Deep learning-based lung segmentation and automatic regional template in chest X-ray images for pediatric tuberculosis

Tuberculosis (TB) is still considered a leading cause of death and a substantial threat to global child health. Both TB infection and disease are curable using antibiotics. However, most children who die of TB are never diagnosed or treated. In clinical practice, experienced physicians assess TB by examining chest X-rays (CXR). Pediatric CXR has specific challenges compared to adult CXR, which makes TB diagnosis in children more difficult. Computer-aided diagnosis systems supported by Artificial Intelligence have shown performance comparable to experienced radiologist TB readings, which could ease mass TB screening and reduce clinical burden. We propose a multi-view deep learning-based solution which, by following a proposed template, aims to automatically regionalize and extract lung and mediastinal regions of interest from pediatric CXR images where key TB findings may be present. Experimental results have shown accurate region extraction, which can be used for further analysis to confirm TB finding presence and severity assessment. Code publicly available at https://github.com/dani-capellan/pTB_LungRegionExtractor.Comment: This work has been accepted at the SPIE Medical Imaging 2023, Image Processing conferenc

Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays

CpG island arrays represent a high-throughput epigenomic discovery platform to identify global disease-specific promoter hypermethylation candidates along bladder cancer progression. DNA obtained from 10 pairs of invasive bladder tumours were profiled vs their respective normal urothelium using differential methylation hybridisation on custom-made CpG arrays (n=12 288 clones). Promoter hypermethylation of 84 clones was simultaneously shown in at least 70% of the tumours. SOX9 was selected for further validation by bisulphite genomic sequencing and methylation-specific polymerase chain reaction in bladder cancer cells (n=11) and primary bladder tumours (n=101). Hypermethylation was observed in bladder cancer cells and associated with lack of gene expression, being restored in vitro by a demethylating agent. In primary bladder tumours, SOX9 hypermethylation was present in 56.4% of the cases. Moreover, SOX9 hypermethylation was significantly associated with tumour grade and overall survival. Thus, this high-throughput epigenomic strategy has served to identify novel hypermethylated candidates in bladder cancer. In vitro analyses supported the role of methylation in silencing SOX9 gene. The association of SOX9 hypermethylation with tumour progression and clinical outcome suggests its relevant clinical implications at stratifying patients affected with bladder cancer

A simple method for detecting oncofetal chondroitin sulfate glycosaminoglycans in bladder cancer urine

Proteoglycans in bladder tumors are modified with a distinct oncofetal chondroitin sulfate (ofCS) glycosaminoglycan that is normally restricted to placental trophoblast cells. This ofCS-modification can be detected in bladder tumors by the malarial VAR2CSA protein, which in malaria pathogenesis mediates adherence of parasite-infected erythrocytes within the placenta. In bladder cancer, proteoglycans are constantly shed into the urine, and therefore have the potential to be used for detection of disease. In this study we investigated whether recombinant VAR2CSA (rVAR2) protein could be used to detect ofCS-modified proteoglycans (ofCSPGs) in the urine of bladder cancer patients as an indication of disease presence. We show that ofCSPGs in bladder cancer urine can be immobilized on cationic nitrocellulose membranes and subsequently probed for ofCS content by rVAR2 protein in a custom-made dot-blot assay. Patients with high-grade bladder tumors displayed a marked increase in urinary ofCSPGs as compared to healthy individuals. Urine ofCSPGs decreased significantly after complete tumor resection compared to matched urine collected preoperatively from patients with bladder cancer. Moreover, ofCSPGs in urine correlated with tumor size of bladder cancer patients. These findings demonstrate that rVAR2 can be utilized in a simple biochemical assay to detect cancer-specific ofCS-modifications in the urine of bladder cancer patients, which may be further developed as a noninvasive approach to detect and monitor the disease

Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer

PURPOSE: Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers. EXPERIMENTAL DESIGN: Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples. RESULTS: We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting. CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening

Bladder Cancer Tissue-Based Biomarkers

This review aims to provide a practical update regarding the current role of tissue-based biomarkers in bladder cancer. Their prognostic and predictive role both in non-muscle-invasive (NMIBC) and in muscle-invasive disease (MIBC) has been reviewed with particular focus to their use in clinical practice. In summary, the literature on the prediction of disease recurrence in NMIBC is inconclusive, and there is little information on prediction of response to intravesical bacillus Calmette-Guerin (BCG). Concerning disease progression, external prospective validation studies suggest that FGFR3 mutation status and gene signatures may improve models that are based only on clinicopathologic information. In MIBC, tissue-based biomarkers are increasingly important, since they may predict the response to systemic chemotherapy and immunotherapy. In particular, the advent of molecular characterization promises to revolutionize the paradigm of decision-making in the treatment of MIBC. Molecular subtyping has been shown to improve the prediction of pathological stage at RC and to predict the response to systemic chemotherapy and immunotherapy. However, external and prospective validations are warranted to confirm these preliminary findings. Several different tissue-based biomarkers such as PD-1/PD-L1 expression, tumor mutational burden, and the analysis of tumor microenvironment, may in future play a role in selecting patients for systemic immunotherapy. However, to date, no pretreatment recommendations can be definitively made on the basis of any molecular predictors. In conclusion, despite the potential of tissue-based biomarkers, their use in bladder cancer should be limited to experimental settings

In Urinary Incontinence Rehabilitation treated there is clinical improvement and decrease in electromyographic values with age

Introduction. The pelvic floor (SP) is formed by a set of muscular structures, which together with the fascias and ligaments make up the pelvic diaphragm. The function of the SP is the support of the pelvic organs and maintain a correct position of these, influencing urination, intercourse, childbirth and defecation. A weakness or injury of these structures predisposes to the appearance of a symptomatology that can occur in isolation or in combination, one of the main problems being UI urinary incontinence and pelvic organ prolapse POP(1). It is estimated a prevalence of UI in adults between 15 and 30%, presenting in all ages, detecting a progressive increase as age advances and POP in 50% of women who have had at least one vaginal delivery.(2-4) Objectives. Evaluate both clinically and electromyographically a group of women diagnosed with UI and / or POP, after performing a rehabilitative treatment and one year of follow-up. Material and methods. This is a longitudinal, analytical observational study of a prospective cohort type, where women aged between 18 and 85 years were evaluated in a period of time between January 2008 and January 2012. The variables used In the present study, they differed in clinical and electromyographic variables. For the evaluation of the MSP an intravaginal surface EMG was performed, which consisted in a quantitative muscular diagnostic evaluation and in which some known muscle parameters were obtained. A rehabilitation treatment protocol was designed, following the guidelines established according to scientific evidence. Results. In the present study a total of 241 women were included, whose average age was 50.4 years (SD = 12.3), the mean BMI was 27.7 kg / m2, the average duration of symptoms was 6.9 years (SD = 8.9). 88% of women consulted by IU and 29% by POP. The most frequent diagnosis was that of IUM in 118 women (49.0%), followed by SUI in 65 women (27.0%). 49.4% were menopausal, 85.1% had vaginal delivery, only 2.9% were nulliparous. The mean number of deliveries was 2.4 (SD = 1.1) and in 89% of the cases they suffered episiotomy. 92.1% of the women in the sample had urine leaks, 96.4% of them related to the effort. Of the total sample, 189 patients (78.4%) performed treatment in the SP Unit. The average number of sessions was 14.2 (SD = 7.8). At the end of the rehabilitation treatment, 92.3% of the patients reported finding themselves better, 42% of the women presented voiding urgencies, and 47.6% suffered from UUI. The analysis of repeated measures of the electromyographic variables before and after the rehabilitation treatment and during the year of follow-up, statistically significant increases were observed in the maximum values of the phasic contractions, the average values of the tonic contractions, the duration of the tonic contraction selected and the total power of the ttonic contraction. When the means of the maximum values of the phasic contractions were compared, the maximum values of the tonic contractions and the average values of the tonic contractions with the degrees of the modified Oxford scale obtained statistically significant results. Conclusions. The rehabilitation treatment has achieved an improvement perceived by the patients in 92% of them after finishing the treatment and an improvement in 75% at one year of follow-up. There is a decrease in the maximum values recorded in the EMG by age, decade by decade, experiencing a significant drop in the group of women ≥70 years

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

DEK expression in Merkel cell carcinoma and small cell carcinoma

Background The chromatin architectural factor DEK maps to chromosome 6p and is frequently overexpressed in several neoplasms, including small cell lung carcinoma, where it is associated with poor prognosis, tumor initiation activity and chemoresistance. DEK expression has not been studied in cutaneous Merkel cell carcinoma. Methods We applied a DEK monoclonal antibody to 15 cases of Merkel cell carcinoma and 12 cases of small cell carcinoma. DEK nuclear immunoreactivity was scored based on percentage (0, negative; 1+, 50%) and intensity (weak, moderate or strong). Results All 15 Merkel cell carcinoma cases (100%) showed diffuse (3+) nuclear positivity (14 strong, 1 weak). Six of 12 small cell carcinoma cases (50%) showed diffuse (3+) and strong nuclear positivity, while one case exhibited focal (1+) weak nuclear positivity. The remaining five cases were negative for DEK expression. Conclusions Our results suggest that DEK may be involved in the pathogenesis of Merkel cell carcinoma and therefore may provide therapeutic implications for Merkel cell carcinomas. In addition, the difference in DEK expression between Merkel cell carcinoma and small cell carcinoma suggests possible separate tumorigenesis pathways for the two tumors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92401/1/cup1941.pd