Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing.

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null-homozygote (N-H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles.

Hepatocytes coordinate immune evasion in cancer via release of serum amyloid A proteins.

T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/STAT3 and secretion of serum amyloid A (SAA) proteins 1 and 2 as important regulators of T cell surveillance of extrahepatic tumors.

A Chronic Increase in Blood-Brain Barrier Permeability Facilitates Intraneuronal Deposition of Exogenous Bloodborne Amyloid-Beta1-42 Peptide in the Brain and Leads to Alzheimer's Disease-Relevant Cognitive Changes in a Mouse Model.

Background: Increased blood-brain barrier (BBB) permeability and amyloid-β (Aβ) peptides (especially Aβ1-42) (Aβ42) have been linked to Alzheimer's disease (AD) pathogenesis, but the nature of their involvement in AD-related neuropathological changes leading to cognitive changes remains poorly understood.

Objective: To test the hypothesis that chronic extravasation of bloodborne Aβ42 peptide and brain-reactive autoantibodies and their entry into the brain parenchyma via a permeable BBB contribute to AD-related pathological changes and cognitive changes in a mouse model.

Methods: The BBB was rendered chronically permeable through repeated injections of Pertussis toxin (PT), and soluble monomeric, fluorescein isothiocyanate (FITC)-labeled or unlabeled Aβ42 was injected into the tail-vein of 10-month-old male CD1 mice at designated intervals spanning ∼3 months.

Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1.

Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the myeloid compartment as a therapeutic vulnerability in mouse models of pancreatic cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor Dectin-1 and the TNF receptor superfamily member CD40.

Clinicians' Prediction of Survival and Prognostic Confidence in Patients with Advanced Cancer in Three East Asian Countries.

Little is known about accuracy and confidence of clinicians' prediction of survival (CPS) in East-Asian countries. We aimed to examine accuracy of CPS for 7-, 21-, and 42-day survival in palliative inpatients and its association with prognostic confidence. An international prospective cohort study in Japan (JP), Korea (KR), and Taiwan (TW).

Nanoscale, antigen encounter-dependent, IL-12 delivery by CAR T cells plus PD-L1 blockade for cancer treatment.

Background: Chimeric antigen receptor (CAR)-T cell therapies for the treatment of hematological malignancies experienced tremendous progress in the last decade. However, essential limitations need to be addressed to further improve efficacy and reduce toxicity to assure CAR-T cell persistence, trafficking to the tumor site, resistance to an hostile tumor microenvironment (TME), and containment of toxicity restricting production of powerful but potentially toxic bioproducts to the TME; the last could be achieved through contextual release upon tumor antigen encounter of factors capable of converting an immune suppressive TME into one conducive to immune rejection.

Methods: We created an HER2-targeting CAR-T (RB-312) using a clustered regularly interspaced short palindromic repeats (CRISPR) activation (CRISPRa) system, which induces the expression of the IL-12 heterodimer via conditional transcription of its two endogenous subunits p35 and p40.

[Detection of Monosodium Urate Crystal of Hand and Wrist in Suspected Gouty Arthritis Patients on Dual-Energy CT and Relationship with Serum Urate Level].

Purpose: We retrospectively investigated the characteristics of patients with monosodium urate (MSU) deposits of the hand and wrist on dual-energy CT (DECT) compared to those without. We also attempted to determine the pattern of MSU distribution in DECT.

Materials And Methods: In total, 93 patients were included who had undergone DECT for evaluation of the hand or wrist pain under the clinical impression of gouty arthritis.

The dynamic nature of the coronavirus receptor, angiotensin-converting enzyme 2 (ACE2) in differentiating airway epithelia.

Once inhaled, SARS-CoV-2 particles enter respiratory ciliated cells by interacting with angiotensin converting enzyme 2 (ACE2). Understanding the nature of ACE2 within airway tissue has become a recent focus particularly in light of the COVID-19 pandemic. Airway mucociliary tissue was generated using primary human nasal epithelial cells and the air-liquid interface (ALI) model of differentiation.

The Effect of Mechanical Tongue Cleaning on Oral Malodor and Tongue Coating.

Background: Mechanical tongue cleaning is an important oral hygiene procedure; it is known that a significant cause of volatile sulfur compounds (VSCs), a major component of bad breath, is due to the bacteria coating the tongue. This study was conducted to identify the effect of mechanical tongue cleaning on reducing bad breath and tongue coating.

Methods: Various mechanical tongue-cleaning methods were studied, including removing tongue coating using a toothbrush, removing tongue coating using a tongue scraper, and removing tongue coating using a toothbrush and a tongue scraper together.

Contextual reprogramming of CAR-T cells for treatment of HER2 cancers.

Background: Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells combined with checkpoint inhibition may prevent T cell exhaustion and improve clinical outcomes. However, the approach is limited by cumulative costs and toxicities.

Methods: To overcome this drawback, we created a CAR-T (RB-340-1) that unites in one product the two modalities: a CRISPR interference-(CRISPRi) circuit prevents programmed cell death protein 1 (PD-1) expression upon antigen-encounter.

Determination of Residual Triflumezopyrim Insecticide in Agricultural Products through a Modified QuEChERS Method.

A rapid and simple analytical method for triflumezopyrim, a new class of mesoionic insecticides and commercialized molecules from DuPont, was developed with a modified QuEChERS method. The pH adjustment was used to improve the extraction efficiency of acetonitrile solvent, and dispersive solid-phase extraction was employed for the clean-up process. The five selected food commodities were used to verify the present optimized method, which displayed good linearity with an excellent correlation coefficient ( = 0.

"The surprise questions" using variable time frames in hospitalized patients with advanced cancer.

Objective: Several studies supported the usefulness of "the surprise question" in terms of 1-year mortality of patients. "The surprise question" requires a "Yes" or "No" answer to the question "Would I be surprised if this patient died in [specific time frame]." However, the 1-year time frame is often too long for advanced cancer patients seen by palliative care personnel.

Repetitive Transcranial Magnetic Stimulation Enhances Recovery in Central Cord Syndrome Patients.

Objective: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on neurological and functional recovery in patients with central cord syndrome (CCS) involving the upper extremities between the treated and non-treated sides of the treated group and whether the outcomes are comparable to that of the untreated control group.

Methods: Nineteen CCS patients were treated with high-frequency (20 Hz) rTMS over the motor cortex for 5 days. The stimulation side was randomly selected, and all the subjects received conventional occupational therapy during the rTMS-treatment period.

Sarcopenia and Hip-Structure Analysis Variables in Korean Elderly Population.

The purpose of this study is comparing the hip-structure analysis (HSA) variables with the skeletal muscle index (SMI) in elderly patients with sarcopenia using nationwide representative data on the Republic of Korea (ROK). The survey data were collected from household interviews and direct standardized physical examinations conducted in specially equipped mobile examination centers. The data were collected in 2008 from 9744 participants.

Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy.

Allogeneic natural killer (NK) cell therapy is a potential therapeutic approach for a variety of solid tumors. We established an expansion method for large-scale production of highly purified and functionally active NK cells, as well as a freezing medium for the expanded NK cells. In the present study, we assessed the effect of cryopreservation on the expanded NK cells in regards to viability, phenotype, and anti-tumor activity.

Malnutrition and chronic inflammation as risk factors for sarcopenia in elderly patients with hip fracture.

Background And Objectives: To evaluate malnutrition and chronic inflammation as risk factors for sarcopenia in elderly patients with hip fractures, as defined by the criteria of the Asian Working Group on Sarcopenia (AWGS).

Methods And Study Design: A total of 327 elderly patients with hip fractures were enrolled in this retrospective observational study. The main outcome measure was the nutritional status and nutritional risk factors for sarcopenia in elderly patients.

Relationship between water intake and skeletal muscle mass in elderly Koreans: A nationwide population-based study.

Objectives: The purposes of this study were to evaluate the correlation between sarcopenia and water intake and investigate lack of daily water intake in the presence of sarcopenia in an elderly population.

Methods: Data from 3656 participants (1582 men and 2074 women) were analyzed using the Korea National Health and Nutrition Examination Survey. Sarcopenia was defined in accordance with the criteria of the Asia Working Group for Sarcopenia.

High prevalence of sarcopenia among binge drinking elderly women: a nationwide population-based study.

Background: Alcohol consumption is considered a risk factor for sarcopenia, but the association between alcohol consumption and the prevalence of sarcopenia has not been evaluated in detail. This study was to identify the relationship between alcohol drinking patterns and the prevalence of sarcopenia in the elderly Korean population.

Methods: The cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey.

Mean Hand Grip Strength and Cut-off Value for Sarcopenia in Korean Adults Using KNHANES VI.

The purpose of this study was to report age- and gender-specific distribution of the hand grip strength (HGS) using data from the Korea National Health and Nutrition Examination Survey (KNHANES) VI-3 (2015) survey and determine cut-off values for low muscle strength of HGS of Koreans. Of a total of 7,380 participants, 4,553 were subjected to measurements of HGS, including 1,997 men and 2,556 women with a mean age of 49.3 years (range, 19-80 years).

Fanconi anemia protein FANCD2 is activated by AICAR, a modulator of AMPK and cellular energy metabolism.

FANCD2 is a pivotal molecule in the pathogenesis of Fanconi anemia (FA), an autosomal recessive human syndrome with diverse clinical phenotypes, including cancer predisposition, short stature, and hematological abnormalities. In our previous study, we detected the functional association of FANC proteins, whose mutations are responsible for the onset of FA, with AMPK in response to DNA interstrand crosslinking lesions. Because AMPK is well known as a critical sensing molecule for cellular energy levels, we checked whether FANCD2 activation occurs after treatments affecting AMPK and/or cellular energy status.

PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front.

Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts.

Local Immune Responses in Children and Adults with Allergic and Nonallergic Rhinitis.

Background: Allergic rhinitis (AR) is the most common allergic disease but little is known about the difference of local immune responses in children and adults with AR.

Objective: To compare local immune responses between children and adults with AR and nonallergic rhinitis (NAR), and to investigate whether the association of local and systemic immune responses is different between the two age groups.

Methods: Fifty-one patients with chronic rhinitis were enrolled and grouped into children (N = 27, mean age 7.

Phase I Study of Random Healthy Donor-Derived Allogeneic Natural Killer Cell Therapy in Patients with Malignant Lymphoma or Advanced Solid Tumors.

Natural killer (NK) cells with mismatched killer cell immunoglobulin-like receptor-ligand pairs have shown efficacy and been proven safe in treatment of cancer patients. Ex vivo-expanded and highly activated NK cells (MG4101) had been generated under good manufacturing practice conditions, which demonstrated potent anticancer activity in vitro and in vivo in preclinical studies. The current phase I clinical trial was designed to evaluate safety and possible clinical efficacy of repetitive administrations of MG4101 derived from random unrelated healthy donors into patients with malignant lymphoma or advanced, recurrent solid tumors.