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Yuan-Yuan Lei,1 Suzanne C Ho,2 Ashley Cheng,3 Carol Kwok,3 Ka Li Cheung,1 Yi-Qian He,1 Chi-Kiu Iris Lee,1 Roselle Lee,1 Winnie Yeo1,4 1Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; 2Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China; 3Department of Clinical Oncology, Princess Margaret Hospital, Kwai Chung, Hong Kong Special Administrative Region, China; 4Hong Kong Cancer Institute, State Key Laboratory in Oncology in South China, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China Background: The diagnosis of cancer can motivate patients to change their dietary habits. Evidence on changes in dietary intake before and after breast cancer diagnosis in Chinese women has been limited. Patients and methods: In an ongoing prospective cohort study which involved 1,462 Chinese women with early-stage breast cancer, validated food frequency questionnaire was used to assess prediagnostic dietary intake (using questionnaire to recall dietary intake before diagnosis, which completed at baseline, ie, 0–12 months after diagnosis) and postdiagnostic dietary intake at 18-month and 36-month follow-ups after diagnosis. This study quantitatively compared dietary intake across three time points before and after breast cancer diagnosis. Results: Breast cancer patients significantly and continuously increased vegetables and fruits consumption, from 4.54 servings/day at prediagnosis to 5.19 and 5.59 servings/day at 18-month and 36-month follow-ups postdiagnosis, respectively (each compared to baseline, P

Wen-Hsuan Tsai,1 Kun-Hua Yu,1 Yi-Cheng Huang,2 Cheng-I Lee1 1Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi, Taiwan, Republic of China; 2Department of Food Science, National Taiwan Ocean University, Keelung City, Taiwan, Republic of China Background: Photodynamic therapy (PDT) is an effective therapy for cancers and is a minimally invasive therapy with low dark toxicity and limited side effects. PDT employs the combination of photosensitizers with a specific light source to produce reactive oxygen species (ROS) to damage tumor cells. Methods: We fabricated nanoparticles encapsulating curcumin through crosslinking chitosan and tripolyphosphate (TPP). Additionally, the chitosan was conjugated to epidermal growth factor in order to target the epidermal growth factor receptor (EGFR), overexpressed on cancer cells. To investigate PDT using fabricated nanoparticles, we measured cell viabilities and ROS production in relation to EGFR-overexpressing gastric cancer cells and non-cancer gastric cells.Results: The targeting nanoparticles displayed a superior PDT effect in the cancer cell, with a resultant approximately fourfold decrease in the IC50. The PDT mechanism of curcumin-encapsulated nanoparticles is further identified as the generation of 1O2, the major pathway in PDT.Conclusion: These curcumin-encapsulated chitosan/TPP nanoparticles are a promising targeted-PDT against EGFR-overexpressing cancers. Keywords: EGFR-targeting, cancer, photodynamic therapy, curcumin, chitosan

Seong-Chul Hong,1 Young-Eun Jung,2 Moon-Doo Kim,2 Chang-In Lee,2 Mi-Yeul Hyun,3 Won-Myong Bahk,4 Bo-Hyun Yoon,5 Kwang Heun Lee6 1Department of Preventive Medicine, 2Department of Psychiatry, School of Medicine, 3College of Nursing, Jeju National University, Jeju, Republic of Korea; 4Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Department of Psychiatry, Naju National Hospital, Naju, Republic of Korea; 6Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju, Republic of Korea Purpose: To define the prevalence of distorted body image in 10–24-year-old Koreans and determine its relationship with sex, age, body weight status, and disordered eating behaviors.Methods: A total of 3,227 young Koreans were recruited from elementary, middle, and high schools, as well as from universities. The participants completed a self-reported questionnaire on body image, eating behaviors (Eating Attitude Test-26), and body weight status.Results: The prevalence of a distorted body image in males was 49.7% and that in females was 51.2%. Distorted body image was more frequent in adolescents (age, 10–17 years) than in young adults (age, 18–24 years). The highest prevalence (55.3%) was reported in female elementary school students (age, 10–12 years). Distorted body image was associated with disordered eating behaviors and abnormal body weight status.Conclusion: These results suggest that distorted body image is a public health problem, given its high frequency in young Koreans, and that it is associated with abnormal body weight status and disordered eating behaviors. Keywords: distorted body image, weight status, disordered eating behaviors, young Koreans, Eating Attitude Test, BMI

Changes to mammography practice, including revised Breast Imaging Reporting and Data System (BI-RADS) density classification guidelines and implementation of digital breast tomosynthesis (DBT), may impact clinical breast density assessment. We investigated temporal trends in clinical breast density assessment among 2 990 291 digital mammography (DM) screens and 221 063 DBT screens interpreted by 722 radiologists from 144 facilities in the Breast Cancer Surveillance Consortium. After age-standardization, 46.3% (95% CI = 44.1% to 48.6%) of DM screens were assessed as dense (heterogeneously/extremely dense) during the BI-RADS 4th edition era (2005-2013), compared to 46.5% (95% CI = 43.8% to 49.1%) during the 5th edition era (2014-2016) (P = .93 from two-sided generalized score test). Among DBT screens in the BI-RADS 5th edition era, 45.8% (95% CI = 42.0% to 49.7%) were assessed as dense (P = .77 from two-sided generalized score test) compared to 46.5% (95% CI = 43.8% to 49.1%) dense on DM in BI-RADS 5th edition era. Results were similar when examining all four density categories and age subgroups. Clinicians, researchers, and policymakers may reasonably expect stable density distributions across screened populations despite changes to the BI-RADS guidelines and implementation of DBT.

Rationale: In atherosclerotic lesions, synthetic smooth muscle cells (sSMCs) induce aberrant microRNA (miR) profiles in endothelial cells (ECs) under flow stagnation. Increase in shear stress induces favorable miR modulation to mitigate sSMC-induced inflammation. Objective: To address the role of miRs in sSMC-induced EC inflammation and its inhibition by shear stress. Methods and Results: Coculturing ECs with sSMCs under static condition causes initial increases of 4 anti-inflammatory miRs (146a/708/451/98) in ECs followed by decreases below basal levels at 7 days; the increases for miR-146a/708 peaked at 24 hours and those for miR-451/98 lasted for only 6 to 12 hours. Shear stress (12 dynes/cm2) to cocultured ECs for 24 hours augments these 4 miR expressions. In vivo, these 4 miRs are highly expressed in neointimal ECs in injured arteries under physiological levels of flow, but not expressed under flow stagnation. MiR-146a, miR-708, miR-451, and miR-98 target interleukin-1 receptor-associated kinase, inhibitor of nuclear factor-κB kinase subunit-γ, interleukin-6 receptor, and conserved helix-loop-helix ubiquitous kinase, respectively, to inhibit nuclear factor-κB signaling, which exerts negative feedback control on the biogenesis of these miRs. Nuclear factor-E2-related factor (Nrf)-2 is critical for shear-induction of miR-146a in cocultured ECs. Silencing either Nrf-2 or miR-146a led to increased neointima formation of injured rat carotid artery under physiological levels of flow. Overexpressing miR-146a inhibits neointima formation of rat or mouse carotid artery induced by injury or flow cessation. Conclusions: Nrf-2-mediated miR-146a expression is augmented by atheroprotective shear stress in ECs adjacent to sSMCs to inhibit neointima formation of injured arteries.

Alternative strategies to increase access to reproductive health services among internally displaced populations are urgently needed. In eastern Burma, continuing conflict and lack of functioning health systems render the emphasis on facility-based delivery with skilled attendants unfeasible. Along the Thailand-Burma border, local organisations have implemented an innovative pilot, the Mobile Obstetric Maternal Health Workers (MOM) Project, establishing a three-tiered collaborative network of community-based reproductive health workers. Health workers from local organisations received practical training in basic emergency obstetric care plus blood transfusion, antenatal care and family planning at a central facility. After returning to their target communities inside Burma, these first-tier maternal health workers trained a second tier of local health workers and a third tier of traditional birth attendants (TBAs) to provide a limited subset of these interventions, depending on their level of training. In this ongoing project, close communication between health workers and TBAs promotes acceptance and coverage of maternity services throughout the community. We describe the rationale, design and implementation of the project and a parallel monitoring plan for evaluation of the project. This innovative obstetric health care delivery strategy may serve as a model for the delivery of other essential health services in this population and for increasing access to care in other conflict settings. [ABSTRACT FROM AUTHOR]

We provide a scheme for inferring causal relations from uncontrolled statistical data based on tools from computational algebraic geometry, in particular, the computation of Groebner bases. We focus on causal structures containing just two observed variables, each of which is binary. We consider the consequences of imposing different restrictions on the number and cardinality of latent variables and of assuming different functional dependences of the observed variables on the latent ones (in particular, the noise need not be additive). We provide an inductive scheme for classifying functional causal structures into distinct observational equivalence classes. For each observational equivalence class, we provide a procedure for deriving constraints on the joint distribution that are necessary and sufficient conditions for it to arise from a model in that class. We also demonstrate how this sort of approach provides a means of determining which causal parameters are identifiable and how to solve for these. Prospects for expanding the scope of our scheme, in particular to the problem of quantum causal inference, are also discussed.

Abstract Background The majority of retirement village residents are at risk of medication misadventure. In a recent survey of retirement village residents in Victoria, two-thirds had at least one medication-related risk factor, and hence were eligible to receive a government-subsidised Home Medicines Review (HMR). However, only 6% of eligible residents had received a HMR in the previous 12 months. Reasons for the poor uptake of HMR, and interventions for improving HMR uptake, have been identified and developed with input from stakeholders. The trial will test the effect of Pharmacist-conducted HMR to Address the Risk of Medication-related Events in Retirement Villages (PHARMER) in improving the uptake of HMRs among retirement village residents. Methods/Design This is a multicentre prospective cluster randomised controlled trial. Ten retirement villages in Victoria, Australia will be recruited for this trial. Retirement villages will be selected in consultation with the Residents of Retirement Villages Victoria Inc. (RRVV), based on geographical locations (e.g. northeast or southwest), size and other factors. Residents from selected villages will be recruited with the help of RRVV Resident Liaison Officers using a range of strategies. Randomisation will be by geographical location to minimise contamination. Participating villages and residents will be allocated to either Pharmacist Intervention Group (PIG) or Usual Care Group (UCG). Each group will include five retirement villages and will have at least 77 residents in total. The intervention (PHARMER) comprises educating residents regarding HMR, and using a risk assessment checklist by residents to notify their General Practitioners of their medication risk. Uptake of HMR and medication adherence will be assessed in both PIG and UCG at three and six months using telephone interviews and questionnaires. Discussion This study is the first to develop and test an intervention to improve the uptake of HMR among Australian residents in retirement villages, with a view to decreasing medication risk. A multi-faceted interventional approach will be used as suggested by stakeholders. The trial is expected to be complete by late 2011 and results will be available in 2012. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN12611000109909)

In settings where active conflict, resource scarcity, and logistical constraints prevail, provision of maternal health services within health centers and hospitals is unfeasible and alternative community-based strategies are needed. In eastern Burma, such conditions necessitated implementation of the 'Mobile Obstetric Maternal Health Worker' (MOM) project, which has employed a community-based approach to increase access to essential maternal health services including emergency obstetric care. Lay Maternal Health Workers (MHWs) are central to the MOM service delivery model and, because they are accessible to both the communities inside Burma and to outside project managers, they serve as key informants for the project. Their insights can facilitate program and policy efforts to overcome critical delays and insufficient management of maternal complications linked to maternal mortality. Focus group discussions (n=9), in-depth interviews (n=18), and detailed case studies (n=14) were collected from MHWs during centralized project management meetings in February and October of 2007. Five case studies are presented to characterize and interpret the realities of reproductive health work in a conflict-affected setting. Findings highlight the process of building supportive networks and staff ownership of the MOM project, accessing and gaining community trust and participation to achieve timely delivery of care, and overcoming challenges to manage and appropriately deliver essential health services. They suggest that some emergency obstetric care services that are conventionally delivered only within healthcare settings might be feasible in community or home-based settings when alternatives are not available. This paper provides an opportunity to hear directly from community-based workers in a conflict setting, perspectives seldom documented in the scientific literature. A rights-based approach to service delivery and its suitability in settings where human rights violations are widespread is highlighted. [ABSTRACT FROM AUTHOR]

The extent and determinants of supplemental screening among women with dense breasts are unclear. We evaluated a retrospective cohort of 498,855 women aged 40-74 years with heterogeneously or extremely dense breasts who obtained 1,176,251 negative screening mammography examinations during 2011-2019 in the United States. Overall, 2.8% and 0.3% of mammograms had supplemental ultrasound or MRI within one year, respectively. Onsite availability was associated with ultrasound (odds ratio [OR]=4.35; 95%CI : 4.21-4.49) but not MRI (OR = 0.94; 95%CI : 0.85-1.04). Facility academic affiliation and for-profit status were inversely associated with supplemental ultrasound (OR = 0.53; 95%CI : 0.49-0.57 and OR = 0.83; 95%CI : 0.81-0.86, respectively) and positively associated with supplemental MRI (OR = 3.04; 95%CI : 2.86-3.46 and OR = 1.88; 95%CI : 1.66-2.12, respectively). Supplemental screening was more likely to occur after passage of state-specific density notification laws than before passage (OR = 3.56; 95%CI 3.30-3.84 and OR = 1.79; 95%CI 1.60-2.00, respectively). These results show that supplemental breast imaging utilization has been uncommon and was related to facility factors and density legislation., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Early breast cancer detection is associated with lower morbidity and mortality., Objective: To examine whether a commercial artificial intelligence (AI) algorithm for breast cancer detection could estimate the development of future cancer., Design, Setting, and Participants: This retrospective cohort study of 116 495 women aged 50 to 69 years with no prior history of breast cancer before they underwent at least 3 consecutive biennial screening examinations used scores from an AI algorithm (INSIGHT MMG, version 1.1.7.2; Lunit Inc; used September 28, 2022, to April 5, 2023) for breast cancer detection and screening data from multiple, consecutive rounds of mammography performed from September 13, 2004, to December 21, 2018, at 9 breast centers in Norway. The statistical analyses were performed from September 2023 to August 2024., Exposure: Artificial intelligence algorithm score indicating suspicion for the presence of breast cancer. The algorithm provided a continuous cancer detection score for each examination ranging from 0 to 100, with increasing values indicating a higher likelihood of cancer being present on the current mammogram., Main Outcomes and Measures: Maximum AI algorithm score for cancer detection and absolute difference in score among breasts of women developing screening-detected cancer, women with interval cancer, and women who screened negative., Results: The mean (SD) age at the first study round was 58.5 (4.5) years for 1265 women with screening-detected cancer in the third round, 57.4 (4.6) years for 342 women with interval cancer after 3 negative screening rounds, and 56.4 (4.9) years for 116 495 women without breast cancer all 3 screening rounds. The mean (SD) absolute differences in AI scores among breasts of women developing screening-detected cancer were 21.3 (28.1) at the first study round, 30.7 (32.5) at the second study round, and 79.0 (28.9) at the third study round. The mean (SD) differences prior to interval cancer were 19.7 (27.0) at the first study round, 21.0 (27.7) at the second study round, and 34.0 (33.6) at the third study round. The mean (SD) differences among women who did not develop breast cancer were 9.9 (17.5) at the first study round, 9.6 (17.4) at the second study round, and 9.3 (17.3) at the third study round. Areas under the receiver operating characteristic curve for the absolute difference were 0.63 (95% CI, 0.61-0.65) at the first study round, 0.72 (95% CI, 0.71-0.74) at the second study round, and 0.96 (95% CI, 0.95-0.96) at the third study round for screening-detected cancer and 0.64 (95% CI, 0.61-0.67) at the first study round, 0.65 (95% CI, 0.62-0.68) at the second study round, and 0.77 (95% CI, 0.74-0.79) at the third study round for interval cancers., Conclusions and Relevance: In this retrospective cohort study of women undergoing screening mammography, mean absolute AI scores were higher for breasts developing vs not developing cancer 4 to 6 years before their eventual detection. These findings suggest that commercial AI algorithms developed for breast cancer detection may identify women at high risk of a future breast cancer, offering a pathway for personalized screening approaches that can lead to earlier cancer diagnosis.

Background: False-positive results on screening mammography may affect women's willingness to return for future screening., Objective: To evaluate the association between screening mammography results and the probability of subsequent screening., Design: Cohort study., Setting: 177 facilities participating in the Breast Cancer Surveillance Consortium (BCSC)., Patients: 3 529 825 screening mammograms (3 184 482 true negatives and 345 343 false positives) performed from 2005 to 2017 among 1 053 672 women aged 40 to 73 years without a breast cancer diagnosis., Measurements: Mammography results (true-negative result or false-positive recall with a recommendation for immediate additional imaging only, short-interval follow-up, or biopsy) from 1 or 2 screening mammograms. Absolute differences in the probability of returning for screening within 9 to 30 months of false-positive versus true-negative screening results were estimated, adjusting for race, ethnicity, age, time since last mammogram, BCSC registry, and clustering within women and facilities., Results: Women were more likely to return after a true-negative result (76.9% [95% CI, 75.1% to 78.6%]) than after a false-positive recall for additional imaging only (adjusted absolute difference, -1.9 percentage points [CI, -3.1 to -0.7 percentage points]), short-interval follow-up (-15.9 percentage points [CI, -19.7 to -12.0 percentage points]), or biopsy (-10.0 percentage points [CI, -14.2 to -5.9 percentage points]). Asian and Hispanic/Latinx women had the largest decreases in the probability of returning after a false positive with a recommendation for short-interval follow-up (-20 to -25 percentage points) or biopsy (-13 to -14 percentage points) versus a true negative. Among women with 2 screening mammograms within 5 years, a false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result., Limitation: Women could receive care at non-BCSC facilities., Conclusion: Women were less likely to return to screening after false-positive mammography results, especially with recommendations for short-interval follow-up or biopsy, raising concerns about continued participation in routine screening among these women at increased breast cancer risk., Primary Funding Source: National Cancer Institute., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0123.

Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts., Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density., Design, Setting, and Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data. Simulated women born in 1980 with average breast cancer risk were included. Modeling analyses were conducted from January 2020 to December 2023., Intervention: Annual or biennial mammography screening with or without supplemental MRI by breast density starting at ages 40, 45, or 50 years through age 74 years., Main Outcomes and Measures: Lifetime breast cancer deaths averted, false-positive recall and false-positive biopsy recommendations per 1000 simulated women followed-up from age 40 years to death summarized as means and ranges across models., Results: Biennial DBT screening for all simulated women started at age 50 vs 40 years averted 7.4 vs 8.5 breast cancer deaths, respectively, and led to 884 vs 1392 false-positive recalls and 151 vs 221 false-positive biopsy recommendations, respectively. Biennial digital mammography had similar deaths averted and slightly more false-positive test results than DBT screening. Adding MRI for women with extremely dense breasts to biennial DBT screening for women aged 50 to 74 years increased deaths averted (7.6 vs 7.4), false-positive recalls (919 vs 884), and false-positive biopsy recommendations (180 vs 151). Extending supplemental MRI to women with heterogeneously or extremely dense breasts further increased deaths averted (8.0 vs 7.4), false-positive recalls (1088 vs 884), and false-positive biopsy recommendations (343 vs 151). The same strategy for women aged 40 to 74 years averted 9.5 deaths but led to 1850 false-positive recalls and 628 false-positive biopsy recommendations. Annual screening modestly increased estimated deaths averted but markedly increased estimated false-positive results., Conclusions and Relevance: In this model-based comparative effectiveness analysis, supplemental MRI for women with dense breasts added to DBT screening led to greater benefits and increased harms. The balance of this trade-off for supplemental MRI use was more favorable when MRI was targeted to women with extremely dense breasts who comprise approximately 10% of the population.

With promising artificial intelligence (AI) algorithms receiving FDA clearance, the potential impact of these models on clinical outcomes must be evaluated locally before their integration into routine workflows. Robust validation infrastructures are pivotal to inspecting the accuracy and generalizability of these deep learning algorithms to ensure both patient safety and health equity. Protected health information concerns, intellectual property rights, and diverse requirements of models impede the development of rigorous external validation infrastructures. The authors propose various suggestions for addressing the challenges associated with the development of efficient, customizable, and cost-effective infrastructures for the external validation of AI models at large medical centers and institutions. The authors present comprehensive steps to establish an AI inferencing infrastructure outside clinical systems to examine the local performance of AI algorithms before health practice or systemwide implementation and promote an evidence-based approach for adopting AI models that can enhance radiology workflows and improve patient outcomes., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the ability of artificial intelligence (AI) to classify breast cancer by mammographic density in an organized screening program., Materials and Method: We included information about 99,489 examinations from 74,941 women who participated in BreastScreen Norway, 2013-2019. All examinations were analyzed with an AI system that assigned a malignancy risk score (AI score) from 1 (lowest) to 10 (highest) for each examination. Mammographic density was classified into Volpara density grade (VDG), VDG1-4; VDG1 indicated fatty and VDG4 extremely dense breasts. Screen-detected and interval cancers with an AI score of 1-10 were stratified by VDG., Results: We found 10,406 (10.5% of the total) examinations to have an AI risk score of 10, of which 6.7% (704/10,406) was breast cancer. The cancers represented 89.7% (617/688) of the screen-detected and 44.6% (87/195) of the interval cancers. 20.3% (20,178/99,489) of the examinations were classified as VDG1 and 6.1% (6047/99,489) as VDG4. For screen-detected cancers, 84.0% (68/81, 95% CI, 74.1-91.2) had an AI score of 10 for VDG1, 88.9% (328/369, 95% CI, 85.2-91.9) for VDG2, 92.5% (185/200, 95% CI, 87.9-95.7) for VDG3, and 94.7% (36/38, 95% CI, 82.3-99.4) for VDG4. For interval cancers, the percentages with an AI score of 10 were 33.3% (3/9, 95% CI, 7.5-70.1) for VDG1 and 48.0% (12/25, 95% CI, 27.8-68.7) for VDG4., Conclusion: The tested AI system performed well according to cancer detection across all density categories, especially for extremely dense breasts. The highest proportion of screen-detected cancers with an AI score of 10 was observed for women classified as VDG4., Clinical Relevance Statement: Our study demonstrates that AI can correctly classify the majority of screen-detected and about half of the interval breast cancers, regardless of breast density., Key Points: • Mammographic density is important to consider in the evaluation of artificial intelligence in mammographic screening. • Given a threshold representing about 10% of those with the highest malignancy risk score by an AI system, we found an increasing percentage of cancers with increasing mammographic density. • Artificial intelligence risk score and mammographic density combined may help triage examinations to reduce workload for radiologists., (© 2024. The Author(s).)

Female infertility affects a significant portion of the population, and recent studies suggest a potential link between glycemic control and reproductive health. This study investigates the association between serum glycated hemoglobin (HbA1c) levels and female infertility, utilizing data from the NHANES 2017-2020 and Mendelian randomization (MR) analysis. A cross-sectional study was conducted with 1578 women aged 20-45 who attempted pregnancy for at least one year. Serum HbA1c levels were analyzed in relation to infertility status, with multivariable logistic regression models adjusting for covariates such as age, body mass index, race/ethnicity, education, marital status, hypertension, and hyperlipidemia. Higher HbA1c levels were significantly associated with increased infertility risk. Each 1% increase in HbA1c was linked to higher odds of infertility (adjusted OR: 1.40, 95% CI: 1.15-1.69, p = 0.003). HbA1c levels ≥ 6.5% showed the strongest association. MR analysis employed single-nucleotide polymorphisms as instrumental variables to assess the causal relationship between HbA1c and infertility, confirming a causal relationship between higher genetically predicted HbA1c levels and infertility (OR: 1.82, 95% CI: 1.33-2.49, p = 0.00018). Sensitivity analyses supported the robustness of these findings. Elevated HbA1c levels are associated with an increased risk of female infertility, suggesting the importance of glycemic control in reproductive health management.

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The placenta experiences a low-oxygen stage during early pregnancy. Aspirin is an effective preventative treatment for preeclampsia if applied early in pregnancy. Elevation of fibronectin (FN) level has been reported to be associated with preeclampsia; however, the role of FN in the physiological hypoxic phase and whether aspirin exerts its effect on FN at this hypoxic stage remain unknown. We determined pregnancy outcomes by injecting saline or recombinant FN protein into C57BL/6 pregnant mice and one group of FN-injected mice was fed aspirin. The effects of FN, the underlying pathways on trophoblast biology, and cilia formation under hypoxia were investigated in FN-pretreated or FN-knockdown HTR-8/SVneo cells in a hypoxic chamber (0.1 % O 2 ). Preeclampsia-like phenotypes, including blood pressure elevation and proteinuria, developed in FN-injected pregnant mice. The fetal weight of FN-injected mice was significantly lower than that of non-FN-injected mice (p < 0.005). Trophoblast FN expression was upregulated under hypoxia, which could be suppressed by aspirin treatment. FN inhibited trophoblast invasion and migration under hypoxia, and this inhibitory effect occurred through downregulating ZEB1/2, MMP 9 and the Akt and MAPK signaling pathways. Ciliogenesis of trophoblasts was stimulated under hypoxia but was inhibited by FN treatment. Aspirin was shown to reverse the FN-mediated inhibitory effect on trophoblast invasion/migration and ciliogenesis. In conclusion, FN overexpression induces preeclampsia-like symptoms and impairs fetal growth in mice. Aspirin may exert its suppressive effect on FN upregulation and FN-mediated cell function in the hypoxic stage of pregnancy and therefore provides a preventative effect on preeclampsia development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Thoracic endovascular aortic repair (TEVAR) is a treatment for traumatic blunt thoracic aortic injury (BTAI) with good survival rates and safety. However, there is limited study on the risk factors for in-hospital mortality and complications. This study aimed to identify risk factors associated with poor in-hospital outcomes after TEVAR., Materials and Methods: This is a population-based, retrospective observational study. Data of adults ≥20 years admitted for BTAI who received TEVAR were extracted from the Nationwide Inpatient Sample (NIS) database 2005 to 2018. The primary outcome was in-hospital mortality, and the secondary outcomes were length of stay (LOS) and unfavorable discharge (ie, non-routine discharge, including nursing homes or long-term care facilities). Associations between study variables and in-hospital outcomes were determined using univariate and multivariable logistic and linear regression analyses., Results: Data of 1095 participants (representing 5360 hospitalized patients in the United States) were analyzed. Multivariable analysis revealed that older age (adjusted odds ratio [aOR]=1.02) and having at least 1 perioperative complication (aOR=4.01) were significantly associated with increased risk for in-hospital mortality. Patients with at least 1 perioperative complication (aOR=11.19) had significantly increased odds for prolonged LOS. Risk for unfavorable discharge was significantly increased by older age (aOR=1.02), household income at quartile 2 (aOR=1.58), Charlson Comorbidity Index (CCI) 2 to 3 (aOR=1.66), and having at least 1 complication (aOR=3.94). Complications including perioperative cerebrovascular accident (CVA) (aOR=2.75), venous thromboembolism (VTE) (aOR=2.87), pneumonia (aOR=3.93), sepsis (aOR=4.69), infection (aOR=4.49), respiratory failure (aOR=4.55), mechanical ventilation (aOR=3.27), and acute kidney injury (AKI) (aOR=3.09) significantly predicted prolonged LOS., Conclusions: In adults with traumatic BTAI undergoing TEVAR, advanced age and perioperative complications are risk factors for poor in-hospital outcomes. Acute kidney injury, CVA, respiratory failure, and sepsis are strong predictors of prolonged LOS, unfavorable discharge, and in-hospital mortality., Clinical Impact: The study identifies advanced age and perioperative complications as key risk factors for poor in-hospital outcomes in patients undergoing TEVAR for BTAI. Clinicians should be vigilant in managing these patients, particularly those with comorbidities, to mitigate risks. The findings suggest a need for tailored perioperative care strategies to improve survival rates and reduce complications. This research highlights the critical importance of early identification and intervention in high-risk patients, offering an innovative approach to refining TEVAR protocols and enhancing patient outcomes in trauma care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Blastocyst vitrification has significantly improved embryo transfer methods, leading to higher implantation success rates and better pregnancy outcomes in subsequent frozen embryo transfer cycles. This study aimed to simulate the transcriptional changes caused by vitrifying human blastocysts using mouse blastocysts as a model and to further investigate these changes' effects. Utilizing a human vitrification protocol, we implanted both vitrified and fresh embryos into mice. We observed the implantation success rates and performed transcriptomic analysis on the blastocysts. To validate the results from messenger RNA sequencing, we conducted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to measure the expression levels of specific genes. Based on mRNA profiling, we predicted the microRNAs responsible for the regulation and used qPCR basic microRNA assays for validation. Our observations revealed a higher implantation success rate for vitrified embryos than fresh embryos. Transcriptomic analysis showed that vitrified-warmed blastocysts exhibited differentially expressed genes (DEGs) primarily associated with thermogenesis, chemical carcinogenesis-reactive oxygen species, oxidative phosphorylation, immune response, and MAPK-related signaling pathways. RT-qPCR confirmed increased expression of genes such as Cdk6 and Nfat2 , and decreased expression of genes such as Dkk3 and Mapk10 . Additionally, gene-microRNA interaction predictions and microRNA expression analysis identified twelve microRNAs with expression patterns consistent with the predicted results, suggesting potential roles in uterine epithelial cell adhesion, trophectoderm development, invasive capacity, and immune responses. Our findings suggest that vitrification induces transcriptomic changes in mouse blastocysts, and even small changes in gene expression can enhance implantation success. These results highlight the importance of understanding the molecular mechanisms underlying vitrification to optimize embryo transfer techniques and improve pregnancy outcomes.

Background: For in vitro fertilization (IVF), mitochondrial DNA (mtDNA) levels in the trophectodermal (TE) cells of biopsied blastocysts have been suggested to be associated with the cells' developmental potential. However, scholars have reached differing opinions regarding the use of mtDNA levels as a reliable biomarker for predicting IVF outcomes. Therefore, this study aims to assess the association of mitochondrial copy number measured by mitoscore associated with embryonic developmental characteristics and ploidy., Methods: This retrospective study analyzed the developmental characteristics of embryos and mtDNA levels in biopsied trophectodermal cells. The analysis was carried out using time-lapse monitoring and next-generation sequencing from September 2021 to September 2022. Five hundred and fifteen blastocysts were biopsied from 88 patients undergoing IVF who met the inclusion criteria. Embryonic morphokinetics and morphology were evaluated at 118 h after insemination using all recorded images. Blastocysts with appropriate morphology on day 5 or 6 underwent TE biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Statistical analysis involved generalized estimating equations, Pearson's chi-squared test, Fisher's exact test, and Kruskal-Wallis test, with a significance level set at P < 0.05., Results: To examine differences in embryonic characteristics between blastocysts with low versus high mitoscores, the blastocysts were divided into quartiles based on their mitoscore. Regarding morphokinetic characteristics, no significant differences in most developmental kinetics and observed cleavage dysmorphisms were discovered. However, blastocysts in mitoscore group 1 had a longer time for reaching 3-cell stage after tPNf (t3; median: 14.4 h) than did those in mitoscore group 2 (median: 13.8 h) and a longer second cell cycle (CC2; median: 11.7 h) than did blastocysts in mitoscore groups 2 (median: 11.3 h) and 4 (median: 11.4 h; P < 0.05). Moreover, blastocysts in mitoscore group 4 had a lower euploid rate (22.6%) and a higher aneuploid rate (59.1%) than did those in the other mitoscore groups (39.6-49.3% and 30.3-43.2%; P < 0.05). The rate of whole-chromosomal alterations in mitoscore group 4 (63.4%) was higher than that in mitoscore groups 1 (47.3%) and 2 (40.1%; P < 0.05). A multivariate logistic regression model was used to analyze associations between the mitoscore and euploidy of elective blastocysts. After accounting for factors that could potentially affect the outcome, the mitoscore still exhibited a negative association with the likelihood of euploidy (adjusted OR = 0.581, 95% CI: 0.396-0.854; P = 0.006)., Conclusions: Blastocysts with varying levels of mitochondrial DNA, identified through biopsies, displayed similar characteristics in their early preimplantation development as observed through time-lapse imaging. However, the mitochondrial DNA level determined by the mitoscore can be used as a standalone predictor of euploidy., (© 2024. The Author(s).)

Objective: Mammography and MRI screening typically occur in combination or in alternating sequence. We compared multimodality screening performance accounting for the relative timing of mammography and MRI and overlapping follow-up periods., Methods: We identified 8,260 screening mammograms performed 2005 to 2017 in the Breast Cancer Surveillance Consortium, paired with screening MRIs within ±90 days (combined screening) or 91 to 270 days (alternating screening). Performance for combined screening (cancer detection rate [CDR] per 1,000 examinations and sensitivity) was calculated with 1-year follow-up for each modality, and with a single follow-up period treating the two tests as a single test. Alternating screening performance was calculated with 1-year follow-up for each modality and also with follow-up ending at the next screen if within 1 year (truncated follow-up)., Results: For 3,810 combined screening pairs, CDR per 1,000 screens was 6.8 (95% confidence interval [CI]: 4.6-10.0) for mammography and 12.3 (95% CI: 9.3-16.4) for MRI as separate tests compared with 13.1 (95% CI: 10.0-17.3) as a single combined test. Sensitivity of each test was 48.1% (35.0%-61.5%) for mammography and 79.7% (95% CI: 67.7%-88.0%) for MRI compared with 96.2% (95% CI: 85.9%-99.0%) for combined screening. For 4,450 alternating screening pairs, mammography CDR per 1,000 screens changed from 3.6 (95% CI: 2.2-5.9) to zero with truncated follow-up; sensitivity was incalculable (denominator = 0). MRI CDR per 1,000 screens changed from 12.1 (95% CI 9.3-15.8) to 11.7 (95% CI: 8.9-15.3) with truncated follow-up; sensitivity changed from 75.0% (95% CI 63.8%-83.6%) to 86.7% (95% CI 75.5%-93.2%)., Discussion: Updating auditing approaches to account for combined and alternating screening sequencing and to address outcome attribution issues arising from overlapping follow-up periods can improve the accuracy of multimodality screening performance evaluation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: To study the effectiveness of federated learning in in vitro fertilization on embryo evaluation tasks., Methods: This is a retrospective cohort analysis. Two datasets were used in this study. The ploidy status dataset consisted of 10,065 embryo records, 3760 treatments, and 2479 infertile couples from 5 hospitals. The clinical pregnancy dataset consisted of 4495 embryo records, 4495 treatments, and 3704 infertile couples from 4 hospitals. Federated learning and the gradient boosting decision tree algorithm were utilized for modeling., Results: On the ploidy status dataset, the areas under the receiver operating characteristic curves of our model trained with federated learning were 71.78%, 73.10%, 69.39%, 69.72%, and 73.46% for 5 hospitals respectively, showing an average increase of 2.5% compared to those of our model trained without federated learning. On the clinical pregnancy dataset, the areas under the receiver operating characteristic curves of our model trained with federated learning were 72.03%, 56.77%, 61.63%, and 58.58% for 4 hospitals respectively, showing an average increase of 3.08%., Conclusions: Federated learning can improve data privacy and data security and meanwhile improve the performance of embryo selection tasks by leveraging data from multiple sources. This study demonstrates the effectiveness of federated learning in embryo evaluation, and the results show the promise for future application., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The influences of oceanographic changes on diet composition and trophic level for pollock (Gadus chalcogrammus) inhabiting the East Sea off the Korean coast were examined based on stomach content and stable isotope analyses during 2016 and 2017. The diets of pollock consisted mainly of benthic crustaceans (particularly carid shrimps and euphausiids) and cephalopods, with a predominance of teleosts in the diets of larger individuals in deeper habitats. In 2016, amphipods, carid shrimps and cephalopods featured strongly in pollock diets, and the contribution of amphipods decreased in the diets of larger individuals and deeper depths. In 2017, euphausiids dominated at shallower depths, whereas the contributions of carid shrimps and teleosts increased in deeper habitats. Body-size-related differences in carbon stable isotope (δ 13 C) values were present in both 2016 and 2017, but size-related differences in nitrogen stable isotope (δ 15 N) values were only observed in 2017. The increased contribution of euphausiids during 2017 resulted in a distinct decrease in the trophic level of pollock compared to co-occurring higher trophic level predators, which can be linked to changes in habitat water temperature. Combined stomach contents and isotopic analyses provide a more comprehensive understanding of how fish diets and trophic levels fluctuate with changes in the type and abundance of prey resources in response to environmental changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study assessed variations in demersal fish assemblages with respect to the study site and water depth. Seasonal samplings from May 2018 to March 2019 were conducted along the northern (Ayajin, Goseong) and southern (Hupo, Uljin) sites of the East Sea off the Korean coast, using commercial gill nets. Samples were collected at depths of ~50, ~80, ~150 m across the study sites, with concurrent monitoring of water column structures. A total of 73 species and 6250 specimens were collected. Distinctive fish species compositions were observed according to the study site and depth. Although Glyptocephalus stelleri was the most abundant fish species in both Ayajin and Hupo, Gadus macrocephalus , Icelus cataphractus , and Alcichthys elongatus were most predominant in Ayajin, whereas Cleisthenes pinetorum , Hippoglossoides dubius , and Gymnocanthus herzensteini were more prevalent in Hupo. In terms of depth layer, in Ayajin, G. stelleri dominated in both intermediate and deeper layers, with Hemilepidotus gilberti , A. elongatus , Enophrys diceraus common in shallower depths. Conversely, in Hupo, G. stelleri , C. pinetorum , and A. nadeshnyi dominated across all depth layers, whereas Dasycottus setiger and G. herzensteini dominated in deeper and shallower depths, respectively. Significant influences of the study site and water depth on fish assemblage structures were observed due to variations in water temperature at the seasonal thermocline boundary.

Objectives : To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods : This prospective case-control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results : After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions : Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM.

Purpose To explore the stand-alone breast cancer detection performance, at different risk score thresholds, of a commercially available artificial intelligence (AI) system. Materials and Methods This retrospective study included information from 661 695 digital mammographic examinations performed among 242 629 female individuals screened as a part of BreastScreen Norway, 2004-2018. The study sample included 3807 screen-detected cancers and 1110 interval breast cancers. A continuous examination-level risk score by the AI system was used to measure performance as the area under the receiver operating characteristic curve (AUC) with 95% CIs and cancer detection at different AI risk score thresholds. Results The AUC of the AI system was 0.93 (95% CI: 0.92, 0.93) for screen-detected cancers and interval breast cancers combined and 0.97 (95% CI: 0.97, 0.97) for screen-detected cancers. In a setting where 10% of the examinations with the highest AI risk scores were defined as positive and 90% with the lowest scores as negative, 92.0% (3502 of 3807) of the screen-detected cancers and 44.6% (495 of 1110) of the interval breast cancers were identified with AI. In this scenario, 68.5% (10 987 of 16 040) of false-positive screening results (negative recall assessment) were considered negative by AI. When 50% was used as the cutoff, 99.3% (3781 of 3807) of the screen-detected cancers and 85.2% (946 of 1110) of the interval breast cancers were identified as positive by AI, whereas 17.0% (2725 of 16 040) of the false-positive results were considered negative. Conclusion The AI system showed high performance in detecting breast cancers within 2 years of screening mammography and a potential for use to triage low-risk mammograms to reduce radiologist workload. Keywords: Mammography, Breast, Screening, Convolutional Neural Network (CNN), Deep Learning Algorithms Supplemental material is available for this article . © RSNA, 2024 See also commentary by Bahl and Do in this issue.

Candida species are escalating resistance to conventional antifungal treatments, intensifying their virulence, and obstructing the effectiveness of antifungal medications. Addressing this challenge is essential for effectively managing Candida infections. The overarching objective is to advance the development of more efficient and precise therapies tailored to counter Candida infections. This study focuses on developing antifungal combined drugs using curcumin-enhanced silver-functionalized graphene nanocomposites (Cur-AgrGO) to effectively target key virulence factors of C. albicans, C. tropicalis, and C. glabrata (Candida spp.). The green reduction of graphene oxide (GO) using bioentities and active molecules makes this approach cost-effective and environmentally friendly. The nanocomposites were characterized using various techniques. Combining Cur-AgrGO with photodynamic therapy (PDT) demonstrated effective antifungal and antibiofilm activity with delayed growth and metabolism. The nanocomposites effectively suppressed hyphal transition and reduced key virulence factors, including proteinases, phospholipases, ergosterol levels, and cell membrane integrity. The findings suggest that Cur-AgrGO + PDT has potential as a treatment option for Candida infections. This innovative approach holds promise for treating Candida infections., (© 2024. The Author(s).)