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While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation. Their accuracy, expressed as sensitivity and specificity, are reported in a number of studies suggests that they have a potential for cost effective, real-time, in situ diagnosis. We review the Third Scientific Meeting of the Head and Neck Optical Diagnostics Society held in Congress Innsbruck, Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual Scientific Meeting was held in association with the International Photodynamic Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The aim was to enhance the interdisciplinary aspects of optical diagnostics and other photodynamic applications. The meeting included 2 sections: oral communication sessions running in parallel to the IPA programme and poster presentation sessions combined with the IPA and EPPM posters sessions. © 2011 Jerjes et al; licensee BioMed Central Ltd.

The complete surgical removal of disease is a desirable outcome particularly in oncology. Unfortunately much disease is microscopic and difficult to detect causing a liability to recurrence and worsened overall prognosis with attendant costs in terms of morbidity and mortality. It is hoped that by advances in optical diagnostic technology we could better define our surgical margin and so increase the rate of truly negative margins on the one hand and on the other hand to take out only the necessary amount of tissue and leave more unaffected non-diseased areas so preserving function of vital structures. The task has not been easy but progress is being made as exemplified by the presentations at the 2nd Scientific Meeting of the Head and Neck Optical Diagnostics Society (HNODS) in San Francisco in January 2010. We review the salient advances in the field and propose further directions of investigation. © 2011 Upile et al; licensee BioMed Central Ltd.

Objectives: To report a small case series of an unusual ingested foreign body and a new method for removal of tongue base foreign bodies. Methods: Three patients were identified with wire bristle foreign bodies between 2009 and 2011 at our academic tertiary medical center. Their medical records were reviewed and are described in this report. Results: Each patient presented to our medical center with progressive pain after ingestion of barbecued food. For 2 patients, the metallic bristle foreign body was imbedded within the lingual tonsil. In these 2 cases, radiofrequency plasma ablation (coblation) assisted partial lingual tonsillectomy was performed to identify the foreign body. In a third case, the foreign body presented as a complex deep space neck abscess and an open trans-cervical approach was required. Conclusion: While oropharyngeal and esophageal foreign bodies are common, there are only a few case reports describing this particular foreign body. The presentation of an imbedded wire grill brush bristle can be insidious. Persistent pain and foreign body sensation should be taken seriously in patients with a history of barbecue food ingestion. Intraoperatively, wire bristles can be difficult to localize and extract. Radiofrequency plasma assisted lingual tonsillectomy may be helpful for identifying and removing foreign bodies that are imbedded in the tongue base. Grill brushes should undergo stringent safety regulation, as ingested wire bristles are difficult to localize and remove and may cause significant morbidity. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prevalence and severity of dental caries in three- to five-year-old preschool children from two communes in Chile: one with a fluoridated public water supply and the other with a non-fluoridated public water supply. Methods: Study design: Cross-sectional observational study. The sample was composed of 200 children from three to five years old, with good general health, of low socioeconomic status, attending four kindergarten schools of the Metropolitan Region of Santiago, Chile. Two schools were located in the commune of Maipú, which does not have fluoridated public water, and two schools were located in the commune of Peñalolen, which has had fluoridated public water since 1996, at a fluoride concentration of 0.6 mg/L. The WHO (World Health Organization) methodology was used to measure the percentage of caries-free children, and the dmft index was used to measure the severity of the disease. Results: The results showed that 24% of the children in Maipú were caries free, compared to 55% in Peñalolen. The dmft index was 3.38 and 1.84 in Maipú and Peñalolen, respectively. These indices increased with age. Conclusion: The prevalence and severity of dental caries in three- to five-year-old preschoolers were higher in Maipú, the commune with non-fluoridated water, than in Peñalolen, the commune with fluoridated water. [ABSTRACT FROM AUTHOR]

Purpose: Antiseptic mouthrinses containing chlorhexidine (CHX) seem to be the most effective chemical agents for plaque control. The CHX concentration is usually 0.12% or 0.20%, but formulations with lower concentrations of CHX (0.05%) in combination with other active agents such as sodium fluoride (0.05%) or cetyl pyridinium chloride (0.05%) (Cpc) are available. Theaim of this study was to compare plaque formation at 24 hours after the use of 0.1% CHX mouthrinse-gel and mouthrinses containing 0.12% and 0.05% CHX plus other active agents. Methods: A controlled, randomized, double-blind, crossover clinical trial was designed. Thirtysubjects underwent four consecutive experimental phases with four treatments: CHX 0.1% +hydroxymethylcellulose 2.5% (HMC), CHX 0.12% + alcohol, CHX 0.12% + 0.05% sodium fluoride, and CHX 0.05% + 0.05% Cpc. On the day of study, the subjects discontinued all other oral hygiene habits and were randomly assigned for treatment with the experimental mouthwash. Each experimental phase was preceded by a 28-day washout period. Plaque formation was recorded after one undisturbed day. Results: Formulations of CHX 0.12% with alcohol and sodium fluoride and CHX 0.1% +HMC 2.5% reduced de novo plaque formation to a greater extent than the mouthwash with CHX 0.05% + Cpc (P < 0.05). Conclusion: The 0.1% CHX gel presents an anti-plaque efficacy similar to that of mouthwashes containing 0.12% CHX and other active agents, and was more effective at inhibiting plaque formation than the mouthwash containing 0.05% CHX with Cpc. [ABSTRACT FROM AUTHOR]

Dental caries continues to be a common chronic disease among various population groups. Patient care can be improved with detection at the earliest stage. However, current techniques do not have sufficient sensitivity and specificity. We discuss 2 new methods - optical coherence tomography (OCT) and polarized Raman spectroscopy (PRS) - that are potentially useful for early caries detection and monitoring. OCT produces morphologic depth images of near-surface tissue structures with a resolution that is an order of magnitude greater than ultrasound imaging. Based on measurement of back-scattered near infrared light, OCT shows that sound enamel causes high-intensity back-scattering at the tooth surface that decreases rapidly with depth. In contrast, incipient lesions cause higher light back-scattering at the tooth surface and subsurface scattering indicative of porosity caused by demineralization. The scatter region within the enamel correlates well with the classical triangular shape of subsurface lesions observed in histologic sections. OCT imaging not only allows identification of incipient lesions, but also provides information on surface integrity and lesion depth. PRS furnishes biochemical information about the tooth"s composition, mineral content and crystallinity. The depolarization ratio derived from the dominant phosphate peak of hydroxyapatite in sound teeth is consistently lower than that from incipient caries. This difference is attributed to the change in enamel crystallite morphology or orientation that occurs with acid demineralization. Thus, PRS can be used to confirm suspect lesions determined by OCT and rule out false-positive signals from non-carious anomalies. The combination of OCT and PRS provides a new detection method with high sensitivity and specificity that will improve caries management and patient care. Future studies are aimed at developing intraoral probes to validate the findings in vivo. [ABSTRACT FROM AUTHOR]

Review the signs and symptoms of Parkinson's disease and available treatment options. [ABSTRACT FROM AUTHOR]

The article focuses on the Kikuchi-Fujimoto disease (KFD). The rare condition is also called histiocytic necrotizing lymphadenitis whose etiology is said to be unknown. It adds that KFD tends to affect people below 30 years of age and is prevalent among women. Characteristics of the disease are cited which include a proliferative and/or necrotizing process in the lymph nodes and the presence of necrosis and karyorrhexis in enlarged lymph nodes.

Based on findings from The Cancer Genome Atlas and the Proactive Molecular Risk Classifier for Endometrial Cancer algorithm, endometrial carcinoma can now be stratified into 4 prognostically distinct subgroups based on molecular alterations and immunohistochemical (IHC) aberrations. In this study, we describe the de novo adoption and clinical reporting of prognostic subgroup classification based on next-generation sequencing (NGS) and IHC analyses of all endometrial carcinoma resections at a single institution, framed by the Exploration, Preparation, Implementation, and Sustainment model. Results from the first 13 months show 188 tumors underwent analysis by a combination of IHC and a medium-sized (56 analyzed genes) NGS-based assay. All cases were assigned as either POLE ( POLE -mutated) (5.3%), mismatch repair deficient (27.7%), no specific molecular profile (45.7%), or p53 abnormal (21.3%) inclusive of multiple-classifier cases. NGS-based analysis revealed additional distinctions among the subgroups, including reduced levels of PI3K pathway activation in the p53 abnormal subgroup, an increased rate of CTNNB1 activating mutation in the no specific molecular profile subgroup, and lower TP53 mutation variant allele frequencies in POLE and mismatch repair deficient subgroups compared with the p53 abnormal subgroup. Overall, we describe the testing protocol, reporting, and results of a combination of NGS and IHC to prospectively prognosticate endometrial carcinomas at a single tertiary care center., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

We describe a web-based tool, MakeSBML (https://sys-bio.github.io/makesbml/), that provides an installation-free application for creating, editing, and searching the Biomodels repository for SBML-based models. MakeSBML is a client-based web application that translates models expressed in human-readable Antimony to the System Biology Markup Language (SBML) and vice-versa. Since MakeSBML is a web-based application it requires no installation on the user's part. Currently, MakeSBML is hosted on a GitHub page where the client-based design makes it trivial to move to other hosts. This model for software deployment also reduces maintenance costs since an active server is not required. The SBML modeling language is often used in systems biology research to describe complex biochemical networks and makes reproducing models much easier. However, SBML is designed to be computer-readable, not human-readable. We therefore employ the human-readable Antimony language to make it easy to create and edit SBML models., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objective: To broadly assess the efficacy of medroxyprogesterone acetate (MPA) for ovulatory suppression during in vitro stimulation compared with gonadotropin-releasing hormone (GnRH) antagonist cycles., Design: Cohort trial., Setting: A single academic-affiliated private fertility practice., Patients: Patients of all diagnoses aged 18-44 years undergoing autologous in vitro fertilization (IVF) for fertility treatment between 2020 and 2023., Interventions: Comparison of MPA vs. antagonist IVF stimulation cycles., Main Outcome Measures: Rates of premature ovulation, oocyte and embryo yield, embryo quality, pregnancy rates, and logistical benefits., Results: Prospective data was collected on 418 patients who underwent MPA protocol ovarian stimulation (MPA group), which was compared with 419 historical control gonadotropin hormone-releasing hormone antagonist cycles (control group). Age was similar between groups (35.6 ± 4.6 vs. 35.7 ± 4.8 years; P = .75). There were no cases of premature ovulation in the MPA group compared with a total of five cases in the control group (0% vs. 1.2%; risk ratio [RR] = 0.09; 95% confidence interval [CI], 0.01, 1.66). No differences were seen between number of oocytes retrieved (14.3 ± 10.2 vs. 14.3 ± 9.7; P = .83), blastocysts (4.9 ± 4.6 vs. 5.0 ± 4.6; P = .89), or euploid blastocysts (2.4 ± 2.6 vs. 2.2 ± 2.4; P = .18) in the MPA vs. control group respectively. Clinical pregnancy rate was similar between groups (70.4% vs. 64.2%; RR = 0.92; 95% CI, 0.72, 1.18). There was no difference in length of IVF stimulation or dose of stimulation medications. Patients in the MPA group saved an average of $491 ± $119 on medications, had an average of one less monitoring visit (4.4 ± 0.9 vs. 5.6 ± 1.1; P<.01), and 5.0 ± 1.2 less injections per cycle. When adjusting for age and ovarian reserve, protocol group (MPA vs. control) did not influence having an embryo available for transfer (76.6% vs. 73.4%; adjusted RR = 1.05; 95% CI, 0.94, 1.14)., Conclusion: For ovulatory suppression during IVF cycles, MPA was effective at preventing ovulation while demonstrating similar cycle and reproductive outcomes, with the additional benefits of patient cost savings, increased convenience with decreased number of visits, and fewer injections., Competing Interests: Declaration of interests A.M.W. has nothing to disclose. C.D.W. has nothing to disclose. L.P.S. has nothing to disclose. S.P. is on the Scientific Advisory Board of PS Fertility (Charlottesville, Virginia) outside the submitted work. L.R.G. is a Consultant to LiNA Medical for research and development of hysteroscopy equipment outside the submitted work., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Modern biological research is increasingly informed by computational simulation experiments, which necessitate the development of methods for annotating, archiving, sharing, and reproducing the conducted experiments. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulation Experiment (MIASE) guidelines outline the information needed to share simulation experiments. SED-ML is a computer-readable format for the information outlined by MIASE, created as a community project and supported by many investigators and software tools. Level 1 Version 5 of SED-ML expands the ability of modelers to define simulations in SED-ML using the Kinetic Simulation Algorithm Onotoloy (KiSAO). While it was possible in Version 4 to define a simulation entirely using KiSAO, Version 5 now allows users to define tasks, model changes, ranges, and outputs using the ontology as well. SED-ML is supported by a growing ecosystem of investigators, model languages, and software tools, including various languages for constraint-based, kinetic, qualitative, rule-based, and spatial models, and many simulation tools, visual editors, model repositories, and validators. Additional information about SED-ML is available at https://sed-ml.org/., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Motivation: Developing biochemical models in systems biology is a complex, knowledge-intensive activity. Some modelers (especially novices) benefit from model development tools with a graphical user interface. However, as with the development of complex software, text-based representations of models provide many benefits for advanced model development. At present, the tools for text-based model development are limited, typically just a textual editor that provides features such as copy, paste, find, and replace. Since these tools are not "model aware," they do not provide features for: (i) model building such as autocompletion of species names; (ii) model analysis such as hover messages that provide information about chemical species; and (iii) model translation to convert between model representations. We refer to these as BAT features., Results: We present VSCode-Antimony, a tool for building, analyzing, and translating models written in the Antimony modeling language, a human readable representation of Systems Biology Markup Language (SBML) models. VSCode-Antimony is a source editor, a tool with language-aware features. For example, there is autocompletion of variable names to assist with model building, hover messages that aid in model analysis, and translation between XML and Antimony representations of SBML models. These features result from making VSCode-Antimony model-aware by incorporating several sophisticated capabilities: analysis of the Antimony grammar (e.g. to identify model symbols and their types); a query system for accessing knowledge sources for chemical species and reactions; and automatic conversion between different model representations (e.g. between Antimony and SBML)., Availability and Implementation: VSCode-Antimony is available as an open source extension in the VSCode Marketplace https://marketplace.visualstudio.com/items?itemName=stevem.vscode-antimony. Source code can be found at https://github.com/sys-bio/vscode-antimony., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: Posterior tracheomalacia (TM) is characterized by excessive intraluminal displacement of the tracheal membranous wall. Recently, novel surgical strategies for repair of posterior TM have been introduced. To our knowledge, these strategies have not been evaluated in a model of posterior TM. Thus, we sought to design an ex vivo mechanical model of posterior TM to evaluate potential repair interventions., Methods: A model for posterior TM was created with partial thickness longitudinal incisions to the posterior aspect of ex vivo porcine trachea. Three groups of tracheas were tested: (1) control (unmanipulated), (2) posterior TM (injury), and (3) intervention (repair). Interventions included external splinting with 0.3 and 0.5 mm bioresorbable plates, posterior tracheopexy, and injection tracheoplasty with calcium hydroxylapatite. An airtight tracheal system was created to measure tracheal wall collapse with changes in negative pressure. A bronchoscope and pressure transducer were connected to either end. Cross-sectional area of the tracheal lumen was analyzed using ImageJ software (National Institutes of Health, Bethesda, MD)., Results: Average percent reduction in cross-sectional area of the tracheal lumen was compared using a two-tailed paired t-test. Significant differences were found between control and TM groups (p < 0.019). There was no significant difference between control and external splinting and posterior tracheopexy groups (p > 0.14)., Conclusion: We describe an ex vivo model for posterior TM that replicates airway collapse. External splinting and tracheopexy interventions showed recovery of the injured tracheal segment. Injection tracheoplasty did not improve the TM., Level of Evidence: N/A Laryngoscope, 133:2000-2006, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Computational models are increasingly used in high-impact decision making in science, engineering, and medicine. The National Aeronautics and Space Administration (NASA) uses computational models to perform complex experiments that are otherwise prohibitively expensive or require a microgravity environment. Similarly, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have began accepting models and simulations as forms of evidence for pharmaceutical and medical device approval. It is crucial that computational models meet a standard of credibility when using them in high-stakes decision making. For this reason, institutes including NASA, the FDA, and the EMA have developed standards to promote and assess the credibility of computational models and simulations. However, due to the breadth of models these institutes assess, these credibility standards are mostly qualitative and avoid making specific recommendations. On the other hand, modeling and simulation in systems biology is a narrower domain and several standards are already in place. As systems biology models increase in complexity and influence, the development of a credibility assessment system is crucial. Here we review existing standards in systems biology, credibility standards in other science, engineering, and medical fields, and propose the development of a credibility standard for systems biology models., (© 2023. The Author(s).)

Thyroid carcinoma originating in struma ovarii comprises a small minority of all cases of struma ovarii. Given the rarity of this diagnosis, literature to guide evaluation and management is limited. The most common carcinoma originating from struma ovarii is papillary thyroid carcinoma. Treatment includes surgery, including a fertility sparing approach if disease is confined to the ovary, with consideration of total thyroidectomy and radioactive iodine ablation for high-risk pathologic features or disease spread beyond the ovary. This review discusses the histopathologic findings, molecular pathology, clinical implications and management, and prognosis of thyroid carcinomas originating in struma ovarii., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Adenocarcinoma of the uterine cervix, gastric-type (GAS) is a rare, well-differentiated subtype of HPV-independent endocervical adenocarcinoma. It classically arises in middle-aged women with symptoms, including profuse watery vaginal discharge and abnormal uterine bleeding. Given the rarity of this disease, misdiagnosis is common and prognosis remains poorly defined. Distinct pathology and imaging findings can aid in diagnosis. A literature review was performed to ascertain recurring pathologic and radiologic characteristics of GAS. Key pathologic features of GAS include cytologically benign appearing mucinous glands that infiltrate into the deep stroma and may demonstrate lymphovascular or perineural invasion. Multiple imaging modalities including transvaginal ultrasound, CT, and MRI may aid in diagnosis of GAS, which characteristically is seen as a multicystic mass with solid components. MRI in particular is the preferred imaging study because it offers the best chance of identifying a potential solid component, which is key to making the diagnosis of GAS and distinguishing it from other endocervical diseases processes. Careful attention to histopathologic and radiologic details, in conjunction with clinical correlation, is necessary to distinguish GAS from other multicystic cervical lesions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett's esophagus compared to 40 Barrett's patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett's tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures. The critical distinction between stable Barrett's versus those who progress to cancer is acquisition and expansion of TP53-/- cell populations having complex structural variants and high-level amplifications, which are detectable up to six years prior to a cancer diagnosis. These findings reveal the timing of common somatic genome dynamics in stable Barrett's esophagus and define key genomic features specific to progression to esophageal adenocarcinoma, both of which are critical for cancer prevention and early detection strategies., (© 2022. The Author(s).)

Objectives: To optimize a 3D printed tissue-engineered tracheal construct using a combined in vitro and a two-stage in vivo technique., Methods: A 3D-CAD (Computer-aided Design) template was created; rabbit chondrocytes were harvested and cultured. A Makerbot Replicator™ 2x was used to print a polycaprolactone (PCL) scaffold which was then combined with a bio-ink and the previously harvested chondrocytes. In vitro: Cell viability was performed by live/dead assay using Calcein A/Ethidium. Gene expression was performed using quantitative real-time PCR for the following genes: Collagen Type I and type II, Sox-9, and Aggrecan. In vivo: Surgical implantation occurred in two stages: 1) Index procedure: construct was implanted within a pocket in the strap muscles for 21 days and, 2) Final surgery: construct with vascularized pedicle was rotated into a segmental tracheal defect for 3 or 6 weeks. Following euthanasia, the construct and native trachea were explanted and evaluated., Results: In vitro: After 14 days in culture the constructs showed >80% viable cells. Collagen type II and sox-9 were overexpressed in the construct from day 2 and by day 14 all genes were overexpressed when compared to chondrocytes in monolayer., In Vivo: By day 21 (immediately before the rotation), cartilage formation could be seen surrounding all the constructs. Mature cartilage was observed in the grafts after 6 or 9 weeks in vivo., Conclusion: This two-stage approach for implanting a 3D printed tissue-engineered tracheal replacement construct has been optimized to yield a high-quality, printable segment with cellular growth and viability both in vitro and in vivo., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Combining tissue engineering and three-dimensional (3D) printing may allow for the introduction of a living functional tracheal replacement graft. However, defining the biomechanical properties of the native trachea is a key prerequisite to clinical translation. To achieve this, we set out to define the rotation, axial stretch capacity, and positive intraluminal pressure capabilities for ex vivo porcine tracheas., Study Design: Animal study., Materials and Methods: Six full-length ex vivo porcine tracheas were bisected into 5.5 cm segments. Maximal positive intraluminal pressure was measured by sealing segment ends with custom designed 3D printed caps through which a pressure transducer was introduced. Axial stretch capacity and rotation were evaluated by stretching and rotating the segments along their axis between two clamps, respectively., Results: Six segments were tested for axial lengthening and the average post-stretch length percentage was 148.92% (range 136.81-163.48%, 95% CI 153-143%). The mean amount of length gain achieved per cartilaginous ring was 7.82% (range 4.71-10.95%, 95% CI 6.3-9.35%). Four tracheal segments were tested for maximal positive intraluminal pressure, which was over 400 mmHg. Degree of rotation testing found that the tracheal segments easily transformed 180° in anterior-posterior bending, lateral bending, and axial rotational twisting., Conclusions: We define several biomechanical properties of the ex vivo porcine trachea by reporting the rotation, axial stretch capacity, and positive intraluminal pressure capabilities. We hope that this will aid future work in the clinical translation of 3D bioprinted airway replacement grafts and ensure their compatibility with native tracheal properties., (Copyright © 2021. Published by Elsevier Inc.)

Background: Burn injury and operating room fires are significant risks for both surgical patients and staff. The purpose of this study was to examine the fire and burn risks associated with two types of fiberoptic light cables and evaluate the efficacy of a novel device in reducing the risk of these fire and burn injuries., Methods: A 300-W light source was connected sequentially to two standard fiberoptic cables (Storz and Olympus). The distal ends were buried in, or rested on, standard operating room materials including a cotton green towel and a blue propylene drape to assess the risk of fire formation or burn injury. The Gloshield device was then attached to the ends of the cables and the experiment was repeated. Trials simulating improper use of the device were then conducted with the Gloshield device placed either too deep or too shallow on the end of the light cable. All trials were conducted for a maximum of 10 min or until a positive result (burn or fire) was achieved. Trials were conducted in room air or with supplemental 100% oxygen and repeated for accuracy., Results: Both the Storz and Olympus fiber optic cables were capable of producing burns in standard operating room towels and drapes in control trials. The Gloshield device prevented thermal injury when properly attached in all conditions. Improper use trials demonstrated that the device may be ineffective when not applied properly., Conclusions: The Gloshield device is effective in reducing the risk of thermal burn injury by protecting the distal ends of endoscopic light cables from operating room materials. However, the device needs to be attached appropriately in order to provide protective benefits., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Computational simulation experiments increasingly inform modern biological research, and bring with them the need to provide ways to annotate, archive, share and reproduce the experiments performed. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulation Experiment (MIASE) guidelines outline the information needed to share simulation experiments. SED-ML is a computer-readable format for the information outlined by MIASE, created as a community project and supported by many investigators and software tools. The first versions of SED-ML focused on deterministic and stochastic simulations of models. Level 1 Version 4 of SED-ML substantially expands these capabilities to cover additional types of models, model languages, parameter estimations, simulations and analyses of models, and analyses and visualizations of simulation results. To facilitate consistent practices across the community, Level 1 Version 4 also more clearly describes the use of SED-ML constructs, and includes numerous concrete validation rules. SED-ML is supported by a growing ecosystem of investigators, model languages, and software tools, including eight languages for constraint-based, kinetic, qualitative, rule-based, and spatial models, over 20 simulation tools, visual editors, model repositories, and validators. Additional information about SED-ML is available at https://sed-ml.org/., Competing Interests: Authors state no conflict of interest., (2021 Lucian P. Smith et al.)

Objectives/hypothesis: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality., Study Design: Delphi method-based survey series., Methods: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up., Results: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18)., Conclusion: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes., Level of Evidence: 5 Laryngoscope, 131:E1941-E1949, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Patients undergoing tonsillectomy and adenoidectomy traditionally receive anesthesia with endotracheal intubation (ETT) for airway management. The laryngeal mask airway (LMA) may be used instead and may be associated with less airway stimulation and shorter operating room times. The purpose of this study was to report on a large cohort of patients undergoing tonsillectomy and/or adenoidectomy while using the LMA for airway maintenance during anesthesia., Methods: Patients undergoing tonsillectomy and adenoidectomy between January 6, 2017 and January 6, 2020 with a LMA were reviewed for safety outcomes. We compared two cohorts of patients with LMA and ETT to analyze the effect on operating room times., Results: Our study identified 1042 patients who met criteria for review. The incidence of cases requiring conversion to ETT (1.2%) and laryngospasm (0.3%) in our cohort is lower than previously suggested by the literature. The patients who underwent surgery with the LMA spent less time in the operating room (p = 0.004) compared to the ETT group., Conclusion: The use of the LMA may be a safe and effective option for airway management during tonsillectomy and adenoidectomy. There may be a benefit of OR time reduction in patients undergoing anesthesia with an LMA compared to ETT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.g., chromothripsis) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,778 tumor whole-genome sequences, we uncovered three novel complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early-replicating regions, superenhancers, and breast or ovarian cancers. Rigma comprise "chasms" of low-JCN deletions enriched in late-replicating fragile sites and gastrointestinal carcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold-back inversions associated with expressed protein-coding fusions, breakend hypermutation, and acral, but not cutaneous, melanomas. Clustering of tumors according to genome graph-derived features identified subgroups associated with DNA repair defects and poor prognosis., Competing Interests: Declaration of Interests J.S.R.-F. reports receiving personal/consultancy fees from VolitionRx, Paige.AI, Goldman Sachs, REPARE Therapeutics, GRAIL, Ventana Medical Systems, Roche, Genentech, and InviCRO outside of the scope of the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Barrett's Esophagus is a neoplastic condition which progresses to esophageal adenocarcinoma in 5% of cases. Key events affecting the outcome likely occur before diagnosis of Barrett's and cannot be directly observed; we use phylogenetic analysis to infer such past events. We performed whole-genome sequencing on 4-6 samples from 40 cancer outcome and 40 noncancer outcome patients with Barrett's Esophagus, and inferred within-patient phylogenies of deconvoluted clonal lineages. Spatially proximate lineages clustered in the phylogenies, but temporally proximate ones did not. Lineages with inferred loss-of-function mutations in both copies of TP53 and CDKN2A showed enhanced spatial spread, whereas lineages with loss-of-function mutations in other frequently mutated loci did not. We propose a two-phase model with expansions of TP53 and CKDN2A mutant lineages during initial growth of the segment, followed by relative stasis. Subsequent to initial expansion, mutations in these loci as well as ARID1A and SMARCA4 may show a local selective advantage but do not expand far: The spatial structure of the Barrett's segment remains stable during surveillance even in patients who go on to cancer. We conclude that the cancer/noncancer outcome is strongly affected by early steps in formation of the Barrett's segment., Competing Interests: None declared., (© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., (© 2020 California Institute of Technology Published under the terms of the CC BY 4.0 license.)

Multigene panel testing for cancer predisposition mutations is becoming routine in clinical care. However, the gene content of panels offered by testing laboratories vary significantly, and data on mutation detection rates by gene and by the panel is limited, causing confusion among clinicians on which test to order. Using results from 147,994 multigene panel tests conducted at Ambry Genetics, we built an interactive prevalence tool to explore how differences in ethnicity, age of onset, and personal and family history of different cancers affect the prevalence of pathogenic mutations in 31 cancer predisposition genes, across various clinically available hereditary cancer gene panels. Over 13,000 mutation carriers were identified in this high-risk population. Most were non-Hispanic white (74%, n = 109,537), but also Black (n  = 10,875), Ashkenazi Jewish (n  = 10,464), Hispanic (n  = 10,028), and Asian (n  = 7,090). The most prevalent cancer types were breast (50%), ovarian (6.6%), and colorectal (4.7%), which is expected based on genetic testing guidelines and clinician referral for testing. The Hereditary Cancer Multi-Gene Panel Prevalence Tool presented here can be used to provide insight into the prevalence of mutations on a per-gene and per-multigene panel basis, while conditioning on multiple custom phenotypic variables to include race and cancer type., (© 2020 The Authors. Human Mutation Published by Wiley Periodicals LLC.)

Biological models often contain elements that have inexact numerical values, since they are based on values that are stochastic in nature or data that contains uncertainty. The Systems Biology Markup Language (SBML) Level 3 Core specification does not include an explicit mechanism to include inexact or stochastic values in a model, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactic constructs. The SBML Distributions package for SBML Level 3 adds the necessary features to allow models to encode information about the distribution and uncertainty of values underlying a quantity.

Rule-based modeling is an approach that permits constructing reaction networks based on the specification of rules for molecular interactions and transformations. These rules can encompass details such as the interacting sub-molecular domains and the states and binding status of the involved components. Conceptually, fine-grained spatial information such as locations can also be provided. Through "wildcards" representing component states, entire families of molecule complexes sharing certain properties can be specified as patterns. This can significantly simplify the definition of models involving species with multiple components, multiple states, and multiple compartments. The systems biology markup language (SBML) Level 3 Multi Package Version 1 extends the SBML Level 3 Version 1 core with the "type" concept in the Species and Compartment classes. Therefore, reaction rules may contain species that can be patterns and exist in multiple locations. Multiple software tools such as Simmune and BioNetGen support this standard that thus also becomes a medium for exchanging rule-based models. This document provides the specification for Release 2 of Version 1 of the SBML Level 3 Multi package. No design changes have been made to the description of models between Release 1 and Release 2; changes are restricted to the correction of errata and the addition of clarifications.

Purpose: Despite the rapid uptake of multigene panel testing (MGPT) for hereditary cancer predisposition, there is limited guidance surrounding indications for testing and genes to include., Methods: To inform the clinical approach to hereditary cancer MGPT, we comprehensively evaluated 32 cancer predisposition genes by assessing phenotype-specific pathogenic variant (PV) frequencies, cancer risk associations, and performance of genetic testing criteria in a cohort of 165,000 patients referred for MGPT., Results: We identified extensive genetic heterogeneity surrounding predisposition to cancer types commonly referred for germline testing (breast, ovarian, colorectal, uterine/endometrial, pancreatic, and melanoma). PV frequencies were highest among patients with ovarian cancer (13.8%) and lowest among patients with melanoma (8.1%). Fewer than half of PVs identified in patients meeting testing criteria for only BRCA1/2 or only Lynch syndrome occurred in the respective genes (33.1% and 46.2%). In addition, 5.8% of patients with PVs in BRCA1/2 and 26.9% of patients with PVs in Lynch syndrome genes did not meet respective testing criteria., Conclusion: Opportunities to improve upon identification of patients at risk for hereditary cancer predisposition include revising BRCA1/2 and Lynch syndrome testing criteria to include additional clinically actionable genes with overlapping phenotypes and relaxing testing criteria for associated cancers.

Motivation: CNValidator assesses the quality of somatic copy-number calls based on coherency of haplotypes across multiple samples from the same individual. It is applicable to any copy-number calling algorithm, which makes calls independently for each sample. This test is useful in assessing the accuracy of copy-number calls, as well as choosing among alternative copy-number algorithms or tuning parameter values., Results: On a dataset of somatic samples from individuals with Barrett's Esophagus, CNValidator provided feedback on the correctness of sample ploidy calls and also detected data quality issues., Availability and Implementation: CNValidator is available on GitHub at https://github.com/kuhnerlab/CNValidator., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2018. Published by Oxford University Press.)