Surgical process modelling: a review

Automation of surgical processes (SPs) is an utterly complex, yet highly demanded feature by medical experts. Currently, surgical tools with advanced sensory and diagnostic capabilities are only available. A major criticism towards the newly developed instruments that they are not fitting into the existing medical workflow often creating more annoyance than benefit for the surgeon. The first step in achieving streamlined integration of computer technologies is gaining a better understanding of the SP. Surgical ontologies provide a generic platform for describing elements of the surgical procedures. Surgical Process Models (SPMs) built on top of these ontologies have the potential to accurately represent the surgical workflow. SPMs provide the opportunity to use ontological terms as the basis of automation, allowing the developed algorithm to easily integrate into the surgical workflow, and to apply the automated SPMs wherever the linked ontological term appears in the workflow. In this work, as an example to this concept, the subtask level ontological term “blunt dissection” was targeted for automation. We implemented a computer vision-driven approach to demonstrate that automation on this task level is feasible. The algorithm was tested on an experimental silicone phantom as well as in several ex vivo environments. The implementation used the da Vinci surgical robot, controlled via the Da Vinci Research Kit (DVRK), relying on a shared code-base among the DVRK institutions. It is believed that developing and linking further building blocks of lower level surgical subtasks could lead to the introduction of automated soft tissue surgery. In the future, the building blocks could be individually unit tested, leading to incremental automation of the domain. This framework could potentially standardize surgical performance, eventually improving patient outcomes.

A new dataset and versatile multi-task surgical workflow analysis framework for thoracoscopic mitral valvuloplasty.

Surgical Process Modeling is a growing field of biomedical data science, aiming to create and support context aware surgical systems. As a part of it, novel research intends to provide standardized, formal description of surgical processes. Surgical workflow recordings based on ontologies can provide objective measurements of surgical skill, thus standardizing surgical performance. Comparing the operational phase to the calculated optimal process could allow for new, context aware surgical training, evaluation and assistant systems. In this paper, we present a new software tool, named OntoFlow, developed to record ontology-based surgical workflow during the clinical practice, with post-event editing and reviewing capabilities. OntoFlow directly accesses the background ontology, therefore it can speed up the process of ontology development. As a surgical workflow reviewing software it can also be used as a training tool for surgical residents.

Batch Normalization’s (BN) unique property of depending on other samples in a batch is known to cause problems in several tasks, including sequence modeling. Yet, BN-related issues are hardly studied for long video understanding, despite the ubiquitous use of BN in CNNs (Convolutional Neural Networks) for feature extraction. Especially in surgical workflow analysis, where the lack of pretrained feature extractors has led to complex, multi-stage training pipelines, limited awareness of BN issues may have hidden the benefits of training CNNs and temporal models end to end. In this paper, we analyze pitfalls of BN in video learning, including issues specific to online tasks such as a ’cheating’ effect in anticipation. We observe that BN’s properties create major obstacles for end-to-end learning. However, using BN-free backbones, even simple CNN–LSTMs beat the state of the art on three surgical workflow benchmarks by utilizing adequate end-to-end training strategies which maximize temporal context. We conclude that awareness of BN’s pitfalls is crucial for effective end-to-end learning in surgical tasks. By reproducing results on natural-video datasets, we hope our insights will benefit other areas of video learning as well. Code is available at: https://gitlab.com/nct_tso_public/pitfalls_bn.

Who is sensitising whom? A participatory interview guide development as an awareness tool within a health care research project

References and Further Reading

Low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels contribute to the excess rate of cardiovascular events seen in subjects with type 2 diabetes. Fenofibrate treatment partially reverses dyslipidemia in these subjects. However, a paradoxical marked reduction in HDL-C and HDL's major protein, apolipoprotein A-I, is a complication of fenofibrate in combination with rosiglitazone, an insulin-sensitizing agent. Risk factors for this condition, termed hypoalphalipoproteinemia, have yet to be identified. Using a case-control study design with subjects enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we tested the hypothesis that alterations in HDL's protein cargo predispose diabetic subjects to fenofibrate/rosiglitazone-induced hypoalphalipoproteinemia. HDL was isolated from blood obtained from controls (no decreases or increase in HDL-C while receiving fenofibrate/rosiglitazone therapy) and cases (developed hypoalphalipoproteinemia after fenofibrate/rosiglitazone treatment) participating in the ACCORD study before they began fenofibrate/rosiglitazone treatment. HDL proteins were quantified by targeted parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) with isotope dilution. This approach demonstrated marked increases in the relative concentrations of paraoxonase/arylesterase 1 (PON1), apolipoprotein C-II (APOC2), apolipoprotein C-I, and apolipoprotein H in the HDL of subjects who developed hypoalphalipoproteinemia. The case and control subjects did not differ significantly in baseline HDL-C levels or other traditional lipid risk factors. We used orthogonal biochemical techniques to confirm increased levels of PON1 and APOC2. Our observations suggest that an imbalance in HDL proteins predisposes diabetic subjects to develop hypoalphalipoproteinemia on fenofibrate/rosiglitazone therapy.

MURINE IL-2 SECRETING RECOMBINANT BACILLUS CALMETTE-GUÉRIN AUGMENTS MACROPHAGE-MEDIATED CYTOTOXICITY AGAINST MURINE BLADDER CANCER MBT-2

Intestinal Replacement Therapy: Timing and Indications for Referral of Patients to an Intestinal Rehabilitation and Transplant Program

This study investigated the dynamics of ubiquitinated proteins after the inflammatory stimulation of RAW 264.7 macrophage-like cells with bacterial lipopolysaccharide. Ubiquitination is a common protein post-translational modification that regulates many key cellular functions. We demonstrated that levels of global ubiquitination and K48 and K63 polyubiquitin chains change after lipopolysaccharide stimulation. Quantitative proteomic analysis identified 1199 ubiquitinated proteins, 78 of which exhibited significant changes in ubiquitination levels following stimulation. Integrating the ubiquitinome data with global proteomic and transcriptomic results allowed us to identify a subset of 88 proteins that were targeted for degradation after lipopolysaccharide stimulation. Using cellular assays and Western blot analyses, we biochemically validated DBC1 (a histone deacetylase inhibitor) as a degradation substrate that is targeted via an orchestrated mechanism utilizing caspases and the proteasome. The degradation of DBC1 releases histone deacetylase activity, linking lipopolysaccharide activation to chromatin remodeling in caspase- and proteasome-mediated signaling.

Lichen Sclerosus: Review of the Literature and Current Recommendations for Management

Double-Strand Breaks in Heterochromatin Move Outside of a Dynamic HP1a Domain to Complete Recombinational Repair

Bak is a prototypic pro-apoptotic Bcl-2 family protein expressed in a wide variety of tissues and cells. Recent studies have revealed that Bcl-2 family proteins regulate apoptosis as well as autophagy. To investigate whether and how Bak exerts a regulatory role on autophagy-related events, we treated independent cell lines, including MN9D neuronal cells, with nigericin, a K(+)/H(+) ionophore. Treatment of MN9D cells with nigericin led to an increase of LC3-II and p62 levels with concomitant activation of caspase. Ultrastructural examination revealed accumulation of autophagic vacuoles and swollen vacuoles in nigericin-treated cells. We further found that the LC3-II accumulated as a consequence of impaired autophagic flux and the disrupted degradation of LC3-II in nigericin-treated cells. In this cell death paradigm, both transient and stable overexpression of various forms of Bak exerted a protective role, whereas it did not inhibit the extent of nigericin-mediated activation of caspase-3. Subsequent biochemical and electron microscopic studies revealed that overexpressed Bak maintained autophagic flux and reduced the area occupied by swollen vacuoles in nigericin-treated cells. Similar results were obtained in nigericin-treated non-neuronal cells and another proton ionophore-induced cell death paradigm. Taken together, our study indicates that a protective role for Bak during ionophore-induced cell death may be closely associated with its regulatory effect on maintenance of autophagic flux and vacuole homeostasis.

Immune Thrombocytopenia during Childhood: New Approaches to Classification and Management

The folding pathways of some proteins include the population of partially structured species en route to the native state. Identification and characterization of these folding intermediates are particularly difficult as they are often only transiently populated and play different mechanistic roles, being either on-pathway productive species or off-pathway kinetic traps. To define the role of folding intermediates, a quantitative analysis of the folding and unfolding rate constants over a wide range of denaturant concentration is often required. Such a task is further complicated by the reversible nature of the folding reaction, which implies the observed kinetics to be governed by a complex combination of different microscopic rate constants. Here, we tackled this problem by measuring directly the folding rate constant under highly denaturing conditions, namely by inducing the folding of a PDZ domain through a quasi-irreversible binding reaction with a specific peptide. In analogy with previous works based on hydrogen exchange experiments, we present evidence that the folding pathway of the PDZ domain involves the formation of an obligatory on-pathway intermediate. The results presented exemplify a novel type of kinetic test to detect an on-pathway folding intermediate.