational health.

Why comply? Risk and efficacy perceptions drive compliance in mass marketing scams.

Using a mix-method design, we examined participants' willingness to respond to mass marketing scams (MMS). In Experiment 1, we examined the effect of age (young versus older) and letter style ("hot" versus "cold") on the intention to respond. The intention of responding was negatively associated with risk ( < .

Efficient and error-free correction of sickle mutation in human erythroid cells using prime editor-2.

Sickle cell anaemia (SCA) is one of the common autosomal recessive monogenic disorders, caused by a transverse point mutation (GAG > GTG) at the sixth codon of the beta-globin gene, which results in haemolytic anaemia due to the fragile RBCs. Recent progress in genome editing has gained attention for the therapeutic cure for SCA. Direct correction of SCA mutation by homology-directed repair relies on a double-strand break (DSB) at the target site and carries the risk of generating beta-thalassaemic mutations if the editing is not error-free.

[Pandemic Management in the Context of Everyday Care and the need for Good Care: Results and Recommendations for Action from the Coronacare Workshops].

The Covid-19 pandemic, officially declared in March 2020 by the WHO, poses major challenges to public, private, and occupational life. CoronaCare is an ethnographic research project that investigates the everyday life of people during the Covid-19 pandemic in Germany with a particular focus on social health. The aim of the project was to develop recommendations for pandemic preparedness planning focusing on expanding social health care.

Scalable detection of technically challenging variants through modified next-generation sequencing.

Background: Some clinically important genetic variants are not easily evaluated with next-generation sequencing (NGS) methods due to technical challenges arising from high- similarity copies (e.g., PMS2, SMN1/SMN2, GBA1, HBA1/HBA2, CYP21A2), repetitive short sequences (e.

Ingrained: An Automated Framework for Fusing Atomic-Scale Image Simulations into Experiments.

To fully leverage the power of image simulation to corroborate and explain patterns and structures in atomic resolution microscopy, an initial correspondence between the simulation and experimental image must be established at the outset of further high accuracy simulations or calculations. Furthermore, if simulation is to be used in context of highly automated processes or high-throughput optimization, the process of finding this correspondence itself must be automated. In this work, "ingrained," an open-source automation framework which solves for this correspondence and fuses atomic resolution image simulations into the experimental images to which they correspond, is introduced.

CoronaCare study protocol: an ethnographic study of the risks to and potential for social health during the COVID-19 pandemic.

Introduction: German government regulations such as physical distancing and limited group numbers, designed to curb the spread of COVID-19, have had far-reaching consequences for the very foundations of social life. They have, to name only a few, transformed greetings and goodbyes, blurred private and public worlds, and complicated basic communication with mandatory mask wearing. The ethnographic study CoronaCare investigates how these sociopolitical measures affect social health, a form of health which unfolds through and across social relations.

A validated audio-visual educational module on examination skills in ophthalmology for undergraduate medical students in the COVID-19 season - An observational longitudinal study.

Purpose: The aim of this study was to assess the impact of an audio visual (AV) teaching module on basic torchlight examination of the eye and direct ophthalmoscopy for undergraduate medical students.

Methods: This observational longitudinal study was done on 33 consecutive medical interns during their Ophthalmology posting from December 2019 to March 2020 at a medical college in South-India. An AV-module was created using animation graphics, narratives, demonstrations on normal individuals and on patients with positive signs.

Synthetic cannabinoid induced ocular self-injury.

Synthetic cannabinoids are a relatively new and increasingly popular recreational drug. While used for their hallucinogenic properties similar to natural cannabis, they have a greater and more serious side effect profile, including potentially severe neuropsychiatric toxicity. We report the cases of two patients with untreated schizophrenia who presented after ocular self-injury while intoxicated on K2.

An experimental study to test the efficacy of Mesenchymal Stem Cells in reducing corneal scarring in an ex-vivo organ culture model.

In this study, we evaluated the effect of placenta-derived Mesenchymal Stem Cells (MSCs) versus placebo in improving corneal transparency following experimental injury in an ex-vivo organ culture model of post-mortem human corneas. We also compared the influence of MSCs on the basic histopathology of the cornea and the immunohistochemistry markers of fibrotic corneal scarring. Mesenchymal Stem Cells extracted from the placenta were isolated and expanded in-vitro.

Performance and emission reduction characteristics of cerium oxide nanoparticle-water emulsion biofuel in diesel engine with modified coated piston.

In the present scenario, the utilization of petroleum fuel is expanding forcefully worldwide in the vitality store and plays a highly hazardous role in the ecological system. Biofuel stands out among the most tenable keys for this issue. The lemongrass oil is used as a biofuel because of low density and viscosity when compared with diesel.

A Rigorous Interlaboratory Examination of the Need to Confirm Next-Generation Sequencing-Detected Variants with an Orthogonal Method in Clinical Genetic Testing.

Orthogonal confirmation of next-generation sequencing (NGS)-detected germline variants is standard practice, although published studies have suggested that confirmation of the highest-quality calls may not always be necessary. The key question is how laboratories can establish criteria that consistently identify those NGS calls that require confirmation. Most prior studies addressing this question have had limitations: they have been generally of small scale, omitted statistical justification, and explored limited aspects of underlying data.

Cytomorphometric Neutrophil and Monocyte Markers May Strengthen the Diagnosis of Sepsis.

Background:: The diagnosis of sepsis is challenging in the absence of a gold standard test. Recent studies have explored the role of neutrophil and monocyte volume, conductivity, and scatter (VCS), derived from automated hematology analyzers, in diagnosing sepsis. We assessed the diagnostic accuracy of VCS parameters in critically ill patients with sepsis.

Prevalence and properties of intragenic copy-number variation in Mendelian disease genes.

Purpose: We investigated the frequencies and characteristics of intragenic copy-number variants (CNVs) in a deep sampling of disease genes associated with monogenic disorders.

Methods: Subsets of 1507 genes were tested using next-generation sequencing to simultaneously detect sequence variants and CNVs in >143,000 individuals referred for genetic testing. We analyzed CNVs in gene panels for hereditary cancer syndromes and cardiovascular, neurological, or pediatric disorders.

Tuberculin skin test versus interferon-gamma release assay in refugee children: A retrospective cohort study.

Aim: The aim of this study was to assist clinicians evaluating refugee children for latent tuberculosis infection (LTBI) by comparing paired tuberculin skin test (TST) and Quantiferon Gold In-Tube (QGIT) test results with clinical management decisions and follow-up data in a large cohort of newly arrived refugee children.

Methods: This was a retrospective analysis of all refugee children (<15 years of age) evaluated for LTBI with both TST and interferon-γ release assay between 2007 and 2010 in the Illawarra-Shoalhaven region of New South Wales, Australia. Demographics, country of origin, bacille Calmette-Guerin (BCG) vaccination status, chest X-ray results, TST and QGIT test results, clinical management and outcome on long-term follow-up were assessed.

A PROSPECTIVE, RANDOMIZED TRIAL COMPARING PLAIN GUT TO POLYGLACTIN 910 (VICRYL) SUTURES FOR SCLEROTOMY CLOSURE AFTER 23-GAUGE PARS PLANA VITRECTOMY.

Purpose: To report a prospective, randomized comparative study assessing clinical outcomes of plain gut versus polyglactin 910 (PG910) sutures for sclerotomy closure after 23-gauge pars plana vitrectomy.

Methods: A single-masked, randomized, prospective study was undertaken with 49 eyes of 49 patients undergoing 23-gauge pars plana vitrectomy randomized to sclerotomy closure with either plain gut suture, PG910 (Vicryl) suture or a combination of the two. Assessment was based on both a postoperative pain scale and a standardized assessment of scleral inflammation at each suture site.

Topology-Scaling Identification of Layered Solids and Stable Exfoliated 2D Materials.

The Materials Project crystal structure database has been searched for materials possessing layered motifs in their crystal structures using a topology-scaling algorithm. The algorithm identifies and measures the sizes of bonded atomic clusters in a structure's unit cell, and determines their scaling with cell size. The search yielded 826 stable layered materials that are considered as candidates for the formation of two-dimensional monolayers via exfoliation.

Transcription elongation factor ELL2 drives Ig secretory-specific mRNA production and the unfolded protein response.

Differentiation of B cells into Ab-secreting cells induces changes in gene transcription, IgH RNA processing, the unfolded protein response (UPR), and cell architecture. The transcription elongation factor eleven nineteen lysine-rich leukemia gene (ELL2) stimulates the processing of the secreted form of the IgH mRNA from the H chain gene. Mice (mus musculus) with the ELL2 gene floxed in either exon 1 or exon 3 were constructed and crossed to CD19-driven cre/CD19(+).