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Abstract Backgrounds Preoperative imaging, particularly with magnetic resonance imaging (MRI) and computed tomography (CT) scans, plays a crucial role in distinguishing between benign and malignant parotid gland tumors, while the reliability of Ultrasound-Guided Fine Needle Aspiration (FNA) in diagnosing these masses remains a topic of debate. Methods This two-center retrospective analysis was conducted on 347 patients with parotid gland tumors who had FNA and preoperative imaging (CT or MRI). All patients underwent surgery and final histopathological examination was available, along with complete medical records between January 2008 and May 2023. Results Among the 347 patients, 318 (92%) had benign and 10 (3%) had malignant tumors based on FNA, with 19 (5%) unsatisfactory specimens. Final histological diagnosis revealed 303 (87%) benign and 44 (13%) malignant lesions, with a false-negative rate of 10.6% for FNA. Multivariate analysis identified irregular shape and invasion as independent predictors of malignancy in patient with benign or unsatisfactory FNA results. The odds ratio for irregular shape was 3.06 and for invasion was 12.73. Conclusion Imaging characteristics, such as irregular shape and invasion may indicate towards malignant parotid tumors, even in patients with false-negative benign findings in FNA.

Abstract Background Periodontal disease (PD) is a condition that can be treated and managed. This study aimed to determine if chronic PD status is associated with the risk of developing hypertension, utilizing data from the National Health Insurance Database of Korea. Methods Participants who received oral health examinations both in 2003 and in 2005–2006 were included. Those with a history of hypertension were excluded. Hypertension was defined as at least one outpatient or inpatient claim diagnosis (primary or secondary) of hypertension (International Classification of Diseases (ICD)-10 codes I10-I11) with prescription for antihypertensive medication or at least one incident of systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg during a health examination. Changes of PD status was determined during two oral examinations. Study participants were divided into 4 groups according to the changes of PD status: PD-free (those consistently free of disease in both exams), PD-recovered (individuals with disease initially but not in the second exam), PD-developed (no disease initially, but present in the second exam), and PD-chronic (disease throughout both exams). The incidence of hypertension after the second oral health examination (index date) was monitored. Participants were observed from the index date until the earliest occurrence of hypertension onset, mortality, or December 2020. Results The study comprised 706,584 participants: 253,003(35.8%) in the PD-free group, 140,143(19.8%) in the PD-recovered group, 132,397(18.7%) in the PD-developed group, and 181,041(25.6%) in the PD-chronic group. Over a median follow-up duration of 14.3 years, 239,937 (34.0%) cases of hypertension were recorded. The PD-recovered group had a lower risk of hypertension compared to the PD-chronic group, while the PD-developed group had a higher risk of hypertension compared to the PD-free group. Conclusion Chronic PD is associated with an increased risk of developing hypertension. Although the increase in risk is modest, recovery from PD may have beneficial effects in reducing hypertension risk. Further studies are needed to confirm the importance of regular dental examinations and effective management of PD to reduce hypertension risk.

Abstract Background This study aimed to elucidate the nature and extent of the associations between diabetes mellitus (DM) and migraine through a systematic review and meta-analysis. Methods We searched the PubMed, Web of Science, and Scopus databases without a specified start date until June 2, 2024. Cross-sectional and cohort studies analyzing the risk of migraine in individuals with DM and vice versa were included. Studies without at least age and sex adjustments were excluded. Data were extracted to calculate odds ratios (ORs) and hazard ratios (HRs). Risk of bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. Results Eight cross-sectional studies (131,361 patients with DM and 1,005,604 patients with migraine) and four cohort studies (103,205 patients with DM patients and 32,197 patients with migraine) were included. Meta-analyses of the cross-sectional studies showed no significant overall association between DM and migraine. Subgroup analyses revealed that type 1 diabetes reduced the odds of having migraine (OR 0.48, 95% confidence interval [CI] 0.30–0.77), while migraine without aura (MO) increased the odds of having DM (OR 1.19, 95% CI 1.02–1.39). The cohort studies indicated that DM decreased the risk of developing migraine (HR 0.83, 95% CI 0.76–0.90), and a history of migraine increased the risk of developing DM (HR 1.09, 95% CI 1.01–1.17). Conclusions DM, particularly type 1 diabetes, is negatively associated with migraine occurrence, whereas migraine, especially MO, is positively associated with DM occurrence. However, most of the results remained at a low or very low level of evidence, indicating the need for further research.

Abstract Background Limited research has analyzed the association between diastolic blood pressure (DBP) and survival after pediatric cardiopulmonary resuscitation (CPR). This study aimed to explore the association between post-resuscitation diastolic blood pressure and survival in pediatric patients who underwent CPR. Method This retrospective single-center study included pediatric patients admitted to the pediatric intensive care unit of Asan Medical Center between January 2016 to November 2022. Patients undergoing extracorporeal CPR and those with unavailable data were excluded. The primary endpoint was survival to ICU discharge. Results A total of 106 patients were included, with 67 (63.2%) achieving survival to ICU discharge. Multivariate logistic regression analysis identified DBP within 1 h after ROSC as the sole significant variable (p = 0.002, aOR, 1.043; 95% CI, 1.016–1.070). Additionally, DBP within 1 h demonstrated an area under the ROC curve of 0.7 (0.592–0.809) for survival to ICU discharge, along with mean blood pressure within the same timeframe. Conclusion Our study highlights the importance of DBP within 1-hour post-ROSC as a significant prognostic factor for survival to ICU discharge. However, further validation through further prospective large-scale studies is warranted to confirm the appropriate post-resuscitation DBP of pediatric patients.

Abstract Obesity is the one of the most important components of metabolic syndrome. Because obesity related hypertension accounts for two thirds of essential hypertension, managing obesity and metabolic syndrome is a crucial task in the management of hypertension. However, the current non-pharmacological therapies have limitations for achieving or maintaining ideal body weight. Recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated excellent weight control effects, accompanied by corresponding reductions in blood pressure. GLP1-RAs have shown cardiovascular and renal protective effects in cardiovascular outcome trials both in primary and secondary prevention. In this document, the Korean Society of Hypertension intends to remark the current clinical results of GLP1-RAs and recommend the government and health-policy makers to define obesity as a disease and to establish forward-looking policies for GLP1-RA treatment for obesity treatment, including active reimbursement policies.

Abstract Background This study evaluated the impact of the tax increase in January 2019 on changes in intention to quit and the effect of cigarette prices on quit attempts and successful quitting among male cigarette smokers in Vietnam. Methods Data were derived from the ITC project in Vietnam, which included 1585 adult smokers at baseline (Wave 1, Aug-Oct 2018) followed up to waves 2 (Sep-Nov 2019) and 3 (Sep-Dec 2020). Generalized estimating equations regression was performed to estimate changes in the intention to quit. Multiple logistic regression analysis was used to evaluate the cigarette price of a cigarette pack in relation to quit attempts and successful quitting. Results The increase in cigarette tax in 2019 did not significantly increase the likelihood of the intention to quit. After the tax increase, 63.6% of participants who smoked made a quit attempt, and 27.6% successfully quit smoking in the follow-up waves. However, the price of a cigarette pack was not significantly associated with quit attempts and successful quitting. The study did not observe a significant impact of cigarette prices on quit attempts and successful quitting in all subgroups of household income. Factors associated with quit attempts included the number of cigarettes smoked and the intention to quit, while those associated with successful quitting included age, dual use of cigarettes and other tobacco products, and the intention to quit. Conclusion Current cigarette prices were not associated with cessation behaviors even within the lowest household income group. Therefore, a sharp rise in cigarette tax is required to incentivize smokers to quit smoking.

Abstract Background Asians and Asian Americans have the lowest rate of mental health service utilization (25%) in the US compared to other racial/ethnic groups (39 − 52%), despite high rates of depression, anxiety, and suicidal ideation. The lack of culturally-responsive mental health trainings hinders access to mental health services for these populations. We assessed the mental health priorities of Asian communities in Greater Boston and evaluated cultural responsiveness of the Mental Health First Aid (MHFA), a first-responder training teaching participants skills to recognize signs of mental health and substance use challenges, and how to appropriately respond. Methods This is community-based participatory research with the Boston Chinatown Neighborhood Center (BCNC), Asian Women For Health (AWFH), and the Addressing Disparities in Asian Populations through Translational Research (ADAPT) Coalition. We conducted focus groups with community-based organization staff and community members to assess mental health priorities of Asian populations in Boston, MA. We then evaluated the utility and cultural-responsiveness of the English-language MHFA for Asian populations through pre- and post-training questionnaires and focus groups with community participants. Paired t-tests were used to evaluate questionnaire responses. Thematic analysis was used to analyze interviews. Results In total, ten staff and eight community members participated in focus groups, and 24 community members completed the MHFA and pre- and post-training questionnaires. Common mental health challenges in the Asian communities reported by participants were loneliness, high stigma around mental illnesses, academic pressure, and acculturation stress. Compared to pre-training, MHFA participants demonstrated lower personal mental health stigma (p

Abstract Background Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. Methods We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1–2 and 3–6 months of treatment. Results Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3–6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. Conclusion Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

Abstract Background As the number of adolescent cancer survivors increases, detailed and effective healthcare policies on adolescent cancer survivors returning to school and workplace are needed. The study aimed to explore the perception of healthy adolescents on cancer and adolescent cancer survivors. Methods This study conducted a face-to-face cross-sectional study in the Republic of Korea in 2021 on adolescent selected through proportional population allocation sampling by sex, age, and region. According to research questions, survey questionnaire organized and collected data on adolescents' perceptions of cancer, differences in perceptions from tuberculosis, measles, asthma, perceptions of adolescent cancer survivors, and health information sources that led to these perceptions. Results Of the total 500 adolescents, less than 10% of healthy adolescents responded that cancer is contagious, while three-quarters of the respondents believed that cancer is preventable. In addition, compared to tuberculosis, measles, and asthma, they recognized differences by disease. The majority of healthy adolescents embraced community values advocating the return of adolescent cancer survivors to school and work. However, they expressed a negative view of the situation in which adolescent cancer survivors could interact with them as classmates or co-workers. Adolescents mainly obtained health information on cancer from the Internet and television, Conclusions The perception of healthy adolescents on cancer was relatively accurate; however, they have dualistic thinking involving living with adolescent cancer survivors. To facilitate reintegration of adolescent cancer survivors into daily lives, education is needed for healthy adolescents to live with cancer survivors.

Abstract Background The pathogenesis of migraine remains unclear; however, a large body of evidence supports the hypothesis that immunological mechanisms play a key role. Therefore, we aimed to review current studies on altered immunity in individuals with migraine during and outside attacks. Methods We searched the PubMed database to investigate immunological changes in patients with migraine. We then added other relevant articles on altered immunity in migraine to our search. Results Database screening identified 1,102 articles, of which 41 were selected. We added another 104 relevant articles. We found studies reporting elevated interictal levels of some proinflammatory cytokines, including IL-6 and TNF-α. Anti-inflammatory cytokines showed various findings, such as increased TGF-β and decreased IL-10. Other changes in humoral immunity included increased levels of chemokines, adhesion molecules, and matrix metalloproteinases; activation of the complement system; and increased IgM and IgA. Changes in cellular immunity included an increase in T helper cells, decreased cytotoxic T cells, decreased regulatory T cells, and an increase in a subset of natural killer cells. A significant comorbidity of autoimmune and allergic diseases with migraine was observed. Conclusions Our review summarizes the findings regarding altered humoral and cellular immunological findings in human migraine. We highlight the possible involvement of immunological mechanisms in the pathogenesis of migraine. However, further studies are needed to expand our knowledge of the exact role of immunological mechanisms in migraine pathogenesis.

Abstract Objectives Poorly visualized images that appear during small bowel capsule endoscopy (SBCE) can confuse the interpretation of small bowel lesions and increase the physician’s workload. Using a validated artificial intelligence (AI) algorithm that can evaluate the mucosal visualization, we aimed to assess whether SBCE reading after the removal of poorly visualized images could affect the diagnosis of SBCE. Methods A study was conducted to analyze 90 SBCE cases in which a small bowel examination was completed. Two experienced endoscopists alternately performed two types of readings. They used the AI algorithm to remove poorly visualized images for the frame reduction reading (AI user group) and conducted whole frame reading without AI (AI non-user group) for the same patient. A poorly visualized image was defined as an image with

Abstract Background This study aimed to investigate the impact of tobacco industry interference on the implementation and management of tobacco control and the tobacco epidemic using the Tobacco Industry Interference Index (TIII) and MPOWER—a package of measures for tobacco control—and adult daily smoking prevalence in 30 countries. Methods The TIII was extracted from the Global Tobacco Industry Interference Index 2019 and Global Center for Good Governance in Tobacco Control (GGTC). MPOWER measures and adult daily smoking prevalence rate were extracted from the World Health Organization (WHO) report on the global tobacco epidemic in 2021. We assessed the ecological cross-lagged association between TIII and MPOWER scores and between TIII and age-standardized prevalence rates for adult daily tobacco users. Results Tobacco industry interference was inversely correlated with a country’s package of tobacco control measures (β = -0.088, P = 0.035). The TIII was correlated with weaker warnings about the dangers of tobacco (β = -0.016, P = 0.078) and lack of enforcement of bans on tobacco advertising promotion and sponsorship (β = -0.023, P = 0.026). In turn, the higher the TIII, the higher the age-standardized prevalence of adult daily tobacco smokers for both sexes (β = 0.170, P = 0.036). Adult daily smoking prevalence in males (β = 0.417, P = 0.004) was higher in countries where the tobacco industry received incentives that benefited its business. Conclusion Where the interference of the tobacco industries was high, national compliance with the Framework Convention on Tobacco Control (FCTC) was lower, and the prevalence of adult daily smokers higher. National governments and global society must work together to minimize the tobacco industry’s efforts to interfere with tobacco control policies.

Abstract Background Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Abstract Background Ticks are ectoparasites capable of directly damaging their hosts and transmitting vector-borne diseases. The ixodid tick Haemaphysalis flava has a broad distribution that extends from East to South Asia. This tick is a reservoir of severe fever with thrombocytopenia syndrome virus (SFTSV) that causes severe hemorrhagic disease, with cases reported from China, Japan and South Korea. Recently, the distribution of H. flava in South Korea was found to overlap with the occurrence of SFTSV. Methods This study was undertaken to discover the molecular resources of H. flava female ticks using the Illumina HiSeq 4000 system, the Trinity de novo sequence assembler and annotation against public databases. The locally curated Protostome database (PANM-DB) was used to screen the putative adaptation-related transcripts classified to gene families, such as angiotensin-converting enzyme, aquaporin, adenylate cyclase, AMP-activated protein kinase, glutamate receptors, heat shock proteins, molecular chaperones, insulin receptor, mitogen-activated protein kinase and solute carrier family proteins. Also, the repeats and simple sequence repeats (SSRs) were screened from the unigenes using RepeatMasker (v4.0.6) and MISA (v1.0) software tools, followed by the designing of SSRs flanking primers using BatchPrimer 3 (v1.0) software. Results The transcriptome produced a total of 69,822 unigenes, of which 46,175 annotated to the homologous proteins in the PANM-DB. The unigenes were also mapped to the EuKaryotic Orthologous Groups (KOG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) specializations. Promiscuous presence of protein kinase, zinc finger (C2H2-type), reverse transcriptase, and RNA recognition motif domains was observed in the unigenes. A total of 3480 SSRs were screened, of which 1907 and 1274 were found as tri- and dinucleotide repeats, respectively. A list of primer sequences flanking the SSR motifs was detailed for validation of polymorphism in H. flava and the related tick species. Conclusions The reference transcriptome information on H. flava female ticks will be useful for an enriched understanding of tick biology, its competency to act as a vector and the study of species diversity related to disease transmission. Graphical abstract

Abstract Background Human papillomavirus (HPV) has been detected in eyelid sebaceous gland carcinoma (SGC) and squamous cell carcinoma (SCC), and detection rates greatly varied across studies. This study aimed to investigate the presence of HPV in eyelid SGC and SCC among Koreans and its correlation with clinicopathological characteristics. Methods Surgically resected eyelid samples diagnosed as SGC or SCC from January 1999 to June 2011 were identified from the pathology database of three referral centres in Korea. Clinicopathological information including origin (skin vs. tarsal conjunctiva) and treatment outcomes were retrospectively reviewed. Immunohistochemistry (IHC) for p16, HPV DNA in situ hybridisation (ISH), and polymerase chain reaction-based DNA microarray were performed in paraffin-embedded tissue sections. Results Our cohort included 34 SGC and 12 SCC cases with Asian ethnicity. HPV was detected in 4 SGC and 6 SCC by DNA microarray, while 2 SCC (16.7%) showed positivity in ISH. SCC of tarsal conjunctival origin was significantly more common in HPV-positive SCC than in HPV-negative SCC (5 of 6 vs. 0 of 6, P = 0.015, Fisher’s exact test). Among samples showing positive staining in p16 IHC, HPV positivity rates were 0.0% (0/19) in SGC and 100% (3/3) in SCC. There was no significant difference in overall and local recurrence rate in eyelid SGC and SCC according to the HPV status (P > 0.99). Conclusions HPV was found in a subset of eyelid SGC and SCC among Koreans and might be aetiologically related to SCC of tarsal conjunctival origin. Overexpression of p16 is considered to be inappropriate as an indicator of HPV infection in eyelid SGC. Further investigation is required to elucidate the transmission route and pathogenic roles of HPV.

Abstract Background This study aimed to investigate how aging alters the homeostasis of the colonic intestinal epithelium and regeneration after tissue injury using organoid models and to identify its underlying molecular mechanism. Methods To investigate aging-related changes in the colonic intestinal epithelium, we conducted organoid cultures from old (older than 80 weeks) and young (6–10 weeks) mice and compared the number and size of organoids at day 5 of passage 0 and the growth rate of organoids between the two groups. Results The number and size of organoids from old mice was significantly lower than that from young mice (p

Abstract Background In South Korea, commercial postpartum care centres, known as Sanhujoriwons, have emerged as important institutions aiding mothers’ physical recovery after childbirth. Although previous studies have measured mothers’ satisfaction level with Sanhujoriwons, this study applies Bronfenbrenner’s ecological model to identify the factors influencing first-time mothers’ satisfaction with Sanhujoriwons. Methods This descriptive correlational study involved 212 first-time mothers admitted to Sanhujoriwons for two weeks with their new-borns (healthy babies weighing at least 2.5 kg) after giving birth after 37 weeks of pregnancy. Data were collected using a self-report questionnaire at five postpartum care centres in the metropolitan area of South Korea from October to December 2021, on the day of the mothers’ discharge. This study considered ecological factors such as perceived health status, postpartum depression, childcare stress, maternal identity at the individual level; partnership with Sanhujoriwon staff at the microsystem level; and the Sanhujoriwons’ education support system at the exo-system level. The data were analysed using descriptive statistics, t-test, one-way ANOVA, correlation analysis, and hierarchical regression analysis using the SPSS 25.0 Win program. Results The mean score of satisfaction with Sanhujoriwons was 59.67 ± 10.14 out of 70, indicating a high level of satisfaction. The hierarchical regression analysis showed that satisfaction with Sanhujoriwons was significantly affected by the perceived health status (β = 0.19, p

Abstract Background The outcomes of education and counseling by medical professionals for patients with type 2 diabetes mellitus (T2DM) are unclear. This study examined the effects of the Chronic Disease Management Program (CDMP), a health insurance fee-for-service benefit, on the incidence of diabetic complications in patients newly diagnosed with T2DM using the National Health Insurance data. Methods Patients newly diagnosed with T2DM aged ≥ 20 years from 2010 to 2014 were followed up until 2015. Selection bias was minimized using propensity score matching. A stratified Cox proportional hazards model was used to analyze the association between the CDMP and the risk of incident diabetic complications. Subgroup analysis was performed for patients with high medication adherence, which was indicated by a medication possession ratio (MPR) ≥ 80. Results Among the 11,915 patients with T2DM in the cohort, 4,617 were assigned to the CDMP and non-CDMP group each. The CDMP helped reduce the overall and microvascular risks of complications compared to the non-CDMP group; however, the protective effect against macrovascular complications was only observed in those aged ≥ 40 years. Subgroup analysis of the group aged ≥ 40 years with high adherence (an MPR ≥ 80) showed that the CDMP effectively reduced the incidence of micro- and macrovascular complications. Conclusions Effective management of T2DM is crucial in preventing complications in patients with the condition, and includes regular monitoring and adjustment of treatment by qualified physicians. Nevertheless, long-term prospective studies on the effects of CDMP are required to confirm this finding.

Abstract Background Korea is expected to become a super-aged society in 2026, and improving nutritional status, which is directly related to health problems, is therefore important for increasing healthy life expectancy. Frailty is the most complex phenotype of aging, and leads to adverse health outcomes, disability, poor quality of life, hospitalization, and mortality. Malnutrition is a major risk factor for frailty syndrome. This study aimed to investigate the incidence of pre-frailty or frailty in the second wave (T2, 2018–2019) according to general characteristics and nutritional status in the first wave (T1, 2016–2017); and examine the longitudinal association of nutritional status in T1 and the incidence of pre-frailty or frailty in T2 among older adults living in a community. Methods A secondary data analysis was performed using the Korean Frailty and Aging Cohort Study (KFACS). Participants comprised 1125 community-dwelling older Korean adults aged 70–84 years (mean age: 75.03 ± 3.56 years; 53.8% males). Frailty was assessed using the Fried frailty index, and nutritional status was assessed using the Korean version of the Mini Nutritional Assessment Short-Form and blood nutritional biomarkers. Binary logistic regression was used to identify longitudinal associations between the nutritional status at T1 and pre-frailty or frailty at T2. Results Over the two-year follow-up period, 32.9% and 1.7% of the participants became pre-frail and frail, respectively. After the potential confounders were adjusted (sociodemographic, health behaviors, and health status characteristics), pre-frailty or frailty had a significant longitudinal association with severe anorexia (adjusted odds ratio [AOR], 4.17; 95% confidence interval [CI], 1.05–16.54), moderate anorexia (AOR, 2.31; 95% CI, 1.46–3.64), psychological stress or acute disease (AOR, 2.61; 95% CI, 1.26–5.39), and body mass index (BMI) less than 19 (AOR, 4.11; 95% CI, 1.20–14.04). Conclusions Anorexia, psychological stress, acute disease, and low BMI are the most significant longitudinal risk factors for pre-frailty or frailty in older adults. As nutritional risk factors may be preventable or modifiable, it is important to develop interventions targeting the same. Community-based health professionals in health-related fields should recognize and manage these indicators appropriately to prevent frailty among older adults living in the community.

Abstract Background Dung beetles recycle organic matter through the decomposition of feces and support ecological balance. However, these insects are threatened by the indiscriminate use of agrochemicals and habitat destruction. Copris tripartitus Waterhouse (Coleoptera: Scarabaeidae), a dung beetle, is listed as a class-II Korean endangered species. Although the genetic diversity of C. tripartitus populations has been investigated through analysis of mitochondrial genes, genomic resources for this species remain limited. In this study, we analyzed the transcriptome of C. tripartitus to elucidate functions related to growth, immunity and reproduction for the purpose of informed conservation planning. Results The transcriptome of C. tripartitus was generated using next-generation Illumina sequencing and assembled de novo using a Trinity-based platform. In total, 98.59% of the raw sequence reads were processed as clean reads. These reads were assembled into 151,177 contigs, 101,352 transcripts, and 25,106 unigenes. A total of 23,450 unigenes (93.40%) were annotated to at least one database. The largest proportion of unigenes (92.76%) were annotated to the locally curated PANM-DB. A maximum of 5,512 unigenes had homologous sequences in Tribolium castaneum. Gene Ontology (GO) analysis revealed a maximum of 5,174 unigenes in the Molecular function category. Further, in Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, a total of 462 enzymes were associated with established biological pathways. Based on sequence homology to known proteins in PANM-DB, representative immunity, growth, and reproduction-related genes were screened. Potential immunity-related genes were categorized into pattern recognition receptors (PRRs), the Toll-like receptor signaling pathway, the MyD88- dependent pathway, endogenous ligands, immune effectors, antimicrobial peptides, apoptosis, and adaptation-related transcripts. Among PRRs, we conducted detailed in silico characterization of TLR-2, CTL, and PGRP_SC2-like. Repetitive elements such as long terminal repeats, short interspersed nuclear elements, long interspersed nuclear elements and DNA elements were enriched in the unigene sequences. A total of 1,493 SSRs were identified among all unigenes of C. tripartitus. Conclusions This study provides a comprehensive resource for analysis of the genomic topography of the beetle C. tripartitus. The data presented here clarify the fitness phenotypes of this species in the wild and provide insight to support informed conservation planning.

Abstract Background Physical activity (PA) changes throughout an individual’s life, but the association between such changes and cancer risk seems to be overlooked in the literature. Thus, this study aimed to examine the association between the trajectories of PA frequency and cancer incidence among middle-aged Korean adults. Methods A total of 1,476,335 eligible participants (992,151 men and 484,184 women) aged ≥40 years from the National Health Insurance Service cohort (2002–2018) were included. Assessment of PA frequency was a self-reported measure, based on the question: “How many times per week do you perform exercise that makes you sweat?”. PA frequency trajectories (i.e., trajectory classes of change in PA frequency) from 2002 to 2008 were identified using group-based trajectory modeling. Cox proportional hazards regression was used to assess the associations between the PA trajectories and cancer incidence. Results Five PA frequency trajectories over 7 years were identified: persistently low (men:73.5%; women:74.7%), persistently moderate (men:16.2%; women:14.6%), high-to-low (men:3.9%; women:3.7%), low-to-high (men:3.5%; women:3.8%), and persistently high (men:2.9%; women:3.3%). Compared with persistently low frequency, maintaining a high PA frequency was associated with a lower risk of all cancers (Hazard ratio (HR) = 0.92, 95%CI = 0.87–0.98) and breast cancer (HR = 0.82, 95%CI = 0.70–0.96) among women. There was a lower risk for thyroid cancer among men in the high-to-low (HR = 0.83, 95%CI = 0.71–0.98), low-to-high (HR = 0.80, 95%CI = 0.67–0.96), and high PA trajectories (HR = 0.82, 95%CI = 0.68–0.99). There was a significant association between moderate trajectory and lung cancer in men (HR = 0.88, 95%CI = 0.80–0.95), in both smoking and non-smoking men. Conclusion Long-term persistent high frequency of PA as part of the daily routine should be widely promoted and encouraged to reduce the risk for all cancer development in women.

Abstract Stratifying breast cancer into specific molecular or histologic subtypes aids in therapeutic decision-making and predicting outcomes; however, these subtypes may not be as distinct as previously thought. Patients with luminal-like, estrogen receptor (ER)-expressing tumors have better prognosis than patients with more aggressive, triple-negative or basal-like tumors. There is, however, a subset of luminal-like tumors that express lower levels of ER, which exhibit more basal-like features. We have found that breast tumors expressing lower levels of ER, traditionally considered to be luminal-like, represent a distinct subset of breast cancer characterized by the emergence of basal-like features. Lineage tracing of low-ER tumors in the MMTV-PyMT mouse mammary tumor model revealed that basal marker-expressing cells arose from normal luminal epithelial cells, suggesting that luminal-to-basal plasticity is responsible for the evolution and emergence of basal-like characteristics. This plasticity allows tumor cells to gain a new lumino-basal phenotype, thus leading to intratumoral lumino-basal heterogeneity. Single-cell RNA sequencing revealed SOX10 as a potential driver for this plasticity, which is known among breast tumors to be almost exclusively expressed in triple-negative breast cancer (TNBC) and was also found to be highly expressed in low-ER tumors. These findings suggest that basal-like tumors may result from the evolutionary progression of luminal tumors with low ER expression.

Abstract Background Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. Findings This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. Conclusions The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr ).

Abstract COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People’s Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.

Abstract Background Various cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. Methods To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1). Results Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-associated low-risk (CSC-LR; n = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (–) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. Conclusion The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (–) status who were classified in more detail.

Abstract Background As the life expectancy of people living with HIV increases with the advancements in antiretroviral treatment, the continuity of long-term therapy and health care for people living with HIV has gained more importance. However, the estimated proportion of people living with HIV who have access to treatment or are virally suppressed is unsatisfactory. Therefore, it is necessary to build strategies to improve treatment continuity by identifying the barriers and facilitators that affect the HIV care continuum. To enable this, we will conduct a scoping review to explore the barriers and facilitators related to the care continuum in high-income countries for adults living with HIV. Methods The review question will be identified based on the JBI guidelines for the development of scoping review protocols. Studies exploring the barriers to and facilitators of the HIV care continuum among adults living with HIV in high-income countries will be included in this review. A literature search will be conducted on the databases (platform) of MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (EBSCO), Embase (Ovid), and the Cochrane Central Register of Controlled Trials (Cochrane Library). Four researchers will screen articles for inclusion and subsequently build a charting form and collate the data to provide results. Discussion The results of this scoping review will provide comprehensive evidence for the barriers and facilitators to be considered in the care continuum of people living with HIV. Importantly, the results will provide insight for healthcare providers and researchers to develop interventions and research the continuity in caring for people living with HIV.

Abstract Background Cardiac rehabilitation (CR) is a prognostic management strategy to help patients with CVD achieve a good quality of life and lower the rates of recurrence, readmission, and premature death from disease. Globally, cardiac rehabilitation is poorly established in hospitals and communities. Hence, this study aimed to investigate the discrepancies in the perceptions of the need for CR programs and relevant health policies between directors of hospitals and health policy personnel in South Korea to shed light on the status and to establish practically superior and effective strategies to promote CR in South Korea. Methods We sent a questionnaire to 592 public health policy managers and directors of selected hospitals, 132 of whom returned a completed questionnaire (response rate: 22.3%). The participants were categorized into five types of organizations depending on their practice of PCI (Percutaneous Coronary Intervention), establishment of cardiac rehabilitation, director of hospital, and government's policy makers. Differences in the opinions between directors of hospitals that perform/do not perform PCI, directors of hospitals with/without cardiac rehabilitation, and between hospital directors and health policy makers were analyzed. Results Responses about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, hospitals’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive among hospitals that perform PCI than those that do not. Responses to questions about the effectiveness of cardiac rehabilitation and hospitals’ roles in cardiac rehabilitation tended to be more positive in hospitals with cardiac rehabilitation than in those without. Hospital directors responded more positively to questions about targeting diseases for cardiac rehabilitation and governmental health policies’ roles in cardiac rehabilitation than policy makers, and both hospitals and public organizations provided negative responses to the question about patients’ roles in cardiac rehabilitation. Responses to questions about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive in hospitals that perform PCI than those that do not and public organizations. Conclusions Hospitals must ensure timely referral, provide education, and promote the need for cardiac rehabilitation. In addition, governmental socioeconomic support is needed in a varity of aspects.

Abstract Background Perception of harm plays an important role in predicting intention to quit—an integral part of the cessation process. Perception on harm from bamboo waterpipe tobacco was unknown, even the predominant of this type of tobacco use. This study investigated the effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit among adult male Vietnamese tobacco users. Methods From the nationally-representative 2015 Global Adult Tobacco Survey, we included 1,351 adult males (≥ 18 years old) who used cigarettes, bamboo waterpipes, or both. Demographic characteristics, tobacco use behaviors, perceived harm from tobacco use, and regulation/policy exposure were measured. Effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit were assessed by logistic regression. Results Intention to quit prevalence was 59.0%, 55.0%, and 58.4% for cigarette, waterpipe, and dual users, respectively. Tobacco users who perceived that “using cigarettes and/or waterpipe could cause severe illness” and “waterpipe use is less harmful than cigarette smoking”, had tobacco use bans at home, or were exposed to anti-smoking campaigns or encouragement to quit information were more likely to intend to quit. When analyzed by tobacco users, intention to quit was more likely for those users who perceived their tobacco product as more harmful than the other product type, although statistical significance was only observed for cigarette users. Conclusions Misperceptions regarding harm from tobacco use could negatively affect intention to quit. Dissemination of accurate information on the risks from all forms of tobacco use and enforcement of tobacco control policies are important for encouraging intention to quit.

Abstract Background Obesity is a chronic disease that causes various medical health problems, increases morbidity, and reduces the quality of life. Obesity (especially central obesity) in older adults is expected to act with the development of sarcopenia. However, the relationship between obesity, central obesity, and sarcopenia remains controversial. This study aimed to investigate the impact of obesity on sarcopenia. Methods In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 1,827 community-dwelling older adults (883 men and 944 women) aged 70–84 years were recruited. The Asian Working Group for Sarcopenia (AWGS) criteria were used to evaluate sarcopenia. Subjects with a low appendicular skeletal muscle mass index (ASMI; men:

Abstract Background This study aimed to compare the prognostic significance of pre and postoperative lactate levels and postoperative lactate clearance in the prediction of in-hospital mortality after surgery for gastrointestinal (GI) perforation. Methods Among patients who underwent surgery for GI perforation between 2013 and 2017, only patients whose lactate were measured before and after surgery were included and divided into an in-hospital mortality group and a survival group. Data on demographics, comorbidities, pre and postoperative laboratory test results, and operative findings were collected. Risk factors for in-hospital mortality were identified, and receiver-operating characteristic (ROC) curve analysis was performed for pre and postoperative lactate levels and postoperative lactate clearance. Results Of 104 included patients, 17 patients (16.3%) died before discharge. The in-hospital mortality group demonstrated higher preoperative lactate (6.3 ± 5.1 vs. 3.5 ± 3.2, P = 0.013), SOFA score (4.5 ± 1.7 vs. 3.4 ± 2.3, P = 0.004), proportions of patients with lymphoma (23.5% vs. 2.3%, P = 0.006), and rates of contaminated ascites (94.1% vs. 68.2%, P = 0.036) and lower preoperative hemoglobin (10.4 ± 1.6 vs. 11.8 ± 2.4, P = 0.018) compare to the survival group. Multivariate analysis revealed that postoperative lactate (HR 1.259, 95% CI 1.084–1.463, P = 0.003) and preoperative hemoglobin (HR 0.707, 95% CI 0.520–0.959, P = 0.026) affected in-hospital mortality. In the ROC curve analysis, the largest area under the curve (AUC) was shown in the postoperative lactate level (AUC = 0.771, 95% CI 0.678–0.848). Conclusion Of perioperative lactate levels in patients underwent surgery for GI perforation, postoperative lactate was the strongest predictor for in-hospital mortality.

Abstract Background/aim In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients. Methods This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child–Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response. Results After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2 months, p = 0.070) and PFS (4.6 vs 2.4 months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96–2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5 months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group. Conclusions Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC.

Abstract Background Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. Methods The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. Results αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. Conclusion This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU–induced augmentation of CSCs via the Notch signaling pathway.

Abstract Background Although the proportion of older patients with type 2 diabetes mellitus (T2DM) has increased, few studies have reported the factors affecting glucose levels in older patients with long-standing T2DM. This study assessed the determinants of glycemic control in older adults with T2DM of a duration of ≥10 years, including muscle mass, muscle quality, and β-cell function. Methods This was a prospective study of older patients aged ≥60 years with a T2DM duration of ≥10 years. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index, handgrip strength (HGS), and body composition through bioelectrical impedance analysis were assessed. The primary outcome was a composite of: (i) increment of glycated hemoglobin (HbA1c) from the baseline ≥0.6% and (ii) HbA1c ≥ 9% at any time point during the follow-up period. To find the predicting determinants of the outcome, we performed the Cox proportional hazard analysis. Results Among 100 patients (mean age, 64.0 ± 8.6 years; median duration of diabetes, 20 [interquartile range (IQR), 17–23] years; median HbA1c at baseline, 7.1 [IQR, 6.7–7.4] %), the primary outcome was observed in 40 (40.0%) patients during 4.0 (IQR 2.3–5.0) years of follow-up. A Cox proportional hazards model adjusted for age, sex, baseline HbA1c, obesity, duration of DM and anti-diabetic medication at baseline showed that low HGS and insulin resistance at the baseline were independent determinants of the primary outcome (hazard ratio [HR] = 2.23 [95% confidence interval (CI), 1.06–4.72] and 2.39 [95% CI, 1.18–4.83], respectively). Sex stratification confirmed that HGS and muscle mass were independent determinants of the primary outcome only in women (HR per quartile, 0.58 [95% CI, 0.37–0.93] and 0.46 [95% CI, 0.25–0.85], respectively). `. Conclusions Low HGS and insulin resistance were independent risk factors for aggravated glycemic control among older patients with long standing T2DM.

Abstract Background Recent resting-state fMRI studies demonstrated functional dysconnectivity within the central pain matrix in migraineurs. This study aimed to investigate the spatial distribution and amplitude of low-frequency oscillations (LFOs) using fractional amplitude of low-frequency fluctuation (fALFF) analysis in migraine patients without aura, and to examine relationships between regional LFOs and clinical variables. Methods Resting-state fMRI data were obtained and preprocessed in 44 migraine patients without aura and 31 matched controls. fALFF was computed according to the original method, z-transformed for standardization, and compared between migraineurs and controls. Correlation analysis between regional fALFF and clinical variables was performed in migraineurs as well. Results Compared with controls, migraineurs had significant fALFF increases in bilateral ventral posteromedial (VPM) thalamus and brainstem encompassing rostral ventromedial medulla (RVM) and trigeminocervical complex (TCC). Regional fALFF values of bilateral VPM thalamus and brainstem positively correlated with disease duration, but not with migraine attack frequency or Migraine Disability Assessment Scale score. Conclusions We have provided evidence for abnormal LFOs in the brainstem including RVM/TCC and thalamic VPM nucleus in migraine without aura, implicating trigeminothalamic network oscillations in migraine pathophysiology. Our results suggest that enhanced LFO activity may underpin the interictal trigeminothalamic dysrhythmia that could contribute to the impairments of pain transmission and modulation in migraine. Given our finding of increasing fALFF in relation to increasing disease duration, the observed trigeminothalamic dysrhythmia may indicate either an inherent pathology leading to migraine headaches or a consequence of repeated attacks on the brain.

Abstract Background Fatigability has recently emerged in oncology as a concept that anchors patients’ perceptions of fatigue to defined activities of specified duration and intensity. This study aimed to examine the psychometric properties of the Korean version of the Pittsburgh Fatigability Scale (K-PFS) for women with breast cancer. Methods This cross-sectional study involved 196 women with breast cancer recruited from a tertiary hospital in Seoul, Korea. Reliability was evaluated using Cronbach’s alpha, and confirmatory factor analysis was conducted to examine the factor structure of the K-PFS. Four goodness-of-fit values were evaluated: (1) the comparative fit index (CFI), (2) the Tucker–Lewis index (TLI), (3) the root mean square error of approximation (RMSEA), and (4) the standardized root mean square residual (SRMR). Results Of the 196 survivors, 71.1% had greater physical fatigability (K-PFS Physical score ≥ 15) and 52.6% had greater mental fatigability (K-PFS Mental score ≥ 13). The Cronbach’s alpha coefficient for the total K-PFS scale was 0.926, and the coefficients for the physical and mental fatigability domains were 0.870 and 0.864, respectively. In the confirmatory factor analysis for physical fatigability, the SRMR value (0.076) supported goodness of fit, but other model fit statistics did not (CFI = 0.888, TLI = 0.826, and RMSEA = 0.224). For mental fatigability, although three goodness-of-fit values were acceptable (CFI = 0.948, TLI = 0.919, and SRMR = 0.057), the RMSEA value (0.149) did not indicate good model fit. However, each item coefficient was statistically significant (> 0.5), and the K-PFS was therefore found to be valid from a theoretical perspective. Conclusion This study provides meaningful information on the reliability and validity of the K-PFS instrument, which was developed to meet an important need in the context of breast cancer survivors. Additional research should examine its test–retest reliability and construct validity with performance measures.

Abstract Background Fatigue is one of the most common and burdensome symptoms experienced by cancer patients. In interventions intended to reduce fatigue in such patients, fatigability, or perception of fatigue contextualized to activities of fixed intensity and duration, may also be measured. This study investigated the effects of a 15-month intervention on fatigue and fatigability in breast cancer survivors (BCS); explored the fatigue-fatigability relationship; and evaluated the impacts of fatigue and fatigability on anxiety, depression, sleep disturbance, and endocrine symptoms. Methods A randomized controlled trial design was applied to an exercise program called BLESS (Better Life after cancer, Energy, Strength, and Support). The intervention included this 12-week exercise program and four follow-up contacts intended to promote exercise adherence over the following year. Participants were women aged 20 to 69 who had been diagnosed with stage I, II, or III breast cancer; had completed active treatment; and had moderate or higher fatigue. At the completion of the intervention, the survey responses of 40 BCS were evaluated using the chi-square test and multiple regression analysis. The Korean versions of the Revised Piper Fatigue Scale and Pittsburgh Fatigability Scale were used to measure fatigue and fatigability, respectively. Results There was no significant difference in fatigue or fatigability between the experimental and control groups at intervention completion. However, the control group showed a stronger association than the experimental group between fatigue and physical fatigability. In the control group, fatigue and fatigability were significantly associated with anxiety, depression, sleep disturbance, and endocrine symptoms. In the experimental group, only the cognitive/mood fatigue score and depression were significantly associated. Only endocrine symptoms influenced mental fatigability (B = − 0.185, P

Abstract Background Migraine is a neurological, primary headache disorder affecting more than 1 billion people worldwide, with a multi-faceted burden that can significantly impact the everyday life of a patient, both during and between attacks. However, studies on patient awareness, burden, and clinical management of migraine in Korea are limited and outdated. The aim of this study was to comprehensively investigate the current difficulties and unmet needs that Korean patients with migraine encounter from their perspective. Methods A total of 207 patients with episodic or chronic migraine aged between 15 and 76 years, completed a survey designed to cover the following topics: diagnosis, understanding of the disease, treatment experience, disability, and quality of life. Patients were recruited by their neurologists from 11 specialized headache clinics in Korea and completed the survey between 22 July and 19 August 2019. Validated scales such as the Migraine Disability Assessment (MIDAS) questionnaire and Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) were used to assess levels of disability and quality of life, respectively, in patients. Results On average, it took 10.1 years from onset of symptoms to diagnosis and a mean of 3.9 hospitals were visited for treatment prior to the patient’s current hospital. There was a lack of understanding among respondents about migraine, with 55.6% believing that unilateral headache is a unique feature of migraine compared with other headache disorders. On average, high levels of disability and poor quality of life were reported by patients, as assessed by MIDAS and MSQv2.1, respectively, but only 23.7% had regularly taken preventive medication in the past. Overall satisfaction with previous doctor-patient relationships was reported by 29.5% of respondents, and satisfaction with preventive and acute medications by only 40.8% and 27.1% of the respondents, respectively. Conclusion Korean patients with migraine experience significant disability and reduced quality of life as a result of the disease and have clear unmet needs in terms of diagnosis, understanding of the disease, and disease management including treatment.

Abstract Background Pazopanib, a multitargeted tyrosine kinase inhibitor, is recommended as the standard treatment for refractory soft tissue sarcoma (STS). However, there are comparatively few molecular determinants for predicting pazopanib efficacy. Based on correlative studies regarding the predictive impact of PD-L1, we investigated the clinical relevance of PD-L1 expression and evaluated its value for predicting pazopanib efficacy. Methods Tumour tissues from patients with advanced STS who went on to receive pazopanib were assessed for PD-L1 expression. Immunohistochemistry was performed using an anti-PD-L1 antibody, and the PD-L1 tumour proportion score (TPS) was calculated as the percentage of at least 100 viable cells with positive expression, defined as TPS ≥ 1%. Results Among the 67 patients, 8 (11.9%) achieved partial response and a median progression-free survival (PFS) of 4.8 months (95% CI 3.8–5.7). PD-L1 expression in tumour cells was detected in 13 (19.4%) cases and the TPS scores ranged from 1 to 100%, as follows: 0 (n = 54, 80.6%), 1–9% (n = 3, 4.5%), 10–49% (n = 9, 13.4%), and ≥ 50% (n = 1, 1.5%). PD-L1 positive tumours exhibited a poorer response to pazopanib treatment than the PD-L1 negative tumours (0% vs 14.8%, P = 0.07). PD-L1-positive tumours had significantly shorter PFS than the PD-L1-negative tumours (median PFS 2.8 vs 5.1 months, P = 0.003), and PD-L1 positivity was an independent predictor of poor response to pazopanib treatment (HR 2.77, 95% CI; 1.45–5.56, P = 0.006). Conclusion We identified that PD-L1 expression can help predict the clinical outcome of patients with advanced STS treated with pazopanib. Based on our study, stratification should be actively considered in order to identify patients who will benefit from pazopanib or further therapeutic strategies for future clinical trials.

Abstract Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells. Methods In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT characteristics, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells. Results The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT traits of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT characteristics in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis.

Abstract Background Some sea anemone toxins cause renal injuries resembling hemolytic uremic syndrome (HUS). To date, only a few cases of HUS caused by sea anemone stings have been reported. In this case report, we have described an HUS case caused by a sea anemone sting. Case presentation In November 2019, a 37-year-old man with no underlying disease was admitted to our hospital. He presented with intense pain, a rash on, and swelling in his right thigh. Two days prior, he had been stung by a sea anemone while scuba diving in Cebu, Philippines. His blood tests revealed renal dysfunction, and his platelet count was normal. However, on day three, the platelet count decreased rapidly. His blood haptoglobin level decreased, and schistocytes were identified on the peripheral blood smear. We suspected thrombotic microangiopathy and started the conventional treatment, comprising hemodialysis, blood transfusion, and antibiotic administration. ADAMTS-13 and genetic test results associated with atypical HUS were normal. Therefore, the patient was diagnosed with HUS caused by a sea anemone toxin. Conclusions HUS caused by a sea anemone toxin is rare, but it is a serious medical disease. Clinicians should consider HUS in patients with such clinical presentations, and they should make prompt treatment-related decisions.

Abstract Background Herpes zoster (HZ) infection of hematopoietic stem cell transplant (HSCT) patients is of clinical concern. Vaccination could help restore immunity to varicella zoster virus (VZV); however, temporal changes in immunogenicity and safety of live HZ vaccines after HSCT is still unclear. The aim of this study was to elucidate the temporal immunogenicity and safety of the HZ vaccine according to time since HSCT and to determine optimal timing of vaccination. Methods Live HZ vaccine was administered to patients 2–5 years or > 5 years post-HSCT. Control groups comprised patients with a hematologic malignancy who received cytotoxic chemotherapy and healthy volunteers. Humoral and cellular immunogenicity were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) and an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Vaccine-related adverse events were also monitored. Results Fifty-six patients with hematologic malignancy (41 in the HSCT group and 15 in the chemotherapy group) along with 30 healthy volunteers were enrolled. The geometric mean fold rises (GMFRs) in humoral immune responses of the 2–5 year and > 5 year HSCT groups, and the healthy volunteer group, were comparable and significantly higher than that of the chemotherapy group (3.15, 95% CI [1.96–5.07] vs 5.05, 95% CI [2.50–10.20] vs 2.97, 95% CI [2.30–3.83] vs 1.42, 95% CI [1.08–1.86]). The GMFR of cellular immune responses was highest in the HSCT 2–5 year group and lowest in the chemotherapy group. No subject suffered clinically significant adverse events or reactivation of VZV within the follow-up period. Conclusion Our findings demonstrate that a live HZ vaccine is immunogenic and safe when administered 2 years post-HSCT.

Abstract Background By investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice. Methods This is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care. Results A total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24–89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620). Conclusions In patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.

Abstract Background Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD). Recently, atherogenic index of plasma (AIP) has been proposed as a novel predictive marker for CVD, and few cross sectional studies have demonstrated a relationship between AIP and coronary artery disease. The present study investigated the association between AIP and the progression of coronary artery calcification (CAC) in Korean adults without CVD. Methods A total of 1124 participants who had undergone CAC measurement at least twice by multi-detector computed tomography (CT) at a health check-up center were enrolled. Their anthropometric measurements and various cardiovascular risk factors were assessed. AIP was defined as the base 10 logarithm of the ratio of the concentration of triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C). CAC progression was defined as either incident CAC in a CAC-free population at baseline, or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACS) in subjects with detectable CAC at baseline. Results CAC progression was observed in 290 subjects (25.8%) during the mean follow-up of 4.2 years. All subjects were stratified into three groups according to AIP. There were significant differences in cardiovascular parameters among groups at baseline. The follow-up CAC and the incidence of CAC progression increased gradually with rising AIP tertiles. In logistic regression analysis, the odds ratio for CAC progression was 2.27 when comparing the highest to the lowest tertile of AIP (95% CI: 1.61–3.19; P for trend

Abstract Background Poor quality obstetric and newborn care persists in sub-Saharan Africa and weak provider competence is an important contributor. To be competent, providers need to be both knowledgeable and confident in their ability to perform necessary clinical actions. Confidence or self-efficacy has not been extensively studied but may be related to individuals’ knowledge, ability to practice their skills, and other modifiable factors. In this study, we investigated how knowledge and scope of practice are associated with provider confidence in delivering obstetric and newborn health services in Uganda and Zambia. Methods This study was a secondary analysis of data from an obstetric and newborn care program implementation evaluation. Provider knowledge, scope of practice (completion of a series of obstetric tasks in the past 3 months) and confidence in delivering obstetric and newborn care were measured post intervention in intervention and comparison districts in Uganda and Zambia. We used multiple linear regression models to investigate the extent to which exposure to a wider range of clinical tasks associated with confidence, adjusting for facility and provider characteristics. Results Of the 574 providers included in the study, 69% were female, 24% were nurses, and 6% were doctors. The mean confidence score was 71%. Providers’ mean knowledge score was 56% and they reported performing 57% of basic obstetric tasks in the past 3 months. In the adjusted model, providers who completed more than 69% of the obstetric tasks reported a 13-percentage point (95% CI 0.08, 0.17) higher confidence than providers who performed less than 50% of the tasks. Female providers and nurses were considerably less confident than males and doctors. Provider knowledge was moderately associated with provider confidence. Conclusions Our study showed that scope of practice (the range of clinical tasks routinely performed by providers) is an important determinant of confidence. Ensuring that providers are exposed to a variety of services is crucial to support improvement in provider confidence and competence. Policies to improve provider confidence and pre-service training should also address differences by gender and by cadres.

Abstract Background Systematic in vitro loss-of-function screens provide valuable resources that can facilitate the discovery of drugs targeting cancer vulnerabilities. Results We develop a deep learning-based method to predict tumor-specific vulnerabilities in patient samples by leveraging a wealth of in vitro screening data. Acquired dependencies of tumors are inferred in cases in which one allele is disrupted by inactivating mutations or in association with oncogenic mutations. Nucleocytoplasmic transport by Ran GTPase is identified as a common vulnerability in Her2-positive breast cancers. Vulnerability to loss of Ku70/80 is predicted for tumors that are defective in homologous recombination and rely on nonhomologous end joining for DNA repair. Our experimental validation for Ran, Ku70/80, and a proteasome subunit using patient-derived cells shows that they can be targeted specifically in particular tumors that are predicted to be dependent on them. Conclusion This approach can be applied to facilitate the development of precision therapeutic targets for different tumors.

Abstract Background Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients. Methods Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI

Abstract Background The differentiation of human mesenchymal stem cells (hMSCs) into osteoblasts (OBs) is a prerequisite for bone formation. However, little is known about the definitive surface markers for OBs during osteogenesis. Methods To study the surface markers on OBs, we generated and used monoclonal antibodies (MAbs) against surface molecules on transforming growth factor-β1 (TGF-β1)-treated cancer cells. The generated MAbs were further selected toward expression changes on hMSCs cultured with TGF-β1/bone morphogenetic protein-2 (BMP-2) or osteogenic differentiation medium (ODM) by flow cytometry. Immunoprecipitation and mass spectrometry were performed to identify target antigens of selected MAbs. Expression changes of the target antigens were evaluated in hMSCs, human periodontal ligament cells (hPDLCs), and human dental pulp cells (hDPCs) during osteogenic and adipogenic differentiation by quantitative polymerase chain reaction (qPCR) and flow cytometry. hMSCs were also sorted by the MAbs using magnetic-activated cell sorting system, and osteogenic potential of sorted cells was evaluated via Alizarin Red S (ARS) staining and qPCR. Results The binding reactivity of MR14-E5, one of the MAbs, was downregulated in hMSCs with ODM while the binding reactivity of ER7-A7, ER7-A8, and MR1-B1 MAbs was upregulated. Mass spectrometry and overexpression identified that MR14-E5, ER7-A7/ER7-A8, and MR1-B1 recognized integrin α2, α3, and αV, respectively. Upon osteogenic differentiation of hMSCs, the expression of integrin α2 was drastically downregulated, but the expression of integrin α3 and αV was upregulated in accordance with upregulation of osteogenic markers. Expression of integrin α3 and αV was also upregulated in hPDLCs and hDPCs during osteogenic differentiation. Cell sorting showed that integrin αV-high hMSCs have a greater osteogenic potential than integrin αV-low hMSCs upon the osteogenic differentiation of hMSCs. Cell sorting further revealed that the surface expression of integrin αV is more dramatically induced even in integrin αV-low hMSCs. Conclusion These findings suggest that integrin α3 and αV induction is a good indicator of OB differentiation. These findings also shed insight into the expression dynamics of integrins upon osteogenic differentiation of hMSCs and provide the reason why different integrin ligands are required for OB differentiation of hMSCs.

Abstract Background Our aim was to investigate the relationship between coexisting cluster headache (CH) and migraine with anxiety and depression during active cluster bouts, and how symptoms change during remission. Methods We analyzed data from 222 consecutive CH patients and 99 age- and sex-matched controls using a prospective multicenter registry. Anxiety or depression was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9), respectively. Moderate-to-severe anxiety or depression was defined as a score of ≥10 at baseline (during a cluster bout). We assessed for changes in anxiety and depression during CH remission periods. Results Among the CH patients, the prevalence of moderate-to-severe anxiety and depression was seen in 38.2% and 34.6%, respectively. Compared with controls, CH patients were associated with moderate-to-severe anxiety and depression (multivariable-adjusted odds ratio [aOR] = 7.32, 95% confidence intervals [CI] = 3.35–15.99 and aOR = 4.95, 95% CI = 2.32–10.57, respectively). CH patients with migraine were significantly more likely to have moderate-to-severe anxiety and depression (aOR = 32.53, 95% CI = 6.63–159.64 and aOR = 16.88, 95% CI = 4.16–68.38, respectively), compared to controls without migraine. The GAD-7 and PHQ-9 scores were significantly reduced between cluster bout and remission periods (from 6.8 ± 5.6 to 1.6 ± 2.8; P

Abstract Background Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely used techniques for the treatment of gastric epithelial dysplasia. Previous studies have compared the clinical outcome of endoscopic resection for early gastric cancer, but few studies have focused on gastric dysplasia alone. This study aimed to evaluate the long-term prognosis following endoscopic procedures for gastric epithelial dysplasia, investigate differences in local recurrence rates according to the treatment modality, and identify risk factors associated with local recurrence. Methods In this retrospective study, local recurrence rates and risk factors associated with local recurrence were compared between 599 patients who underwent EMR and 306 who underwent ESD for gastric epithelial dysplasia from January 2011 to December 2015. Results The en bloc resection rate (32.2% vs. 100%, p 2 cm (p = 0.002) or red in color (p = 0.03). The ESD group had a significantly lower local recurrence rate, with a higher complete resection rate, than that in the EMR group (p 2 cm or showing redness due to an increased risk of local recurrence and EMR may be possible for low-grade dysplasia that is less than 2 cm without surface changes such as redness, depression and nodularity.

Abstract Background Until recently, it is generally considered safe to perform magnetic resonance imaging (MRI) in patients with an intrathecal drug administration system (ITDAS) device. In this study, we presented a case of morphine overdose due to ITDAS malfunction during MRI evaluation for the diagnosis of stroke. Case presentation A 58-year-old woman was referred to the emergency department for left-sided hemiparesis and dysarthria. She had undergone ITDAS implantation 4 years ago because of intractable back pain. Her brain MRI examination did not show any abnormalities except an old hemorrhagic infarction in the right basal ganglia. After MRI was performed, her symptoms completely resolved. Approximately 3 h after the MRI scan, the patient showed progressive stuporous consciousness and decreased respiration with decreased peripheral oxygen saturation of 80%. Initial arterial blood gas analysis revealed respiratory acidosis with hypoxia and hypercapnia. We suspected the opioid overdose for her unconciousness, small and sluggish pupils, and slow respiration. The patient regained consciousness within 3 min after the administration of naloxone with severe anxiety and irritability, without any respiratory symptoms or focal neurological deficits. In the pump interrogation and actual reservoir checks performed 6 h after the MRI scan, there was no significant difference between the expected reservoir volume and actual reservoir volume. Follow-up MRI performed to rule out posterior circulation infarction showed no structural lesions. The patient was eventually discharged without further neurologic or functional deterioration, with diagnosis of transient ischemia attack for initial symptoms of focal neurologic deficits. Conclusion Although both ex vivo and in vivo studies have provided evidence that ITDAS devices are MRI-compatible, the pump is made of titanium and has ferromagnetic components. Since misdiagnosis of overinfusion could lead to mortality, early awareness of overinfusion of the intrathecal drug is needed to all clinicians in case of performing MRI in ITDAS implanted patients.