Prospective Analysis Using a Novel CNN Algorithm to Distinguish Atypical Ductal Hyperplasia From Ductal Carcinoma in Situ in Breast

IntroductionWe previously developed a convolutional neural networks (CNN)-based algorithm to distinguish atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS) using a mammographic dataset. The purpose of this study is to further validate our CNN algorithm by prospectively analyzing an unseen new dataset to evaluate the diagnostic performance of our algorithm.Materials and MethodsIn this institutional review board-approved study, a new dataset composed of 280 unique mammographic images from 140 patients was used to test our CNN algorithm. All patients underwent stereotactic-guided biopsy of calcifications and underwent surgical excision with available final pathology. The ADH group consisted of 122 images from 61 patients with the highest pathology diagnosis of ADH. The DCIS group consisted of 158 images from 79 patients with the highest pathology diagnosis of DCIS. Two standard mammographic magnification views (craniocaudal and mediolateral/lateromedial) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D slicer and resized to fit a 128 × 128 pixel bounding box. Our previously developed CNN algorithm was used. Briefly, a 15 hidden layer topology was used. The network architecture contained 5 residual layers and dropout of 0.25 after each convolution. Diagnostic performance metrics were analyzed including sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. The “positive class” was defined as the pure ADH group in this study and thus specificity represents minimizing the amount of falsely labeled pure ADH cases.ResultsArea under the receiver operating characteristic curve was 0.90 (95% confidence interval, ± 0.04). Diagnostic accuracy, sensitivity, and specificity was 80.7%, 63.9%, and 93.7%, respectively.ConclusionProspectively tested on new unseen data, our CNN algorithm distinguished pure ADH from DCIS using mammographic images with high specificity.     

Objective assessment of movement competence in children using wearable sensors: An instrumented version of the TGMD-2 locomotor subtest

Movement competence (MC) is defined as the development of sufficient skill to assure successful performance in different physical activities. Monitoring children MC during maturation is fundamental to detect early minor delays and define effective intervention. To this purpose, several MC assessment batteries are available. When evaluating movement strategies, with the aim of identifying specific skill components that may need improving, widespread MC assessment is limited by high time consumption for scoring and the need for trained operators to ensure reliability. This work aims to facilitate and support the assessment by designing, implementing and validating an instrumented version of the TGMD-2 locomotor subtest based on Inertial Measurement Units (IMUs) to quantify MC in children rapidly and objectively. 45 typically developing children, aged 6–10, performed the TGMD-2 locomotor subtest (six skills). During the tests, children wore five IMUs mounted on lower back, on ankles and on wrists. Sensor and video recordings of the tests were collected. Three expert evaluators performed the standard assessment of TGMD-2. Using theoretical and modelling approaches, algorithms were implemented to automatically score children tests based on IMUs’ data. The automatic assessment, compared to the standard one, showed an agreement higher than 87% on average on the entire group for each skill and a reduction of time for scoring from 15 to 2 min per participant. Results support the use of IMUs for MC assessment: this approach will allow improving the usability of MC assessment, supporting objectively evaluator decisions and reducing time requirement for the evaluation of large groups.     

miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1

BackgroundNon-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance.MethodsTo identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3′-untranslated region (3′-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay.ResultsCompared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3′-UTR of FZD1.ConclusionThe amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.     

User-identified electronic cigarette behavioral strategies and device characteristics for cigarette smoking reduction

BackgroundThere is limited evidence on how cigarette smokers use electronic cigarettes (ECIGs) for smoking cessation and reduction. This study used concept mapping, a participatory mixed-methods research approach, to identify ECIG use behaviors and device characteristics perceived to be associated with cigarette smoking cessation or reduction.MethodsCurrent ECIG users aged 18–64 were recruited from seven cities selected randomly from U.S. census tract regions. Participants were invited to complete concept mapping tasks: brainstorming, sorting and rating (n = 72). During brainstorming, participants generated statements in response to a focus prompt (“A SPECIFIC WAY I HAVE USED electronic cigarettes to reduce my cigarette smoking or a SPECIFIC WAY electronic cigarettes help me reduce my cigarette smoking is…”) and then sorted and rated the statements. Multidimensional scaling and hierarchical cluster analyses were used to generate a cluster map that was interpreted by the research team.ResultsEight thematic clusters were identified: Convenience, Perceived Health Effects, Ease of Use, Versatility and Variety, Advantages of ECIGs over Cigarettes, Cigarette Substitutability, Reducing Harms to Self and Others, and Social Benefits. Participants generated several statements that related to specific behavioral strategies used when using ECIGs for smoking reduction/complete switching behaviors such as making rapid transitions from smoking to ECIG use or using certain ECIG liquids or devices. Former smokers rated the Perceived Health Effects cluster and several behavioral strategy statements higher than current smokers.ConclusionsThese results help to identify ECIG use behaviors and characteristics perceived by ECIG users to aid in cigarette smoking cessation or reduction.     

Squamous cell carcinoma of the pancreas: A systematic review and pooled survival analysis

The diagnosis and treatment of squamous cell carcinoma of the pancreas pose dilemmas in the clinical practice. The present study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to 30th April 2016. A pooled Cox regression analysis was performed to evaluate factors potentially associated with overall survival (OS) and relapse-free survival (RFS). Fifty-four cases of pure squamous cell pancreatic carcinomas were identified in total. The mean age was 61.9 years, and most patients were males (61.1%). The median OS was 7 months. Resectability (p = 0.003) and more recent publication year (p < 0.001) were associated with better OS, as was low/intermediate tumour grade (p = 0.032) with RFS. Despite its poor prognosis, survival rates of pancreatic squamous cell carcinoma seem improved during the recent years; resectability and low/intermediate grade emerged as favourable prognostic factors. Collaborative epidemiological studies are deemed necessary to further validate the results stemming from the published case reports of this rare entity.     

Feasibility of biochemical verification in a web-based smoking cessation study

Background and aimsCogent arguments have been made against the need for biochemical verification in population-based studies with low-demand characteristics. Despite this fact, studies involving digital interventions (low-demand) are often required in peer review to report biochemically verified abstinence. To address this discrepancy, we examined the feasibility and costs of biochemical verification in a web-based study conducted with a national sample.MethodsParticipants were 600 U.S. adult current smokers who registered on a web-based smoking cessation program and completed surveys at baseline and 3 months. Saliva sampling kits were sent to participants who reported 7-day abstinence at 3 months, and analyzed for cotinine.ResultsThe response rate at 3-months was 41.2% (n = 247): 93 participants reported 7-day abstinence (38%) and were mailed a saliva kit (71% returned). The discordance rate was 36.4%. Participants with discordant responses were more likely to report 3-month use of nicotine replacement therapy or e-cigarettes than those with concordant responses (79.2% vs. 45.2%, p = 0.007). The total cost of saliva sampling was $8280 ($125/sample).ConclusionsBiochemical verification was both time- and cost-intensive, and yielded a relatively small number of samples due to low response rates and use of other nicotine products during the follow-up period. There was a high rate of discordance of self-reported abstinence and saliva testing. Costs for data collection may be prohibitive for studies with large sample sizes or limited budgets. Our findings echo previous statements that biochemical verification is not necessary in population-based studies, and add evidence specific to technology-based studies.     

Regulation and functions of NLRP3 inflammasome during influenza virus infection

The NLRP3 inflammasome constitutes a major antiviral host defense mechanism during influenza virus infection. Inflammasome assembly in virus-infected cells facilitates autocatalytic processing of pro-caspase-1 and subsequent cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is critical for induction of both innate and adaptive immune responses during influenza virus infection. Inflammasome-dependent antiviral responses also regulate immunopathology and tissue repair in the infected lungs. The regulation of NLRP3 inflammasome assembly is an area of active research and recent studies have unraveled multiple cellular and viral factors involved in inflammasome assembly. Emerging studies have also identified the cross talk between inflammasome activation and programmed cell death pathways in influenza virus-infected cells. Here, we review the current literature regarding regulation and functions of NLRP3 inflammasome during influenza virus infection.     

The effects of merit-based financial aid on drinking in college

We study the effect of state-level merit aid programs (such as Georgia's HOPE scholarship) on alcohol consumption among college students. Such programs have the potential to affect drinking through a combination of channels – such as raising students’ disposable income and increasing the incentive to maintain a high GPA – that could theoretically raise or lower alcohol use. We find that the presence of a merit-aid program in one's state generally leads to an overall increase in (heavy) drinking. This effect is concentrated among men, students with lower parental education, older students, and students with high college GPA's. Our findings are robust to several alternative empirical specifications including event-study analyses by year of program adoption. Furthermore, no difference in high-school drinking is observed for students attending college in states with merit-aid programs.     

Elasticity standard values of the thoracolumbar fascia assessed with acoustic radiation force impulse elastography on healthy volunteers: A cross section study

IntroductionDetermining the normal values for acoustic radiation force impulse (ARFI) shear wave elastography of the thoracolumbar fascia (TLF) and define possible factors of influence.MethodsWe measured the shear wave velocity (SWV) in m/s and the diameter (anterior-posterior) in mm of the TLF bilateral in 267 healthy participants with the Acuson S3000™ (Siemens) using the virtual touch image quantification mode (VTIQ). The parameters were tested for correlations with the anthropometric data of the participants, between different age groups and the genders, as well as information obtained from the history, such as smoking and sporting activities.ResultsWe determined a mean SWV of 3.28 ± 0.55 m/s for the left thoracolumbar fascia and 3.44 ± 0.55 m/s for the right. The diameter on the right was 2.7 ± 0.8 mm. On the left, it was 2.7 ± 0.9 mm. Neither body mass index (BMI) nor gender had a significant effect on either of the measured parameters (p > 0.05). The same goes for regular medication, sporting activity or the consumption of alcohol (p > 0.05). The results concerning the effect of smoking and age were inconclusive as they only had a significant influence to either the right or the left side of the TLF but not on the other side.ConclusionsWe collected the normal value for ARFI shear wave elastography of the TLF in 267 healthy participants. Furthermore, neither gender, BMI, sports activity nor the consumption of alcohol affected the elasticity or the diameter of the thoracolumbar fascia.     

Genome-wide pathway-based association study implicates complement system in the development of Kashin-Beck disease in Han Chinese

Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of KBD remains unknown. To identify relevant biological pathways for KBD, we conducted a genome-wide pathway-based association study (GWPAS) following by replication analysis, totally using 2743 Chinese Han adults. A modified gene set enrichment algorithm was used to detect association between KBD and 963 biological pathways. Cartilage gene expression analysis and serum complement measurement were performed to evaluate the functional relevance of identified pathway with KBD. We found that the Complement and Coagulation Cascades (CACC) pathway was significantly associated with KBD (P value = 3.09 × 10^− 5, false-discovery rate = 0.042). Within the CACC pathway, the most significant association was observed at rs1656966 (P value = 1.97 × 10^− 4) of KNG1 gene. Further replication study observed that rs1656966 (P value = 0.037) was significantly associated with KBD in an independent validation sample of 1026 subjects. Gene expression analysis observed that CFD (ratio = 3.39 ± 2.68), A2M (ratio = 3.67 ± 5.63), C5 (ratio = 2.65 ± 2.52) and CD46 (ratio = 2.29 ± 137) genes of the CACC pathway were up-regulated in KBD articular cartilage compared to healthy articular cartilage. The serum level of complement C5 in KBD patients were significantly higher than that in healthy controls (P value = 0.038). Our study is the first to suggest that complement system-related CACC pathway contributed to the development of KBD.