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Xue-Qing Guan,1 Chuan-He Wang,1 Peng Cheng,1 Ling-Yu Fu,2 Qi-Jun Wu,3– 5 Gong Cheng,1 Lin Guan,1 Zhi-Jun Sun1 1Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China; 2Department of Clinical Epidemiology and Evidence-Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, 110021, People’s Republic of China; 3Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China; 4Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of China; 5Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, 110021, People’s Republic of ChinaCorrespondence: Zhi-Jun Sun, Department of Cardiology, Shengjing Hospital of China Medical University, No. 39 of Huaxiang Road, Tiexi District, Shenyang, 110021, People’s Republic of China, Tel +86 02496615, Email sunzhijunszj8@126.comAbstract: Although empagliflozin has been recommended for individuals with heart failure, its effects on heart failure with preserved ejection fraction (HFpEF) remain uncertain from a physiopathological standpoint. The metabolites produced by gut microbiota have been shown to have a crucial role in the development of heart failure. Sodium-glucose cotransporter-2 inhibitors (SGLT2) have been shown to change the make-up of the gut microbiota in rodent studies. There is mixed evidence from similar studies investigating whether or not SGLT2 can affect the microbiota in the human gut. This trial is a pragmatic, randomized, open-label controlled study with empagliflozin as an intervention. We will enroll 100 patients with HFpEF and randomly assign them to one of two groups to receive either empagliflozin or a placebo. Patients in the Empagliflozin group will be given 10 mg of the drug daily, while those in the Control group will not be given empagliflozin or any other SGLT2. The purpose of the trial is to validate the changes that occur in gut microbiota in patients with HFpEF who take empagliflozin and to investigate the function of gut microbiota and their metabolites in the process.Keywords: derived metabolite, gut microbiota, heart failure, HF, myocardial fibrosis, SGLT2, short-chain fatty acids, SCFAs, sodium-glucose cotransporter-2 inhibitor

Ming-Jun Shi,1,2 Xiang-Yu Meng,3,4 Qiu-Ji Wu,5 Xiong-Hui Zhou31Institut Curie, PSL Research University, CNRS, UMR 144, Paris F-75005, France; 2Department of Urology, Beijing Friendship Hospital, Capital Medical Univeristy , Beijing, 430071, People’s Republic of China; 3Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China; 4Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 5Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of ChinaBackground: Bladder cancer is a common malignancy that affects the human urinary tract. Muscle-invasive bladder cancer (MIBC) is aggressive and has poor prognosis. Previous studies have reported that the tumor-infiltrating lymphocytes (TILs) were associated with MIBC outcome; however, inconsistency remains and mRNA level TIL markers’ prognostic significance in MIBC is unclear. Materials and methods: In the present study, we reanalyzed data from four public datasets (the Cancer Genome Atlas for investigation; and CIT, GSE5287, and GSE31684 for validation) to examine the prognostic significance of CD3D, CD4, CD8A, CD3D/CD4 and CD3D/CD8A in MIBC. Results: We found that the CD3D/CD4 ratio was a stable independent prognostic factor in MIBC (beta = −0.87, P = 0.025); high CD3D/CD4 ratio predicted better survival in MIBC, and the power of this association was much stronger in basal-squamous tumors (beta = −4.73, P = 2.67E-06). We also noted that the CD4 expression was significantly higher than CD3D (P < 0.05), indicating the presence of CD3−,CD4+, cells which could be immune-suppressing.Conclusion: The CD3D/CD4 ratio can be viewed as a prognostic marker and a rough measurement for the interaction between immune-effecting CD3+, TILs and immune-suppressing CD3−,CD4+, cells in MIBC, and this interaction may play a particularly important role in anti-cancer immunity in basal-squamous tumors as it has a very strong association with survival in this subtype, and may be used to select potential responders to immunotherapy.Keywords: bladder cancer, muscle-invasive, tumor-infiltrating lymphocytes, CD3, CD4, CD8, prognosis, immunotherapy, basal-squamous subtype

Purpose: This clinical study evaluates the feasibility of using volumetric arc-modulated treatment (VMAT) for spine stereotactic body radiotherapy (SBRT) to achieve highly conformal dose distributions that spare adjacent organs at risk (OAR) with reduced treatment time. Methods and Materials: Ten spine SBRT patients were studied retrospectively. The intensity-modulated radiotherapy (IMRT) and VMAT plans were generated using either one or two arcs. Planning target volume (PTV) dose coverage, OAR dose sparing, and normal tissue integral dose were measured and compared. Differences in treatment delivery were also analyzed. Results: The PTV DVHs were comparable between VMAT and IMRT plans in the shoulder (D(99%)-D(90%)), slope (D(90%)-D(10%)), and tail (D(10%)-D(1%)) regions. Only VMAT(2arc) had a better conformity index than IMRT (1.09 vs. 1.15, p = 0.007). For cord sparing, IMRT was the best, and VMAT(1arc) was the worst. Use of IMRT achieved greater than 10% more D(1%) sparing for six of 10 cases and 7% to 15% more D(10%) sparing over the VAMT(1arc). The differences between IMRT and VAMT(2arc) were smaller and statistically nonsignificant at all dose levels. The differences were also small and statistically nonsignificant for other OAR sparing. The mean monitor units (MUs) were 8711, 7730, and 6317 for IMRT, VMAT(1arc), and VMAT(2arc) plans, respectively, with a 26% reduction from IMRT to VMAT(2arc). The mean treatment time was 15.86, 8.56, and 7.88 min for IMRT, VMAT(1arc,) and VMAT(2arc). The difference in integral dose was statistically nonsignificant. Conclusions: Although VMAT provided comparable PTV coverage for spine SBRT, 1arc showed significantly worse spinal cord sparing compared with IMRT, whereas 2arc was comparable to IMRT. Treatment efficiency is substantially improved with the VMAT. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the dosimetric impact of various treatment techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of tumors -- spine tumors, brain tumors abutting the brainstem, and liver tumors. These lesions often present challenges in maximizing dose to target volumes without exceeding critical organ tolerance. Specifically, this study evaluated the dosimetric benefits of various techniques and collimator leaf sizes as a function of lesion size and shape.Methods: Fifteen cases (5 for each site) were studied retrospectively. All lesions either abutted or were an integral part of critical structures (brainstem, liver or spinal cord). For brain and liver lesions, treatment plans using a 3D-conformal static technique (3D), dynamic conformal arcs (DARC) or intensity modulation (IMRT) were designed with a conventional linear accelerator with standard 5 mm leaf width multi-leaf collimator, and a linear accelerator dedicated for radiosurgery and hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave spine lesions, intensity modulation was required to provide adequate conformality; hence, only IMRT plans were evaluated using either the standard or small leaf-width collimators.A total of 70 treatment plans were generated and each plan was individually optimized according to the technique employed. The Generalized Estimating Equation (GEE) was used to separate the impact of treatment technique from the MLC system on plan outcome, and t-tests were performed to evaluate statistical differences in target coverage and organ sparing between plans.Results: The lesions ranged in size from 2.6 to 12.5 cc, 17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups, respectively. As a group, brain lesions were smaller than spine and liver lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions were more complex in shape, as they were all concave. Therefore, the brain and the liver groups were compared for volume effect, and the liver and spine groups were compared for shape. For the brain and liver groups, both the radiosurgery MLC and the IMRT technique contributed to the dose sparing of organs-at-risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%, compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also, the dose reduction contributed by the fine leaf-width MLC decreased, as dose savings at all levels diminished from 4 - 11% for the brain group to 1 - 5% for the liver group, as the target structures decreased in volume. The fine leaf-width collimator significantly improved spinal cord sparing, with dose reductions of 14 - 19% in high to middle dose regions, compared to the 5 mm leaf width collimator.Conclusion: The fine leaf-width MLC in combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from use of a fine leaf-width MLC and the use of IMRT. [ABSTRACT FROM AUTHOR]

Purpose: &#xD;To develop a deep reinforcement learning (DRL) agent to self-interact with the treatment planning system (TPS) to automatically generate intensity modulated radiation therapy (IMRT) treatment plans for head-and-neck (HN) cancer with consistent organ-at-risk (OAR) sparing performance.&#xD;Methods:&#xD;With IRB approval, one hundred and twenty HN patients receiving IMRT were included. The DRL agent was trained with 20 patients. During each inverse optimization process, the intermediate dosimetric endpoints' value, dose volume constraints value and structure objective function loss were collected as the DRL states. By adjusting the objective constraints as actions, the agent learned to seek optimal rewards by balancing OAR sparing and planning target volume (PTV) coverage. Reward computed from current dose-volume-histogram (DVH) endpoints and clinical objectives were sent back to the agent to update action policy during model training. The trained agent was evaluated with the rest 100 patients. &#xD;Results:&#xD;The DRL agent was able to generate a clinically acceptable IMRT plan within 12.4±3.1 minutes without human intervention. DRL plans showed lower PTV maximum dose (109.2%) compared to clinical plans (112.4%) (p<.05). Average median dose of left parotid, right parotid, oral cavity, larynx, pharynx of DRL plans were 15.6Gy, 12.2Gy, 25.7Gy, 27.3Gy and 32.1Gy respectively, comparable to 17.1 Gy,15.7Gy, 24.4Gy, 23.7Gy and 35.5Gy of corresponding clinical plans. The maximum dose of cord+5mm, brainstem and mandible were also comparable between the two groups. In addition, DRL plans demonstrated reduced variability, as evidenced by smaller 95% confidence intervals. The total MU of the DRL plans was 1611 vs 1870 (p<.05) of clinical plans. The results signaled the DRL's consistent planning strategy compared to the planners' occasional back-and-forth decision-making during planning.&#xD;Conclusion:&#xD;The proposed deep reinforcement learning (DRL) agent is capable of efficiently generating HN IMRT plans with consistent quality. &#xD., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Purpose: Although (poly)phenols have shown potential in anti-cancer activities, their impact on improving ovarian cancer (OC) survival remains unknown. Therefore, we aim to first investigate the association between dietary polyphenol intake and OC survival, providing valuable insights into potential interventions., Methods: The prospective cohort recruited 560 patients with OC to assess the associations of polyphenol intake, not only pre- and post-diagnosis but also the change from pre- to post-diagnosis with OC survival. Dietary intakes of total (poly)phenols and their five classes (flavonoids, phenolic acids, lignans, stilbenes, and other polyphenols) were assessed using a validated 111-item food frequency questionnaire. Overall survival (OS) was tracked through active follow-up and medical records until February 16th, 2023. Cox proportional hazard regression models were applied to calculate the hazard ratios (HR) and 95% confidence intervals (CI)., Results: During a median follow-up of 44.4 months, 211 all-cause deaths were identified. We observed significant associations between higher polyphenol intake with lower risk of mortality among patients with OC ((HR T3 vs. T1 = 0.55, 95%CI = 0.35-0.87 for pre-diagnosis; and HR T3 vs. T1 = 0.59, 95%CI = 0.39-0.90 for post-diagnosis). Consistently, an evident linear trend was observed for polyphenol and flavonoid intake with OC survival. Of note, compared to the stable group (change within 10%), the decreased intake (change of more than 10%) of total (poly)phenols and five polyphenol classes was significantly associated with worse OS., Conclusion: Dietary (poly)phenols, as well as its five classes, have an inverse association with OC survival., Competing Interests: Declarations. Ethics approval and consent to participate: The OOPS was approved by the Institutional Review Board of the Ethics Committee of Shengjing Hospital of China Medical University. All participants signed informed consent. Competing interests: The authors declare that they have no conflict of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective. Artificial intelligence (AI) based treatment planning tools are being implemented in clinic. However, human interactions with such AI tools are rarely analyzed. This study aims to comprehend human planner's interaction with the AI planning tool and incorporate the analysis to improve the existing AI tool. Approach. An in-house AI tool for whole breast radiation therapy planning was deployed in our institution since 2019, among which 522 patients were included in this study. The AI tool automatically generates fluence maps of the tangential beams to create an AI plan . Human planner makes fluence edits deemed necessary and after attending physician approval for treatment, it is recorded as final plan . Manual modification value maps were collected, which is the difference between the AI-plan and the final plan . Subsequently, a human-AI interaction (HAI) model using full scale connected U-Net was trained to learn such interactions and perform plan enhancements. The trained HAI model automatically modifies the AI plan to generate AI-modified plans ( AI-m plan ), simulating human editing. Its performance was evaluated against original AI-plan and final plan. Main results. AI-m plan showed statistically significant improvement in hotspot control over the AI plan , with an average of 25.2cc volume reduction in breast V105% ( p = 0.011) and 0.805% decrease in Dmax ( p < .001). It also maintained the same planning target volume (PTV) coverage as the final plan , demonstrating the model has captured the clinic focus of improving PTV hot spots without degrading coverage. Significance. The proposed HAI model has demonstrated capability of further enhancing the AI plan via modeling human-AI tool interactions. This study shows analysis of human interaction with the AI planning tool is a significant step to improve the AI tool., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background and Purpose: To describe the clinical commissioning of an in-house artificial intelligence (AI) treatment planning platform for head-and-neck (HN) Intensity Modulated Radiation Therapy (IMRT)., Materials and Methods: The AI planning platform has three components: (1) a graphical user interface (GUI) is built within the framework of a commercial treatment planning system (TPS). The GUI allows AI models to run remotely on a designated workstation configured with GPU acceleration. (2) A template plan is automatically prepared involving both clinical and AI considerations, which include contour evaluation, isocenter placement, and beam/collimator jaw placement. (3) A well-orchestrated suite of AI models predicts optimal fluence maps, which are imported into TPS for dose calculation followed by an optional automatic fine-tuning. Six AI models provide flexible tradeoffs in parotid sparing and Planning Target Volume (PTV)-organ-at-risk (OAR) preferences. Planners could examine the plan dose distribution and make further modifications as clinically needed. The performance of the AI plans was compared to the corresponding clinical plans., Results: The average plan generation time including manual operations was 10-15  min per case, with each AI model prediction taking ∼1 s. The six AI plans form a wide range of tradeoff choices between left and right parotids and between PTV and OARs compared with corresponding clinical plans, which correctly reflected their tradeoff designs., Conclusion: The in-house AI IMRT treatment planning platform was developed and is available for clinical use at our institution. The process demonstrates outstanding performance and robustness of the AI platform and provides sufficient validation., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Environmental pollution has emerged as a significant determinant in ovarian cancer prognosis. However, limited evidence exists regarding the correlations between heavy metals and ovarian cancer prognosis., Objective: To elucidate the relationship between urinary heavy metals and their mixtures with overall survival (OS) of advanced high-grade serous ovarian cancer (HGSOC)., Methods: Within the Ovarian Cancer Follow-Up Study, we conducted a nested case-control study. A sum of 159 deceased patients and an equal number of alive patients were included, matched by sample date, body mass index, and age at diagnosis. Urinary concentrations of five heavy metals were quantified: arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). Conditional logistic regression models were employed to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs). To elucidate joint effects, we utilized quantile g-computation and Bayesian kernel machine regression models., Results: For the multivariable adjusted conditional logistic regression model, significant associations were found between high urinary levels of As (OR=1.99, 95 %CI: 1.05-3.79), Cd (OR=2.56, 95 %CI: 1.29-5.05), Hg (OR=2.24, 95 %CI: 1.09-4.62), and Pb (OR=3.80, 95 %CI: 1.75-8.27) and worse OS of HGSOC, comparing the highest tertile to the lowest. Analysis of joint effects showed that elevated concentrations of heavy metal mixtures were related to poor OS of HGSOC. Pb exhibited the highest contribution to the overall association within the metal mixtures., Conclusions: High urinary heavy metal concentrations were linked to worse OS of HGSOC. Future research is necessary to validate our findings., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR) T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA) (OR T3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed ( P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increased by 20% (OR = 1.20, 95% CI = 1.01-1.43) for each standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression ( P nonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.

Background: Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring., Methods: PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544)., Results: The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02-1.12), prostate cancer (OR = 1.02, 95% CI = 1.00-1.05), leukemia (OR = 1.18, 95% CI = 1.13-1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12-1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16-6.71); and a linear dose-response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09-1.24), respectively., Conclusions: Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility., (© 2024. The Author(s).)

Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence., 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 B.V. All rights reserved.)

Background: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions., Methods: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales., Results: Throughout a median follow-up of 37.60 (interquartile: 24.77-50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend < 0.01), whereas no significant associations were found between either overall PDI or hPDI and OC survival. Higher APS (HR for per interquartile range = 1.27, 95 % CI = 1.01, 1.60) was significantly associated with worse OC survival, and the association was exacerbated by adherence to uPDI. Notably, an additive interaction was identified between combined air pollution and uPDI (P < 0.005 for high APS and high uPDI). We also found that adherence to overall PDI aggravated associations of air pollution with OC survival (P-interaction = 0.006)., Conclusions: Joint exposure to various ambient air pollutants was significantly associated with lower survival among patients with OC, particularly for those who predominantly consumed unhealthy plant-based foods., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is currently a lack of comprehensive evidence regarding the correlation between Alternate Mediterranean Diet (AMED) and the survival of patients with ovarian cancer (OC). This prospective cohort study first assessed the association of AMED, not only pre-diagnosis and post-diagnosis but also the change from pre-diagnosis to post-diagnosis with OC survival., Methods: A total of 560 OC patients were included in the study, and their dietary intake was assessed using a reliable 111-item food frequency questionnaire. The overall survival (OS) of the patients was monitored through active follow-up and review of medical records until February 16th, 2023. Cox proportional hazard regression models were utilized to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs)., Results: Out of the total 560 patients with OC, 211 (37.68%) succumbed during a median follow-up period of 44.40 months (interquartile range: 26.97-61.37). Comparative analysis indicated a significant association between the highest tertiles of pre-diagnosis (HR = 0.59; 95% CI 0.38-0.90; P trend  < 0.05) and post-diagnosis (HR = 0.61; 95% CI 0.41-0.91; P trend  < 0.05) AMED intake and improved OS as opposed to the lowest tertile. Additionally, a significant linear trend was observed for AMED and OC survival. Notably, decreased intake (more than 5% change) and significantly increased intake (more than 15% change) of AMED from pre-diagnosis to post-diagnosis were linked to worse and better OS, respectively, when compared to the stable intake group (change within 5%). Furthermore, patients displaying consistently higher AMED intake both before and after diagnosis experienced enhanced OS in comparison to those with consistently low AMED intake (HR High-High vs. Low-Low  = 0.47; 95% CI 0.31-0.70)., Conclusion: High pre-diagnosis and post-diagnosis AMED was associated with an improved OS in patients with OC, suggesting that maintaining a consistently high intake of AMED could potentially benefit the prognosis of OC., (© 2024. The Author(s).)

Acute lung injury (ALI) is defined as the acute onset of diffuse bilateral pulmonary infiltration, leading to PaO 2 /FiO 2 ≤ 300 mmHg without clinical evidence of left atrial hypertension. Acute respiratory distress syndrome (ARDS) involves more severe hypoxemia (PaO 2 /FiO 2 ≤ 200 mmHg). Treatment of ALI and ARDS has received renewed attention as the incidence of ALI caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased. Itaconate and its derivatives have shown therapeutic potential against ALI. This review provides an in-depth summary of the mechanistic research of itaconate in the field of acute lung injury, including inducing autophagy, preventing ferroptosis and pyroptosis, shifting macrophage polarization to an anti-inflammatory M2 phenotype, inhibiting neutrophil activation, regulating epigenetic modifications, and repressing aerobic glycolysis. These compounds merit further consideration in clinical trials. We anticipate that the clinical translation of itaconate-based drugs can be accelerated., Competing Interests: None., (AJTR Copyright © 2024.)

Background : Previous studies on the association between diet quality and ovarian cancer (OC) survival are limited and inconsistent. We evaluated the relationship between pre- and post-diagnosis diet quality based on the Healthy Eating Index-2020 (HEI-2020), as well as their changes and OC survival. Methods : This prospective cohort study involved 1082 patients with OC aged 18-79 years, enrolled between 2015 and 2022. Detailed dietary intake before and after diagnosis was recorded using a validated food frequency questionnaire. Deaths were ascertained until February 16th, 2023 via medical records and active follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results : We included 549 OC cases with a median follow-up of 44.9 months, representing 206 total deaths. Higher HEI scores were associated with better OS (pre-diagnosis: HR T3 vs. T1 0.66, 95%CI: 0.46-0.93, HR 1-SD 0.84, 95%CI: 0.73-0.96; post-diagnosis: HR T3 vs. T1 0.68, 95%CI: 0.49-0.96, HR 1-SD 0.80, 95%CI: 0.69-0.92). Compared to the stable group, the group with decreased HEI scores (>3%) from pre- to post-diagnosis had worse OS (HR 1.93, 95%CI: 1.26-2.97). Conclusion : High pre- and post-diagnosis diet quality was associated with improved OC survival, whereas deterioration in diet quality after diagnosis was associated with decreased OC survival.

Background: Currently, neck dissection is a standard treatment for the majority of oral squamous cell carcinoma (OSCC) patients. However, the procedure can lead to a series of complications, significantly reducing patient quality of life and even affecting the antitumor immune response in patients undergoing immunotherapy. Therefore, in the era of precision surgery, gaining a deeper understanding of the patterns of lymph node metastasis (LNM) in OSCC is crucial., Materials and Methods: Literature searches were performed on PubMed, Embase, Web of Science, Cochrane Library, WANFANGDATA and China National Knowledge Infrastructure (CNKI) (inception to April 10, 2024). In addition, a manual searching was conducted in Scopus, Google Scholar, and Education Resources Information Center (ERIC). We included observational studies that evaluated the frequency of LNM in OSCC patients. Systematic review and a random effects model meta-analysis were performed., Results: The search identified 4694 articles, of which 17 studies included in our study. We calculated the frequency of LNM according to the data reported in the articles. Frequency of LNM=number of patients with positive lymph node / number of patients with OSCC. The frequency of LNM was 12% in level I (95%CI: 0.11 to 0.15, I2=38.01%), 20% in level II (95%CI: 0.17 to 0.22, I2=47.71%), 10% in level III (95%CI: 0.08 to 0.12, I2=49.10%), 2% in level VI (95%CI: 0.01 to 0.03, I2=27.58%), 1% in level V (95%CI: 0.00 to 0.01, I2=11.37%)., Conclusion: The frequency of LNM is consistent with the "cascade theory" and appears to be no significant difference from different primary sites. The frequency of LNM were low in levels I-III and were very low in level IV-V which implicated that more conservative treatments may be considered for OSCC in the future. This study will help clinicians better determine the extent of surgery and preserve lymph nodes during neck dissection., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective. This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART). Approach. The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection. Main results. Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose, V 20 , and V 5 were significantly reduced by 1.13 Gy ( p < .001), 2.01% ( p < .001), and 6.66% ( p < .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy ( p < .01), fV 20 by 0.90% ( p = 0.099), and fV 5 by 5.07% ( p < .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection. Significance. AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans., (Creative Commons Attribution license.)

Renal cell carcinoma (RCC) is a malignant tumor originating from the epithelial cells of the renal tubules. The clear cell RCC subtype is closely linked to a poor prognosis due to its rapid progression. Circular RNA (circRNA) is a novel class of regulatory RNA molecules that play a role in the development of ccRCC, although their functions have not been fully elucidated. In this study, we identified a significant downregulation of circ-IP6K2 in ccRCC tissues based on data from the GSE100186 dataset. The decreased expression of circ-IP6K2 correlated with the progression of TNM stage and histological grade, and was also associated with decreased overall survival rates in ccRCC patients. Moreover, our findings revealed that circ-IP6K2 expression suppressed proliferation, migration, and invasion capabilities in vitro, and inhibited xenograft growth in vivo. Mechanistically, circ-IP6K2 acted as a sponge for miR-1292-5p in ccRCC cells, which in turn targeted the 3'UTR of CAMK2N1, leading to a decrease in its expression. CAMK2N1 was identified as a tumor suppressor that negatively regulated the β-catenin/c-Myc oncogenic signaling pathway. Additionally, we confirmed a positive correlation between the expression of circ-IP6K2 and CAMK2N1 in ccRCC. Circ-IP6K2 functions to impede the progression of ccRCC by modulating the miR-1292-5p/CAMK2N1 axis. These findings shed new light on the molecular mechanisms driving ccRCC progression and suggest potential therapeutic targets for the treatment of ccRCC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated., Methods: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817)., Results: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence., Conclusion: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels., 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 B.V. All rights reserved.)

Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review., Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules., Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period., Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1986/coif). All authors report that this study was supported by the National High Level Hospital Clinical Research Funding (No. BJ-2022-185). The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background & aims : Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods : A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results : No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers ( P trend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; P trend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk ( P < 0.05). Conclusions : Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.

Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a destructive insect pest of many crops. Rickettsia infection in different cryptic species of B. tabaci has been observed worldwide. Understanding the interactions between these 2 organisms is critical to developing Rickettsia-based strategies to control B. tabaci and thereby reduce the transmission of related vector-borne viruses. In this study, we investigated the effects of Rickettsia infection on the biological characteristics of the Middle East Asia Minor 1 (MEAM1) strain of B. tabaci through biological analysis of infected and uninfected individuals. The results of this study suggest that Rickettsia may confer fitness benefits. These benefits include increased fertility, improved survival rates, accelerated development, and resulted in female bias. We also investigated the transcriptomics impact of Rickettsia infection on B. tabaci by performing a comparative RNA-seq analysis of nymphs and adult females, both with and without the infection. Our analysis revealed 218 significant differentially expressed genes (DEGs) in infected nymphs compared to uninfected ones and 748 significant DEGs in infected female adults compared to their uninfected whiteflies. Pathway analysis further revealed that Rickettsia can affect many important metabolic pathways in whiteflies. The results suggest that Rickettsia plays an essential role in energy metabolism, and nutrient synthesis in the B. tabaci MEAM1, and depends on metabolites obtained from the host to ensure its survival. Overall, our findings suggest that Rickettsia has beneficial effects on B. tabaci and offered insights into the potential molecular mechanisms governing the interactions between Rickettsia and B. tabaci MEAM1., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS., (© 2024. The Author(s).)

Use of magnetic resonance (MR) imaging in radiation therapy has increased substantially in recent years as more radiotherapy centers are having MR simulators installed, requesting more time on clinical diagnostic MR systems, or even treating with combination MR linear accelerator (MR-linac) systems. With this increased use, to ensure the most accurate integration of images into radiotherapy (RT), RT immobilization devices and accessories must be able to be used safely in the MR environment and produce minimal perturbations. The determination of the safety profile and considerations often falls to the medical physicist or other support staff members who at a minimum should be a Level 2 personnel as per the ACR. The purpose of this guidance document will be to help guide the user in making determinations on MR Safety labeling (i.e., MR Safe, Conditional, or Unsafe) including standard testing, and verification of image quality, when using RT immobilization devices and accessories in an MR environment., (© 2024 American Association of Physicists in Medicine.)

Background: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations., Methods: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070)., Findings: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer., Interpretation: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease., Funding: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence., Methods: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587)., Results: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index., Conclusion: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases., (© 2024. The Author(s).)

Background: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking., Methods: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547)., Results: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I 2  = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE., Conclusions: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk., (© 2024. The Author(s).)

Deep learning neural networks (DLNN) in Artificial intelligence (AI) have been extensively explored for automatic segmentation in radiotherapy (RT). In contrast to traditional model-based methods, data-driven AI-based models for auto-segmentation have shown high accuracy in early studies in research settings and controlled environment (single institution). Vendor-provided commercial AI models are made available as part of the integrated treatment planning system (TPS) or as a stand-alone tool that provides streamlined workflow interacting with the main TPS. These commercial tools have drawn clinics' attention thanks to their significant benefit in reducing the workload from manual contouring and shortening the duration of treatment planning. However, challenges occur when applying these commercial AI-based segmentation models to diverse clinical scenarios, particularly in uncontrolled environments. Contouring nomenclature and guideline standardization has been the main task undertaken by the NRG Oncology. AI auto-segmentation holds the potential clinical trial participants to reduce interobserver variations, nomenclature non-compliance, and contouring guideline deviations. Meanwhile, trial reviewers could use AI tools to verify contour accuracy and compliance of those submitted datasets. In recognizing the growing clinical utilization and potential of these commercial AI auto-segmentation tools, NRG Oncology has formed a working group to evaluate the clinical utilization and potential of commercial AI auto-segmentation tools. The group will assess in-house and commercially available AI models, evaluation metrics, clinical challenges, and limitations, as well as future developments in addressing these challenges. General recommendations are made in terms of the implementation of these commercial AI models, as well as precautions in recognizing the challenges and limitations., (Copyright © 2023. Published by Elsevier Inc.)

The diagnosis of cancer is typically based on histopathological sections or biopsies on glass slides. Artificial intelligence (AI) approaches have greatly enhanced our ability to extract quantitative information from digital histopathology images as a rapid growth in oncology data. Gynecological cancers are major diseases affecting women's health worldwide. They are characterized by high mortality and poor prognosis, underscoring the critical importance of early detection, treatment, and identification of prognostic factors. This review highlights the various clinical applications of AI in gynecological cancers using digitized histopathology slides. Particularly, deep learning models have shown promise in accurately diagnosing, classifying histopathological subtypes, and predicting treatment response and prognosis. Furthermore, the integration with transcriptomics, proteomics, and other multi-omics techniques can provide valuable insights into the molecular features of diseases. Despite the considerable potential of AI, substantial challenges remain. Further improvements in data acquisition and model optimization are required, and the exploration of broader clinical applications, such as the biomarker discovery, need to be explored., Competing Interests: The authors report no conflict of interest., (© 2024 The Authors.)

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality., Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004)., Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p  < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p  = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p  = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p  = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p  = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p  = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p  = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p  = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p  = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p  = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p  = 0.008)., Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER., Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG)., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: The relationship between handgrip strength (HGS) and depression in patients undergoing hemodialysis (HD) was unknown. Therefore, we aimed to clarify this association in a cohort of patients., Methods: HGS was used as a representative indicator of muscle strength and was measured with a handheld dynamometer. Depressive symptoms were assessed with the self-reported Patient Health Questionnaire-9. A multivariable logistic regression model and restricted cubic spline analysis were used to assess the relationship between HGS and depression., Results: The prevalence of depression in our study was 34% in 568 Chinese patients undergoing HD. Compared with patients in the lowest tertiles of absolute and weighted HGS, patients in the highest tertiles of HGS had an approximately 59% lower [odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.24-0.68; OR = 0.41, 95%CI = (0.24-0.69)] prevalence of depressive symptoms after multivariate adjustments. Besides, the risk of depression in hemodialysis patients decreased by 33% (OR = 0.67, 95%CI = 0.53-0.85) and 32% (OR = 0.68, 95%CI = 0.54-0.85) for each standard deviation increase in absolute HGS and weighted HGS, respectively. The prevalence of depressive symptoms decreased with both increasing absolute HGS and weighted HGS after multivariate adjustments (p for trend < 0.05). Furthermore, a linear dose-response relationship was observed between absolute HGS and weighted HGS and the prevalence of depressive symptoms (p nonlinearity >0.05)., Conclusions: This study suggests that lower handgrip strength, a simple and modifiable parameter, is associated with a higher prevalence of depression in Chinese patients undergoing HD. Considering that depression is often unrecognized or underdiagnosed in HD patients, lowered muscle strength should be an important indicator and incentive for medical staff to screen for depression., (© 2024. The Author(s).)

Cancer vaccines based on tumor cell components have shown promising results in animal and clinical studies. The vaccine system contains abundant tumor antigen components, which can activate the immune system by antigens. However, their efficacy has been limited by the inability of antigens delivery, which are the core components of vaccines, further fail to be presented and activation of effective cells. Nanotechnology offers a novel platform to enhance the immunogenicity of tumor-associated antigens and deliver them to antigen-presenting cells (APCs) more efficiently. In addition, nanotreatment of tumor cells derivate active ingredients could also help improve the effectiveness of cancer vaccines. In this review, we summarize recent advances in the development of cancer vaccines by the combination of nanotechnology and tumor-based ingredients, including liposomes, polymeric nanoparticles, metallic nanoparticles, virus-like particles and tumor cells membrane, tumor lysate, and specific tumor antigens. These nanovaccines have been designed to increase antigen uptake, prolong antigen presentation, and modulate immune responses through codelivery of immunostimulatory agents. We also further discuss challenges and opportunities in the clinical translation of these nanovaccines., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Qing-Juan Wu and Wen-Liang Lv.)

Background: Patients of interstitial lung disease (ILD) combined with pulmonary lesions are increasingly common in clinical practice. Patients with ILD are at significantly higher risk for complications after pulmonary resection (including lobectomy and sublobar resection), especially acute exacerbations of ILD (AE-ILD). The purpose of this study is to summarize the short-term and long-term outcomes after pulmonary resection in ILD patients and to analyze the clinical factors affecting surgical safety., Methods: From January 2004 to January 2022, a total of 78 patients who were diagnosed with ILD and underwent pulmonary resection at our center were enrolled in this study. Clinical data, pathological findings, surgical procedures, and intraoperative safety of these patients were collected retrospectively. Postoperative 90-day complications and mortality, long-term surgical outcomes from postoperative 90 days to 24 months, and changes in ILD condition were investigated. Logistic regression analysis was used to identify the risk factors associated with postoperative complications., Results: The median age of patients was 66.5 (range 33-86) years, 82.1% (64/78) of patients were male, and 78.2% (61/78) of patients had comorbidities. Idiopathic ILD and secondary ILD accounted for 86% and 14%, thoracotomy and video-assisted thoracoscopic surgery accounted for 12.8% and 87.2%, and lobectomy and sublobar resection accounted for 37.2% and 62.8%, respectively. Postoperative 90-day complications occurred in 25.6% (20/78) of patients, with pulmonary complications and AE-ILD occurring in 15.4% and 9.0% of patients, respectively. The postoperative 90-day mortality rate was 5.1% (4/78), and the cause of death was AE-ILD. Exacerbation of ILD or other complications occurred in 12.8% (10/78) of patients from postoperative 90 days to 24 months. Univariate logistic regression analysis showed that comorbidity, extent of resection, systemic lymph node dissection, operation time, intraoperative blood loss, and pathology of pulmonary lesion were associated with postoperative 90-day complications. In multivariate logistic regression analysis, age-adjusted Charlson Comorbidity Index and intraoperative blood loss were identified as independent risk factors of postoperative 90-day complications., Conclusions: Patients with ILD have a significantly higher risk of postoperative 90-day complications and mortality after pulmonary resection, especially pulmonary complications and AE-ILD. After postoperative 90 days, the risk of deterioration of pulmonary status remains high, including exacerbation of ILD and complications associated with long-term use of glucocorticoids and immunosuppressant. Age, comorbidity and intraoperative blood loss are high risk factors for postoperative 90-day complications., (© 2024. The Author(s).)

Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance., (© 2024. The Author(s).)

Scope: The study aims to investigate the role of the sulfur microbial diet in the survival of ovarian cancer (OC)., Methods and Results: A prospective cohort study is conducted with 703 patients diagnosed with OC between 2015 and 2020. Diet information is collected using a validated food frequency questionnaire. Deaths are ascertained up to March 31, 2021, via the death registry linkage. During the follow-up period (median: 37.2 months, interquartile range: 24.7-50.2 months), 130 deaths are observed. A higher sulfur microbial diet score is significantly associated with an increased risk of all-cause mortality among OC patients (tertile 3 vs tertile 1: HR = 1.93, 95% CI = 1.11-3.35). Each 1-standard deviation increment in the sulfur microbial diet score increases the all-cause mortality risk by 33% (95% CI = 1.04-1.71). Stratified analysis shows that significant associations are found in OC patients diagnosed over 50 years of age, with body mass index ≥24  kg m -2 , who changed their diet after diagnosis, or without residual lesions., Conclusions: Adherence to the sulfur microbial diet, characterized by high intakes of red meats and processed meats, and low intakes of fruits, vegetables, and whole grains, is associated with poor survival in OC patients., (© 2023 Wiley-VCH GmbH.)

Phytochemical investigations on the fruits of Cascabela thevetia (L.) Lippold led to obtain three new cardenolides ( 1 - 3 ) and five known analogues ( 4 - 7 ). Their structures were elucidated by means of UV, IR, HR-ESI-MS, 1D and 2D NMR spectroscopic data analysis. Compounds 1 and 2 represent the first examples of naturally occurring cardenolides with 19- nor -5(10)-ene group and α - l -3-demethyl-thevetose, respectively. Compound 3 is a rare C -nor- D-homocardenolide in nature. All isolated cardenolides ( 1 - 7 ) were evaluated for their cytotoxic activities against four human cancer cell lines (MCF-7, HCT-116, HeLa and HepG2), and the results indicated the compounds with sugar units ( 1 , 2 , 4 , and 5 ) exhibited stronger cytotoxic activities with IC 50 values ranging between 0.022 and 0.308  μ M.

Objective: To construct a cellular senescence-related DNA methylation model to act as an independent prognosis predictor for patients with head and neck squamous cell carcinoma (HNSCC)., Methods: Methylome, transcriptome and clinical information for 499 HNSCC patients were received from The Cancer Genome Atlas (TCGA) as a training set. An extra independent methylation dataset of 54 patients with oral squamous cell carcinoma (OSCC) was downloaded from the NCBI Gene Expression Omnibus (GEO) database as the validation set. To assess the cellular senescence level of each sample, the senescence score (SS) of each patient was calculated using the transcriptome data via single-sample gene set enrichment analysis (ssGSEA). Least absolute shrinkage and selection operator (LASSO) Cox regression analyses were conducted to confirm Cytosine, phosphoric acid and Guanine (CpG) sites for the development of a cellular senescence-related DNA methylation signature., Results: Based on the SS of each HNSCC patient in the TCGA cohort, the patients were divided into high- and low-SS subgroups. The high-SS group showed a better prognosis than the low-SS group. Moreover, 3,261 differentially methylated CpG sites (DMCs) were confirmed between the two groups. Among them, 16 DMCs were included to develop a 16-DNA methylation signature for evaluation of HNSCC prognosis using LASSO and multivariate Cox regression analysis., Conclusion: A novel cellular senescence-related 16-DNA methylation signature was determined, which can be used as an independent index to evaluate the prognosis of HNSCC patients and select appropriate treatment strategies.