Purpose: This study aimed to identify the concrete educational needs of visiting nurses working in a community health setting in Korea. Methods: We conducted four focus group interviews from October 7 to October 18, 2021. Twenty-five visiting nurses who worked in public health centers were recruited through purposive sampling. A qualitative content analysis was used to analyze the interview data. Results: The demands of educational contents for visiting nurse safety management practical training were: (1) coping with physical and verbal violence, (2) coping with sexual violence, (3) infection control for infectious diseases with a high prevalence in the community, and (4) preventing and coping with animal bites during home visits. In addition, visiting nurses suggested training programs that comprised: (1) case-based learning, (2) short video clips, and (3) recurrent integrated education. Conclusion Safety management training programs for visiting nurses should be implemented to the extent that they add no burden on their workload and are easily accessible at any time. In addition, training programs should be based on actual cases and be focused on contents that can be applied in home visit situations. A practical safety management training program should be developed based on the educational needs of visiting nurses, as identified through this study.

Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials. However, to date none of these HGF/cMET inhibitors have shown significant efficacy in clinical trials. Furthermore, no receptor tyrosine kinase inhibitors primarily targeting cMET have been approved. Given that neutralization of HGF or cMET does not cause significant adverse effects, inhibition of the HGF/cMET signaling pathway appears to be safe. In this review, we summarized the completed and ongoing clinical trials testing antibody- or protein-based anticancer drugs targeting cMET and HGF.
Antibodies ; Carcinogenesis ; Drug Resistance ; Hepatocyte Growth Factor ; Humans ; Neoplasm Metastasis ; Protein-Tyrosine Kinases

The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. NT-proBNP exhibits heavy O-linked glycosylation, and it is quite difficult to develop an antibody that exhibits glycosylation-independent binding. We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. The epitope was defined as Gly63-Lys68 based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. The nearest O-glycosylation residues are Thr58 and Thr71; therefore, four amino acid residues intervene between the epitope and those residues in both directions. In conclusion, we report that an antibody reactive to Gly63-Lys68 of NT-proBNP exhibits O-glycosylation-independent binding.
Amino Acid Sequence ; Animals ; Antibodies/*immunology ; Antigen-Antibody Reactions ; Epitope Mapping ; Epitopes/chemistry/genetics/*immunology ; Glycosylation ; HEK293 Cells ; Heart Failure/immunology ; Humans ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Natriuretic Peptide, Brain/chemistry/genetics/*immunology ; Peptide Fragments/chemistry/genetics/*immunology ; Rabbits ; Recombinant Fusion Proteins/chemistry/genetics/immunology

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.
Adoptive Transfer ; Animals ; Autoimmune Diseases ; Cell- and Tissue-Based Therapy* ; Disease Progression ; Graft vs Host Disease ; Humans ; In Vitro Techniques ; Kidney ; Leukemia ; Liver ; Mice ; T-Lymphocytes ; T-Lymphocytes, Regulatory* ; Transplantation ; Transplants

We present a bispecific antibody that recognizes an antigen and a hapten and can be applied to various biological assays, including immunoblotting and immunoprecipitation. In immunoblot analysis of serum, an anti-C5 x anti-cotinine bispecific tandem single-chain variable fragment (scFv)-Fc fusion protein and cotinine-conjugated horseradish peroxidase (HRP) generated a clean signal without the high background that was observed in a parallel experiment using HRP-conjugated goat anti-rabbit immunoglobulin G (Fc-specific) antibody. In immunoprecipitation analysis of serum, use of the bispecific tandem scFv-Fc fusion protein and cotinine-crosslinked magnetic beads significantly reduced the amount of protein contaminants compared with a parallel experiment done with protein A agarose beads. In subsequent immunoblot analysis, use of cotinine-HRP as the secondary probe instead of HRP-conjugated goat anti-rabbit IgG (Fc-specific) antibody successfully eliminated the band corresponding to the bispecific tandem scFv-Fc fusion protein.
Animals ; Antibodies, Bispecific/*immunology ; HEK293 Cells ; Haptens/*immunology ; Humans ; Immunoblotting/*methods ; Immunoprecipitation/methods ; Rabbits ; Single-Chain Antibodies/immunology

The complement system is a part of the innate immune system that potentiates the ability of antibodies and phagocytic cells to clear microbes and damaged cells. The complement system consists of a number of proteins circulating as inactive precursors. It is stimulated mainly by three pathways: the classical pathway, the alternative pathway, and the lectin pathway. There are many genetic polymorphisms in this system, which can over-activate the immune system. In this study, we collected the polymorphisms reported to over-activate complement cascades that affect the immune system and induce autoimmune diseases.
Antibodies ; Autoimmune Diseases ; Complement System Proteins* ; Immune System ; Phagocytes ; Polymorphism, Genetic*

To identify the interchangeability of V(H) and V(L) framework region (FR) residues, we artificially introduced random mutations at all residue positions in a chicken monoclonal antibody, which has only one functional V(H) and Vλ gene. When we classified the amino acids into 5 groups by their physicochemical properties, all FR residues could be replaced by another group except L23 (C), H36 (W), H86 (D), H104 (G), and H106 (G). Eighty-two (50.9%), 48 (29.8%), 17 (10.6%), and 9 FR residues (5.6%) could be replaced by 4, 3, 2, and 1 group(s), individually, without significant loss of reactivity. We also confirmed a similar level of versatility with 2 different chicken antibodies. This high level of versatility on FR residues has not been predicted because it has not been observed in the 150 chicken antibodies that we previously generated or in the 1,269 naïve chicken V(H) sequences publically available. In conclusion, chicken antibody FR residues are highly interchangeable and this property can be applied for improving the physicochemical property of antibody including thermal stability, solubility and viscosity.
Amino Acids ; Antibodies ; Chickens* ; Immunoglobulin Variable Region ; Solubility ; Somatic Hypermutation, Immunoglobulin ; Viscosity

Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation in vitro and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the in vitro and in vivo data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.
Animals ; Antibodies, Neutralizing* ; Cell Line ; Cell Proliferation ; Glioblastoma ; Half-Life ; Hepatocyte Growth Factor ; Heterografts ; Humans* ; In Vitro Techniques ; Macaca fascicularis ; Mice ; Mice, Nude ; Pharmacokinetics ; Phosphorylation ; Phosphotransferases ; Toxicokinetics

The C-terminal domain of RNA polymerase II is an unusual series of repeated residues appended to the C-terminus of the largest subunit and serves as a flexible binding scaffold for numerous nuclear factors. The binding of these factors is determined by the phosphorylation patterns on the repeats in the domain. In this study, we generated a synthetic antibody library by replacing the third heavy chain complementarity-determining region of an anti-HER2 (human epidermal growth factor receptor 2) antibody (trastuzumab) with artificial sequences of 7–18 amino-acid residues. From this library, antibodies were selected that were specific to serine phosphopeptides that represent typical phosphorylation patterns on the functional unit (YSPTSPS)₂ of the RNA polymerase II C-terminal domain (CTD). Antibody clones pCTD-1stS2 and pCTD-2ndS2 showed specificity for peptides with phosphoserine at the second residues of the first or second heptamer repeat, respectively. Additional clones specifically reacted to peptides with phosphoserine at the fifth serine of the first repeat (pCTD-1stS5), the seventh residue of the first repeat and fifth residue of the second repeat (pCTD-S7S5) or the seventh residue of either the first or second repeat (pCTD-S7). All of these antibody clones successfully reacted to RNA polymerase II in immunoblot analysis. Interestingly, pCTD-2ndS2 precipitated predominately RNA polymerase II from the exonic regions of genes in genome-wide chromatin immunoprecipitation sequencing analysis, which suggests that the phosphoserine at the second residue of the second repeat of the functional unit (YSPTSPS)2 is a mediator of exon definition.
Antibodies ; Chromatin Immunoprecipitation ; Clone Cells ; Complementarity Determining Regions ; DNA-Directed RNA Polymerases* ; Exons* ; Peptides ; Phosphopeptides ; Phosphorylation* ; Phosphoserine ; Receptor, Epidermal Growth Factor ; RNA Polymerase II* ; RNA* ; Sensitivity and Specificity ; Serine

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the “Stroke Statistics in Korea” project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.
Adult ; Aged ; Alcohol Drinking ; Ambulances ; Atrial Fibrillation ; Cerebral Hemorrhage ; Emergency Medical Services ; Emergency Service, Hospital ; Epidemiology ; Female ; Hemorrhage ; Hope ; Humans ; Hypertension ; Incidence ; Korea ; Male ; Mortality ; Prevalence ; Reperfusion ; Risk Factors ; Smoke ; Smoking ; Stroke ; Subarachnoid Hemorrhage ; Writing