Synergistic and Additive Effects of Menadione in Combination with Antibiotics on Multidrug-Resistant Staphylococcus aureus: Insights from Structure-Function Analysis of Naphthoquinones.

Antimicrobial resistance (AMR) interferes with the effective treatment of infections and increases the risk of microbial spread and infection-related illness and death. The synergistic activities of combinations of antimicrobial compounds offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 group at C2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphylococcus aureus and its biofilms. We found an additive (0.590 %) were also observed. However, preformed biofilms were not affected. Dent formation was also evident in S. aureus treated with the test compounds. The structure-function relationship (SFR) of NQs was used to determine and predict their activity pattern against pathogens. Analysis of 10 structurally distinct NQs revealed that the compounds with -Cl, -Br, -CH3 , or -OH groups displayed the lowest MICs (32-256 µg/mL). Furthermore, 1,4-NQs possessing a halogen or -CH3 moiety showed elevated ROS activity, whereas molecules with an -OH group affected cell integrity. Improved activity of antimicrobial combinations and SFR approaches are significant in antimicrobial therapies.

Efficacy of fusion imaging for immediate post-ablation assessment of malignant liver neoplasms: A systematic review.

BACKGROUND: Percutaneous thermal ablation has become the preferred therapeutic treatment option for liver cancers that cannot be resected. Since ablative zone tissue changes over time, it becomes challenging to determine therapy effectiveness over an extended period. Thus, an immediate post-procedural evaluation of the ablation zone is crucial, as it could influence the need for a second-look treatment or follow-up plan. Assessing treatment response immediately after ablation is essential to attain favorable outcomes. This study examines the efficacy of image fusion strategies immediately post-ablation in liver neoplasms to determine therapeutic response. METHODOLOGY: A comprehensive systematic search using PRISMA methodology was conducted using EMBASE, MEDLINE (via PUBMED), and Cochrane Library Central Registry electronic databases to identify articles that assessed the immediate post-ablation response in malignant hepatic tumors with fusion imaging (FI) systems. The data were retrieved on relevant clinical characteristics, including population demographics, pre-intervention clinical history, lesion characteristics, and intervention type. For the outcome metrics, variables such as average fusion time, intervention metrics, technical success rate, ablative safety margin, supplementary ablation rate, technical efficacy rate, LTP rates, and reported complications were extracted. RESULTS: Twenty-two studies were included for review after fulfilling the study eligibility criteria. FI's immediate technical success rate ranged from 81.3% to 100% in 17/22 studies. In 16/22 studies, the ablative safety margin was assessed immediately after ablation. Supplementary ablation was performed in 9 studies following immediate evaluation by FI. In 15/22 studies, the technical effectiveness rates during the first follow-up varied from 89.3% to 100%. CONCLUSION: Based on the studies included, we found that FI can accurately determine the immediate therapeutic response in liver cancer ablation image fusion and could be a feasible intraprocedural tool for determining short-term post-ablation outcomes in unresectable liver neoplasms. There are some technical challenges that limit the widespread adoption of FI techniques. Large-scale randomized trials are warranted to improve on existing protocols. Future research should emphasize improving FI's technological capabilities and clinical applicability to a broader range of tumor types and ablation procedures.

Integrative toxicogenomics: Advancing precision medicine and toxicology through artificial intelligence and OMICs technology.

More information about a person's genetic makeup, drug response, multi-omics response, and genomic response is now available leading to a gradual shift towards personalized treatment. Additionally, the promotion of non-animal testing has fueled the computational toxicogenomics as a pivotal part of the next-gen risk assessment paradigm. Artificial Intelligence (AI) has the potential to provid new ways analyzing the patient data and making predictions about treatment outcomes or toxicity. As personalized medicine and toxicogenomics involve huge data processing, AI can expedite this process by providing powerful data processing, analysis, and interpretation algorithms. AI can process and integrate a multitude of data including genome data, patient records, clinical data and identify patterns to derive predictive models anticipating clinical outcomes and assessing the risk of any personalized medicine approaches. In this article, we have studied the current trends and future perspectives in personalized medicine & toxicology, the role of toxicogenomics in connecting the two fields, and the impact of AI on personalized medicine & toxicology. In this work, we also study the key challenges and limitations in personalized medicine, toxicogenomics, and AI in order to fully realize their potential.

Dense-PSP-UNet: A neural network for fast inference liver ultrasound segmentation.

Liver Ultrasound (US) or sonography is popularly used because of its real-time output, low-cost, ease-of-use, portability, and non-invasive nature. Segmentation of real-time liver US is essential for diagnosing and analyzing liver conditions (e.g., hepatocellular carcinoma (HCC)), assisting the surgeons/radiologists in therapeutic procedures. In this paper, we propose a method using a modified Pyramid Scene Parsing (PSP) module in tuned neural network backbones to achieve real-time segmentation without compromising the segmentation accuracy. Considering widespread noise in US data and its impact on outcomes, we study the impact of pre-processing and the influence of loss functions on segmentation performance. We have tested our method after annotating a publicly available US dataset containing 2400 images of 8 healthy volunteers (link to the annotated dataset is provided); the results show that the Dense-PSP-UNet model achieves a high Dice coefficient of 0.913±0.024 while delivering a real-time performance of 37 frames per second (FPS).

Micropatterned Neurovascular Interface to Mimic the Blood-Brain Barrier's Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model.

A hybrid blood-brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet-outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte-endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus.

A lightweight neural network with multiscale feature enhancement for liver CT segmentation.

Segmentation of abdominal Computed Tomography (CT) scan is essential for analyzing, diagnosing, and treating visceral organ diseases (e.g., hepatocellular carcinoma). This paper proposes a novel neural network (Res-PAC-UNet) that employs a fixed-width residual UNet backbone and Pyramid Atrous Convolutions, providing a low disk utilization method for precise liver CT segmentation. The proposed network is trained on medical segmentation decathlon dataset using a modified surface loss function. Additionally, we evaluate its quantitative and qualitative performance; the Res16-PAC-UNet achieves a Dice coefficient of 0.950 ± 0.019 with less than half a million parameters. Alternatively, the Res32-PAC-UNet obtains a Dice coefficient of 0.958 ± 0.015 with an acceptable parameter count of approximately 1.2 million.

Practical utility of liver segmentation methods in clinical surgeries and interventions.

Clinical imaging (e.g., magnetic resonance imaging and computed tomography) is a crucial adjunct for clinicians, aiding in the diagnosis of diseases and planning of appropriate interventions. This is especially true in malignant conditions such as hepatocellular carcinoma (HCC), where image segmentation (such as accurate delineation of liver and tumor) is the preliminary step taken by the clinicians to optimize diagnosis, staging, and treatment planning and intervention (e.g., transplantation, surgical resection, radiotherapy, PVE, embolization, etc). Thus, segmentation methods could potentially impact the diagnosis and treatment outcomes. This paper comprehensively reviews the literature (during the year 2012-2021) for relevant segmentation methods and proposes a broad categorization based on their clinical utility (i.e., surgical and radiological interventions) in HCC. The categorization is based on the parameters such as precision, accuracy, and automation.

Feasibility and Efficacy of Fusion Imaging Systems for Immediate Post Ablation Assessment of Liver Neoplasms: Protocol for a Rapid Systematic Review.

INTRODUCTION: Percutaneous thermal ablation is widely adopted as a curative treatment approach for unresectable liver neoplasms. Accurate immediate assessment of therapeutic response post-ablation is critical to achieve favourable outcomes. The conventional technique of side-by-side comparison of pre- and post-ablation scans is challenging and hence there is a need for improved methods, which will accurately evaluate the immediate post-therapeutic response. OBJECTIVES AND SIGNIFICANCE: This review summarizes the findings of studies investigating the feasibility and efficacy of the fusion imaging systems in the immediate post-operative assessment of the therapeutic response to thermal ablation in liver neoplasms. The findings could potentially empower the clinicians with updated knowledge of the state-of-the-art in the assessment of treatment response for unresectable liver neoplasms. METHODS AND ANALYSIS: A rapid review will be performed on publicly available major electronic databases to identify articles reporting the feasibility and efficacy of the fusion imaging systems in the immediate assessment of the therapeutic response to thermal ablation in liver neoplasms. The risk of bias and quality of articles will be assessed using the Cochrane risk of bias tool 2.0 and Newcastle Ottawa tool. ETHICS AND DISSEMINATION: Being a review, we do not anticipate the need for any approval from the Institutional Review Board. The outcomes of this study will be published in a peer-reviewed journal. HIGHLIGHTS: Evaluation of the therapeutic response in liver neoplasms immediately post-ablation is critical to achieve favourable patient outcomes. We will examine the feasibility and technical efficacy of different fusion imaging systems in assessing the immediate treatment response post-ablation. The findings are expected to guide the clinicians with updated knowledge on the state-of-the-art when assessing the immediate treatment response for unresectable liver neoplasms.

Advances in Smoking Related In Vitro Inhalation Toxicology: A Perspective Case of Challenges and Opportunities from Progresses in Lung-on-Chip Technologies.

The inhalation toxicology of multifaceted particulate matter from the environment, cigarette smoke, and e-cigarette liquid vapes is a major research topic concerning the adverse effect of these items on lung tissue. In vitro air-liquid interface (ALI) culture models hold more potential in an inhalation toxicity assessment. Apropos to e-cigarette toxicity, the multiflavor components of the vapes pose a complex experimental bottleneck. While an appropriate ALI setup has been one part of the focus to overcome this, parallel attention towards the development of an ideal exposure system has pushed the field forward. With the advent of microfluidic devices, lung-on-chip (LOC) technologies show enormous opportunities in in vitro smoke-related inhalation toxicity. In this review, we provide a framework, establish a paradigm about smoke-related inhalation toxicity testing in vitro, and give a brief overview of breathing LOC experimental design concepts. The capabilities with optimized bioengineering approaches and microfluidics and their fundamental pros and cons are presented with specific case studies. The LOC model can imitate the structural, functional, and mechanical properties of human alveolar-capillary interface and are more reliable than conventional in vitro models. Finally, we outline current perspective challenges as well as opportunities of future development to smoking lungs-on-chip technologies based on advances in soft robotics, machine learning, and bioengineering.

Emerging Technologies for In Vitro Inhalation Toxicology.

Respiratory toxicology remains a major research area in the 21st century since current scenario of airborne viral infection transmission and pollutant inhalation is expected to raise the annual morbidity beyond 2 million. Clinical and epidemiological research connecting human exposure to air contaminants to understand adverse pulmonary health outcomes is, therefore, an immediate subject of human health assessment. Important observations in defining systemic effects of environmental contaminants on inhalation metabolic dysfunction, liver health, and gastrointestinal tract have been well explored with in vivo models. In this review, a framework is provided, a paradigm is established about inhalation toxicity testing in vitro, and a brief overview of breathing Lungs-on-Chip (LoC) as design concepts is given. The optimized bioengineering approaches and microfluidics with their fundamental pros, and cons are presented. There are different strategies that researchers apply to inhalation toxicity studies to assess a variety of inhalable substances and relevant LoC approaches. A case study from published literature and frame arguments about reproducibility as well as in vitro/in vivo correlations are discussed. Finally, the opportunities and challenges in soft robotics, systems inhalation toxicology approach integrating bioengineering, machine learning, and artificial intelligence to address a multitude model for future toxicology are discussed.

Leveraging hallmark Alzheimer's molecular targets using phytoconstituents: Current perspective and emerging trends.

Alzheimer's disease (AD), a type of dementia, severely distresses different brain regions. Characterized by various neuropathologies, it interferes with cognitive functions and neuropsychiatrical controls. This progressive deterioration has negative impacts not only on an individual's daily activity but also on social and occupational life. The pharmacological approach has always remained in the limelight for the treatment of AD. However, this approach is condemned with several side effects. Henceforth, a change in treatment approach has become crucial. Plant-based natural products are garnering special attention due to lesser side effects associated with their use. The current review emphasizes the anti-AD properties of phytoconstituents, throws light on those under clinical trials, and compiles information on their specific mode of actions against AD-related different neuropathologies. The phytoconstituents alone or in combinations will surely help discover new potent drugs for the effective treatment of AD with lesser side effects than the currently available pharmacological treatment.

Emerging Application of Nanorobotics and Artificial Intelligence To Cross the BBB: Advances in Design, Controlled Maneuvering, and Targeting of the Barriers.

The blood-brain barrier (BBB) is a prime focus for clinicians to maintain the homeostatic function in health and deliver the theranostics in brain cancer and number of neurological diseases. The structural hierarchy and in situ biochemical signaling of BBB neurovascular unit have been primary targets to recapitulate into the in vitro modules. The microengineered perfusion systems and development in 3D cellular and organoid culture have given a major thrust to BBB research for neuropharmacology. In this review, we focus on revisiting the nanoparticles based bimolecular engineering to enable them to maneuver, control, target, and deliver the theranostic payloads across cellular BBB as nanorobots or nanobots. Subsequently we provide a brief outline of specific case studies addressing the payload delivery in brain tumor and neurological disorders (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.). In addition, we also address the opportunities and challenges across the nanorobots' development and design. Finally, we address how computationally powered machine learning (ML) tools and artificial intelligence (AI) can be partnered with robotics to predict and design the next generation nanorobots to interact and deliver across the BBB without causing damage, toxicity, or malfunctions. The content of this review could be references to multidisciplinary science to clinicians, roboticists, chemists, and bioengineers involved in cutting-edge pharmaceutical design and BBB research.

Lattice-Boltzmann interactive blood flow simulation pipeline.

PURPOSE: Cerebral aneurysms are one of the prevalent cerebrovascular disorders in adults worldwide and caused by a weakness in the brain artery. The most impressive treatment for a brain aneurysm is interventional radiology treatment, which is extremely dependent on the skill level of the radiologist. Hence, accurate detection and effective therapy for cerebral aneurysms still remain important clinical challenges. In this work, we have introduced a pipeline for cerebral blood flow simulation and real-time visualization incorporating all aspects from medical image acquisition to real-time visualization and steering. METHODS: We have developed and employed an improved version of HemeLB as the main computational core of the pipeline. HemeLB is a massive parallel lattice-Boltzmann fluid solver optimized for sparse and complex geometries. The visualization component of this pipeline is based on the ray marching method implemented on CUDA capable GPU cores. RESULTS: The proposed visualization engine is evaluated comprehensively and the reported results demonstrate that it achieves significantly higher scalability and sites updates per second, indicating higher update rate of geometry sites' values, in comparison with the original HemeLB. This proposed engine is more than two times faster and capable of 3D visualization of the results by processing more than 30 frames per second. CONCLUSION: A reliable modeling and visualizing environment for measuring and displaying blood flow patterns in vivo, which can provide insight into the hemodynamic characteristics of cerebral aneurysms, is presented in this work. This pipeline increases the speed of visualization and maximizes the performance of the processing units to do the tasks by breaking them into smaller tasks and working with GPU to render the images. Hence, the proposed pipeline can be applied as part of clinical routines to provide the clinicians with the real-time cerebral blood flow-related information.

Moving object tracking in clinical scenarios: application to cardiac surgery and cerebral aneurysm clipping.

BACKGROUND AND OBJECTIVES: Surgical procedures such as laparoscopic and robotic surgeries are popular since they are invasive in nature and use miniaturized surgical instruments for small incisions. Tracking of the instruments (graspers, needle drivers) and field of view from the stereoscopic camera during surgery could further help the surgeons to remain focussed and reduce the probability of committing any mistakes. Tracking is usually preferred in computerized video surveillance, traffic monitoring, military surveillance system, and vehicle navigation. Despite the numerous efforts over the last few years, object tracking still remains an open research problem, mainly due to motion blur, image noise, lack of image texture, and occlusion. Most of the existing object tracking methods are time-consuming and less accurate when the input video contains high volume of information and more number of instruments. METHODS: This paper presents a variational framework to track the motion of moving objects in surgery videos. The key contributions are as follows: (1) A denoising method using stochastic resonance in maximal overlap discrete wavelet transform is proposed and (2) a robust energy functional based on Bhattacharyya coefficient to match the target region in the first frame of the input sequence with the subsequent frames using a similarity metric is developed. A modified affine transformation-based registration is used to estimate the motion of the features following an active contour-based segmentation method to converge the contour resulted from the registration process. RESULTS AND CONCLUSION: The proposed method has been implemented on publicly available databases; the results are found satisfactory. Overlap index (OI) is used to evaluate the tracking performance, and the maximum OI is found to be 76% and 88% on private data and public data sequences.

Semiautomated hybrid algorithm for estimation of three-dimensional liver surface in CT using dynamic cellular automata and level-sets.

Liver segmentation continues to remain a major challenge, largely due to its intense complexity with surrounding anatomical structures (stomach, kidney, and heart), high noise level and lack of contrast in pathological computed tomography (CT) data. We present an approach to reconstructing the liver surface in low contrast CT. The main contributions are: (1) a stochastic resonance-based methodology in discrete cosine transform domain is developed to enhance the contrast of pathological liver images, (2) a new formulation is proposed to prevent the object boundary, resulting from the cellular automata method, from leaking into the surrounding areas of similar intensity, and (3) a level-set method is suggested to generate intermediate segmentation contours from two segmented slices distantly located in a subject sequence. We have tested the algorithm on real datasets obtained from two sources, Hamad General Hospital and medical image computing and computer-assisted interventions grand challenge workshop. Various parameters in the algorithm, such as [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text], play imperative roles, thus their values are precisely selected. Both qualitative and quantitative evaluation performed on liver data show promising segmentation accuracy when compared with ground truth data reflecting the potential of the proposed method.

A strategic approach for cardiac MR left ventricle segmentation.

Quantitative evaluation of cardiac function from cardiac magnetic resonance (CMR) images requires the identification of the myocardial walls. This generally requires the clinician to view the image and interactively trace the contours. Especially, detection of myocardial walls of left ventricle is a difficult task in CMR images that are obtained from subjects having serious diseases. An approach to automated outlining the left ventricular contour is proposed. In order to segment the left ventricle, in this paper, a combination of two approaches is suggested. Difference of Gaussian weighting function (DoG) is newly introduced in random walk approach for blood pool (inner contour) extraction. The myocardial wall (outer contour) is segmented out by a modified active contour method that takes blood pool boundary as the initial contour. Promising experimental results in CMR images demonstrate the potentials of our approach.

Automatic left ventricular contour extraction from cardiac magnetic resonance images using cantilever beam and random walk approach.

Heart failure is a well-known debilitating disease. From clinical point of view, segmentation of left ventricle (LV) is important in a cardiac magnetic resonance (CMR) image. Accurate parameters are desired for better diagnosis. Proper and fast image segmentation of LV is of paramount importance prior to estimation of these parameters. We prefer random walk approach over other existing techniques due to two of its advantages: (1) robustness to noise and, (2) it does not require any special condition to work. Performance of the method solely depends on the selection of initial seed and parameter ß. Problems arise while applying this method to different kind of CMR images bearing different ischemia. It is due due to their implicit geometry definitions unlike general images, where the boundary of LV in the image is not available in an explicit form. This type of images bear multi-labeled LV and the manual seed selection in these images introduces variability in the results. In view of this, the paper presents two modifications in the algorithm: (1) automatic seed selection and, (2) automatic estimation of ß from the image. The highlight of our method is its ability to succeed with minimum number of initial seeds.