Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study.

BACKGROUND: This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). METHODS: From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. RESULTS: In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05). CONCLUSION: When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.

Does vitamin D level associate with pregnancy outcomes in Chinese women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer? A retrospective cohort study.

AIM: To explore the relationship between serum 25(OH)D level and pregnancy outcomes (clinical pregnancy rate [CPR] and live birth rate [LBR]) in Chinese women receiving in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET) (IVF/ICSI-ET). METHODS: A total of 612 patients included in the study were divided into four cohorts according to serum 25(OH)D with the threshold of 20 ng/ml, 25 ng/ml, 30 ng/ml, and retrospectively analyzed. RESULTS: None of the baseline characteristics of participants was significantly different in the four cohorts except gravid status. The trend of 25(OH)D concentration was positively correlated with CPR and LBR. The younger (age: p < 0.001 both in CPR and LBR) women with primary infertility (infertility type: p = 0.004 in LBR) were more likely to get a better pregnancy outcome under the same 25(OH)D concentration stages. As shown on heatmap plots, CPR, and LBR were significantly increased for 25(OH)D concentrations above 30.00 ng/ml and women younger than 30 years old. The adjusted binary logistic regression and restricted cubic spline (RCS) showed that there existed a nonlinear positive correlation between 25(OH)D concentration and pregnancy outcome (CPR and LBR) (Pnonlinear < 0.001, respectively). The women with a sufficient 25(OH)D concentration (30 ng/ml) had 1.07 (clinical pregnancy) and 1.05 (live birth) times higher successful birth outcomes compared to women with an insufficient 25(OH)D concentration (25 ng/ml). (OR25 ng/ml, ref = 30 ng/ml [95% CI] = 0.935 [0.932-0.938] and 0.947 [0.945-0.950], p < 0.001, respectively). CONCLUSION: In Chinese women receiving IVF/ICSI-ET, the serum level of 25(OH)D demonstrated a nonlinear positive correlation with pregnancy outcomes (CPR and LBR), with stronger correlations above 25 ng/ml and worse yields below 30 ng/ml. However, it could not yet be considered different in distinct ages.

Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: A prospective cohort study.

BACKGROUND: For locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (nCRT), there are no reliable indicators to accurately predict pathological complete response (pCR) before surgery. For patients with clinical complete response (cCR), a "Watch and Wait" (W&W) approach can be adopted to improve quality of life. However, W&W approach may increase the recurrence risk in patients who are judged to be cCR but have minimal residual disease (MRD). Magnetic resonance imaging (MRI) is a major tool to evaluate response to nCRT; however, its ability to predict pCR needs to be improved. In this prospective cohort study, we explored the value of circulating tumor DNA (ctDNA) in combination with MRI in the prediction of pCR before surgery and investigated the utility of ctDNA in risk stratification and prognostic prediction for patients undergoing nCRT and total mesorectal excision (TME). METHODS AND FINDINGS: We recruited 119 Chinese LARC patients (cT3-4/N0-2/M0; median age of 57; 85 males) who were treated with nCRT plus TME at Fudan University Shanghai Cancer Center (China) from February 7, 2016 to October 31, 2017. Plasma samples at baseline, during nCRT, and after surgery were collected. A total of 531 plasma samples were collected and subjected to deep targeted panel sequencing of 422 cancer-related genes. The association among ctDNA status, treatment response, and prognosis was analyzed. The performance of ctDNA alone, MRI alone, and combining ctDNA with MRI was evaluated for their ability to predict pCR/non-pCR. Ranging from complete tumor regression (pathological tumor regression grade 0; pTRG0) to poor regression (pTRG3), the ctDNA clearance rate during nCRT showed a significant decreasing trend (95.7%, 77.8%, 71.1%, and 66.7% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.008), while the detection rate of acquired mutations in ctDNA showed an increasing trend (3.8%, 8.3%, 19.2%, and 23.1% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.02). Univariable logistic regression showed that ctDNA clearance was associated with a low probability of non-pCR (odds ratio = 0.11, 95% confidence interval [95% CI] = 0.01 to 0.6, P = 0.04). A risk score predictive model, which incorporated both ctDNA (i.e., features of baseline ctDNA, ctDNA clearance, and acquired mutation status) and MRI tumor regression grade (mrTRG), was developed and demonstrated improved performance in predicting pCR/non-pCR (area under the curve [AUC] = 0.886, 95% CI = 0.810 to 0.962) compared with models derived from only ctDNA (AUC = 0.818, 95% CI = 0.725 to 0.912) or only mrTRG (AUC = 0.729, 95% CI = 0.641 to 0.816). The detection of potential colorectal cancer (CRC) driver genes in ctDNA after nCRT indicated a significantly worse recurrence-free survival (RFS) (hazard ratio [HR] = 9.29, 95% CI = 3.74 to 23.10, P < 0.001). Patients with detectable driver mutations and positive high-risk feature (HR_feature) after surgery had the highest recurrence risk (HR = 90.29, 95% CI = 17.01 to 479.26, P < 0.001). Limitations include relatively small sample size, lack of independent external validation, no serial ctDNA testing after surgery, and a relatively short follow-up period. CONCLUSIONS: The model combining ctDNA and MRI improved the predictive performance compared with the models derived from individual information, and combining ctDNA with HR_feature can stratify patients with a high risk of recurrence. Therefore, ctDNA can supplement MRI to better predict nCRT response, and it could potentially help patient selection for nonoperative management and guide the treatment strategy for those with different recurrence risks.

Radiomic features of pretreatment MRI could identify T stage in patients with rectal cancer: Preliminary findings.

BACKGROUND: Recent studies have shown that magnetic resonance (MR) radiomic analysis is feasible and has some value in identifying tumor characteristics, but there are few data regarding the role of MR-based radiomic features in rectal cancer. PURPOSE: The aim of this study was to determine whether radiomic features extracted from T2 -weighted imaging (T2 WI) can identify pathological features in rectal cancer. STUDY TYPE: Retrospective study. POPULATION/SUBJECTS: A cohort comprising 119 rectal cancer patients who underwent surgery between January 2015 and November 2016. FIELD STRENGTH/SEQUENCE: 3.0T, axial high-resolution T2 -weighted turbo spin echo (TSE) sequence. ASSESSMENT: Patients were classified according to pathological features such as T stage, N stage, perineural invasion, histological grade, lymph-vascular invasion, tumor deposits, and circumferential resection margin (CRM). The whole tumor volume (WTV) was distinguished, and segments were quantified on axial high-resolution T2 WI by a radiologist. A total of 256 radiomic features were extracted. STATISTICAL TESTS: To achieve reliable results, cluster analysis and least absolute shrinkage and selection operator (LASSO) were implemented. In the cluster analysis, the patients were divided into two groups, and chi-square tests were performed to investigate the relationship between the pathological features and the radiomic-based clusters. The area under the curve (AUC) was calculated to evaluate the predictability of the model in the LASSO analysis. RESULTS: The cluster results revealed that patients could be stratified into two groups, and the chi-square test results indicated that the pT stage was correlated with the radiomic feature cluster results (P = 0.002). The prediction model AUC for the diagnostic T stage was 0.852 (95% confidence interval: 0.677-1; sensitivity: 79.0%, specificity: 82.0%). DATA CONCLUSION: The use of MRI-derived radiomic features to identify the T stage is feasible in rectal cancer. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Diffusion kurtosis imaging in the characterisation of rectal cancer: utilizing the most repeatable region-of-interest strategy for diffusion parameters on a 3T scanner.

OBJECTIVES: Our goal was to investigate the correlation between histopathology and diffusion parameters by utilising the most repeatable region-of-interest (ROI) strategy for diffusion parameters in rectal cancer on a 3T scanner. METHODS: 113 patients underwent DKI-MR and 66 of these patients received surgery without neoadjuvant chemoradiotherapy. Two readers independently measured the parameters using three slice protocols including single slice, three slices and whole-tumour slice (WTS), combined with one of two ROIs, including outline and round ROI. ANOVA, Kruskal-Wallis, a paired sample t-test, interclass correlation coefficient (ICC), Bland-Altman, Student's t-tests, receiver operating characteristic curves and z statistic were used for statistical analysis. RESULTS: There were no significant differences among the three slice protocols in ADC values (p = 0.822, 0.987), K values (p = 0.842, 0.859) and D values (p = 0.917, 0.988) using round and outline ROI, respectively. The ADC and D values derived from outline ROIs were higher than those from round ROIs (all p < 0.001 for ADC, all p < 0.001 for D), while K values derived from outline ROIs were lower than those from round ROIs (p < 0.001, p = 0.001, p < 0.001) using three slice protocols, respectively. The WTS-outline ROI resulted in the best intra- and inter-observer ICC. Utilising the WTS-outline ROI method, the AUC for assessment of well-differentiated tumours was 0.871 by K and 0.809 by ADC; and the AUC for T2 was 0.768 by K. CONCLUSIONS: The most repeatable strategy was the WTS-outline ROI method. In addition to DWI, DKI also have diagnostic value for rectal cancer histopathological characteristics utilising the WTS-outline ROI on a 3T scanner. KEY POINTS: • DKI using a 3T scanner is feasible for assessing rectal cancer. • ROI and slice protocol show considerable influence on DKI parameters. • DKI parameters exhibit excellent repeatability using whole-tumour slice-outline ROI on 3T scanner. • DKI has considerable diagnostic value for the estimation of rectal cancer characteristics.

Dynamic contrast-enhanced MRI: Use in predicting pathological complete response to neoadjuvant chemoradiation in locally advanced rectal cancer.

PURPOSE: To determine the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict pathological complete response (pCR) before preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer. MATERIALS AND METHODS: In a prospective clinical trial, 38 enrolled patients underwent pre- and post-CRT DCE-MRI at 3.0T. The tumor length and the following perfusion parameters (K(trans) , kep , ve ) were measured for the tumor and compared between the pCR group and the non-pCR group, as well as before and after CRT. For categorical variable comparison, the Kruskal-Wallis test was used. P < 0.05 was considered significant. RESULTS: No difference in tumor length was found between the pCR and non-pCR group pre- and post-CRT (P = 0.26 (0.15,0.45), 0.35 (0.21,0.52), respectively). Before CRT, the mean tumor K(trans) in the pCR group was significantly higher than in the non-pCR group (P = 0.01). A K(trans) of 0.66 emerged as the best cutoff for distinguishing pCR from non-pCR. Regarding kep and ve , significant differences were also observed between the pCR and non-pCR groups (P = 0.02, 0.01, respectively). The mean K(trans) , kep , and ve values post-CRT were lower in the pCR group than in the non-pCR group, although there was no significant difference (P = 0.10 (0.04,0.16), 0.11 (0.07,0.26), 0.10 (0.06,0.23), respectively). CONCLUSION: Before neoadjuvant chemoradiotherapy in rectal cancer, DCE-MRI can distinguish between complete and incomplete response using a K(trans) threshold of 0.66 with a sensitivity of 100%.

Multi-task reconstruction network for synthetic diffusion kurtosis imaging: Predicting neoadjuvant chemoradiotherapy response in locally advanced rectal cancer.

PURPOSE: To assess the feasibility and clinical value of synthetic diffusion kurtosis imaging (DKI) generated from diffusion weighted imaging (DWI) through multi-task reconstruction network (MTR-Net) for tumor response prediction in patients with locally advanced rectal cancer (LARC). METHODS: In this retrospective study, 120 eligible patients with LARC were enrolled and randomly divided into training and testing datasets with a 7:3 ratio. The MTR-Net was developed for reconstructing Dapp and Kapp images from apparent diffusion coefficient (ADC) images. Tumor regions were manually segmented on both true and synthetic DKI images. The synthetic image quality and manual segmentation agreement were quantitatively assessed. The support vector machine (SVM) classifier was used to construct radiomics models based on the true and synthetic DKI images for pathological complete response (pCR) prediction. The prediction performance for the models was evaluated by the receiver operating characteristic (ROC) curve analysis. RESULTS: The mean squared error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM) for tumor regions were 0.212, 24.278, and 0.853, respectively, for the synthetic Dapp images and 0.516, 24.883, and 0.804, respectively, for the synthetic Kapp images. The Dice similarity coefficient (DSC), positive predictive value (PPV), sensitivity (SEN), and Hausdorff distance (HD) for the manually segmented tumor regions were 0.786, 0.844, 0.755, and 0.582, respectively. For predicting pCR, the true and synthetic DKI-based radiomics models achieved area under the curve (AUC) values of 0.825 and 0.807 in the testing datasets, respectively. CONCLUSIONS: Generating synthetic DKI images from DWI images using MTR-Net is feasible, and the efficiency of synthetic DKI images in predicting pCR is comparable to that of true DKI images.

TGF-ß1/Smad3 Signaling Is Required to Alleviate Fluoride-Induced Enamel Hypomineralization.

Excessive fluoride intake during enamel development can affect enamel mineralization, leading to dental fluorosis. However, its potential mechanisms remain largely unexplored. In the present study, we aimed to investigate the impact of fluoride on the expressions of RUNX2 and ALPL during mineralization and the effect of TGF-ß1 administration on fluoride treatment. A dental fluorosis model of newborn mice and an ameloblast cell line ALC were both used in the present study. The mice of the NaF group, including the mothers and newborns, were fed with water containing 150 ppm NaF after delivery to induce dental fluorosis. The mandibular incisors and molars showed significant abrasion in the NaF group. Immunostaining, qRT-PCR, and Western blotting analysis indicated that exposure to fluoride markedly down-regulated RUNX2 and ALPL in mouse ameloblasts and ALCs. Besides, fluoride treatment significantly decreased the mineralization level detected by ALP staining. Furthermore, exogenous TGF-ß1 up-regulated RUNX2 and ALPL and promoted mineralization, while the addition of SIS3 could block such TGF-ß1-induced up-regulation. In TGF-ß1 conditional knockout mice, the immunostaining of RUNX2 and ALPL was weaker compared with wild-type mice. Exposure to fluoride inhibited the expressions of TGF-ß1 and Smad3. Co-treatment of TGF-ß1 and fluoride up-regulated RUNX2 and ALPL compared with the fluoride alone treatment, promoting mineralization. Collectively, our data indicated that TGF-ß1/Smad3 signaling pathway was necessary for the regulatory effects of fluoride on RUNX2 and ALPL, and the fluoride-induced suppression of ameloblast mineralization was mitigated by activating TGF-ß1/Smad3 signaling pathway.

Magnetic resonance imaging-based radiomics analysis for prediction of treatment response to neoadjuvant chemoradiotherapy and clinical outcome in patients with locally advanced rectal cancer: A large multicentric and validated study.

Our study investigated whether magnetic resonance imaging (MRI)-based radiomics features could predict good response (GR) to neoadjuvant chemoradiotherapy (nCRT) and clinical outcome in patients with locally advanced rectal cancer (LARC). Radiomics features were extracted from the T2 weighted (T2W) and Apparent diffusion coefficient (ADC) images of 1070 LARC patients retrospectively and prospectively recruited from three hospitals. To create radiomic models for GR prediction, three classifications were utilized. The radiomic model with the best performance was integrated with important clinical MRI features to create the combined model. Finally, two clinical MRI features and ten radiomic features were chosen for GR prediction. The combined model, constructed with the tumor size, MR-detected extramural venous invasion, and radiomic signature generated by Support Vector Machine (SVM), showed promising discrimination of GR, with area under the curves of 0.799 (95% CI, 0.760-0.838), 0.797 (95% CI, 0.733-0.860), 0.754 (95% CI, 0.678-0.829), and 0.727 (95% CI, 0.641-0.813) in the training and three validation datasets, respectively. Decision curve analysis verified the clinical usefulness. Furthermore, according to Kaplan-Meier curves, patients with a high likelihood of GR as determined by the combined model had better disease-free survival than those with a low probability. This radiomics model was developed based on large-sample size, multicenter datasets, and prospective validation with high radiomics quality score, and also had clinical utility.

Study protocol of short-course radiotherapy combined with CAPOX and PD-1 inhibitor for locally advanced colon cancer: a randomised, prospective, multicentre, phase II trial (TORCH-C).

INTRODUCTION: The preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC. METHODS AND ANALYSIS: TORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12). TRIAL REGISTRATION NUMBER: NCT05732493.

Radiomic score for lung nodules as a prognostic biomarker in locally advanced rectal cancer patients: A bi-institutional study.

BACKGROUND: Undetermined lung nodules are common in locally advanced rectal cancer (LARC) and lack precise risk stratification. This study aimed to develop a radiomic-based score (Rad-score) to distinguish metastasis and predict overall survival (OS) in patients with LARC and lung nodules. METHODS: Retrospective data from two institutions (July 10, 2006-September 24, 2015) was used to develop and validate the Rad-score for distinguishing lung nodule malignancy. The prognostic value of the Rad-score was investigated in LARC cohorts, leading to the construction and validation of a clinical and radiomic score (Cli-Rad-score) that incorporates both clinical and radiomic information for the purpose of improving personalized clinical prognosis prediction. Descriptive statistics, survival analysis, and model comparison were performed to assess the results. RESULTS: The Rad-score demonstrated great performance in distinguishing malignancy, with C-index values of 0.793 [95% CI: 0.729-0.856] in the training set and 0.730 [95% CI: 0.666-0.874] in the validation set. In independent LARC cohorts, Rad-score validation achieved C-index values of 0.794 [95% CI: 0.737-0.851] and 0.747 [95% CI: 0.615-0.879]. Regarding prognostic prediction, Rad-score effectively stratified patients. Cli-Rad-score outperformed the clinicopathological information alone in risk stratification, as evidenced by significantly higher C-index values (0.735 vs. 0.695 in the internal set and 0.618 vs. 0.595 in the external set). CONCLUSIONS: CT-based radiomics could serve as a reliable and powerful tool for lung nodule malignancy distinction and prognostic prediction in LARC patients. Rad-score predicts prognosis independently. Incorporation of Cli-Rad-score significantly enhances the persionalized clinical prognostic capacity in LARC patients with lung nodules.

Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

Predictors of Medical Students' Perceptions of Psilocybin-Assisted Therapy for Use in Medical Practice.

Background Psilocybin use, along with other psychedelics, has seen an increased interest among professionals in the medical community due to its potential therapeutic benefits for psychiatric disorders, substance use disorders (SUD), and palliative care. While it is certain that more research is necessary as psychedelic-assisted therapy becomes more prevalent, it will most likely be future physicians at the forefront of this neoteric care. Currently, physicians receive minimal training because of psilocybin's contextual information and its current enlistment as a Schedule 1 drug per the United States Drug Enforcement Administration. Schedule 1 drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse. As a rule, formal education on psilocybin is not included in medical school curricula, and very little is known about how medical students perceive it. The aim of this study was thus to assess current medical students' perceptions of their knowledge, concern for possible negative effects, and perceptions about medical psilocybin to provide a deeper understanding of which factors may predict their overall perceptions of its future therapeutic use. Methods Medical students' knowledge, concern for potential adverse effects, and perceptions of medical psilocybin were investigated using a cross-sectional survey study design. Data were collected in January 2023 from a convenience sample of United States medical students in years one to four of their program using a 41-item anonymous quantitative online survey. Multivariate linear regression modeling was performed to determine if perceived knowledge and beliefs about legalization would predict medical students' attitudes about psilocybin use for therapeutic purposes. Results Two hundred and thirteen medical students completed the survey. Seventy-three percent (n=155) were osteopathic medical students (OMS), and 27% (n=58) were allopathic medical students (MDS). Regression modeling produced a statistically significant equation: (F(3, 13) = 78.858, p < .001), with an R2 = 0.573 (adjusted R2 = 0.567), indicating that greater (perceived) knowledge about medical psilocybin, less concern for its possible adverse effects, and greater belief in the legalization of psilocybin for recreational use significantly contributed to positive perceptions of psilocybin use in medical practice. Conclusions In this sample, medical students with greater self-assessment of their knowledge about medical psilocybin, less concern for its potential adverse effects, and more positive views about recreational psilocybin legalization predicted positive attitudes about its medical use. Interestingly, although some participants had positive perceptions about the legalization of psilocybin for medical use, endorsing its legalization for recreation was related to greater positive attitudes toward medical psilocybin in general, a finding that appears to be somewhat counterintuitive. More research is warranted to further explore medical trainees' attitudes toward it, as psilocybin is a promising therapeutic intervention. If medicinal psilocybin continues to gain attention among patients and physicians alike, it will be imperative to evaluate its therapeutic efficacy, proper use, dosing, and potential for negative effects, in addition to preparing students to endorse therapeutic psilocybin when warranted.

Radiomics for predicting survival in patients with locally advanced rectal cancer: a systematic review and meta-analysis.

Background: Radiomics has recently received considerable research attention for providing potential prognostic biomarkers for locally advanced rectal cancer (LARC). We aimed to comprehensively evaluate the methodological quality and prognostic prediction value of radiomic studies for predicting survival outcomes in patients with LARC. Methods: The Cochrane, Embase, Medline, and Web of Science databases were searched. The radiomics quality score (RQS), Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) checklist, the Image Biomarkers Standardization Initiative (IBSI) guideline, and the Prediction Model Risk of Bias Assessment Tool were used to assess the quality of the selected studies. A further meta-analysis of hazard ratio (HR) regarding disease-free survival (DFS) and overall survival (OS) was performed. Results: Among the 358 studies reported, 15 studies were selected for our review. The mean RQS score was 7.73±4.61 (21.5% of the ideal score of 36). The overall TRIPOD adherence rate was 64.4% (251/390). Most of the included studies (60%) were assessed as having a high risk of bias (ROB) overall. The pooled estimates of the HRs were 3.14 [95% confidence interval (CI): 2.12-4.64, P<0.01] for DFS and 3.36 (95% CI: 1.74-6.49, P<0.01) for OS. Conclusions: Radiomics has potential to noninvasively predict outcome in patients with LARC. However, the overall methodological quality of radiomics studies was low, and the adherence to the TRIPOD statement was moderate. Future radiomics research should put a greater focus on enhancing the methodological quality and considering the influence of higher-order features on reproducibility in radiomics.

Breast Fibroglandular Tissue Segmentation for Automated BPE Quantification With Iterative Cycle-Consistent Semi-Supervised Learning.

Background Parenchymal Enhancement (BPE) quantification in Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) plays a pivotal role in clinical breast cancer diagnosis and prognosis. However, the emerging deep learning-based breast fibroglandular tissue segmentation, a crucial step in automated BPE quantification, often suffers from limited training samples with accurate annotations. To address this challenge, we propose a novel iterative cycle-consistent semi-supervised framework to leverage segmentation performance by using a large amount of paired pre-/post-contrast images without annotations. Specifically, we design the reconstruction network, cascaded with the segmentation network, to learn a mapping from the pre-contrast images and segmentation predictions to the post-contrast images. Thus, we can implicitly use the reconstruction task to explore the inter-relationship between these two-phase images, which in return guides the segmentation task. Moreover, the reconstructed post-contrast images across multiple auto-context modeling-based iterations can be viewed as new augmentations, facilitating cycle-consistent constraints across each segmentation output. Extensive experiments on two datasets with various data distributions show great segmentation and BPE quantification accuracy compared with other state-of-the-art semi-supervised methods. Importantly, our method achieves 11.80 times of quantification accuracy improvement along with 10 times faster, compared with clinical physicians, demonstrating its potential for automated BPE quantification. The code is available at https://github.com/ZhangJD-ong/Iterative-Cycle-consistent-Semi-supervised-Learning-for-fibroglandular-tissue-segmentation.

Progress in nanoparticle-based regulation of immune cells.

Immune cells are indispensable defenders of the human body, clearing exogenous pathogens and toxicities or endogenous malignant and aging cells. Immune cell dysfunction can cause an inability to recognize, react, and remove these hazards, resulting in cancers, inflammatory diseases, autoimmune diseases, and infections. Immune cells regulation has shown great promise in treating disease, and immune agonists are usually used to treat cancers and infections caused by immune suppression. In contrast, immunosuppressants are used to treat inflammatory and autoimmune diseases. However, the key to maintaining health is to restore balance to the immune system, as excessive activation or inhibition of immune cells is a common complication of immunotherapy. Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors, nucleic acid, and proteins. Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function. In this review, we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.

Predictors of Pharmacy Students' Attitudes About the Therapeutic Use of Psilocybin.

Background Psilocybin has been studied for its potential therapeutic benefits, particularly for the treatment of psychiatric disorders such as anxiety, depression, and obsessive-compulsive disorder. While more research is needed as psilocybin-assisted therapy becomes more prevalent, future pharmacists will probably be involved at some level. At present, pharmacists receive minimal training on psilocybin, and little is known about their attitudes toward its use for medical purposes. Findings from recent clinical studies have attempted to establish the safety and medical efficacy of psilocybin, leading to an increased interest in therapeutic psilocybin use in the United States. This study aimed to assess if self-assessed knowledge of psilocybin, concerns about adverse effects, and opinions about legalization will make statistically significant contributions to pharmacy students' attitudes about psilocybin use in practice. Methods Pharmacy students' self-assessed knowledge, concern for potential adverse effects, and perceptions of psilocybin were investigated using a cross-sectional survey study design. Data were collected from March 13 to April 7, 2023, from a convenience sample of 161 pharmacy students enrolled in an accredited pharmacy school in the southern region of the United States using a 41-item anonymous quantitative survey developed by the researchers that contained validated scales. The survey was delivered electronically. Multiple regression modeling was conducted to determine if self-assessed knowledge, concerns for adverse effects, and opinions about legalization would predict pharmacy students' attitudes about therapy-assisted psilocybin use. This study was approved by the Institutional Review Board of the authors' university. Results The mean age of the 161 participants was 24 years (SD = 2.981; range 20-40 years). Twenty (12.4%) participants reported previous use of psilocybin for recreational purposes and two (1.2%) reported having used it therapeutically. Many (n =121; 75.2%) of the participants believed that psilocybin should be decriminalized for therapeutic use, but only 54 (33.5%) thought it should be decriminalized for recreational use. A multiple linear regression model predicting "attitudes about psilocybin" (dependent variable) produced significant results: (F(4, 122) = 40.575, p < 0.001), with an R2 = 0.571 (adjusted R2 = 0.557). Greater "self-assessed knowledge about psilocybin," less "concern about possible negative effects," greater "belief in the decriminalization of psilocybin for recreational use," and greater "belief in the decriminalization of psilocybin for therapeutic use" (all independent variables) were associated with more positive perceptions about medical psilocybin. The percentage of variance in the scores accounted for by the model was 57%. Conclusions Pharmacy students may lack information and training regarding psilocybin and report a desire to learn more about it. Their attitudes about medical psilocybin may be driven by this desire to learn in addition to concerns about adverse effects and legalization issues. Due to the dearth of published information regarding the knowledge and acceptance of psilocybin as a viable treatment option for patients, further research in psychedelic-assisted treatments may be warranted.

Analysis of Chinese Machine Translation Training Based on Deep Learning Technology.

With the advent of the information age, people can establish good communication through Internet technology. Mechanical translation has become a key means to solve people's communication problems. However, there are still obstacles to communication between different languages. In order to solve this problem, this paper uses existing neural network technology to the English-Chinese bidirectional machine translation model in the field of marine science and technology. Based on deep learning technology, we collect Chinese and English abstracts and partial full texts of Chinese and English papers with marine science and technology as the key words and build a professional corpus in English and Chinese about marine science and technology. In the Chinese-English bidirectional translation model, the local weight sharing is introduced into the Chinese encoder and the English encoder, and the output of the Chinese encoder sublayer and the English encoder sublayer is fused as the output of the respective encoders, and the performance of the translation model is evaluated using the BLEU parameters. Through the training of the translation model, compared with the transformer model, the BLEU value of the model with local weight sharing and encoder sublayer fusion output is improved by 1.6 and 3.8 in the Chinese-English and English-Chinese translation directions, respectively. The PPL values in the Chinese-English and English-Chinese translation directions decreased by 18.72% and 14.62%, respectively. We demonstrate the effectiveness of the language translation model. Experiments show that the research on machine language adaptive technology based on deep learning can more smoothly realize the two-way translation of literature in the field of marine science and technology. Compared with traditional mechanical translation, this paper proposes a translation model based on the deep neural algorithm, which improves the effect of model training by constructing a Chinese-English corpus with the theme of marine science and technology.

Effect of TiC on Microstructure and Properties of Wear-Resistant Mo2FeB2 Claddings.

Alloy blocks with different TiC content were designed, and Mo2FeB2 cermets were prepared by carbon arc surfacing process. The interaction law of TiC content and the microstructure, phase, composition, hardness and wear resistance of the cladding were studied in detail by the combination of experiment and theoretical analysis. On the other hand, the phase transition process of the weldpool is theoretically analyzed by thermodynamic calculation method. XRD test results show that in addition to Mo2FeB2 synthesized in situ, the cladding also forms phases such as TiC, CrB, MoB and Fe-Cr. The number of Mo2FeB2 hard phases gradually increases when TiC content varies from 0% to 15%. The average microhardness of the cladding with 0%, 5%, 10%, and 15% TiC was 992 HV0.5, 1035 HV0.5, 1018 HV0.5 and 689 HV0.5, respectively, with 5% TiC being the largest. Moreover, the cladding with 5% TiC content has excellent wear resistance, which is 14.6 times that of the substrate.

Percentage of Tumor Invasion at Pretreatment High-Resolution Magnetic Resonance Imaging: Associating With Aggressive and Tumor Response in Chinese T3 Rectal Cancer-Preliminary Results.

Purpose: The purpose of the study was to assess the ability of percentage of tumor invasion (PTI) of T3 rectal cancer on pretreatment MRI as an imaging biomarker to reflect aggressiveness and to predict tumor response after neoadjuvant chemoradiation (NCRT) in Chinese population. Methods: A total of 107 Chinese rectal cancer patients who underwent pretreatment MRI staging as T3 were included. The extramural depth of tumor invasion (EMD), the distance between outer border of muscularis propria (MP) and mesorectal fascia (MRF) we called "thickness of the mesorectum (TM)") at the same slice and direction were measured at pretreatment MRI, and PTI was equal to EMD/TM, was calculated. The EMD and PTI of subgroups based on pretreatment CEA, CA19-9 levels; N category and pathological complete response (pCR) were compared. The parameters, which described tumor invasion, were compared between pCR and non-pCR group. Student t-tests and logistic analysis were applied. Results: The pretreatment PTI was higher in CEA ≥5.2 ng/ml patients (58.52% ± 27.68%) than in CEA <5.2 ng/ml patients (47.27% ± 24.15%) (p = 0.034). The pretreatment EMD in non-pCR group (7.21 ± 2.85 mm) was higher than in pCR group (6.14 ± 3.56 mm) (p = 0.049). The pretreatment PTI in non-pCR group (57.4% ± 26.4%) was higher than in pCR group (47.3% ± 29.1%) (p = 0.041). Compared with patients with PTI ≥50%, MRF (+), more patients with PTI <50%, MRF (-) showed pCR (OR = 8.44, p = 0.005; OR = 6.32, p = 0.024). Conclusion: The PTI obtained at pretreatment MRI may serve as an imaging biomarker to reflect tumor aggressiveness and predict which T3 rectal cancer patients may benefit from NCRT in Chinese population.