Haplotype editing with CRISPR/Cas9 as a therapeutic approach for dominant-negative missense mutations in .

Inactivation of disease alleles by allele-specific editing is a promising approach to treat dominant-negative genetic disorders, provided the causative gene is haplo-sufficient. We previously edited a dominant missense mutation with inactivating frameshifts and rescued disease-relevant phenotypes in induced pluripotent stem cell (iPSC)-derived motor neurons. However, a multitude of different missense mutations cause disease.

Trastuzumab-Induced Early Corneal Melt in HER2-Positive Breast Cancer: A Case Report and Review.

BACKGROUND Trastuzumab (Herceptin) is a recombinant DNA-derived humanized monoclonal antibody that the US Food and Drug Administration (FDA) approved in 1998 for metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer therapy. It selectively binds to the extracellular domain of HER2 and mediates an antibody-dependent cellular toxicity in various tissues. Trastuzumab use alone does not typically cause aggressive ocular complications.

Low-valent Main-group Catalysis under Ambient Conditions using a Germylene Cation.

Catalysis using low-valent main-group compounds is usually done under inert conditions; no example of such catalysis has been doable entirely in ambient conditions until now. This aspect is addressed in this work through an air- and water-stable germylene cation [DPMGe][(OH)B(CF)] (2) (DPM=dipyrromethene); it efficiently catalyzes aldehyde and ketone hydrosilylations under ambient conditions. Detailed theoretical studies reveal that compound 2's stability is bolstered by the interaction between the anion and germanium's frontier orbitals.

Efficacy of a portable non-mydriatic fundus camera for "rule-out papilledema" consultations: A prospective study.

Purpose: Ophthalmology is frequently consulted to "rule-out papilledema." We assessed the efficacy of a portable, non-mydriatic fundus camera in detecting optic disc edema in the inpatient and emergency room settings during "rule-out papilledema" consultations, comparing to the gold standard dilated fundus examination (DFE).

Methods: This prospective, blinded, cohort study included 124 non-mydriatic fundus photographs (62 patients) that were obtained over the 11-month enrollment period.

Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases.

Certolizumab pegol (CZP; CIMZIA™) is the only Fc-free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases were assessed using a population PK model based on data from the CHERISH study (NCT04163016), a longitudinal, prospective, open-label PK phase IB study. Model development was performed in NONMEM using a frequentist prior approach, with prior information based on a population PK model for certolizumab pegol in non-pregnant adult patients (NCT04740814).

Unravelling the Mechanism of CO Activation: Insights Into Metal-Metal Cooperativity and Spin-Orbit Coupling with {3d-4f} Catalysts.

Converting CO into useful chemicals using metal catalysts is a significant challenge in chemistry. Among the various catalysts reported, transition metal lanthanide hybrid {3d-4f} complexes stand out for their superior efficiency and site selectivity. However, unlike transition metal catalysts, understanding the origin of this efficiency in lanthanides poses a challenge due to their orbital degeneracy, rendering the application of DFT methods ineffective.

Pharmacogenomic biomarkers in coronary artery disease: a narrative review.

Coronary artery disease (CAD) has a high mortality rate. Despite various therapeutic targets, non-responsiveness to drugs remains a prevalent issue. Pharmacogenomics assesses the way an individual's genetic attributes affect their likely response to drug therapy.

Deep Learning Models for Classification of Deciduous and Permanent Teeth From Digital Panoramic Images.

Introduction: Dental radiographs are essential in the diagnostic process in dentistry. They serve various purposes, including determining age, analyzing patterns of tooth eruption/shedding, and treatment planning and prognosis. The emergence of digital radiography technology has piqued interest in using artificial intelligence systems to assist and guide dental professionals.

Use of mini implants for the two-implant retained mandibular overdenture: A prospective study.

Background: The two-implant retained mandibular overdenture utilizing nonsplinted implants is a proven treatment modality for completely edentulous patients. However, a lacuna still exists regarding the suitability of mini dental implants for this purpose. The purpose of the study was to evaluate implant stability and crestal bone loss in single-piece mini dental implants loaded with immediate or conventional loading protocols to retain a mandibular overdenture.

Development of Long Asymmetric siRNA Structure for Target Gene Silencing and Immune Stimulation in Mammalian Cells.

Post-transcriptional regulation of transcript abundances by RNA interference (i) is a widely conserved regulatory mechanism to control cellular processes. We previously introduced an alternative siRNA structure called asymmetric siRNA (asiRNA), and showed that asiRNA exhibits comparable gene-silencing efficiency with reduced off-target effects compared with conventional siRNAs. However, to what extent the length of the guide strand affects the gene-silencing efficiency of asiRNAs is still elusive.

Extensively drug-resistant panophthalmitis from contaminated artificial tears.

is one of the common gram-negative organisms that cause severe invasive infections in different organ systems. has unique intrinsic mechanisms to develop antimicrobial resistance quickly, making it extremely difficult to treat. We report a case of extensively drug-resistant (XDR) panophthalmitis due to contaminated artificial tears.

Management of compromised residual alveolar ridges using hollow denture with three-dimensional printed spacer and specialized impression technique.

Impression making in compromised residual alveolar ridge is a regular challenge in rehabilitating patients with conventional removable complete dentures. In patients who cannot afford implant-supported dentures, specialized impression technique is a viable and justified option for fabrication of complete dentures. More often, the stability of denture in such patients becomes a deciding factor between failure and success.

Synchronization in Cycles of China and India During Recent Crises: A Markov Switching Analysis.

We study the impact of recent crisis episodes viz the Great Recession of 2007-09, the Euro Area crisis of 2010-12 and the COVID-19 pandemic of 2020-21 on the Emerging Market Economies (EMEs) of China and India using data from January, 1986 till June, 2021. A Markov-switching (MS) analysis is applied to discern economy-specific cycles/regimes and common cycles/regimes in the growth rates of the economies. We apply the univariate MS Autoregressive (MS-AR) model to characterize country-specific negative growth, moderate growth and high growth regimes of China and India.

Integration of Digital and Analog Workflow to Achieve Predictable Esthetics: A Novel Approach.

The use of digital smile designing simplifies the restoration of esthetics. In this article, a case of diastema and incisal notching in anterior teeth was rehabilitated with porcelain laminate veneers using combination of digital and analog workflow.

Sociopolitical solidarity in STEM education: youth-centered relationships that resist learning as just achievement data.

In this paper, we-a participatory action group-use the tenants of critical pedagogy to articulate how youths developed relationships for and with STEM disciplinary practices through participation in spaces outside of the official scripts of their high school STEM classrooms in the United States. Spaces included their robotics team, a hybrid digital collaborative space, and in an extra project with a teacher. Each of these cases surfaces youth's ongoing orientation to the fact that STEM learning is relational, and political, exemplifying pockets of resistance against the structures of schooling that foreground learning as an act of individuals.

Population PK and PD Analysis of Domagrozumab in Pediatric Patients with Duchenne Muscular Dystrophy.

Myostatin, a negative regulator of skeletal muscle growth, is a therapeutic target in muscle-wasting diseases. Domagrozumab, a humanized recombinant monoclonal antibody, binds myostatin and inhibits activity. Domagrozumab was investigated in a phase II trial (NCT02310763) as a potential treatment for boys with Duchenne muscular dystrophy (DMD).

Superparamagnetic and Perfect-Paramagnetic Zinc Ferrite Quantum Dots from Microwave-Assisted Tunable Synthesis.

The properties of quantum dot (QD)-size material depend directly upon its unit cell structure. Spinel zinc ferrite QD powder is produced via a one-pot microwave-assisted hydrothermal synthesis for just 5 min. Varying initial pH values of the preparation sol from 6 to 12 enlarges the Zn/Fe atomic ratio (by ca.

Lp-PLA2 as a biomarker and its possible associations with SARS-CoV-2 infection.

Lp-PLA2 is an enzyme encoded by the gene located at chromosome 6p12-21, which is included in different signal transduction pathways. The potential of serum levels of Lp-PLA2 as a marker of inflammation quantifying cardio-metabolic risk, renal impairment and oxidative stress has been explored in earlier studies. It has also been used in chronic obstructive pulmonary disease, hepatic disease, metabolic conditions and exercise tolerance.

RIG-I-Mediated Innate Immune Stimulation by Chemically Synthesized Long Double-Stranded RNAs Is Structure and Sequence Dependent.

Double-stranded RNAs (dsRNAs) longer than 30 bp have not been considered desirable RNA interference (RNAi) triggering structures in mammalian cells as they nonspecifically activate innate immune response. However, in earlier studies, not only dsRNA length but also 5'-triphosphate moiety produced by transcription might have affected the stimulation of innate immune system. Herein, using chemically synthesized long dsRNAs without 5'-triphosphate, we elucidated direct relationship between length of dsRNAs and innate immune stimulation.

Physicochemical and biological analysis of river Yamuna at Palla station from 2009 to 2019.

Yamuna is one of the main tributaries of the river Ganga and passes through Delhi, the national capital of India. In the last few years, it is considered one of the most polluted rivers of India. We carried out the analysis for the physiochemical and biological conditions of the river Yamuna based on measurements acquired at Palla station, Delhi during 2009-19.

Regime Shifts in the Behaviour of International Currency and Equity Markets: A Markov-Switching Analysis.

This paper examines regime switching behaviour and dynamic linkages among currency and equity markets of Eurozone, India, Japan and U.S. using a Markov-switching framework.

Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disorder caused by mutations in the DMD gene, leading to severe reduction or absence of the protein dystrophin. Gene therapy strategies that aim to increase expression of a functional dystrophin protein (mini-dystrophin) are under investigation. The ability to accurately quantify dystrophin/mini-dystrophin is essential in assessing the level of gene transduction.