Monoterpene antifungal activities: evaluating geraniol, citronellal, and linalool on Candida biofilm, host inflammatory responses, and structure-activity relationships.

Introduction: Despite the rising concern with fungal resistance, a myriad of molecules has yet to be explored. Geraniol, linalool, and citronellal are monoterpenes with the same molecular formula (C10H18O), however, neither the effect of these compounds on inflammatory axis induced by Candida spp. nor the antibiofilm Structure-Activity Relationship (SAR) have been well-investigated. Herein we analyzed geraniol, linalool and citronellal antifungal activity, cytotoxicity, and distinctive antibiofilm SAR, also the influence of geraniol on Candida spp induced dysregulated inflammatory axis, and in vivo toxicity. Methods: Minimal inhibitory (MIC) and fungicidal (MFC) concentrations against Candida spp were defined, followed by antibiofilm activity (CFU-colony forming unit/mL/g of dry weight). Cytotoxic activity was assessed using human monocytes (THP-1) and oral squamous cell (TR146). Geraniol was selected for further analysis based on antifungal, antibiofilm and cytotoxic results. Geraniol was tested using a dual-chamber co-culture model with TR146 cells infected with C. albicans, and THP-1 cells, used to mimic oral epithelium upon fungal infection. Expression of Candida enzymes (phospholipase-PLB and aspartyl proteases-SAP) and host inflammatory cytokines (interleukins: IL-1ß, IL-6, IL-17, IL-18, IL-10, and Tumor necrosis factor-TNF) were analyzed. Lastly, geraniol in vivo toxicity was assessed using Galleria mellonella. Results: MIC values obtained were 1.25-5 mM/mL for geraniol, 25-100 mM/mL for linalool, and 100-200 mM/mL for citronellal. Geraniol 5 and 50 mM/mL reduced yeast viability during biofilm analysis, only 500 mM/mL of linalool was effective against a 72 h biofilm and no biofilm activity was seen for citronellal. LD50 for TR146 and THP-1 were, respectively: geraniol 5.883 and 8.027 mM/mL; linalool 1.432 and 1.709 mM/mL; and citronellal 0.3006 and 0.1825 mM/mL. Geraniol was able to downregulate expression of fungal enzymes and host pro-inflammatory cytokines IL-1ß, IL-6, and IL-18. Finally, safety in vivo parameters were observed up to 20 mM/Kg. Discussion: Despite chemical similarities, geraniol presented better antifungal, antibiofilm activity, and lower cytotoxicity when compared to the other monoterpenes. It also showed low in vivo toxicity and capacity to downregulate the expression of fungal enzymes and host pro-inflammatory cytokines. Thus, it can be highlighted as a viable option for oral candidiasis treatment.

The potential for cascading failures in the international trade network.

In our study, we introduce indicators that quantify the influence of each country in complex trade scenarios involving the exchange of raw materials, intermediate goods, and final products across multiple countries. We systematically employ an agent-based model to simulate the propagation of failures from one node to the entire network. This approach allows for the assessment of the impact of each country and the identification of patterns of interaction in the multi-step trade network. Unlike conventional analyses of trade networks, which depict straightforward single-step import/export transactions, our approach captures the intricate realities of processes like raw material procurement, production, and sales in numerous countries from a macroscopic perspective. The findings of our analysis of trade data spanning from 1990 to 2022 reveal several key insights. Firstly, sensitivity to changes in trade volume leading to global failures within interconnected networks has intensified over time. The potential of failure propagation across countries has increased over time, as has the interconnectedness of countries in the global trade landscape. Secondly, despite the increased sensitivity to changes in global trade volume, many countries have become less vulnerable to the influence of others within their multi-step trade networks. This trend aligns with deglobalization, which is evidenced by events such as Brexit and the surge in protectionist measures; these changes indicate a shift in the balance of influence within global trade networks. Thirdly, the results of our analysis of the relationship between load changes and global failures from a regional perspective reveal an intriguing phenomenon: despite limited direct trade connectivity, the interaction between the Latin American and Sub-Saharan African regions is considerable. This suggests the existence of hidden connections between intermediary countries, such that one region's actions can alter the load sensitivity of another, impacting them in unforeseen ways. Furthermore, intra-regional interactions are diminishing in East Asia, while Europe is experiencing a gradual increase in interactions. These trends reflect evolving regional influence, the dynamics of geographic proximity, and the results of economic integration efforts. Additionally, even though the observed period was not long enough to confirm a long-term trend, the previous trend direction was affirmed to persist despite a temporary decrease in trading and reduced sensitivity due to the COVID-19 pandemic. Our study highlights the complexity of global trade dynamics and the need to consider multi-step trade networks and their potential cascading effects when analyzing trade patterns and vulnerabilities.

Who are the key players? Listeners vs spreaders vs others.

The literature on social learning examines how people learn from their neighbors and reach a consensus. The DeGroot social learning model describes the social learning process as one in which people form their opinions by taking a weighted average of their neighbors' opinions. In the model, the influence structure is represented by a single matrix. In this paper, we empirically identify the role of the hub and authority centralities based on this matrix using data on microfinance adoption in rural Indian villages. Controlling for other well-known centrality measures, authority centrality is positively associated with final adoption rates in the villages, but hub centrality is not. Furthermore, we find that authority centrality is the most informative variable predicting microfinance diffusion success from LASSO regressions.

Evolution of fairness in the divide-a-lottery game.

In this paper, we show that fairness can evolve in the divide-a-lottery game which is more general than the divide-a-dollar game by using an indirect evolutionary approach. In the divide-a-lottery game, the size of a pie is uncertain. Two players sequentially bid for a share and they get their bid if the allocation based on the bids turns out to be feasible and otherwise neither gets anything. In this game, rational players over-compete for a higher share, resulting in a high probability of failure in agreement, whereas fair players who dislike the disparity between shares lower their bids thereby reducing the failure probability and thus increasing the expected payoff. As a result, fairness strictly dominates rationality. This is the mechanism through which fairness evolves. However, this result is not robust against even a slight uncertainty about the opponent's type. Surprisingly, we show a contrasted simulation result that only rational players who are strictly dominated by fair players survive evolutionarily for most of the parameter values if players have even a slight chance of not knowing the opponent's type. Our simulation results in a local interaction model in which players only know the type of closer neighbors capture both insights and demonstrate that moderate proportions of both types coexist evolutionarily over time, and that the population average fitness of this polymorphic population is higher than monomorphic population consisting only of fair types or rational types.

Correction: Navigating optimal treaty-shopping routes using a multiplex network model.

[This corrects the article DOI: 10.1371/journal.pone.0256764.].

Risk factors associated with idiopathic sudden sensorineural hearing loss in pregnant South Korean women: a nationwide population-based study.

OBJECTIVE: Sudden sensorineural hearing loss (SSNHL) is rare in pregnancy and can be attributed to pregnancy-induced changes in hormone levels that increase thrombogenic risk and alter cochlear microcirculation with consequent development of sudden deafness. The study aimed to analyze the risk factors associated with SSNHL in pregnant South Korean. METHODS: A retrospective study of the incidence and risk factors associated with SSNHL before pregnancy enrolled 401,470 Korean women who delivered between January 2010 and December 2014. All participants underwent a pre-pregnancy national health screening examination through the National Health Insurance Corporation. We investigated the risk factors in 459 pregnant women with sudden sensorineural hearing loss and in 401,011 pregnant women without SSNHL through the pre-pregnancy national health screening examination and adverse perinatal outcome. RESULTS: No statistically significant intergroup differences were observed in the maternal age, parity, method of delivery, gestational age at delivery, body mass index, blood pressure, as well as fasting blood glucose and cholesterol levels. After adjusting for maternal age, the pre-pregnancy body mass index was associated with an increased risk of sensorineural hearing loss in pregnancy (adjusted odds ratio 1.52, 95% confidence interval 1.04-2.22). The sensorineural hearing loss did not increase the risk for gestational hypertension, preterm birth (<37 weeks' gestation), small- and large-for-gestational-age infants, postpartum hemorrhage, placenta previa, and placental abruption. CONCLUSION: SSNHL can occur throughout pregnancy and is associated with maternal pre-pregnancy obesity. Notably, it does not increase risks during delivery or cause adverse perinatal outcomes.

Navigating optimal treaty-shopping routes using a multiplex network model.

The international tax treaty system is a highly integrated and complex network. In this system, many multinational enterprises (MNEs) explore ways of reducing taxes by choosing optimal detour routes. Treaty abuse by these MNEs causes significant loss of tax revenues for many countries, but there is no systematic way of regulating their actions. However, it may be helpful to find a way of detecting the optimal routes by which MNEs avoid taxes and observe the effects of this behavior. In this paper, we investigate the international tax treaty network system of foreign investment channels based on real data and introduce a novel measure of tax-routing centrality and other centralities via network analysis. Our analysis of tax routing in a multiplex network reveals not only various tax-minimizing routes and their rates, but also new paths which cannot be found by navigating a single network layer. In addition, we identify strongly connected components of the multiplex tax treaty system with minimal tax shopping routes; more than 80 countries are included in this system. This means that there are far more pathways to be observed than can be detected on any given individual single layer. We provide a unified framework for analyzing the international tax treaty system and observing the effects of tax avoidance by MNEs.

Electrochemical Synthesis of Glycine from Oxalic Acid and Nitrate.

In manufacturing C-N bond-containing compounds, it is an important challenge to alternate the conventional methodologies that utilize reactive substrates, toxic reagents, and organic solvents. In this study, we developed an electrochemical method to synthesize a C-N bond-containing molecule avoiding the use of cyanides and amines by harnessing nitrate (NO3- ) as a nitrogen source in an aqueous electrolyte. In addition, we utilized oxalic acid as a carbon source, which can be obtained from electrochemical conversion of CO2. Thus, our approach can provide a route for the utilization of anthropogenic CO2 and nitrate wastes, which cause serious environmental problems including global warming and eutrophication. Interestingly, the coreduction of oxalic acid and nitrate generated reactive intermediates, which led to C-N bond formation followed by further reduction to an amino acid, namely, glycine. By carefully controlling this multireduction process with a fabricated Cu-Hg electrode, we demonstrated the efficient production of glycine with a faradaic efficiency (F.E.) of up to 43.1 % at -1.4 V vs. Ag/AgCl (current density≈90 mA cm-2 ).

Pre-Pregnancy Risk Factors for Severe Hyperemesis Gravidarum: Korean Population Based Cohort Study.

Hyperemesis gravidarum is known to be associated with poor perinatal outcomes. This study aimed to identify pre-pregnancy risk factors for hospital admission in women with hyperemesis gravidarum. We enrolled women who had delivered between 1 January 2013 and 31 December 2015, and had undergone a national health screening examination through the National Health Insurance Corporation 1-2 years before their first delivery. Multiple logistic regression analysis was performed to estimate the risk factors for hospital admission due to hyperemesis gravidarum. Of the 216,373 study participants with hyperemesis gravidarum, 2210 (1.02%) pregnant women were hospitalized. These women had lower waist circumference and were underweight based on body mass index compared to pregnant women who did not require hospitalization due to hyperemesis gravidarum. On multivariate analysis, primiparity, multiple pregnancies, female fetus, alcohol consumption, and pre-pregnancy underweight status were associated with an increased risk of hospitalization due to the condition. In this population-based cohort study, we found that hospitalization due to hyperemesis gravidarum was associated with pre-pregnancy lifestyle characteristics. Early recognition and management of these pre-pregnancy factors may help control the need for hospitalization in women with the condition in subsequent pregnancies.

Evaluation of maternal rhesus blood type as a risk factor in adverse pregnancy outcomes in Korea: a nationwide health insurance database study.

OBJECTIVES: The current study aimed to investigate whether pregnancy outcomes are affected by maternal rhesus (Rh) status by comparing the primigravida pregnancy outcomes of Rh-negative women with those of Rh-positive women. METHODS: The study data were collected from the Korea National Health Insurance Claims Database and the National Health Screening Program for Infants and Children. In total, 1,664,882 primigravida women who gave birth between January 1, 2007 and December 31, 2014, were enrolled in this study. As the risk and severity of sensitization response increases with each subsequent pregnancy, only primigravida women were enrolled. The patients were divided into 2 groups according to Rh status, and the pregnancy outcomes were compared. RESULTS: In total, 1,661,320 women in the Rh-positive group and 3,290 in the Rh-negative group were assessed. With regard to adverse pregnancy outcomes, there was no statistically significant difference between the 2 groups in terms of the prevalence of preeclampsia, postpartum hemorrhage, abruptio placenta, placenta previa, and uterine artery embolization. A univariate analysis revealed that none of the adverse pregnancy outcomes were significantly correlated to Rh status (preeclampsia: odds ratio [OR], 1.00, 95% confidence interval [CI], 0.81-1.23; postpartum hemorrhage: OR, 1.10, 95% CI, 0.98-1.24; abruptio placenta: OR, 0.80, 95% CI, 0.46-1.37; and placenta previa: OR, 1.08, 95% CI, 0.78-1.42). The adjusted ORs of postpartum hemorrhage and preterm birth did not significantly differ. CONCLUSION: Maternal Rh status is not associated with adverse outcomes in primigravida women.

Association between dental caries and adverse pregnancy outcomes.

Poor oral health is not only associated with diabetes and cardiovascular disease but adverse pregnancy outcomes. However the influence of dental caries on pregnancy is unknown. The aim of this study was to evaluate the association between dental caries and adverse pregnancy outcomes and the effect of treatment for dental caries on adverse pregnancy outcomes. Primiparas who delivered a singleton between January 1, 2010 and December 31, 2014 and underwent both general health examination and oral health examination during a National Korea Health Screening Examination within 1 year of pregnancy were eligible. The data of the women who met the inclusion criteria were linked to the data of their offspring contained within the National Korea Health Screening Program for Infants and Children database. Among 120,622 women who delivered during the study period, 28,623 (23.7%) women had dental caries. Among them, 4,741 (16.6%) women were treated for dental caries after diagnosis. In a multivariable analysis, women with dental caries had an increased risk of delivering large-for-gestational-age infants (odds ratio, 1.15; 95% confidence interval, 1.07, 1.23) compared to those without dental caries. When women with dental caries were divided on the basis of the treatment of dental caries, women with dental caries but no treatment had an increased risk of delivering large-for-gestational-age infants (odds ratio, 1.15; 95% confidence interval, 1.06, 1.24); conversely, there was no increased risk in women with dental caries and treatment compared with those without. Dental caries and its treatment were not associated with preterm birth and preeclampsia. Untreated dental caries was not associated with preterm birth or preeclampsia but with the risk of delivering large-for-gestational-age infants. These whole observation may be attributed to the various characteristics of mothers who develop dental caries are not treated.

Clinical Predictors Implicated in the Incidence of Acute Pyelonephritis during the Antepartum Period: A Population-Based Cohort Study.

INTRODUCTION: Acute pyelonephritis (APN) is a common infection during pregnancy that increases the risk of unfavorable maternal and fetal outcomes. However, it has not been clearly elucidated which demographic and clinical characteristics are associated with the incidence of APN during pregnancy. OBJECTIVE: This population-based cohort study aimed to determine the risk factors for APN during pregnancy. METHODS: Using the database of the Health Insurance Review and Assessment Service of South Korea, we enrolled Korean women who delivered infants between 2010 and 2014 in Korea and had complete health examination records within 1 year of pregnancy. We performed multivariate logistic regression analysis to evaluate the risk factors for APN during pregnancy. RESULTS: Of 370,248 women, 2,526 (0.7% of the total participants) were treated for APN while in hospitalization during pregnancy. Younger age, history of previous APN within 1 year of pregnancy, and abnormal results of health examination before pregnancy, such as high fasting glucose level (>100 mg/dL) and proteinuria, were associated with an increased risk of APN during pregnancy. CONCLUSION: Certain maternal demographic and clinical characteristics were associated with the incidence of APN during pregnancy, and these should be monitored closely during antenatal care.

Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics.

BACKGROUND: Obstetric hemorrhage is one of the most common causes of obstetrical morbidity and mortality, and transfusion is the most important management for hemorrhage. The aim of our study was to investigate the pre-pregnancy and pregnancy risk factors for peripartum transfusion. METHODS: Women who delivered a baby from 2010 to 2014 in Korea and participated in the Korean National Health Screening Program for Infants and Children were included. To analyze pre-pregnant risk factors for peripartum transfusion, an additional analysis was done for women who underwent a National Health Screening Examination within 1 year before pregnancy, including maternal waist circumference, body mass index, blood pressure, laboratory tests and history of smoking. Multivariable logistic regression analysis was used to estimate the risk factors for peripartum transfusion. RESULTS: Of the total 1,980,126 women who met the inclusion criteria, 36,868 (1.86%) were transfused at peripartum. In a multivariable regression model, the pregnancy risk factors for peripartum transfusion included maternal age above 35 years [odds ratio (OR): 1.41; 95% confidence interval (CI): 1.32-1.50], preterm birth (OR: 2.39; 95% CI: 2.15-2.65), and maternal hypertension (OR: 2.49; 95% CI: 2.24-2.77). Pre-pregnancy risk factors including fasting glucose level of more than 126 mg/dL (OR: 1.11; 95% CI: 1.02-1.20), current-smoker status (OR: 1.20; 95% CI: 1.06-1.37), and waist-circumference less than 80 cm (OR: 1.18; 95% CI: 1.06-1.30) were independently associated with peripartum blood transfusion. CONCLUSIONS: Several pre-pregnancy and pregnancy risk factors were associated with peripartum blood transfusion. Some identified factors are modifiable before conception, and our study validated peripartum blood transfusion as a form of triage.

Association Between Waist Circumference and Dementia in Older Persons: A Nationwide Population-Based Study.

OBJECTIVE: This study examined whether a positive association exists between waist circumference (WC) and dementia among older persons. METHODS: The study population comprised 872,082 participants aged 65 years and older who participated in a Korean national health screening examination between January 1, 2009, and December 31, 2009. Adjusted hazard ratios and 95% CIs for dementia during follow-up from 2009 to 2015 were calculated according to baseline BMI and WC categories. RESULTS: After a multivariate adjustment that included BMI, the hazard ratios for dementia showed a stepwise increase according to the increase in WC categories by 5 cm from 85 to 90 cm in men and from 80 to 85 cm in women until ≥ 110 cm (from 1.06 [95% CI: 1.03-1.09] to 1.64 [95% CI: 1.37-1.94] in men and from 1.04 [95% CI: 1.02-1.07] to 1.58 [95% CI: 1.36-1.84] in women). The influence of the current WC category for abdominal obesity on the risk of dementia was different according to BMI; especially, the normal weight men and women with abdominal obesity had a prominent increased risk of dementia compared with those without abdominal obesity. CONCLUSIONS: Abdominal obesity, as measured by WC, was associated with significantly increased risk of dementia after adjustment for general obesity.

Bronchoscopic management of solitary bronchial myelolipoma: a case report.

BACKGROUND: Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported. CASE PRESENTATION: A previously healthy 38-year-old male developed dyspnea and a productive cough. Computed tomography revealed an endobronchial mass at the right bronchus intermedius and subsequent atelectasis of the right middle and lower lobes. Flexible bronchoscopy found a total obstruction of the right bronchus intermedius due to an endobronchial tumor. Using a rigid bronchoscope, the endobronchial tumor was resected and the base of the tumor was additionally ablated with a diode laser to prevent recurrence. The removed endobronchial tumor was a 13 mm × 20 mm-sized oval-shaped mass and was pathologically diagnosed as bronchial myelolipoma. Chest radiographs, obtained on the day following the procedure, showed an improvement of atelectasis, and accompanying symptoms were immediately improved. Follow-up bronchoscopy performed after 12 months evidenced no recurrence of the bronchial myelolipoma. CONCLUSIONS: We used bronchoscopic intervention in patients with solitary bronchial myelolipoma and there was no evidence of recurrence.

Clinical outcomes of radial probe endobronchial ultrasound using a guide sheath for diagnosis of peripheral lung lesions in patients with pulmonary emphysema.

BACKGROUND: Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a guide sheath (EBUS-GS) to diagnose peripheral lesions in patients with emphysema. METHODS: This retrospective study was performed to identify the clinical outcomes of EBUS-GS in patients with pulmonary emphysema. This study included 393 consecutive patients who received EBUS-GS between February 2017 and April 2018. The patients were classified according to the severity of their emphysema, and factors possibly contributing to a successful EBUS-GS procedure were evaluated. RESULTS: The overall diagnostic yield of EBUS-GS in patients with no or mild emphysema was significantly higher than in those with moderate or severe pulmonary emphysema (78% vs. 61%, P = 0.007). There were no procedure-related complications. The presence of a bronchus sign on CT (P <  0.001) and a "within the lesion" status on EBUS (P = 0.009) were independently associated with a successful EBUS-GS procedure. Although the diagnostic yield of EBUS-GS in patients with moderate-to-severe emphysema was relatively low, a bronchus sign and "within the lesion" status on EBUS were contributing factors for a successful EBUS-GS. CONCLUSIONS: EBUS-GS is a safe procedure with an acceptable diagnostic yield, even when performed in patients with pulmonary emphysema. The presence of a bronchus sign and "within the lesion" status on EBUS were predictors of a successful procedure.

Time to appropriate treatment in patients with multidrug-resistant tuberculosis in South Korea: Are we still in 2010?

BACKGROUND: This study investigated the time to appropriate treatment and factors affecting late treatment initiation in patients with multidrug-resistant tuberculosis (MDR-TB) in South Korea. METHODS: Data from patients with culture-confirmed pulmonary MDR-TB who received treatment at Pusan National University Hospital (PNUH) between January 2010 and July 2018 were reviewed retrospectively. Patients were divided into two groups according to the first institution they visited [patients who were transferred to PNUH after diagnosis of MDR-TB (Group A) and patients who were initially diagnosed with TB at PNUH (Group B)]. RESULTS: A total of 100 patients were included (53 in Group A and 47 in Group B). The percentage of patients in whom line probe assays (LPAs) for isoniazid and rifampin or Xpert MTB/RIF assays were performed was higher in Group B than in Group A [20.8 vs. 57.4% (P < 0.001) and 17.0 vs. 46.8% (P = 0.001), respectively]. The median time from the first visit to appropriate treatment initiation was longer in Group A (102.0 vs. 77.0 days, P = 0.002). However, a subgroup analysis of patients with pre-extensively or extensively drug-resistant TB (pre-XDR- or XDR-TB) revealed that the time to appropriate treatment did not differ between Groups A and B. Although the time to appropriate treatment decreased during the study period in both Groups A and B, this trend was not evident in patients with pre-XDR- or XDR-TB in Group B. Based on multivariate analyses, performance of LPAs for isoniazid and rifampin, performance of Xpert MTB/RIF assays, and the presence of uncomplicated MDR-TB were protective against delays in appropriate treatment initiation. CONCLUSIONS: The time to appropriate treatment in patients with MDR-TB in South Korea was not acceptable, particularly for patients diagnosed outside of PNUH and for patients with pre-XDR- or XDR-TB. The use of rapid molecular drug susceptibility tests in various healthcare settings and introduction of second-line LPAs are required.

Risk of Adverse Obstetric Outcomes and the Abnormal Growth of Offspring in Women with a History of Thyroid Cancer.

Background: It is unclear whether a history of thyroid cancer is associated with an increased risk of adverse pregnancy outcomes in subsequent pregnancies. This study aimed to evaluate the risk of adverse obstetric outcomes and the abnormal growth of offspring in women with a history of thyroid cancer. Methods: This retrospective observational study used nationwide data from between 2006 and 2014 to compare pregnancy outcomes of women with a history of thyroid cancer and those with no such history. Cases of thyroid cancer were identified using ICD-10 codes. Results: During the study period, 7232 women with a history of thyroid cancer and 2,269,051 women without a history of thyroid cancer gave birth. The risks of cesarean section, preterm birth, low birth weight, large for gestational age, preeclampsia, placental abruption, placenta previa, and stillbirth were not different between the groups. Women with a history of thyroid cancer had a statistically higher risk of postpartum hemorrhage (odds ratio [OR] = 1.23 [confidence interval (CI) 1.15-1.32], p < 0.05, corrected with the false discovery rate). Additionally, generalized estimating equations analysis showed that there was no difference in the risk of underweight (OR = 1.05 [CI 0.93-1.19]) and obese (OR = 0.94 [CI 0.84-1.05]) offspring assessed over a period of 80 months after adjusting for confounding factors. Conclusions: Women with a history of thyroid cancer have similar pregnancy outcomes and offspring growth to those with no such history.

Correction: Long-term effect of pregnancy-related factors on the development of endometrial neoplasia: A nationwide retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0214600.].

Long-term effect of pregnancy-related factors on the development of endometrial neoplasia: A nationwide retrospective cohort study.

OBJECTIVE: By identifying pregnancy-related risk factors for endometrial neoplasia, women's risk of developing this disease after childbirth can be predicted and high-risk women can be screened for early detection. METHODS: Study data from women who gave birth in Korea in 2007 were collected from the Korea National Health Insurance (KNHI) claims database between 2007 and 2015. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of endometrial neoplasia were estimated by multivariate Cox proportional hazards models. RESULTS: Data from 386,614 women were collected for this study. By 2015, 3,370 women from the initial cohort had been diagnosed with endometrial neoplasia secondary to delivery. Multivariate Cox proportional hazards regression revealed that preeclampsia (HR 1.55, 95% CI 1.29, 1.86), advanced maternal age (≥ 35; HR 1.52, 95% CI 1.39, 1.66), multifetal pregnancy (HR 1.81, 95% CI 1.46, 2.23), multiparity (HR 1.16, 95% CI 1.08, 1.24), cesarean section (HR 1.15, 95% CI 1.07, 1.23) and delivery of a large-for-gestational-age infant (HR 1.19, 95% CI 1.02, 1.39) were independent risk factors for future endometrial neoplasia. The risk for endometrial neoplasia increased as the number of risk factors increased (risk factors ≥3: HR 2.11, 95% CI 1.86-2.40). CONCLUSION: This study showed that six pregnancy-related factors-advanced maternal age, multiparity, multifetal pregnancy, cesarean section, delivery of a large-for-gestational-age infant, and preeclampsia-are positively correlated with future development of endometrial neoplasia, including endometrial hyperplasia or cancer. Close observation and surveillance are warranted to enable early diagnosis of endometrial diseases, including endometrial cancer after pregnancy in high-risk women. However, due to unavailability of clinical information, many clinical/epidemiological factors can become confounders. Further research is needed on factors associated with the risk of endometrial neoplasia.