Discrepancy Between Genetically Predicted and Observed BMI Predicts Incident Type 2 Diabetes.

Objective: Obesity is a key predictor of type 2 diabetes (T2D). However, metabolic complications are not solely due to increased BMI. We hypothesized that differences between genetically predicted BMI and observed BMI (BMI-diff) could reflect deviation from individual set point and may predict incident T2D.

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.

Anti-Cancer Roles of Probiotic-Derived P8 Protein in Colorectal Cancer Cell Line DLD-1.

A novel probiotics-derived protein, P8, suppresses the growth of colorectal cancer (CRC). P8 can penetrate the cell membrane via endocytosis and cause cell cycle arrest in DLD-1 cells through down-regulation of CDK1/Cyclin B1. However, neither the protein involved in the endocytosis of P8 nor the cell cycle arrest targets of P8 are known.

Prediction of efficiencies for diverse prime editing systems in multiple cell types.

Applications of prime editing are often limited due to insufficient efficiencies, and it can require substantial time and resources to determine the most efficient pegRNAs and prime editors (PEs) to generate a desired edit under various experimental conditions. Here, we evaluated prime editing efficiencies for a total of 338,996 pairs of pegRNAs including 3,979 epegRNAs and target sequences in an error-free manner. These datasets enabled a systematic determination of factors affecting prime editing efficiencies.

Massively parallel electro-optic sampling of space-encoded optical pulses for ultrafast multi-dimensional imaging.

High-speed and high-resolution imaging of surface profiles is critical for the investigation of various structures and mechanical dynamics of micro- and nano-scale devices. In particular, recent emergence of various nonlinear, transient and complex mechanical dynamics, such as anharmonic vibrations in mechanical resonators, has necessitated real-time surface deformation imaging with higher axial and lateral resolutions, speed, and dynamic range. However, real-time capturing of fast and complex mechanical dynamics has been challenging, and direct time-domain imaging of displacements and mechanical motions has been a missing element in studying full-field structural and dynamic behaviours.

The matricellular protein CCN5 induces apoptosis in myofibroblasts through SMAD7-mediated inhibition of NFκB.

We previously showed that the matricellular protein CCN5 reverses established cardiac fibrosis (CF) through inducing apoptosis in myofibroblasts (MyoFBs) but not in cardiomyocytes or fibroblasts (FBs). In this study, we set out to elucidate the molecular mechanisms underlying CCN5-mediated selective apoptosis of MyoFBs. We first observed that the apoptotic protein p53 and the anti-apoptotic protein NFκB are simultaneously induced in MyoFBs.

Comparative Pharmacodynamics of Three Different Botulinum Toxin Type A Preparations following Repeated Intramuscular Administration in Mice.

Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units.

Nitro-Group-Containing Thiopeptide Derivatives as Promising Agents to Target .

The US Centers for Disease Control and Prevention (CDC) lists as an urgent bacterial threat. Yet, only two drugs, vancomycin and fidaxomicin, are approved by the FDA for the treatment of infections as of this writing, while the global pipeline of new drugs is sparse at best. Thus, there is a clear and urgent need for new antibiotics against that organism.

Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection.

Background: There is a need for oral antibiotic agents that are effective against multidrug-resistant gram-negative uropathogens. Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem with activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase-producing and fluoroquinolone-resistant strains.

Methods: In this phase 3, international, double-blind, double-dummy trial, we evaluated the efficacy and safety of orally administered tebipenem pivoxil hydrobromide as compared with intravenous ertapenem in patients with complicated urinary tract infection or acute pyelonephritis.

Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children.

Objectives: Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children.

Dual Sensory Impairment and Cognitive Impairment in the Korean Longitudinal Elderly Cohort.

Objective: To investigate the effects of single sensory impairment (SSI; visual or auditory) or dual sensory impairment (DSI; visual and auditory) on dementia and longitudinal changes of neuropsychological test scores.

Methods: In this nationwide, prospective, community-based elderly cohort study, KLOSCAD (the Korean Longitudinal Study on Cognitive Aging and Dementia), 6,520 elderly individuals (58-101 years) representing the general population were included. We defined visual and auditory sensory impairment via self-report questionnaire: 932 had normal sensory function, 2,957 had an SSI, and 2,631 had a DSI.

Model-Based Prediction to Evaluate Residence Time of Hyaluronic Acid Based Dermal Fillers.

Dermal fillers are gel-type substances for nonsurgical medical-device use to achieve facial rejuvenation. Currently, the most widely used skin fillers are hyaluronic-acid-based dermal fillers. This study aimed to explain the change in the volume of injected dermal fillers by developing a mathematical kinetic model for various dermal fillers.

Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer.

Background: Recently, molecular classifications of gastric cancer (GC) have been proposed that include TP53 mutations and their functional activity. We aimed to demonstrate the correlation between p53 immunohistochemistry (IHC) and TP53 mutations as well as their clinicopathological significance in GC.

Methods: Deep targeted sequencing was performed using surgical or biopsy specimens from 120 patients with GC.

Unsupervised Cluster Analysis of Patients With Aortic Stenosis Reveals Distinct Population With Different Phenotypes and Outcomes.

Background: There is a lack of studies investigating the heterogeneity of patients with aortic stenosis (AS). We explored whether cluster analysis identifies distinct subgroups with different prognostic significances in AS.

Methods: Newly diagnosed patients with moderate or severe AS were prospectively enrolled between 2013 and 2016 (n=398, mean 71 years, 55% male).

Association of Total Reproductive Years With Incident Atrial Fibrillation, and Subsequent Ischemic Stroke in Women With Natural Menopause.

Background: The association of lifetime exposure to endogenous sex hormone with incident atrial fibrillation (AF) and subsequent ischemic stroke has never been studied.

Methods: This study involved 4 638 299 natural postmenopausal waomen aged ≥40 years without prior history of AF and with national breast cancer check-up between January 1, 2009 and December 31, 2014. The primary end point was incident AF, and the secondary end point was subsequent ischemic stroke once AF has developed.

Vibrio sp. dhg as a platform for the biorefinery of brown macroalgae.

Although brown macroalgae holds potential as an alternative feedstock, its utilization by conventional microbial platforms has been limited due to the inability to metabolize one of the principal sugars, alginate. Here, we isolate Vibrio sp. dhg, a fast-growing bacterium that can efficiently assimilate alginate.

Balloon Guide Catheter Is Beneficial in Endovascular Treatment Regardless of Mechanical Recanalization Modality.

Background and Purpose- Based on its mechanism, the use of balloon guide catheters (BGCs) may be beneficial during endovascular treatment, regardless of the type of mechanical recanalization modality used-stent retriever thrombectomy or thrombaspiration. We evaluated whether the use of BGCs can be beneficial regardless of the first-line mechanical endovascular modality used. Methods- We retrospectively reviewed consecutive acute stroke patients who underwent stent retriever thrombectomy or thrombaspiration from the prospectively maintained registries of 17 stroke centers nationwide.

Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care.

Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) require multiple wires connected to rigid sensors with strongly adherent interfaces to the skin. We introduce a pair of ultrathin, soft, skin-like electronic devices whose coordinated, wireless operation reproduces the functionality of these traditional technologies but bypasses their intrinsic limitations. The enabling advances in engineering science include designs that support wireless, battery-free operation; real-time, in-sensor data analytics; time-synchronized, continuous data streaming; soft mechanics and gentle adhesive interfaces to the skin; and compatibility with visual inspection and with medical imaging techniques used in the NICU.

Role of SIRT1 in Modulating Acetylation of the Sarco-Endoplasmic Reticulum Ca-ATPase in Heart Failure.

Rationale: SERCA2a, sarco-endoplasmic reticulum Ca-ATPase, is a critical determinant of cardiac function. Reduced level and activity of SERCA2a are major features of heart failure. Accordingly, intensive efforts have been made to develop efficient modalities for SERCA2a activation.

Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea.

Background: Antibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea.

Number of Stent Retriever Passes Associated With Futile Recanalization in Acute Stroke.

Background and Purpose- Stent retriever (SR) thrombectomy has become the mainstay of treatment of acute intracranial large artery occlusion. However, it is still not much known about the optimal limit of SR attempts for favorable outcome. We evaluated whether a specific number of SR passes for futile recanalization can be determined.

Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread.

The root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix.

Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease.

Objective: To investigate the effects of completed pregnancy with childbirth and incomplete pregnancy without childbirth on the late-life cognition and the risk of Alzheimer disease (AD) in women.

Methods: Using the pooled data of 3,549 women provided by 2 population-based cohort studies, we conducted logistic regression analyses to examine retrospectively the associations of completed and incomplete pregnancy with the risks of mild cognitive impairment and AD. For women without dementia, we also conducted analyses of covariance to examine the associations of completed and incomplete pregnancy with Mini-Mental State Examination (MMSE) score.

Rescue Stenting for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Multicenter Experience.

Background And Purpose: Effective rescue treatment has not yet been suggested in patients with mechanical thrombectomy (MT) failure. This study aimed to test whether rescue stenting (RS) improved clinical outcomes in MT-failed patients.

Methods: This is a retrospective analysis of the cohorts of the 16 comprehensive stroke centers between September 2010 and December 2015.

Applying Ultrasound-Guided Core Needle Biopsy for Diagnosis of Thyroid Masses: Preliminary Results From a Single Institution.

Objectives: The purpose of this study was to investigate the level of conclusive results obtained with ultrasound (US)-guided core needle biopsy (CNB) and how this method should be applied for diagnosis of thyroid nodules.

Methods: From January 2013 to November 2014, US-guided CNB was performed in 84 thyroid lesions of 83 patients. Based on CNB pathologic reports, thyroid nodules were divided into 2 categories: conclusive (nodules reaching a definite pathologic diagnosis suggesting benignity or malignancy) and inconclusive (nodules that were not able to reach a definite diagnosis because of ambiguous results).