Artificial Intelligence-Powered Hematoxylin and Eosin Analyzer Reveals Distinct Immunologic and Mutational Profiles among Immune Phenotypes in Non-Small-Cell Lung Cancer.

The tumor microenvironment can be classified into three immune phenotypes: inflamed, immune excluded, and immune-desert. Immunotherapy efficacy has been shown to vary by phenotype; yet, the mechanisms are poorly understood and demand further investigation. This study unveils the mechanisms using an artificial intelligence-powered software called Lunit SCOPE. Artificial intelligence was used to classify 965 samples of non-small-cell lung carcinoma from The Cancer Genome Atlas into the three immune phenotypes. The immune and mutational profiles that shape each phenotype using xCell, gene set enrichment analysis with RNA-sequencing data, and cBioportal were described. In the inflamed subtype, which showed higher cytolytic score, the enriched pathways were generally associated with immune response and immune-related cell types were highly expressed. In the immune excluded subtype, enriched glycolysis, fatty acid, and cholesterol metabolism pathways were observed. The KRAS mutation, BRAF mutation, and MET splicing variant were mostly observed in the inflamed subtype. The two prominent mutations found in the immune excluded subtype were EGFR and PIK3CA mutations. This study is the first to report the distinct immunologic and mutational landscapes of immune phenotypes, and demonstrates the biological relevance of the classification. In light of these findings, the study offers insights into potential treatment options tailored to each immune phenotype.

Associations of only-child status with health outcomes and risky behaviors in Korean middle- and high-school students: An outcome-wide analysis.

The proportion of children who are the only child in the family are increasing. Several associations between only-child status and health outcomes or risky behaviors have been identified, but no study has explored associations across a wide range of outcomes in a single study. We used the 2019 Korea Youth Risk Behavior Survey, a nationwide cross-sectional survey of 57,303 middle and high school students, to perform an outcome-wide analysis on six health outcomes and risky behaviors, i.e. alcohol use, asthma, body mass index, sexual activity, smoking, and suicide attempt. Individual multivariable logistic regression models examined associations between single-child status and each outcome or behavior. Of the eligible 38,211 students, 5,334 students (14.0 %) were the only child in their family, while 32,877 students (86.0 %) had siblings. Of the six selected outcomes and behaviors, alcohol use (aOR 0.88, 95 % CI 0.82-0.94), asthma (aOR 1.22, 95 % CI 1.10-1.35) and sexual activity (aOR 1.16, 95 % CI 1.02-1.31) were significantly associated with only-child status. Thus, being the only child among South Korean adolescents is both a potential protective factor and risk factor for different health outcomes and behaviors. Future research is warranted to corroborate these findings and identify mechanisms, which could provide evidence for reducing adverse outcomes and behaviors in adolescents.

Racial/Ethnic Disparity in Association Between Fetal Alcohol Syndrome and Alcohol Intake During Pregnancy: Multisite Retrospective Cohort Study.

BACKGROUND: Alcohol consumption during pregnancy is associated with a range of adverse birth-related outcomes, including stillbirth, low birth weight, preterm birth, and fetal alcohol syndrome (FAS). With more than 10% of women consuming alcohol during pregnancy worldwide, it is increasingly important to understand how racial/ethnic variations affect FAS onset. However, whether race and ethnicity inform FAS risk assessment when daily ethanol intake is controlled for remains unknown. OBJECTIVE: This study aimed to assess racial/ethnic disparities in FAS risk associated with alcohol consumption during pregnancy. METHODS: We used data from a longitudinal cohort study (the Collaborative Initiative on Fetal Alcohol Spectrum Disorders) at 5 hospital sites around the United States of 595 women who consumed alcohol during pregnancy from 2007 to 2017. Questionnaires, in-person interviews, and reviews of medical, legal, and social service records were used to gather data on average alcoholic content (AAC) during pregnancy. Self-reports of maternal race (American Indian/Alaska Native [AI/AN], Asian, Native Hawaiian or other Pacific Islander, Black or African American, White, more than one race, and other) and ethnicity (Hispanic/Latino or not Hispanic/Latino), as well as FAS diagnoses based on standardized dysmorphological criteria, were used for analysis. Log-binomial regression was used to examine the risk of FAS associated with each 1-gram increase in ethanol consumption during pregnancy, stratified by race/ethnicity. RESULTS: A total of 3.4% (20/595) of women who reported consuming alcohol during pregnancy gave birth to a baby with FAS. Women who gave birth to a baby with FAS had a mean AAC of 32.06 (SD 9.09) grams, which was higher than that of women who did not give birth to a baby with FAS (mean 12.07, SD 15.87 grams). AI/AN mothers with FAS babies had the highest AAC (mean 42.62, SD 8.35 grams), followed by White (mean 30.13, SD 4.88 grams) and Black mothers (mean 27.05, SD 12.78 grams). White (prevalence ratio [PR] 1.10, 95% CI 1.03-1.19), Black (PR 1.13, 95% CI 1.04-1.23), and AI/AN (PR 1.10, 95% CI 1.00-1.21) mothers had 10% to 13% increased odds of giving birth to a baby with FAS given the same exposure to alcohol during pregnancy. Regardless of race, a 1-gram increase in AAC resulted in a 4% increase (PR 1.04, 95% CI 1.02-1.07) in the chance of giving birth to a baby with ≥2 facial anomalies (ie, short palpebral fissures, thin vermilion border of the upper lip, and smooth philtrum) and a 4% increase (PR 1.04, 95% CI 1.01-1.07) in the chance of deficient brain growth. CONCLUSIONS: The risk of delivering a baby with FAS was comparable among White, Black, and AI/AN women at similar levels of drinking during pregnancy. Regardless of race, a 1-gram increase in AAC resulted in increased odds of giving birth to a baby with facial anomalies or deficient brain growth.

Correction: Racial/Ethnic Disparity in Association Between Fetal Alcohol Syndrome and Alcohol Intake During Pregnancy: Multisite Retrospective Cohort Study.

[This corrects the article DOI: 10.2196/45358.].

Papillary thyroid cancer immune phenotypes via tumor-infiltrating lymphocyte spatial analysis.

Standard-of-care treatment options provide an excellent prognosis for papillary thyroid cancers (PTCs); however, approximately 10% of cases are advanced PTCs, resulting in less than 50% 5-year survival rates. Understanding the tumor microenvironment is essential for understanding cancer progression and investigating potential biomarkers for treatment, such as immunotherapy. Our study focused on tumor-infiltrating lymphocytes (TILs), which are the main effectors of antitumor immunity and related to the mechanism of immunotherapy. Using an artificial intelligence model, we analyzed the density of intratumoral and peritumoral TILs in the pathologic slides of The Cancer Genome Atlas PTC cohort. Tumors were classified into three immune phenotypes (IPs) based on the spatial distribution of TILs: immune-desert (48%), immune-excluded (34%), and inflamed (18%). Immune-desert IP was mostly characterized by RAS mutations, high thyroid differentiation score, and low antitumor immune response. Immune-excluded IP predominantly consisted of BRAF V600E-mutated tumors and had a higher rate of lymph node metastasis. Inflamed IP was characterized by a high antitumor immune response, as demonstrated by a high cytolytic score, immune-related cell infiltrations, expression of immunomodulatory molecules (including immunotherapy target molecules), and enrichment of immune-related pathways. This study is the first to investigate IP classification using TILs in PTC through a tissue-based approach. Each IP had unique immune and genomic profiles. Further studies are warranted to assess the predictive value of IP classification in advanced PTC patients treated with immunotherapy.

A Systematic Review of Systematic Reviews on the Epidemiology, Evaluation, and Treatment of Plantar Fasciitis.

The number of systematic review and meta-analyses on plantar fasciitis is expanding. The purpose of this review was to provide a comprehensive summary of reviews on the topic pertaining to plantar fasciitis, identify any conflicting and inconsistent results, and propose future research direction. A qualitative review of all systematic reviews and meta-analyses related to plantar fasciitis up to February 2021 was performed using PubMed, Embase, Web of Science, and the Cochrane Database. A total of 1052 articles were initially identified and 96 met the inclusion criteria. Included articles were summarized and divided into the following topics: epidemiology, diagnosis, and treatment. While the majority of reviews had high level of heterogeneity and included a small number of studies, there was general consensus on certain topics, such as BMI as a risk factor for plantar fasciitis and extracorporeal shockwave therapy as an effective mode of therapy. A qualitative summary of systematic reviews and meta-analyses published on plantar fasciitis provides a single source of updated information for clinicians. Evidence on topics such as the epidemiology, exercise therapy, or cost-effectiveness of treatment options for plantar fasciitis are lacking and warrant future research.

The importance of timely contact tracing - A simulation study.

BACKGROUND: While the role of contact tracing in the containment of the COVID-19 epidemic remains important until vaccines are widely available, literature on objectively measurable indicators for the effectiveness of contact tracing is scarce. We suggest the diagnostic serial interval, the time between the diagnosis of the infector and infectee, as a new indicator for the effectiveness of contact tracing. METHODS: Using an agent-based simulation model, we demonstrate how the diagnostic serial interval correlates with the course of the epidemic. We consider four scenarios of how diagnosis and subsequent isolation are triggered: 1. never, 2. by symptoms, 3. by symptoms and loose contact tracing, 4. by symptoms and tight contact tracing. We further refine scenarios 3 and 4 with different lengths of target diagnostic serial intervals. RESULTS: Scenarios 1 and 2 did not yield a notable difference. In scenarios 3 and 4, however, contact tracing led to a decrease of the height of the epidemic as well as the cumulative proportion of infected agents. Generally, the shorter the diagnostic serial interval was, the smaller the peak of the epidemic became, and the more proportion of the population remained susceptible at the end of the epidemic. CONCLUSION: A short target diagnosis interval is critical for contact tracing to be effective in the epidemic control. The diagnosis interval can be used to assess and guide the contact tracing strategy.

Changes in Subway Ridership in Response to COVID-19 in Seoul, South Korea: Implications for Social Distancing.

Introduction While numerous episodes of Coronavirus disease 2019 (COVID-19) infection and subsequent government announcements in South Korea were accompanied by widespread social distancing efforts by the people, it is unclear whether these episodes and government announcements were actually influential in improving social distancing, or whether the level of response among different demographic groups varied. Methods Data were downloaded from Seoul Data Open Plaza, and changes in the number of passengers on the Seoul Metropolitan Subway network between January 1, 2020, and March 31, 2020, were used to assess the extent to which people in Seoul practiced social distancing. Five events regarding COVID-19 that received wide public attention between January and March 2020 were identified and the changes in the number of passengers before and after each event were analyzed. Also, similar analyses were performed for 16 stations that were specific in either the age or purpose of the visit of the passengers. Results Compared to the third week of January 2020 (January 13-19), the mean daily number of passengers in all stations decreased by 2,984,857.4 or 40.6% by the first week of March (March 2-8). The percentage decrease in individual stations between this period was not significantly different between "young" and "old" stations (46.3% vs. 49.2%; p = 0.551) but was significantly smaller in "work" stations than in "leisure" stations (36.2% vs. 51.6%; p = 0.021). Of the five events, the first reported death due to COVID-19 in South Korea and the identification of a mass infection cluster in Daegu on February 20 were accompanied by the greatest decrease of the mean daily number of passengers (1,352,153.3 or 20.8%), while the first mass infection in Seoul on March 10 and the announcement of aggressive social distancing campaign on March 22 were accompanied by an increase in the number of passengers. Conclusions The number of subway passengers in Seoul decreased markedly during late February but slowly increased afterward, suggesting decreasing levels of risk perception and adherence to social distancing. Understanding the differing patterns of subway use by age or purpose of the visit may guide policymakers and the general public in shaping their future response to the current pandemic.

Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis.

BACKGROUND: Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic review and meta-analysis to determine the effect of citrulline supplements on the post-exercise rating of perceived exertion (RPE), muscle soreness, and blood lactate levels. METHODS: A random effects model was used to calculate the effect sizes due to the high variability in the study design and study populations of the articles included. A systematic search of PubMed, Web of Science, and ClinicalTrials.gov was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving healthy individuals and that investigated the acute effect of citrulline supplements on RPE, muscle soreness, and blood lactate levels. The supplementation time frame was limited to 2 h before exercise. The types and number of participants, types of exercise tests performed, supplementation protocols for L-citrulline or citrulline malate, and primary (RPE and muscle soreness) and secondary (blood lactate level) study outcomes were extracted from the identified studies. RESULTS: The analysis included 13 eligible articles including a total of 206 participants. The most frequent dosage used in the studies was 8 g of citrulline malate. Citrulline supplementation significantly reduced RPE (n = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; n = 6, p = 0.25, respectively). However, citrulline supplementation did not significantly reduce muscle soreness 72-h post-exercise (n = 4, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17). CONCLUSION: Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting blood lactate levels.

Medical students' perspectives on recommencing clinical rotations during coronavirus disease 2019 at one institution in South Korea.

PURPOSE: Clinical rotations of medical students across the world have inevitably been affected due to the coronavirus disease 2019 (COVID-19) pandemic. The aims of this study were to explore medical students' perception on the school's response and management of clinical rotation during the COVID-19 pandemic and on how it had affected the quality of their education. METHODS: An online questionnaire was distributed to third year medical students at one institution whose clinical rotations re-started during the pandemic. The questions asked about the students' satisfaction with the school's policy and feelings of safety, and the impact of COVID-19 on clinical learning. RESULTS: The students' perception on the school's response to the pandemic was mixed. Re-commencement of the clinical rotations and procurement of personal protective equipment was positive but a third of students still felt unsafe. The decreased number of hospital patients did not seem to have impacted their overall clinical education with praise on the role of the supervising physicians. Seventy-six-point seven percent of students conferred the positive educational opportunities on medical professionalism presented to them only as the clinical rotation during the ongoing pandemic. CONCLUSION: Our observations on the re-commencement of clerkship during this pandemic may help equip medical institutions on future public health crisis.

Clinical and radiological outcomes of hemivertebra resection for congenital scoliosis in children under age 10 years: More than 5-year follow-up.

The surgical treatment of congenital scoliosis under 10 years is difficult as it involves resecting vertebrae. Moreover, patient follow-up after surgery is extremely important because the patient is a child whose growth has not been completed. However, there are very few long-term follow-up studies after surgical treatment of congenital scoliosis. Therefore, this study is designed to evaluate surgical outcomes after posterior hemivertebra resection in children under 10 years and its long-term effects.Twenty-one patients with congenital scoliosis who were younger than 10 years at the time of the surgery and received posterior hemivertebra resection and fusion using pedicle screw fixation were included in this study.There were significant improvements in the main curve, coronal balance, sagittal vertical axis, thoracic kyphosis, and lumbar lordosis after surgery (P < .001, .021, .047, .043, .006, respectively). Coronal balance, sagittal vertical axis, thoracic kyphosis, and lumbar lordosis remained within the normal range during the follow-up period; however, main curve deteriorated significantly (P = .005). Trunk appearance of perception scale improved significantly after surgery (P = .031) and was maintained during the follow-up period (P = .078).In conclusion, posterior hemivertebra resection and fusion using pedicle screw fixation in patients under 10 years old with congenital scoliosis is a safe and effective procedure that can achieve rigid fixation and deformity correction. Complete resection of the hemivertebra is important for deformity correction and prevention of curve progression, and careful long-term follow-up is necessary.

Association between Allergic Rhinitis and Regular Physical Activity in Adults: A Nationwide Cross-Sectional Study.

Evidence regarding the association between allergic rhinitis (AR) and physical activity (PA) is conflicting. Previous studies have mostly relied only on self-reported symptoms to define AR, did not classify AR by severity or persistence, and included only children or athletes. The present cross-sectional study evaluated the association between PA and objectively-defined AR and its subtypes in the general adult population using data for 1932 eligible participants aged 19 years or older in the 2010 Korea National Health and Nutrition Examination Survey. Multivariable logistic regression analyses were performed to evaluate the relationship between three types of PA and overall AR, AR subtypes, and rhinoscopy findings showed that moderate-severe AR was positively associated with vigorous (odds ratio [OR] = 3.392, p = 0.002) and moderate (OR = 3.623, p = 0.007) PA compared to mild AR, while persistent AR was associated with vigorous (OR = 3.954, p = 0.004) and moderate (OR = 3.411, p = 0.022) PA compared to intermittent AR. On rhinoscopy, vigorous PA was significantly associated with watery rhinorrhea (OR = 2.203, p = 0.048) but not pale mucosa. Total immunoglobulin E (IgE) and three allergen-specific IgE were not significantly elevated in participants who performed PA. Therefore, regular vigorous PA is associated with subjective and objective aggravation of AR symptoms, which may not necessarily manifest as increased serum IgE levels.