Nonclinical Pharmacokinetics Study of OLX702A-075-16, -Acetylgalactosamine Conjugated Asymmetric Small Interfering RNA (GalNAc-asiRNA).

In this study, the nonclinical pharmacokinetics of OLX702A-075-16, an RNA interference therapeutic currently in development, were investigated. OLX702A-075-16 is a novel -acetylgalactosamine conjugated asymmetric small-interfering RNA (GalNAc-asiRNA) used for the treatment of an undisclosed liver disease. Its unique 16/21-mer asymmetric structure reduces nonspecific off-target effects without compromising efficacy.

What's in the Shadows? Formal Analysis: Art History Method to Improve Interpretation Skills for Mammography and Chest Radiographs in Resident Education.

Rationale And Objectives: To assess the feasibility of using an art history tool of formal analysis in resident education for interpretations of mammography and chest radiographs METHODS: In a pre-post study design, residents were shown pre-selected 10 mammograms and 10 chest radiographs for a total of 20 unique anonymized patient cases. After the pretest, residents attended four formal analysis art history lessons. The formal elements included line, light, dark, shade, proportion and balance.

Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: The OCTIVUS Randomized Clinical Trial.

Background: Intravascular imaging-guided percutaneous coronary intervention (PCI) with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) showed superior clinical outcomes compared with angiography-guided PCI. However, the comparative effectiveness of OCT-guided and IVUS-guided PCI regarding clinical outcomes is unknown.

Methods: In this prospective, multicenter, open-label, pragmatic trial, we randomly assigned 2008 patients with significant coronary artery lesions undergoing PCI in a 1:1 ratio to undergo either an OCT-guided or IVUS-guided PCI.

Artificial Intelligence in Lung Imaging.

Recently, interest and advances in artificial intelligence (AI) including deep learning for medical images have surged. As imaging plays a major role in the assessment of pulmonary diseases, various AI algorithms have been developed for chest imaging. Some of these have been approved by governments and are now commercially available in the marketplace.

LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody.

Content-based Image Retrieval by Using Deep Learning for Interstitial Lung Disease Diagnosis with Chest CT.

Background Evaluation of interstitial lung disease (ILD) at CT is a challenging task that requires experience and is subject to substantial interreader variability. Purpose To investigate whether a proposed content-based image retrieval (CBIR) of similar chest CT images by using deep learning can aid in the diagnosis of ILD by readers with different levels of experience. Materials and Methods This retrospective study included patients with confirmed ILD after multidisciplinary discussion and available CT images identified between January 2000 and December 2015.

Enhanced genome editing efficiency of CRISPR PLUS: Cas9 chimeric fusion proteins.

Efforts to improve CRISPR-Cas9 genome editing systems for lower off-target effects are mostly at the cost of its robust on-target efficiency. To enhance both accuracy and efficiency, we created chimeric SpyCas9 proteins fused with the 5'-to-3' exonuclease Recombination J (RecJ) or with GFP and demonstrated that transfection of the pre-assembled ribonucleoprotein of the two chimeric proteins into human or plant cells resulted in greater targeted mutagenesis efficiency up to 600% without noticeable increase in off-target effects. Improved activity of the two fusion proteins should enable editing of the previously hard-to-edit genes and thus readily obtaining the cells with designer traits.

SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.

Treatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack of ideal target antigens that are both absolutely tumor specific and homogeneously expressed. We show that multi-antigen prime-and-kill recognition circuits provide flexibility and precision to overcome these challenges in the context of glioblastoma. A synNotch receptor that recognizes a specific priming antigen, such as the heterogeneous but tumor-specific glioblastoma neoantigen epidermal growth factor receptor splice variant III (EGFRvIII) or the central nervous system (CNS) tissue-specific antigen myelin oligodendrocyte glycoprotein (MOG), can be used to locally induce expression of a CAR.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Two Weeks.

These 2 weeks of attending are ones that I will never forget, but I worry about what the next 2 weeks will bring.

Impact of Interferon-Based Treatment on Quality of Life and Work-Related Productivity of Korean Patients with Chronic Hepatitis C.

Background/aims: Chronic hepatitis C virus (HCV) infections put patients at risk of serious liver disease and adversely affects patient quality of life (QoL). MOSAIC (International Multicenter Prospective Observational Study to Evaluate the Epidemiology, Humanistic and Economic Outcomes of Treatment for Chronic Hepatitis C Virus) was a prospective, non-interventional, international, multicenter study that aimed to describe the epidemiology of the infection, the impact of the infection on health-related QoL (HRQoL) and daily activities, and healthcare resource use related to HCV and treatment. Here, we present the results on HRQoL and daily activity impairment in consecutively enrolled South Korean patients treated with interferon (IFN)-containing regimens prospectively followed for up to 48 weeks.

Comparison of genomic predictions for carcass and reproduction traits in Berkshire, Duroc and Yorkshire populations in Korea.

Objective: A genome-based best linear unbiased prediction (GBLUP) method was applied to evaluate accuracies of genomic estimated breeding value (GEBV) of carcass and reproductive traits in Berkshire, Duroc and Yorkshire populations in Korean swine breeding farms.

Methods: The data comprised a total of 1,870, 696, and 1,723 genotyped pigs belonging to Berkshire, Duroc and Yorkshire breeds, respectively. Reference populations for carcass traits consisted of 888 Berkshire, 466 Duroc, and 1,208 Yorkshire pigs, and those for reproductive traits comprised 210, 154, and 890 dams for the respective breeds.

Moderating effect of ε4 on the relationship between sleep-wake cycle and brain β-amyloid.

Objectives: To clarify the relationships between sleep-wake cycle and cerebral β-amyloid (Aβ) deposition in cognitively normal (CN) older adults, focusing primarily on the moderating effects of the ε4 allele.

Methods: The present study included 133 CN older adults who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease cohort. All participants underwent [C] Pittsburgh compound B-PET imaging to quantify Aβ deposition in the brain and blood sampling for genotyping.

Competency-Based Medical Education in the Internal Medicine Clerkship: A Report From the Alliance for Academic Internal Medicine Undergraduate Medical Education Task Force.

As medical educators continue to redefine learning and assessment across the continuum, implementation of competency-based medical education in the undergraduate setting has become a focus of many medical schools. While standards of competency have been defined for the graduating student, there is no uniform approach for defining competency expectations for students during their core clerkship year. The authors describe the process by which an Alliance for Academic Internal Medicine task force developed a paradigm for competency-based assessment of students during their inpatient internal medicine (IM) clerkship.

Coronary Computed Tomography Angiography Predicts Guidewire Crossing and Success of Percutaneous Intervention for Chronic Total Occlusion: Korean Multicenter CTO CT Registry Score as a Tool for Assessing Difficulty in Chronic Total Occlusion Percutaneous Coronary Intervention.

Background: We developed a model that predicts difficulty of percutaneous coronary intervention for coronary chronic total occlusion (CTO) using coronary computed tomographic angiography.

Methods And Results: A total of 684 CTO lesions with preprocedural computed tomographic angiography were enrolled from 4 centers. Data were randomly divided into derivation and validation datasets at 2:1 ratio.

Synergistic effects of longitudinal amyloid and vascular changes on lobar microbleeds.

Objective: To determine whether amyloid and hypertensive cerebral small vessel disease (hCSVD) changes synergistically affect the progression of lobar microbleeds in patients with subcortical vascular mild cognitive impairment (svMCI).

Methods: Among 72 patients with svMCI who underwent brain MRI and [C] Pittsburgh compound B (PiB)-PET, 52 (72.2%) completed the third year of follow-up.

Echoing Plaque Activity of the Coronary and Intracranial Arteries in Patients With Stroke.

Background And Purpose: Atherosclerosis is a systemic disease, and both coronary and intracranial atherosclerosis are common in the elderly. Unlike coronary artery disease (CAD), intracranial atherosclerotic disease can cause intracranial atherosclerotic stroke by branch occlusive disease (B-type) and coronary-type rupture of plaque (C-type). We hypothesized that plaque characteristics of intracranial arteries are associated with those of coronary arteries.

Shortening the Miles to the Milestones: Connecting EPA-Based Evaluations to ACGME Milestone Reports for Internal Medicine Residency Programs.

The Next Accreditation System requires internal medicine training programs to provide the Accreditation Council for Graduate Medical Education (ACGME) with semiannual information about each resident's progress in 22 subcompetency domains. Evaluation of resident "trustworthiness" in performing entrustable professional activities (EPAs) may offer a more tangible assessment construct than evaluations based on expectations of usual progression toward competence. However, translating results from EPA-based evaluations into ACGME milestone progress reports has proven to be challenging because the constructs that underlay these two systems differ.

Early- vs late-onset subcortical vascular cognitive impairment.

Objective: To evaluate the differences between early-onset subcortical vascular cognitive impairment (EO-SVCI) and late-onset subcortical vascular cognitive impairment (LO-SVCI) with regard to pathologic burden, structural changes, and cognitive function.

Methods: We prospectively recruited 142 patients from a single referral center. Patients were divided into EO-SVCI (n = 30, age at onset <65 years) and LO-SVCI (n = 112, age at onset ≥ 65 years) groups.