Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Enhanced Piezoelectric Response Attained by Defect Dipoles in BiFeO-based Lead-Free Ceramics.

The impact of defects on the performance of piezoelectric materials has been a topic of considerable debate, due to the competing actions of the deteriorating effect of the defects themselves on the ceramic resistance and the positive effect on the piezoelectric performance resulting from the defect polarization. In order to probe its combined influence on piezoelectric properties, here, we designed BiFeO (BF)-based ceramics with different defect concentrations. It has been demonstrated that the incorporation of an appropriate concentration of defects into ceramics can effectively enhance their piezoelectric properties while maintaining their insulating properties.

Investigation on the interfacial and emulsion stabilized behavior of dextran/ferritin/resveratrol composite nanoparticles.

Glycation of ferritin provides a viable approach to enhance its physicochemical and functional properties. However, there is limited research on the interfacial adsorption properties of glycated ferritin-based colloidal particles. Therefore, this study selected recombinant human H-chain ferritin (rHuHF), rHuHF encapsulated with resveratrol (rHuHF-Res), and rHuHF-dextran glycoconjugates loaded with resveratrol (Dex-rHuHF-Res) as emulsifiers to investigate their interfacial adsorption properties.

Homocysteine S-Methyltransferase 3 Positively Regulates Cadmium Tolerance in Maize.

The increasing contamination of agricultural soils with cadmium (Cd) poses a significant threat to human health and global food security. Plants initiate a series of mechanisms to reduce Cd toxicity. However, the response of maize to Cd toxicity remains poorly understood.

Economic evaluation of hepatocellular carcinoma surveillance in chronic hepatitis B patients with virological remission.

Background: Subsequent risk of hepatocellular carcinoma (HCC) persists in chronic hepatitis B (CHB) patients with virological remission. We aimed to assess the cost-effectiveness of HCC surveillance in those patients and determine appropriate age to commence or discontinue surveillance.

Methods: We developed an individual-based state transition model, simulating the advancement of HCC in CHB patients with virological remission.

Development and validation of prediction models for nosocomial infection and prognosis in hospitalized patients with cirrhosis.

Background: Nosocomial infections (NIs) frequently occur and adversely impact prognosis for hospitalized patients with cirrhosis. This study aims to develop and validate two machine learning models for NIs and in-hospital mortality risk prediction.

Methods: The Prediction of Nosocomial Infection and Prognosis in Cirrhotic patients (PIPC) study included hospitalized patients with cirrhosis at the Qingchun Campus of the First Affiliated Hospital of Zhejiang University.

Modeling multi-component separation in hydrophobic interaction chromatography with improved parameter-by-parameter estimation method.

Mechanistic models are powerful tools for chromatographic process development and optimization. However, hydrophobic interaction chromatography (HIC) mechanistic models lack an effective and logical parameter estimation method, especially for multi-component system. In this study, a parameter-by-parameter method for multi-component system (called as mPbP-HIC) was derived based on the retention mechanism to estimate the six parameters of the Mollerup isotherm for HIC.

Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel.

Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions.

Child Opportunity Index Mobility, Recurrent Wheezing, and Asthma in Early Childhood: A Population-Based Prospective Cohort Study.

We prospectively examined associations between mobility in neighborhood opportunity and early childhood recurrent wheezing/asthma. Downward mobility was associated with developing asthma, but not recurrent wheezing, though associations were attenuated after adjusting for family-level socioeconomic status. Elucidating how neighborhoods impact asthma may inform asthma equity initiatives in early childhood.

Theoretical simulation of TADF character of 3,9'-bicarbazole-modified 2,4,6-triphenyl-1,3,5-triazine.

Context: Three donor (D)-acceptor (A)-type temperature-activated delayed fluorescent (TADF) molecules of 9-(2-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9H-3,9'-bicarbazole (o-TrzDCz), 9-(3-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9H-3,9'-bicarbazole (m-TrzDCz), and 9-(4-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-9H-3,9'-bicarbazole (p-TrzDCz) were designed in this paper, and the photophysical properties, including the intersystem crossing rate, the reorganization energies (λ), and the intersystem crossing/reverse intersystem crossing (ISC/RISC) rate, were simulated to explore the effect of substitution sites on their TADF character. The values of the twist angle between the D and A moieties in ground state and the molecular root-mean-square deviation (RMSD) of the S and T states referenced to the S state indicate that o-TrzDCz possess bigger steric hindrance and stabler molecular configuration. The λ values of the ISC/RISC process should be 0.

Approach to the Patient: Concept and Application of Targeted Radiotherapy in the Paraganglioma Patient.

Paragangliomas can metastasize, posing potential challenges both in symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma-targeted radiotherapies.

Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis.

Background: Various mitral repair techniques have been described. Though these repair techniques can be highly effective when performed correctly in suitable patients, limited quantitative biomechanical data are available. Validation and thorough biomechanical evaluation of these repair techniques from translational large animal in vivo studies in a standardized, translatable fashion are lacking.

Lessons Learned in Building Expertly Annotated Multi-Institution Datasets and Hosting the RSNA AI Challenges.

The Radiological Society of North America (RSNA) has held artificial intelligence competitions to tackle real-world medical imaging problems at least annually since 2017. This article examines the challenges and processes involved in organizing these competitions, with a specific emphasis on the creation and curation of high-quality datasets. The collection of diverse and representative medical imaging data involves dealing with issues of patient privacy and data security.

Type 2 Diabetes Modifies the Association of CAD Genomic Risk Variants With Subclinical Atherosclerosis.

Background: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.

Methods: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program.

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression.

Immune escape is a prerequisite for tumor growth. We previously described a decline in intratumor activated cytotoxic T cells and T cell receptor (TCR) clonotype diversity in invasive breast carcinomas compared to ductal carcinoma in situ (DCIS), implying a central role of decreasing T cell responses in tumor progression. To determine potential associations between peripheral immunity and breast tumor progression, here, we assessed the peripheral blood TCR clonotype of 485 breast cancer patients diagnosed with either DCIS or de novo stage IV disease at younger (<45) or older (≥45) age.

Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy.

Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival.

A Highly Flexible Piezoelectric Ultrasonic Sensor for Wearable Bone Density Testing.

Driven by the loss of bone calcium, the elderly are prone to osteoporosis, and regular routine checks on bone status are necessary, which mainly rely on bone testing equipment. Therefore, wearable real-time healthcare devices have become a research hotspot. Herein, we designed a high-performance flexible ultrasonic bone testing system using axial transmission technology based on quantitative ultrasound theory.