Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study

Introduction Mammographic breast density is one of the strongest known risk factors for breast cancer. We present a novel technique for estimating breast density based on 3D T1-weighted Magnetic Resonance Imaging (MRI) and evaluate its performance, including for breast cancer risk prediction, relative to two standard mammographic density-estimation methods.Methods The analyses were based on MRI (n = 655) and mammography (n = 607) images obtained in the course of the UK multicentre magnetic resonance imaging breast screening (MARIBS) study of asymptomatic women aged 31 to 49 years who were at high genetic risk of breast cancer. The MRI percent and absolute dense volumes were estimated using our novel algorithm (MRIBview) while mammographic percent and absolute dense area were estimated using the Cumulus thresholding algorithm and also using a 21-point Visual Assessment scale for one medio-lateral oblique image per woman. We assessed the relationships of the MRI and mammographic measures to one another, to standard anthropometric and hormonal factors, to BRCA1/2 genetic status, and to breast cancer risk (60 cases) using linear and Poisson regression.Results MRI percent dense volume is well correlated with mammographic percent dense area (R = 0.76) but overall gives estimates 8.1 percentage points lower (P < 0.0001). Both show strong associations with established anthropometric and hormonal factors. Mammographic percent dense area, and to a lesser extent MRI percent dense volume were lower in BRCA1 carriers (P = 0.001, P = 0.010 respectively) but there was no association with BRCA2 carrier status. The study was underpowered to detect expected associations between percent density and breast cancer, but women with absolute MRI dense volume in the upper half of the distribution had double the risk of those in the lower half (P = 0.009).Conclusions The MRIBview estimates of volumetric breast density are highly correlated with mammographic dense area but are not equivalent measures; the MRI absolute dense volume shows potential as a predictor of breast cancer risk that merits further investigation

Kartezio: Evolutionary Design of Explainable Pipelines for Biomedical Image Analysis

An unresolved issue in contemporary biomedicine is the overwhelming number and diversity of complex images that require annotation, analysis and interpretation. Recent advances in Deep Learning have revolutionized the field of computer vision, creating algorithms that compete with human experts in image segmentation tasks. Crucially however, these frameworks require large human-annotated datasets for training and the resulting models are difficult to interpret. In this study, we introduce Kartezio, a modular Cartesian Genetic Programming based computational strategy that generates transparent and easily interpretable image processing pipelines by iteratively assembling and parameterizing computer vision functions. The pipelines thus generated exhibit comparable precision to state-of-the-art Deep Learning approaches on instance segmentation tasks, while requiring drastically smaller training datasets, a feature which confers tremendous flexibility, speed, and functionality to this approach. We also deployed Kartezio to solve semantic and instance segmentation problems in four real-world Use Cases, and showcase its utility in imaging contexts ranging from high-resolution microscopy to clinical pathology. By successfully implementing Kartezio on a portfolio of images ranging from subcellular structures to tumoral tissue, we demonstrated the flexibility, robustness and practical utility of this fully explicable evolutionary designer for semantic and instance segmentation.Comment: 36 pages, 6 main Figures. The Extended Data Movie is available at the following link: https://www.youtube.com/watch?v=r74gdzb6hdA. The source code is available on Github: https://github.com/KevinCortacero/Kartezi

Y-Chromosome and mtDNA Genetics Reveal Significant Contrasts in Affinities of Modern Middle Eastern Populations with European and African Populations

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of FST's, RST's, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations

Reconstruction and simulation of neocortical microcircuitry

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm3 containing ∼31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ∼8 million connections with ∼37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies

PD-L1 protein expression by Combined Positive Score (CPS) in patients with muscle invasive or advanced urothelial carcinoma: a single institution experience

Abstract Introduction Immune checkpoint inhibitors have revolutionized the treatment of patients with advanced urothelial carcinoma (UC) in the frontline and relapsed settings. Lebanon has one of the highest incidence of UC worldwide, yet no data exists regarding the expression of PD-L1 by Combined Positive Score (CPS) in advanced disease. Methods We reviewed all patients treated at our institution for high grade UC, stage pT2 and above, between January 2017 and March 2021. We assessed the expression of PD-L1 by immunohistochemistry using 22C3 clone, and analyzed the association between PD-L1 expression and clinicopathological characteristics. PD-L1 positivity was defined as CPS score ≥ 10. Results A total of 101 patients with advanced UC were included, with a median age of 71 years (range, 38 to 96 years); 78% were ever-smokers. Ninety-three of 101 patients (92%) had conventional UC and 43 patients (43%) had positive PD-L1 expression, with 12 patients having CPS of 100. The analysis by molecular subtype showed that patients with maximal CPS of 100 were enriched in “basal” molecular subtype. However, no association was found between PD-L1 expression (positive versus negative) and clinicopathological characteristics. Conclusion The positivity of PD-L1 expression as assessed by CPS using the 22C3 clone in our population was almost comparable to the results reported in the occidental literature. Therefore, PD-L1 expression, as a potential predictor of response to immunotherapy, concerns the same percentage of the Lebanese UC patients

The Impact of Multidisciplinary Conferences on Healthcare Utilization in Chronic Pain Patients.

Approximately 100 million adults in the United States have chronic pain, though only a subset utilizes the vast majority of healthcare resources. Multidisciplinary care has been shown to improve outcomes in a variety of clinical conditions. There is concern that multidisciplinary care of chronic pain patients may overwhelm existing resources and increase healthcare utilization due to the volume of patients and the complexity of care. We report our findings on the use of multidisciplinary conferences (MDC) to facilitate care for the most complex patients seen at our tertiary center. Thirty-two of nearly 2,000 patients seen per year were discussed at the MDC, making up the top 2% of complex patients in our practice. We evaluated patients\u27 numeric rating score (NRS) of pain, medication use, hospitalizations, emergency department visits, and visits to pain specialists prior to their enrollment in MDC and 1 year later. Matched samples were compared using Wilcoxon\u27s signed rank test. Patients\u27 NRS scores significantly decreased from 7.64 to 5.54 after inclusion in MDC

A case of partial sirenomelia and possible vitamin A teratogenesis

Prenatal echographical findings of a partial sirenomelic fetus are described. An attempt was made to terminate pregnancy by administration of prostaglandin F2 alpha, but uterine rupture occurred. The teratogenic role of vitamin A ingested by the mother in the periconceptional period is discussed.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe