Background and purpose:
Adaptive radiotherapy (ART) can compensate for the dosimetric impacts induced by anatomic and geometric variations in patients with nasopharyngeal carcinoma (NPC); Yet, the ...need for ART can only be assessed during the radiation treatment and the implementation of ART is resource intensive. Therefore, we aimed to determine tumoral biomarkers using pre-treatment MR images for predicting ART eligibility in NPC patients prior to the start of treatment.
Methods:
Seventy patients with biopsy-proven NPC (Stage II-IVB) in 2015 were enrolled into this retrospective study. Pre-treatment contrast-enhanced T1-w (CET1-w), T2-w MR images were processed and filtered using Laplacian of Gaussian (LoG) filter before radiomic features extraction. A total of 479 radiomics features, including the first-order (
n
= 90), shape (
n
= 14), and texture features (
n
= 375), were initially extracted from Gross-Tumor-Volume of primary tumor (GTVnp) using CET1-w, T2-w MR images. Patients were randomly divided into a training set (
n
= 51) and testing set (
n
= 19). The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied for radiomic model construction in training set to select the most predictive features to predict patients who were replanned and assessed in the testing set. A double cross-validation approach of 100 resampled iterations with 3-fold nested cross-validation was employed in LASSO during model construction. The predictive performance of each model was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC).
Results:
In the present cohort, 13 of 70 patients (18.6%) underwent ART. Average AUCs in training and testing sets were 0.962 (95%CI: 0.961–0.963) and 0.852 (95%CI: 0.847–0.857) with 8 selected features for CET1-w model; 0.895 (95%CI: 0.893–0.896) and 0.750 (95%CI: 0.745–0.755) with 6 selected features for T2-w model; and 0.984 (95%CI: 0.983–0.984) and 0.930 (95%CI: 0.928–0.933) with 6 selected features for joint T1-T2 model, respectively. In general, the joint T1-T2 model outperformed either CET1-w or T2-w model alone.
Conclusions:
Our study successfully showed promising capability of MRI-based radiomics features for pre-treatment identification of ART eligibility in NPC patients.
Recent literature has suggested that tumor sidedness in colorectal cancer (CRC) is an independent prognostic and potentially predictive marker of survival. The aims of the study were to determine the ...prognostic significance of tumor sidedness in colorectal cancer patients undergoing primary tumor resection and to assess associated tumor biology.
A total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012 were analyzed for association with tumor biologic factors and with overall survival. Metastatic patients were excluded from analysis.
Left sided CRCs were associated with a number of additional key prognostic markers including BRAFV600E wildtype status (P<0.001), mismatch repair proficiency (p<0.001), absence of peritumoral lymphocytic response (p = 0.001), high lymphocyte-to-monocyte ratio (p<0.001) and low neutrophil-to-lymphocyte ratio (p<0.001). In primary analysis with 3067 patients, there was no statistical difference in sidedness in the univariate analysis (p = 0.291). Three further subgroup analyses were performed. In the first subgroup, only stage III patients were analyzed. In the second, patients with mismatch repair deficiency were removed. In the third, additional clinicopathologic variables known to be independently prognostic were added into analysis. In all three subgroup analyses tumor sidedness was not an independent prognostic marker.
Tumor sidedness was not an independent prognostic marker of CRC. However, right sided CRCs were associated with several key independent prognostic markers supporting a hypothesis that tumor sidedness is a surrogate for other biomarkers.
Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine ...methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established. We performed full-length mRNA sequencing on CHL1 and A375 melanoma cell lines treated with the CDK4/6 inhibitor palbociclib and the PRMT5 inhibitor GSK3326595 and analysed data for differential gene expression and differential pre-mRNA splicing induced by these agents. Changes in gene expression and RNA splicing were more extensive under PRMT5 inhibition than under CDK4/6 inhibition. Although PRMT5 inhibition and CDK4/6 inhibition induced common RNA splicing events and gene expression profiles, the majority of events induced by CDK4/6 inhibition were distinct. Our findings indicate CDK4/6 has the ability to regulate alternative splicing in a manner that is distinct from PRMT5 inhibition, resulting in divergent changes in gene expression under each therapy.
Inflammation is a hallmark of cancer whose activity is modulated within the tumor microenvironment by low tumoral pH. Recent evidence in the literature has suggested a link between low serum ...bicarbonate, low tumoral pH and cancer related inflammation. There is however little clinical evidence in human patients regarding the prognostic role of serum bicarbonate. Therefore, the primary aim of this study was to investigate the short and long-term prognostic utility of serum bicarbonate in colorectal cancer (CRC) patients undergoing resection of their primary tumor. The study also aimed to investigate the association of serum bicarbonate with known markers of systemic inflammation.
A total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012. Of these, 2223 stage I-IV patients had available data for analysis. The association of serum bicarbonate with overall survival was assessed using univariate and multivariate cox regression analyses. The association of bicarbonate with other clinicopathological variables was assessed by chi squared and Fisher's exact tests.
Serum bicarbonate was associated with peri-operative mortality in multivariate analysis (p<0.001). Age (p = 0.004), grade (p = 0.043), creatinine (p = 0.036) and sodium (p = 0.036) were also markers associated with peri-operative mortality. For long term survival at 5 years, bicarbonate was significantly associated with overall survival in univariate analysis (p<0.001) but was not significant in multivariate analysis (p = 0.075). In exploratory analysis, serum bicarbonate was found to be significantly associated with the lymphocyte-to-monocyte ratio (p<0.001) and neutrophil-to-lymphocyte ratio (p<0.001).
In peri-operative colorectal cancer patients, serum bicarbonate was associated with 30-day survival but not 5-year survival.
Adequate empirical antimicrobial coverage is instrumental in clinical management of community-onset Enterobacteriaceae bacteraemia in areas with high ESBL prevalence, while balancing the risk of ...carbapenem overuse and emergence of carbapenem-resistant organisms. It is unknown whether machine learning offers additional advantages to conventional statistical methods in prediction of ESBL production. To develop a validated model to predict ESBL production in Enterobacteriaceae causing community-onset bacteraemia. 5625 patients with community-onset bacteraemia caused by
Escherichia coli
,
Klebsiella
species and
Proteus mirabilis
during 1 January 2015–31 December 2019 from three regional hospitals in Hong Kong were included in the analysis, after exclusion of blood cultures obtained beyond 48 h of admission. The prevalence of ESBL-producing Enterobacteriaceae was 23.7% (1335/5625). Deep neural network and other machine learning algorithms were compared against conventional statistical model via multivariable logistic regression. Primary outcomes compared consisted of predictive model area under curve of receiver-operator characteristic curve (AUC), and macro-averaged F1 score. Secondary outcomes included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Deep neural network yielded an AUC of 0.761 (95% CI 0.725–0.797) and F1 score of 0.661 (95% CI 0.633–0.689), which was superior to logistic regression (AUC 0.667 (95% CI 0.627–0.707), F1 score 0.596 (95% CI 0.567–0.625)). Deep neural network had a specificity of 91.5%, sensitivity of 37.5%, NPV of 82.5%, and PPV of 57.9%. Deep neural network is superior to logistic regression in predicting ESBL production in Enterobacteriaceae causing community-onset bacteraemia in high-ESBL prevalence area. Machine learning offers clinical utility in guiding judicious empirical antibiotics use.
Neural stem cells (NSCs) derived from human pluripotent stem cells (hPSCs) are considered a major cell source for reconstructing damaged neural circuitry and enabling axonal regeneration. However, ...the microenvironment at the site of spinal cord injury (SCI) and inadequate intrinsic factors limit the therapeutic potential of transplanted NSCs. Here, it is shown that half dose of SOX9 in hPSCs‐derived NSCs (hNSCs) results in robust neuronal differentiation bias toward motor neuron lineage. The enhanced neurogenic potency is partly attributed to the reduction of glycolysis. These neurogenic and metabolic properties retain after transplantation of hNSCs with reduced SOX9 expression in a contusive SCI rat model without the need for growth factor‐enriched matrices. Importantly, the grafts exhibit excellent integration properties, predominantly differentiate into motor neurons, reduce glial scar matrix accumulation to facilitate long‐distance axon growth and neuronal connectivity with the host as well as dramatically improve locomotor and somatosensory function in recipient animals. These results demonstrate that hNSCs with half SOX9 gene dosage can overcome extrinsic and intrinsic barriers, representing a powerful therapeutic potential for transplantation treatments for SCI.
Spinal cord injury (SCI) causes nerve damage and the injury environment favors SOX9 expression, inhibiting neurogenesis and promoting astrocytic scar formation. Grafting of hNSCs with a half dose of SOX9 acquires unique intrinsic capacity resulting in enhanced neurogenesis, long axonal growth, and establishing neuronal connectivity with the host that restores locomotor activity and somatosensory function of the SCI animals.
Recent advancements in Artificial-Intelligence-based computer vision systems demonstrated impressive image and pattern recognition capabilities. A special class of neural networks known as ...Convolutional Neural Networks are used in a wide variety of computer vision tasks such as image classification, object detection and autonomous driving. There is a huge potential to adopt such technology in the domain of pathology. Image data in pathology are considerably larger in size than in typical image recognition problems. Dissecting the image into smaller bits, known as tiling, are often carried out. This paper aims to compare and contrast common model architectures and input tile sizes systematically and find the optimal configuration in the context of lung cancer classification problems.
A dataset composed of 87 annotated whole slide images of lung cancer specimens were collected and annotated by two pathologists. Annotated areas were grouped into four classes (Tumor area, Non-tumor area, Necrosis area, and Immune cells). Annotations were converted into labelled tiles at different tile sizes, from 296 to 10000 pixels, (74–2500 μm). The problem was framed as a supervised 4-class classification problem using deep learning.
For each tile size, three models, VGG19, InceptionResnetv2 and EfficientNet b3, were trained. Model performances were measured on holdout dataset using standard quantitative metrics including F1-score and AUC-ROC. Our best model instance with tile size at 500 × 500 pixels (125 × 125 μm) achieved an F1-score at 0.9685 and AUC-ROC score at 0.9627.
Our results showed that tile size had a significant impact on model performance. The optimal tile size was between 500 and 1000 pixel (125–250 μm) after both quantitative and qualitative assessments. VGG19 marginally outperformed other model architectures.
Background: Early intensive care unit (ICU) protocolized rehabilitative programs have been described previously, yet with differing starting time points and mostly on mechanically ventilated ...patients. We extended the concept to all admitted ICU patients and investigate the efficacy of early mobilization in improving mobility of the critically ill, address issues surrounding the timing and intensity of an early rehabilitative program.Methods: Prospective cohorts of patients admitted consecutively before-and-after (control, n=92; intervention, n=90) the introduction of an early mobilization program in a single center, general hospital ICU. Improvement in mobility as assessed by ICU mobility score, on ICU admission and upon ICU discharge, was measured as a primary outcome.Results: Those receiving early mobilization in the intensive care unit had higher ICU mobility score (2.63; 95% confidence interval, 0.65–4.61; P<0.001) upon discharge from the intensive care, with earlier out of bed mobilization on day 5 compared to the control group of day 21 (P<0.001). No differences were found in terms of mortality, intensive care hospitalization and subsequent hospitalization duration after discharge from ICU.Conclusions: Here, we report that improvement in mobility score earlier in the course of intensive care hospitalization with the introduction of a protocolized early rehabilitative program.
PDF
