Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

Objectives: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam.

Methods: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear.

NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA.

SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells.

The secreted products of cells drive many functions in vivo; however, methods to link this functional information to surface markers and transcriptomes have been lacking. By accumulating secretions close to secreting cells held within cavity-containing hydrogel nanovials, we demonstrate workflows to analyze the amount of IgG secreted from single human B cells and link this information to surface markers and transcriptomes from the same cells. Measurements using flow cytometry and imaging flow cytometry corroborate the association between IgG secretion and CD38/CD138.

Developing a mechanistic understanding of the nonlinear pharmacokinetics of letermovir and prospective drug interaction with everolimus using physiological-based pharmacokinetic modeling.

Letermovir is approved for use in cytomegalovirus-seropositive hematopoietic stem cell transplant recipients and is investigated in other transplant settings. Nonlinear pharmacokinetics (PKs) were observed in clinical studies after intravenous and oral dosing across a wide dose range, including the efficacious doses of 240 and 480 mg. A physiologically-based PK (PBPK) model for letermovir was built to develop a plausible explanation for the nonlinear PKs observed in clinical studies.

Lentiviral Gene Therapy for Artemis-Deficient SCID.

Background: The DNA-repair enzyme Artemis is essential for rearrangement of T- and B-cell receptors. Mutations in , which encodes Artemis, cause Artemis-deficient severe combined immunodeficiency (ART-SCID), which is poorly responsive to allogeneic hematopoietic-cell transplantation.

Methods: We carried out a phase 1-2 clinical study of the transfusion of autologous CD34+ cells, transfected with a lentiviral vector containing , in 10 infants with newly diagnosed ART-SCID.

Use of Hormone Replacement Therapy and Risk of Dementia: A Nationwide Cohort Study.

Background And Objectives: Estrogen has the potential to influence brain physiology implicated in dementia pathogenesis. Hormone replacement therapy (HRT) might be expected to influence the risk of dementia. Observational data indicated that HRT was associated with reductions in dementia risk, but experimental evidence demonstrates that HRT increases the incidence of dementia.

Zebrafish (Danio rerio) Is an Economical and Efficient Animal Model for Screening Potential Anti-cataract Compounds.

Purpose: To develop a zebrafish cataract model for screening potential anti-cataract compounds.

Methods: Living zebrafish were anesthetized and exposed to ultraviolet-C (UV-C) irradiation at a dosage of 3250 mJ/cm2/d until they developed severe cataracts. These cataracts were graded based on photographs analyzed with ImageQuant TL version 7.

Paradoxical mortality of high estimated glomerular filtration rate reversed by 24-h urine creatinine excretion rate adjustment: sarcopenia matters.

Background: Muscle wasting may explain the paradoxical mortality of patients with high estimated glomerular filtration rates (eGFRs) derived from equation methods. However, empirical evidence and solutions remain insufficient.

Methods: In this retrospective cohort study, we compared the performance of equation methods for predicting all-cause mortality; we used 24-h creatinine clearance (24-h CrCl), equation-based eGFRs, and a new eGFR estimating equation weighting for population 24-h urine creatinine excretion rate (U-CER).

Anti-Fatigue Effect of a Dietary Supplement from the Fermented By-Products of Taiwan Tilapia Aquatic Waste and Oligosaccharide Complex.

The Taiwan Tilapia is an important aquaculture product in Taiwan. The aquatic by-products generated during Tilapia processing, such as fish bones and skin, are rich in minerals and protein. We aimed to explore the effect of a dietary supplement, comprising a mixture of fermented Tilapia by-products and oligosaccharides as the raw materials, combined with physical training on exercise performance and fatigue.

Modeling human adaptive immune responses with tonsil organoids.

Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination.

Utility of Screening Chest Radiographs in Patients with Asymptomatic or Minimally Symptomatic COVID-19 in Singapore.

Background Singapore saw an escalation of coronavirus disease 2019 (COVID-19) cases from fewer than 4000 in April 2020 to more than 40 000 in June 2020, with most of these cases attributed to spread within shared facilities housing foreign workers. Appropriate triage and escalation of clinical care are crucial for this patient group managed in community care facilities (CCFs). Purpose To evaluate the imaging guideline recommendations for COVID-19 from the Fleischner Society and to analyze the clinical utility of screening chest radiography for asymptomatic or minimally symptomatic patients with COVID-19.

KRAS Inhibition with Sotorasib in Advanced Solid Tumors.

Background: No therapies for targeting mutations in cancer have been approved. The p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers.

Global Left Atrial Longitudinal Strain Using 3-Beat Method Improves Risk Prediction of Stroke Over Conventional Echocardiography in Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with a risk of ischemic stroke, and functional myocardial imaging has offered novel insights on its pathophysiology and prognosis, but its use in AF-related stroke remains limited. We aimed to evaluate the feasibility of left atrial (LA) deformations and its prognostic values of ischemic stroke in a large-scale AF population.

Methods: Peak atrial longitudinal strain (LA strain), left ventricular strain (global longitudinal strain), LA strain rate (LA SR) at reservoir (LA longitudinal systolic strain rate), and early diastolic conduit (LA longitudinal early diastolic strain rate) phases were analyzed using 2-dimensional speckle tracking echocardiography.

Lentiviral gene therapy for X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34 hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685).

Delayed Dopamine Dysfunction and Motor Deficits in Female Parkinson Model Mice.

This study analyzed gender differences in the progressive dopamine (DA) deficiency phenotype in the MitoPark (MP) mouse model of Parkinson's disease (PD) with progressive loss of DA release and reuptake in midbrain DA pathways. We found that the progressive loss of these DA presynaptic parameters begins significantly earlier in male than female MP mice. This was correlated with behavioral gender differences of both forced and spontaneous motor behavior.

Variation Among Primary Care Physicians in 30-Day Readmissions.

Background: Whether readmission rates vary by primary care physician (PCP) is unknown, although federal policy holds PCPs accountable for reducing readmissions.

Objective: To determine whether 30-day readmission rates vary by PCP.

Design: Retrospective cohort study using marginal models and multilevel logistic regression with 100% of data on Texas Medicare claims from 2008 to 2015.

Diagnostic Performance of 4D CT and Sestamibi SPECT/CT in Localizing Parathyroid Adenomas in Primary Hyperparathyroidism.

Background There currently is no consensus on the optimal localization procedure and imaging protocol for parathyroid adenoma. Parathyroid four-dimensional (4D) CT has emerged as a promising method for preoperative localization. Purpose To evaluate the diagnostic performance of parathyroid 4D CT and technetium 99m-sestamibi (hereafter, referred to as sestamibi) SPECT/CT in preoperative localization in patients with primary hyperparathyroidism.

TLR2 Promotes Vascular Smooth Muscle Cell Chondrogenic Differentiation and Consequent Calcification via the Concerted Actions of Osteoprotegerin Suppression and IL-6-Mediated RANKL Induction.

Objective- Vascular smooth muscle cell (VSMC) transformation to an osteochondrogenic phenotype is an initial step toward arterial calcification, which is highly correlated with cardiovascular disease-related morbidity and mortality. TLR2 (Toll-like receptor 2) plays a pathogenic role in the development of vascular diseases, but its regulation in calcification of arteries and VSMCs remains unclear. We postulate that TLR2-mediated inflammation participates in mediating atherosclerotic arterial calcification and VSMC calcification.

Age, Sex, and Blood Pressure-Related Influences on Reference Values of Left Atrial Deformation and Mechanics From a Large-Scale Asian Population.

Background: Left atrial (LA) function is tightly linked to several cardiovascular diseases and confers key prognostic information. Speckle tracking-based deformation as a feasible and sensitive LA mechanical assessment has proven its clinical significance beyond volume measures; however, the reference values remain largely unknown.

Methods And Results: We studied 4042 participants undergoing annual cardiovascular survey.

Breast Cancer: Radiogenomic Biomarker Reveals Associations among Dynamic Contrast-enhanced MR Imaging, Long Noncoding RNA, and Metastasis.

Purpose: To perform a radiogenomic analysis of women with breast cancer to study the multiscale relationships among quantitative computer vision-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging phenotypes, early metastasis, and long noncoding RNA (lncRNA) expression determined by means of high-resolution next-generation RNA sequencing.

Materials And Methods: In this institutional review board-approved study, an automated image analysis platform extracted 47 computational quantitative features from DCE MR imaging data in a training set (n = 19) to screen for MR imaging biomarkers indicative of poor metastasis-free survival (MFS). The lncRNA molecular landscape of the candidate feature was defined by using an RNA sequencing-specific negative binomial distribution differential expression analysis.