Drawing Guideline for JKMS Manuscripts (06): Scatter Plot.

The appropriate plot effectively conveys the author's conclusions to the readers. Journal of Korean Medical Science is providing a series of guidelines to show you how to make consistent and excellent plots more easily. In this article, we introduce scatter plots and more.

Association Between Flexible Work Arrangement and Sleep Problems Among Paid Workers: Using 6th Korean Working Conditions Survey.

Background: As social distancing persists and interest in work-life balance grows, more companies are adopting flexible work policies. While there have been studies on sleep disorders associated with different types of work, such as shift work, research exploring the relationship between flexible work schedules and sleep disorders is still limited, particularly among Korean workers. Methods: We performed a secondary analysis of the 6th Korean Working Conditions Survey, focusing on 31,243 paid workers out of a total of 50,538 participants. We defined flexible workers as those who set their own working hours. Sleep disorders were divided into three categories: 'difficulty falling asleep,' 'frequent waking during sleep,' and 'waking up feeling exhausted and fatigued.' Using scores derived from three specific symptoms, the Minimal Insomnia Symptoms Scale (MISS) was calculated to assess the prevalence of insomnia. We used chi-square tests to analyze demographic and job-related differences. A multivariate logistic regression analysis was employed to identify any relationship between flexible work schedules and sleep disorders. Results: Significant differences were found between flexible and non-flexible workers regarding age, income level, education level, and job type. Flexible workers reported sleep-related symptoms significantly more often. The odds ratio for insomnia was 1.40 (95% CI 1.21-1.61). For males, the odds ratio was 1.68 (1.36-2.08). Conclusion: This study establishes a correlation between flexible work schedules and sleep disorders among Korean salaried workers. Potential causes could include changes in circadian rhythm, increased work demands, and extended working hours. To precisely determine causality and associated diseases, further research is required.

Low-threshold 2†µm InAs/InP quantum dash lasers enabled by punctuated growth.

2 µm photonics and optoelectronics is promising for potential applications such as optical communications, LiDAR, and chemical sensing. While the research on 2 µm detectors is on the rise, the development of InP-based 2 µm gain materials with 0D nanostructures is rather stalled. Here, we demonstrate low-threshold, continuous wave lasing at 2 µm wavelength from InAs quantum dash/InP lasers enabled by punctuated growth of the quantum structure. We demonstrate low threshold current densities from the 7.1 µm width ridge-waveguide lasers, with values of 657, 1183, and 1944 A/cm2 under short pulse wave (SPW), quasi-continuous wave (QCW), and continuous wave operation. The lasers also exhibited good thermal stability, with a characteristic temperature T0 of 43 K under SPW mode. The lasing spectra is centered at 1.97 µm, coinciding with the ground-state emission observed from photoluminescence studies. We believe that the InAs quantum dash/InP lasers emitting near 2 µm will be a key enabling technology for 2 µm communication and sensing.

Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases.

Genetic neuromuscular diseases are clinically and genetically heterogeneous genetic disorders that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study aimed to identify pathogenic variants, calculate carrier frequency, and predict the genetic prevalence of autosomal recessive neuromuscular diseases (AR-NMDs). We selected 268 AR-NMD genes and analyzed their genetic variants sourced from the gnomAD database. After identifying the pathogenic variants using an algorithm, we calculated the carrier frequency and predicted the genetic prevalence of AR-NMDs. In total, 10,887 pathogenic variants were identified, including 3848 literature verified and 7039 manually verified variants. In the global population, the carrier frequency of AR-NMDs is 32.9%, with variations across subpopulations ranging from 22.4% in the Finnish population to 36.2% in the non-Finnish European population. The predicted genetic prevalence of AR-NMDs was estimated to be 24.3 cases per 100,000 individuals worldwide, with variations across subpopulations ranging from 26.5 to 41.4 cases per 100,000 individuals in the Latino/Admixed American and the Ashkenazi Jewish populations, respectively. The AR-NMD gene with the highest carrier frequency was GAA (1.3%) and the variant with the highest allele frequency was c.-32-13 T>G in GAA with 0.0033 in the global population. Our study revealed a higher-than-expected frequency of AR-NMD carriers, constituting approximately one-third of the global population, highlighting ethnic heterogeneity in genetic susceptibility.

Beyond working hours: the association between long working hours, the use of work-related communication devices outside regular working hours, and anxiety symptoms.

OBJECTIVES: The present study aimed to identify and compare the associations between long working hours and use of work-related communication devices outside regular working hours and anxiety symptoms, thereby providing insight into redefining working hours. METHODS: Based on the cross-sectional data from the sixth Korean Working Conditions Survey (KWCS), specifically the responses from 46 055 workers, the use of work-related communication devices outside of regular working hours, long working hours, and anxiety symptoms were assessed. To investigate the associations between using work-related communication devices outside regular working hours or long working hours with anxiety symptoms, odds ratios (ORs) and 95% CIs were calculated using multiple logistic regression models. RESULTS: Among 46 055 participants, 25 659 (55.7%) used work-related communication devices outside working hours, 8145 (17.7%) worked long hours, and 2664 (5.8%) experienced anxiety symptoms. Compared with the reference group, those who used work-related communication devices outside regular working hours without working long hours, had higher OR of anxiety symptoms (OR: 2.18; 95% CI, 1.97-2.41) than those who worked long hours without using work-related communication devices during off-hours (OR: 1.32; 95% CI, 1.09-1.59). Furthermore, the group that both worked long hours and used work-related communication devices outside working hours exhibited the highest OR of anxiety symptoms (OR: 2.57; 95% CI, 2.24-2.97). CONCLUSIONS: Using work-related communication devices outside regular working hours is associated with a higher risk of anxiety symptoms compared with long working hours. This result suggests that using work-related devices outside regular working hours, in addition to regular work time, should be considered when redefining working hours.

Single-incision versus conventional multiport laparoscopic cholecystectomy in acute cholecystitis according to disease severity: single center retrospective study in Korea.

Purpose: The safety of single-incision laparoscopic cholecystectomy (SILC) for acute cholecystitis (AC) has not yet been confirmed. Methods: This single-center retrospective study included patients who underwent laparoscopic cholecystectomy (LC) for AC between April 2010 and December 2020. Propensity scores were used to match patients who underwent SILC with those who underwent conventional multiport LC (CMLC) in the entire cohort and in the two subgroups. Results: A total of 1,876 patients underwent LC for AC, and 427 (22.8%) underwent SILC. In the propensity score-matched analysis of the entire cohort (404 patients in each group), the length of hospital stay (2.9 days vs. 3.5 days, p = 0.029) was shorter in the SILC group than in the CMLC group. No significant differences were observed in other surgical outcomes. In grade I AC (336 patients in each group), the SILC group showed poorer surgical outcomes than the CMLC group, regarding operation time (57.6 minutes vs. 52.4 minutes, p = 0.001) and estimated blood loss (22.9 mL vs. 13.1 mL, p = 0.006). In grade II/III AC (58 patients in each group), there were no significant differences in surgical outcomes between the two groups. Postoperative pain outcomes were also not significantly different in the two groups, regardless of severity. Conclusion: This study demonstrated that SILC had similar surgical and pain outcomes to CMLC in patients with AC; however, subgroup analysis showed that SILC was associated with poor surgical outcomes than CMLC in grade I AC. Therefore, SILC should be carefully performed in patients with AC by experienced hepatobiliary surgeons.

HIF-1α inhibition by MO-2097, a novel chiral-free benzofuran targeting hnRNPA2B1.

INTRODUCTION: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator mediating adaptive responses to hypoxia. It is up-regulated in the tumor microenvironment and recognized as an effective anticancer drug target. Previously, we discovered that the natural compound moracin-O and its synthetic derivative MO-460 inhibited HIF-1α via hnRNPA2B1. OBJECTIVES: This study aimed to develop novel HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural products moracins-O and P. METHODS: In an ongoing search for novel HIF-1 inhibitors, a series of nature-inspired benzofurans with modifications on the chiral rings of moracins-O and P were synthesized. They showed improved chemical tractability and were evaluated for their inhibitory activity on HIF-1α accumulation under hypoxic conditions in HeLa CCL2 cells. The most potent derivative's chemical-based toxicities, binding affinities, and in vivo anti-tumorigenic effects were evaluated. Further, we examined whether our compound, MO-2097, exhibited anticancer effects in three-dimensional cultured organoids. RESULTS: Herein, we identified a novel synthetic chiral-free compound, MO-2097, with reduced structural complexity and increased efficiency. MO-2097 exhibited inhibitory effects on hypoxia-induced HIF-1α accumulation in HeLa CCL2 cells via inhibition of hnRNPA2B1 protein, whose binding affinities were confirmed by isothermal titration calorimetry analysis. In addition, MO-2097 demonstrated in vivo efficacy and biocompatibility in a BALB/c mice xenograft model. The immunohistochemistry staining of MO-2097-treated tissues showed decreased expression of HIF-1α and increased levels of apoptosis marker cleaved caspase 3, confirming in vivo efficacy. Furthermore, we confirmed that MO-2097 works effectively in cancer patient-based organoid models. CONCLUSION: MO-2097 represents a promising new generation of chemotherapeutic agents targeting HIF-1α inhibition via hnRNPA2B1, requiring further investigation.

Reduction of Structural Defects in the GaSb Buffer Layer on (001) GaP/Si for High Performance InGaSb/GaSb Quantum Well Light-Emitting Diodes.

Monolithic integration of GaSb-based optoelectronic devices on Si is a promising approach for achieving a low-cost, compact, and scalable infrared photonics platform. While tremendous efforts have been put into reducing dislocation densities by using various defect filter layers, exploring other types of extended crystal defects that can exist on GaSb/Si buffers has largely been neglected. Here, we show that GaSb growth on Si generates a high density of micro-twin (MT) defects as well as threading dislocations (TDs) to accommodate the extremely large misfit between GaSb and Si. We found that a 250 nm AlSb single insertion layer is more effective than AlSb/GaSb strained superlattices in reducing both types of defects, resulting in a 4× and 13× reduction in TD density and MT density, respectively, compared with a reference sample with no defect filter layer. InGaSb quantum well light-emitting diodes were grown on the GaSb/Si templates, and the effect of TD density and MT density on their performance was studied. This work shows the importance of using appropriate defect filter layers for high performance GaSb-based optoelectronic devices on standard on-axis (001) Si via direct epitaxial growth.

The relationship between exposure to environmental noise and risk of atopic dermatitis, asthma, and allergic rhinitis.

BACKGROUND: Noise is defined as unwanted sound. It may induce negative emotions and mental health problems and may even lead to increased suicide risk. However, the impact of noise exposure on environmental diseases and disease severity is not well understood. This study aimed to elucidate the association between night-time noise exposure and the prevalence of environmental diseases in South Korea. METHODS: We conducted an analysis of the Environmental Disease Database provide by the National Health Insurance Service (NHIS) from 2013 to 2017. After spatially interpolating the noise data provided by the National Noise Information System (NNIS), night-time noise values in the district level were obtained by calculating the mean noise values at the administrative district level. The linear regression analyses were performed to test the association between the age-standardized prevalence ratio (SPR) and the night-time noise exposure in the district level. RESULTS: In areas with high night-time noise exposure (≥55 dB), the SPR for atopic dermatitis and allergic rhinitis were 1.0515 (95 % confidence interval [CI]:1.0508-1.0521) and 1.0202 (95 % CI:1.0201-1.0204), respectively, which were higher than those in the general population. The SPR for environmental diseases, including atopic dermatitis, asthma, and allergic rhinitis, was 1.0104 (95 % CI:1.0103-1.0105). Additionally, a significant linear association was observed between the level of nocturnal noise exposure and the total hospitalization period for atopic dermatitis (ß = 399.3, p < 0.01). CONCLUSION: We provide evidence of a significant association between night-time environmental noise and environmental diseases, particularly atopic dermatitis and allergic rhinitis. Furthermore, we observed a significant linear association between night-time noise exposure and the severity of atopic dermatitis.

Stereochemical assignment of clerodane-type diterpenes from the fruits of Casearia grewiifolia and their ability to inhibit PCSK9 expression.

More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1-9 and 12-14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay. Among the undescribed compounds, the stereochemistry of two diastereomeric grewiifolins A and B (1 and 2) were extensively elucidated using 2D Nuclear Overhauser Effect Spectroscopy (NOESY) experiments, excitation-sculptured indirect detection experiments (EXSIDE), interproton distance analyses, and computational calculations that included quantum chemical shift calculations combined with DP4+ analysis. All isolates were assessed for their inhibitory activity against PCSK9 and IDOL mRNA expression. Among the compounds tested, compound 3 inhibited PCSK9 and IDOL mRNA expression.

A wireless, solar-powered, optoelectronic system for spatial restriction-free long-term optogenetic neuromodulations.

Numerous wireless optogenetic systems have been reported for practical tether-free optogenetics in freely moving animals. However, most devices rely on battery-powered or coil-powered systems requiring periodic battery replacement or bulky, high-cost charging equipment with delicate antenna design. This leads to spatiotemporal constraints, such as limited experimental duration due to battery life or animals' restricted movement within specific areas to maintain wireless power transmission. In this study, we present a wireless, solar-powered, flexible optoelectronic device for neuromodulation of the complete freely behaving subject. This device provides chronic operation without battery replacement or other external settings including impedance matching technique and radio frequency generators. Our device uses high-efficiency, thin InGaP/GaAs tandem flexible photovoltaics to harvest energy from various light sources, which powers Bluetooth system to facilitate long-term, on-demand use. Observation of sustained locomotion behaviors for a month in mice via secondary motor cortex area stimulation demonstrates the notable capabilities of our device, highlighting its potential for space-free neuromodulating applications.

Acute cholecystitis in old adults: the impact of advanced age on the clinical characteristics of the disease and on the surgical outcomes of laparoscopic cholecystectomy.

BACKGROUND: Impact of advanced age on disease characteristics of acute cholecystitis (AC), and surgical outcomes after laparoscopic cholecystectomy (LC) has not been established. METHODS: This single-center retrospective study included patients who underwent LC for AC between April 2010 and December 2020. We analyzed the disease characteristics and surgical outcomes according to age: Group 1 (age < 60 years), Group 2 (60 ≤ age < 80 years), and Group 3 (age ≥ 80 years). Risk factors for complications were assessed using logistic regression analysis. RESULTS: Of the 1,876 patients (809 [43.1%] women), 723 were in Group 1, 867 in Group 2, and 286 in Group 3. With increasing age, the severity of AC and combined common bile duct stones increased. Group 3 demonstrated significantly worse surgical outcomes when compared to Group 1 and 2 for overall (4.0 vs. 9.1 vs. 18.9%, p < 0.001) and serious complications (1.2 vs. 4.2 vs. 8.0%, p < 0.001), length of hospital stay (2.78 vs. 3.72 vs. 5.87 days, p < 0.001), and open conversion (0.1 vs. 1.0 vs. 2.1%, p = 0.007). Incidental gallbladder cancer was also the most common in Group 3 (0.3 vs. 1.5 vs. 3.1%, p = 0.001). In the multivariate analysis, body mass index < 18.5, moderate/severe AC, and albumin < 2.5 g/dL were significant risk factors for serious complications in Group 3. CONCLUSION: Advanced age was associated with severe AC, worse surgical outcomes, and a higher rate of incidental gallbladder cancer following LC. Therefore, in patients over 80 years of age with AC, especially those with poor nutritional status and high severity grading, urgent surgery should be avoided, and surgery should be performed after sufficient supportive care to restore nutritional status before LC.

Association between lone work and self-rated health status: using the 5th Korean Working Conditions Survey.

Background: Lone workers are generally defined as individuals who work alone without supervision, including self-employed people. While lone workers are considered a vulnerable group in some countries, there is a lack of research on their health status in domestic studies. Globally, the number of lone workers has been increasing, and this trend has been further accelerated since the coronavirus disease 2019 (COVID-19) pandemic with the rise of remote work. Methods: The study analyzed data from 44,281 participants, excluding unpaid family workers, soldiers, and those with missing data. Lone workers were defined as individuals who reported having no colleagues with the same job at their current workplace. Self-rated health status was categorized as "good" or "poor." Results: This study found a statistically significant higher number of lone workers among women compare to men. The largest occupational category for lone workers was service and sales workers, followed by agriculture and fisheries workers. A majority of non-lone workers reported working 40 hours or less per week, while the majority of lone workers reported working 53 hours or more per week. In addition, lone workers had significantly poorer health status evaluations compared to non-lone workers (odds ratio: 1.297; 95% confidence interval: 1.165-1.444). Conclusions: Further research is needed to investigate the causal relationship between lone work and health, using data collected after the COVID-19 pandemic.

Drawing Guideline for JKMS Manuscripts (05): Plots for Numeric Data.

The appropriate plot effectively conveys the author's conclusions to the readers. Journal of Korean Medical Science will provide a series of special articles to show you how to more easily make consistent and excellent plots. In this article, we will cover plots with numeric data.

Effect and mechanism of Magnolia officinalis pharmacopuncture for treating localized fat via network pharmacology and experimental study.

Background: Recently, for various reasons, the need for non-invasive treatment for localized fat has emerged. This study confirmed whether Magnolia officinalis (MO) pharmacopuncture reduces localized fat by promoting lipolysis and inhibiting adipogenesis. Methods: The network was built using genes related to the active compound of MO and the mode of action of MO was predicted by the functional enrichment analysis. Based on the result from network analysis, 100 µL of 2 mg/mL MO pharmacopuncture was injected into the inguinal fat pad for 6 weeks in obese C57BL/6J mice. Normal saline was injected into the right-side inguinal fat pad as a self-control. Results: It was expected that the 'AMP-activated protein kinase (AMPK) signaling pathway' would be affected by the MO Network. MO pharmacopuncture reduced the weight and size of inguinal fat in HFD-induced obese mice. The phosphorylation of AMPK along with the increases of lipases was significantly increased by MO injection. Also, the expression levels of fatty acid synthesize-related mediators were suppressed by MO injection. Conclusion: Our results demonstrated that MO pharmacopuncture promoted the expression of AMPK, which has beneficial effects on activation of lipolysis and inhibition of lipogenesis. Pharmacopuncture of MO can be a non-surgical alternative therapy in the treatment of local fat tissue.

Development of new TAK-285 derivatives as potent EGFR/HER2 inhibitors possessing antiproliferative effects against 22RV1 and PC3 prostate carcinoma cell lines.

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (9a-h) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound 9f exhibited IC50 values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound 9f also showed high selectivity profile when tested over a small kinase panel. Compounds 9a-h showed IC50 values in the range of 1.0-7.3 nM and 0.8-2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma.

Graphene/III-V Quantum Dot Mixed-Dimensional Heterostructure for Enhanced Radiative Recombinations via Hole Carrier Transfer.

Fabrication of high quantum efficiency nanoscale device is challenging due to increased carrier loss at surface. Low dimensional materials such 0D quantum dots and 2D materials have been widely studied to mitigate the loss. Here, we demonstrate a strong photoluminescence enhancement from graphene/III-V quantum dot mixed-dimensional heterostructures. The distance between graphene and quantum dots in the 2D/0D hybrid structure determines the degree of radiative carrier recombination enhancement from 80% to 800% compared to the quantum dot only structure. Time-resolved photoluminescence decay also shows increased carrier lifetimes when the distance decreases from 50 to 10 nm. We propose that the optical enhancement is due to energy band bending and hole carrier transfer, which repair the imbalance of electron and hole carrier densities in quantum dots. This 2D graphene/0D quantum dot heterostructure shows promise for high performance nanoscale optoelectronic devices.

Dimethyl Itaconate Inhibits Melanogenesis in B16F10 Cells.

Itaconate is a metabolite produced to counteract and resolve pro-inflammatory responses when macrophages are challenged with intracellular or extracellular stimuli. In the present study, we have observed that dimethyl itaconate (DMI) inhibits melanogenesis in B16F10 cells. DMI inhibits microphthalmia-associated transcription factor (MITF) and downregulates the expression of MITF target genes, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). DMI also decreases the level of melanocortin 1 receptor (MC1R) and the production of α-melanocyte stimulating hormone (α-MSH), resulting in the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and MITF activities. The structure-activity relationship (SAR) study illustrates that the α,ß-unsaturated carbonyl moiety in DMI, a moiety required to target KELCH-like ECH-associated protein 1 (KEAP1) to activate NF-E2-related factor 2 (NRF2), is necessary to inhibit melanogenesis and knocking down Nrf2 attenuates the inhibition of melanogenesis by DMI. Together, our study reveals that the MC1R-ERK1/2-MITF axis regulated by the KEAP1-NRF2 pathway is the molecular target responsible for the inhibition of melanogenesis by DMI.

Cancer risk in Vietnam war veterans from the Korean Vietnam war veterans' health study cohort.

Introduction: During the Vietnam War, several unknown chemicals, such as Agent Orange, were used in Vietnam by the military. Therefore, there have been continuous health concerns among the Vietnamese population and veterans exposed to these hazardous chemicals. This study aimed to investigate the risk of all cancers and also organ-specific cancers among Korean veterans of the Vietnam War. Methods: This study used a national representative cohort that included all Korean Vietnam War veterans as the interest group, with 1:4 age-sex-region-matched general Korean citizens as the reference group, from 2002 to 2018. Age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for all cancers and for 31 organ-specific cancer categories based on the medical facility visit data. Results: An increased SIR of 1.07 (95% CI, 1.06-1.08) was observed for all cancers among the veterans. There was a significantly increased risk of cancer among 22/31 organspecific cancers, with 18 cancer categories showing a significantly higher risk than all cancers. The highest risk was observed for "malignant neoplasms of other parts of the central nervous system" (SIR, 1.71; 95% CI, 1.51-1.92). Discussion: This study evaluated the risk of cancer among Korean Vietnam War veterans. Further studies are warranted to investigate various health determinants in the veterans as well as the Vietnamese population.

Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator.

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.