A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer

Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor's genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease's genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer

Anatomy and pathology of the canal of Nuck.

The canal of Nuck is the female equivalent of the processus vaginalis in the male but is less well known than its male counterpart. It is a rare entity not commonly encountered by radiologists, particularly in the adult population. Knowledge of the embryology and anatomy of the canal of Nuck is essential for identification of the various pathologic conditions that may occur in this location. Moreover, radiologists should be familiar with this entity to compose an appropriate and thorough differential diagnosis of a labial mass/swelling. In this review, we discuss both the anatomy and the more common pathology that can be encountered within it

Characterization of solid renal neoplasms using MRI-based quantitative radiomics features

PURPOSE To assess the diagnostic value of magnetic resonance imaging (MRI)-based radiomics features using machine learning (ML) models in characterizing solid renal neoplasms, in comparison/combination with qualitative radiologic evaluation. METHODS Retrospective analysis of 125 patients (mean age 59 years, 67% males) with solid renal neoplasms that underwent MRI before surgery. Qualitative (signal and enhancement characteristics) and quantitative radiomics analyses (histogram and texture features) were performed on T2-weighted imaging (WI), T1-WI pre- and post-contrast, and DWI. Mann-Whitney U test and receiver-operating characteristic analysis were used in a training set (n = 88) to evaluate diagnostic performance of qualitative and radiomics features for differentiation of renal cell carcinomas (RCCs) from benign lesions, and characterization of RCC subtypes (clear cell RCC [ccRCC] and papillary RCC [pRCC]). Random forest ML models were developed for discrimination between tumor types on the training set, and validated on an independent set (n = 37). RESULTS We assessed 104 RCCs (51 ccRCC, 29 pRCC, and 24 other subtypes) and 21 benign lesions in 125 patients. Significant qualitative and quantitative radiomics features (area under the curve [AUC] between 0.62 and 0.90) were included for ML analysis. Models with best diagnostic performance on validation sets showed AUC of 0.73 (confidence interval [CI] 0.5-0.96) for differentiating RCC from benign lesions (using combination of qualitative and radiomics features); AUC of 0.77 (CI 0.62-0.92) for diagnosing ccRCC (using radiomics features), and AUC of 0.74 (CI 0.53-0.95) for diagnosing pRCC (using qualitative features). CONCLUSION ML models incorporating MRI-based radiomics features and qualitative radiologic assessment can help characterize renal masses

Doha Metro Network, Doha, Qatar, 2012-2019

UNStudio has won the competition to design 33 metro stations in Doha with a themed design - vaulted spaces. My role was to work on the layout and design of the overground shelters as recognizable branded elements in the urban space. My research was to define and optimize the vertical transportation infrastructures and adapt it to a variety of urban situations where the airconditioned shelters are located throughout the city. A modular shell system is designed to adapt to all the urban situation, depths and access logistics of the stations. I was developing a family of basic modules that integrated structure, skylights and MEP exhausts, and a family of additional extensions to provide more shade and give a unique look to the shelters. As I had experience with the overground structures, in DD phase I was given a chance to lead the design for the development of a similar modular system and design of the generic elevated stations (GEI). Several GEI type stations were built in the city of Doha. The biggest experience in this project was to communicate all the information through a large team and to provide to the client a “branding manual” book to ensure maintaining the design quality - knowing that 10 different contractors will build the stations.International Award 2020, Chartered Institute of Highways and TransportationNapomena administratora: Autorski tim je naveden od strane Nemanje Kordića

Salt-responsive gut commensal modulates TH17 axis and disease

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (T(H)17) cells, which can also contribute to hypertension. Induction of T(H)17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating T(H)17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased T(H)17 cells and increased blood pressure. Our results connect high salt intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions