Prediction of outcomes for rescue cerclage in cervical insufficiency: A multicenter retrospective study.

Purpose: Cervical insufficiency is a significant risk factor for preterm birth and miscarriage during the second trimester; cervical cerclage is a treatment option. This study seeks to evaluate the predictive roles of various clinical factors and to develop predictive models for immediate and long-term outcomes after rescue cerclage. Methods: We conducted a multicenter retrospective study on patients who underwent rescue cerclage at 14 to 26 weeks of gestation. Data were collected from the Electronic Medical Record systems of participating hospitals. Outcomes were dichotomized into immediate failure (inability to maintain pregnancy for at least 48 hours post-cerclage, gestational latency < 2 days) and long-term success (maintenance of pregnancy until at least 28 weeks of gestation). Clinical factors influencing these outcomes were analyzed. Results: The study included 98 patients. Immediate failure correlated with longer prolapsed membrane lengths, elevated C-reactive protein levels at admission, and extended operation time. The successful maintenance of pregnancy until at least 28 weeks was associated with earlier gestational age at diagnosis, negative AmniSure test results, longer lengths of the functional cervix, and smaller cervical dilatation at the time of cerclage. Binary logistic regression models for immediate failure and long-term success exhibited excellent and good predictive abilities, respectively (AUROC = 0.912, 95% CI: 0.834-0.989; and AUROC = 0.872, 95% CI: 0.788-0.956). Conclusion: The developed logistic regression models offer a valuable tool for the prognostic assessment of patients undergoing rescue cerclage, enabling informed clinical decision-making.

Design, synthesis, and evaluation of purine and pyrimidine-based KRAS G12D inhibitors: Towards potential anticancer therapy.

Oncogenic RAS mutations, commonly observed in human tumors, affect approximately 30% of cancer cases and pose a significant challenge for effective cancer treatment. Current strategies to inhibit the KRAS G12D mutation have shown limited success, emphasizing the urgent need for new therapeutic approaches. In this study, we designed and synthesized several purine and pyrimidine analogs as inhibitors for the KRAS G12D mutation. Our synthesized compounds demonstrated potent anticancer activity against cell lines with the KRAS G12D mutation, effectively impeding their growth. They also exhibited low toxicity in normal cells, indicating their selective action against cancer cells harboring the KRAS G12D mutation. Notably, the lead compound, PU1-1 induced the programmed cell death of KRAS G12D-mutated cells and reduced the levels of active KRAS and its downstream signaling proteins. Moreover, PU1-1 significantly shrunk the tumor size in a pancreatic xenograft model induced by the KRAS G12D mutation, further validating its potential as a therapeutic agent. These findings highlight the potential of purine-based KRAS G12D inhibitors as candidates for targeted cancer therapy. However, further exploration and optimization of these compounds are essential to meet the unmet clinical needs of patients with KRAS-mutant cancers.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Glucose tolerance test with a single abnormal value as a predictor of type 2 diabetes mellitus: a multicenter retrospective study.

Clinical implication of a single abnormal value (SAV) in the 100 g oral glucose tolerance test during pregnancy has not been established. We aimed to evaluate the risk of postpartum type 2 diabetes mellitus (T2DM) and investigate adverse pregnancy outcomes in women with SAV, using a retrospective database, from seven medical centers of Korea. Based on the Carpenter-Coustan criteria using two-step approach, pregnancy and postpartum outcomes were compared, among normoglycemic, SAV, and gestational diabetes mellitus (GDM) groups. Among 9353 women, 342 (3.66%) and 418(4.47%) women were included in SAV and GDM groups, respectively. SAV and GDM groups showed significantly higher rates of postpartum T2DM than normoglycemic group (7.60%, 14.83%, and 1.82%, respectively, p < 0.001). And SAV group showed significantly higher rates of pregnancy associated hypertension, preterm birth, and neonatal hypoglycemia and sepsis, compared to normoglycemic group (neonatal sepsis, p = 0.008; the others, p < 0.001). In multivariate analysis, postpartum T2DM was associated with SAV, GDM (with/without insulin), nulliparity, pre-pregnancy BMI, chronic hypertension, hyperlipidemia, and DM family history. A scoring model to predict postpartum T2DM within 5 years, achieved an area under the curve of 0.74. This study demonstrated that not only GDM, but also SAV is a significant risk factor for postpartum T2DM.

Risk factors for pregnancy-associated heart failure with preserved ejection fraction and adverse pregnancy outcomes: a cross-sectional study.

BACKGROUND: Although pregnancy-associated heart failure with preserved ejection fraction (HFpEF) is increasing and contributing to maternal morbidity, little is known about its impact on pregnancy. We examined the risk factors for and adverse pregnancy outcomes of HFpEF in pregnant women. METHODS: We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2009 to 2020 using the perinatal database of seven multicenters. Cases of HFpEF were identified using the International Classification of Diseases and echocardiography findings. The patients were categorized into the HFpEF and control groups. Risk factors were evaluated using multivariate logistic regression analysis to generate odds ratios (OR) and 95% confidence intervals (CI). Furthermore, adjusted associations between HFpEF and adverse pregnancy outcomes were determined. Risk scores for the stratification of women at a high risk of HFpEF were calculated using a statistical scoring model. RESULTS: Of the 34,392 women identified, 258 (0.76%) were included in the HFpEF group. In multivariate analysis, HFpEF was significantly associated with old maternal age (OR, 1.04; 95% CI 1.02-1.07), multiple pregnancy (OR, 2.22; 95% CI 1.53-3.23), rheumatic disease (OR, 2.56; 95% CI 1.54-4.26), pregnancy induce hypertension (OR 6.02; 95% CI 3.61-10.05), preeclampsia (OR 24.66; 95% CI 18.61-32.66), eclampsia or superimposed preeclampsia (OR 32.74; 95% CI 21.60-49.64) and transfusion in previous pregnancy (OR 3.89; 95% CI 1.89-8.01). A scoring model to predict HFpEF with those factors achieved an area under the curve of 0.78 at cutoff value of 3. Women with HFpEF also had increased odds ratios of intensive care unit admission during the perinatal period (odds ratio, 5.98; 95% confidence interval, 4.36-8.21) and of postpartum hemorrhage (odds ratio, 5.98; 95% confidence interval, 2.02-3.64). CONCLUSIONS: Pregnancy-associated HFpEF is associated with adverse pregnancy outcomes. A scoring model may contribute to screening HFpEF using echocardiography and preparing adverse pregnancy outcomes.

Self-controllable proteinic antibacterial coating with bacteria-triggered antibiotic release for prevention of periprosthetic infection.

Periprosthetic infection is a devastating postimplantation complication in which a biofilm layer harboring invasive microorganisms forms around orthopedic implants, leading to severe implant failure and patient morbidity. Despite the development of several infection-triggered antibiotic release approaches, most current antibacterial coatings are susceptible to undesired antibiotic leakage or mechanical disintegration during prosthesis installation. Herein, we propose a self-controllable proteinic antibacterial coating capable of both long-lasting adherence onto titanium implant substrates over the implant fixation period and instantaneous bacterial eradication. Importantly, the pH-dependent reversible metal coordination of mussel adhesive protein (MAP) enabled bacterial concentration-dependent antibiotic delivery in response to infection-induced acidification. In addition, the MAP coating exhibited superior self-healable adhesive properties and scratch resistance, which enabled to avert issues associated with mechanical damages, including peeling and cracking, often occurring in conventional implant coating systems. The gentamicin-loaded MAP coating exhibited complete inhibition of bacterial growth in vivo against Staphylococcus aureus penetrations during implantation surgery (immediate infection) and even 4 weeks after implantation (delayed infection). Thus, our antibiotic-loaded MAP hydrogel coating can open new avenues for self-defensive antibiotic prophylaxis to achieve instant and sustainable bacteriocidal activity in orthopedic prostheses. © 2017 Elsevier Inc. All rights reserved.

Predicting Public Cooperation with Face Covering at the Early Phases of COVID-19: Building Public Trust, Confidence, Knowledge Through Governmental Two-Way Symmetrical Communication.

Despite the agreement on the importance of two-way communication during governmental response to pandemics, few studies provided empirical evidence to support the effectiveness of such communication strategy in times of a public health crisis. Integrating the concept of two-way symmetrical communication and the Trust, Confidence, and Cooperation model (the TCC model), this study investigates how strategic communication practices, in particular two-way symmetrical communication, is related to public's perceived trust and confidence in governments (i.e., CDC in this study), and how these perceptions may affect decisions to comply with the preventive behaviors (i.e., face covering in this study), while taking the moderating role of knowledge into consideration. An online survey was conducted with 502 participants who were living in the United States in early April 2020. The findings showed that two-way symmetrical communication may increase public trust and confidence in governments, and improve individuals' knowledge about the pandemic, which all subsequently leads to compliance with recommended behaviors. The results contribute to the theoretical understanding of pandemic communication and provide implications for practitioners in pandemic management, suggesting that health institutions should adopt two-way symmetrical communication practices in respond to public health emergencies.

Navigating the Decision to Disclose Mental Illness in the Workplace: The Role of Leader Motivating Language and Perceived Organizational Support.

Mental health disclosure in the workplace has drawn much attention as it comes with multiple benefits such as reducing financial burden, facilitating relationships, and counteracting related stress. Drawing on insights from the disclosure decision-making model, motivating language theory, and organizational support theory, the study presents a model that pictures the underlying mechanisms of the disclosure decision-making process. The findings from a survey of 416 participants suggested that the direction-giving and empathic language strategy can lead to employees' perceived organizational support. Such perception can help them reduce anticipated negative outcomes when considering disclosure and increase their disclosure efficacy, which in turn increases their disclosure intention.

Prediction of gestational diabetes mellitus in Asian women using machine learning algorithms.

This study developed a machine learning algorithm to predict gestational diabetes mellitus (GDM) using retrospective data from 34,387 pregnancies in multi-centers of South Korea. Variables were collected at baseline, E0 (until 10 weeks' gestation), E1 (11-13 weeks' gestation) and M1 (14-24 weeks' gestation). The data set was randomly divided into training and test sets (7:3 ratio) to compare the performances of light gradient boosting machine (LGBM) and extreme gradient boosting (XGBoost) algorithms, with a full set of variables (original). A prediction model with the whole cohort achieved area under the receiver operating characteristics curve (AUC) and area under the precision-recall curve (AUPR) values of 0.711 and 0.246 at baseline, 0.720 and 0.256 at E0, 0.721 and 0.262 at E1, and 0.804 and 0.442 at M1, respectively. Then comparison of three models with different variable sets were performed: [a] variables from clinical guidelines; [b] selected variables from Shapley additive explanations (SHAP) values; and [c] Boruta algorithms. Based on model [c] with the least variables and similar or better performance than the other models, simple questionnaires were developed. The combined use of maternal factors and laboratory data could effectively predict individual risk of GDM using a machine learning model.

Prediction of Pregnancy-Associated Hypertension Using a Scoring System: A Multicenter Cohort Study.

This study aimed to develop an early pregnancy risk scoring model for pregnancy-associated hypertension (PAH) based on maternal pre-pregnancy characteristics, such as mean arterial pressure (MAP), pregnancy-associated plasma protein-A (PAPP-A) or neither. The perinatal databases of seven hospitals from January 2009 to December 2020 were randomly divided into a training set and a test set at a ratio of 70:30. The data of a total pregnant restricted population (women not taking aspirin during pregnancy) were analyzed separately. Three models (model 1, pre-pregnancy factors only; model 2, adding MAP; model 3, adding MAP and PAPP-A) and the American College of Obstetricians and Gynecologists (ACOG) risk factors model were compared. A total of 2840 (8.11%) and 1550 (3.3%) women subsequently developed PAH and preterm PAH, respectively. Performances of models 2 and 3 with areas under the curve (AUC) over 0.82 in both total population and restricted population were superior to those of model 1 (with AUCs of 0.75 and 0.748, respectively) and the ACOG risk model (with AUCs of 0.66 and 0.66) for predicting PAH and preterm PAH. The final scoring system with model 2 for predicting PAH and preterm PAH showed moderate to good performance (AUCs of 0.78 and 0.79, respectively) in the test set. "A risk scoring model for PAH and preterm PAH with pre-pregnancy factors and MAP showed moderate to high performances. Further prospective studies for validating this scoring model with biomarkers and uterine artery Doppler or without them might be required".

Cell recognitive bioadhesive-based osteogenic barrier coating with localized delivery of bone morphogenetic protein-2 for accelerated guided bone regeneration.

Titanium mesh (Ti-mesh) for guided bone regeneration (GBR) approaches has been extensively considered to offer space maintenance in reconstructing the alveolar ridge within bone defects due to its superb mechanical properties and biocompatibility. However, soft tissue invasion across the pores of the Ti-mesh and intrinsically limited bioactivity of the titanium substrates often hinder satisfactory clinical outcomes in GBR treatments. Here, a cell recognitive osteogenic barrier coating was proposed using a bioengineered mussel adhesive protein (MAP) fused with Alg-Gly-Asp (RGD) peptide to achieve highly accelerated bone regeneration. The fusion bioadhesive MAP-RGD exhibited outstanding performance as a bioactive physical barrier that enabled effective cell occlusion and a prolonged, localized delivery of bone morphogenetic protein-2 (BMP-2). The MAP-RGD@BMP-2 coating promoted in vitro cellular behaviors and osteogenic commitments of mesenchymal stem cells (MSCs) via the synergistic crosstalk effects of the RGD peptide and BMP-2 in a surface-bound manner. The facile gluing of MAP-RGD@BMP-2 onto the Ti-mesh led to a distinguishable acceleration of the in vivo formation of new bone in terms of quantity and maturity in a rat calvarial defect. Hence, our protein-based cell recognitive osteogenic barrier coating can be an excellent therapeutic platform to improve the clinical predictability of GBR treatment.

Effects of Amnioreduction before Physical Examination-Indicated Cerclage on Pregnancy Outcomes: A Propensity Score Matched Study.

This study investigated the effects of amnioreduction before physical examination-indicated cerclage on pregnancy outcomes using a propensity score matching analysis. This multicenter retrospective cohort study included women who underwent cerclage operations due to painless cervical dilation in the second trimester (14-28 weeks). The primary outcome was the time from operation until delivery. Secondary outcomes included preterm birth rate and neonatal outcomes. Primary and secondary outcomes were compared between those with amnioreduction and those without amnioreduction. Of 103 women, 31 received preoperative amnioreduction (amnioreduction group) and 72 women did not (no-amnioreduction group). Since there were differences in baseline characteristics and preoperative ultrasound findings between the two groups, we matched 25 women with amnioreduction and 25 women without amnioreduction using a propensity score. In the matched cohort, the amnioreduction group showed a shorter time from operation to delivery than the group without amnioreduction and the hazard ratio of amnioreduction was 2.5 (95% confidence interval; 1.4-4.7). In addition, the preterm birth rate before 28 weeks of gestation and the neonatal composite outcome were higher in the amnioreduction group than that in the group without amnioreduction. Amnioreduction before physical examination-indicated cerclage was associated with poor pregnancy and neonatal outcomes. Therefore, careful consideration is required when performing amnioreduction before cerclage operation.

Cinnamon Roll Technique with WALANT for Nipple Reduction.

BACKGROUND: Nipple hypertrophy is a common esthetic problem in Asian women. Many patients are uncomfortable and seek plastic surgeons for correction. Although several reduction methods have been published, the new nipple size is not always decided by patients under conventional anesthesia. We describe a novel cinnamon roll technique with wide-awake local anesthesia no tourniquet (WALANT) to decrease pain, provide a bloodless field and allow on-table discussion of the ideal nipple size during surgery. METHODS: Between November 2015 and October 2022, fifteen patients with 30 nipples were enrolled. The patient's characteristic data, nipple height and width, and VAS while infiltration were recorded. Aesthetic results were evaluated by rating a satisfactory score from 0 to 10 at follow-up. Sensory recovery was also evaluated for 1, 3, 6, and 12 months sequentially after the surgery. RESULTS: Before surgery, the mean diameter and height of the nipples were 13.2 ± 1.8 mm and 12 ± 2.2 mm, respectively. Immediately after surgery, the mean diameter and height of the nipples were 8.8 ± 1.2 mm and 8.7 ± 1.2 mm, respectively. The mean VAS while infiltration was 1.3 ± 0.5 and the mean satisfactory score at the latest clinic follow-up was 9.3 ± 0.6. No complications such as nipple necrosis, infection, numbness or hypertrophic scar occurred. The mean clinical follow-up period was 3.4 months. CONCLUSIONS: Cinnamon roll technique with WALANT is a simple, safe and reliable method with short learning curve and high satisfaction. Our technique offers a chance for patients to control subjective pleasing size of their own nipples. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Predicting Public Cooperation Toward Government Actions in the Early Stages of an Influenza Pandemic in the United States: The Role of Authentic Governmental Communication and Relational Quality.

During a public health crisis, government sector is considered the natural leader for overall preparedness and management efforts. Integrating the literature from public relations and public health disciplines, this study proposes a theoretical model to predict individuals' perceptions, communicative action, as well as their behaviors to follow the governments' instructions in the early stages of the COVID-19 outbreak in the United States. Linking relationship management factors and the framework of the situational theory of problem-solving, the findings of this study demonstrate that authentic communication and relational quality can help increase positive perceptual, attitudinal, and behavioral outcomes desired by governments regarding pandemic management. However, our findings suggested that unproductive uses of authentic governmental communication may create adverse effects on publics' perceptions and interpretations and thus pose potential risks, particularly when a public health issue is significantly politicized. Specifically, this study found that, in the case of the COVID-19 pandemic in which the Trump administration was blamed for lack of planning and halting responses in the fight against the virus, conservatives who believe that the federal government is practicing authentic communication during the pandemic would consider the issue less important and irreverent; meanwhile, they would recognize more barriers to adopt preventive actions. Theoretical and practical implications are discussed.

Clinical and Economic Impact of Pharmacists' Intervention on Care of Pediatric Hematology and Oncology Patients.

INTRODUCTION: Children with cancer may be one of the most vulnerable groups to drug-related adverse events because they possess characteristics of patients with cancer as well as pediatric patients. To evaluate the clinical and economic impact of pharmacists' intervention on the care of pediatric hematology and oncology patients in the inpatient and outpatient settings of a children's hospital. METHODS: The pharmacist-intervention records from 2017 were retrospectively reviewed. Intervention rate, type of drug-related problems, acceptance rate, and frequently involved drugs in pharmacist interventions were analyzed. One physician and one pharmacist evaluated the clinical significance of each intervention. A cost-benefit analysis was conducted from hospital and patient perspective. The benefit from cost savings by reducing the number of prescribed drugs that are disposed was estimated as the benefit from hospital perspective. The benefit from cost avoidance based on the potential to avoid an adverse drug event (ADE) was estimated as the benefit from patient perspective. The cost of reviewing prescriptions was estimated based on the pharmacists' salary and the time involved. RESULTS: In 2017, 2361 interventions were performed in 381 pediatric patients with cancer. The acceptance rate was 97.2%. More than half of the interventions were regarded as clinically "significant" (58.8%) and "very significant" (14.6%). The cost-benefit of US$28,705 was determined from hospital perspective, with a cost-benefit ratio of 1.45:1. The cost-benefit of US$35,611 was calculated from patient perspective, with a cost-benefit ratio of 1.55:1. CONCLUSIONS: Pharmacists' intervention in the care of hematology and oncology pediatric patients was effective in preventing clinically significant ADEs and had a positive economic impact on the health-care budget from both hospital and patient perspective.

Enhancing Employee Engagement via Leaders' Motivational Language in times of crisis: Perspectives from the COVID-19 outbreak.

By bridging theoretical perspectives from diverse disciplines including public relations, organizational communication, psychology, and management, this study advances a sequential mediation process model that links leaders' motivational communication-specifically, direction-giving, empathetic, and meaning-making language-to employees' organizational engagement during times of crisis. The model incorporates employees' psychological needs satisfaction and their subsequent crisis coping strategies so as to explain the process that underlies the effects of leader communication on employee engagement. We tested the model in a unique yet underexplored crisis context: organizational crises triggered by the global pandemic of COVID-19. The results of an online survey of 490 full-time U.S. employees provide strong support to the model's predictions. Our research extends internal crisis communication scholarship in public relations by addressing what types of leader communication strategies as well as how these strategies contribute to employee engagement in a holistic fashion. It also advances theoretical development of the motivational language theory, self-determination theory, transactional model of stress and coping, and organizational engagement-the four theoretical bases of our study-in the context of organizational crises. Lastly, the study results provide timely practical insights on effective internal crisis communication.

Home-Based Transcranial Direct Current Stimulation to Enhance Cognition in Stroke: Randomized Controlled Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising tool for improving poststroke cognitive function. Home-based rehabilitation is increasingly required for patients with stroke, and additional benefits are expected if supplemented with remotely supervised tDCS (RS-tDCS). We evaluated the cognitive improvement effect and feasibility of RS-tDCS in patients with chronic stroke. METHODS: Twenty-six patients with chronic stroke and cognitive impairment (Korean version of the Montreal Cognitive Assessment [K-MoCA] score <26) were randomized into real and sham RS-tDCS groups and underwent concurrent computerized cognitive training and RS-tDCS. Patients and caregivers underwent training to ensure correct tDCS self-application, were monitored, and treated 5 d/wk for 4 weeks. We investigated several cognition tests including K-MoCA, Korean version of the Dementia Rating Scale-2, Korean-Boston Naming Test, Trail Making Test, Go/No Go, and Controlled Oral Word Association Test at the end of the training sessions and one month later. Repeated-measures ANOVA was used for comparison between the groups and within each group. The adherence rate of the appropriate RS-tDCS session was also investigated. RESULTS: In within-group comparison, unlike the sham group, the real group showed significant improvement in K-MoCA (Preal=0.004 versus Psham=0.132), particularly in patients with lower baseline K-MoCA (K-MoCA10-17; Preal=0.001 versus Psham=0.835, K-MoCA18-25; Preal=0.060 versus Psham=0.064) or with left hemispheric lesions (left; Preal=0.010 versus Psham=0.454, right; Preal=0.106 versus Psham=0.128). In between-group comparison, a significant difference was observed in K-MoCA in the lower baseline K-MoCA subgroup (K-MoCA10-17; Ptime×group=0.048), but no significant difference was found in other cognitive tests. The adherence rate of successful application of the RS-tDCS was 98.4%, and no serious adverse effects were detected. CONCLUSIONS: RS-tDCS is a safe and feasible rehabilitation modality for poststroke cognitive dysfunction. Specifically, RS-tDCS is effective in patients with moderate cognitive decline. Additionally, these data demonstrate the potential to enhance home-based cognitive training, although significant differences were not consistently found in between-group comparisons; therefore, further larger studies are needed. REGISTRATION: URL: https://cris.nih.go.kr; Unique identifier: KCT0003427.

Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients.

OBJECTIVES: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. METHODS: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. RESULTS: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. CONCLUSIONS: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.

Impact of pre-pandemic travel mobility patterns on the spatial diffusion of COVID-19 in South Korea.

Introduction: Physical mobility is critical for the spread of infectious diseases in humans. However, few studies have conducted empirical investigations on the impact of pre-pandemic travel mobility patterns on the diffusion of coronavirus disease 2019 (COVID-19). Therefore, this study examines its impact at the city-county level on the diffusion by the wave period during the two-year pandemic in South Korea. Methods: This study first employs factor analysis by using the travel origin-destination data by travel mode at the county level as of 2019 to derive pre-pandemic travel mobility patterns. Next, the study identifies how they had affected the diffusion of COVID-19 over time by employing the negative binomial regression models on confirmed COVID-19 cases for each wave, including the entire pandemic period. Results: The study derived five pre-pandemic mobility patterns: 1) rail-oriented mobility, 2) intra-county bus-oriented mobility, 3) road-oriented mobility, 4) high-speed rail-oriented mobility, and 5) inter-county bus-oriented mobility. Among them, the biggest risk to the diffusion of COVID-19 was the rail-oriented mobility before the pandemic if controlling such measures as accessibility, physical environment, and demographic and socioeconomic indicators. In addition, the order of the magnitudes for the impact of pre-pandemic travel mobility factors on its spatial diffusion had not changed during experiencing the three different wave periods during the two-year pandemic in South Korea. Conclusions: The study concludes that the rail-oriented travel mobility pattern before the pandemic could pose the greatest threat factor to the spatial spread of COVID-19 at any scale and time. Policymakers should develop strategies to prevent the spatial spread of COVID-19 by reducing human mobility for daily living in areas with strong rail mobility patterns formed before the pandemic.

Bioengineered Co-culture of organoids to recapitulate host-microbe interactions.

The recent spike in the instances of complex physiological host-microbe interactions has raised the demand for developing in vitro models that recapitulate the microbial microenvironment in the human body. Organoids are steadily emerging as an in vitro culture system that closely mimics the structural, functional, and genetic features of complex human organs, particularly for better understanding host-microbe interactions. Recent advances in organoid culture technology have become new avenues for assessing the pathogenesis of symbiotic interactions, pathogen-induced infectious diseases, and various other diseases. The co-cultures of organoids with microbes have shown great promise in simulating host-microbe interactions with a high level of complexity for further advancement in related fields. In this review, we provide an overview of bioengineering approaches for microbe-co-cultured organoids. Latest developments in the applications of microbe-co-cultured organoids to study human physiology and pathophysiology are also highlighted. Further, an outlook on future research on bioengineered organoid co-cultures for various applications is presented.