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Qi Zeng,1,&ast; Jinjie Li,2,&ast; Yanrong Liu,1 Yiran Zhang,1 Hang Su,1 Faping Tu1 1Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of China; 2Operating Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faping Tu, Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China, Tel +86-13808270833, Email tfpnc@163.comPurpose: Sufentanil is a potent opioid analgesic frequently used to suppress the tracheal intubation response. The pathophysiological changes of obesity may affect opioid pharmacokinetics and increase the risk of opioid-induced adverse effects. Dexmedetomidine as an adjunct to anesthetic induction could save the dosage of sufentanil and attenuate hemodynamic response to tracheal intubation. This study was aimed at investigating the effect of intravenous dexmedetomidine premedication on the median effective concentration (EC50) of sufentanil for tracheal intubation in obese patients.Patients and Methods: Fifty obese patients undergoing elective bariatric or non-bariatric surgery under general anesthesia with tracheal intubation were equally randomized into the dexmedetomidine group and the saline group. Depending on the group, the patients were intravenously premedicated with 1 μg/kg dexmedetomidine or saline before anesthesia induction. Anesthesia was induced with target-controlled infusion of propofol (at 3.5 μg/mL) and sufentanil. The effect-site concentration of sufentanil for the first patient in the two groups was set at 0.4 ng/mL. The concentration of sufentanil for the next patient was determined using Dixon’s up-and-down sequential method with an interval of 0.05 ng/mL, according to the responses of the previous patient. Hemodynamic variables and sufentanil dose were recorded. The EC50 and 95% confidence interval (CI) of sufentanil were determined using probit regression analysis.Results: The EC50 of sufentanil and 95% CI were 0.25 (95% CI, 0.17– 0.31) ng/mL in the dexmedetomidine group and 0.43 (95% CI, 0.34– 0.46) ng/mL in the saline group (P < 0.05). The dosage of sufentanil was significantly lower in the former than in the latter. The hemodynamics were stable in both groups during the study.Conclusion: Intravenous premedication with 1 μg/kg dexmedetomidine significantly decreased the EC50 of sufentanil and sufentanil requirement for tracheal intubation in obese patients.Keywords: dexmedetomidine, median effective concentration, sufentanil, obesity

Hailan Su,1,&ast; Danfeng Liao,2,&ast; Chaolin Huang,2 Qin Liu,3 Lingfang Yu1 1Department of Gynecology, Suzhou Ninth People’s Hospital, Suzhou, People’s Republic of China; 2Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China; 3Department of Emergency Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingfang Yu, Department of Gynecology, Suzhou Ninth People’s Hospital, No. 2666, Ludang Road, Wujiang District, Suzhou City, Jiangsu Province, 215200, People’s Republic of China, Email yulingfang2024@163.com Qin Liu, Department of Emergency Medicine, The First Affiliated Hospital of Chengdu Medical College, No. 278, The Middle Section of Baoguang Avenue, Xindu District, Chengdu City, Sichuan Province, 610500, People’s Republic of China, Email 519791695@qq.comObjective: Previous studies reported that low cholinesterase (ChE) levels were associated with poor prognosis in various cancers, including bladder, pancreatic, lung, and colorectal cancers. This study aimed to evaluate the clinical significance of serum ChE levels as a prognostic biomarker in ovarian cancer.Materials and Methods: A retrospective cohort analysis was conducted on 168 patients diagnosed with epithelial ovarian cancer at the Suzhou Ninth People’s Hospital from 2019 to 2020. Serum ChE levels were measured before initiating treatment and stratified into low and high groups based on the median level (7600 U/L). Clinical and pathological data, such as FIGO stage, age, tumor histological type, and survival outcomes, were collected. Kaplan-Meier analysis and Cox proportional hazards regression were used to assess the relationship between ChE levels and overall survival and disease-free survival.Results: ChE levels were significantly correlated with clinicopathological features of epithelial ovarian cancer, including FIGO stage (p < 0.001), surgery completeness (p = 0.001), and platinum-resistant (p = 0.001). Kaplan-Meier analysis demonstrated that patients in the low ChE group had significantly worse overall survival (p = 0.003) and disease-free survival (p = 0.005) than those in the high ChE group. Multivariate Cox regression analysis identified low serum ChE levels as an independent predictor of poor overall survival and disease-free survival.Conclusion: Low serum ChE levels are independently associated with poor prognosis in ovarian cancer patients, reflecting systemic inflammation, malnutrition, and potential hepatic dysfunction. These findings suggest that ChE could serve as a cost-effective and non-invasive biomarker for risk stratification and prognosis in clinical practice.Keywords: cholinesterase, ovarian cancer, disease-free survival, overall survival

Yang Zhang,1,&ast; Pinglang Zhou,2,&ast; Chuan Xu,3,&ast; Hua Su,1 Rendong Li,1 Longhua Sun,2 Yihan Yang1 1Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yihan Yang, Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Diseases, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China, Email yangyihan@email.ncu.edu.cn Longhua Sun, The Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China, Email ndyfy05715@ncu.edu.cnObjective: To investigate the relationship between serum ferritin levels and OSA in overweight/obese individuals and assess the association between ferritin levels and all-cause mortality in overweight/obese female OSA patients.Methods: Cross-sectional (n = 4,809) and prospective (n = 832) data from overweight/obese adults from the 2005– 2008, and 2015-March 2020 NHANES cycles were analyzed. Participants were categorized into quartiles (Q1-Q4) based on their ln-transformed serum ferritin levels. Multivariable logistic regression and restricted cubic spline regression (RCS) investigate associations. Kaplan-Meier survival analyses and Cox proportional hazards regression examined the relationship between ferritin levels and all-cause mortality in OSA patients.Results: After adjusting for potential confounding factors, we found that ln-transformed ferritin levels were associated with an increased risk of OSA (Q4 vs Q2: OR = 1.07, 95% CI: 1.01– 1.13, P = 0.020, P for trend = 0.010). A non-linear U-shaped association was observed between ferritin levels and OSA risk (P-non-linear = 0.029), with an inflection point at ln-transformed ferritin of 4.58 (corresponding to a serum ferritin concentration of 97.51 ng/mL). In female OSA patients, elevated ferritin levels were associated with increased all-cause mortality risk (Q4 vs Q2: HR: 5.46, 95% CI: 1.18– 25.16, P = 0.029, P for trend = 0.032).Conclusion: Ferritin levels in overweight/obese individuals show a U-shaped relationship with OSA risk, and elevated levels correlate with increased all-cause mortality in female overweight/obese OSA patients. In the future, further research is needed to explore the potential associations between ferritin, inflammation, obesity, and OSA.Keywords: ferritin, obstructive sleep apnea, overweight/obese, all-cause mortality, NHANES

Hao Su,1,&ast; Xiao Shang,1,&ast; Hongruo Liu,2 Yutong Wang,1 Yang Yu,3 Yanhua Xu,4 Kui Jiang,2,&ast; Fengzhi Feng1,&ast; 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Obstetrics and Gynecology, Xing’an League People’s Hospital, Xing’an League, Inner Mongolia, People’s Republic of China; 4Department of Obstetrics and Gynecology, Jinan Maternity and Child Health Care Hospital, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengzhi Feng, Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, People’s Republic of China, Email fengfz1969@sina.com Kui Jiang, Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116023, People’s Republic of China, Email jk0411@163.comPurpose: Therapeutic options for patients with platinum-resistant ovarian cancer (PROC) remain a major unmet need. PROC patients with multiple recurrences are unable to continue highly toxic treatment after prior multiple lines of systemic therapy. Chemotherapy-free option lenvatinib plus anti-programmed cell death protein-1 (PD-1) combination therapy has shown promising results in several malignancies including ovarian cancer, but the toxicity of a high starting dose of lenvatinib is also notable and needs to be improved. Our previous pilot study indicated that a reduced starting dose of lenvatinib may maintain comparable anti-tumor activity with favorable safety in heavily pre-treated ovarian cancer. This study is designed to further validate the efficacy and safety of the combination therapy of low-dose lenvatinib and PD-1 inhibitor toripalimab in patients with recurrent PROC.Study Design and Methods: The study is designed as a multicenter, open-label, single-arm, prospective phase II study. Patients with recurrent epithelial ovarian cancer who have disease progression either during or within 6 months after completion of platinum-based therapy will be included. A total of 69 participants will receive low-dose lenvatinib (8 mg or 12 mg, daily, orally, based on patient’s body weight) and toripalimab (240 mg, every 21 days, intravenously). Treatment will continue until the development of unacceptable toxicity or disease progression. The primary endpoint is the progression-free survival. The secondary endpoints include objective response rate, duration of response, disease control rate, overall survival, toxicity and patients’ quality of life. Exploratory objectives aim to identify biomarkers and molecular signatures for predicting response or prognosis.Keywords: ovarian cancer, platinum-resistant, immune checkpoint inhibitor, lenvatinib, dose adjustment

Zi-Teng Wang,1,2,&ast; Wen-Tao Tan,1,&ast; Jia-Li Huang,1 Peng-Fei Zhang,3 Qian Li,1 Miao-Miao Wang,1 Ming-Ming Meng,1 Hui Su,1 Chun-Mei Guo,1 Hong Liu1 1Gastroenterology Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Gastroenterology Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Emergency Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Liu, Email liuhong_sjt@ccmu.edu.cnBackground: Our study examines the relationship between gastroesophageal reflux disease (GERD) and small intestinal bacterial overgrowth (SIBO), focusing on the potential impact of acid-suppressive drugs. We also explore changes in gut microbiota and metabolism in patients with both conditions.Methods: This study included patients from the Department of Gastroenterology, Beijing Shijitan Hospital, between February 2021 and November 2023. All patients underwent assessments including questionnaires, hydrogen and methane breath tests, and gastroscopy. GERD was diagnosed using the GERD-Q scale and gastroscopy, while SIBO was diagnosed via breath tests. We analyzed the correlation between GERD and SIBO, identified risk factors for SIBO, and examined the gut microbiota using 16S rRNA sequencing to explore the relationship between GERD and SIBO.Results: The retrospective study included 394 patients.148 with GERD and 287 with positive SIBO results. Among these, 270 had a positive methane (CH4) breath test and 97 had a positive hydrogen (H2) breath test. GERD was more common in patients with positive SIBO (P = 0.007), and the link between CH4 breath tests and GERD was stronger than that with H2 breath tests (P = 0.020). Logistic regression showed GERD is an independent risk factor for SIBO. Short-term, low-dose acid-suppressive drugs did not affect SIBO development. 16S rRNA sequencing of fecal microbiota from 24 patients showed dominant microbiota in SIBO-positive GERD patients included bacteroides uniformis and bacteroides stercoris. Patients with both GERD and SIBO had differential metabolites, mainly associated with ATP-Binding Cassette transporters (ABC transporters).Conclusion: GERD is strongly linked to SIBO, especially in patients with a positive CH4 breath test. The gut microbiota in GERD and SIBO patients differs from healthy individuals, with bacteroides uniformis as a key marker. Metabolic changes are mainly related to ABC transporter metabolites.Keywords: gastroesophageal reflux disease, small intestinal bacterial overgrowth, hydrogen-methane breath test, gut microbiota, microbial metabolites

Hongyun Shu,1,&ast; Sisi Han,1,&ast; Weiping Qiu,1 Jianhong Li,1 Xiaoyong Zhang,1 Haicui Su,1 Hongjie Wu,2 Guojun Zhao,1 Qiaowen Li3 1Department of Cardiovascular Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital) of Guangzhou Medical University, Qingyuan, Guangdong, People’s Republic of China; 2Department of Urology, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital) of Guangzhou Medical University, Qingyuan, Guangdong, People’s Republic of China; 3Institute of Gerontology, The Affiliated Guangzhou Geriatric Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaowen Li, Institute of Gerontology, Guangzhou Geriatric Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China, Email Stevenxzf@sina.com Guojun Zhao, Department of Cardiovascular Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital) of Guangzhou Medical University, Qingyuan, Guangdong, People’s Republic of China, Email zhaoguojun@gzhmu.edu.cnBackground: The monocyte to high-density lipoprotein cholesterol (MHR) and neutrophil to high-density lipoprotein cholesterol ratio (NHR) are novel comprehensive indicators reflecting the body’s inflammation and lipid metabolism. Previous studies have found that MHR and NHR are associated with the risk of cardiovascular and cerebrovascular events and death. However, the correlation between MHR, NHR, and the severity of newly diagnosed coronary artery disease (CAD) has not been thoroughly explored.Methods: In this retrospective study, we enrolled 1489 patients who underwent coronary angiography for the first time between January 2022 and December 2023, of which 1143 were diagnosed with CAD. The severity of CAD was gauged by the Gensini score (GS). The relationship between MHR and NHR with CAD was validated through logistic regression analysis, adjusting for traditional cardiovascular risk factors and medication therapy. The nonlinear relationship between MHR and NHR with CAD and GS was assessed by using restricted cubic spline (RCS) models. Their independent and combined predictive effects on CAD were evaluated through receiver operating characteristic (ROC) curve analysis.Results: MHR and NHR were independently associated with CAD (both P< 0.001). In the fully adjusted model, an increase in MHR was significantly associated with an increased odds ratio (OR) for CAD (OR=4.29, 95% CI 2.72– 6.78, P< 0.001). Sensitivity analysis revealed a consistent trend (P for trend< 0.05). RCS curve analysis indicated a nonlinear relationship between the two biomarkers and GS (P< 0.05) and there were clear inflection points. The area under the curve for predicting CAD was 0.68 for MHR and 0.69 for NHR, with optimal cut-off values of 0.42 (Youden index:0.29) and 5.43 (Youden index:0.31) respectively. Combined MHR and NHR has higher predictive value.Conclusion: MHR and NHR are independently associated with CAD, and there is a nonlinear correlation with the GS. Both have some predictive value for the severity of CAD.Keywords: monocyte to high-density lipoprotein cholesterol ratio, neutrophil to high-density lipoprotein cholesterol, coronary artery disease, coronary artery disease severity, Gensini score

BACKGROUND: A myriad of federal, state, and organizational policies are designed to improve access to evidence-based healthcare, but the impact of these policies likely varies due to contextual determinants of, reinterpretations of, and poor compliance with policy requirements throughout implementation. Strategies enhancing implementation and compliance with policy intent can improve population health. Critically assessing the multi-level environments where health policies and their related health services are implemented is essential to designing effective policy-level implementation strategies. California passed a 2019 health insurance benefit mandate requiring coverage of fertility preservation services for individuals at risk of infertility due to medical treatments, in order to improve access to services that are otherwise cost prohibitive. Our objective was to document and understand the multi-level environment, relationships, and activities involved in using state benefit mandates to facilitate patient access to fertility preservation services. METHODS: We conducted a mixed-methods study and used the policy-optimized exploration, preparation, implementation, and sustainment (EPIS) framework to analyze the implementation of Californias fertility preservation benefit mandate (SB 600) at and between the state insurance regulator, insurer, and clinic levels. RESULTS: Seventeen publicly available fertility preservation benefit mandate-relevant documents were reviewed. Interviews were conducted with four insurers; 25 financial, administrative, and provider participants from 16 oncology and fertility clinics; three fertility pharmaceutical representatives; and two patient advocates. The mandate and insurance regulator guidance represented two Big P (system level) policies that gave rise to a host of little p (organizational) policies by and between the regulator, insurers, clinics, and patients. Many little p policies were bridging factors to support implementation across levels and fertility preservation service access. Characterizing the mandates functions (i.e., policy goals) and forms (i.e., ways that policies were enacted) led to identification of (1) intended and unintended implementation, service, and patient outcomes, (2) implementation processes by level and EPIS phase, (3) actor-delineated key processes and heterogeneity among them, and (4) inner and outer context determinants that drove adaptations. CONCLUSIONS: Following the midstream and downstream implementation of a state health insurance benefit mandate, data generated will enable development of policy-level implementation strategies, evaluation of determinants and important outcomes of effective implementation, and design of future mandates to improve fit and fidelity.

Non-invasively evaluating gene expression products in human pre-implantation embryos remains a significant challenge. Here, we develop a non-invasive method for comprehensive characterization of the extracellular RNAs (exRNAs) in a single droplet of spent media that was used to culture human in vitro fertilization embryos. We generate the temporal extracellular transcriptome atlas (TETA) of human pre-implantation development. TETA consists of 245 exRNA sequencing datasets for five developmental stages. These data reveal approximately 4,000 exRNAs at each stage. The exRNAs of the developmentally arrested embryos are enriched with the genes involved in negative regulation of the cell cycle, revealing an exRNA signature of developmental arrest. Furthermore, a machine-learning model can approximate the morphology-based rating of embryo quality based on the exRNA levels. These data reveal the widespread presence of coding gene-derived exRNAs at every stage of human pre-implantation development, and these exRNAs provide rich information on the physiology of the embryo.

IntroductionMeta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility.ObjectiveThe objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework.MethodsWe used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure.ResultsOnly 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P  100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.

Zhen Zhang,1,&ast; Qiang Chen,2,&ast; Qiping Chen,3,&ast; Jun Hou,1 Xin Li,1 Jinjuan Fu,1 Yan Luo,1 Hong Su,1 Yu Long,1 Qiao Feng,1 Xiufen Peng,1 Maoling Jiang,1 Daiqian Wu,1 Hanxiong Liu,1 Lin Cai,1 Shiqiang Xiong1,4 1Department of Cardiology, College of Medicine, Southwest Jiaotong University, Chengdu Cardiovascular Disease Research Institute, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of China; 2Department of Cardiology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Cardiology, Sichuan Provincial Third People’s Hospital, Affiliated Hospital of Sichuan Nursing Vocational College, Chengdu, Sichuan, People’s Republic of China; 4Institute of Biomedical Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiqiang Xiong; Lin Cai, Email xionglliu@163.com; clin63@yeah.netBackground: Increased levels of remnant cholesterol (RC) and inflammation are linked to higher risks of atherosclerotic cardiovascular disease. Whether a combination of C-reactive protein (CRP) and RC improves the predictive ability for evaluating the severity of coronary artery lesions remains unknown.Methods: A total of 1675 patients with coronary artery disease were stratified according to the Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score ≤ 22 versus SYNTAX score > 22). Logistic regression and restricted cubic spline models were used to evaluate the relationship between RC, CRP and the severity of coronary artery lesions. Multivariate logistic regression was used to identify predictors of a mid/high SYNTAX score (SYNTAX score > 22). The predictive value of RC combined with CRP was estimated by the ROC curve, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI).Results: The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of RC were 2.143 (1.450– 3.166) for a mid/high SYNTAX score (SYNTAX score > 22). The association of RC with severity of coronary artery lesions was maintained significant in the subsample of patients, regardless of traditional cardiovascular risk factors like LDL-C levels and glycemic metabolism status. Moreover, the addition of CRP and RC to the baseline risk model had an incremental effect on the predictive value for a mid/high SYNTAX score (increase in C‑statistic value from 0.650 to 0.698; IDI 0.03; NRI 0.306; all P < 0.01).Conclusion: Elevated RC levels were significantly associated with the severity of coronary artery lesions even in patients with optimal low-density lipoprotein cholesterol levels. Adjustment of the RC by CRP further improved the predictive ability for the severity of coronary artery lesions. The combination of RC and CRP might serve as a noninvasive predictor of CAD complexity and could potentially influence the management and therapeutic approach.Keywords: coronary artery disease, coronary angiography, remnant cholesterols, C-reactive protein, inflammation, SYNTAX score

Huanjun Su,1,2 Rachel Ka Man Chun,1,3– 5 Elie De Lestrange-Anginieur1,3– 5 1School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong; 2Department of Optometry, Liuzhou Worker’s Hospital, Liuzhou, Guangxi Zhuang Autonomous Region, 545005, People’s Republic of China; 3Research Centre for SHARP Vision (RCSV), the Hong Kong Polytechnic University, Kowloon, Hong Kong; 4Laboratory of Experimental Optometry, Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong; 5Centre for Eye and Vision Research (CEVR), Hong Kong, Hong KongCorrespondence: Elie De Lestrange-Anginieur, School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, Tel +852 2766 4186, Fax +852 2764 6051, Email elie.delestrangeanginieur@polyu.edu.hkPurpose: Animal studies have suggested that visual degradation impacts eye growth due to the attenuation of high spatial frequencies. However, the influence of perceptual visibility remains unclear in humans. The aim of this study was to investigate the impact of visibility on visual attenuation-related eye changes during reading.Methods: Axial length (AxL) and choroidal thickness (ChT) changes associated with reading tasks were measured in two separate experiments. In the first experiment, the reading task was conducted under different forms of visual attenuation (contrast, resolution, defocus, noise, and crowding). For each form of visual attenuation, the text was set at a sub-threshold level of visibility, evaluated via prior measurement of reading performance, and kept constant via adaptive control of the intensity of the stimulation. Each sub-threshold reading condition was compared with a supra-threshold reading text, serving as control. In the second experiment, the effect of visibility on lens-induced defocus was further examined by comparing the effect of text stimulation with an equivalent dioptric of 5.5 D under sub- and supra-threshold levels of resolution.Results: Near distance reading with supra-threshold texts caused eye elongation (AxL: +12.942 μm ± 2.147 μm; ChT: − 3.192 μm ± 1.158 μm). Additional defocusing failed to exacerbate axial elongation under sub-threshold text visibility (mean difference: − 0.135 μm ± 2.783 μm), revealing a clear inhibitory effect of lowering visibility on eye changes. Other forms of visual degradation, including crowding (mean difference: 6.153 μm ± 2.127 μm) and noise (mean difference: 5.02 μm ± 2.812 μm) also showed an inhibitory effect on eye elongation. The significant effect of crowding indicated that post-retinal mechanisms, involving attentional processes related to crowded characters, may play a role in the influence of visibility.Conclusion: Although the featural composition of visual stimulation can drastically influence eye changes, this study revealed an important mediating role of visibility, previously underscored in chick studies, which warrants further explorations of the impact of post-retinal processes in eye growth.Keywords: reading, crowding, myopia, axial length, choroidal thickness

Purpose: Oncofertility counseling of female cancer patients lacks efficient access to tailored and valid infertility risk estimates to support shared decision-making on fertility preservation treatments. The objective was to develop, conduct user-centered design, and plan clinic-based implementation of the Cancer Related Infertility Score Predictor (CRISP), a web-based tool to support infertility risk counseling. Methods: Using a mixed methods design, literature review was undertaken to abstract data on infertility, primary ovarian insufficiency, and amenorrhea risks of common cancer treatments. The CRISP website was programmed to take user input about patient ages and cancer treatments and generate a risk summary. Using user experience methodology and semistructured interviews, usability testing and implementation assessment were conducted with 12 providers recruited from 5 medical centers in Southern California. Results: The web-based CRISP tool encompasses infertility risk data for 60 treatment regimens among 10 cancer types. Usability testing demonstrated that the tool is intuitive and informed minor modifications, including adding crowd-sourced submission of additional cancer treatments. Participants rated the tool as credible, advantageous over current provider methods to ascertain infertility risks, and useful for tailoring treatment planning and counseling patients. A key barrier was lack of information on some cancer treatments. Fit within clinical workflow was feasible, particularly with electronic health record integration. Conclusions: The novel, web-based CRISP tool is a feasible, acceptable, and appropriate tool to address provider knowledge gap about cancer related infertility risks and use for patient counseling. CRISP has significant potential to support tailored oncofertility counseling in the heterogeneous young cancer patient population.

PURPOSE: Pregnancy intentions are associated with preconception health behaviors but are understudied among female adolescent and young adult (AYA) cancer survivors. Preconception health is critical for survivors because they face unique risks to fertility and pregnancy from late effects of cancer treatments. This study prospectively assessed the effect of pregnancy intention on physical activity (PA) and smoking behaviors among female AYA survivors. METHODS: A cohort of 1049 female AYA survivors were recruited between 2013 and 2017. Participants were 18-39 years and had completed primary cancer treatment. Longitudinal mixed effects analysis was conducted on participants who completed at least 2 of 4 questionnaires over 1.5 years. Two measures were used to capture multiple dimensions of pregnancy intention. The pregnancy intention score (PIS) captured wanting and planning dimensions and represented a scaled response of low to high intention. The trying dimension captured urgent intention and ranged from not trying, ambivalent (neither attempting nor avoiding pregnancy), and trying now. Intention change was assessed between each consecutive time points. Final analysis was conducted with multiple imputations. RESULTS: Survivors with increased intention measured by trying was associated with increased PA over time (adjusted B [95%CI]: 0.3 [0.01, 0.5]) compared to survivors with no changes or decreased trying intention. PIS was not significantly associated with preconception behaviors. No measure of intention was associated with smoking behavior. CONCLUSIONS: Increasingly urgent pregnancy intention (trying dimension) was associated with higher preconception PA. IMPLICATIONS FOR CANCER SURVIVORS: Screening for immediate intentions can identify AYA survivors in need of early preconception health promotion.

Border effects are very common in many finite signals analysis and processing approaches using convolution operation. Alleviating the border effects that can occur in the processing of finite-length signals using wavelet transform is considered in this paper. Traditional methods for alleviating the border effects are suitable to compression or coding applications. We propose an algorithm based on Fourier series which is proved to be appropriate to the application of time-frequency analysis of nonlinear signals. Fourier series extension method preserves the time-varying characteristics of the signals. A modified signal duration expression for measuring the extent of border effects region is presented. The proposed algorithm is confirmed to be efficient to alleviate the border effects in comparison to the current methods through the numerical examples.

PURPOSE: Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS: A cross-sectional survey was distributed to 220 Childrens Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Of these, 65 (45.1%) reported routine discussions of fertility with all female patients and 55 (38.5%) all male patients (P = .25). Ninety-two (63.8%) reported no specific criteria for offering females fertility preservation (FP), compared with 40 (27.7%) for males (P < .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION: Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Childrens Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

Purpose: Oncofertility care for pediatric, adolescent, and young adult cancer patients remains under-implemented across adult and pediatric oncology settings. We pilot tested an electronic health record (EHR)-enabled multicomponent oncofertility intervention (including screening, referral, and fertility consult) in an adult academic oncology program and systematically assessed intervention fit to pediatric and community oncology programs. Methods: Using surveys (n = 33), audits (n = 143), and interviews (n = 21) guided by implementation science frameworks, we pilot tested the EHR-enabled intervention for oncofertility care in young cancer patients at an adult oncology program and evaluated implementation outcomes. We interviewed health care providers from seven regional oncology and fertility programs about intervention fit to their clinical contexts. Results: We recruited 33 health care providers from an adult oncology setting and 15 health care providers from seven additional oncology and fertility settings. At the adult oncology setting, the intervention was found to be appropriate, acceptable, and feasible and improved the screening of fertility needs (from 30% pre- to 51% post-intervention); yet, some patients did not receive appropriate referrals to fertility consults. Providers across all settings suggested content and context modifications, such as adding options to the intervention or allowing the screening component to pop up at a second visit, to improve and adapt the intervention to better fit their clinical care contexts. Conclusions: We found that the EHR-enabled intervention increased the rate of goal-concordant oncofertility care delivery at an adult oncology program. We also identified facilitators, barriers, and needed adaptations to the intervention required for implementation and scaling-up across diverse oncology settings.

Jie Liu,1,&ast; Xiajie Huang,1,&ast; Hongjie Su,1 Jie Yu,1 Xinyu Nie,1 Kaibing Liu,1 Wencong Qin,1 Yongxin Zhao,1 Yongfeng Su,1 Xiaocong Kuang,2 Di Chen,3 William W Lu,4 Yan Chen,1 Qikai Hua1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Yulin Campus of Guangxi Medical University, Yulin, Guangxi, People’s Republic of China; 3Research Center for Computer-Aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 4Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Qikai Hua, Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email cy003@connect.hku.hk; hqk100@yeah.netPurpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration.Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA.Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001).Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.Keywords: distraction osteogenesis, tibial cortex transverse transport, diabetic foot, HIF-1α, angiogenesis

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (β = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (β = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

Jingcheng Ding,1,&ast; Qian Shi,1,&ast; Ling Dong,2 Hong Su,3 Yijun Du,1 Tianrong Pan,1 Xing Zhong1 1Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Zhong, Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei City, Anhui province, People’s Republic of China, Tel +86 18905692292, Email zhongxing761@163.comPurpose: To investigate the relationship between HbA1c variability and vibrating perception threshold (VPT) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 367 middle-aged and elderly patients with T2DM were enrolled. All patients were categorized into the control and vibration sensation deficiency group (VSD) based on VPT. Clinical data were collected. The coefficient of variation of glycated hemoglobin A1c (HbA1c-CV) and the mean glycated hemoglobin A1c(HbA1c-Mean) are considered as indexes of HbA1c variability. Multivariate logistic regression analysis, the generalized linear model and ROC curve correlation analysis were used to analyze the correlation of various factors and VPT.Results: The multivariate logistic regression analysis revealed that age, systolic blood pressure (SBP), and HbA1c-CV were identified as risk factors for vibration sensation deficiency in middle-aged and elderly patients with T2DM, while estimated glomerular filtration rate (eGFR), triiodothyronine (T3), and alanine aminotransferase (ALT) were considered as protective factors. In the unadjusted generalized linear model, a significant association was observed between HbA1c-CV and VPT values. After adjusting for age, diabetic duration, SBP, homeostatic model assessment for beta-cell function (HOMA-β), ALT, eGFR, T3, 24-hour urinary protein excretion levels, and HbA1c-Mean, HbA1c-CV remained significantly correlated with VPT values on both sides. (left side, B=2.560, 95% CI 1.298~3.823; P< 0.001; right side, B=2.608, 95% CI 1.498~3.718, P< 0.001). The area under the curve (AUC) for HbA1c-CV and VSD prevalence was 0.723, with a sensitivity of 79.85%, specificity of 56.22%.Conclusion: The risk of developing VSD increases proportionally with higher HbA1c-CV levels in middle-aged and elderly patients with T2DM. Reaching and maintaining blood glucose stability is essential to the mitigation of diabetes peripheral neuropathy occurrence.Keywords: type 2 diabetes mellitus, HbA1c variability, vibrating perception threshold, diabetic peripheral neuropathy

Biological soil crusts (biocrusts) release the reactive nitrogen gases (Nr) nitrous acid (HONO) and nitric oxide (NO) into the atmosphere, but the underlying microbial process controls have not yet been resolved. In this study, we analyzed the activity of microbial consortia relevant in Nr emissions during desiccation using transcriptome and proteome profiling and fluorescence in situ hybridization. We observed that < 30 min after wetting, genes encoding for all relevant nitrogen (N) cycling processes were expressed. The most abundant transcriptionally active N-transforming microorganisms in the investigated biocrusts were affiliated with Rhodobacteraceae, Enterobacteriaceae, and Pseudomonadaceae within the Alpha- and Gammaproteobacteria. Upon desiccation, the nitrite (NO2-) content of the biocrusts increased significantly, which was not the case when microbial activity was inhibited. Our results confirm that NO2- is the key precursor for biocrust emissions of HONO and NO. This NO2- accumulation likely involves two processes related to the transition from oxygen-limited to oxic conditions in the course of desiccation: (i) a differential regulation of the expression of denitrification genes; and (ii) a physiological response of ammonia-oxidizing organisms to changing oxygen conditions. Thus, our findings suggest that the activity of N-cycling microorganisms determines the process rates and overall quantity of Nr emissions.

BackgroundFemale adolescent and young adult (AYA) cancer survivors face higher infertility and pregnancy risks than peers with no cancer history. Preconception health behaviors such as physical activity (PA), tobacco smoking, and alcohol intake influence reproductive outcomes. In general populations, pregnancy intention is positively associated with healthy preconception behaviors, but it has not been studied among AYA survivors. The authors hypothesized that higher pregnancy intention would be associated with healthier behaviors, especially among AYA survivors with perceived infertility risk.MethodsA cross-sectional analysis was conducted with data collected between 2013 and 2017 from 1071 female AYA survivors aged 18 to 39 years who had completed their primary cancer treatment and enrolled in an ovarian function study. Self-reported intention dimensions were measured as a pregnancy intention score (PIS) and trying now to become pregnant. Multivariable linear (PA), binary (smoking), and ordinal (alcohol use) logistic regressions were used to estimate associations between intentions and preconception behaviors, with adjustments made for demographic and cancer characteristics. Effect modification by perceived infertility risk was assessed.ResultsThe mean PIS was 1.1 (SD, 0.77) on a 0 to 2 scale (2 = high intention), and 8.9% were attempting pregnancy now. A higher PIS was associated with increased PA (β, 0.08; 95% CI, 0.11-1.04), whereas ambivalence in pregnancy intention was associated with lower alcohol consumption (odds ratio, 0.72; 95% CI, 0.55-0.95). Pregnancy intentions were not associated with smoking. Perceived infertility risk strengthened the relationship between PIS and PA (P < .05).ConclusionsPregnancy intentions were associated with some healthier preconception behaviors in AYA survivors. Medical professionals caring for AYA survivors may consider pregnancy intention screening to guide conversations on preconception health.

Author(s): Lauren S. Weiner [sup.1] [sup.2] , Stori Nagel [sup.3] , H. Irene Su [sup.2] [sup.4] , Samantha Hurst [sup.1] , Susan S. Levy [sup.5] , Elva M. Arredondo [sup.6] [...], Younger breast cancer survivors (YBCS) consistently report poorer quality of life (QOL) than older survivors. Increasing physical activity (PA) may improve QOL, but this has been understudied in YBCS. This single arm pilot study evaluated the feasibility and acceptability of a 3-month, peer-delivered, remote intervention to increase PA and improve QOL in YBCS. Data were collected from October 2019 - July 2020. Participants (n = 34, 43.1 ± 5.5 years old, 46 ± 34.4 months post-diagnosis, BMI = 30.2 ± 7.4 kg/m.sup.2) completed six video sessions with a trained peer mentor; self-monitored PA with a Fitbit activity tracker; and interacted with a private Fitbit Community for social support. At baseline, 3-and 6-months, participants completed QOL questionnaires and PA was measured through accelerometer (moderate-to-vigorous PA [MVPA]) and self-report (strength and flexibility). A parallel mixed-methods approach (qualitative interviews and quantitative satisfaction survey at 3-months) explored intervention feasibility and acceptability. One-way repeated-measures ANOVAs examined impacts on PA and QOL at 3-and 6-months. The intervention was feasible as evidenced by efficient recruitment, high retention, and adherence to intervention components. Remote delivery, working with a peer mentor, and using Fitbit tools were highly acceptable. From baseline to 3-months, participants increased time spent in objectively measured MVPA, strength, and flexibility exercises, and reported meaningful improvements to body image, fatigue, anxiety, and emotional support. A fully remote, peer-to-peer intervention is an acceptable and promising strategy to increase PA and improve QOL in YBCS. Refinements to the intervention and its delivery should be further assessed in future studies, toward the goal of disseminating an evidence-based, scalable intervention to the growing number of YBCS. Trial registration Prospectively registered as NCT04064892.

Qian Shi,1,&ast; Jingcheng Ding,1,&ast; Hong Su,2 Yijun Du,1 Tianrong Pan,1 Xing Zhong1 1Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China; 2Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei City, Anhui Province, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Zhong, No. 678 Furong Road, Hefei City, Anhui Province, 230601, People’s Republic of China, Tel +86 18905692292, Email zhongxing761@163.comPurpose: To explore the relationship between long-term glycemic variability and anxiety and depression in patients with type 2 diabetes.Participants and Methods: A cohort comprising 214 individuals diagnosed with type 2 diabetes participated in this study. Comprehensive demographic and laboratory information was gathered for them. The evaluation of anxiety relied on the 7-item Generalized Anxiety Disorder Scale (GAD-7), while depression was assessed utilizing the 9-item Health Questionnaire (PHQ-9). Based on the presence or absence of anxiety and depression, participants were categorized into either the mood disorder or control groups. Subsequently, univariate and stepwise multiple binary logistic regression analyses were conducted to investigate the potential correlations between factors and the presence of anxiety and depression.Results: The prevalence of anxiety disorders is 23%, and depression is 32%. The prevalence of smoking, diabetic autonomic neuropathy, stroke, and osteoporosis in the mood disorder group was significantly higher than that in the control group (P < 0.05), the glycated hemoglobin A1c variability score (HVS), mean hemoglobin A1c value, total cholesterol, urinary albumin/creatinine and systemic immune-inflammatory index (SII) were significantly higher in the control group (P < 0.05). The level of high-density lipoprotein in the mood disorder group was significantly lower than the control group (P < 0.05). In stepwise multiple binary logistic regression analyses, the main factors associated with anxiety were depression (P < 0.001, OR=117.581) and gender (P < 0.001, OR=9.466), and the main factors related to depression included anxiety (P < 0.001, OR=49.424), smoking (P=0.042, OR=2.728), HVS (P=0.004, OR=8.664), and SII (P=0.014, OR=1.002).Conclusion: Persistent fluctuations in blood glucose levels have been linked to anxiety and depression. Consequently, maintaining an optimal level of glycemic control and minimizing fluctuations becomes imperative in the comprehensive management of diabetes.Keywords: type 2 diabetes, anxiety, depression, long-term glycemic variability

Study questionIs psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)?Summary answerWe observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors.What is known alreadyPsychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown.Study design, size, durationA cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants.Participants/materials, setting, methodsAYA survivor participants were ages 15-35 at cancer diagnosis and ages 18-40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3-7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry.Main results and the role of chanceThe median age of participants was 34.0 years (range 19-41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0-36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures.Limitations, reasons for cautionOur analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress.Wider implications of the findingsThe lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans.Study funding/competing interest(s)NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests.Trial registration numberN/A.

PurposeToday, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium.MethodsThe Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process.ResultsThis interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity.ConclusionThe goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

On behalf of the journal, AGU, and the scientific community, the editors would like to sincerely thank those who reviewed the manuscripts for Geophysical Research Letters in 2019. The hours reading and commenting on manuscripts not only improve the manuscripts but also increase the scientific rigor of future research in the field. We particularly appreciate the timely reviews in light of the demands imposed by the rapid review process at Geophysical Research Letters. With the revival of the “major revisions” decisions, we appreciate the reviewers' efforts on multiple versions of some manuscripts. With the advent of AGU's data policy, many reviewers have helped immensely to evaluate the accessibility and availability of data associated with the papers they have reviewed, and many have provided insightful comments that helped to improve the data presentation and quality. We greatly appreciate the assistance of the reviewers in advancing open science, which is a key objective of AGU's data policy. Many of those listed below went beyond and reviewed three or more manuscripts for our journal, and those are indicated in italics.