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As the coronavirus (COVID-19) epidemic passed initial infection peak in Washington State, phased re-opening lifted stay-at-home orders and restrictions leading to increased non-essential work, social activities and gathering, especially among younger persons. A longitudinal cohort analysis of Washington State Department of Health COVID-19 confirmed case age distribution 1) March-April 2020 (N = 13,934) and 2) March-August 2020 (N = 76,032) for proportional change over time using chi square tests for significance. From March 1st to April 19, 2020 COVID-19 age distribution shifted with a 10% decline in cases age 60 years and older and a 20% increase in age 0-19/20-39 years (chi-square = 223.10, p < .001). Number of cases over the initial analysis period were 0-19 years n = 515, 20-39 years n = 4078, 40-59 years n = 4788, 60-79 years n = 3221, 80+ years n = 1332. After the peak (March 22, 2020), incidence declined in older age groups and increased among age 0-19 and 20-39 age groups from 20% to 40% of total cases by April 19 and 50% by May 3. During this time testing expanded with more testing among older age groups and less testing among younger age groups while case positivity shifted young. Percent positive cases age 0-19/20-39 years through August 2020 increased to a consistent average of 60% [age 0-19 increased to 19% (N = 10257), age 20-39 increased to 42% (N = 30215)]. An increased sustained proportion of COVID-19 incidence is present among children (age 0-19) and young adults (age 20-39) indicating an elevated role in disease spread during the epidemic creating a possible reservoir of disease with spillover risk to more vulnerable older persons and those with comorbid conditions. Media savvy age-appropriate messaging to enhance mitigation compliance among less vulnerable, more mobile and lower priority vaccination age groups will be a continued necessity and priority to reduce overall population incidence.

This article examines the unique self-organised spatial and social structure of the Kat O coastal settlements in Hong Kong. By problematising the identity politics between built forms and landscapes , this paper analyses the village’s deep-rooted history within the land‒water dichotomies, which have been shaped by government survey methods and conservation-development policies. Specifically, it presents the peri-urban condition of Kat O’s coastal settlements as a departure from the traditional urban‒rural continuum perspectives. Empirically, the field documentation of the self-built additions presents critical perspectives into the static understanding of land ownership, addition and adaptation strategies and the building materialities embedded within the government survey methods and conservation-development policies. Theoretically, this study provides an understanding of these coastal settlements as cultural landscapes that are dynamically related to the environment, as well as the changing sociocultural relationships among different communities on the basis of their unique conceptions of habitation and living. By examining past and current conservation policies, this article advocates for a water-centric vision for countryside conservation in Hong Kong that transcends the commonly adopted terrecentric perspective.

Drought stress is a major environmental threat that limits plant growth and crop productivity. Therefore, it is necessary to uncover the molecular mechanisms behind drought tolerance in crops. Here, OsWRKY76 positively regulated drought stress in rice. OsWRKY76 expression was induced by PEG treatment, dehydration stress, and exogenous MeJA rather than by no treatment. Notably, OsWRKY76 knockout weakened drought tolerance at the seedling stage and decreased MeJA sensitivity. OsJAZ12 was significantly induced by drought stress, and its expression was significantly higher in OsWRKY76 -knockout mutants than in wild-type ZH11 under drought stress. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that OsWRKY76 interacted with OsJAZ12. OsWRKY76 weakened the interaction between OsbHLH148 and OsJAZ12 in yeast cells. The OsJAZ12 protein repressed the transactivation activity of OsbHLH148, and this repression was partly restored by OsWRKY76 in rice protoplasts. Moreover, OsDREB1E expression was lower in OsWRKY76 -knockout mutants than in wild-type ZH11 under drought stress, but it was upregulated under normal growth conditions. Yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays showed that OsWRKY76 and OsbHLH148 bound directly to the OsDREB1E promoter and activated OsDREB1E expression in response to drought stress. These results suggest that OsWRKY76 confers drought tolerance through OsbHLH148-mediated jasmonate signaling in rice, offering a new clue to uncover the mechanisms behind drought tolerance.

Introduction Prior reviews synthesized findings of studies on long-term cardiac complications of COVID-19. However, the reporting and methodological quality of these studies has not been systematically evaluated. Here, we conducted a systematic review and meta-analysis on long-term cardiac complications of COVID-19 and examined patterns of reported findings by study quality and characteristics. Methods We searched for studies examining long-term cardiac complications of COVID-19 that persisted for 4 weeks and over. A customized Newcastle–Ottawa scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed to generate prevalence estimates of long-term cardiac complications across studies. Stratified analyses were further conducted to examine the prevalence of each complication by study quality and characteristics. The GRADE approach was used to determine the level of evidence for complications included in the meta-analysis. Results A total number of 150 studies describing 57 long-term cardiac complications were included in this review, and 137 studies reporting 17 complications were included in the meta-analysis. Only 25.3% ( n  = 38) of studies were of high quality based on the NOS quality assessment. Chest pain and arrhythmia were the most widely examined long-term complications. When disregarding study quality and characteristics, summary prevalence estimates for chest and arrhythmia were 9.79% (95% CI 7.24–13.11) and 8.22% (95% CI 6.46–10.40), respectively. However, stratified analyses showed that studies with low-quality scores, small sample sizes, unsystematic sampling methods, and cross-sectional design were more likely to report a higher prevalence of complications. For example, the prevalence of chest pain was 22.17% (95% CI 14.40–32.55), 11.08% (95% CI 8.65–14.09), and 3.89% (95% CI 2.49–6.03) in studies of low, medium, and high quality, respectively. Similar patterns were observed for arrhythmia and other less examined long-term cardiac complications. Conclusion There is a wide spectrum of long-term cardiac complications of COVID-19. Reported findings from previous studies are strongly related to study quality, sample sizes, sampling methods, and designs, underscoring the need for high-quality epidemiologic studies to characterize these complications and understand their etiology.

Background Higher embryonic mortality, especially in aged breeding hens, is associated with insufficient hepatic functionality in maintaining redox homeostasis. Our previous study demonstrated that egg exosome-derived miRNAs may play a key role in modulating embryonic oxidation-reduction process, whereas the exact function and mechanism were still poorly understood. The present study aimed to investigate the roles of egg exosome miRNAs in maintaining dynamic equilibrium of free radicals and peroxide agents in embryonic liver, as well as demonstrate the specific mechanism using oxidative stress-challenged hepatocytes. Results Compared to 36-week-old breeding hens, decreased hatchability and increased embryonic mortality were observed in 65-week-old breeding hens. Meanwhile, the older group showed the increased MDA levels and decreased SOD and GSH-Px activities in embryonic liver, muscle and serum. Embryonic mortality was significantly positively correlated with MDA level and negatively correlated with GSH-Px activity in embryonic liver. In addition, 363 differentially expressed genes (DEGs) were identified in embryonic liver, 13 differentially expressed miRNAs (DE-miRNAs) were identified in egg exosomes. These DEGs and DE-miRNAs were involved in oxidoreductase activity, glutathione metabolic process, MAPK signaling pathway, apoptosis and autophagy. miRNA-mRNA network analysis further found that DEGs targeted by DE-miRNAs were mainly enriched in programmed cell death, such as apoptosis and autophagy. Wherein, MAPK10 with highest MCC and AUC values was significantly related to GSH-Px activity and MDA level, and served as the target gene of miR-145-5p based on dual luciferase reporter experiment and correlation analysis. Bioinformatics analysis found that miR-145-5p/ MAPK10 axis might alleviate peroxide generation and apoptosis. In primary hepatocytes of chick embryos, miR-145-5p transfection significantly reversed H 2 O 2 -induced mitochondrial ROS increase, MAPK10 , BAX and CASP3 overexpression and excessive apoptosis. Conclusion Exosome miR-145-5p in eggs could target MAPK10 and decrease mitochondrial ROS, attenuating oxidative damage and apoptosis in hepatocytes of chick embryos. These findings may provide new theoretical basis for the improvement of maternal physiological status to maintain embryonic redox homeostasis by nutritional or genetic modifications. Graphical Abstract

Key messageOsWRKY28 confers salinity tolerance by directly binding to OsDREB1B promoter and increasing its transcriptional activity, and negatively regulates abscisic acid mediated seedling establishment in rice. WRKY transcription factors have been reported to play a vital role in plants growth, development, abiotic and biotic stress responses. In this study, we explored the functions of a transcription factor OsWRKY28 in rice. The transcript level of OsWRKY28 was strikingly increased under drought, chilling, salt and abscisic acid treatments. The OsWRKY28 overexpression lines showed enhanced salinity stress tolerance, whereas the oswrky28 mutants displayed salt sensitivity compared to wild-type plants. Under salt stress treatment, the expression levels of OsbZIP05, OsHKT1;1 and OsDREB1B were significantly lower yet the level of OsHKT2;1 was significantly higher in oswrky28 mutants than those in wide type plants. Our data of yeast one-hybrid assay and dual-luciferase assay supported that OsWRKY28 could directly bind to the promoter of OsDREB1B to enhance salinity tolerance in rice. In addition, OsWRKY28 overexpression lines displayed hyposensitivity and the oswrky28 mutants showed hypersensitivity compared to wild-type plants under exogenous abscisic acid treatment. Based on the results of yeast two-hybrid assay and GAL4-dependent chimeric transactivation assay, OsWRKY28 physically interacts with OsMPK11 and its transcriptional activity could be regulated by OsMPK11. Together, OsWRKY28 confers salinity tolerance through directly targeting OsDREB1B promoter and further activating its transcription in rice.

Breast cancer is a heterogeneous disease with multiple established risk factors, which include high-penetrance germline variants in cancer predisposition genes such as ATM, BRCA1, BRCA2, CHEK2, and PALB2. Additionally, individual and behavioral factors such as age at menarche, parity, number of births, age at first full-term pregnancy, breastfeeding, age at natural menopause, height, pre- and post-menopausal body mass index (BMI), use of menopausal hormone treatment (PMH) and oral contraceptives (OC), history of benign breast disease (BBD), smoking and alcohol consumption have been consistently observed to be associated with breast cancer risk and may potentially modify the risk associated with pathogenic variants (PV). However, existing gene-environment interaction (GE) studies of rare PVs in breast cancer predisposition genes have been limited by sample size and the number of interactions assessed. GE studies have rarely been replicated, due to issues related to statistical power, exposure measurement errors, and difficulties in harmonizing data across different studies. Further, breast cancer is often treated as one disease, without consideration of molecular subtypes, primarily defined by estrogen receptor (ER) status, ignoring well-known differences in etiologies. Further, women who have been identified to have an elevated lifetime risk of breast cancer through genetic testing for hereditary cancer syndromes can benefit from risk management options such as enhanced screening and preventive surgery. However, these recommended risk management strategies are underutilized in current clinical practice, and healthcare utilization patterns following genetic testing remain poorly understood, particularly in underserved populations facing access barriers to genetic services.In this dissertation, we explored how genetic, epidemiological, and behavioral factors collectively influence breast cancer risk. Specifically, we aimed to 1) examine GE interactions between high penetrance breast cancer susceptibility genes and well-established epidemiological risk factors; 2) assess the impact of modifiable epidemiological risk factors on breast cancer risk across categories defined by nonmodifiable risk factors including a polygenic risk score (PRS) of common genetic variants; 3) examine the uptake of recommended risk management strategies for breast cancer subsequent to the disclosure of genetic testing results.To achieve these aims, we first explored GE interactions on both multiplicative and additive scales in a sample of women drawn from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium and the UK Biobank, comprising of 28,745 breast cancer cases and 102,997 controls. Subsequently, we developed a breast cancer risk prediction model that integrated breast cancer predisposition genes, a PRS, an epidemiologic risk score (ERS) for non-modifiable risk factors, and another ERS for modifiable risk factors, to examine the joint effects of these factors on breast cancer risk. Our findings demonstrated that an ERS, when combined with the PRS, could contribute to risk stratification for women who have a rare PV in a high-penetrance breast cancer susceptibility gene. The integration of rare high-penetrant and common low-penetrant genetic variation with epidemiologic risk factors into breast cancer risk prediction models has the potential to inform personalized screening and prevention strategies.Next, we assessed the utilization of recommended risk management options following genetic testing for hereditary cancer syndromes based on data from 680 patients who were part of the Cancer Health Assessments Reaching Many (CHARM) study, a multimodal cancer genetics services delivery program. We identified post-testing screening and surgical procedures using electronic health records, and examined utilization in participants who did and did not receive actionable risk management recommendations from study genetic counselors following national guidelines. Our results indicate that implementing CHARM’s risk assessment and testing model increased access to evidence-based genetic services and provided opportunities for patients to engage in recommended preventive care, without encouraging excessive use of risk management strategies.The findings of this dissertation could be useful to identify population subgroups who are especially susceptible to developing breast cancer and help establish personalized risk prevention recommendations for high-risk women.

PurposeEvaluate the COVID-19 pandemic impact on breast cancer detection method, stage and treatment before, during and after health care restrictions.MethodsIn a retrospective tertiary cancer care center cohort, first primary breast cancer (BC) patients, years 2019–2021, were reviewed (n = 1787). Chi-square statistical comparisons of detection method (patient (PtD)/mammography (MamD), Stage (0-IV) and treatment by pre-pandemic time 1: 2019 + Q1 2020; peak-pandemic time 2: Q2-Q4 2020; pandemic time 3: Q1-Q4 2021 (Q = quarter) periods and logistic regression for odds ratios were used.ResultsBC case volume decreased 22% in 2020 (N = 533) (p = .001). MamD declined from 64% pre-pandemic to 58% peak-pandemic, and increased to 71% in 2021 (p < .001). PtD increased from 30 to 36% peak-pandemic and declined to 25% in 2021 (p < .001). Diagnosis of Stage 0/I BC declined peak-pandemic when screening mammography was curtailed due to lock-down mandates but rebounded above pre-pandemic levels in 2021. In adjusted regression, peak-pandemic stage 0/I BC diagnosis decreased 24% (OR = 0.76, 95% CI: 0.60, 0.96, p = .021) and increased 34% in 2021 (OR = 1.34, 95% CI: 1.06, 1.70, p = .014). Peak-pandemic neoadjuvant therapy increased from 33 to 38% (p < .001), primarily for surgical delay cases.ConclusionsThe COVID-19 pandemic restricted health-care access, reduced mammography screening and created surgical delays. During the peak-pandemic time, due to restricted or no access to mammography screening, we observed a decrease in stage 0/I BC by number and proportion. Continued low case numbers represent a need to re-establish screening behavior and staffing.

Purpose The optimal duration of first-line trastuzumab (T) treatment for de novo stage IV HER2-positive metastatic breast cancer (MBC) patients after complete response (CR) is not known. Methods A retrospective cohort study of de novo stage IV HER2-positive MBC patients who had trastuzumab included in their initial treatment ( n  = 69), 1999–2018, was conducted with follow-up for CR, progressive disease (PD), vital status, and disease-specific survival (DSS). Statistics included Kaplan–Meier plots and Cox proportional hazards models. Results Mean trastuzumab treatment time was 4.1 years (range 0.1–15). 54% of patients experienced CR at average time 9 months on treatment ( n  = 37). Eight CR patients discontinued T treatment after 18 months average post-CR time (range 0–86) and twenty-nine stayed on T treatment post CR [average 65 months (range 10–170)]. Average follow-up was 6 years, range 1–15 years. 5-year DSS was 92% for CR on T patients ( N  = 29); 88% CR off T ( n  = 8); 73% No CR on T ( n  = 14); and 29% No CR off T ( n  = 18) ( p  < 0.001). In forward Cox proportional hazards modeling, CR = yes [HzR = 0.31, (95% CI 0.14, 0.73), p  = 0.007], continuous T treatment > 2 years [HzR = 0.24, (95% CI 0.10, 0.62), p  = 0.003], and age < 65 [HzR = 0.29, (95% CI 0.11, 0.81), p  = 0.018] were significantly associated with better DSS. Conclusion Maximum trastuzumab treatment time to CR was 27 months with 2 or more years trastuzumab treatment independently associated with better survival. Survival comparisons and hazard modeling both indicate as good or better survival associated with continuous trastuzumab treatment regardless of CR status. Word count ( n  = 250).

The urban metabolism concept is crucial for understanding city–environment interactions. Yet, its use in urban design is limited, and the examination of diverse design hypotheses with the potential to influence metabolic activities is seldom undertaken. This research addresses this gap and aims to analyze how the concept of metabolism (1) Can be leveraged by professionals for making urban design hypotheses, and (2) allows for the assessment of each of these hypotheses to reduce adverse environmental impacts and inform urban design decisions. Focusing on Paris’ Champs–Elysées redesign, in collaboration with PCA-STREAM, an urban design and architecture firm, this research employs fieldwork observations, tenant/store owner interviews, and specific metabolic models for water, energy, and materials. The results demonstrate that while redesigning the avenue’s public space potentially impacts the whole Champs–Elysées metabolism, this impact remains relatively limited. Intervening on objects with higher metabolic activities and using more efficient technologies might be more fruitful in terms of adverse environmental impact reduction, at least in this context.