bluuebunny/crossref_metadata_2025 huggingface dataset:
Catch-up-ESUS - follow-up in embolic stroke of undetermined source (ESUS) in a prospective, open-label, observational study: study protocol and initial baseline data
Authors: Feil Katharina , Heinrich Johanna , Küpper Clemens , Müller Katharina , Laub Christoph , von Falkenhausen Aenne S , Becker Regina , Wollenweber Frank A , Kääb Stefan , Sinner Moritz F , Kellert Lars
Published: December 2019

Introduction

So far there is no uniform, commonly accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). Recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation. As ESUS comprises heterogeneous subgroups including a wide age-range, concomitant patent foramen ovale (PFO), and variable probability for atrial fibrillation (AF), an individualised approach is urgently needed. This prospective registry study aims to provide initial data towards an individual, structured diagnostic and therapeutic approach in ESUS patients.

Methods and analysis

The open-label, investigator-initiated, prospective, single-centre, observational registry study (Catch-up-ESUS) started in 01/2018. Consecutive ESUS patients ≥18 years who give informed consent are included and will be followed up for 3 years. Stratified by age <60 or ≥60 years, the patients are processed following a standardised diagnostic and treatment algorithm with an interdisciplinary design involving neurologists and cardiologists. Depending on the strata, patients receive a transesophageal echocardiogram; all patients receive an implantable cardiac monitor. Patients <60 years with PFO and without evidence of concomitant AF are planned for PFO closure within 6 months after stroke. The current diagnostic and therapeutic workup of ESUS patients requires improvement by both standardisation and a more individualised approach. Catch-up-ESUS will provide important data with respect to AF detection and PFO closure and will estimate stratified stroke recurrence rates after ESUS.

Ethics and dissemination

The study has been approved by the responsible ethics committee at the Ludwig Maximilian University, Munich, Germany (project number 17–685). Catch-Up-ESUS is conducted in accordance with the Declaration of Helsinki. All patients will have to give written informed consent or, if unable to give consent themselves, their legal guardian will have to provide written informed consent for their participation. The first observation period of the registry study is 1 year, followed by the first publication of the results including follow-up of the patients. Further publications will be considered according the predefined individual follow-up dates of the stroke patients up to 36 months.

Trial registration number

Clinicaltrialsregister.gov registry (NCT03820375).
Speaking Up for Fundamental Care: the ILC Aalborg Statement
Authors: Kitson Alison , Carr Devin , Conroy Tiffany , Feo Rebecca , Grønkjær Mette , Huisman-de Waal Getty , Jackson Debra , Jeffs Lianne , Merkley Jane , Muntlin Athlin Åsa , Parr Jennifer , Richards David A , Sørensen Erik Elgaard , Wengström Yvonne
Published: December 2019

Objective

The International Learning Collaborative (ILC) is an organisation dedicated to understanding why fundamental care, the care required by all patients regardless of clinical condition, fails to be provided in healthcare systems globally. At its 11th annual meeting in 2019, nursing leaders from 11 countries, together with patient representatives, confirmed that patients’ fundamental care needs are still being ignored and nurses are still afraid to ‘speak up’ when these care failures occur. While the ILC’s efforts over the past decade have led to increased recognition of the importance of fundamental care, it is not enough. To generate practical, sustainable solutions, we need to substantially rethink fundamental care and its contribution to patient outcomes and experiences, staff well-being, safety and quality, and the economic viability of healthcare systems.

Key arguments

We present five propositions for radically transforming fundamental care delivery:

Value: fundamental care must be foundational to all caring activities, systems and institutions

Talk: fundamental care must be explicitly articulated in all caring activities, systems and institutions.

Do: fundamental care must be explicitly actioned and evaluated in all caring activities, systems and institutions.

Own: fundamental care must be owned by each individual who delivers care, works in a system that is responsible for care or works in an institution whose mission is to deliver care.

Research: fundamental care must undergo systematic and high-quality investigations to generate the evidence needed to inform care practices and shape health systems and education curricula.

Conclusion

For radical transformation within health systems globally, we must move beyond nursing and ensure all members of the healthcare team—educators, students, consumers, clinicians, leaders, researchers, policy-makers and politicians—value, talk, do, own and research fundamental care. It is only through coordinated, collaborative effort that we will, and must, achieve real change.
Social integration and loneliness among long-term care home residents: protocol for a scoping review
Authors: Bethell Jennifer , Babineau Jessica , Iaboni Andrea , Green Robin , Cuaresma-Canlas Rachelle , Karunananthan Roobika , Schon Barbara , Schon Denise , McGilton Katherine S
Published: December 2019

Introduction

Social well-being is associated with better physical and mental health. It is also important for quality of life, including from the perspectives of those living in long-term care (LTC) homes. However, given the characteristics of the LTC home environment and the people who live there, the nature and influence of social integration and loneliness, and strategies to address them, may differ in this population compared with those living in the community. The objective of this scoping review is to provide an overview of the nature and extent of research on social integration and loneliness among LTC home residents, including a summary of how these concepts have been operationalised and any evidence from specific groups.

Methods and analysis

This study protocol describes the methods of a scoping review of peer-reviewed literature related to social integration and loneliness among LTC home residents. A literature search was developed by an Information Specialist and will be conducted in MEDLINE(R) ALL (in Ovid, including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily) and then translated into CINAHL (EBSCO), PsycINFO (Ovid), Scopus, Sociological Abstracts (Proquest), Embase and Embase Classic (Ovid), Emcare Nursing (Ovid) and AgeLine (EBSCO). Two reviewers will independently screen titles and abstracts of articles identified in the search. Two reviewers will then independently review full text articles for inclusion. Data extraction will also be carried out in duplicate. We will engage LTC home community members, including residents, family and staff, to refine the review questions, assist in interpreting the results and participate in knowledge translation.

Ethics and dissemination

Ethics approval is not required. We will present findings at conferences and publish in a peer-reviewed journal. Ultimately, we hope to inform future observational and interventional research aimed at improving the health and quality of life of LTC home residents.
Instruments that measure psychosocial factors related to vaccination: a scoping review protocol
Authors: Kaufman Jessica , Ryan Rebecca , Betsch Cornelia , Parkhill Anne , Shapiro Gilla , Leask Julie , Menning Lisa , Tugwell Peter , Costa Daniel SJ , Danchin Margaret , Rada Gabriel , Hill Sophie
Published: December 2019

Introduction

As vaccine-preventable disease outbreaks increase, there is growing international interest in monitoring public attitudes towards vaccination and implementing and evaluating vaccine promotion interventions. Outcome selection and measurement are central to intervention evaluation. Measuring uptake rates alone cannot determine which elements in a multicomponent vaccine-promotion intervention are most effective, why specific populations are undervaccinated or when confidence in vaccines is wavering. To develop targeted and cost-effective interventions and policies, it is necessary to measure vaccination-related psychosocial factors such as knowledge, attitudes and aspects of decision-making. This scoping review aims to identify, compare and summarise the properties and validation of instruments for measuring vaccination-related psychosocial factors and identify gaps where no instruments exist.

Methods and analysis

We will search Medline OVID, Embase OVID, CINAHL and PsycINFO with no date restriction, using a pilot-tested search strategy of terms related to vaccination: knowledge, attitudes, trust, acceptance and decision-making and measurement, psychometric testing or validation. This search will be supplemented with manual search and expert consultation. We will include studies that describe instrument development, adaptation or testing and include evaluation of at least two measurement properties (eg, content, criterion, or construct validity; test–retest reliability; internal consistency; sensitivity; responsiveness). Instruments measuring a vaccination-related psychosocial factor in any population will be included. All studies will be screened by one reviewer, with a sample double-screened to confirm accuracy. Disagreements will be resolved with a third reviewer. Data will be synthesised narratively and through summary tables to chart and compare instrument characteristics such as factors measured, date and/or location of development or validation, measurement properties evaluated and population.

Ethics and dissemination

This scoping review aims to provide an overview of existing instruments and ascertain measurement gaps where no measurement instruments currently exist. The identified instruments will form the basis of an open-access online repository of instruments.
Imaging for acute aortic syndromes
Authors: Carroll Brett J , Schermerhorn Marc L , Manning Warren J
Published: December 2019

Acute aortic syndromes (AAS) represent a spectrum of disorders with a common theme of disruption in aortic integrity. AAS are associated with high morbidity and mortality and warrant emergent medical or surgical intervention as delayed treatment is associated with worse outcomes. There are multiple advanced imaging modalities for the diagnosis and complimentary assessment of AAS, each with advantages and limitations. CT angiography remains the imaging modality of choice for diagnosis in the overwhelming majority of patients as it is rapidly acquired and widely available; however, transoesophageal echocardiogram also offers excellent diagnostic accuracy in addition to complimentary data for surgical repair in those with type A dissection. Transthoracic echocardiography and magnetic resonance angiography can also be valuable in select patients. Imaging is increasingly important for risk stratification in the subacute and chronic phases of AAS. Additionally, imaging is vital for planning of interventions in both acute and delayed intervention. Endovascular treatment options are used with increasing frequency—multimodality imaging during the procedure allows for optimisation of these increasingly complex procedures.
Inline perfusion mapping provides insights into the disease mechanism in hypertrophic cardiomyopathy
Authors: Camaioni Claudia , Knott Kristopher D , Augusto Joao B , Seraphim Andreas , Rosmini Stefania , Ricci Fabrizio , Boubertakh Redha , Xue Hui , Hughes Rebecca , Captur Gaby , Lopes Luis Rocha , Brown Louise Anne Elizabeth , Manisty Charlotte , Petersen Steffen Erhard , Plein Sven , Kellman Peter , Mohiddin Saidi A , Moon James C
Published: December 2019

Objective

In patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. We measured MBF using cardiovascular magnetic resonance fully quantitative perfusion mapping to determine the relationship between perfusion, hypertrophy and late gadolinium enhancement (LGE) in HCM.

Methods

101 patients with HCM with unobstructed epicardial coronary arteries and 30 controls (with matched cardiovascular risk factors) underwent pixel-wise perfusion mapping during adenosine stress and rest. Stress, rest MBF and the myocardial perfusion reserve (MPR, ratio of stress to rest) were calculated globally and segmentally and then associated with segmental wall thickness and LGE.

Results

In HCM, 79% had a perfusion defect on clinical read. Stress MBF and MPR were reduced compared with controls (mean±SD 1.63±0.60 vs 2.30±0.64 mL/g/min, p<0.0001 and 2.21±0.87 vs 2.90±0.90, p=0.0003, respectively). Globally, stress MBF fell with increasing indexed left ventricle mass (R2for the model 0.186, p=0.036) and segmentally with increasing wall thickness and LGE (both p<0.0001). In 21% of patients with HCM, MBF was lower during stress than rest (MPR <1) in at least one myocardial segment, a phenomenon which was predominantly subendocardial. Apparently normal HCM segments (normal wall thickness, no LGE) had reduced stress MBF and MPR compared with controls (mean±SD 1.88±0.81 mL/g/min vs 2.32±0.78 mL/g/min, p<0.0001).

Conclusions

Microvascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker.
Strengthening of shear deficient RC deep beams using GFRP sheets and mechanical anchors
Authors: Kumari A. , Nayak A.N.
Published: December 2019

This paper presents the test results of an experimental study on shear deficient reinforced concrete (RC) deep beams strengthened with externally bonded glass fibre reinforced polymer (GFRP) sheets and mechanical anchors. A total of nine deep beams are prepared. One beam is kept as un-strengthened. Four beams are strengthened using GFRP sheets only at shear spans by varying the number of layers. The remaining four beams are strengthened using both GFRP sheets and mechanical anchors at shear spans. The shear capacity, failure mode, and deflections are studied with respect to the different strengthening techniques. The optimum enhancement in shear capacity of these beams is observed as 25.64% and 55.5% for GFRP strengthened beams and GFRP strengthened anchored beams, respectively with respect to the un-strengthened beam. Moreover, the experimental results are also compared with the results predicted from the design guidelines and models available in the literature, which shows good agreement.
An overview of in situ digital canopy photography in forestry
Authors: Chianucci Francesco
Published: December 2019

Since the 1960s, canopy photography has been widely used in forestry. Hemispherical photography has been the most widely used technique, but a great drawback of this method is its perceived sensitivity to hemispherical image acquisition and processing. Over the last decade, several alternative photographic approaches using restricted view angle have been proposed. Cover photography acquired via a normal lens was the first of the recently introduced photographic techniques. Use of a restricted view (often fixed) lens has subsequently contributed to the extension of canopy photography to new sensors and platforms, which ultimately have provided answers to some previous challenges regarding within-crown clumping correction, isolated and urban tree measurements, understory assessment, operational leaf inclination angle measurements, and phenological monitoring. This study provides a comprehensive review of the use of canopy photography in forestry and describes the theory and definitions of the variables used to quantify canopy structure. A case study is presented to illustrate and compare the different features and performance of the existing overstory photographic techniques; the results make it possible to suggest sampling strategies for consistent overstory canopy photographic measurements. Emerging operational fields of canopy photography are also described and discussed.
Multistability and Coexisting Attractors in a New Circulant Chaotic System
Authors: Rajagopal Karthikeyan , Akgul Akif , Pham Viet-Thanh , Alsaadi Fawaz E. , Nazarimehr Fahimeh , Alsaadi Fuad E. , Jafari Sajad
Published: December 2019

In this paper, a new four-dimensional chaotic flow is proposed. The system has a cyclic symmetry in its structure and shows a complicated, chaotic attractor. The dynamical properties of the system are investigated. The system shows multistability in an interval of its parameter. Fractional order model of the proposed system is discussed in various fractional orders. Bifurcation analysis of the fractional order system shows that it has a kind of multistability like the integer order system, which is a very rare phenomenon. Circuit realization of the proposed system is also carried out to show that it is usable for engineering applications.
A New Imprisoned Strange Attractor
Authors: Nazarimehr Fahimeh , Pham Viet-Thanh , Rajagopal Karthikeyan , Alsaadi Fawaz E. , Hayat Tasawar , Jafari Sajad
Published: December 2019

This paper proposes a new chaotic system with a specific attractor which is bounded in a sphere. The system is offered in the spherical coordinate. Dynamical properties of the system are investigated in this paper. The system shows multistability, and all of its attractors are inside or on the surface of the specific sphere. Bifurcation diagram of the system displays an inverse period-doubling route to chaos. Lyapunov exponents of the system are studied to show its chaotic attractors and predict its bifurcation points.
Double Hopf Bifurcation and the Existence of Quasi-Periodic Invariant Tori in a Generalized Gopalsamy Delayed Neural Network Model
Authors: Wu Fang , Li Xuemei
Published: December 2019

In this paper, we discuss the double Hopf bifurcation and the existence of quasi-periodic invariant tori in a generalized Gopalsamy neural network model. Regarding the connection weight and the delay as bifurcation parameters of the double Hopf bifurcation, we derive the normal form up to the fifth order near the critical point by using the center manifold theorem and the normal form method, and obtain sufficient conditions on the existence of invariant 2-tori for the truncated normal form. Moreover, we investigate the effect of higher-order terms on these 2-tori by a KAM theorem. It is proved that in a sufficiently small neighborhood of the bifurcation point, the neural network model has quasi-periodic invariant 2-tori for most of the parameter set where its truncated normal form possesses invariant 2-tori. We give a numerical example to verify the conditions on all results in remarks.
Simplest Megastable Chaotic Oscillator
Authors: Jafari Sajad , Rajagopal Karthikeyan , Hayat Tasawar , Alsaedi Ahmed , Pham Viet-Thanh
Published: December 2019

Recently, chaotic systems with hidden attractors and multistability have been of great interest in the field of chaos and nonlinear dynamics. Two special categories of systems with multistability are systems with extreme multistability and systems with megastability. In this paper, the simplest (yet) megastable chaotic oscillator is designed and introduced. Dynamical properties of this new system are completely investigated through tools like bifurcation diagram, Lyapunov exponents, and basin of attraction. It is shown that between its countable infinite coexisting attractors, only one is self-excited and the rest are hidden.
Instability of some k-essence spacetimes
Authors: Bronnikov K. A. , Fabris J. C. , Rodrigues Denis C.
Published: December 2019

We study the stability properties of static, spherically symmetric configurations in [Formula: see text]-essence theories with the Lagrangians of the form [Formula: see text], [Formula: see text]. The instability under spherically symmetric perturbations is proved for the two recently obtained exact solutions for [Formula: see text] and for [Formula: see text], where [Formula: see text] and [Formula: see text] are constants. The first solution describes a black hole in an asymptotically singular spacetime, the second one contains two horizons of infinite area connected by a wormhole. It is argued that spherically symmetric [Formula: see text]-essence configurations with [Formula: see text] are generically unstable because the perturbation equation is not of hyperbolic type.
AMIR
Authors: Kalbasi Amir , Krishnamurthy Diwakar , Rolia Jerry
Published: December 2019

Service demand burstiness, or serial correlations in resource service demands, has previously been shown to have an adverse impact on system performance metrics such as response time. This article proposes
AMIR
, an analytic framework to characterize burstiness and identify strategies to reduce its impact on performance. AMIR considers an overtake-free system model consisting of multiple queues that service multiple classes of sessions, i.e., sequences of requests. Given the per-class service demand distributions and number of sessions belonging to each class, AMIR can identify an ordering of sessions, i.e., a schedule, that minimizes burstiness at the bottleneck. Hence, it is likely to improve system responsiveness metrics, including mean session wait time and total schedule processing time. To characterize burstiness, the technique uses an order
O
schedule burstiness metric β

O

representing the mean probability that
O
+ 1 consecutive sessions in the schedule have resource demands at the bottleneck greater than the mean bottleneck demand of the schedule. For a given
O
, AMIR uses Integer Linear Programming (ILP) to identify schedules that progressively minimize β

i

∀
i
∈ {1, …
O
}. We conduct an extensive simulation study to provide insights on the conditions under which such schedules can improve system responsiveness. These results show that schedules derived from AMIR can significantly outperform those derived from baseline policies such as Shortest Job First (SJF) and random scheduling when session classes are dissimilar from one another in terms of their service demand distributions. Furthermore, minimizing for higher orders of schedule burstiness is most critical when the bottleneck is heavily utilized and when the service demands of a workload are highly variable. For the system model that we consider, we are not aware of other techniques that are designed to analytically derive insights on the performance impact of high-order service demand burstiness.
Using lectures to identify student misconceptions: a study on the paradoxical effects of hyperkalemia on vascular smooth muscle
Authors: Bordes Stephen J. , Gandhi Jason , Bauer Blake , Protas Matthew , Solomon Nadia , Bogdan Lukasz , Brummund Dieter , Bass Brittany , Clunes Mark , Murray Ian V. J.
Published: December 2019

Medical students have difficulty understanding the mechanisms underlying hyperkalemia-mediated local control of blood flow. Such control mechanisms are crucial in the brain, kidney, and skeletal muscle vasculature. We aimed to identify medical students’ misconceptions via assessment of students’ in-class knowledge and, subsequently, improve future teaching of this concept. In-class polling was performed with the TurningPoint clicker response system ( n = 860) to gauge students’ understanding of three physiological concepts related to hyperkalemia: membrane potential ( Vm), conductance, and smooth muscle response. Vm includes the concepts of equilibrium potential ( Veq) for specific ions, as well as driving force (DF =  Vm − Veq). Students understood the concept of DF (~70% answered correctly), suggesting their understanding of Vm. However, students misunderstood that hyperkalemia results in depolarization (~52% answered correctly) and leads to an increase in potassium conductance (~31% answered correctly). Clarification of the type of smooth muscle as vascular increased the percentage of correct responses (~51 to 73%). The data indicate that students lacked knowledge of specific potassium conductance in various muscle types, resulting in divergent responses, such as the canonical depolarization in skeletal muscle versus hyperpolarization in smooth muscle cells during hyperkalemia. Misunderstanding of this crucial concept of conductance is directly related to the students’ performance. Furthermore, we connected the paradoxical effect of hyperkalemia to pathological acute and chronic hyperkalemia clinical scenarios.
Blended learning in basic medical laboratory courses improves medical students’ abilities in self-learning, understanding, and problem solving
Authors: Chen Jian , Zhou Junhai , Wang Yong , Qi Guangying , Xia Chunbo , Mo Gang , Zhang Zhiyong
Published: December 2019

Blended learning, is a teaching approach that integrates online self-learning and classroom teaching. When designed well, blended learning courses in medicine can facilitate students to improve themselves in self-learning, understanding, and problem solving, ultimately enhancing their learning efficiency. However, blended teaching methods are usually used in only a single course, so it is unclear whether these methods can work well in a variety of basic medical courses. The goal of this study is to explore students’ perceptions of whether blended laboratory courses are helpful for them in overcoming the difficulties they experience. Blended laboratory courses were taken by medical students at Guilin Medical University. Approximately 71.1% of the students agreed that online lecture courses improved their understanding of threshold concepts and the underlying theories. The majority of the students (63.01%) held the opinion that the blended laboratory courses were more effective than other types of courses in achieving the knowledge goals. The majority of the teachers believed that students’ interest in experimentation operations, hands-on abilities, confidence, and other factors were greatly improved compared with those of students taught using the traditional teaching model (face to face). In addition, the average scores for the quizzes of laboratory courses were significantly improved in the blended learning method compared with the traditional learning method. Blended laboratory courses are successful and welcomed by both students and teachers in undergraduate laboratory courses.
Interaction between accumulated 21-deoxysteroids and mineralocorticoid signaling in 21-hydroxylase deficiency
Authors: Travers Simon , Bouvattier Claire , Fagart Jérôme , Martinerie Laetitia , Viengchareun Say , Pussard Eric , Lombès Marc
Published: December 2019

21-Hydroxylase deficiency (21OHD) is a rare genetic disorder in which salt-wasting syndrome occurs in 75% of cases, due to inability to synthesize cortisol and aldosterone. Recent mass spectrometry progress allowed identification of 21-deoxysteroids, i.e., 17-hydroxyprogesterone (17OHP), 21-deoxycortisol (21DF), and 21-deoxycorticosterone (21DB). We hypothesized that they may interfere with mineralocorticoid signaling and fludrocortisone therapy in patients with congenital adrenal hyperplasia (CAH) without effective glucocorticoid replacement and ACTH suppression. Our goal was to quantify circulating 21-deoxysteroids in a pediatric cohort with CAH related to 21OHD and to examine their impact on mineralocorticoid receptor (MR) activation. Twenty-nine patients with salt-wasting phenotype were classified in two groups according to their therapeutic control. During routine follow-up, 17OHP, 21DF, 21DB, and cortisol levels were quantified by liquid chromatography with tandem mass spectrometry before hydrocortisone intake and 1 and 2.5 h following treatment administration. Luciferase reporter gene assays were performed on transfected HEK293T cells while in silico modeling examined structural interactions between these steroids within ligand-binding domain of MR. Plasma 17OHP, 21DF, and 21DB accumulate in uncontrolled patients reaching micromolar concentrations even after hydrocortisone intake. 21DF and 21DB act as partial MR agonists with antagonist features similar to 17OHP, consistent with altered anchoring to Asn770 and unfavorable contact with Ala773 in ligand-binding pocket of MR. Our results demonstrate a complex interaction between all accumulating 21-deoxysteroids in uncontrolled 21OHD patients and mineralocorticoid signaling and suggest that appropriate steroid profiling should optimize management and follow-up of such patients, as keeping those steroids to low plasma levels should attest therapeutic efficacy and prevent interference with MR signaling.
Expression Analysis of ATP-Binding Cassette Transporters ABCB11 and ABCB4 in Primary Sclerosing Cholangitis and Variety of Pediatric and Adult Cholestatic and Noncholestatic Liver Diseases
Authors: Thoeni Cornelia , Waldherr Ruediger , Scheuerer Jutta , Schmitteckert Stefanie , Roeth Ralph , Niesler Beate , Cutz Ernest , Flechtenmacher Christa , Goeppert Benjamin , Schirmacher Peter , Lasitschka Felix
Published: December 2019

ATP-binding cassette (ABC) transporters are the members of the efflux pumps that are responsible for the removal of cytotoxic substances by active transport. ABCB11, the bile salt efflux pump of hepatocytes, coordinates cellular excretion of numerous conjugated bile salts into the bile canaliculi, whereas ABCB4 acts as an ATP-dependent floppase translocating phosphatidylcholine from the inner to the outer leaflet of the bile canalicular membrane. Loss of functional ABCB11 and ABCB4 proteins causes early-onset refractory cholestasis or cholangiopathy. In this study, we investigated the expression and localization pattern of ABCB11 and ABCB4 using immunohistochemistry and RNA profiling in liver samples from patients with different types and stages of chronic cholestatic liver disease, with emphasis on primary sclerosing cholangitis (PSC), compared to a variety of cholestatic and noncholestatic hepatopathies. Therefore, ABCB11 and ABCB4 expressions were investigated on formalin-fixed and paraffin-embedded (FFPE) material in a patient cohort of total 43 patients with or without cholestatic liver diseases, on protein level using immunohistochemistry and on RNA level using nanoString technology. Intriguingly, our results demonstrated increased expression of ABCB11 and ABCB4 on protein as well as RNA level in PSC, and the expression pattern correlated with disease progression. We concluded from our study that patients with PSC demonstrate altered expression levels and pattern of ABCB11 and ABCB4 which correlated with disease progression; thereby, ABCB11 and ABCB4 analysis may be a useful tool for assessment of disease stages in PSC.
Leiomyosarcoma of the Rectum as a Radiation-Induced Second Malignancy after Cervical Cancer Treatment: Case Report with Review of the Literature
Authors: Makhmudov Dmytro E. , Kolesnik Olena O. , Lagoda Natalia N. , Volk Maryna O.
Published: December 2019

Background. Incidence of cervical cancer among women of reproductive age still remains significantly high. In regard to prognostic features and risk factors, the standard treatment for most types of cervical cancer represents a combination of surgical treatment and radiation therapy, such as external beam radiation therapy and brachytherapy. Despite significant advances of long-term oncological outcomes, radiation-induced secondary malignancies among cervical cancer survivors are still an issue. Current case report describes an incredibly rare case of radiation-induced leiomyosarcoma of the rectum, which occurred 32 years after cervical cancer treatment. Case Presentation. A 62-year-old female had a past medical history of FIGO stage IIB cervical cancer (squamous cell carcinoma pT2bN0M0). In 1987, she underwent radical hysterectomy with bilateral iliac lymph node dissection, followed by adjuvant radiation therapy—70 Gy external beam pelvic irradiation followed by 30.5 Gy of brachytherapy. Thirty-two years later, she presented with signs of rectal bleeding. Regarding past medical history, radiologic, endoscopic, and pathologic data, the patient was initially diagnosed with a malignant nonepithelial lower rectal tumor of the unknown origin and staged as mrT3a mrN0 cM0. Total mesorectal excision with complete mesocolic excision and central vascular ligation (CME/CVL) carried by an open approach was carried out. In an attempt to identify the tissue of origin, an immunohistochemistry assay had been performed. Tumor cells showed a high rate of mitotic activity with a 45% rate of Ki-67 expression, positive reaction for desmin, and SMA in all samples. Negative reaction for CD117 and S100 was observed. As a conclusion, the immunophenotype was identified as a grade 3 leiomyosarcoma (ISD-code 8890/3). Conclusions. We suggest that up to date, radical surgery with curative intent, as it was performed in our study, is the most evidence-based treatment option for patients with radiation-induced sarcomas of the rectum.
Structural Design of Mechanical Property for Biodegradable Polymeric Stent
Authors: Wei Yunbo , Wang Minjie , Zhao Danyang , Li Hongxia , Jin Yifei
Published: December 2019

How to improve stent mechanical properties is a key issue for designing biodegradable polymeric stents (BPSs). In this study, a new design method of BPS was proposed based on the force analysis of supporting rings and bridges during stent implantation, and a novel BPS called open C-shaped stent (OCS) with superior comprehensive mechanical properties was developed accordingly. The key mechanical properties including radial force, radial recoil, and axial foreshortening of the OCS have been comprehensively studied and compared with those of the Abbott BVS using finite element analysis (FEA). In addition, the effects of the stent geometries on these mechanical properties have also been discussed in detail. Besides, in vitro mechanical tests including stent expansion and planar compression experiments have been performed to verify the simulation results. Based on the FEA results, it is found that the radial force and radial recoil of the designed OCS are 30% higher and 24% lower than those of the BVS, respectively. Meanwhile, the OCS is not shortened during expansion. Radial force and radial recoil are mainly dependent on the supporting ring structure, and the utilization of designed unequal-height supporting ring (UHSR) can effectively improve these two properties. Axial foreshortening is mainly determined by the bridge geometry as well as the connecting position of the bridge with the adjacent supporting rings. It is feasible to improve the axial foreshortening by using the bridges with a curved structure and locating the connecting position in the middle of the straight section of the supporting elements. The rationality of the proposed OCS and the effectiveness of the finite element method have been verified by in vitro experiments.
Aberrant Expression of EZH2 in Pediatric Patients with Myelodysplastic Syndrome: A Potential Biomarker of Leukemic Evolution
Authors: de Souza Fernandez Teresa , Fonseca Alvarenga Tatiana , Almeida Antônio de Kós Elaiza , Lamim Lovatel Viviane , Tavares Rita de Cássia , da Costa Elaine Sobral , de Souza Fernandez Cecília , Abdelhay Eliana
Published: December 2019

Pediatric myelodysplastic syndrome (MDS) is an uncommon disease and little is known about the molecular alterations of its development and evolution to acute myeloid leukemia (AML). The Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PCR2). It is a histone methyltransferase, that targets lysine 27 of histone 3. This methylated H3–K27 is usually associated with the silencing of genes that are involved in fundamental cellular processes, such as cell proliferation and differentiation. There are only few studies showing the status of EZH2 expression in patients with MDS and they were performed in adult MDS patients. The aim of this study was to analyze the EZH2 expression in pediatric patients with MDS and its association with karyotypes and evolution to acute myeloid leukemia (AML). We conducted the first study of EZH2 expression in pediatric patients with MDS. Considering the EZH2 expression levels in 42 patients and 17 healthy pediatric donors, it was possible to define three groups of expression in patients: low, intermediate, and high. The intermediate level encompassed patients with normal karyotypes, low level included patients with monosomy 7 and del(7q) and high level included patients with trisomy 8 and del(11q) (p<0.0001). Comparing the leukemic evolution, the low expression group presented disease evolution in 100% (8/8) of the cases, the intermediate expression group showed disease evolution in 4.34% (1/23) and in the high expression group, 63.63% (7/11) patients showed evolution from MDS to AML (p<0.0001). It is important to note that low and high EZH2 expression are associated with leukemic evolution, however low expression showed a stronger association with evolution from MDS to AML than the high expression. Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution.
Effect of Lonicera caerulea var. emphyllocalyx Fruit on Biofilm Formed by Porphyromonas gingivalis
Authors: Minami Masaaki , Takase Hiroshi , Nakamura Mineo , Makino Toshiaki
Published: December 2019

Porphyromonas gingivalis is an important pathogenic anaerobic bacterium that causes aspiration pneumonia. This bacterium frequently forms biofilms in the oral cavity and in respiratory tract-associated medical devices. Bacterial colonization that occurs in association with this biofilm formation is the main reason for incurable aspiration pneumonia. The Lonicera caerulea var. emphyllocalyx (LCE) fruit has been used in folk medicine in Hokkaido, the northern part of Japan. The aim of this study was to elucidate one of the antimicrobial mechanisms of LCE methanol extract (LCEE)—the inhibitory effect of LCEE on biofilm formation by P. gingivalis. Our results show that LCEE significantly reduced biofilm formation by three different P. gingivalis isolates in a concentration- and time-dependent manner that were quantified by the adsorption of safranin red. When LCEE was added to biofilms already formed by P. gingivalis, LCEE did not degrade the biofilm. However, treatment with LCEE significantly promoted the removal of existing biofilm by vibration compared to that of control. We also confirmed biofilm formation in LCEE-treated P. gingivalis in tracheal tubes using scanning electron microscopic (SEM) analysis. Cyanidin 3-O-glucoside (C3G), one of the components of LCE, also inhibited the formation of biofilm by P. gingivalis in a concentration-dependent manner. Our results reveal that LCEE may be an effective antibacterial substance for P. gingivalis-induced aspiration pneumonia because of its role in the suppression of bacterial biofilm formation in the oral cavity.
Development and Validation of Discriminative Dissolution Method for Metformin Immediate-Release Film-Coated Tablets
Authors: Mitrevska Ivana , Achkoska Tina , Brezovska Katerina , Toshev Krume , Dimitrovska Aneta , Ugarkovic Sonja
Published: December 2019

The purpose of this study was to develop and validate a discriminative dissolution method for the metformin film-coated tablet with immediate release of the active substance that belongs to class III of the Biopharmaceutical Classification System (BCS). Different conditions such as type of dissolution medium, volume of dissolution medium, rotation speed, apparatus, and filter suitability were evaluated. The most discriminative release profile for the metformin film-coated tablet was accomplished by using Apparatus II (paddle) and 1000 mL of phosphate buffer pH 6.8 as the dissolution medium and maintained on 37 ± 0.5°C with a rotation speed of 75 rpm. The quantification of the released active substance was performed by UV/Vis spectrophotometry, at 232 nm. Acceptance criteria for not less than 75% (Q) of the labeled content for 45 minutes were set. The dissolution method was validated according to the current international guidelines using the following parameters: specificity, accuracy, precision, linearity, robustness, and stability of the solutions, found to be meeting the predetermined acceptance criteria. A developed dissolution method has discriminatory power to reflect the characteristics of the medicinal product and is able to distinguish any changes related to quantitative formulation and can be also applied for routine batch testing.
Fully Autonomous Buses: A Literature Review and Future Research Directions
Authors: Azad Mojdeh , Hoseinzadeh Nima , Brakewood Candace , Cherry Christopher R. , Han Lee D.
Published: December 2019

Autonomous vehicles (AVs) represent a new, growing segment of transportation research. While there have been prior studies and deployments of AVs worldwide, full autonomy in bus transit has gained interest among researchers and practitioners within the last decade, which presents an opportunity to synthesize early trends. Therefore, the objective of this paper is to provide a review of the latest research on fully autonomous buses to summarize findings and identify gaps needing future research. Forty studies were reviewed in detail, and five main themes were identified, which are (1) technology deployment; (2) user acceptance; (3) safety; (4) social and economic aspects; and (5) regulations, policies, and legal issues. The results reveal that most prior studies have focused on technology development, and the area of regulation and policy would benefit from additional study. Noteworthy differences between research in Europe and the United States were also identified. In Europe, large funded projects involving real-world deployments have focused on user acceptance, security and safety, costs, and related legal issues, whereas in the United States, research has primarily concentrated on simulation modelling with limited real-world deployments. The results of this review are important for policy-makers and researchers as AV technology continues to evolve and become more widely available.
In Vivo, Proteomic, and In Silico Investigation of Sapodilla for Therapeutic Potential in Gastrointestinal Disorders
Authors: Ansari Sameen Fatima , Khan Arif-ullah , Qazi Neelum Gul , Shah Fawad Ali , Naeem Komal
Published: December 2019

This study aims to delineate the effects of Manilkara zapota Linn. (Sapodilla) fruit chloroform (Mz.CHCl3) and aqueous (Mz.Aq) extracts tested through different techniques. Antidiarrheal activity and intestinal fluid accumulation were examined by using castor oil-induced diarrhea and castor oil fluid accumulation models. Isolated rabbit jejunum tissues were employed for in vitro experiments. Antimotility and antiulcer were performed through charcoal meal transient time and ethanol-induced ulcer assay, molecular studies were conducted through proteomic analysis, and virtual screening was performed by using a discovery studio visualizer (DSV). Mz.CHCl3 and Mz.Aq extracts attributed dose-dependent (50–300 mg/kg) protection (20–100%) against castor oil-induced diarrhea and dose-dependently (50–300 mg/kg) inhibited intestinal fluid secretions in mice. Mz.CHCl3 and Mz.Aq extracts produce relaxation of spontaneous and K+ (80 Mm) induced contractions in isolated tissue preparations and decreased the distance moved by charcoal in the gastrointestinal transit model in rats. It showed gastroprotective effect in ulcerative stomach of rats and decreased levels of IL-18 quantified by proteomic analysis. Histopathological results showed ethanol-induced significant gastric injury, leading to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all gastric zones using hematoxylin and eosin (H&E) staining. Moreover, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), cyclooxygenase (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFκB). In silico results were comparative to in vitro results evaluated through virtual screening. Moreover, ethanol increased the activation and expression of tumor necrotic factor, cyclooxygenase, and nuclear factor kappa-light-chain-enhancer of activated B cells. This study exhibits the gastroprotective effect of Manilkara zapota extracts in the peritoneal cavity using a proteomic and in silico approach which reveals different energy values against target proteins, which mediate the gastrointestinal functions.
Preparation and Performance Analysis of High‐Viscosity and Elastic Recovery Modified Asphalt Binder
Authors: Qu Liangchen , Gao Yingli , Yao Hui , Cao Dandan , Pei Ganpeng , He Bei , Duan Kairui , Zhou Wenjuan
Published: December 2019

This study presented the preparation and performance of a kind of high viscosity and elastic recovery asphalt (HVERA) by using some modifiers. The performance of styrene‐butadiene‐styrene (SBS), rock asphalt (RA), crumb rubber (CR), and stabilizing agent (SA) for different modifiers was investigated by conventional binder test. Effects of modifiers on the high‐ and low‐temperature properties of HVERA were investigated. The dynamic viscosity (DV) test, dynamic shear rheometer (DSR), and bending beam rheometer (BBR) analysis indicated that the high‐ and low‐temperature rheological properties of asphalt were improved attribute to the addition of mixture of modifiers. Meanwhile, the short‐term aging and long‐term aging were simulated by rolling thin film oven (RTFO) and pressure aging vessel (PAV) tests. Furthermore, the Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) measurements were conducted for obtaining the mechanism and microstructure distribution of the modified asphalt binders. From the test results in this study, it was evident that the addition of SBS, RA, CR, and SA into a neat asphalt binder could both significantly improve the viscosity of the binder at high temperature and lower the creep stiffness at low temperature, which was beneficial to better both high‐temperature stability and low‐temperature cracking resistance of asphalt pavements. It was proved that the high temperature grade of HVERA could be increased by increasing of RA and a proper percentage of modifiers could be improved by the low temperature grade of HVERA.
Subacute Stroke in a Young Female: A Case of Moyamoya Syndrome Initially Anchoring with Anxiety
Authors: Chaughtai Saira , Chaughtai Zeeshan , Haider Muhammad Shaheryar , Ijaz Hasnan M. , Elmedani Sarah , Bakr Mohamed , Hossain Mohammad A. , Asif Arif
Published: December 2019

Moyamoya disease is an arterial disorder causing stroke in a young patient. This is a chronic condition causing progressive cerebrovascular disease due to bilateral stenosis and occlusion of the arteries around the circle of Willis, with prominent arterial collateral circulation. It was first described in Japan and subsequently reported in other Asian countries, but infrequently found in the Western world. Interestingly, there may be racial differences in the presentation and subsequent prognostication of treatment of moyamoya. It is diagnosed with classic angiographic findings of stenosis or occlusion of the circle of Willis vessels. Here, we describe a 28-year-old Caucasian female who was initially diagnosed with anxiety when she presented with symptoms of impaired concentration and fatigue. After the development of remitting slurred speech and facial droop, magnetic resonance imaging and cerebral angiogram yielded the discovery of high-grade stenosis of the origin of the left middle cerebral artery with associated thrombosis in that area. She did well after getting surgery and rehabilitation. This demonstrates a unique presentation of prominent psychiatric symptoms initially thought to be anxiety and culminated in the finding of ischemic stroke in an adult patient with moyamoya.