The use of technology in cancer prehabilitation: a systematic review.

Aim: This review aimed to evaluate the effectiveness and feasibility of cancer prehabilitation programs delivered through technological enablers compared to conventional face-to-face interventions. Methods: A systematic review was conducted, searching PubMed, Embase, and CINAHL for studies published from inception to February 6, 2024. Studies were included if they involved adult cancer patients in primary research, utilized technology for prehabilitation, and assessed functional, psychological, and quality of life outcomes. Results: Sixteen studies were included, encompassing wearables, apps, teleprehabilitation, and virtual reality. All studies reported feasibility, but challenges included technical issues, lack of supervision, and non-compliance. Effectiveness depended on intervention rigor and technology type. Wearables offered objective monitoring but faced compliance issues. Videoconferencing provided supervision and could mitigate compliance concerns. Multimodal programs and intervention-specific outcome measures were recommended. Conclusion: Technology-based prehabilitation programs seem feasible, but effectiveness depends on intervention design and technology employed. Future research should focus on developing robust evidence to guide clinical practice and explore the potential of integrated technological solutions. Systematic review registration: PROSPERO, identifier CRD42022376028.

Production and use of dry-rolled hybrid rye grain as a replacement for barley grain on growth performance and carcass quality of feedlot steers.

The objectives were to compare cereal grain and straw yield between barley and hybrid rye (HR) and to evaluate whether the inclusion of dry-rolled HR grain as a replacement for barley grain affected feed intake and growth for growing cattle, and feed intake, growth, and carcass characteristics for finishing cattle. Crop yield was measured by directly weighing harvested grain and straw bales (n = 3 plots/grain type). Three-hundred sixty steers with an initial body weight (BW) of 348 ±â€…40 kg were stratified by BW and randomly assigned to 1 of the 24 pens during the growing phase (n = 8; 65 d). The control diet (BCON) included 60.22% barley grain with HR included by replacing 50 (BMID) or 100% (BHIGH) of the barley grain on a dry matter (DM) basis. Steers were re-randomized for the finishing phase (n = 6; 118 d) and treatments included a control diet containing 88.60% barley grain (FCON) with HR replacing 33 (FLOW), 67 (FMED), or 100% (FHIGH) of the barley grain (DM basis). The grain yield was greater (P = 0.04) and straw yield tended (P = 0.06) to be less for HR than barley. There were no effects of HR inclusion on DM intake (DMI) or G:F during the growing phase, but average daily gain (ADG) responded quadratically (P = 0.02) with cattle fed 50% HR having the greatest gain. During finishing, DMI decreased linearly as HR grain inclusion increased (P < 0.01). ADG initially increased from FCON to FLOW followed by a decrease with increasing HR inclusion (quadratic, P < 0.01), but G:F was not affected. Hot carcass weight was greatest for FCON with the magnitude of difference between FCON and the HR treatments increasing with increasing inclusion of HR (quadratic, P = 0.02). There was a linear increase in dressing percentage (P = 0.02) and a linear reduction in back fat thickness (P = 0.04) with increasing inclusion of HR. Increasing the inclusion of HR during finishing cubically (P < 0.01) affected the proportion of minor and severe liver abscesses with an average of 34.60% severely abscessed livers when HR was included compared to 11.11% for BCON. HR may have greater grain yield than barley, and partial replacement of barley grain with HR may improve ADG without affecting DMI or G:F during the growing phase. However, replacing barley grain in finishing diets with HR decreases DMI, and increases the risk of minor and severe liver abscesses, but does not affect feed conversion, suggesting HR should not replace more than 33% of the barley grain to maintain ADG.

Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy.

DNA double-strand breaks (DSBs) yield highly determines radiotherapy efficacy. However, improving the inherent radiosensitivity of tumor DNA to promote radiation-induced DSBs remains a challenge. Using theoretical and experimental models, the underexplored impact of Z-DNA conformations on radiosensitivity, yielding higher DSBs than other DNA conformations, is discovered. Thereout, a radiosensitization strategy focused on inducing Z-DNA conformation, utilizing CBL@HfO2 nanocapsules loaded with a Z-DNA inducer CBL0137, is proposed. A hollow mesoporous HfO2 (HM-HfO2) acts as a delivery and an energy depositor to promote Z-DNA breakage. The nanocapsule permits the smart DSBs accelerator that triggers its radiosensitization with irradiation stimulation. Impressively, the CBL@HfO2 facilitates the B-Z DNA conformational transition, augmenting DSBs about threefold stronger than irradiation alone, generating significant tumor suppression with a 30% cure rate. The approach enables DSBs augmentation by improving the inherent radiosensitivity of DNA. As such, it opens up an era of Z-DNA conformation manipulation in radiotherapy.

Application of Recombinant Human Superoxide Dismutase in Radical Concurrent Chemoradiotherapy for Cervical Cancer to Prevent and Treat Radiation-induced Acute Rectal Injury: A Multi-center, Randomized, Open-label, Prospective Trial.

PURPOSE: To evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer. METHODS: In this phase III, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiotherapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiotherapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiotherapy-induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea; ≥G1 and ≥G2 diarrhea lasting at least 3 days; and damage to the rectal mucosa due to radiotherapy measured by endoscopy. RESULTS: Two-hundred-and-eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 140). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs. 14.8 and 4.5 days, respectively; P<0.001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs. 55.7%, P<0.001). Three patients felt intolerable or abdominal pain following rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P=0.061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P<0.001). CONCLUSION: The results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa.

Prognostic model incorporating immune checkpoint genes to predict the immunotherapy efficacy for lung adenocarcinoma: a cohort study integrating machine learning algorithms.

This study aimed to develop and validate a nomogram based on immune checkpoint genes (ICGs) for predicting prognosis and immune checkpoint blockade (ICB) efficacy in lung adenocarcinoma (LUAD) patients. A total of 385 LUAD patients from the TCGA database and 269 LUAD patients in the combined dataset (GSE41272 + GSE50081) were divided into training and validation cohorts, respectively. Three different machine learning algorithms including random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression analysis, and support vector machine (SVM) were employed to select the predictive markers from 82 ICGs to construct the prognostic nomogram. The X-tile software was used to stratify patients into high- and low-risk subgroups based on the nomogram-derived risk scores. Differences in functional enrichment and immune infiltration between the two subgroups were assessed using gene set variation analysis (GSVA) and various algorithms. Additionally, three lung cancer cohorts receiving ICB therapy were utilized to evaluate the ability of the model to predict ICB efficacy in the real world. Five ICGs were identified as predictive markers across all three machine learning algorithms, leading to the construction of a nomogram with strong potential for prognosis prediction in both the training and validation cohorts (all AUC values close to 0.800). The patients were divided into high- (risk score ≥ 185.0) and low-risk subgroups (risk score < 185.0). Compared to the high-risk subgroup, the low-risk subgroup exhibited enrichment in immune activation pathways and increased infiltration of activated immune cells, such as CD8 + T cells and M1 macrophages (P < 0.05). Furthermore, the low-risk subgroup had a greater likelihood of benefiting from ICB therapy and longer progression-free survival (PFS) than did the high-risk subgroup (P < 0.05) in the two cohorts receiving ICB therapy. A nomogram based on ICGs was constructed and validated to aid in predicting prognosis and ICB treatment efficacy in LUAD patients.

Exploring the causal effects of depression and antidepressants on COVID-19.

BACKGROUND: While existing studies have suggested an increased risk of COVID-19 in patients with depression, the causal impact of MDD on the severity of COVID-19 remains to be validated. Additionally, the potential impact of antidepressant medication on the risk of COVID-19 is not known. METHODS: In our study, we applied a Mendelian Randomization (MR) method, leveraging summary data from GWAS, to evaluate the potential causal effects of depression on three COVID-19 outcomes. Furthermore, we investigated the causal effects of antidepressants on COVID-19 outcomes. The COVID-19 datasets contain information on various stages of the disease, including SARS-CoV-2 infection (N = 2,597,856), hospitalized COVID-19 (N = 2,095,324), and critical COVID-19 (N = 1,086,211). Datasets for depression and antidepressants were comprised of 1,349,887 and 106,785 participants, respectively. RESULTS: Employing the inverse variance-weighted (IVW) method, we show a causal association between depression and three COVID-19 outcomes. Specifically, we found that genetic liability to depression is linked to critical COVID-19 (OR: 1.28, 95 % CI: 1.13-1.46), hospitalized COVID-19 (OR: 1.23, 95 % CI: 1.13-1.34), and SARS-CoV-2 infection (OR: 1.06, 95 % CI: 1.02-1.10). Interestingly, the use of antidepressants was not associated with COVID-19, with the odds ratios for critical COVID-19 (OR: 1.05, 95 % CI: 0.88-1.26), hospitalization (OR: 1.01, 95 % CI: 0.90-1.13), and SARS-CoV-2 infection (OR: 1.03, 95 % CI: 0.99-1.08) indicating no causal impact. CONCLUSION: Our study indicates that genetic liability to depression may increase the susceptibility to COVID-19 and its severe forms. The lack of causal effect of antidepressant use on COVID-19 implies antidepressant medication may counteract the detrimental effect of depression on COVID-19.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography.

BACKGROUND: Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. METHODS: This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. RESULTS: The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. CONCLUSIONS: Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

Comparison of outcomes between early-stage cervical cancer patients without high-risk factors undergoing adjuvant concurrent chemoradiotherapy and radiotherapy alone after radical surgery.

PURPOSE: For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. PATIENTS AND METHODS: The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. RESULTS: A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. CONCLUSION: There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.

Causal Associations between Posttraumatic Stress Disorder and COVID-19.

OBJECTIVE: We aimed to evaluate bidirectional genetic relationships between posttraumatic stress disorder (PTSD) and COVID-19. METHODS: We investigated potential causal associations between PTSD and two COVID-19 conditions (COVID-19 hospitalization and SARS-CoV-2 infection) via Mendelian randomization (MR) analyses. Three genome-wide association study (GWAS) summary datasets were used in the study, including PTSD (N = 174,659), SARS-CoV-2 infection (N = 2,597,856), and COVID-19 hospitalization (N = 2,095,324). We performed a literature-based analysis to uncover molecular pathways connecting PTSD and COVID-19. RESULTS: We found that PTSD exerts a causal effect on SARS-CoV-2 infection (odds ratio (OR): 1.10, 95% confidence interval (CI): 1.00-1.21, p = 0.048) and hospitalized COVID-19 (OR: 1.34, 95% CI: 1.07-1.67, p = 0.001). However, both SARS-CoV-2 infection and hospitalized COVID-19 were not associated with the risk of PTSD. Pathway analysis revealed that several immunity-related genes may link PTSD to COVID-19. CONCLUSIONS: Our study suggests that PTSD was associated with increased risks for COVID-19 susceptibility and severity. Early diagnosis and effective treatment of PTSD in individuals infected with the coronavirus may improve the management of the outcomes of COVID-19.

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

OBJECTIVE: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. METHODS: Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. RESULTS: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. CONCLUSION: Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms.

We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS<1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (P<0.05) and greater infiltration of immune suppression cells compared to LTS (P<0.05). Four genes, namely, OSMR, FMOD, CXCL14, and TIMP1, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (C-index, 0.791; 0.772-0.817) and validation cohort (C-index, 0.770; 0.751-0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.

Exploration of radiotherapy strategy for brain metastasis patients with driver gene positivity in lung cancer.

Objective: To assess the disparities in effectiveness and identify outcome predictors in the treatment of a targeted-first and radiotherapy-first regimen with driver gene-positive lung cancer brain metastases. Materials and Methods: This retrospective study analyzed patients with driver gene-positive lung cancer brain metastases who received first-targeted and first-radiotherapy regimens, respectively, with SIB-WBRT (whole brain tissue 40 Gy/20 fractions, tumor tissue boosted to 56-60 Gy/20 fractions) and local irradiation (prescription dose range of 20-60 Gy/2-25 fractions, most commonly delivered as 30 Gy/5 fractions, with a BED range of 28-100.8 Gy) at Peking Union Medical College Hospital from September 2015 to December 2021. The primary endpoint was intracranial progression free survival (iPFS). Secondary endpoints included overall survival (OS), intracranial new lesions, and tumor control. The Kaplan-Meier method was utilized to depict and estimate iPFS, OS, intracranial new lesions and tumor control. The Cox regression analysis was conducted to assess the association between relevant factors and outcomes. Results: 88 patients were enrolled in targeted-first and radiotherapy-first regimen, totally. And no difference was found in the comparison of iPFS between the two groups (HR=1.180, 95%CI: 0.622-2.237, P=0.613). No difference was found in the comparison of OS between the two groups (HR=1.208, 95%CI: 0.679-2.150, P=0.520). No difference was found in the comparison of intracranial new lesions between the two groups (HR=1.184, 95%CI: 0.569-2.463, P=0.652). There was a difference in the local control time between the two groups, with radiotherapy-first regimen being superior (HR=2.397, 95% CI:1.453-3.954, P<0.001). Patient age (HR=1.054, 95%CI: 1.026- 1.082, P<0.001), radiotherapy modality (HR=0.128, 95%CI: 0.041-0.401, P<0.001), metastasis volume (HR=1.426, 95%CI: 1.209-1.682, P<0.001), number of metastases(HR=14.960, 95%CI: 1.990-112.444, P=0.009), extracranial disease status (HR=0.387, 95%CI: 0.170-0.880, P=0.023) and therapy sequence (HR=13.800, 95%CI: 4.455-42.751, P<0.001) were associated with local control. Conclusion: Targeted-first regimen was not found to improve patients' iPFS relative to radiotherapy-first regimen in patients with brain metastases. Radiotherapy-first regimen for brain metastases demonstrated superior local control compared to targeted-first regimen. Patient's age, radiotherapy modality, metastasis volume, number of metastases, extracranial disease status and therapy sequence may be related to local control of metastases.

Exploring the influences of education, intelligence and income on mental disorders.

Background: Previous studies have shown that educational attainment (EA), intelligence and income are key factors associated with mental disorders. However, the direct effects of each factor on major mental disorders are unclear. Aims: We aimed to evaluate the overall and independent causal effects of the three psychosocial factors on common mental disorders. Methods: Using genome-wide association study summary datasets, we performed Mendelian randomisation (MR) and multivariable MR (MVMR) analyses to assess potential associations between the 3 factors (EA, N=766 345; household income, N=392 422; intelligence, N=146 808) and 13 common mental disorders, with sample sizes ranging from 9907 to 807 553. Inverse-variance weighting was employed as the main method in the MR analysis. Results: Our MR analysis showed that (1) higher EA was a protective factor for eight mental disorders but contributed to anorexia nervosa, obsessive-compulsive disorder (OCD), bipolar disorder (BD) and autism spectrum disorder (ASD); (2) higher intelligence was a protective factor for five mental disorders but a risk factor for OCD and ASD; (3) higher household income protected against 10 mental disorders but confers risk for anorexia nervosa. Our MVMR analysis showed that (1) higher EA was a direct protective factor for attention-deficit/hyperactivity disorder (ADHD) and insomnia but a direct risk factor for schizophrenia, BD and ASD; (2) higher intelligence was a direct protective factor for schizophrenia but a direct risk factor for major depressive disorder (MDD) and ASD; (3) higher income was a direct protective factor for seven mental disorders, including schizophrenia, BD, MDD, ASD, post-traumatic stress disorder, ADHD and anxiety disorder. Conclusions: Our study reveals that education, intelligence and income intertwine with each other. For each factor, its independent effects on mental disorders present a more complex picture than its overall effects.

Bidirectional associations between mental disorders, antidepressants and cardiovascular disease.

BACKGROUND: Mental disorders have a high comorbidity with cardiovascular disease (CVD), but the causality between them has not been fully appreciated. OBJECTIVE: This study aimed to systematically explore the bidirectional causality between the two broad categories of diseases. METHODS: We conducted Mendelian randomisation (MR) and multivariable MR (MVMR) analyses to evaluate potential causal links between 10 mental disorders, the use of antidepressants and 7 CVDs. FINDINGS: We discovered that major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and insomnia exhibit connections with elevated risks of two or more CVDs. Moreover, the use of antidepressants is linked to heightened risks of each CVD. Each distinct CVD is correlated with a greater probability of taking antidepressants. Our MVMR analysis demonstrated that the use of antidepressants is correlated with the elevation of respective risks across all cardiovascular conditions. This includes arrhythmias (OR: 1.28), atrial fibrillation (OR: 1.44), coronary artery disease (OR: 1.16), hypertension (OR: 1.16), heart failure (OR: 1.16), stroke (OR: 1.44) and entire CVD group (OR: 1.35). However, MDD itself was not linked to a heightened risk of any CVD. CONCLUSIONS: The findings of our study indicate that MDD, insomnia and ADHD may increase the risk of CVD. Our findings highlight the utilisation of antidepressants as an independent risk factor for CVD, thus explaining the influence of MDD on CVD through the mediating effects of antidepressants. CLINICAL IMPLICATIONS: When treating patients with antidepressants, it is necessary to take into consideration the potential beneficial and detrimental effects of antidepressants.

Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19.

Objective: The relationships between circulating inflammatory proteins and COVID-19 have been observed in previous cohorts. However, it is not unclear which circulating inflammatory proteins may boost the risk of or protect against COVID-19. Methods: We performed Mendelian randomization (MR) analysis using GWAS summary result of 91 circulating inflammation-related proteins (N = 14,824) to assess their causal impact on severe COVID-19. The COVID-19 phenotypes encompassed both hospitalized (N = 2,095,324) and critical COVID-19 (N = 1,086,211). Moreover, sensitivity analyses were conducted to evaluate the robustness and reliability. Results: We found that seven circulating inflammatory proteins confer positive causal effects on severe COVID-19. Among them, serum levels of IL-10RB, FGF-19, and CCL-2 positively contributed to both hospitalized and critical COVID-19 conditions (OR: 1.10~1.16), while the other 4 proteins conferred risk on critical COVID-19 only (OR: 1.07~1.16), including EIF4EBP1, IL-7, NTF3, and LIF. Meanwhile, five proteins exert protective effects against hospitalization and progression to critical COVID-19 (OR: 0.85~0.95), including CXCL11, CDCP1, CCL4/MIP, IFNG, and LIFR. Sensitivity analyses did not support the presence of heterogeneity in the majority of MR analyses. Conclusions: Our study revealed risk and protective inflammatory proteins for severe COVID-19, which may have vital implications for the treatment of the disease.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Causal influences of neuropsychiatric disorders on Alzheimer's disease.

Previous studies have observed a significant comorbidity between Alzheimer's disease (AD) and some other neuropsychiatric disorders. However, the mechanistic connections between neuropsychiatric disorders and AD are not well understood. We conducted a Mendelian randomization analysis to appraise the potential influences of 18 neurodegenerative and neuropsychiatric disorders on AD. We found that four disorders are causally associated with increased risk for AD, including bipolar disorder (BD) (OR: 1.09), migraine (OR: 1.09), schizophrenia (OR: 1.05), and Parkinson's disease (PD) (OR: 1.07), while attention-deficit/hyperactivity disorder (ADHD) was associated with a decreased risk for AD (OR: 0.80). In case of amyotrophic lateral sclerosis (OR: 1.04) and Tourette's syndrome (OR: 1.05), there was suggestive evidence of their causal effects of on AD. Our study shows that genetic components predisposing to BD, migraine, schizophrenia, and PD may promote the development of AD, while ADHD may be associated with a reduced risk of AD. The treatments aimed at alleviating neuropsychiatric diseases with earlier onset may also influence the risk of AD-related cognitive decline, which is typically observed later in life.

Evaluation of PTV margins with daily iterative online adaptive radiotherapy for postoperative treatment of endometrial and cervical cancer: a prospective single-arm phase 2 study.

BACKGROUND: To determine the optimal planning target volume (PTV) margins for adequate coverage by daily iterative cone-beam computed tomography (iCBCT)-guided online adaptive radiotherapy (oART) in postoperative treatment of endometrial and cervical cancer and the benefit of reducing PTV margins. METHODS: Fifteen postoperative endometrial and cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective phase 2 study. Pre- and posttreatment iCBCT images of 125 fractions from 5 patients were obtained as a training cohort, and clinical target volumes (CTV) were contoured separately. Uniform three-dimensional expansions were applied to the PTVpre to assess the minimum margin required to encompass the CTVpost. The dosimetric advantages of the proposed online adaptive margins were compared with conventional margin plans (7-15 mm) using an oART emulator in another cohort of 125 iCBCT scans. A CTV-to-PTV expansion was verified on a validation cohort of 253 fractions from 10 patients, and further margin reduction and acute toxicity were studied. RESULTS: The average time from pretreatment iCBCT to posttreatment iCBCT was 22 min. A uniform PTV margin of 5 mm could encompass nodal CTVpost in 100% of the fractions (175/175) and vaginal CTVpost in 98% of the fractions (172/175). The margin of 5 mm was verified in our validation cohort, and the nodal PTV margin could be further reduced to 4 mm if ≥ 95% CTV coverage was predicted to be achieved. The adapted plan with a 5 mm margin significantly improved pelvic organ-at-risk dosimetry compared with the conventional margin plan. Grade 3 toxicities were observed in only one patient with leukopenia, and no patients experienced acute urinary toxicity. CONCLUSION: In the postoperative treatment of endometrial and cervical cancer, oART could reduce PTV margins to 5 mm, which significantly decrease the dose to critical organs at risk and potentially lead to a lower incidence of acute toxicity.

Prospects for daily online adaptive radiotherapy for cervical cancer: Auto-contouring evaluation and dosimetric outcomes.

BACKGROUND: Training senior radiation therapists as "adapters" to manage influencers and target editing is critical in daily online adaptive radiotherapy (oART) for cervical cancer. The purpose of this study was to evaluate the accuracy and dosimetric outcomes of automatic contouring and identify the key areas for modification. METHODS: A total of 125 oART fractions from five postoperative cervical cancer patients and 140 oART fractions from five uterine cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective study. The same adaptive treatments were replanned using the Ethos automatic contours workflow without manual contouring edits. The clinical target volume (CTV) was subdivided into several separate regions, and the average surface distance dice (ASD), centroid deviation, dice similarity coefficient (DSC), and 95% Hausdorff distance (95% HD) were used to evaluate contouring for the above portions. Dosimetric results from automatic oART plans were compared to supervised oART plans to evaluate target volumes and organs at risk (OARs) dose changes. RESULTS: Overall, the paired CTV had high overlap rates, with an average DSC value greater than 0.75. The uterus had the largest consistency differences, with ASD, centroid deviation, and 95% HD being 2.67 ± 1.79 mm, 17.17 ± 12 mm, and 10.45 ± 5.68 mm, respectively. The consistency differences of the lower nodal CTVleft and nodal CTVright were relatively large, with ASD, centroid deviation, and 95% HD being 0.59 ± 0.53 mm, 3.6 ± 2.67 mm, and 5.41 ± 4.08 mm, and 0.59 ± 0.51 mm, 3.6 ± 2.54 mm, and 4.7 ± 1.57 mm, respectively. The automatic online-adapted plan met the clinical requirements of dosimetric coverage for the target volume and improved the OAR dosimetry. CONCLUSIONS: The accuracy of automatic contouring from the Ethos adaptive platform is considered clinically acceptable for cervical cancer, and the uterus, upper vaginal cuff, and lower nodal CTV are the areas that need to be focused on in training.

Causal association of attention-deficit/hyperactivity disorder and autism spectrum disorder with post-traumatic stress disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two neurodevelopmental disorders that often result in individuals experiencing traumatic events. However, little is known about the connection between ADHD/ASD and post-traumatic stress disorder (PTSD). This study aimed to investigate the genetic associations between these disorders. METHODS: Genetic correlation analysis was used to examine the genetic components shared between ADHD (38 691 cases and 275 986 controls), ASD (18 381 cases and 27 969 controls) and PTSD (23 212 cases and 151 447 controls). Two-sample Mendelian randomization analyses were employed to explore the bidirectional causal relationships between ADHD/ASD and PTSD. RESULTS: The results of the genetic correlation analysis revealed significant positive correlations of PTSD with ADHD(r g = 0.70) and ASD (r g = 0.34). Furthermore, the Mendelian randomization analysis revealed that genetic liabilities to ADHD [odds ratio (OR) = 1.14; 95% confidence interval (CI), 1.06-1.24; P  = 7.88 × 10 -4 ] and ASD (OR = 1.04; CI, 1.01-1.08; P  = 0.014) were associated with an increased risk of developing PTSD later in life. However, no evidence supported that genetic liability to PTSD could elevate the risk of ADHD or ASD. CONCLUSION: The findings of this study supported that ADHD and ASD may increase the risk of PTSD, but not vice versa.