Lytic transglycosylase repertoire diversity enables intrinsic antibiotic resistance and daughter cell separation in Escherichia coli under acidic stress.

Peptidoglycan (PG) is an important architectural element that imparts physical toughness and rigidity to the bacterial envelope. It is also a dynamic structure that undergoes continuous turnover or autolysis. Escherichia coli possesses redundant PG degradation enzymes responsible for PG turnover; however, the advantage afforded by the existence of numerous PG degradation enzymes remains incompletely understood. In this study, we elucidated the physiological roles of MltE and MltC, members of the lytic transglycosylase (LTG) family that catalyze the cleavage of glycosidic bonds between disaccharide subunits within PG strands. MltE and MltC are acidic LTGs that exhibit increased enzymatic activity and protein levels under acidic pH conditions, respectively, and deletion of these two LTGs results in a pronounced growth defect at acidic pH. Furthermore, inactivation of these two LTGs induces increased susceptibility at acidic pH against various antibiotics, particularly vancomycin, which seems to be partially caused by elevated membrane permeability. Intriguingly, inactivation of these LTGs induces a chaining morphology, indicative of daughter cell separation defects, only under acidic pH conditions. Simultaneous deletion of PG amidases, known contributors to daughter cell separation, exacerbates the chaining phenotype at acidic pH. This suggests that the two LTGs may participate in the cleavage of glycan strands between daughter cells under acidic pH conditions. Collectively, our findings highlight the role of LTG repertoire diversity in facilitating bacterial survival and antibiotic resistance under stressful conditions.

Associations between gestational residential radon exposure and term low birthweight in Connecticut, USA.

BACKGROUND: Studies suggest biologic mechanisms for gestational exposure to radiation and impaired fetal development. We explored associations between gestational radon exposure and term low birthweight, for which evidence is limited. METHODS: We examined data for 68,159 singleton full-term births in Connecticut, USA, 2016-2018. Using a radon spatiotemporal model, we estimated ZIP code-level basement and ground-level exposures during pregnancy and trimesters for each participant's address at birth or delivery. We used logistic regression models, including confounders, to estimate odds ratios (ORs) for term low birth weight in four exposure quartiles (Q1 to Q4) with the lowest exposure group (Q1) as the reference. RESULTS: Exposure levels to basement radon throughout pregnancy (0.27-3.02 pCi/L) were below the guideline level set by the US Environmental Protection Agency (4 pCi/L). The ORs for term low birth weight in the second-highest (Q3; 1.01-1.33 pCi/L) exposure group compared to the reference (<0.79 pCi/L) group for basement radon during the first trimester was 1.22 (95% confidence interval [CI]: 1.02, 1.45). The OR in the highest (Q4; 1.34-4.43 pCi/L) quartile group compared to the reference group during the first trimester was 1.26 (95% CI: 1.05, 1.50). Risks from basement radon were higher for participants with lower income, lower maternal education levels, or living in urban regions. CONCLUSION: This study found increased term low birth weight risks for increases in basement radon. Results have implications for infants' health for exposure to radon at levels below the current national guideline for indoor radon concentrations and building remediations.

A systematic review of animal feeding operations including concentrated animal feeding operations (CAFOs) for exposure, health outcomes, and environmental justice.

BACKGROUND: Despite growing literature on animal feeding operations (AFOs) including concentrated animal feeding operations (CAFOs), research on disproportionate exposure and associated health burden is relatively limited and shows inconclusive findings. OBJECTIVE: We systematically reviewed previous literature on AFOs/CAFOs, focusing on exposure assessment, associated health outcomes, and variables related to environmental justice (EJ) and potentially vulnerable populations. METHODS: We conducted a systematic search of databases (MEDLINE/PubMed and Web of Science) and performed citation screening. Screening of titles, abstracts, and full-text articles and data extraction were performed independently by pairs of reviewers. We summarized information for each study (i.e., study location, study period, study population, study type, study design, statistical methods, and adjusted variables (if health association was examined), and main findings), AFO/CAFO characteristics and exposure assessment (i.e., animal type, data source, measure of exposure, and exposure assessment), health outcomes or symptoms (if health association was examined), and information related to EJ and potentially vulnerable populations (in relation to exposure and/or health associations, vulnerable populations considered, related variables, and main findings in relation to EJ and vulnerable populations). RESULTS: After initial screening of 10,963 papers, we identified 76 eligible studies. This review found that a relatively small number of studies (20 studies) investigated EJ and vulnerability issues related to AFOs/CAFOs exposure and/or associated health outcomes (e.g., respiratory diseases/symptoms, infections). We found differences in findings across studies, populations, the metrics used for AFO/CAFO exposure assessment, and variables related to EJ and vulnerability. The most commonly used metric for AFO/CAFO exposure assessment was presence of or proximity to facilities or animals. The most investigated variables related to disparities were race/ethnicity and socioeconomic status. CONCLUSION: Findings from this review provide suggestive evidence that disparities exist with some subpopulations having higher exposure and/or health response in relation to AFO/CAFO exposure, although results varied across studies.

Watching videos of a drawing hand improves students' understanding of the normal probability distribution.

Understanding normal probability distributions is a crucial objective in mathematics and statistics education. Drawing upon cognitive psychology research, this study explores the use of drawings and visualizations as effective scaffolds to enhance students' comprehension. Although much research has documented the helpfulness of drawing as a research tool to reveal students' knowledge states, its direct utility in advancing higher-order cognitive processes remains understudied. In Study 1, qualitative methods were utilized to identify common misunderstandings among students regarding canonical depictions of the normal probability distribution. Building on these insights, Study 2 experimentally compared three instructional videos (static slides, dynamic drawing, and dynamic drawings done by a visible hand). The hand drawing video led to better learning than the other versions. Study 3 examined whether the benefits from observing a hand drawing could be reproduced by a dynamic cursor moving around otherwise static slides (without the presence of a hand). Results showed no significant learning difference between observing a hand drawing and a moving cursor, both outperforming a control. This research links the cognitive process of drawing with its educational role and provides insights into its potential to enhance memory, cognition, and inform instructional methods.

Combination Analysis of PCDHGA12 and CDO1 DNA Methylation in Bronchial Washing Fluid for Lung Cancer Diagnosis.

BACKGROUND: When suspicious lesions are observed on computer-tomography (CT), invasive tests are needed to confirm lung cancer. Compared with other procedures, bronchoscopy has fewer complications. However, the sensitivity of peripheral lesion through bronchoscopy including washing cytology is low. A new test with higher sensitivity through bronchoscopy is needed. In our previous study, DNA methylation of PCDHGA12 in bronchial washing cytology has a diagnostic value for lung cancer. In this study, combination of PCDHGA12 and CDO1 methylation obtained through bronchial washing cytology was evaluated as a diagnostic tool for lung cancer. METHODS: A total of 187 patients who had suspicious lesions in CT were enrolled. PCDHGA12 methylation test, CDO1 methylation test, and cytological examination were performed using 3-plex LTE-qMSP test. RESULTS: Sixty-two patients were diagnosed with benign diseases and 125 patients were diagnosed with lung cancer. The sensitivity of PCDHGA12 was 74.4% and the specificity of PCDHGA12 was 91.9% respectively. CDO1 methylation test had a sensitivity of 57.6% and a specificity of 96.8%. The combination of both PCDHGA12 methylation test and CDO1 methylation test showed a sensitivity of 77.6% and a specificity of 90.3%. The sensitivity of lung cancer diagnosis was increased by combining both PCDHGA12 and CDO1 methylation tests. CONCLUSION: Checking DNA methylation of both PCDHGA12 and CDO1 genes using bronchial washing fluid can reduce the invasive procedure to diagnose lung cancer.

Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Oral habits and temporomandibular joint disorders according to stress levels among military personnel in South Korea: A cross-sectional study.

BACKGROUND: Military personnel suffer from stress-induced temporomandibular joint disorders (TMD). No previous studies have evaluated the oral habits and TMD in military personnel based on their stress levels. OBJECTIVES: To examine the correlation between oral habits and TMD based on stress levels. In addition, we assessed the relationship between stress levels and TMD by military rank as well as the impact of oral habits on TMD. METHOD: This cross-sectional survey included 89 military personnel who visited the Armed Forces Medical Center in Korea with discomfort in the temporomandibular joint (TMJ) discomfort. Oral habits, stress level, TMD and general characteristics of the subjects were investigated. A questionnaire was distributed to the subjects who agreed to the study, and they were asked to respond in a self-written form. Multiple linear regression analysis was performed to examine the factors that affect oral habits and TMJ symptoms. RESULTS: Stress scores and oral habits were highest in the 'Private' rank. In contrast, temporomandibular joint symptoms were highest in the 'Corporal' rank. Additionally, the high-risk stress group exhibited higher scores in oral habits and TMD compared to the potential stress group. Furthermore, there was a positive correlation between an increase in high-risk stress scores and a rise in oral habits. And individuals with more oral habits are at an increased likelihood of experiencing TMD. CONCLUSION: Our study findings suggest that military personnel with prevent TMD and improve oral habits by addressing stress levels.

Development of Non-Invasive miRNA Markers for Assessing the Quality of Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods.

Associations between traumatic dental injuries due to violence and various drinking behaviors in Korea: A cross-sectional study.

BACKGROUND AND AIM: Various patterns of alcohol consumption are associated with trauma and violence. The aim of this study was to assess the association between traumatic dental injuries (TDI) due to violence and different patterns of alcohol consumption in Korean adults. MATERIALS AND METHODS: A cross-sectional study was conducted with representative sample of Korean adults. Among the total participants, 11.8% (6489/58,999) experienced TDI, and 0.9% (520/58,999) experienced TDI due to violence. The associations between various types of alcohol consumption (frequency of drinking, frequency of binge drinking, age of first drinking) and TDI due to violence were assessed using logistic regression analyses. We confirmed differences in the prevalence experience of TDI due to violence with various types of alcohol consumption by confounders (socioeconomic status). RESULTS: All types of drinking (frequency of drinking, frequency of binge drinking, age of first drinking) were strongly associated with TDI due to violence. After adjusting for confounders, those who started drinking at the age of 18 or younger and drank 4 or more days a week (OR: 2.86, 95% CI: 1.68-4.88), those who started drinking at the age of 18 or younger and drank 3 days or less a week (OR: 2.37, 95% CI: 1.40-4.02), and those who started drinking at the age of 18 or younger and binge drinking at least once a week (OR: 3.18, 95% CI: 1.79-5.65) had higher prevalence of TDI due to violence compared to those with no alcohol drinking. CONCLUSIONS: This study presents evidence of an association between various types of alcohol consumption and TDI due to violence in Korean adults. These findings suggest the necessity for policies aimed at reducing alcohol consumption, frequency of drinking, and access to drinking especially in adolescent to reduce the prevalence experience of TDI due to violence.

Developing a Practical Tool for Predicting Wound Healing Outcomes of Patients with Diabetic Forefoot Ulcers: Focus on Vasculopathy and Infection.

OBJECTIVE: To develop a preliminary risk scoring system to predict the prognosis of patients with diabetic forefoot ulcers based on the severity of vasculopathy and infection, which are the major risk factors for amputation. METHODS: Forefoot was defined as the distal part of the foot composed of the metatarsal bones and phalanges and associated soft tissue structures. The degree of vasculopathy was graded as V0, V1, or V2 according to transcutaneous partial oxygen tension values and toe pressure. The degree of infection was graded as I0, I1, or I2 according to tissue and bone biopsy culture results. The risk scores were calculated by adding the scores for the degree of vasculopathy and infection and ranged from 0 to 4. Wound healing outcomes were graded as healed without amputation, minor amputation, or major amputation. The authors evaluated wound healing outcomes according to risk scores. RESULTS: As the risk score increased, the proportion of patients who underwent both major and minor amputations increased (P < .001). In the multivariate logistic analysis, the odds ratios of amputation also increased as the risk score increased. Patients with a risk score of 4 were 75- and 19-fold more likely to undergo major and minor amputations, respectively, than patients with a risk score of 0 (P = .006 and P < .001). CONCLUSIONS: The risk score can be used as an indicator to predict the probability of amputation in patients with diabetic forefoot ulcers.

A library for innovative category exemplars (ALICE) database: Streamlining research with printable 3D novel objects.

This paper introduces A Library for Innovative Category Exemplars (ALICE) database, a resource that enhances research efficiency in cognitive and developmental studies by providing printable 3D objects representing 30 novel categories. Our research consists of three experiments to validate the novelty and complexity of the objects in ALICE. Experiment 1 assessed the novelty of objects through adult participants' subjective familiarity ratings and agreement on object naming and descriptions. The results confirm the general novelty of the objects. Experiment 2 employed multidimensional scaling (MDS) to analyze perceived similarities between objects, revealing a three-dimensional structure based solely on shape, indicative of their complexity. Experiment 3 used two clustering techniques to categorize objects: k-means clustering for creating nonoverlapping global categories, and hierarchical clustering for allowing global categories that overlap and have a hierarchical structure. Through stability tests, we verified the robustness of each clustering method and observed a moderate to good consensus between them, affirming the strength of our dual approach in effectively and accurately delineating meaningful object categories. By offering easy access to customizable novel stimuli, ALICE provides a practical solution to the challenges of creating novel physical objects for experimental purposes.

Exsolution of Ru Nanoparticles on BaCe0.9 Y0.1 O3-δ Modifying Geometry and Electronic Structure of Ru for Ammonia Synthesis Reaction Under Mild Conditions.

Green ammonia is an efficient, carbon-free energy carrier and storage medium. The ammonia synthesis using green hydrogen requires an active catalyst that operates under mild conditions. The catalytic activity can be promoted by controlling the geometry and electronic structure of the active species. An exsolution process is implemented to improve catalytic activity by modulating the geometry and electronic structure of Ru. Ru nanoparticles exsolved on a BaCe0.9 Y0.1 O3-δ support exhibit uniform size distribution, 5.03 ± 0.91 nm, and exhibited one of the highest activities, 387.31 mmolNH3  gRu -1  h-1 (0.1 MPa and 450 °C). The role of the exsolution and BaCe0.9 Y0.1 O3-δ support is studied by comparing the catalyst with control samples and in-depth characterizations. The optimal nanoparticle size is maintained during the reaction, as the Ru nanoparticles prepared by exsolution are well-anchored to the support with in-plane epitaxy. The electronic structure of Ru is modified by unexpected in situ Ba promoter accumulation around the base of the Ru nanoparticles.

Synthesis and Volatility Characterization of Mo(II) and W(II) Compounds for Thin Films.

Mo(II) and W(II) compounds, Mo(η3-allyl)(CO)2(Tri-MEDA)Br (1), Mo(η3-allyl)(CO)2(TMEDA)Br (2), W(η3-allyl)(CO)2(Tri-MEDA)Br (3), and W(η3-allyl)(CO)2(TMEDA)Br (4) (Tri-MEDA = N,N,N'-trimethylethylenediamine), were synthesized and characterized. The molecular structures of 1 and 3 were nearly identical with a pseudo-octahedral geometry except for the different Mo and W metal centers. The thermogravimetric analysis of 1 and 3 showed approximately 53 and 64% residues at 550 °C, respectively, which were significantly higher than the values for the expected materials. However, 1 and 3 sublimed at 100 °C under 0.40 Torr and 120 °C under 0.50 Torr, respectively, confirming that they were volatile. For 1 and 3, the temperatures at a vapor pressure of 1 Torr and enthalpies of vaporization (ΔHvap) were 168.78 °C and 143.8 kJ mol-1, and 167.48 °C and 148.5 kJ mol-1, respectively. The tungsten compound (3) exhibited good durability for 5 weeks under a thermal stability test at a sublimation temperature of 120 °C.

Developing and Establishing a Wound Dressing Team: Experience and Recommendations.

BACKGROUND: The existing literature has comprehensively examined the benefits of specialized wound-care services and multidisciplinary team care. However, information on the development and integration of wound-dressing teams for patients who do not require specialized wound care is scarce. Therefore, the present study aimed to elucidate the benefits of a wound-dressing team by reporting our experiences with the establishment of a wound-dressing team. METHODS: The wound-dressing team was established at Korea University Guro Hospital. Between July 2018 and June 2022, 180,872 cases were managed for wounds at the wound-dressing team. The data were analyzed to assess the types of wounds and their outcomes. In addition, questionnaires assessing the satisfaction with the service were administered to patients, ward nurses, residents/internists, and team members. RESULTS: Regarding the wound type, 80,297 (45.3%) were catheter-related, while 48,036 (27.1%), 26,056 (14.7%), and 20,739 (11.7%) were pressure ulcers, dirty wounds, and simple wounds, respectively. In the satisfaction survey, the scores of the patient, ward nurse, dressing team nurse, and physician groups were 8.9, 8.1, 8.2, and 9.1, respectively. Additionally, 136 dressing-related complications (0.08%) were reported. CONCLUSION: The wound dressing team can enhance satisfaction among patients and healthcare providers with low complications. Our findings may provide a potential framework for establishing similar service models.

Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal College of Surgeons Rats by Targeting the Mitogen-Activated Protein Kinase Pathway.

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.

Interdental cleaning and periodontal status among older Koreans: Findings from KNHANES VII.

OBJECTIVE: To assess the association between the usage of interdental cleaning and periodontal status among older people in Korea. BACKGROUND: In order to maintain oral health in older people, it is very important to use interdental cleaning devices. However, there is a lack of research on periodontal status and interdental cleaning device use in older people. METHODS: This study used data collected from the 7th National Health Nutrition Survey (KNHANES VII: 2016-2018). A total of 3426 older people adults aged 65 years or older were selected from 16 489 participants. Data on sociodemographic status (sex, age, level of education, income, residential area), personal health practice (subjective health status, smoking, physical activity, hypertension, and diabetes mellitus), oral health practice (subjective oral health status, tooth brushing frequency, dental visits, and chewing problem), the number of teeth and periodontitis were collected. Periodontitis was defined as having a World Health Organisation community periodontal index (CPI) code greater than or equal to three, and severe periodontitis was defined as a CPI code 4. Participants having a CPI code of 3 or 4 were considered to have periodontal disease in this study. Logistic regression analysis investigated the association between interdental cleaning devices usage and periodontitis controlling the confounding factors. RESULTS: Those who do not use dental floss had a higher rate of periodontal disease (AOR = 1.47, 95% confidence interval [CI]: 1.05 to 2.1). However, there were no significant differences by interdental brush use. In those with 20 or more teeth, non-users of dental floss had a higher risk of periodontitis in all models. Conversely, in those with fewer than 20 teeth, no significant differences were observed. CONCLUSIONS: Older people with mostly intact dentitions have better periodontal health if they clean between their teeth.

Adoptive cell therapy in gynecologic cancers: A systematic review and meta-analysis.

Adoptive cell therapy (ACT) has shown promise in hematologic and solid tumors. While data supports immunogenicity of gynecologic cancers, the benefit of ACT is not yet clear. To address this question, we performed a comprehensive systematic review and meta-analysis. Eligible studies included those reporting oncologic response or toxicity data in at least one patient with any gynecologic cancer treated with ACT. Chi-square test and multivariable logistic regression were performed to identify predictors of response. We retrieved 281 articles, and 28 studies met our inclusion criteria. These comprised of 401 patients including 238 patients with gynecologic cancers (61.8% ovarian, 34.0% cervical, 2.9% endometrial, and 1.2% other). In patients with gynecologic cancers, response rates to ACT were 8.1% complete response, 18.2% partial response, and 31.4% stable disease, for an objective response rate (ORR) of 26.3%, disease control rate (DCR) of 57.6%, and median response duration of 5.5 months. Patients in studies reporting ≤1 median line of prior therapy had a higher ORR (52.9% vs. 22.6% for >1, p < 0.001), although DCR in the >1 group was still 53.2%. ORRs by ACT type were tumor infiltrating lymphocytes (TIL) 41.4%, natural killer cells 26.7%, peripheral autologous T-cells 18.4%, T-cell receptor-modified T-cells 15.4%, and chimeric antigen receptor T-cells 9.5% (p = 0.001). ORR was significantly improved with inclusion of lymphodepletion (34.8% vs. 15.4% without, p = 0.001). On multivariable analysis controlling for cancer type and lymphodepletion, TIL therapy was predictive of objective response (odds ratio 2.6, p = 0.011). The rate of grade 3 or 4 toxicity was 46.0%. All grade adverse events included fever, hypotension, dyspnea, confusion, hematologic changes, nausea/vomiting, fatigue, and diarrhea. In conclusion, ACT is a promising treatment modality in gynecologic cancer. We observed a particular benefit of TIL therapy and suggest inclusion of lymphodepletion in future trials.

Exposure to heat during pregnancy and preterm birth in North Carolina: Main effect and disparities by residential greenness, urbanicity, and socioeconomic status.

BACKGROUND: Although previous literature suggested that several factors may be associated with higher risk of adverse health outcomes related to heat, research is limited for birth outcomes. OBJECTIVES: We investigated associations between exposure to heat/heat waves during the last week of gestation and preterm birth (PTB) in North Carolina (NC) and evaluated effect modification by residential greenness, urbanicity, and socioeconomic status (SES). METHODS: We obtained individual-level NC birth certificate data for May-September 2003-2014. We estimated daily mean temperature at each maternal residential address using Parameter-elevation Regressions on Independent Slopes Model (PRISM) data. We created 3 definitions of heat waves (daily temperature ≥95th, 97th, 99th percentile for NC warm season temperature, for ≥2 consecutive days). Normalized Difference Vegetation Index (NDVI) was used to assess residential greenness. Community-level modifiers (e.g., income, urbanicity) were considered. We applied Cox proportional hazard models to estimate the association between exposure to heat/heat waves and PTB, controlling for covariates. Stratified analyses were conducted to evaluate whether the association between heat and PTB varied by several individual and community characteristics. RESULTS: Of the 546,441 births, 8% were preterm. Heat exposure during the last week before delivery was significantly associated with risk of PTB. The hazard ratio for a 1 °C increase in temperature during the last week before delivery was 1.01 (95% CI: 1.00, 1.02). Higher heat-PTB risk was associated with some characteristics (e.g., areas that were urbanized, low SES, or in the Coastal Plain). We also found significant PTB-heat risk in areas with low greenness for urbanized area. For heat waves, we did not find significantly positive associations with PTB. DISCUSSION: Findings provide evidence that exposure to heat during pregnancy increases risk of PTB and suggest disparities in these risks. Our results have implications for future studies of disparity in heat and birth outcomes associations.

Workload of Healthcare Workers During the COVID-19 Outbreak in Korea: A Nationwide Survey.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, heavy workload of healthcare workers (HCWs) is a concern. This study investigated the workload of HCWs responding to the COVID-19 outbreak in South Korea. METHODS: A nationwide cross-sectional survey was conducted from September 16 to October 15, 2020, involving 16 healthcare facilities (4 public medical centers, 12 tertiary-care hospitals) that provide treatment for COVID-19 patients. RESULTS: Public medical centers provided the majority (69.4%) of total hospital beds for COVID-19 patients (n = 611), on the other hand, tertiary care hospitals provided the majority (78.9%) of critical care beds (n = 57). The number of beds per doctor (median [IQR]) in public medical centers was higher than in tertiary care hospitals (20.2 [13.0, 29.4] versus 3.0 [1.3, 6.6], P = 0.006). Infectious Diseases physicians are mostly (80%) involved among attending physicians. The number of nurses per patient (median [interquartile range, IQR]) in tertiary-care hospitals was higher than in public medical centers (4.6 [3.4-5] vs. 1.1 [0.8-2.1], P = 0.089). The median number of nurses per patient for COVID-19 patients was higher than the highest national standard in South Korea (3.8 vs. 2 for critical care). All participating healthcare facilities were also operating screening centers, for which a median of 2 doctors, 5 nurses, and 2 administrating staff were necessary. CONCLUSION: As the severity of COVID-19 patients increases, the number of HCWs required increases. Because the workload of HCWs responding to the COVID-19 outbreak is much greater than other situations, a workforce management plan regarding this perspective is required to prevent burnout of HCWs.