bluuebunny/crossref_metadata_2025 huggingface dataset:
Controls on the distribution of volcanism and intra-basaltic sediments in the Cambo–Rosebank region, West of Shetland
Authors: Hardman Jonathon , Schofield Nick , Jolley David , Hartley Adrian , Holford Simon , Watson Douglas
Published: January 2018

The NE Atlantic margin is one of the last frontier areas of hydrocarbon exploration within the UK Continental Shelf. In 2004, a major oil and gas discovery (Rosebank) was made within Paleocene–Eocene-age lavas in the Faroe–Shetland Basin. The Rosebank Field consists of intra-basaltic terrestrial to marginal-marine reservoir sequences, separated by basaltic lava flows and volcaniclastics. Despite the identification of a major intra-lava-incised drainage system running parallel to the SW–NE-trending Rosebank Field, the controls on the distribution of both the volcanics and the intra-basaltic sediments were previously unclear, in part due to the difficulties that volcanic sequences pose to seismic acquisition, processing and interpretation. This has led to uncertainty in defining the wider intra-basaltic play. However, the examination of the recently acquired FSB 2011–12 MultiClient GeoStreamer® Survey has facilitated an increased definition of the geological units within and below the volcanic succession, and a reinterpretation of the Late Paleocene–Early Eocene stratigraphy. Through integration of 3D seismic data and well analysis, we present a regional overview of the volcanics and intra-basaltic sediments in the Rosebank region of the Faroe–Shetland Basin. We find that the structural setting of the Rosebank Field, in addition to lava-flow morphology, strongly influences the distribution of the intra-basaltic play fairway within the Paleocene–Eocene-aged Flett Formation. Restriction of fluvial siliciclastic sediments adjacent to the Corona Ridge extends the theorized Rosebank play fairway to the area SW of the Rosebank Field. Our analysis indicates that understanding the underlying basin structure is integral to the success of intra-basaltic plays.
A Real-Time Framework for Task Assignment in Hyperlocal Spatial Crowdsourcing
Authors: Tran Luan , To Hien , Fan Liyue , Shahabi Cyrus
Published: January 2018

Spatial Crowdsourcing (SC)
is a novel platform that engages individuals in the act of collecting various types of spatial data. This method of data collection can significantly reduce cost and turnover time and is particularly useful in urban environmental sensing, where traditional means fail to provide fine-grained field data. In this study, we introduce hyperlocal spatial crowdsourcing, where all workers who are located within the spatiotemporal vicinity of a task are eligible to perform the task (e.g., reporting the precipitation level at their area and time). In this setting, there is often a
budget
constraint, either for every time period or for the entire campaign, on the number of workers to activate to perform tasks. The challenge is thus to maximize the number of assigned tasks under the budget constraint despite the dynamic arrivals of workers and tasks. We introduce a taxonomy of several problem variants, such as
budget-per-time-period
vs.
budget-per-campaign
and
binary-utility
vs.
distance-based-utility
. We study the hardness of the task assignment problem in the
offline
setting and propose
online
heuristics which exploit the spatial and temporal knowledge acquired over time. Our experiments are conducted with spatial crowdsourcing workloads generated by the SCAWG tool, and extensive results show the effectiveness and efficiency of our proposed solutions.
Targeted and Nontargeted α-Particle Therapies
Authors: McDevitt Michael R. , Sgouros George , Sofou Stavroula
Published: January 2018

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease.
Measuring Entropy in Molecular Recognition by Proteins
Authors: Wand A. Joshua , Sharp Kim A.
Published: January 2018

Molecular recognition by proteins is fundamental to the molecular basis of biology. Dissection of the thermodynamic landscape governing protein–ligand interactions has proven difficult because determination of various entropic contributions is quite challenging. Nuclear magnetic resonance relaxation measurements, theory, and simulations suggest that conformational entropy can be accessed through a dynamical proxy. Here, we review the relationship between measures of fast side-chain motion and the underlying conformational entropy. The dynamical proxy reveals that the contribution of conformational entropy can range from highly favorable to highly unfavorable and demonstrates the potential of this key thermodynamic variable to modulate protein–ligand interactions. The dynamical so-called entropy meter also refines the role of solvent entropy and directly determines the loss in rotational–translational entropy that occurs upon formation of high-affinity complexes. The ability to quantify the roles of entropy through an entropy meter based on measurable dynamical properties promises to highlight its role in protein function.
Immune Response to Dengue and Zika
Authors: Elong Ngono Annie , Shresta Sujan
Published: January 2018

Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection. As DENV and ZIKV are closely related, knowledge based on DENV studies has been used to prioritize investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV diagnostic, therapeutic, and vaccine design. This review discusses the following topics related to innate and adaptive immune responses to DENV and ZIKV: the interferon system as the key mechanism of host defense and viral target for immune evasion, antibody-mediated protection versus antibody-dependent enhancement, and T cell–mediated protection versus original T cell antigenic sin. Understanding the mechanisms that regulate the balance between immune-mediated protection and pathogenesis during DENV and ZIKV infections is critical toward development of safe and effective DENV and ZIKV therapeutics and vaccines.
Unwelcome Change: Coming to Terms with Democratic Backsliding
Authors: Waldner David , Lust Ellen
Published: January 2018

Scholars have paid increasing attention to democratic backsliding, yet efforts to explain this phenomenon remain inchoate. This article seeks to place the study of democratic backsliding on sturdier conceptual, operational, and theoretical foundations. Conceptually, the challenge of backsliding is to define changes that take place within a political regime. Methodologically, the challenge involves measurement of intraregime changes, as alternative coding schemes change the population of units that have experienced democratic backsliding. Theoretical challenges are dual: First, despite a rich and diverse literature, we lack readily available theories to explain backsliding, and second, the theoretical debates that do exist—centered on the causes of democratic transitions, democratic breakdowns, authoritarian resilience, and democratic consolidation—remain unresolved. We consider how these theories might be called into service to explain backsliding. By doing so, the article aims to set the terms of the debate to create a common focal point around which research can coalesce.
Fibrin turnover and pleural organization: bench to bedside
Authors: Komissarov Andrey A. , Rahman Najib , Lee Y. C. Gary , Florova Galina , Shetty Sreerama , Idell Richard , Ikebe Mitsuo , Das Kumuda , Tucker Torry A. , Idell Steven
Published: January 2018

Recent studies have shed new light on the role of the fibrinolytic system in the pathogenesis of pleural organization, including the mechanisms by which the system regulates mesenchymal transition of mesothelial cells and how that process affects outcomes of pleural injury. The key contribution of plasminogen activator inhibitor-1 to the outcomes of pleural injury is now better understood as is its role in the regulation of intrapleural fibrinolytic therapy. In addition, the mechanisms by which fibrinolysins are processed after intrapleural administration have now been elucidated, informing new candidate diagnostics and therapeutics for pleural loculation and failed drainage. The emergence of new potential interventional targets offers the potential for the development of new and more effective therapeutic candidates.
Spectroscopic and Electrochemical Properties of (1-x)[PVA/PVP] : x[MgCl26H2O] Blend Polymer Electrolyte Films
Authors: Basha Sk. Shahenoor , Rao M. C.
Published: January 2018

Blend polymer electrolytes were prepared with different wt% compositions of [PVA/PVP-MgCl2·6H2O] : x% using solution cast technique. Structural, morphological, vibrational, thermal, and ionic conductivity and electrochemical properties were studied on the prepared polymer films. XRD revealed the crystalline nature of the polymer electrolyte films. The morphology and the degree of roughness of the prepared films were analyzed by SEM. FTIR and Raman studies confirmed the chemical complex nature of the ligands, interlinking bond formation between the blend polymers and the dopant salt. The glass transition temperature (Tg) of polymer electrolytes was confirmed by DSC studies. Ionic conductivity measurements were carried out on the prepared films in the frequency ranging between 5000 Hz and 50000 KHz and found to be maximum (2.42 × 10−4 S/cm) for the prepared film with wt% composition 35PVA/35PVP : 30MgCl2·6H2O at room temperature. The electrochemical studies were also performed on the prepared films. The galvanostatic charge/discharge performance was carried out from 2.9 to 4.4 V for the configuration Mg+/(PVA/PVP + MgCl2·6H2O)/(I2 + C + electrolyte).
Multistability Analysis and Function Projective Synchronization in Relay Coupled Oscillators
Authors: Taher Azar Ahmad , Adele Ngo Mouelas , Tewa Alain Kammogne Soup , Kengne Romanic , Bertrand Fotsin Hilaire
Published: January 2018

Regions of stability phases discovered in a general class of Genesio−Tesi chaotic oscillators are proposed. In a relatively large region of two‐parameter space, the system has coexisting point attractors and limit cycles. The variation of two parameters is used to characterize the multistability by plotting the isospike diagrams for two nonsymmetric initial conditions. The parameters window in which the jerk system exhibits the unusual and striking feature of multiple attractors (e.g., coexistence of six disconnected periodic chaotic attractors and three‐point attraction) is investigated. The second aspect of this study presents the synchronization of systems that act as mediators between two dynamical units that, in turn, show function projective synchronization (FPS) with each other. These are the so‐called relay systems. In a wide range of operating parameters; this setup leads to synchronization between the outer circuits, while the relaying element remains unsynchronized. The results show that the coupled systems can achieve function projective synchronization in a determined time despite the unpredictability of the scaling function. In the coupling path, the outer dynamical systems show finite‐time synchronization of their outputs, that is, displaying the same dynamics at exactly the same moment. Further, this effect is rather general and it has a wide range of applications where sustained oscillations should be retained for proper functioning of the systems.
Asymmetric Dimethyl Arginine as a Biomarker of Atherosclerosis in Rheumatoid Arthritis
Authors: Di Franco Manuela , Lucchino Bruno , Conti Fabrizio , Valesini Guido , Spinelli Francesca Romana
Published: January 2018

Cardiovascular disease is the main cause of morbidity and mortality in rheumatoid arthritis (RA). Despite the advent on new drugs targeting the articular manifestations, the burden of cardiovascular disease is still an unmet need in the management of RA. The pathophysiology of accelerated atherosclerosis associated to RA is not yet fully understood, and reliable and specific markers of early cardiovascular involvement are still lacking. Asymmetric dimethylarginine is gaining attention for its implication in the pathogenesis of endothelial dysfunction and as biomarkers of subclinical atherosclerosis. Moreover, the metabolic pathway of methylarginines offers possible targets for therapeutic interventions to decrease the cardiovascular risk. The purpose of this review is to describe the main causes of increased methylarginine levels in RA, their implication in accelerated atherosclerosis, the possible role as biomarkers of cardiovascular risk, and finally the available data on current pharmacological treatment.
Computational Investigation on the Biomechanical Responses of the Osteocytes to the Compressive Stimulus: A Poroelastic Model
Authors: Wang Liping , Dong Jianghui , Xian Cory J.
Published: January 2018

Osteocytes, the major type of bone cells embedded in the bone matrix and surrounded by the lacunar and canalicular system, can serve as biomechanosensors and biomechanotranducers of the bone. Theoretical analytical methods have been employed to investigate the biomechanical responses of osteocytes in vivo; the poroelastic properties have not been taken into consideration in the three-dimensional (3D) finite element model. In this study, a 3D poroelastic idealized finite element model was developed and was used to predict biomechanical behaviours (maximal principal strain, pore pressure, and fluid velocity) of the osteocyte-lacunar-canalicular system under 150-, 1000-, 3000-, and 5000-microstrain compressive loads, respectively, representing disuse, physiological, overuse, and pathological overload loading stimuli. The highest local strain, pore pressure, and fluid velocity were found to be highest at the proximal region of cell processes. These data suggest that the strain, pore pressure, and fluid velocity of the osteocyte-lacunar-canalicular system increase with the global loading and that the poroelastic material property affects the biomechanical responses to the compressive stimulus. This new model can be used to predict the mechanobiological behaviours of osteocytes under the four different compressive loadings and may provide an insight into the mechanisms of mechanosensation and mechanotransduction of the bone.
Primary Pancreatic Burkitt’s Lymphoma: A Case Report and Review of the Literature
Authors: Konjeti Venkata Rajesh , Hefferman Gerald M. , Paluri Sravanthi , Ganjoo Prerna
Published: January 2018

Primary pancreatic lymphoma (PPL) is of very rare occurrence as an extra nodal site of Non-Hodgkin’s lymphoma (NHL). It represents less than 1% of NHL. Out of which Burkitt lymphoma of pancreas is of a rare presentation. It usually occurs in children and presenting in adults is uncommon. The prevalence of pancreatic Burkitt lymphoma is not known as the incidence is significantly low. Clinical features of PPL are predominantly nonspecific and can become difficult with associated inflammation of pancreas. Differentiation of lymphoma to adenocarcinoma is important as chemotherapy is the main stay of treatment in lymphoma. We report a case of 68-year-old female who presented with nonspecific symptoms and was found to have obstructive jaundice secondary to pancreatic head neoplasm which was proved to be pancreatic Burkitt lymphoma which is a rare presentation.
Confidence amongst Multidisciplinary Professionals in Managing Paediatric Rheumatic Disease in Australia
Authors: Cassidy Samuel , Coda Andrea , West Kerry , Hendry Gordon , Grech Debra , Jones Julie , Hawke Fiona , Singh-Grewal Davinder
Published: January 2018

Objective. Interprofessional collaboration is a crucial component of care for children with rheumatic disease. Interprofessional care, when delivered appropriately, prevents disability and improves long-term prognosis in this vulnerable group. Methods. The aim of this survey was to explore allied health professionals’ and nurses’ confidence in treating paediatric rheumatology patients. Results. Overall, 117 participants were recruited, 77.9% of participants reported being “not confident at all,” “not confident,” or “neutral” in treating children with rheumatic diseases (RD) despite 65.1% of participants reporting having treated >1 paediatric rheumatology case in the past month. Furthermore, 67.2% of participants felt their undergraduate education in paediatric rheumatology was inadequate. “Journals” or “texts books” were used by 49.3% of participants as their primary source of continuing professional development (CPD) and 39.3% of participants indicated that they did not undertake any CPD related to paediatric rheumatology. Small group and online education were perceived to be potentially of “great benefit” for CPD. Conclusion. This paper highlights allied health professionals’ and nurses’ perceived inadequacy of their undergraduate education in paediatric RD and their low confidence in recognising and treating RD. Undergraduate and postgraduate education opportunities focusing on interprofessional collaboration should be developed to address this workforce deficiency.
Vehicle Remote Health Monitoring and Prognostic Maintenance System
Authors: Shafi Uferah , Safi Asad , Shahid Ahmad Raza , Ziauddin Sheikh , Saleem Muhammad Qaiser
Published: January 2018

In many industries inclusive of automotive vehicle industry, predictive maintenance has become more important. It is hard to diagnose failure in advance in the vehicle industry because of the limited availability of sensors and some of the designing exertions. However with the great development in automotive industry, it looks feasible today to analyze sensor’s data along with machine learning techniques for failure prediction. In this article, an approach is presented for fault prediction of four main subsystems of vehicle, fuel system, ignition system, exhaust system, and cooling system. Sensor is collected when vehicle is on the move, both in faulty condition (when any failure in specific system has occurred) and in normal condition. The data is transmitted to the server which analyzes the data. Interesting patterns are learned using four classifiers, Decision Tree, Support Vector Machine, K Nearest Neighbor, and Random Forest. These patterns are later used to detect future failures in other vehicles which show the similar behavior. The approach is produced with the end goal of expanding vehicle up-time and was demonstrated on 70 vehicles of Toyota Corolla type. Accuracy comparison of all classifiers is performed on the basis of Receiver Operating Characteristics (ROC) curves.
Honey as a Potential Natural Antioxidant Medicine: An Insight into Its Molecular Mechanisms of Action
Authors: Ahmed Sarfraz , Sulaiman Siti Amrah , Baig Atif Amin , Ibrahim Muhammad , Liaqat Sana , Fatima Saira , Jabeen Sadia , Shamim Nighat , Othman Nor Hayati
Published: January 2018

Honey clasps several medicinal and health effects as a natural food supplement. It has been established as a potential therapeutic antioxidant agent for various biodiverse ailments. Data report that it exhibits strong wound healing, antibacterial, anti‐inflammatory, antifungal, antiviral, and antidiabetic effects. It also retains immunomodulatory, estrogenic regulatory, antimutagenic, anticancer, and numerous other vigor effects. Data also show that honey, as a conventional therapy, might be a novel antioxidant to abate many of the diseases directly or indirectly associated with oxidative stress. In this review, these wholesome effects have been thoroughly reviewed to underscore the mode of action of honey exploring various possible mechanisms. Evidence‐based research intends that honey acts through a modulatory road of multiple signaling pathways and molecular targets. This road contemplates through various pathways such as induction of caspases in apoptosis; stimulation of TNF‐α, IL‐1β, IFN‐γ, IFNGR1, and p53; inhibition of cell proliferation and cell cycle arrest; inhibition of lipoprotein oxidation, IL‐1, IL‐10, COX‐2, and LOXs; and modulation of other diverse targets. The review highlights the research done as well as the apertures to be investigated. The literature suggests that honey administered alone or as adjuvant therapy might be a potential natural antioxidant medicinal agent warranting further experimental and clinical research.
Repetitive Transcranial Magnetic Stimulation, Cognition, and Multiple Sclerosis: An Overview
Authors: Nasios Grigorios , Messinis Lambros , Dardiotis Efthimios , Papathanasopoulos Panagiotis
Published: January 2018

Multiple sclerosis (MS) affects cognition in the majority of patients. A major aspect of the disease is brain volume loss (BVL), present in all phases and types (relapsing and progressive) of the disease and linked to both motor and cognitive disabilities. Due to the lack of effective pharmacological treatments for cognition, cognitive rehabilitation and other nonpharmacological interventions such as repetitive transcranial magnetic stimulation (rTMS) have recently emerged and their potential role in functional connectivity is studied. With recently developed advanced neuroimaging and neurophysiological techniques, changes related to alterations of the brain’s functional connectivity can be detected. In this overview, we focus on the brain’s functional reorganization in MS, theoretical and practical aspects of rTMS utilization in humans, and its potential therapeutic role in treating cognitively impaired MS patients.
Sectional Fixed Orthodontic Extrusion Technique in Management of Teeth with Complicated Crown-Root Fractures: Report of Two Cases
Authors: M. P. Sockalingam S. Nagarajan , Kong Loh Seu Katherine , Mohamed Noor Halimah , Irfani Zakaria Ahmad Shuhud
Published: January 2018

Complicated crown-root fractures account for a small percentage of traumatic dental injuries seen in children; however, management of these injuries can be very challenging to clinicians. Factors such as complexity of the injury, patient’s age and dentition stage, patient’s cooperation, and parental demands may have some bearing on the type of treatment undertaken and its outcomes. In some children, these injuries may have significant impact on their quality of life. The purpose of this article is to describe two cases of complicated crown-root fracture which were successfully managed through orthodontic extrusion using a sectional fixed orthodontic technique. The basis for the treatment technique and its favourable outcomes were highlighted with its advantages and drawbacks.
Lifetime Traumatic Experiences and Disordered Eating among University Students: The Role of Posttraumatic Stress Symptoms
Authors: Malinauskiene Vilija , Malinauskas Romualdas
Published: January 2018

The associations between lifetime traumatic events (TEs), posttraumatic stress (PTS) symptoms, and disordered eating (DE) were studied in a sample of 614 university students (mean age 20 years). An anonymous questionnaire included 32 lifetime TEs, IES-revised measured PTS symptoms, and EAT-26 evaluated DE symptoms. Statistical analyses included Pearson correlations and structural equation models (SEM) with bootstrapping method. Findings reveal the prevalence of DE in 8.1% of participants, while 73.9% of students experienced at least one lifetime TE. 52.0% of students with DE had PTS symptoms (p<0.0001) and 30.8% of students with lifetime TEs had PTS symptoms (p<0.001). In SEM, direct paths from lifetime TEs to PTS symptoms (0.38, p<0.0001) and from PTS symptoms to DE (0.40, p<0.0001) were observed. The final SEM confirmed the mediating role of PTS symptoms in the path between some TEs (traffic accident and seriously injured) and DE among the university students. If PTS symptoms are associated with DE, then addressing PTS symptoms in the context of DE treatment may improve treatment efficacy.
La mirada decolonial al management
Authors: Mandiola Marcela
Published: January 2018

La teoría del management tradicional, que se investiga y enseña en la mayoría de las escuelas de negocios, ha recibido variadas críticas en el ámbito académico. Una de estas se inspira en el enfoque “decolonial”, que desafía a las teorías que se replican y diseminan por el orbe sin considerar adecuadamente el contexto en el que estas se aplican. Esta mirada decolonial busca hacer evidente el proceso de colonización del conocimiento que acompaña a la expansión del management, y con ello el segundo lugar en el que queda nuestra escasa producción de conocimiento y su consiguente práctica.
CART Targeting of Solid Tumors: More Pieces to the Puzzle
Authors: Kalos Michael
Published: January 2018

Chimeric antigen receptor–modified T (CART)-cell–based targeting of solid tumors remains a considerable and worthwhile challenge in the field of immunotherapy. The role of chemotherapy to target stroma and enhance chimeric antigen receptor (CAR) cell antitumor function, expansion, and persistence is still unresolved. Clin Cancer Res; 24(6); 1246–7. ©2018 AACR.

See related article by Guo et al., p. 1277
Reprogramming of Glucose Metabolism by Zerumbone Suppresses Hepatocarcinogenesis
Authors: Wani Nissar Ahmad , Zhang Bo , Teng Kun-yu , Barajas Juan M. , Motiwala Tasneem , Hu Peng , Yu Lianbo , Brüschweiler Rafael , Ghoshal Kalpana , Jacob Samson T.
Published: January 2018

Hepatocellular carcinoma (HCC) is the most prevalent and highly aggressive liver malignancy with limited therapeutic options. Here, the therapeutic potential of zerumbone, a sesquiterpene derived from the ginger plant Zingiber zerumbet, against HCC was explored. Zerumbone inhibited proliferation and clonogenic survival of HCC cells in a dose-dependent manner by arresting cells at the G2–M phase and inducing apoptosis. To elucidate the underlying molecular mechanisms, a phosphokinase array was performed that showed significant inhibition of the PI3K/AKT/mTOR and STAT3 signaling pathways in zerumbone-treated HCC cells. Gene expression profiling using microarray and analysis of microarray data by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) revealed that zerumbone treatment resulted in significant deregulation of genes regulating apoptosis, cell cycle, and metabolism. Indeed, tracing glucose metabolic pathways by growing HCC cells with 13C6-glucose and measuring extracellular and intracellular metabolites by 2D nuclear magnetic resonance (NMR) spectroscopy showed a reduction in glucose consumption and reduced lactate production, suggesting glycolytic inhibition. In addition, zerumbone impeded shunting of glucose-6-phosphate through the pentose phosphate pathway, thereby forcing tumor cells to undergo cell-cycle arrest and apoptosis. Importantly, zerumbone treatment suppressed subcutaneous and orthotopic growth and lung metastasis of HCC xenografts in immunocompromised mice. In conclusion, these findings reveal a novel and potentially effective therapeutic strategy for HCC using a natural product that targets cancer cell metabolism.

Implications: Dietary compounds, like zerumbone, that impact cell cycle, apoptosis, and metabolic processes may have therapeutic benefits for HCC patients. Mol Cancer Res; 16(2); 256–68. ©2017 AACR.
Prevention of Aortic Dissection Suggests a Diameter Shift to a Lower Aortic Size Threshold for Intervention
Authors: Mansour Ahmed M. , Peterss Sven , Zafar Mohammad A. , Rizzo John A. , Fang Hai , Charilaou Paris , Ziganshin Bulat A. , Darr Umer M. , Elefteriades John A.
Published: January 2018

Background: Multiple studies have quantified the relationship between aortic size and risk of dissection. However, these studies estimated the risk of dissection without accounting for any increase in aortic size from the dissection process itself. Objectives: This study aims to compare aortic size before and after dissection and to evaluate the change in size consequent to the dissection itself. Methods: Fifty-five consecutive patients (29 type A; 26 type B) with aortic dissection and incidental imaging studies prior to dissection were identified and compared to a control group of aneurysm patients (n = 205). The average time between measurement at and prior to dissection was 1.7 ± 1.9 years (1.9 ± 2.0 years mean inter-image time in the control group). A multivariate regression model controlling for growth rate, age, and gender was created to estimate the effect of dissection itself on aortic size. Results: The mean aortic sizes at and prior to dissection were 54.2 ± 7.0 and 45.1 ± 5.7 mm for the ascending aorta, and 47.1 ± 13.8 and 39.5 ± 13.1 mm for the descending aorta, respectively. The multivariable analysis revealed a significant impact of the dissection itself (p < 0.001) and estimated an increase in size of 7.65 mm (ascending aorta) and 6.38 mm (descending aorta). Thus, a proportional estimate of 82.8% (ascending aorta) and 80.8% (descending aorta) of dissections are made at a size lower than the guideline-recommended threshold (55 mm). Conclusions: The aortic diameter increases substantially due to aortic dissection itself and, thus, aortas are being dissected at clinically meaningfully smaller sizes than natural history analyses have previously suggested. These findings have important implications regarding the size at which the risk of dissection is increased.
Impulsivity and Saliva Cortisol in Patients with Suicide Attempt and Controls
Authors: Lewitzka Ute , Bauer Michael , Ripke Bettina , Bronisch Thomas , Günther Lydia
Published: January 2018

Objectives: The objective of this study was to prove concepts in the characterization of suicidal patients and the possible usefulness of those markers to potentially identify patients with a higher risk for suicidality. Methods: Patients with a recent suicide attempt were compared with patients suffering from depression, adjustment disorder, anxiety, or eating disorders without suicidality, healthy controls and remitted patients with a history of at least 1 suicide attempt (≥1 year). We analyzed impulsivity (Barratt Impulsivity Scale, BIS) and saliva cortisol concentrations. Results: Independently of suicidality and disease state patients display higher BIS scores than healthy controls. Saliva cortisol levels tend to be higher in patients in the acute disease state than in remitted patients and healthy controls. Conclusions: Saliva cortisol may be a useful marker that reveals alterations in nonsuicidal patients suffering from depression, adjustment disorder, anxiety, or eating disorders who might be at risk.
A Tale of Absent Crystalline Lens in an Eye with Retinoblastoma
Authors: Bansal Aditya , Noronha Veena , Krishnakumar Subramanian , Khetan Vikas
Published: January 2018

Purpose: To report the clinicopathological correlation of absent crystalline lens in an eye with retinoblastoma. Methods: A 1-year-old female child was brought to our patient services for pain and swelling in the right eye since the past few months. The child was diagnosed to have bilateral retinoblastoma and was suspected to have absence of crystalline lens in the right eye on the basis of clinical findings and ocular imaging. After 3 cycles of chemotherapy for suspected extraocular extension of tumor, she underwent enucleation. Absence of crystalline lens was confirmed on both gross and microscopic pathology. Results: We present a child with retinoblastoma, suspected to have absence of crystalline lens clinically and on ocular imaging (ultrasound and MRI), which was finally confirmed on ocular pathology examination post enucleation. Conclusion: We report for the first time clinicopathologically proven absence of crystalline lens in an eye with retinoblastoma.
Multivisceral Resection for Locally Invasive Colorectal Liver Metastases: Outcomes of a Matched Cohort Analysis
Authors: Hand Fiona , Sanabria Mateos Rebeca , Durand Michael , Fennelly David , McDermott Ray , Maguire Donal , Geoghegan Justin , Winter Des , Hoti Emir
Published: January 2018

Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no longer considered an absolute contraindication to curative hepatic resection. A growing number of observational analyses have illustrated the feasibility of such resections; however, the evidence base is at best heterogeneous with a lack of evidence comparing similar patient groups. We aimed to evaluate the outcomes of hepatectomy for CRLM when combined with other viscera and compare to a matched cohort of isolated hepatic resections. Methods: From 2005 to 2015, 523 patients underwent hepatic resection for CRLM at our institution, 19 of whom underwent hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was performed between those who underwent isolated hepatectomy (control group) and those who underwent hepatectomy with extrahepatic resection (combined group). Clinicopathological data were reviewed along with 30-day postoperative morbidity and mortality. Furthermore, overall survival for the multivisceral cohort was compared to all other isolated hepatectomies over the same time period. Results: Nineteen patients underwent liver resection accompanied by either/or diaphragmatic resection (n = 13), major vein resection and reconstruction (n = 5), and visceral resection (n = 3). Maximum tumor size was significantly larger in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3- and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival showed no significant difference between combined and control groups (p = 0.78). Similarly, when compared to the total cohort of isolated liver resections (n = 504), no significant difference in overall mortality was noted. Conclusion: In patients presenting with concomitant CRLM and extrahepatic extension where R0 margins can be achieved, this present study supports the rationale to proceed to ­surgery with comparable morbidity and mortality rates to ­isolated hepatectomy.
Conjunctival Squamous Cell Carcinoma with Corneal Stromal Invasion in Presumed Pterygia: A Case Series
Authors: Mendoza Pia R. , Craven Caroline M. , Ip Matthew H. , Wilson Matthew W. , Coroneo Minas T. , Grossniklaus Hans E.
Published: January 2018

Aim: To describe 4 cases of conjunctival squamous cell carcinoma (SCC) with corneal stromal invasion. Methods: Retrospective, clinicopathologic case series. Results: All patients had prior resections of presumed pterygia. The degree of corneal involvement dictated the extent of surgical management. One eye with localized invasion was treated with lamellar keratoplasty and plaque brachytherapy. Another case with widespread invasion warranted penetrating keratoplasty and eventual enucleation. Two cases were treated medically prior to surgical intervention: one with localized invasion was treated with topical interferon and retinoic acid; another with significant inflammation was treated with doxycycline and fluorometholone. The patient who underwent keratoplasty and brachytherapy had no recurrence after 7 years of follow-up. Those initially treated medically had resections of recurrence but ultimately required enucleation. Histologically, specimens demonstrated SCC invading the deep corneal stroma, with 2 tumors of the mucoepidermoid type. Conclusions: This series demonstrates the importance of maintaining clinical suspicion of conjunctival squamous neoplasia in pterygia. We recommend that all excised pterygia be submitted for histopathologic evaluation and be carefully evaluated for dysplasia and variants of SCC associated with increased risk of intraocular invasion. Undetected ocular surface squamous neoplasia may give rise to potentially vision- and eye-threatening invasive corneal SCC.
A Fair Chance for Everyone: Total Tumor Volume as a Selection Tool in Liver Transplantation for Hepatocellular Carcinoma
Authors: Pinto-Marques Hugo , Silva Silvia , Sobral Mafalda , Perdigoto Rui , Martins Américo , Barroso Eduardo
Published: January 2018

Total tumor volume (TTV) has been proposed as a more accurate means of selecting patients for liver transplantation (LT) due to hepatocellular carcinoma (HCC). We aim to analyze the role of TTV in a population with a short waiting time on list. Methods: Analysis of a prospective database of patients submitted to LT for HCC between September 1992 and February 2014. TTV, Milan criteria (MC), UCSF (University of California San Francisco), and “Up to Seven” criteria were calculated both with preoperative imaging exams and histological data. Results: The study population consisted of 231 out of patients. Median waiting time on list was 62.5 days. MC included 187 patients, while TTV ≤115 cm3 included 214. Microvascular invasion (HR 2.601, 95% CI 1.529–4.426), MC (HR 1.666, 95% CI 0.990–2.804), UCSF criteria (HR 2.995, 95% CI 1.875–4.875), TTV ≤115 cm3 (HR 2.898, 95% CI 1.398–6.007), and “Up to Seven” criteria (HR 2.139, 95% CI 1.353–3.383) proved to be independent factors for prognosis for disease-free survival. Conclusions: TTV ≤115 cm3 may be a useful tool to properly identify the best HCC candidates for LT in a population with a short waiting time on list. TTV gives more patients the opportunity of undergoing LT while maintaining similar rates of tumor recurrence and patient survival.
Pancreaticoduodenectomy and Outcomes for Groove Pancreatitis
Authors: Aguilera Fabiola , Tsamalaidze Levan , Raimondo Massimo , Puri Ruchir , Asbun Horacio J. , Stauffer John A.
Published: January 2018

Background/Aims: The operative management of groove pancreatitis (GP) is still a matter of controversy and pancreaticoduodenectomy (PD) can be a high-risk procedure for patients. The aim of this study was to report our 9-year experience of surgical resection for GP and to review relevant literature. Methods: A retrospective review of patients undergoing pancreatectomy for GP from August 1, 2008, through May 31, 2017 was performed. Patients with clinical, radiologic, and final pathologic confirmation of GP were included. Literature on the current understanding of GP was reviewed. Results: Eight patients from total 449 pancreatectomies met inclusion criteria. Four male and 4 female patients (mean age, 51.9 years; mean body mass index, 25.3) underwent pylorus-preserving pancreatoduodenectomy (3 by laparoscopy and 5 by open approach). Mean (range) operative time and blood loss was 343 (167–525) min and 218 (40–500) mL respectively. Pancreatic fistula and delayed gastric emptying were noted in one patient each. No major complications occurred, but minor complications occurred in 5 (62%) patients. Mean hospital stay was 6.1 (range 3–14) days. At median follow-up of 18.15 (interquartile range 7.25–33.8) months, all patients experienced a resolution of pancreatitis and improvement in symptoms. Conclusions: PD is a safe procedure for GP. Short-term surgical outcomes are acceptable and long-term outcomes are associated with improved symptom control.
Por uma fala: o negro corpo do discurso
Authors: Silva Fabiana Carneiro da
Published: January 2018

A necessidade de conceder centralidade ao debate sobre negritude e racismo no Brasil é uma reivindicação de longa data, realizada, sobretudo, pela população negra articulada em uma variedade de agrupamentos político-culturais. Ela remete a um dado concreto e complexo da sociedade brasileira contemporânea: a exclusão e/ou subalternização do negro e da negra do processo que em diversos âmbitos constituiu o que se entende como este estado-nação.  Neste artigo, tendo como pressuposto desdobramentos analíticos sobre a dicção de Kehinde, narradora do romance Um defeito de cor, pretendo refletir sobre o gesto de escrita da autora negra Ana Maria Gonçalves e num encadeamento autorreflexivo sobre meu próprio gesto de escrita enquanto intelectual não-branca. Na medida em que essas vozes buscam  visibilizar uma herança violenta, monstruosa, de um sistema em que a perversão escravista foi administrada sob o respaldo da racionalidade, proponho a investigação dos fundamentose limites de um discurso sobre negritude, os quais se inscrevem no corpo do sujeito enunciador. Desse modo,  retomo o debate sobre experiência e teoria,  atribuindo ao corpo negro o poder de interpelar a ideologia nacionalista e exigir que se repense o vínculo dos lugares de enunciação com o sistema historicamente engendrado e atualmente operante no Brasil.
Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis
Authors: Koupenova Milka , Clancy Lauren , Corkrey Heather A. , Freedman Jane E.
Published: January 2018

Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular importance of platelets has been attributed to their essential role in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism. Increasing knowledge on the platelets’ role in the vasculature has led to many advances in understanding not only how platelets interact with the vessel wall but also how they convey changes in the environment to other circulating cells. In addition to their well-described hemostatic function, platelets are active participants in the immune response to microbial organisms and foreign substances. Although incompletely understood, the immune role of platelets is a delicate balance between its pathogenic response and its regulation of thrombotic and hemostatic functions. Platelets mediate complex vascular homeostasis via specific receptors and granule release, RNA transfer, and mitochondrial secretion that subsequently regulates hemostasis and thrombosis, infection, and innate and adaptive immunity.
Translational Research in Cardiovascular Repair
Authors: Chamuleau Steven A.J. , van der Naald Mira , Climent Andreu M. , Kraaijeveld Adriaan O. , Wever Kim E. , Duncker Dirk J. , Fernández-Avilés Francisco , Bolli Roberto
Published: January 2018

The international consortium TACTICS (Transnational Alliance for Regenerative Therapies in Cardiovascular Syndromes) has recently addressed key priorities in the field of cell-based therapy for cardiac repair, identifying the efficacy of translational research as one of the main challenges to ultimately improve the quality of life of patients with ischemic disease. Much of the controversy and confusion surrounding cardiac regenerative therapy stems from insufficient rigor in the conduct of preclinical studies, and there is an increasing recognition of a number of problems that undermine its quality that may contribute to translational failure. Here, we introduce well defined stages for preclinical research, and put forth proposals that should promote more rigorous preclinical work, in an effort to improve its quality and translatability. To augment the utility of preclinical research and its translation, it is necessary to (1) improve the quality of preclinical research, (2) promote collaborative efforts, and (3) enhance the sharing of knowledge and protocols. In particular, confirmatory (stage III) preclinical studies should be considered as a preamble to clinical studies and therefore must adhere to their standards of quality (including internal validity, standardization of protocols, and multicenter design). To increase transparency and minimize bias, these studies should be prospectively registered in an independent, open database. Ultimately, these recommendations should be implemented in the daily routine of investigators and in the policies of institutions, journals, and funding agencies.
Phosphoinositide 3-Kinase Gamma Inhibition Protects From Anthracycline Cardiotoxicity and Reduces Tumor Growth
Authors: Li Mingchuan , Sala Valentina , De Santis Maria Chiara , Cimino James , Cappello Paola , Pianca Nicola , Di Bona Anna , Margaria Jean Piero , Martini Miriam , Lazzarini Edoardo , Pirozzi Flora , Rossi Luca , Franco Irene , Bornbaum Julia , Heger Jacqueline , Rohrbach Susanne , Perino Alessia , Tocchetti Carlo G. , Lima Braulio H.F. , Teixeira Mauro M. , Porporato Paolo E. , Schulz Rainer , Angelini Annalisa , Sandri Marco , Ameri Pietro , Sciarretta Sebastiano , Lima-Júnior Roberto César P. , Mongillo Marco , Zaglia Tania , Morello Fulvio , Novelli Francesco , Hirsch Emilio , Ghigo Alessandra
Published: January 2018

Background:

Anthracyclines, such as doxorubicin (DOX), are potent anticancer agents for the treatment of solid tumors and hematologic malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of phosphoinositide 3-kinase γ (PI3Kγ) in DOX-induced cardiotoxicity and the potential cardioprotective and anticancer effects of PI3Kγ inhibition.

Methods:

Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ-selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography, and DOX-mediated signaling was assessed in whole hearts or isolated cardiomyocytes. The dual cardioprotective and antitumor action of PI3Kγ inhibition was assessed in mouse mammary tumor models.

Results:

PI3Kγ kinase-dead mice showed preserved cardiac function after chronic low-dose DOX treatment and were protected against DOX-induced cardiotoxicity. The beneficial effects of PI3Kγ inhibition were causally linked to enhanced autophagic disposal of DOX-damaged mitochondria. Consistently, either pharmacological or genetic blockade of autophagy in vivo abrogated the resistance of PI3Kγ kinase-dead mice to DOX cardiotoxicity. Mechanistically, PI3Kγ was triggered in DOX-treated hearts, downstream of Toll-like receptor 9, by the mitochondrial DNA released by injured organelles and contained in autolysosomes. This autolysosomal PI3Kγ/Akt/mTOR/Ulk1 signaling provided maladaptive feedback inhibition of autophagy. PI3Kγ blockade in models of mammary gland tumors prevented DOX-induced cardiac dysfunction and concomitantly synergized with the antitumor action of DOX by unleashing anticancer immunity.

Conclusions:

Blockade of PI3Kγ may provide a dual therapeutic advantage in cancer therapy by simultaneously preventing anthracyclines cardiotoxicity and reducing tumor growth.