bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

BackgroundResuscitative 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.MethodsAnesthetized 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.ResultsAll 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.DiscussionProlonged 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 evidenceII.
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.
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.
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

Abstract

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

AbstractPurpose: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.
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.
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.
Population Stereotypes for Objects and Representations: Response Tendencies for Interacting With Everyday Objects and Interfaces
Authors: Vu Kim-Phuong L. , Sun Yuting 
Published: January 2019

Objective: The objective of the study is to replicate and extend population stereotypes from a broad range of users for display-control relations of common interfaces using pictures/images of the objects. Background: Population stereotypes for display-control configurations refer to people’s tendencies to associate certain control actions with display properties. An interface will benefit by being designed in a manner that is consistent with the stereotypes. The stimuli used in the present study include conceptual replications of objects that have been examined previously and new ones. Method: An online survey was designed to collect data about participants’ natural response tendencies or interpretations of the meaning associated with objects, representations, and colors. Participants were obtained through MTurk from the United States, India, and UK. Results: We replicated 76% and partially replicated an additional 16% of the stereotypic responses found in prior studies. Considering the full data set, we found stereotypic responses for 62% of the stimuli that are consistent across the three countries in which the participants were located, although the strength of these stereotypes may differ by location. For the remaining 38% of the stimuli, population stereotypes still emerged for some locations. Few gender differences were found. Conclusion: Cross-cultural stereotypic responses exist for many objects, representations, and display-control configurations. However, because stereotypes can be limited to specific regions or change over time, we recommend that they be captured periodically to ensure design guidelines based on the stereotypes remain valid. Application: Designers can use the stereotypic responses to guide design decisions.
Eighteen-Year Follow-Up of 160 Consecutive Individuals Born With Unilateral Cleft Lip or Cleft Lip and Alveolus Treated by the Oslo Cleft Lip and Palate Team
Authors: Mandal Emeline , Filip Charles , Andersson Maud Els-Marie , Øgaard Bjørn 
Published: January 2019

Objective: Describe patients born with unilateral cleft lip with or without cleft alveolus (CL±A) in relation to cleft severity and laterality, gender, associated anomalies and syndromes, number and type of lip- and nose operations, and time of alveolar bone graft (ABG) treatment in relation to dental status in cleft area. Materials and Methods: Patients included 220 children born with unilateral CL±A, born between 1988 and 1997 referred to the Oslo Cleft Lip and Palate Team. The data were collected retrospectively. All patients were followed up until 18 years of age. Results: Among all CL±A, 3.6% had recognized syndromes, 6.8% had associated anomalies, and in 89.6% CL±A was the only malformation. CL±A was more common, but not more severe, on the left side. Among the 160 individuals with CL±A without syndromes and associated anomalies, 66.9% had an isolated soft tissue CL, and 33.1% were diagnosed with a CL alveolus (CL+A). Male predominance was observed. Children with CL+A had more severe soft tissue clefts of the lip and underwent more lip and nose surgeries than children born with CL. The time of ABG was found to be at a younger age when the patient had a lateral incisor in the cleft area than when this tooth was missing. Conclusion: Findings provide a reference for morphologic variations in CL±A, and insight into the surgical burden of care until the age of 18 years.