Purpose: To evaluate ability of radiomic (computer-extracted imaging) features to distinguish non-small cell lung cancer adenocarcinomas from granulomas at noncontrast CT. Materials and Methods: For this retrospective study, screening or standard diagnostic noncontrast CT images were collected for 290 patients (mean age, 68 years; range, 18–92 years; 125 men [mean age, 67 years; range, 18–90 years] and 165 women [mean age, 68 years; range, 33–92 years]) from two institutions between 2007 and 2013. Histopathologic analysis was available for one nodule per patient. Corresponding nodule of interest was identified on CT axial images by a radiologist with manually annotation. Nodule shape, wavelet (Gabor), and texture-based (Haralick and Laws energy) features were extracted from intra- and perinodular regions. Features were pruned to train machine learning classifiers with 145 patients. In a test set of 145 patients, classifier results were compared against a convolutional neural network (CNN) and diagnostic readings of two radiologists. Results: Support vector machine classifier with intranodular radiomic features achieved an area under the receiver operating characteristic curve (AUC) of 0.75 on the test set. Combining radiomics of intranodular with perinodular regions improved the AUC to 0.80. On the same test set, CNN resulted in an AUC of 0.76. Radiologist readers achieved AUCs of 0.61 and 0.60, respectively. Conclusion: Radiomic features from intranodular and perinodular regions of nodules can distinguish non-small cell lung cancer adenocarcinomas from benign granulomas at noncontrast CT. Summary Perinodular and intranodular radiomic features corresponding to texture and shape (radiomics) were evaluated to distinguish nonsmall cell lung cancer adenocarcinomas from benign granulomas at noncontrast CT.

1. Humans experiencing intermittent hypoxia (IH) owing to recurrent apnoea syndromes exhibit serious cardiovascular morbidity, including high blood pressure, increased sympathetic nerve activity, cardiac arrhythmia and myocardial infarction. Although apnoeas are accompanied by a simultaneous decrease in arterial O(2) (hypoxia) and an increase in CO(2) (hypercapnia), studies on experimental animals suggest that hypoxia, rather than hypercapnia, is the primary stimulus for developing hypertension and enhanced sympathetic nerve activity. Enhanced hypoxic-sensing ability of the carotid bodies and the ensuing reflex activation of the sympathetic nervous system have been suggested to play a critical role in cardiorespiratory alterations resulting from recurrent apnoeas. 2. The purpose of the present review is to highlight recent studies demonstrating the effects of IH on carotid body sensory activity and its consequences on sympathetic activation in a rodent model of chronic IH. Adult rats exposed to chronic IH (15 s of 5% O(2) followed by 5 min of 21% O(2), nine episodes per h, 8 h/day for 10 days) exhibited selective enhancement of carotid body sensory response to hypoxia. In addition, chronic IH induced a novel form of sensory plasticity in the carotid body, manifested as sensory long-term facilitation (LTF). Functional changes in the carotid body occurred in the absence of morphological changes in the chemoreceptor tissue. 3. Acute hypoxia increased expiratory modulated splanchnic nerve activity (SNA) and acute IH-induced LTF in SNA. Hypoxia-induced SNA activation was prevented by bilateral sectioning of the sinus nerves. Rats exposed to chronic IH exhibited enhanced hypoxia-induced sympathetic activation and augmented LTF of the SNA. Bilateral sectioning of the sinus nerves abolished these responses, suggesting chronic IH-induced alterations in carotid body sensitivity contribute to LTF in SNA and the subsequent cardiovascular alterations.

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1-10 days) and adult (6-8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.

phox , the membrane subunit of the NADPH oxidase complex, showed no sensory LTF, although responding to 5-HT with initial afferent nerve activation, whereas both LTF and initial excitation by 5-HT were seen in wild-type mice. These results demonstrate that spaced but not mass application of 5-HT elicits sensory LTF of the carotid body via activation of 5-HT 2 receptors, which involves a novel signalling mechanism coupled to PKC-dependent activation of NADPH oxidase.

Sepsisis a clinical syndrome characterized by a multi-system response to a microbial pathogenic insult consisting of a mosaic of interconnected biochemical, cellular, and organ-organ interaction networks. A central thread that connects these responses is inflammation, which, while attempting to defend the body and prevent further harm, causes further damage through the feed-forward, pro-inflammatory effects of damage-associated molecular pattern molecules. In this review, we address the epidemiology and current definitions of sepsis, and focus specifically on the biological cascades that comprise the inflammatory response to sepsis. We suggest that attempts to improve clinical outcomes by targeting specific components of this network have been unsuccessful due to the lack of an integrative, predictive, and individualized systems-based approach to define the time-varying, multi-dimensional state of the patient. We highlight the translational impact of computational modeling and other complex systems approaches as applied to sepsis, including in silico clinical trials, patient-specific models, and complexity-based assessments of physiology.