bluuebunny/crossref_metadata_2025 huggingface dataset:
How to use clinical signs of meningitis
Authors: Tracy Alexander , Waterfield Thomas
Published: January 2019

Meningitis is a critical diagnosis not to miss in children presenting with fever. Since the early 20th century, classical clinical signs have been used to aid the diagnosis of meningitis. These classical signs are nuchal rigidity, Kernig’s sign and Brudzinski’s sign. Each of these relies on the principle that stretching the inflamed meningeal membranes causes clinically detectable irritation. Several primary studies have quantified the diagnostic performance of clinical examination in detecting meningitis in children. The results of these studies vary significantly due to methodological differences, clinical heterogeneity and interobserver variability. However, their findings demonstrate that positive meningitic signs increase the likelihood of a diagnosis of meningitis, and the absence of meningitic signs reduces this probability. These signs have greatest utility when combined with other features in the history and examination to contribute to a comprehensive clinical assessment.
Can social robots help children in healthcare contexts? A scoping review
Authors: Dawe Julia , Sutherland Craig , Barco Alex , Broadbent Elizabeth
Published: February 2019

Objective

To review research on social robots to help children in healthcare contexts in order to describe the current state of the literature and explore future directions for research and practice.

Design

Scoping review.

Data sources

Engineering Village, IEEE Xplore, Medline, PsycINFO and Scopus databases were searched up until 10 July 2017. Only publications written in English were considered. Identified publications were initially screened by title and abstract, and the full texts of remaining publications were then subsequently screened.

Eligibility criteria

Publications were included if they were journal articles, conference proceedings or conference proceedings published as monographs that described the conceptualisation, development, testing or evaluation of social robots for use with children with any mental or physical health condition or disability. Publications on autism exclusively, robots for use with children without identified health conditions, physically assistive or mechanical robots, non-physical hardware robots and surgical robots were excluded.

Results

Seventy-three publications were included in the review, of which 50 included user studies with a range of samples. Most were feasibility studies with small sample sizes, suggesting that the robots were generally accepted. At least 26 different robots were used, with many of these still in development. The most commonly used robot was NAO. The evidence quality was low, with only one randomised controlled trial and a limited number of experimental designs.

Conclusions

Social robots hold significant promise and potential to help children in healthcare contexts, but higher quality research is required with experimental designs and larger sample sizes.
Prospective observational study of universal newborn eye screening in a hospital and community setting in New Zealand
Authors: Simkin Samantha Kaye , Misra Stuti L , Battin Malcolm , McGhee Charles N J , Dai Shuan
Published: February 2019

Objective

Early detection of ocular abnormalities in newborn infants is essential for timely diagnosis and treatment. This study aimed to assess wide-field digital imaging for universal newborn eye screening (UNES) to determine the prevalence of ocular abnormalities, including retinal haemorrhages, in newborn infants in New Zealand.

Design

Prospective ocular screening study of infants.

Setting

A public hospital maternity ward and a community birth centre in Auckland, New Zealand.

Patients

A total of 350 infants were enrolled in UNES, those with birth weight <1250 g or gestational age <30 weeks were excluded.

Methods

Wide-field digital images of the external eye and retina were captured by RetCam (Natus Medical, San Carlos, California, USA) and reviewed by an ophthalmologist via an established telemedicine methodology.

Main outcome measures

Detection of ocular abnormalities, including retinal haemorrhages. Correlation between haemorrhages and maternal, obstetric and neonatal factors.

Results

A total of 346 infants completed screening (median age 2 days). Retinal haemorrhages were present in 50 cases (14.5%), two cases exhibited persistent retinal haemorrhages at 6-week follow-up. A significant increase in the odds of retinal haemorrhages was present for vaginal delivery compared with caesarean section. Other ocular abnormalities, including congenital cataract and optic nerve hypoplasia, were present in 1.4% of infants.

Conclusions

Ocular abnormalities were detected by UNES including congenital cataract and optic nerve hypoplasia. However, retinal haemorrhages, significantly associated with delivery modality, were the most common abnormality detected. The majority of retinal haemorrhages resolved spontaneously.
Firstline a direct aspiration first pass technique versus firstline stent retriever for acute basilar artery occlusion: a systematic review and meta-analysis
Authors: Ye Gengfan , Lu Jun , Qi Peng , Yin Xiaoliang , Wang Lijun , Wang Daming
Published: January 2019

Introduction

Acute basilar artery occlusion (BAO) can result in extremely high disability and mortality. Stent retrievers (SRs) can achieve a high recanalization rate for BAO, therefore improving favorable outcomes. However, the efficacy of a direct aspiration first pass technique (ADAPT) to treat BAO is unclear. Our aim was to compare the efficacy and safety of firstline ADAPT with that of firstline SR for patients with acute BAO.

Methods

Three databases were systematically searched for literature reporting outcomes on thrombectomy for acute BAO with both firstline ADAPT and firstline SR. The modified Newcastle–Ottawa scale was applied to assess bias risk. The random effects model was used.

Results

Of 50 articles, 5 cohort studies (2 prospective and 3 retrospective) were included in our research. 193 cases were treated with firstline ADAPT and 283 cases received firstline SR. Successful recanalization rate was significantly higher in the firstline ADAPT group (OR=2.0, 95% CI 1.1 to 3.5). Procedure time (mean difference=−27.6 min, 95% CI −51.0 to −4.3) and the incidence of new territory embolic event (OR=0.2, 95% CI 0.05 to 0.83) was significantly less in the firstline ADAPT group. No significant difference was observed between the firstline ADAPT and firstline SR groups for rate of complete recanalization, rescue therapy, any hemorrhagic complication, favorable outcomes, or mortality at 90 days.

Conclusions

Our meta-analysis suggested that for patients with acute BAO, firstline ADAPT might achieve higher and faster recanalization, comparable neurological improvement and safety compared with firstline SR. Further studies are needed to confirm these results.
Extended resuscitative endovascular balloon occlusion of the aorta (REBOA)-induced type 2 myocardial ischemia: a time-dependent penalty
Authors: Wasicek Philip J , Teeter William A , Yang Shiming , Banchs Hector , Galvagno Samuel M , Hu Peter , Gamble William B , Hoehn Melanie R , Scalea Thomas M , Morrison Jonathan J
Published: February 2019

Background

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) increases cardiac-afterload and is used for patients in hemorrhagic shock. The cardiac tolerance of prolonged afterload augmentation in this context is unknown. The aim of this study is to quantify cardiac injury, if any, following 2, 3 and 4 hours of REBOA.

Methods

Anesthetized swine (70–90 kg) underwent a 40% controlled hemorrhage, followed by supraceliac resuscitative endovascular balloon occlusion of the aorta (REBOA) for 2 (n=5), 3 (n=5), and 4 hours (n=5). High-fidelity arterial wave form data were collected, and signal processing techniques were used to extract key inflection points. The adjusted augmentation index (AIx@75; augmentation pressure/pulse pressure, normalized for heart rate) was derived for use as a measure of aortic compliance (higher ratio = less compliance). Endpoints consisted of electrocardiographic, biochemical, and histologic markers of myocardial injury/ischemia. Regression modeling was used to assess the trend against time.

Results

All animals tolerated instrumentation, hemorrhage, and REBOA. The mean (±SD) systolic blood pressure (mm Hg) increased from 65±11 to 212±39 (p<0.001) during REBOA. The AIx@75 was significantly higher during REBOA than baseline, hemorrhage, and resuscitation phases (p<0.05). A time-dependent rise in troponin (R2=0.95; p<0.001) and T-wave deflection (R2=0.64; p<0.001) was observed. The maximum mean troponin (ng/mL) occurred at 4 hours (14.6±15.4) and maximum T-wave deflection (mm) at 65 minutes (3.0±1.8). All animals demonstrated histologic evidence of acute injury with increasing degrees of cellular myocardial injury.

Discussion

Prolonged REBOA may result in type 2 myocardial ischemia, which is time-dependent. This has important implications for patients where prolonged REBOA may be considered beneficial, and strategies to mitigate this effect require further investigation.

Level of evidence

II.
Registration of 11S null food-grade soybean [Glycine max (L.) Merr.] germplasm HS-181
Authors: Yu K. , Woodrow L. , Shi M. Chun , Anderson D.
Published: January 2019

HS-181 is an 11S glycinin null food-grade soybean line [Glycine max (L.) Merr.] with yellow hilum. The absence of 11S subunits would result in a relatively higher concentration of 7S β-conglycinin in soy food. β-conglycinins suppress food intake, which can help to fight obesity. HS-181 is adapted to areas of southwest Ontario with 3100 or more crop heat units and has a relative maturity of 2.5 (MG 2.5).
Hypergraphs and proper forcing
Authors: Zapletal Jindřich
Published: January 2019

Given a Polish space [Formula: see text] and a countable collection of analytic hypergraphs on [Formula: see text], I consider the [Formula: see text]-ideal generated by Borel anticliques for the hypergraphs in the family. It turns out that many of the quotient posets are proper. I investigate the forcing properties of these posets, certain natural operations on them, and prove some related dichotomies.
Personalized Emotion Recognition by Personality-Aware High-Order Learning of Physiological Signals
Authors: Zhao Sicheng , Gholaminejad Amir , Ding Guiguang , Gao Yue , Han Jungong , Keutzer Kurt
Published: January 2019

Due to the subjective responses of different subjects to physical stimuli, emotion recognition methodologies from physiological signals are increasingly becoming personalized. Existing works mainly focused on modeling the involved physiological corpus of each subject, without considering the psychological factors, such as interest and personality. The latent correlation among different subjects has also been rarely examined. In this article, we propose to investigate the influence of personality on emotional behavior in a hypergraph learning framework. Assuming that each vertex is a compound tuple (subject, stimuli), multi-modal hypergraphs can be constructed based on the personality correlation among different subjects and on the physiological correlation among corresponding stimuli. To reveal the different importance of vertices, hyperedges, and modalities, we learn the weights for each of them. As the hypergraphs connect different subjects on the compound vertices, the emotions of multiple subjects can be simultaneously recognized. In this way, the constructed hypergraphs are vertex-weighted multi-modal multi-task ones. The estimated factors, referred to as emotion relevance, are employed for emotion recognition. We carry out extensive experiments on the ASCERTAIN dataset and the results demonstrate the superiority of the proposed method, as compared to the state-of-the-art emotion recognition approaches.
Efficient Traffic Load-Balancing via Incremental Expansion of Routing Choices
Authors: Yin Ping , Yang Sen , Xu Jun , Dai Jim , Lin Bill
Published: January 2019

Routing policies play a major role in the performance of communication networks. Backpressure-based adaptive routing algorithms where traffic is load balanced along different routing paths on a per-packet basis have been studied extensively in the literature. Although backpressure-based algorithms have been shown to be networkwide throughput optimal, they typically have poor delay performance under light or moderate loads, because packets may be sent over unnecessarily long routes. Further, backpressure-based algorithms have required every node to compute differential backlogs for every per-destination queue with the corresponding per-destination queue at every adjacent node, which is expensive given the large number of possible pairwise differential backlogs between neighbor nodes. In this article, we propose new backpressure-based adaptive routing algorithms that only use shortest-path routes to destinations when they are sufficient to accommodate the given traffic load, but the proposed algorithms will incrementally expand routing choices as needed to accommodate increasing traffic loads. We show analytically by means of fluid analysis that the proposed algorithms retain networkwide throughput optimality, and we show empirically by means of simulations that our proposed algorithms provide substantial improvements in delay performance. Our evaluations further show that, in practice, our approach dramatically reduces the number of pairwise differential backlogs that have to be computed and the amount of corresponding backlog information that has to be exchanged, because routing choices are only incrementally expanded as needed.
Stochastic Assume-Guarantee Contracts for Cyber-Physical System Design
Authors: Nuzzo Pierluigi , Li Jiwei , Sangiovanni-Vincentelli Alberto L. , Xi Yugeng , Li Dewei
Published: January 2019

We present an assume-guarantee contract framework for cyber-physical system design under probabilistic requirements. Given a stochastic linear system and a set of requirements captured by bounded Stochastic Signal Temporal Logic (StSTL) contracts, we propose algorithms to check contract compatibility, consistency, and refinement, and generate a sequence of control inputs that satisfies a contract. We leverage encodings of the verification and control synthesis tasks into mixed integer optimization problems, and conservative approximations of probabilistic constraints that produce sound and tractable problem formulations. We illustrate the effectiveness of our approach on three case studies, including the design of controllers for aircraft power distribution networks.
Virtual Portraitist
Authors: Hu Chuan-Shen , Hsieh Yi-Tsung , Lin Hsiao-Wei , Yeh Mei-Chen
Published: January 2019

Smart photography carries the promise of quality improvement and functionality extension in making aesthetically appealing pictures. In this article, we focus on self-portrait photographs and introduce new methods that guide a user in how to best pose while taking a selfie. While most of the current solutions use a post processing procedure to beautify a picture, the developed tool enables a novel function of recommending a good look before the photo is captured. Given an input face image, the tool automatically estimates the pose-based aesthetic score, finds the most attractive angle of the face, and suggests how the pose should be adjusted. The recommendation results are determined adaptively to the appearance and initial pose of the input face. We apply a data mining approach to find distinctive, frequent itemsets and association rules from online profile pictures, upon which the aesthetic estimation and pose recommendation methods are developed. A simulated and a real image set are used for experimental evaluation. The results show the proposed aesthetic estimation method can effectively select user-favorable photos. Moreover, the recommendation performance for the vertical adjustment is moderately related to the degree of conformity among the professional photographers’ recommendations. This study echoes the trend of instant photo sharing, in which a user takes a picture and then immediately shares it on a social network without engaging in tedious editing.
Model-based, Mutation-driven Test-case Generation Via Heuristic-guided Branching Search
Authors: Fellner Andreas , Krenn Willibald , Schlick Rupert , Tarrach Thorsten , Weissenbacher Georg
Published: January 2019

This work introduces a heuristic-guided branching search algorithm for model-based, mutation-driven test-case generation. The algorithm is designed towards the efficient and computationally tractable exploration of discrete, non-deterministic models with huge state spaces. Asynchronous parallel processing is a key feature of the algorithm. The algorithm is inspired by the successful path planning algorithm Rapidly exploring Random Trees (RRT). We adapt RRT in several aspects towards test-case generation. Most notably, we introduce parametrized heuristics for start and successor state selection, as well as a mechanism to construct test cases from the data produced during the search.

We implemented our algorithm in the existing test-case generation framework MoMuT. We present an extensive evaluation of the proposed heuristics and parameters of the algorithm, based on a diverse set of demanding models obtained in an industrial context. In total, we continuously utilized 128 CPU cores on three servers for several weeks to gather the experimental data presented. We show that branching search works well and the use of multiple heuristics is justified. With our new algorithm, we are now able to process models consisting of over 2,300 concurrent objects. To our knowledge, there is no other mutation-driven test-case generation tool that is able to process models of this magnitude.
Special Section on Multimodal Understanding of Social, Affective, and Subjective Attributes
Authors: Alameda-Pineda Xavier , Redi Miriam , Soleymani Mohammad , Sebe Nicu , Chang Shih-Fu , Gosling Samuel
Published: January 2019

Multimedia scientists have largely focused their research on the recognition of
tangible
properties of data such as objects and scenes. Recently, the field has started evolving toward the modeling of more complex properties. For example, the understanding of social, affective, and subjective attributes of visual data has attracted the attention of many research teams at the crossroads of computer vision, multimedia, and social sciences. These
intangible
attributes include, for example, visual beauty, video popularity, or user behavior. Multiple, diverse challenges arise when modeling such properties from multimedia data. The sections concern technical aspects such as reliable groundtruth collection, the effective learning of subjective properties, or the impact of context in subjective perception; see Refs. [2] and [3].
A Survey of Communication Protocols for Internet of Things and Related Challenges of Fog and Cloud Computing Integration
Authors: Dizdarević Jasenka , Carpio Francisco , Jukan Admela , Masip-Bruin Xavi
Published: January 2019

The fast increment in the number of IoT (Internet of Things) devices is accelerating the research on new solutions to make cloud services scalable. In this context, the novel concept of fog computing as well as the combined fog-to-cloud computing paradigm is becoming essential to decentralize the cloud, while bringing the services closer to the end-system. This article surveys e application layer communication protocols to fulfill the IoT communication requirements, and their potential for implementation in fog- and cloud-based IoT systems. To this end, the article first briefly presents potential protocol candidates, including request-reply and publish-subscribe protocols. After that, the article surveys these protocols based on their main characteristics, as well as the main performance issues, including latency, energy consumption, and network throughput. These findings are thereafter used to place the protocols in each segment of the system (IoT, fog, cloud), and thus opens up the discussion on their choice, interoperability, and wider system integration. The survey is expected to be useful to system architects and protocol designers when choosing the communication protocols in an integrated IoT-to-fog-to-cloud system architecture.
Federated Machine Learning
Authors: Yang Qiang , Liu Yang , Chen Tianjian , Tong Yongxin
Published: January 2019

Today’s artificial intelligence still faces two major challenges. One is that, in most industries, data exists in the form of isolated islands. The other is the strengthening of data privacy and security. We propose a possible solution to these challenges: secure federated learning. Beyond the federated-learning framework first proposed by Google in 2016, we introduce a comprehensive secure federated-learning framework, which includes horizontal federated learning, vertical federated learning, and federated transfer learning. We provide definitions, architectures, and applications for the federated-learning framework, and provide a comprehensive survey of existing works on this subject. In addition, we propose building data networks among organizations based on federated mechanisms as an effective solution to allowing knowledge to be shared without compromising user privacy.
Flexible Load Balancing with Multi-dimensional State-space Collapse
Authors: Zhou Xingyu , Tan Jian , Shroff Ness
Published: January 2019

Heavy traffic delay analysis for load balancing policies has relied heavily on a condition called state-space collapse onto a single-dimensional line. In this paper, via Lyapunov driftbased method, we rigorously prove that even under a multidimensional state-space collapse, steady-state heavy-traffic delay optimality can still be achieved for a general load balancing system. This result directly implies that achieving steady-state heavy-traffic delay optimality simply requires that no server is kept idling while others are busy at heavy loads, thus complementing and extending the result obtained by diffusion approximations. Further, we explore the greater flexibility provided by allowing a multidimensional state-space collapse in designing new load balancing policies that are both throughput optimal and heavytraffic delay optimal in steady state.
A central limit theorem for a Markov-modulated infinite-server queue with batch Poisson arrivals and binomial catastrophes
Authors: Yajima M. , Phung-Duc T.
Published: January 2019

This paper considers the stationary queue length distribution of a Markov-modulated MX/M/∞queue with binomial catastrophes. When a binomial catastrophe occurs, each customer is either removed with a probability or is retained with the complementary probability. We focus on our model under a heavy traffic regime because its exact analysis is difficult if not impossible. We establish a central limit theorem for the stationary queue length of our model in a heavy traffic regime. The central limit theorem can be used to approximate the queue length distribution of our model with large arrival rates.
The Mean-field Behavior of Processor Sharing Systems with General Job Lengths Under the SQ(d) Policy
Authors: Vasantam Thirupathaiah , Mukhopadhyay Arpan , Mazumdar Ravi R.
Published: January 2019

In this paper, we derive the mean-field behavior of empirical distributions of large systems that consist of N (large) identical parallel processor sharing servers with Poisson arrival process having intensity Nλ and generally distributed job lengths under the randomized SQ(d) load balancing policy. Under this policy, an arrival is routed to the server with the least number of progressing jobs among d randomly chosen servers. The mean-field is then used to approximate the statistical properties of the system. In particular, we show that in the limit as N grows, individual servers are statistically independent of others (propagation of chaos) and more importantly, the equilibrium point of the mean-field is insensitive to the job length distributions. This has important engineering relevance for the robustness of such routing policies that are often used in web server farms. We use a measure-valued process approach and martingale techniques to obtain our results. We also provide numerical results to support our analysis.
Achieving fairness for EV charging in overload
Authors: Zeballos Martin , Ferragut Andres , Paganini Fernando
Published: January 2019

With the emergence of Electrical Vehicles (EVs), there is a growing investment in power infrastructure to provide charging stations. In an EV parking lot, typically not all vehicles can be charged simultaneously, and thus some scheduling must be performed, taking into account the time the users are willing to spend in the system.

In this paper, we analyze the performance of several common scheduling policies through a fluid model. We show that in overload, the amount of unfinished work is the same for all policies, but these can distribute the work performed unfairly across users. We also introduce a new policy called Least Laxity Ratio that achieves a suitable notion of fairness across jobs, and validate its performance by simulation.
Hierarchical Beamforming
Authors: Floquet Julien , Combes Richard , Altman Zwi
Published: January 2019

We consider hierarchical beamforming in wireless networks. For a given population of flows, we propose computationally efficient algorithms for fair rate allocation including proportional fairness and max-min fairness. We further propose closed-form formulas for flow level performance, for both elastic and streaming traffic (1).
Congestion Avoidance in Low-Voltage Networks by using the Advanced Metering Infrastructure
Authors: Vinot Benoit , Cadoux Florent , Gast Nicolas
Published: January 2019

Large-scale decentralized photovoltaic (PV) generators are currently being installed in many low-voltage distribution networks. Without grid reinforcements or production curtailment, they might create current and/or voltage issues. In this paper, we consider the use the advanced metering infrastructure (AMI) as the basis for PV generation control. We show that the advanced metering infrastructure may be used to infer some knowledge about the underlying network, and we show how this knowledge can be used by a simple feed-forward controller to curtail the solar production efficiently. By means of numerical simulations, we compare our proposed controller with two other controller structures: open-loop, and feed-back P(U) and Q(U). We demonstrate that our feed-forward controller - that requires no prior knowledge of the underlying electrical network - brings significant performance improvements as it can effectively suppress over-voltage and over-current while requiring low energy curtailment. This method can be implemented at low cost and require no specific information about the network on which it is deployed.
BlockSim
Authors: Alharby Maher , van Moorsel Aad
Published: January 2019

Both in the design and deployment of blockchains many configuration choices need to be made. Investigating different implementation and design choices is not feasible or practical on real systems. Therefore, we propose BlockSim as a framework to build discrete-event dynamic system models for blockchain systems. BlockSim is organized in three layers: incentive layer, connector layer and system layer and is implemented in Python. This paper introduces BlockSim, with a particular emphasis on the modeling and simulation of block creation through the Proof of Work consensus algorithm.
Feedforward Neural Networks for Caching
Authors: Fedchenko Vladyslav , Neglia Giovanni , Ribeiro Bruno
Published: January 2019

We propose a caching policy that uses a feedforward neural network (FNN) to predict content popularity. Our scheme outperforms popular eviction policies like LRU or ARC, but also a new policy relying on the more complex recurrent neural networks. At the same time, replacing the FNN predictor with a naive linear estimator does not degrade caching performance significantly, questioning then the role of neural networks for these applications.
Emotion Recognition in Low-Spatial Frequencies Is Partly Preserved following Traumatic Brain Injury
Authors: Celeghin Alessia , Galetto Valentina , Tamietto Marco , Zettin Marina
Published: January 2019

After a Traumatic Brain Injury (TBI), emotion recognition is typically impaired. This is commonly attributed to widespread multifocal damage in cortical areas involved in emotion processing as well as to Diffuse Axonal Injury (DAI). However, current models suggest that emotional recognition is subserved by a distributed network cantered on the amygdala, which involves both cortical and subcortical structures. While the cortical system is preferentially tuned to process high spatial frequencies, the subcortical networks are more sensitive to low-spatial frequencies. The aim of this study was to evaluate whether emotion perception from low-spatial frequencies underpinning the subcortical system is relatively preserved in TBI patients. We tested a group of 14 subjects with severe TBI and 20 matched healthy controls. Each participant was asked to recognize the emotion expressed by each stimulus that consisted of happy and fearful faces, filtered for their low and high spatial frequencies components. Results in TBI patients’ performances showed that low-spatial frequency expressions were recognized with higher accuracy and faster reaction times when compared to high spatial frequency stimuli. On the contrary, healthy controls did not show any effect in the two conditions, neither for response accuracy nor for reaction times. The outcomes of this study indicate that emotion perception from low-spatial frequencies is relatively preserved in TBI, thereby suggesting spare of functioning in the subcortical system in mediating emotion recognition.
The Transcriptional Regulator Sin3A Contributes to the Oncogenic Potential of STAT3
Authors: Gambi Giovanni , Di Simone Elisabetta , Basso Veronica , Ricci Luisa , Wang Rui , Verma Akanksha , Elemento Olivier , Ponzoni Maurilio , Inghirami Giorgio , Icardi Laura , Mondino Anna
Published: January 2019

Epigenetic silencing of promoter and enhancer regions is a common phenomenon in malignant cells. The transcription factor STAT3 is aberrantly activated in several tumors, where its constitutive acetylation accounts for the transcriptional repression of a number of tumor suppressor genes (TSG) via molecular mechanisms that remain to be understood. Using nucleophosmin-anaplastic lymphoma kinase–positive (NPM-ALK+) anaplastic large-cell lymphoma (ALCL) as model system, we found in cells and patient-derived tumor xenografts that STAT3 is constitutively acetylated as a result of ALK activity. STAT3 acetylation relied on intact ALK-induced PI3K- and mTORC1-dependent signaling and was sensitive to resveratrol. Resveratrol lowered STAT3 acetylation, rescued TSG expression, and induced ALCL apoptotic cell death. STAT3 constitutively bound the Sin3A transcriptional repressor complex, and both STAT3 and Sin3A bound the promoter region of silenced TSG via a resveratrol-sensitive mechanism. Silencing SIN3A caused reexpression of TSG, induced ALCL apoptotic cell death in vitro, and hindered ALCL tumorigenic potential in vivo. A constitutive STAT3–Sin3A interaction was also found in breast adenocarcinoma cells and proved critical for TSG silencing and cell survival. Collectively, these results suggest that oncogene-driven STAT3 acetylation and its constitutive association with Sin3A represent novel and concomitant events contributing to STAT3 oncogenic potential.

Significance:

This study delineates the transcriptional regulatory complex Sin3A as a mediator of STAT3 transcriptional repressor activity and identifies the STAT3/Sin3A axis as a druggable target to antagonize STAT3-addicted tumors.
Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer
Authors: Tokunaga Ryuma , Xiu Joanne , Johnston Curtis , Goldberg Richard M. , Philip Philip A. , Seeber Andreas , Naseem Madiha , Lo Jae Ho , Arai Hiroyuki , Battaglin Francesca , Puccini Alberto , Berger Martin D. , Soni Shivani , Zhang Wu , Hwang Jimmy J. , Shields Anthony F. , Marshall John L. , Baba Hideo , Korn W. Michael , Lenz Heinz-Josef
Published: January 2019

Purpose:

The natural history and prognosis of appendiceal adenocarcinomas differ from those of adenocarcinomas arising in other large bowel sites. We aimed to compare the molecular profiles exhibited by appendiceal adenocarcinomas and colorectal cancers, or between the histopathologic subtypes of appendiceal adenocarcinoma.

Experimental Design:

A total of 183 samples from appendiceal adenocarcinoma [46 adenocarcinoma, not otherwise specified (NOS), 66 pseudomyxoma peritonei (PMP), 44 mucinous adenocarcinoma (MU), and 27 signet ring cell carcinoma (SR)], 994 from right-sided colorectal cancer (R-CRC), and 1,080 from left-sided CRC (L-CRC) were analyzed by next-generation sequencing (NGS) and IHC markers. Microsatellite instability (MSI) and tumor mutational burden (TMB) were tested by NGS, and programmed death ligand 1 (PD-L1) by IHC.

Results:

We observed high mutation rates in appendiceal adenocarcinoma samples for KRAS (55%), TP53 (40%), GNAS (31%), SMAD4 (16%), and APC (10%). Appendiceal adenocarcinoma exhibited higher mutation rates in KRAS and GNAS, and lower mutation rates in TP53, APC, and PIK3CA (6%) than colorectal cancers. PMP exhibited much higher mutation rates in KRAS (74%) and GNAS (63%), and much lower mutation rates in TP53 (23%), APC (2%), and PIK3CA (2%) than NOS. Alterations associated with immune checkpoint inhibitor response (MSI-high, TMB-high, PD-L1 expression) showed similar frequency in appendiceal adenocarcinoma compared with L-CRC, but not R-CRC, and those of NOS were higher than other subtypes of appendiceal adenocarcinoma and L-CRC.

Conclusions:

Molecular profiling of appendiceal adenocarcinoma revealed different molecular characteristics than noted in R-CRC and L-CRC, and molecular heterogeneity among the histopathologic subtypes of appendiceal adenocarcinoma. Our findings may be critical to developing an individualized approach to appendiceal adenocarcinoma treatment.
Precision Diabetes Is Slowly Becoming a Reality
Authors: Mohan Viswanathan , Radha Venkatesan
Published: January 2019

The concept of precision medicine is becoming increasingly popular. The use of big data, genomics and other “omics” like metabolomics, proteomics and transcriptomics could make the dream of personalised medicine become a reality in the near future. As far as polygenic forms of diabetes like type 2 and type 1 diabetes are concerned, interesting leads are emerging, but precision diabetes is still in its infancy. However, with regard to monogenic forms of diabetes like maturity-onset diabetes of the young and neonatal diabetes mellitus, rapid strides have been made and precision diabetes has already become part of the clinical tools used at advanced diabetes centres. In patients with some monogenic form of diabetes, if the appropriate gene defects are identified, insulin injections can be stopped and be replaced by oral sulphonylurea drugs. In the coming years, rapid advances can be expected in the field of precision diabetes, thereby making the control of diabetes more effective and hopefully leading to prevention of its complications and improvement of the quality of life of people afflicted with diabetes.
ЗАЛЕЖНІСТЬ СКЛАДОВИХ КОМПОНЕНТІВ МАСИ ТІЛА ВІД ФУНКЦІОНАЛЬНОГО СТАНУ АВТОНОМНОЇ РЕГУЛЯЦІЇ У ЗДОРОВИХ ОСІБ ЧОЛОВІЧОЇ СТАТІ МОЛОДОГО ВІКУ
Authors: Kentesh O. P. , Nemesh M. I. , Palamarchuk O. S. , Kostenchak-Svystak O. E. , Feketa V. P.
Published: January 2019

Зрушення, які виникають у діяльності ефекторів, пов’язані, насамперед, з характеристиками функціонального стану автономної нервової системи (парасимпатикотонічна або симпатикотонічна її спрямованість). На наш погляд, зміну вегетативного забезпечення необхідно розглядати як донозологічний критерій соматичного неблагополуччя. Саме тому незбалансованість регуляторних систем може бути пусковим механізмом розвитку надмірної маси тіла та ожиріння, яке є найбільш вірогідним предиктором серцево-судинних захворювань. Однак на сьогоднішній день немає чітких даних щодо взаємозв’язку між індексом маси тіла (ІМТ), вмістом загального жиру (ВЗЖ), вмістом вісцерального жиру (ВВЖ), вмістом безжирової маси (ВБМ) з показниками АНС.

Мета – дослідити залежності та встановити взаємозв’язки між функціональними показниками стану АНС та складовими компонентами маси тіла у групах практично здорових осіб чоловічої статі з різним функціональним станом автономної регуляції.

Матеріал і методи. В дослідженні взяв участь 31 чоловік віком 18–25 років. Вимірювання маси тіла, ІМТ та показників компонентного складу проводилося з використанням аналізатора складу тіла Tanita BC-601. Функціональний стан АНС визначали за допомогою аналізу ритмограми варіабельності серцевого ритму (ВСР) у фоновому записі (тривалістю 5 хв). Реєстрацію ритмограми проводили за допомогою комп’ютерного апаратного комплексу «КАРДІОЛАБ» (ХАИ-МЕДИКА, Україна). Результати були статистично опрацьовані за допомогою програми Minitab 17.

Результати. Виявлено, що у осіб чоловічої статі з різним характером вихідного тонусу регуляції АНС статистично значимо відрізняються показники складових компонентів маси тіла, а саме ІМТ, ВЗЖ, ВВЖ та ВБМ. При оцінці результатів кореляційного аналізу було виявлено, що ІМТ має статистично значимий позитивний кореляційний зв’язок з ПАРС та IS.

Висновки. У результаті проведених досліджень було встановлено, що дисбаланс автономної нервової системи, для якого характерне зниження загальної варіабельності серцевого ритму з переважанням центральних нейрогуморальних впливів та надмірне підвищення впливу однієї з ланок АНС призводить до порушення обміну речовин з наступним виникненням надлишкової маси тіла та ожиріння й ряду небажаних станів.
Butterfly fauna (Lepidoptera, Papilionoidea) in an ecotone between two biodiversity hotspots in Minas Gerais, Brazil
Authors: Soldati Déborah , Silveira Fernando Amaral da , Silva André Roberto Melo
Published: January 2019

This paper investigates the butterfly fauna of the ‘Serra do Rola-Moça’ State Park, Minas Gerais, Brazil. We evaluate i) the seasonal variation of species richness and composition; and ii) the variation in composition of the local butterfly assemblage among three sampling sites and between the dry and rainy seasons. Sampling was carried out monthly between November 2012 and October 2013, using entomological nets. After a total sampling effort of 504 net hours, 311 species were recorded, one of them endangered in Brazil, and eight probable new species. Furthermore, two species were new records for the region and seven considered endemic of the Cerrado. There was no significant difference in species richness between the dry and the rainy seasons, however the species composition varies significantly among sampling sites. Due to its special, heterogeneous environment, which is home to a rich butterfly fauna, its preservation is important for the conservation of the regional butterfly fauna.
New records of Helicina schereri (Gastropoda: Helicinidae) from the states of Bahia, Minas Gerais, and Mato Grosso do Sul, Brazil
Authors: Silva Fernanda Dos Santos , Cavallari Daniel Caracanhas , Simone Luiz Ricardo Lopes de
Published: January 2019

New records for Helicina schereri Baker, 1913, are reported. It was a species previously restricted to the states of Ceará, Rio Grande do Norte, Paraíba, Alagoas and Tocantins in Northeastern Brazil, and State of Santa Catarina, much further south. The new occurrences reported herein fill distribution gaps and also significantly expand the range of the species ca. 970 km westwards. The new records are from the following locations: Bahia State (Ituaçu and Itaquara municipalities) in Northeast Brazil; Mato Grosso do Sul State (Bonito Municipality) in the Midwest; and Minas Gerais (Lagoa Santa municipality) in the Southeast.
Protective Effects of Activated Myofibroblasts in the Pressure-Overloaded Myocardium Are Mediated Through Smad-Dependent Activation of a Matrix-Preserving Program
Authors: Russo Ilaria , Cavalera Michele , Huang Shuaibo , Su Ya , Hanna Anis , Chen Bijun , Shinde Arti V. , Conway Simon J. , Graff Jonathan , Frangogiannis Nikolaos G.
Published: January 2019

Rationale:

The heart contains abundant interstitial and perivascular fibroblasts. Traditional views suggest that, under conditions of mechanical stress, cytokines, growth factors, and neurohumoral mediators stimulate fibroblast activation, inducing ECM (extracellular matrix) protein synthesis and promoting fibrosis and diastolic dysfunction. Members of the TGF (transforming growth factor)-β family are upregulated and activated in the remodeling myocardium and modulate phenotype and function of all myocardial cell types through activation of intracellular effector molecules, the Smads (small mothers against decapentaplegic), and through Smad-independent pathways.

Objectives:

To examine the role of fibroblast-specific TGF-β/Smad3 signaling in the remodeling pressure-overloaded myocardium.

Methods and Results:

We examined the effects of cell-specific Smad3 loss in activated periostin-expressing myofibroblasts using a mouse model of cardiac pressure overload, induced through transverse aortic constriction. Surprisingly, FS3KO (myofibroblast-specific Smad3 knockout) mice exhibited accelerated systolic dysfunction after pressure overload, evidenced by an early 40% reduction in ejection fraction after 7 days of transverse aortic constriction. Accelerated systolic dysfunction in pressure-overloaded FS3KO mice was associated with accentuated matrix degradation and generation of collagen-derived matrikines, accompanied by cardiomyocyte myofibrillar loss and apoptosis, and by enhanced macrophage-driven inflammation. In vitro, TGF-β1, TGF-β2, and TGF-β3 stimulated a Smad3-dependent matrix-preserving phenotype in cardiac fibroblasts, suppressing MMP (matrix metalloproteinase)-3 and MMP-8 synthesis and inducing TIMP (tissue inhibitor of metalloproteinases)-1. In vivo, administration of an MMP-8 inhibitor attenuated early systolic dysfunction in pressure-overloaded FS3KO mice, suggesting that the protective effects of activated cardiac myofibroblasts in the pressure-overloaded myocardium are, at least in part, because of suppression of MMPs and activation of a matrix-preserving program. MMP-8 stimulation induces a proinflammatory phenotype in isolated macrophages.

Conclusions:

In the pressure-overloaded myocardium, TGF-β/Smad3-activated cardiac fibroblasts play an important protective role, preserving the ECM network, suppressing macrophage-driven inflammation, and attenuating cardiomyocyte injury. The protective actions of the myofibroblasts are mediated, at least in part, through Smad-dependent suppression of matrix-degrading proteases.
Glottic Stenosis: An Anatomic Analysis and New Treatment With a Self-Retaining Interarytenoid Spring
Authors: Zeitels Steven M. , Lombardo Patrick , Chaves Jaime L. , Burns James A. , Hillman Robert E. , Heaton James T. , Kobler James B.
Published: January 2019

Introduction:

Endotracheal (ET) intubation is a common cause of acquired glottic stenosis. Severe cases often require an irreversible arytenoidectomy/cordectomy, which typically results in poor voice quality. Adult human cadaver larynges were studied to gain insights about ET tube–induced posterior glottic injuries, hoping to create a less invasive remedy.

Study Design:

Human cadaver investigation and case reports.

Methods:

Microlaryngeal assessments were done on 10 human cadaver larynges (5 men, 5 women) with and without ET tubes. After supracricoid soft tissue resection, measurements were obtained, including the distance between the outer diameter of the ET tube and the medial aspect of the cricoarytenoid joint facet. Additionally, measurements of the circumferential arc of differently sized ET tubes were made alongside both cricoarytenoid joint capsules. This information was used to design a silastic stent that would function as a self-retaining interarytenoid spring to treat posterior glottic stenosis in 5 patients. Four of 5 patients included in the clinical study were tracheotomy dependent, primarily because of glottic stenosis. The human surgical technique is described in detail.

Results:

The shortest distance between the outer diameter of the ET tube to the medial cricoid facet averaged 5.02 mm in men and 3.62 mm in women. On the basis of the diameter of the intralaryngeal component of the initially round stent, and the position of the cricoarytenoid joint facets, the interarytenoid spring would have a subtended arc between 110° and 175°. These data helped fashion parameters for modifying a conventional T-tube to form a new self-retaining silastic interarytenoid spring. The first 5 human cases have been successful, allowing effective tracheotomy tube decannulation and excellent voice quality.

Conclusions:

The anatomic investigation herein provided key insights into ET tube–induced glottic stenosis and facilitated a new straightforward procedure to surgically improve the airway yet preserve excellent vocal function in patients with acquired glottic stenosis. Level of Evidence: NA
The Art and Craft of Phonomicrosurgery in Grammy Award–Winning Elite Performers
Authors: Zeitels Steven M.
Published: January 2019

Background:

Since the renowned opera maestro Manuel Garcia presented “Observations on the Human Voice” using mirror laryngoscopy in 1855, there has been an inextricable link between performing vocalists and laryngologists. Today, specialized laryngeal surgeons continue the tradition of integrating medical and surgical management of performers with those skilled in vocal arts, voice science, and voice therapy. With advances in surgical instrumentation and techniques, increasing opportunities have evolved to surgically restore lost performing voices. However, it is especially challenging because of a range of factors, including the need for optimal technical precision, management of expectations, complexity of informed consent, public visibility of these patients, and the economics related to the success and failure of surgery. A number of these key issues apply to phonomicrosurgical procedures in nonsingers as well. Consequently, reviewing the art and craft of phonomicrosurgery in elite performers provides valuable insights into the optimal management of any patient.

Methods:

A retrospective review was done of microlaryngeal procedures for the past 20 years, and 18 elite performers were identified who were Grammy Award winners. Microsurgical methods for different lesions are illustrated. Composite analyses of the group along with their associated pathology was done to provide insights into key issues.

Results:

The 18 patients in this cohort have won 80 Grammy Awards, which were garnered from 242 nominations. All 18 had substantial deterioration in voice quality and could retain more than 1 pathology. Significant loss of superficial lamina propria (SLP) pliability was present in 15 of 18, varices and/or ectasias leading to vocal hemorrhage in 6, vocal polyps in 9, fibrovascular nodules in 6, arytenoid granuloma in 1, sulcus from prior microlaryngeal surgery leading to vocal fold SLP scarring in 4, sulcus from long-term phonotrauma leading to vocal fold SLP scarring in 4, benign cyst in 1, precancerous dysplasia in 2, and invasive carcinoma in 2. Subsequent to phonomicrosurgery, all reported improvement in their performance.

Conclusions:

Laryngologists and laryngeal surgeons have shouldered a burden of responsibility for elite performing vocalists since the origin of our specialty. Most lesions and diagnoses that are encountered result from phonotrauma. Optimizing singers’ care provides surgeons with extremely complex technical, emotional, social, and financial challenges. Focused analysis of managing elite performing vocalists effectively integrates a range of essential issues, which provide key insights to assist clinicians treating nonperforming patients requiring phonomicrosurgery.