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1.
Mol Cell ; 84(13): 2511-2524.e8, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38996460

ABSTRACT

BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression.


Subject(s)
Chromatin , Cryoelectron Microscopy , Humans , Chromatin/metabolism , Chromatin/genetics , Protein Multimerization , Binding Sites , Protein Binding , Transcription Factors/metabolism , Transcription Factors/genetics , Polymerization , HEK293 Cells , Gene Expression Regulation
2.
Proc Natl Acad Sci U S A ; 121(24): e2322009121, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38843187

ABSTRACT

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.


Subject(s)
Cell Differentiation , Lupus Erythematosus, Systemic , Osteopontin , Transcription Factors , Animals , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/pathology , Osteopontin/metabolism , Osteopontin/genetics , Mice , Humans , Transcription Factors/metabolism , Transcription Factors/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , T Follicular Helper Cells/immunology , T Follicular Helper Cells/metabolism , Female , Disease Models, Animal , Mice, Knockout
3.
Ann Surg ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39219553

ABSTRACT

OBJECTIVE: To evaluate the long-term outcomes of laparoscopic pylorus preserving gastrectomy (LPPG) with laparoscopic distal gastrectomy (LDG) for early gastric cancer (EGC). SUMMARY BACKGROUND DATA: PPG is considered as a function preserving surgery for EGC. However, there has been no multicenter randomized controlled trial comparing PPG with DG until now. METHODS: A multicenter randomized controlled trial (KLASS-04) with 256 patients with cT1N0M0 gastric cancer located in the mid portion of the stomach was conducted. The primary endpoint was the incidence of dumping syndrome at postoperative 1 year. Secondary endpoints included survival and recurrence, gallstone formation, nutritional parameters, gastroscopic findings, and quality of life (QOL) for 3 years. RESULTS: In the intention-to-treat analyses, there was no difference in the incidence of dumping syndrome at one year postoperatively (13.2% in LPPG vs. 15.8% in LDG, P=0.622). Gallstone formation after surgery was significantly lower in LPPG than in LDG (2.33% vs. 8.66%, P=0.026). Hemoglobin (+0.01 vs. -0.76 gm/dL, P<0.001) and serum protein (-0.15 vs. -0.35 gm/dL, P=0.002) were significantly preserved after LPPG. However, reflux esophagitis (17.8% vs. 6.3%, P=0.005) and grade IV delayed gastric emptying (16.3% vs. 3.9%, P=0.001) were more common in LPPG. Changes in body weight and postoperative QOL were not significantly different between groups. Three-year overall survival and disease-free survival were not different (1 case of recurrence of in each group, P=0.98). CONCLUSIONS: LPPG can be used as an alternative surgical option for cT1N0M0 gastric cancer in the mid portion of the stomach.

4.
Ann Surg ; 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38269605

ABSTRACT

OBJECTIVE: This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes. SUMMARY BACKGROUND DATA: The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG. METHODS: The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258). RESULTS: The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups. CONCLUSION: The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

5.
Ann Surg Oncol ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085549

ABSTRACT

BACKGROUND: Sentinel node navigation (SNN) has been known as the effective treatment for stomach-preserving surgery in early gastric cancer; however, SNN presents several technical difficulties in real practice. OBJECTIVE: This study aimed to evaluate the feasibility of regional lymphadenectomy omitting SNN, using the post hoc analysis of a randomized controlled trial. METHODS: Using data from the SENORITA trial that compared laparoscopic standard gastrectomy with lymphadenectomy and laparoscopic SNN, 237 patients who underwent SNN were included in this study. Tumor location was divided into longitudinal and circumferential directions. According to the location of the tumor, the presence or absence of lymph node (LN) metastases between sentinel and non-sentinel basins were analyzed. Proposed regional LN stations were defined as the closest area to the primary tumor. Sensitivities, specificities, positive predictive values, and negative predictive values (NPV) of SNN and regional lymphadenectomy were compared. RESULTS: Metastasis to non-sentinel basins with tumor-free in sentinel basins was observed in one patient (0.4%). The rate of LN metastasis to non-regional LN stations without regional LN metastasis was 2.5% (6/237). The sensitivity and NPV of SNN were found to be significantly higher than those of regional lymphadenectomy (96.8% vs. 80.6% [p = 0.016] and 99.5% vs. 97.2% [p = 0.021], respectively). CONCLUSIONS: This study showed that regional lymphadenectomy for stomach-preserving surgery, omitting SNN, was insufficient; therefore, SNN is required in stomach-preserving surgery.

6.
Gastrointest Endosc ; 100(1): 85-96.e9, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38447660

ABSTRACT

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from EUS-guided fine-needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.


Subject(s)
Carcinoma, Pancreatic Ductal , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Organoids , Pancreatic Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Albumins , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/genetics , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Organoids/pathology , Paclitaxel/administration & dosage , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/genetics , Precision Medicine/methods , Prospective Studies
7.
J Nanobiotechnology ; 22(1): 175, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609947

ABSTRACT

Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Liposomes , Nanoparticles , Cell Line , Ribonucleoproteins/genetics
8.
J Korean Med Sci ; 39(13): e120, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38599597

ABSTRACT

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.


Subject(s)
COVID-19 , Pandemics , Humans , Prevalence , Depression/epidemiology , COVID-19/epidemiology , Anxiety/epidemiology , Anxiety Disorders , Health Personnel , Republic of Korea/epidemiology
9.
J Adolesc ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39082197

ABSTRACT

INTRODUCTION: Research demonstrates that child maltreatment can negatively impact adolescent peer relationships. It is not well understood, however, how the type of maltreatment and its timing (when it occurs) affects the dimensions of peer relationship quality (i.e., companionship, conflict, satisfaction, and intimacy) and differences between genders. This study examines the effects of type and timing of child maltreatment on peer relationship quality, while also exploring the role of gender differences. METHODS: This study involved 851 adolescents (56.1% girls, 56.2% Black, and 26.8% low-income) drawn from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). We used Child Protective Services' information for the type and timing of child maltreatment, along with self-reports of peer relationship quality. Generalized Estimating Equations (GEEs) were conducted. RESULTS: Sexual abuse and neglect during adolescence were associated with less satisfaction and lower levels of companionship, respectively. Physical abuse during middle childhood was associated with lower levels of intimacy. We also found interactions between gender and type and timing of maltreatment. Compared to girls, boys exhibited lower levels of companionship and satisfaction if they experienced sexual abuse during adolescence. CONCLUSION: These findings suggest a need for maltreatment-prevention efforts targeting school-aged children and adolescents, as well as gender-sensitive interventions for high-risk boys with a history of maltreatment.

10.
Mol Cancer ; 22(1): 200, 2023 12 09.
Article in English | MEDLINE | ID: mdl-38066564

ABSTRACT

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.


Subject(s)
Lymphoma, Non-Hodgkin , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen , Humans , Antibodies , Antigens, CD19 , Epitopes/metabolism , Immunotherapy, Adoptive/adverse effects , Lymphoma, Non-Hodgkin/therapy , Lymphoma, Non-Hodgkin/metabolism , Neoplasm Recurrence, Local/metabolism , Receptors, Chimeric Antigen/metabolism , Receptors, Antigen, T-Cell/antagonists & inhibitors
11.
Mol Cell Proteomics ; 20: 100017, 2021.
Article in English | MEDLINE | ID: mdl-33592500

ABSTRACT

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. ELISA results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML cell-derived EVs could reflect essential leukemia biology.


Subject(s)
Biomarkers, Tumor/metabolism , Extracellular Vesicles/metabolism , Leukemia, Myeloid, Acute/metabolism , Adolescent , Adult , Aged , Antigens, CD/genetics , Antigens, CD/metabolism , Cells, Cultured , Female , Humans , Male , Middle Aged , Protein Kinases/metabolism , Proteomics , Young Adult
12.
Gastroenterology ; 161(3): 953-967.e15, 2021 09.
Article in English | MEDLINE | ID: mdl-34116028

ABSTRACT

BACKGROUND & AIMS: WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. METHODS: Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. RESULTS: Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. CONCLUSIONS: WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.


Subject(s)
Cell Transformation, Neoplastic/metabolism , Gastric Mucosa/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Interleukin-33/metabolism , Precancerous Conditions/metabolism , Stomach Neoplasms/metabolism , WAP Four-Disulfide Core Domain Protein 2/metabolism , Animals , Atrophy , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Disease Models, Animal , Gastric Mucosa/ultrastructure , Gene Expression Profiling , Intercellular Signaling Peptides and Proteins/genetics , Interleukin-33/genetics , Macrophages/metabolism , Metaplasia , Mice, Inbred C57BL , Mice, Knockout , Phenotype , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Transcriptome , Up-Regulation , WAP Four-Disulfide Core Domain Protein 2/genetics
13.
Opt Express ; 30(24): 43534-43542, 2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36523049

ABSTRACT

The high-dimensional encoding of single photons can offer various possibilities for enhancing quantum information processing. This work experimentally demonstrates the quantum interference of an engineered multidimensional quantum state through the space-division multiplexing of a heralded single-photon state with a spatial light modulator (SLM) and spatial-mode mixing of a single photon through a long multimode fiber (MMF). In our experiment, the heralded single photon generated from a warm 87Rb atomic ensemble was bright, robust, and long-coherent. The multidimensional spatial quantum state of the long-coherent single photon was transported through a 4-m-long MMF and arbitrarily controlled using the SLM. We observed the quantum interference of a single-photon multidimensional spatial quantum state with a visibility of >95%. These results may have potential applications in quantum information processing, for example, in photonic variational quantum eigensolve with high-dimensional single photons and realizing high information capacity per photon for quantum communication.

14.
Opt Express ; 30(13): 23868-23877, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-36225059

ABSTRACT

The realization of a narrowband photonic quantum source based on an atomic device is considered essential in the practical development of photonic quantum information science and technology. In this study, we present the first step toward the development of a photon-pair source based on a microfabricated Cs atomic vapor cell. Time-correlated photon pairs from the millimeter-scale Cs vapor cell are emitted via the spontaneous four-wave mixing process of the cascade-type 6S1/2-6P3/2-8S1/2 transition of 133Cs. The maximum normalized cross-correlation value between the signal and idler photons is measured as 622(8) under a weak pump power of 10 µ;W. Our photon source violates the Cauchy-Schwartz inequality by a factor of >105. We believe that our approach has very important applications in the context of realizing practical scalable quantum networks based on atom-photon interactions.

15.
BMC Public Health ; 22(1): 2392, 2022 12 20.
Article in English | MEDLINE | ID: mdl-36539721

ABSTRACT

Undernutrition is a risk factor of tuberculosis (TB), but the association between duration of undernutrition and occurrence of TB is inconclusive. The objective of this study was to determine whether there is a difference in occurrence of TB according to the duration of undernutrition expressed as accumulated number of underweight in Republic of Korea, an intermediate TB burden country. The National Health Insurance database was used.Eligible subjects were individuals who received a national health examination between 1 and 2009 and 31 December 2010, and who also had received health examinations for four consecutive years prior to 2009.Finally included individuals in the analysis were followed until 31 December 2017. Accumulated number of underweight was defined as the number of times recorded as underweight over four consecutive years. The outcome of the study was newly diagnosed TB according to accumulated number of underweight. Among a study population of 2,396,434, TB was identified in 9,322 (3.89%) cases. The highest accumulated number of underweight was significantly associated with occurrence of TB (adjusted hazard ratio [aHR] 2.563, 95% CI 2.319-2.833). This association remained consistent after adjusting for demographic factors and underlying diseases (aHR 3.326, 95% CI 3.004-3.84). In stratified analysis based on age, sex, diabetes (DM), hypertension (HTN), and waist circumference (WC) in metabolic syndrome (MS), age and sex were identified as effect modifiers. Occurrence of TB was significantly higher in the group with the highest accumulated number of underweight under 65 years of age.


Subject(s)
Malnutrition , Tuberculosis , Humans , Thinness/epidemiology , Retrospective Studies , Tuberculosis/epidemiology , Tuberculosis/complications , Risk Factors , Malnutrition/epidemiology , Malnutrition/complications
16.
BMC Anesthesiol ; 22(1): 166, 2022 05 30.
Article in English | MEDLINE | ID: mdl-35637437

ABSTRACT

BACKGROUND: The head-elevated laryngoscopy position has been described to be optimal for intubation, particularly in obese patients and those with anticipated difficult airways. Horizontal alignment of the external auditory meatus and sternal notch (AM-S) can be used as endpoints for optimal positioning. Thus, we aligned the head-elevated position with the AM-S in the horizontal plane and evaluated its effect on laryngeal visualization and ease of intubation using a McGrath MAC videolaryngoscope in patients with a simulated difficult airway. METHODS: Sixty-four patients were included in this prospective, crossover, randomized controlled trial. A cervical collar was used to restrict neck movement and mouth opening. The head-elevated position was achieved by raising the back section of the operation room table and ensuring that the end point was horizontally aligned with the AM-S (table-ramp method). The laryngeal view was randomly assessed in both head-flat and head-elevated positions based on the percentage of glottic opening (POGO) score and modified Cormack-Lehane (MCL) grade. External laryngeal manipulation was not permitted when laryngeal visualization was scored. The trachea was intubated only once (in the second position). The ease of intubation was assessed based on the need for optimization maneuvers, intubation difficulty scale (IDS) scores and time to intubation. RESULTS: The mean table-ramp angle required to achieve the horizontal alignment of AM-S was 17.5 ± 4.1°. The mean POGO score improved significantly in the head-elevated position (59.4 ± 23.8%) when compared with the head-flat position (37.5 ± 24%) (P <  0.0001). MCL grade 1 or 2a was achieved in 56 (85.9%) and 28 (43.7%) of patients in the head-elevated and head-flat positions, respectively (P <  0.0001). Optimization maneuvers for intubation were required in 7 (21.9%) and 17 (53.1%) patients in the head-elevated and head-flat positions, respectively (P <  0.0001). The IDS scores and time to intubation did not differ significantly between the two positions. CONCLUSION: In the head-elevated position, aligning the AM-S in the horizontal plane consistently improved laryngeal visualization without worsening the view when the McGrath MAC videolaryngoscope was used in patients with simulated difficult airways. It also improved the ease of intubation, which reduced the need for optimization maneuvers. TRIAL REGISTRATION: This trial was registered with www. CLINICALTRIALS: gov , NCT04716218 , on 20/01/2021.


Subject(s)
Laryngoscopes , Cross-Over Studies , Humans , Intubation, Intratracheal/methods , Laryngoscopy/methods , Prospective Studies
17.
J Korean Med Sci ; 37(6): e49, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35166085

ABSTRACT

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, heavy workload of healthcare workers (HCWs) is a concern. This study investigated the workload of HCWs responding to the COVID-19 outbreak in South Korea. METHODS: A nationwide cross-sectional survey was conducted from September 16 to October 15, 2020, involving 16 healthcare facilities (4 public medical centers, 12 tertiary-care hospitals) that provide treatment for COVID-19 patients. RESULTS: Public medical centers provided the majority (69.4%) of total hospital beds for COVID-19 patients (n = 611), on the other hand, tertiary care hospitals provided the majority (78.9%) of critical care beds (n = 57). The number of beds per doctor (median [IQR]) in public medical centers was higher than in tertiary care hospitals (20.2 [13.0, 29.4] versus 3.0 [1.3, 6.6], P = 0.006). Infectious Diseases physicians are mostly (80%) involved among attending physicians. The number of nurses per patient (median [interquartile range, IQR]) in tertiary-care hospitals was higher than in public medical centers (4.6 [3.4-5] vs. 1.1 [0.8-2.1], P = 0.089). The median number of nurses per patient for COVID-19 patients was higher than the highest national standard in South Korea (3.8 vs. 2 for critical care). All participating healthcare facilities were also operating screening centers, for which a median of 2 doctors, 5 nurses, and 2 administrating staff were necessary. CONCLUSION: As the severity of COVID-19 patients increases, the number of HCWs required increases. Because the workload of HCWs responding to the COVID-19 outbreak is much greater than other situations, a workforce management plan regarding this perspective is required to prevent burnout of HCWs.


Subject(s)
COVID-19/epidemiology , Health Personnel , SARS-CoV-2 , Workload , Cross-Sectional Studies , Health Facilities , Humans , Republic of Korea/epidemiology , Surveys and Questionnaires
18.
Minim Invasive Ther Allied Technol ; 31(4): 580-586, 2022 Apr.
Article in English | MEDLINE | ID: mdl-33269633

ABSTRACT

BACKGROUND: The aim of this study was to compare the 1 year incidence of Petersen's hernia between individuals who were treated with the jejunal mesentery fixing (Mefix) method and those with the closure of Petersen's space method. MATERIAL AND METHODS: We retrospectively collected clinical data of patients who underwent gastrectomy for gastric cancers with the closure of Petersen's space defect (N = 49) and Mefix (N = 26). The Mefix method was performed by fixing the jejunal mesentery (jejunojejunostomy below 30 cm) to the transverse mesocolon using nonabsorbable barbed sutures. RESULTS: The procedure time for mesentery fixing (3.7 ± 1.1 mins) was significantly shorter than that for Petersen's space closure (7.5 ± 1.5 mins) (p < .001) although the operation times were similar between the two groups. There was no incidence of Petersen's hernias postoperatively in both groups. One case of reoperation was reported in the closure group due to small bowel obstruction by kinking of the jejunojejunostomy. CONCLUSION: We found no occurrence of Petersen's hernias postoperatively in either group. We also found that the Mefix method was faster and easier to perform than the closure method. The Mefix method is an excellent alternative method to prevent the occurrence of Petersen's hernia after B-II or Roux-en-Y reconstruction.


Subject(s)
Gastric Bypass , Hernia, Abdominal , Laparoscopy , Obesity, Morbid , Gastric Bypass/methods , Hernia, Abdominal/epidemiology , Hernia, Abdominal/etiology , Hernia, Abdominal/surgery , Humans , Laparoscopy/methods , Mesentery/surgery , Obesity, Morbid/complications , Retrospective Studies
19.
J Ethn Subst Abuse ; : 1-18, 2022 May 05.
Article in English | MEDLINE | ID: mdl-35510907

ABSTRACT

This study examined the associations among child abuse types, family/peer substance use, and adolescent substance use, as well as testing whether these associations vary by race. The sample was derived from the Longitudinal Studies of Child Abuse and Neglect (N = 562). Child sexual abuse, family substance use, and peer substance use were associated with a higher likelihood of adolescent substance use. Sexual abuse was more strongly associated with substance use in Black youth than in White youth. Conversely, greater peer substance use had a stronger association with substance use in White youth than in Black youth.

20.
Nat Mater ; 19(9): 980-985, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32601483

ABSTRACT

Antiferromagnetic spin waves have been predicted to offer substantial functionalities for magnonic applications due to the existence of two distinct polarizations, the right-handed and left-handed modes, as well as their ultrafast dynamics. However, experimental investigations have been hampered by the field-immunity of antiferromagnets. Ferrimagnets have been shown to be an alternative platform to study antiferromagnetic spin dynamics. Here we investigate thermally excited spin waves in ferrimagnets across the magnetization compensation and angular momentum compensation temperatures using Brillouin light scattering. Our results show that right-handed and left-handed modes intersect at the angular momentum compensation temperature where pure antiferromagnetic spin waves are expected. A field-induced shift of the mode-crossing point from the angular momentum compensation temperature and the gyromagnetic reversal reveal hitherto unrecognized properties of ferrimagnetic dynamics. We also provide a theoretical understanding of our experimental results. Our work demonstrates important aspects of the physics of ferrimagnetic spin waves and opens up the attractive possibility of ferrimagnet-based magnonic devices.

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