Weighted metrics are required when evaluating the performance of prediction models in nested case-control studies.

Background: Nested case-control (NCC) designs are efficient for developing and validating prediction models that use expensive or difficult-to-obtain predictors, especially when the outcome is rare. Previous research has focused on how to develop prediction models in this sampling design, but little attention has been given to model validation in this context. We therefore aimed to systematically characterize the key elements for the correct evaluation of the performance of prediction models in NCC data.

Personalised decision making to predict absolute metastatic risk in cutaneous squamous cell carcinoma: development and validation of a clinico-pathological model.

Background: Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, affecting more than 2 million people worldwide yearly and metastasising in 2-5% of patients. However, current clinical staging systems do not provide estimates of absolute metastatic risk, hence missing the opportunity for more personalised treatment advice. We aimed to develop a clinico-pathological model that predicts the probability of metastasis in patients with cSCC.

Design, validation and implementation of an automated e-alert for acute kidney injury: 6-month pilot study shows increased awareness.

Background: Acute kidney injury (AKI) is defined as a sudden episode of kidney failure but is known to be under-recognized by healthcare professionals. The Kidney Disease Improving Global Outcome (KDIGO) guidelines have formulated criteria to facilitate AKI diagnosis by comparing changes in plasma creatinine measurements (PCr). To improve AKI awareness, we implemented these criteria as an electronic alert (e-alert), in our electronic health record (EHR) system.

A machine learning approach using endpoint adjudication committee labels for the identification of sepsis predictors at the emergency department.

Accurate sepsis diagnosis is paramount for treatment decisions, especially at the emergency department (ED). To improve diagnosis, clinical decision support (CDS) tools are being developed with machine learning (ML) algorithms, using a wide range of variable groups. ML models can find patterns in Electronic Health Record (EHR) data that are unseen by the human eye.

Transportability and Implementation Challenges of Early Warning Scores for Septic Shock in the ICU: A Perspective on the TREWScore.

The increased use of electronic health records (EHRs) has improved the availability of routine care data for medical research. Combined with machine learning techniques this has spurred the development of early warning scores (EWSs) in hospitals worldwide. EWSs are commonly used in the hospital where they have been developed, yet few have been transported to external settings and/or internationally.

Ambiguous definitions for baseline serum creatinine affect acute kidney diagnosis at the emergency department.

Background: Acute kidney injury (AKI) incidence is increasing, however AKI is often missed at the emergency department (ED). AKI diagnosis depends on changes in kidney function by comparing a serum creatinine (SCr) measurement to a baseline value. However, it remains unclear to what extent different baseline values may affect AKI diagnosis at ED.

Clinicopathologic models predicting non-sentinel lymph node metastasis in cutaneous melanoma patients: Are they useful for patients with a single positive sentinel node?

Background And Objectives: Of clinically node-negative (cN0) cutaneous melanoma patients with sentinel lymph node (SLN) metastasis, between 10% and 30% harbor additional metastases in non-sentinel lymph nodes (NSLNs). Approximately 80% of SLN-positive patients have a single positive SLN.

Methods: To assess whether state-of-the-art clinicopathologic models predicting NSLN metastasis had adequate performance, we studied a single-institution cohort of 143 patients with cN0 SLN-positive primary melanoma who underwent subsequent completion lymph node dissection.

Identification of stage I/IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model.

Purpose: Patients with stage I/IIA cutaneous melanoma (CM) are currently not eligible for adjuvant therapies despite uncertainty in relapse risk. Here, we studied the ability of a recently developed model which combines clinicopathologic and gene expression variables (CP-GEP) to identify stage I/IIA melanoma patients who have a high risk for disease relapse.

Patients And Methods: Archival specimens from a cohort of 837 consecutive primary CMs were used for assessing the prognostic performance of CP-GEP.

Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

Purpose: More than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here we describe a model that combines clinicopathologic and molecular variables to identify patients with thin and intermediate thickness melanomas who may forgo the SLN biopsy procedure due to their low risk of nodal metastasis.

Patients And Methods: Genes with functional roles in melanoma metastasis were discovered by analysis of next generation sequencing data and case control studies.

Real-time three-dimensional jaw tracking in temporomandibular disorders.

When a dysfunction occurs in any component of the stomatognathic system, temporomandibular disorders (TMD) may originate. The aim of this study was to compare the deviations, displacement and the execution speed of mandibular movements among asymptomatic participants and those with TMD. Convenience sampling was used; forty participants diagnosed by clinical evaluation following the Research Diagnostic Criteria for Temporomandibular Disorders were divided into three groups: arthropathy (GART, 10 participants, 40% men), myopathy (GMYO, 10 participants, 30% men), and the control group (CG, 20 asymptomatic participants, 25% men).

Monte-Carlo modeling of the central carbon metabolism of Lactococcus lactis: insights into metabolic regulation.

Metabolic pathways are complex dynamic systems whose response to perturbations and environmental challenges are governed by multiple interdependencies between enzyme properties, reactions rates, and substrate levels. Understanding the dynamics arising from such a network can be greatly enhanced by the construction of a computational model that embodies the properties of the respective system. Such models aim to incorporate mechanistic details of cellular interactions to mimic the temporal behavior of the biochemical reaction system and usually require substantial knowledge of kinetic parameters to allow meaningful conclusions.

A specialized motion capture system for real-time analysis of mandibular movements using infrared cameras.

Background: In the last years, several methods and devices have been proposed to record the human mandibular movements, since they provide quantitative parameters that support the diagnosis and treatment of temporomandibular disorders. The techniques currently employed suffer from a number of drawbacks including high price, unnatural to use, lack of support for real-time analysis and mandibular movements recording as a pure rotation. In this paper, we propose a specialized optical motion capture system, which causes a minimum obstruction and can support 3D mandibular movement analysis in real-time.

Role of phosphate in the central metabolism of two lactic acid bacteria--a comparative systems biology approach.

Lactic acid-producing bacteria survive in distinct environments, but show common metabolic characteristics. Here we studied the dynamic interactions of the central metabolism in Lactococcus lactis, extensively used as a starter culture in the dairy industry, and Streptococcus pyogenes, a human pathogen. Glucose-pulse experiments and enzymatic measurements were performed to parameterize kinetic models of glycolysis.

Response rescaling in bacterial chemotaxis.

Sensory systems rescale their response sensitivity upon adaptation according to simple strategies that recur in processes as diverse as single-cell signaling, neural network responses, and whole-organism perception. Here, we study response rescaling in Escherichia coli chemotaxis, where adaptation dynamically tunes the cells' motile response during searches for nutrients. Using in vivo fluorescence resonance energy transfer (FRET) measurements on immobilized cells, we demonstrate that the design of this prokaryotic signaling network follows the fold-change detection (FCD) strategy, responding faithfully to the shape of the input profile irrespective of its absolute intensity.

Measurement of jaw motion: the proposal of a simple and accurate method.

The analysis of jaw movements has long been used as a measure for clinical diagnosis and assessment. A number of strategies are available for monitoring the trajectory; however most of these strategies make use of expensive tools, which are often not available to many clinics in the world. In this context, this research proposes the development of a new tool capable of quantifying the movements of opening/closing, protrusion and laterotrusion of the mandible.

Stability from structure: metabolic networks are unlike other biological networks.

In recent work, attempts have been made to link the structure of biochemical networks to their complex dynamics. It was shown that structurally stable network motifs are enriched in such networks. In this work, we investigate to what extent these findings apply to metabolic networks.

A computational method for recording and analysis of mandibular movements.

This study proposed the development of a new clinical tool capable of quantifying the movements of opening-closing, protrusion and laterotrusion of the mandible. These movements are important for the clinical evaluation of the temporomandibular function and muscles involved in mastication. Unlike current commercial systems, the proposed system employs a low-cost video camera and a computer program that is used for reconstructing the trajectory of a reflective marker that is fixed on the mandible.

Transgenic overexpression of vascular endothelial growth factor-B isoforms by endothelial cells potentiates postnatal vessel growth in vivo and in vitro.

Vascular endothelial growth factors (VEGFs) play significant roles in endothelial growth, survival, and function, and their potential use as therapeutic agents to promote the revascularization of ischemic tissues in being avidly explored. VEGF-A has received most attention, as it is a potent stimulator of vascular growth. Results in clinical trials of VEGF-A as a therapeutic agent have fallen short of high expectations because of serious edematous side effects caused by its activity in promoting vascular permeability.

Vascular endothelial growth factor-B-deficient mice show impaired development of hypoxic pulmonary hypertension.

Objective: To test the hypothesis that Vegf-B contributes to the pulmonary vascular remodelling, and the associated pulmonary hypertension, induced by exposure of mice to chronic hypoxia.

Methods: Right ventricular systolic pressure, the ratio of right ventricle/[left ventricle+septum] (RV/[LV+S]) and the thickness of the media (relative to vessel diameter) of intralobar pulmonary arteries (o.d.

Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia.

Vascular endothelial growth factor-B (VEGF-B) is closely related to VEGF-A, an effector of blood vessel growth during development and disease and a strong candidate for angiogenic therapies. To further study the in vivo function of VEGF-B, we have generated Vegfb knockout mice (Vegfb(-/-)). Unlike Vegfa knockout mice, which die during embryogenesis, Vegfb(-/-) mice are healthy and fertile.

Cell proliferation in mammalian gastrulation: the ventral node and notochord are relatively quiescent.

During gastrulation, the node of the mammalian embryo appears to be an organising centre, homologous to Hensen's node in the chick and the dorsal lip of the amphibian blastopore. In addition, the node serves as a precursor population for the head process, notochord and foregut endoderm. We have studied node architecture and cell morphology by electron microscopy, and cell proliferation using bromodeoxyuridine incorporation and mitotic counts.

Effects of ethanol and acetaldehyde on rat embryos developing in vitro.

Rat embryos were explanted on Days 9.5 or 10 of gestation and cultured for 48 to 30h, respectively, in rat serum containing 0, 3, 6, 9 mg/ml of Ethanol (Eth); 0, 10, 20 micrograms/ml of Acetaldehyde (Ach); 3 mg/ml Eth + 10 micrograms/ml Ach. At the end of the culture period the embryos were evaluated for vitality, and scored.