Examining B-cell dynamics and responsiveness in different inflammatory milieus using an agent-based model.

Introduction: B-cells are essential components of the immune system that neutralize infectious agents through the generation of antigen-specific antibodies and through the phagocytic functions of naïve and memory B-cells. However, the B-cell response can become compromised by a variety of conditions that alter the overall inflammatory milieu, be that due to substantial, acute insults as seen in sepsis, or due to those that produce low-level, smoldering background inflammation such as diabetes, obesity, or advanced age. This B-cell dysfunction, mediated by the inflammatory cytokines Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α), increases the susceptibility of late-stage sepsis patients to nosocomial infections and increases the incidence or severity of recurrent infections, such as SARS-CoV-2, in those with chronic conditions.

Characterizing the Crosstalk Between Programmed Cell Death Pathways in Cytokine Storm With an Agent-Based Model.

There is increasing recognition of extensive crosstalk between programmed cell death pathways (PCDPs), such as apoptosis, pyroptosis, and necroptosis, resulting in a highly redundant system responsive to a breadth of potential pathogens. However, because pyroptosis and necroptosis propagate inflammation, these redundancies also present challenges for therapeutic control of dysregulated hyperinflammation seen in cytokine storm (CS) generated organ dysfunction. We hypothesize that the conversion of existing knowledge regarding apoptosis, pyroptosis, and necroptosis into a computational model can enhance our understanding of the crosstalk between PCDPs via simulation experiments of microbe interactions and experimental interventions.

Children are small adults (when properly normalized): Transferrable/generalizable sepsis prediction.

Background: Though governed by the same underlying biology, the differential physiology of children causes the temporal evolution from health to a septic/diseased state to follow trajectories that are distinct from adult cases. As pediatric sepsis data sets are less readily available than for adult sepsis, we aim to leverage this shared underlying biology by normalizing pediatric physiological data such that it would be directly comparable to adult data, and then develop machine-learning (ML) based classifiers to predict the onset of sepsis in the pediatric population. We then externally validated the classifiers in an independent adult dataset.

Artificial Intelligence Optical Biopsy for Evaluating the Functional State of Wounds.

Introduction: The clinical characterization of the functional status of active wounds in terms of their driving cellular and molecular biology remains a considerable challenge that currently requires excision via a tissue biopsy. In this pilot study, we use convolutional Siamese neural network (SNN) architecture to predict the functional state of a wound using digital photographs of wounds in a canine model of volumetric muscle loss (VML).

Methods: Digital images of VML injuries and tissue biopsies were obtained in a standardized fashion from an established canine model of VML.

A Virtual Reading Center Model Using Crowdsourcing to Grade Photographs for Trachoma: Validation Study.

Background: As trachoma is eliminated, skilled field graders become less adept at correctly identifying active disease (trachomatous inflammation-follicular [TF]). Deciding if trachoma has been eliminated from a district or if treatment strategies need to be continued or reinstated is of critical public health importance. Telemedicine solutions require both connectivity, which can be poor in the resource-limited regions of the world in which trachoma occurs, and accurate grading of the images.

Detection of trachoma using machine learning approaches.

Background: Though significant progress in disease elimination has been made over the past decades, trachoma is the leading infectious cause of blindness globally. Further efforts in trachoma elimination are paradoxically being limited by the relative rarity of the disease, which makes clinical training for monitoring surveys difficult. In this work, we evaluate the plausibility of an Artificial Intelligence model to augment or replace human image graders in the evaluation/diagnosis of trachomatous inflammation-follicular (TF).

Optical Biopsy Using a Neural Network to Predict Gene Expression From Photos of Wounds.

Background: The clinical characterization of the biological status of complex wounds remains a considerable challenge. Digital photography provides a non-invasive means of obtaining wound information and is currently employed to assess wounds qualitatively. Advances in machine learning (ML) image processing provide a means of identifying "hidden" features in pictures.

The Use of Artificial Neural Networks to Forecast the Behavior of Agent-Based Models of Pathophysiology: An Example Utilizing an Agent-Based Model of Sepsis.

Disease states are being characterized at finer and finer levels of resolution biomarker or gene expression profiles, while at the same time. Machine learning (ML) is increasingly used to analyze and potentially classify or predict the behavior of biological systems based on such characterization. As ML applications are extremely data-intensive, given the relative sparsity of biomedical data sets ML training of artificial neural networks (ANNs) often require the use of synthetic training data.

Agent-Based Modeling of Systemic Inflammation: A Pathway Toward Controlling Sepsis.

Despite nearly 50 years of research there currently remains no mediator-directed therapy approved for the treatment of sepsis. The failure to effectively translate the copious mechanistic knowledge regarding systemic inflammation to effective therapies is a dramatic example of the translational dilemma. Dynamic computational modeling has been proposed as a vital means of integrating community-wide knowledge into an investigatory framework that allows the application of engineering-like principles to the problem of sepsis.

Improved Outcomes Utilizing a Valveless-Trocar System during Robot-assisted Radical Prostatectomy (RARP).

Introduction: To evaluate the effect of valveless trocar system (VTS) on intra-operative parameters, peri-operative outcomes, and 30-day postoperative complications in patients undergoing robotic-assisted laparoscopic prostatectomy.

Methods: A total of 200 consecutive patients undergoing Robot-assisted radical prostatectomy by a single surgeon were prospectively evaluated using either the valveless trocar (n = 100) or standard trocars (n = 100). Patient demographics, intra-operative parameters, length of stay, presence or absence of postoperative nausea and vomiting, analog pain score at 0-6 hours, 6-12 hours, 12-18 hours, and >24 hours, and 30-day postoperative complications were analyzed.

Robot-Assisted Simple Prostatectomy.

Introduction: Benign prostatic obstruction is the leading cause of lower urinary tract symptoms in older males. The management strategies include medical management and surgical therapy. However when the prostate becomes very enlarged medical therapy can be ineffective and transurethral resection may not be feasible.

Examining the controllability of sepsis using genetic algorithms on an agent-based model of systemic inflammation.

Sepsis, a manifestation of the body's inflammatory response to injury and infection, has a mortality rate of between 28%-50% and affects approximately 1 million patients annually in the United States. Currently, there are no therapies targeting the cellular/molecular processes driving sepsis that have demonstrated the ability to control this disease process in the clinical setting. We propose that this is in great part due to the considerable heterogeneity of the clinical trajectories that constitute clinical "sepsis," and that determining how this system can be controlled back into a state of health requires the application of concepts drawn from the field of dynamical systems.

Robot-Assisted Simple Prostatectomy: Expanding on an Established Operative Approach.

Purpose Of Review: The leading cause of voiding dysfunction in older men is benign prostatic obstruction. In the setting of a grossly enlarged prostate (>80cm), an open simple prostatectomy has been the gold standard for surgical treatment. Here, we will discuss the minimally invasive robot-assisted approach and compare it to the classic open approach and holmium laser enucleation of the prostate.

Towards anatomic scale agent-based modeling with a massively parallel spatially explicit general-purpose model of enteric tissue (SEGMEnT_HPC).

Perhaps the greatest challenge currently facing the biomedical research community is the ability to integrate highly detailed cellular and molecular mechanisms to represent clinical disease states as a pathway to engineer effective therapeutics. This is particularly evident in the representation of organ-level pathophysiology in terms of abnormal tissue structure, which, through histology, remains a mainstay in disease diagnosis and staging. As such, being able to generate anatomic scale simulations is a highly desirable goal.

The finished DNA sequence of human chromosome 12.

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.

Anterior maxillary alveolar distraction osteogenesis: a prospective 5-year clinical study.

Purpose: Anterior maxillary alveolar vertical distractions were followed for a 5-year period of time.

Materials And Methods: A total of 30 vertical distractions were done in 28 patients. Two patients had both anterior maxilla and anterior mandibular distractions for a total of 30 distractions.

Nutraceutical interventions may delay aging and the age-related diseases.

Largely due to better control of infectious diseases and to year-round access to a more nutritious diet, life expectancy in developed countries has increased dramatically in the twentieth century. However, as the average age of the population has risen, the incidence of chronic age-related diseases such as Alzheimer's, Parkinson's, cardiovascular disease, cancer, arthritis, osteoporosis, benign prostatic hyperplasia, late-onset diabetes, and macular degeneration have increased. To obtain further significant improvements in both lifespan and the quality of life in this century, treatments and nutritional changes that address the age-related diseases and the aging process itself need to be examined and validated.

Role of influenza B virus in hepatic steatosis and mitochondrial abnormalities in a mouse model of Reye syndrome.

The hepatic steatosis observed in the influenza B virus mouse model of Reye syndrome has been attributed to infectious virus or, alternately, to decreased food intake in the virus-treated mice or impurities in the virus preparation. To resolve this issue, 4- to 6-wk-old male Balb C mice were given, by intravenous injection, 12,800 hemagglutination units of influenza B Lee/40 virus in phosphate buffered saline/1% bovine serum albumin using virus prepared by ultra-centrifugation from infected allantoic fluid, by sucrose density-gradient purification of virus prepared by ultracentrifugation from infected allantoic fluid or by irradiation of virus prepared by ultracentrifugation from infected allantoic fluid to inactivate virus. The infectivity titer of virus prepared by ultracentrifugation from infected allantoic fluid was much higher than that of sucrose density-gradient purified virus prepared from infected allantoic fluid: 50% egg infectious dose for virus prepared by ultracentrifugation from infected allantoic fluid was 3.

Ruthenium red-insensitive Ca2+ uptake and release by mitochondria.

Calcium uptake by rat liver mitochondria driven by an artificial pH gradient is ruthenium red insensitive, electrically neutral, and inhibited by the local anesthetic, nupercaine. This pH-driven Ca2+ transport is also inhibited by NH3, Pi, and acetate. Direct measurements of Pi indicate it is not translocated with Ca2+ during pH-driven Ca2+ uptake.

Uncoupler-stimulated release of Ca2+ from Ehrlich ascites tumor cell mitochondria.

Ruthenium red-insensitive, uncoupler-stimulated release of Ca2+ from Ehrlich ascites tumor cell mitochondria is much slower than from rat liver mitochondria under comparable conditions. In the presence of Pi and at moderate or high Ca2+ loads, ruthenium red-insensitive Ca2+ efflux elicited with uncoupler is approximately 20 times more rapid for rat liver than Ehrlich cell mitochondria. This is attributed to resistance of tumor mitochondria to damage by Ca2+ due to a high level of endogenous Mg2+ that also attenuates Ca2+ efflux.

Calcium transport by rat brain mitochondria and oxidation of 2-oxoglutarate.

Contrary to previous reports brain mitochondria have a substantial capacity for net Ca2+ uptake (approx. 1.2 mueq.

Regulation of the monovalent cation permeability of brain mitochondria.

The Na+ and K+ conductances of rat brain mitochondria were estimated from rates of metabolically dependent swelling and uncoupling of respiration. These were maximal in the presence of EDTA plus Pi. Pi could not be replaced with acetate.

The respiration of brain mitochondria and its regulation by monovalent cation transport.

The Na+ and K+ permeability properties of rat brain mitochondria were determined to explain the influences of these cations upon respiration. A new procedure for isolating exceptionally intact mitochondria with minimal contamination by synaptosomes was developed for this purpose. Respiration was uncoupled by Na+ and less so by K+.