Slim U-Net: Efficient Anatomical Feature Preserving U-net Architecture for Ultrasound Image Segmentation

We investigate the applicability of U-Net based models for segmenting Urinary Bladder (UB) in male pelvic view UltraSound (US) images. The segmentation of UB in the US image aids radiologists in diagnosing the UB. However, UB in US images has arbitrary shapes, indistinct boundaries and considerably large inter- and intra-subject variability, making segmentation a quite challenging task. Our study of the state-of-the-art (SOTA) segmentation network, U-Net, for the problem reveals that it often fails to capture the salient characteristics of UB due to the varying shape and scales of anatomy in the noisy US image. Also, U-net has an excessive number of trainable parameters, reporting poor computational efficiency during training. We propose a Slim U-Net to address the challenges of UB segmentation. Slim U-Net proposes to efficiently preserve the salient features of UB by reshaping the structure of U-Net using a less number of 2D convolution layers in the contracting path, in order to preserve and impose them on expanding path. To effectively distinguish the blurred boundaries, we propose a novel annotation methodology, which includes the background area of the image at the boundary of a marked region of interest (RoI), thereby steering the model's attention towards boundaries. In addition, we suggested a combination of loss functions for network training in the complex segmentation of UB. The experimental results demonstrate that Slim U-net is statistically superior to U-net for UB segmentation. The Slim U-net further decreases the number of trainable parameters and training time by 54% and 57.7%, respectively, compared to the standard U-Net, without compromising the segmentation accuracy.Comment: Accepted in 9th ACM International Conference on Biomedical and Bioinformatics Engineering (ICBBE) 2022 http://www.icbbe.com

Coefficient estimates and partial sums of a new class of functions

This paper investigates boundedness properties of certain classes of functions (which involve partial sums). The usefulness of the main results not only provide unification of results of Choi (where each of the results was proved rather independently), but also generates certain new results. Applications of our main results are pointed out briefly in the concluding section

Some subordination theorems associated with a new operator

In this paper we introduce a linear operator and obtain certain differential subordination properties associated with this linear operator. Some relevant consequences of the main results including new variations of earlier known results are also pointed out

Expert-Agnostic Ultrasound Image Quality Assessment using Deep Variational Clustering

Ultrasound imaging is a commonly used modality for several diagnostic and therapeutic procedures. However, the diagnosis by ultrasound relies heavily on the quality of images assessed manually by sonographers, which diminishes the objectivity of the diagnosis and makes it operator-dependent. The supervised learning-based methods for automated quality assessment require manually annotated datasets, which are highly labour-intensive to acquire. These ultrasound images are low in quality and suffer from noisy annotations caused by inter-observer perceptual variations, which hampers learning efficiency. We propose an UnSupervised UltraSound image Quality assessment Network, US2QNet, that eliminates the burden and uncertainty of manual annotations. US2QNet uses the variational autoencoder embedded with the three modules, pre-processing, clustering and post-processing, to jointly enhance, extract, cluster and visualize the quality feature representation of ultrasound images. The pre-processing module uses filtering of images to point the network's attention towards salient quality features, rather than getting distracted by noise. Post-processing is proposed for visualizing the clusters of feature representations in 2D space. We validated the proposed framework for quality assessment of the urinary bladder ultrasound images. The proposed framework achieved 78% accuracy and superior performance to state-of-the-art clustering methods.Comment: Accepted in IEEE International Conference on Robotics and Automation (ICRA) 202

TARGETING THE MUC1-C ONCOPROTEIN DOWNREGULATES HER2 ACTIVATION AND ABROGATES TRASTUZUMAB RESISTANCE IN BREAST CANCER CELLS

Patients with HER2 positive breast cancer often exhibit intrinsic or acquired resistance to trastuzumab treatment. The transmembrane MUC1-C oncoprotein is aberrantly overexpressed in breast cancer cells and associates with HER2. The present studies demonstrate that silencing MUC1-C in HER2-overexpressing SKBR3 and BT474 breast cancer cells results in downregulation of constitutive HER2 activation. Moreover, treatment with the MUC1-C inhibitor, GO-203, was associated with disruption of MUC1-C/HER2 complexes and decreases in tyrosine phosphorylated HER2 (p-HER2) levels. In studies of trastuzumab-resistant SKBR3R and BT474R cells, we found that the association between MUC1-C and HER2 is markedly increased (~20-fold) as compared to that in sensitive cells. Additionally, silencing MUC1-C in the trastuzumab-resistant cells or treatment with GO-203 decreased p-HER2 and AKT activation. Moreover, targeting MUC1-C was associated with downregulation of phospho-p27 and cyclin E, which confer trastuzumab resistance. Consistent with these results, targeting MUC1-C inhibited the growth and clonogenic survival of both trastuzumab-resistant cells. Our results further demonstrate that silencing MUC1-C reverses resistance to trastuzumab and that the combination of GO-203 and trastuzumab is highly synergistic. These findings indicate that MUC1-C contributes to constitutive activation of the HER2 pathway and that targeting MUC1-C represents a potential approach to abrogate trastuzumab resistance

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Biomaterials as carriers for bone active molecules-An approach to create off-the-shelf bone substitutes

Bone tissue is commonly transplanted during orthopedic surgeries, primarily for the management of bone defects caused by trauma or various orthopedic conditions including, but not limited to, infections and tumours. Bone grafts are a surgeon’s choice, but their associated drawbacks are paving the way for biomaterial based bone graft substitutes. Biomaterials inherently lack the ability to induce significant amount of bone growth due to which they may be combined with cells, biomaterials, growth factors and drugs to regenerate functional bone tissue. This thesis focused on characterizing biomaterial carriers that can locally deliver bone active molecules for bone regeneration and potentially act as an alternative to conventional bone grafting. We focused on the delivery of recombinant human bone morphogenic protein-2 (rhBMP-2) as a bone inducing anabolic growth factor. Simultaneously, we have used an osteoclast inhibiting bisphosphonate, zoledronic acid (ZA) to prevent BMP-2 induced premature bone resorption. Three different biomaterials scaffolds; a microporous calcium sulphate (CaS)/hydroxyapatite (HA), a macroporous gelatin-CaS/HA and a collagen membrane were used in distinct animal models of bone regeneration.The carrier properties of the three biomaterials in the ectopic muscle pouch model (studies 1, 4 and 5) showed that the tested materials were efficient carriers of rhBMP-2 and ZA and that co-delivery of rhBMP-2 and ZA regenerated higher volume of bone compared to rhBMP-2 alone. Studies 2& 3 show that the CaS/HA material locally delivering ZA or ZA+rhBMP-2 could be efficiently used for bone regeneration in clinically relevant bone defect models. These studies also indicated that local delivery of ZA not only has an anti-osteoclast effect but it also has an anabolic role. Study 4 compared the developed porous biomaterial with the current FDA approved collagen sponge and results indicated that the developed biomaterial outperforms the current marketed product for the delivery of rhBMP-2. During this study, it was also established that co-delivery of rhBMP-2 with ZA could reduce the effective rhBMP-2 doses by up to four times, which is crucial to reinstate BMPs into the clinics. Study 5 was a follow-up of study 2 separating the metaphyseal defect healing in two stages; 1) Healing the cancellous bone using a porous material and 2) Guiding cortical regeneration using a thin collagen membrane. Significantly better cortical healing was noted using this approach in comparison to study 2.In summary, this work describes promising strategies for bone regeneration. It established how the release of bone active molecules can be controlled by the choice of carrier material and how we can decrease the minimally effective dose of rhBMP- 2 by up to four times. These findings can potentially be translated from the bench to the bedside. The materials and methods developed within the scope of this work can be used in a variety of orthopedic conditions and can provide the surgeon with an effective off-the-shelf substitute for bone replacement, in turn leading to improved care of the patient