Search

Context.--Most deep learning (DL) studies have focused on neoplastic pathology, with the realm of inflammatory pathology remaining largely untouched. Objective.--To investigate the use of DL for nonneoplastic gastric biopsies. Design.--Gold standard diagnoses were blindly established by 2 gastrointestinal pathologists. For phase 1, 300 classic cases (100 normal, 100 Helicobacter pylori, 100 reactive gastropathy) that best displayed the desired pathology were scanned and annotated for DL analysis. A total of 70% of the cases for each group were selected for the training set, and 30% were included in the test set. The software assigned colored labels to the test biopsies, which corresponded to the area of the tissue assigned a diagnosis by the DL algorithm, termed area distribution (AD). For Phase 2, an additional 106 consecutive nonclassical gastric biopsies from our archives were tested in the same fashion. Results.--For Phase 1, receiver operating curves showed near perfect agreement with the gold standard diagnoses at an AD percentage cutoff of 50% for normal (area under the curve [AUC] = 99.7%) and H pylori (AUC = 100%), and 40% for reactive gastropathy (AUC = 99.9%). Sensitivity/specificity pairings were as follows: normal (96.7%, 86.7%), H pylori (100%, 98.3%), and reactive gastropathy (96.7%, 96.7%). For phase 2, receiver operating curves were slightly less discriminatory, with optimal AD cutoffs reduced to 40% across diagnostic groups. The AUCs were 91.9% for normal, 100% for H pylori, and 94.0% for reactive gastropathy. Sensitivity/ specificity parings were as follows: normal (73.7%, 79.6%), H pylori (95.7%, 100%), reactive gastropathy (100%, 62.5%). Conclusions.--A convolutional neural network can serve as an effective screening tool/diagnostic aid for H pylori gastritis. [ABSTRACT FROM AUTHOR]

The article describes an activity program for secondary education which teaches mathematics students various aspects including parametric curves plotting, using technology to graph parametric equations to fill space, and mathematical conjecture about parameters.

Blood cultures are often obtained in postoperative patients to rule out bloodstream infections. Our study objectives were to determine the efficacy of blood cultures in postoperative patients with suspected sepsis and to determine variables predisposing patients to positive cultures. This was a retrospective study including patients with blood cultures drawn from January to March 2009 at our institution. We recorded demographics, presence of fever (temperature 101.5°F or higher), elevated white blood cell count (12,000/µL or greater), central line, diabetes, intensive care unit admission, postoperative day of blood draw, National Research Council surgical wound classification, and pre- or postoperative antibiotics. Blood cultures were drawn from 150 patients undergoing surgery within 30 days prior. Sixteen had positive cultures and nine were true-positives (6.3%). There was no statistical difference (P > 0.05) between patients with positive and negative cultures except that those with negative cultures were more likely to have received preoperative antibiotics (P = 0.0186). Blood cultures are invasive, expensive tests with low yield. We recommend that blood cultures be drawn in patients not receiving preoperative antibiotics who have undergone surgery more than 4 days before culture. [ABSTRACT FROM AUTHOR]

The goal of this work is to accurately detect and localize boundaries in natural scenes using local image measurements. We formulate features that respond to characteristic changes in brightness, color, and texture associated with natural boundaries. In order to combine the information from these features in an optimal way, we train a classifier using human labeled images as ground truth. The output of this classifier provides the posterior probability of a boundary at each image location and orientation. We present precision-recall curves showing that the resulting detector significantly outperforms existing approaches. Our two main results are 1) that cue combination can be performed adequately with a simple linear model and 2) that a proper, explicit treatment of texture is required to detect boundaries in natural images. [ABSTRACT FROM AUTHOR]

Objectives: The presence of nodal metastases in patients with papillary thyroid carcinoma (PTC) has both staging and treatment implications. However, lymph nodes are often not removed during thyroidectomy. Prior work has demonstrated the capability of artificial intelligence (AI) to predict the presence of nodal metastases in PTC based on the primary tumor histopathology alone. This study aimed to replicate these results with multi-institutional data. Methods: Cases of conventional PTC were identified from the records of 2 large academic institutions. Only patients with complete pathology data, including at least 3 sampled lymph nodes, were included in the study. Tumors were designated "positive" if they had at least 5 positive lymph node metastases. First, algorithms were trained separately on each institution's data and tested independently on the other institution's data. Then, the data sets were combined and new algorithms were developed and tested. The primary tumors were randomized into 2 groups, one to train the algorithm and another to test it. A low level of supervision was used to train the algorithm. Board-certified pathologists annotated the slides. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic curves and the Youden J statistic were used for primary analysis. Results: There were 420 cases used in analyses, 45% of which were negative. The best performing single institution algorithm had an area under the curve (AUC) of 0.64 with a sensitivity and specificity of 65% and 61% respectively, when tested on the other institution's data. The best performing combined institution algorithm had an AUC of 0.84 with a sensitivity and specificity of 68% and 91% respectively. Conclusion: A convolutional neural network can produce an accurate and robust algorithm that is capable of predicting nodal metastases from primary PTC histopathology alone even in the setting of multi-institutional data. [ABSTRACT FROM AUTHOR]

Transferrin receptor (TFRC) is the major mediator for iron entry into a cell. Under excessive iron conditions, TFRC is expected to be reduced to lower iron uptake and toxicity. However, the mechanism whereby TFRC expression is maintained at high levels in iron‐enriched cancer cells and the contribution of TFRC to cancer development are enigmatic. Here the work shows TFRC is induced by adenomatous polyposis coli (APC) gene loss‐driven β‐catenin activation in colorectal cancer, whereas TFRC‐mediated intratumoral iron accumulation potentiates β‐catenin signaling by directly enhancing the activity of tankyrase. Disruption of TFRC leads to a reduction of colonic iron levels and iron‐dependent tankyrase activity, which caused stabilization of axis inhibition protein 2 (AXIN2) and subsequent repression of the β‐catenin/c‐Myc/E2F Transcription Factor 1/DNA polymerase delta1 (POLD1) axis. POLD1 knockdown, iron chelation, and TFRC disruption increase DNA replication stress, DNA damage response, apoptosis, and reduce colon tumor growth. Importantly, a combination of iron chelators and DNA damaging agents increases DNA damage response and reduces colon tumor cell growth. TFRC‐mediated iron import is at the center of a novel feed‐forward loop that facilitates colonic epithelial cell survival. This discovery may provide novel strategies for colorectal cancer therapy. [ABSTRACT FROM AUTHOR]

Context.--Pathology studies using convolutional neural networks (CNNs) have focused on neoplasms, while studies in inflammatory pathology are rare. We previously demonstrated a CNN that differentiates reactive gastropathy, Helicobacter pylori gastritis (HPG), and normal gastric mucosa. Objective.--To determine whether a CNN can differentiate the following 2 gastric inflammatory patterns: autoimmune gastritis (AG) and HPG. Design.--Gold standard diagnoses were blindly established by 2 gastrointestinal (GI) pathologists. One hundred eighty-seven cases were scanned for analysis by HALO-AI. All levels and tissue fragments per slide were included for analysis. The cases were randomized, 112 (60%; 60 HPG, 52 AG) in the training set and 75 (40%; 40 HPG, 35 AG) in the test set. A HALO-AI correct area distribution (AD) cutoff of 50% or more was required to credit the CNN with the correct diagnosis. The test set was blindly reviewed by pathologists with different levels of GI pathology expertise as follows: 2 GI pathologists, 2 general surgical pathologists, and 2 residents. Each pathologist rendered their preferred diagnosis, HPG or AG. Results.--At the HALO-AI AD percentage cutoff of 50% or more, the CNN results were 100% concordant with the gold standard diagnoses. On average, autoimmune gastritis cases had 84.7% HALO-AI autoimmune gastritis AD and HP cases had 87.3% HALO-AI HP AD. The GI pathologists, general anatomic pathologists, and residents were on average, 100%, 86%, and 57% concordant with the gold standard diagnoses, respectively. Conclusions.--A CNN can distinguish between cases of HPG and autoimmune gastritis with accuracy equal to GI pathologists. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer and is also the third leading cause of cancer-related death in the USA. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Macronutrients such as glucose are energy source for a cell. Many tumor cells exhibit increased aerobic glycolysis. Increased tissue micronutrient iron levels in both mice and humans are also associated with increased colon tumorigenesis. However, if iron drives colon carcinogenesis via affecting glucose metabolism is still not clear. Here we found the intracellular glucose levels in tumor colonoids were significantly increased after iron treatment. 13C-labeled glucose flux analysis indicated that the levels of several labeled glycolytic products were significantly increased, whereas several tricarboxylic acid cycle intermediates were significantly decreased in colonoids after iron treatment. Mechanistic studies showed that iron upregulated the expression of glucose transporter 1 (GLUT1) and mediated an inhibition of the pyruvate dehydrogenase (PDH) complex function via directly binding with tankyrase and/or pyruvate dehydrogenase kinase (PDHK) 3. Pharmacological inhibition of GLUT1 or PDHK reactivated PDH complex function and reduced high iron diet-enhanced tumor formation. In conclusion, excess iron promotes glycolysis and colon tumor growth at least partly through the inhibition of the PDH complex function. • Iron increases intracellular glucose accumulation in colon tumor cells. • Iron increases glycolysis via inhibiting PDH complex function in colon tumor cells. • Iron increases PDHE1α Ser293 phosphorylation via directly binding with PDHK3 that is abundant in human colon tumors. • Iron is required for TNKS activity to suppress Axin2-AMPK-PDH signaling. • Inhibition of GLUT1 or PDHK reactivates PDH complex function and reduces iron-driven colon tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Determining the site of origin for metastatic well-differentiated neuroendocrine tumors (WDNETs) is challenging, and immunohistochemical (IHC) profiles do not always lead to a definitive diagnosis. We sought to determine if a deep-learning convolutional neural network (CNN) could improve upon established IHC profiles in predicting the site of origin in a cohort of WDNETs from the common primary sites. Materials and Methods: Hematoxylin and eosin (H&E)-stained tissue microarrays (TMAs) were created using 215 WDNETs arising from the known primary sites. A CNN trained and tested on 60% (n = 130) and 40% (n = 85) of these cases, respectively. One hundred and seventy-nine cases had TMA tissue remaining for the IHC analysis. These cases were stained with IHC markers pPAX8, CDX2, SATB2, and thyroid transcription factor-1 (markers of pancreas/duodenum, ileum/jejunum/duodenum, colorectum/appendix, and lung WDNET sites of origin, respectively). The CNN diagnosis was deemed correct if it designated a majority or plurality of the tumor area as the known site of origin. The IHC diagnosis was deemed correct if the most specific marker for a particular site of origin met an H-score threshold determined by two pathologists. Results: When all cases were considered, the CNN correctly identified the site of origin at a lower rate compared to IHC (72% vs. 82%, respectively). Of the 85 cases in the CNN test set, 66 had sufficient TMA material for IHC stains, thus 66 cases were available for a direct case-by-case comparison of IHC versus CNN. The CNN correctly identified 70% of these cases, while IHC correctly identified 76%, a finding that was not statistically significant (P = 0.56). Conclusion: A CNN can identify WDNET site of origin at an accuracy rate close to the current gold standard IHC methods. [ABSTRACT FROM AUTHOR]

Context.-- Metastatic mucinous tumors present a diagnostic challenge for pathologists as tumor histomorphology is often nonspecific and optimal immunoprofiles are still under investigation. Objective.-- To present a head-to-head comparison of special AT-rich sequence-binding protein 2 (SATB2) and caudal type homeobox 2 (CDX2) expression in a diverse array of primary mucinous tumors. Design.-- SATB2 and CDX2 immunohistochemical stains were performed on whole sections from 44 mucinous colorectal carcinomas and 175 noncolorectal mucinous tumors. A nuclear scoring system measuring intensity (0--3+) and percentage staining (0 = <5%, 1 = 5%--49%, 2 = ≥50%) was implemented, producing an additive histologic score (H-score). Results.-- SATB2 demonstrated acceptable accuracy at low to moderate expression levels (H-scores of 1--4). With these H-score cutoffs, overall accuracy was greater than 90%. In contrast, CDX2's accuracy rivaled that of SATB2 only at an H-score of 5 (89.0%), as its specificity suffered at lower expression levels (<70.0% at H-scores of 1--4). Using a moderate H-score cutoff of 3 or higher, significant differences for both sensitivity and specificity were identified between SATB2 and CDX2 (P = .01 for sensitivity and P < .001 for specificity), though these stains were near equivalent when each was interpreted as positive at its respective optimal H-score (SATB2 ≥ 3 and CDX2 = 5). Conclusions.-- SATB2 is a more accurate marker of colorectal origin across a variety of expression levels compared with CDX2 when applied to mucinous tumors from a host of primary sites. However, these stains are near equivalent when each is interpreted at its optimal expression level. [ABSTRACT FROM AUTHOR]

Although attachment theory has long posited a link between early experiences of care and children's prosocial behavior, investigations of this association have not embraced the multifaceted nature of prosociality. This study is the first to assess associations between child attachment and independent observations of helping, sharing, and comforting. Attachment quality in 3- to 5-year-old children (N = 137) was linked to all three prosocial behaviors. Additionally, bifactor analyses revealed distinct associations between attachment and children's general prosocial dispositions and their specific abilities to meet the unique challenges of helping and, marginally, comforting. These findings underscore the importance of considering multiple explanations for links between attachment and prosocial behavior and provide novel insights into sources of variation in children's prosociality. [ABSTRACT FROM AUTHOR]

Although evidence shows that attachment insecurity and disorganization increase risk for the development of psychopathology (Fearon, Bakermans-Kranenburg, van IJzendoorn, Lapsley, & Roisman, 2010; Groh, Roisman, van IJzendoorn, Bakermans-Kranenburg, & Fearon, 2012), implementation challenges have precluded dissemination of attachment interventions on the broad scale at which they are needed. The Circle of Security–Parenting Intervention (COS-P; Cooper, Hoffman, & Powell, 2009), designed with broad implementation in mind, addresses this gap by training community service providers to use a manualized, video-based program to help caregivers provide a secure base and a safe haven for their children. The present study is a randomized controlled trial of COS-P in a low-income sample of Head Start enrolled children and their mothers. Mothers (N = 141; 75 intervention, 66 waitlist control) completed a baseline assessment and returned with their children after the 10-week intervention for the outcome assessment, which included the Strange Situation. Intent to treat analyses revealed a main effect for maternal response to child distress, with mothers assigned to COS-P reporting fewer unsupportive (but not more supportive) responses to distress than control group mothers, and a main effect for one dimension of child executive functioning (inhibitory control but not cognitive flexibility when maternal age and marital status were controlled), with intervention group children showing greater control. There were, however, no main effects of intervention for child attachment or behavior problems. Exploratory follow-up analyses suggested intervention effects were moderated by maternal attachment style or depressive symptoms, with moderated intervention effects emerging for child attachment security and disorganization, but not avoidance; for inhibitory control but not cognitive flexibility; and for child internalizing but not externalizing behavior problems. This initial randomized controlled trial of the efficacy of COS-P sets the stage for further exploration of “what works for whom” in attachment intervention. [ABSTRACT FROM AUTHOR]

We studied diet and size-related dietary patterns among American Crocodiles (Crocodylus acutus) in marine habitats of coastal Belize (1996-1997). Prey items recovered from crocodile (N = 97) stomach contents included insects, mollusks, crustaceans, fish, amphibians, reptiles, birds, and mammals. Based on an overlapping group analysis of percent occurrence, we concluded that hatchlings and small juveniles feed largely on insects and crustaceans, larger juveniles broaden their diet to include fish and nonfish vertebrates, subadults consume increasing amounts of crustaceans with lesser amounts of insects and nonfish vertebrates, and adults subsist primarily on marine crustaceans. Dietary diversity was uniformly low across all size classes but greatest among small and large juveniles. Conversely, hatchlings, subadults, and adults had the most specialized (least diverse) diet owing to reliance upon a limited selection of prey, largely insects (hatchlings) or crustaceans (subadults and adults). Dietary overlap was greatest between adjacent size classes and lowest between the largest and smallest size classes. The high prevalence of freshly ingested prey among all size classes indicates frequent, regular feeding by C. acutus in coastal habitats, perhaps driven by the relatively small size of frequently consumed prey such as crabs. Because crabs have a blood salt content equivalent to the external medium and comprise a large portion of the diet, these prey likely impose a high osmoregulatory burden on C. acutus inhabiting hyperosmotic coastal environments. Contrary to earlier assertions that salt glands in C. acutus lack the excretory capacity to balance salt and water, we suggest populations in coastal Belize rely on these glands in addition to behavioral strategies to maintain osmotic homeostasis. [ABSTRACT FROM AUTHOR]

Summary Differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR) techniques were used to obtain evidence whether a glassy state exists within fully hydrated dormant Bacillus subtilis spores. DSC thermograms of hydrated dormant spores contained two major transitions; one at ∼60 °C assigned to be associated with the initial ‘activation’ stage for germination, and the other at ∼120 °C assigned to be associated with the ‘inactivation’ process (i.e. killing of the spores). The peak at ∼60 °C had characteristics which were all consistent with at least some region of the compartmentalised structure of fully hydrated dormant spores being in a glassy state. Solid (CPMAS) and liquid state (SPMAS) mobility resolved 13C NMR spectroscopy studies on the calcium dipicolinic acid (CaDPA) resonances, which are only present in the central protoplast of bacterial spores, showed it to be present in an amorphous solid-like environment. The DSC and NMR results were both found to be consistent with the hypothesis that the dormancy of bacterial spores is due to at least the central protoplast region being maintained in a low moisture content glassy state. [ABSTRACT FROM AUTHOR]

Matching visual patterns that appear scaled, rotated, and deformed with respect to each other is a challenging problem. We propose a linear formulation that simultaneously matches feature points and estimates global geometrical transformation in a constrained linear space. The linear scheme enables search space reduction based on the lower convex hull property so that the problem size is largely decoupled from the original hard combinatorial problem. Our method therefore can be used to solve large scale problems that involve a very large number of candidate feature points. Without using prepruning in the search, this method is more robust in dealing with weak features and clutter. We apply the proposed method to action detection and image matching. Our results on a variety of images and videos demonstrate that our method is accurate, efficient, and robust. [ABSTRACT FROM AUTHOR]