bluuebunny/crossref_metadata_2025 huggingface dataset:
Überprüfung von Sicherheit und Anwenderfreundlichkeit einer assistiv-aktiven Kniebewegungsschiene mit Selbstanpassung an den Patienten (SE_BURG)
Authors: Knapp Sebastian , Stöppler Henning , Knoll Angelina , Krischak Gert , Ivlev Oleg
Published: January 2019

Fragestellung  Ziel der Studie war die Überprüfung der Sicherheit, Benutzerfreundlichkeit sowie technischen Funktionsfähigkeit eines neu entwickelten assistiv-aktiven und intuitiv bedienbaren selbstanpassenden bewegungsunterstützenden Robotergeräts – SE_BURG.

Material und Methoden  Die monozentrische Studie wurde in der Federseeklinik Bad Buchau durchgeführt. Eingeschlossen wurden Patienten nach Knietotalendoprothese (Knie-TEP) über 55 Jahre. Die Patienten führten eine 20-minütige praktische Testung der Kniebewegungsschiene SE_BURG durch. Primäre Zielgröße war die sichere Anwendung am Patienten. Sekundäre Zielgrößen waren Benutzerfreundlichkeit und technische Funktionsfähigkeit des SE_BURG-Demonstrators sowie der grafischen Benutzeroberfläche.

Ergebnisse Insgesamt konnten 20 Patienten getestet werden. Der SE_BURG-Demonstrator passte sich mechanisch individuell an die Beinlänge der Patienten an. Es konnte zudem gezeigt werden, dass sich der SE_BURG-Demonstrator in Bewegungsumfang und Kraft dynamisch und individuell der Patientenbewegung anpasst und keine Bewegungsmuster aufgezwungen werden. Die Sicherheit wurde durch die Patienten positiv bewertet. Funktionale als auch strukturelle (physiologische) Patientenparameter wurden durch die Behandlung mit der Bewegungsschiene nicht negativ beeinflusst. Ebenso wurde die Benutzerfreundlichkeit bestätigt.

Diskussion  Die klinische Prüfung konnte zeigen, dass zum einen die mechanische und elektronische Umsetzung der Selbstanpassung gelungen und zum anderen die Sicherheit und Benutzerfreundlichkeit gegeben ist. Die technische Neuheit der Selbstanpassung ermöglicht es, die händische Anlage komplexer Therapierobotik zu ersetzen.

Schlussfolgerung  Eine erfolgreiche Selbstanpassung stellt die Grundlage für eine Vereinfachung wie auch Optimierung der Geräteanwendung für Patienten dar.
Personal Radiation Protection and Corresponding Dosimetry in Interventional Radiology: An Overview and Future Developments
Authors: König Alexander Marc , Etzel Robin , Thomas Rohit Philip , Mahnken Andreas H.
Published: January 2019

Background The increasing number of minimally invasive fluoroscopy-guided interventions is likely to result in higher radiation exposure for interventional radiologists and medical staff. Not only the number of procedures but also the complexity of these procedures and therefore the exposure time as well are growing. There are various radiation protection means for protecting medical staff against scatter radiation. This article will provide an overview of the different protection devices, their efficacy in terms of radiation protection and the corresponding dosimetry.

Method The following key words were used to search the literature: radiation protection, eye lens dose, radiation exposure in interventional radiology, cataract, cancer risk, dosimetry in interventional radiology, radiation dosimetry.

Results and Conclusion Optimal radiation protection always requires a combination of different radiation protection devices. Radiation protection and monitoring of the head and neck, especially of the eye lenses, is not yet sufficiently accepted and further development is needed in this field. To reduce the risk of cataract, new protection glasses with an integrated dosimeter are to be introduced in clinical routine practice.

Key Points: 

Citation Format
Palliativmedizin im ambulanten urologischen Arbeitsalltag
Authors: Gleißner Jochen
Published: January 2019

Urologen und besonders Uro-Onkologen sehen immer wieder nicht urologische Komplikationen, die Maßnahmen zur Symptomkontrolle erfordern. Um diesem Versorgungsauftrag, der sich fließend an unsere genuine urologische Tätigkeit anschließt, gerecht zu werden , ist die Kooperation mit den Partnern der allgemeinen ambulanten Palliativversorgung (AAPV) und der speziellen ambulanten Palliativversorgung (SAPV), Versorgungskliniken und anderen Dienstleistern erforderlich. Viele Urologen haben Basisweiterbildungen Palliativmedizin zum Zugang zur palliativen Versorgung absolviert oder die Prüfung zum qualifizierten Palliativarzt (QPA) abgelegt.

Die Versorgungsstrukturen sind je nach Bundesland und KV-Bezirk unterschiedlich und werden am Beispiel des Versorgungsbereiches Wuppertal detailliert dargestellt. Integrale Voraussetzung für eine vitale Kooperation sind die zeitnahe standardisierte Dokumentation im internetbasierten System und definierte Versorgungsstrategien.
Fertilität
Authors: Geiß Dagmar
Published: January 2019

Ein unerfüllter Kinderwunsch betrifft in Deutschland ca. 10–15 % der Paare im reproduktionsfähigen Alter. Es wird zwischen verschiedenen Formen des unerfüllten Kinderwunsches unterschieden: Infertilität, Sterilität und Subfertilität.

In der Praxis besteht oft Beratungsbedarf. So sind Fragen nach der Dauer des Kinderwunsches, der Häufigkeit des Geschlechtsverkehrs, der Zyklusanamnese, zum Lebensstil unerlässlich, aber auch die Beratung darüber, wann die Konzeptionswahrscheinlichkeit am höchsten ist.

Die Autorin fasst den aktuellen wissenschaftlichen Stand zu den anamnestischen, diagnostischen und therapeutischen Optionen bei unerfülltem Kinderwunsch zusammen sowie wann eine Überweisung in ein Kinderwunschzentrum anzuraten ist.
Psychosomatische Aspekte bei unerfülltem Kinderwunsch
Authors: Pirmorady-Sehouli Adak
Published: January 2019

Ein unerfüllter Kinderwunsch bedeutet eine erhebliche psychische Belastung für die betroffenen Frauen, die Partnerschaft und das Sozialleben der betroffenen Paare. Auch bei immer besseren Behandlungsmethoden stagnieren die Erfolgsraten in der Kinderwunschbehandlung. Soziale Prägungen, unbewusste Muster und die Ambivalenz der bewussten Entscheidung für eine Schwangerschaft bilden eine sehr komplexe und höchst sensible Problematik, die eine ganzheitliche Erfassung der Patientin notwendig macht. Die Berücksichtigung der psychosomatischen Ebene bei der Kinderwunschbehandlung kann die Chancen auf ein Baby erhöhen, aber auch zur psychischen Stabilisierung beitragen, wenn der Kinderwunsch unerfüllt bleibt.

Der Beitrag stellt das mögliche Vorgehen einer psychosomatischen Begleitbehandlung zur Unterstützung der somatischen Therapie vor.
Empfängnisverhütung – Ein Update
Authors: Scholz Alenka
Published: January 2019

Die in der Praxis zur Verfügung stehenden Kontrazeptionsmethoden werden unterteilt in hormonelle und nicht hormonelle Kontrazeption, Barrieremethoden, natürliche Familienplanung und Sterilisation. Ihre Sicherheit wird anhand des PEARL-Index beurteilt.

Erfahren Sie im Refresher, wie sicher die jeweilige Methode ist, für wen sie sich eignet und welche Nebenwirkungen und Kontraindikationen zu beachten sind.
Icariin Attenuates High Glucose-Induced Apoptosis, Oxidative Stress, and Inflammation in Human Umbilical Venous Endothelial Cells
Authors: Sun Si , Liu Le , Tian Xiaojun , Guo Yanghongyun , Cao Yingkang , Mei Yunqing , Wang Changhua
Published: January 2019

Endothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties.
However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high
glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM
glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and
elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on
high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.
Palladium-Catalysed Intramolecular C–N versus C–C Coupling: The Effect of 1,8-peri-Interaction in the Naphthalene System
Authors: Debnath Sudarshan , Mondal Shovan
Published: January 2019

Palladium-catalysed competitive intramolecular C–N and C–C coupling of 2-amino-2′-bromodiarylsulfones has been carried out based on 1,8-peri-interactions for the synthesis of phenothiazinedioxide and benzonaphthathiophenedioxide derivatives. A DFT study has been performed that provides support for the influence of the 1,8-peri-interaction.
Breakthrough in neutron backscattering spectroscopy: Energy resolution improved by one order of magnitude using the GaAs 200 reflection
Authors: Kuhlmann Kristijan , Appel Markus , Frick Bernhard , Magerl Andreas
Published: January 2019

We have developed and tested a demonstrator for a neutron backscattering spectrometer with a tenfold enhanced energy resolution. This is made possible by taking advantage of the narrow intrinsic linewidth of the GaAs 200 Bragg reflection, which is one order of magnitude smaller than the linewidth of the currently used Si 111. First measurements yielded an unprecedented energy resolution of 78 neV FWHM, a factor of 10 narrower than the standard Si 111 configuration and about a factor of 4 smaller than the highest energy resolution currently available with Si 111. These measurements provide proof of concept for the construction of a full-scale user instrument.
Dynamic mechanism of breakdown in polypropylene-based nano-dielectric
Authors: Chi X. H. , Cheng L. , Liu W. F. , Zhang X. H. , Li S. T.
Published: January 2019

The dynamic mechanism of breakdown in polypropylene (PP) were represented based on the discharge-avalanche theory. PP is a typical semi-crystalline thermoplastic polymer with low loss and high thermal stability, which had broad application prospects in recyclable and environment-friendly insulation. Dielectric strength was one of the important properties for polymer insulation, hence research of breakdown mechanism was of great significance for insulation reliability increase and advanced materials development. In this paper, the dielectric strength of PP was enhanced by nano-silica filling, and mechanism of enhancement was discussed based on the change of activation energy measured by thermally stimulated depolarization currents (TSDC).
Bouncing drop on liquid film: Dynamics of interfacial gas layer
Authors: Tang Xiaoyu , Saha Abhishek , Law Chung K. , Sun Chao
Published: January 2019

The transition between merging and bouncing outcomes for a drop impacting on a liquid film is critically controlled by the resistance from the microscopic interfacial gas layer trapped between the interacting and deformable drop and film surfaces. Using high-speed imaging and color interferometry, we have quantified and analyzed the gas layer dynamics during bouncing when the liquid film thickness is comparable to the drop radius. Results show that the gas layer morphology changes dramatically and non-monotonically with the film thickness and that in addition to the centrally located dimple previously observed for impact on thin films, a new, rim-dimple morphology is observed for larger film thicknesses. The effects of capillarity of the drop and film are also delineated by increasing the liquid viscosity and hence damping the respective surface waves.
Analytical model for the intensity dependence of 1500 nm to 980 nm upconversion in Er3+: A new tool for material characterization
Authors: Christiansen Jeppe , Lakhotiya Harish , Eriksen Emil , Madsen Søren P. , Balling Peter , Julsgaard Brian
Published: January 2019

We propose a simplified rate-equation model for the 1500 nm to 980 nm upconversion in Er3+. The simplifications, based on typical experimental conditions as well as on conclusions based on previously published more advanced models, enable an analytical solution of the rate equations, which reproduces known properties of upconversion. We have compared the model predictions with intensity-dependent measurements on four samples with different optical properties, such as upconversion-luminescence yield and the characteristic lifetime of the 4I13/2 state. The saturation of the upconversion is in all cases well-described by the model over several orders of magnitude in excitation intensities. Finally, the model provides a new measure for the quality of upconverter systems based on Er3+—the saturation intensity. This parameter provides valuable information on upconversion parameters such as the rates of energy-transfer upconversion and cross-relaxation. In the present investigation, we used the saturation intensity to conclude that the differences in upconversion performance of the investigated samples are mainly due to differences in the non-radiative relaxation rates.
Enhanced QM/MM sampling for free energy calculation of chemical reactions: A case study of double proton transfer
Authors: Xie Liangxu , Cheng Huimin , Fang Dong , Chen Zhe-Ning , Yang Mingjun
Published: January 2019

Free energy calculations for chemical reactions with a steep energy barrier require well defined reaction coordinates (RCs). However, when multiple parallel channels exist along selected RC, the application of conventional enhanced samplings is difficult to generate correct sampling within limited simulation time and thus cannot give correct prediction about the favorable pathways, the relative stability of multiple products or intermediates. Here, we implement the selective integrated tempering sampling (SITS) method with quantum mechanical and molecular mechanical (QM/MM) potential to investigate the chemical reactions in solution. The combined SITS-QM/MM scheme is used to identify possible reaction paths, intermediate and product states, and the free energy profiles for the different reaction paths. Two double proton transfer reactions were studied to validate the implemented method and simulation protocol, from which the independent and correlated proton transfer processes are identified in two representative systems, respectively. This protocol can be generalized to various kinds of chemical reactions for both academic studies and industry applications, such as in exploration and optimization of potential reactions in DNA encoded compound library and halogen or deuterium substitution of the hit discovery and lead optimization stages of drug design via providing a better understanding of the reaction mechanism along the designed chemical reaction pathways.
A universal emulator for memristor, memcapacitor, and meminductor and its chaotic circuit
Authors: Zhao Qing , Wang Chunhua , Zhang Xin
Published: January 2019

In this paper, a universal charge-controlled mem-elements (including memristor, memcapacitor, and meminductor) emulator consisting of off-the-shelf devices is proposed. With the unchanged topology of the circuit, the emulator can realize memristor, memcapacitor, and meminductor, respectively. The proposed emulation circuit has a simple mathematical relationship and is constructed with few active devices and passive components, which not only reduces the cost but also facilitates reproduction and facilitates future application research. The grounding and floating forms of the circuit are demonstrated, and Multisim circuit simulation and breadboard experiments validate the emulator's effectiveness. Furthermore, a universal mem-elements chaotic circuit is designed by using the proposed mem-elements emulator and other circuit elements, which is a deformation circuit of Chua's dual circuit. In this circuit, no matter whether the mem-element is memristor, memcapacitor, or meminductor, the chaotic circuit structure does not change, and all can generate hyper-chaos.
Vibrational coherence in the composition-selected wavepacket of photoexcited pyrimidine
Authors: Ling Fengzi , Li Shuai , Wang Yanmei , Wang Pengfei , Zhang Bing
Published: January 2019

Coherent wavepacket motion in photoexcited pyrimidine has been initiated and visualized in real time using femtosecond time-resolved ion-yield spectroscopy. A coherent superposition of at least four low-frequency Frank-Condon (FC) active modes is created in the first excited electronic state (S1), leading to a vibrational wavepacket. Its composition is manipulated experimentally by tuning the excitation wavelength in the range 309–313 nm to populate the selected vibrational levels. Interference among these vibrational levels is directly characterized by a clear quantum beat superimposed on a single-exponential decay. Fourier transform analysis of the wavelength-dependent transients shows modulation at different frequencies, providing a direct signature of multi-mode vibrational coherence resulting from the coherent excitation process. The sensitivity of the parent-ion transient to the vibrational wavepacket dynamics probably arises because different modes are connected by variable FC factors to the 3s and 3p Rydberg states.
Rapid construction of TiO2/SiO2 composite film on Ti foil as lithium-ion battery anode by plasma discharge in solution
Authors: Wu Jie , He Xiaodong , Li Guozheng , Deng Jianhua , Chen Lin , Xue Wenbin , Li Dejun
Published: January 2019

We employ the plasma discharge phenomenon in an alkaline electrolyte for the rapid construction of a TiO2/SiO2 composite film by a one-step process in 2 min without any heating or post-treatment to obtain a high-capacity anode with an excellent cycling stability for Li-ion batteries. The core temperature of the plasma discharge region fluctuates between 3000 K and 5000 K. The formed oxide film consists of anatase and rutile phases of TiO2 with amorphous SiO2 uniformly distributed on it. The battery performance shows a stable capacity above 400 mAh g−1 at the current density of 100 μA cm−2 due to the porous morphology of the composite film and the enhanced electrochemical reactions by SiO2. This work provides a promising approach for the preparation of Li-ion battery oxide anode materials with high efficiency and low cost.
Gas layer dynamics when drop bounces off a liquid surface
Authors: Berkowitz Jacob
Published: January 2019

Researchers observe the shape and evolution of the interfacial gas layer on the surface of a deformable, drop-impacted liquid.
Blocking CXCR4 alleviates desmoplasia, increases T-lymphocyte infiltration, and improves immunotherapy in metastatic breast cancer
Authors: Chen Ivy X. , Chauhan Vikash P. , Posada Jessica , Ng Mei R. , Wu Michelle W. , Adstamongkonkul Pichet , Huang Peigen , Lindeman Neal , Langer Robert , Jain Rakesh K.
Published: January 2019

Significance

Although immune checkpoint blockade (ICB) along with nab-paclitaxel has increased progression-free survival in triple-negative breast cancer patients, a large fraction of metastatic breast cancer (mBC) patients do not benefit from ICBs. The presence of a fibrotic tumor microenvironment can suppress the immune response to cancer. Here we found fibrosis and immunosuppression in both primary and metastatic breast cancer lesions. We show that targeting CXCR4/CXCL12 signaling, using plerixafor, an Food and Drug Administration-approved drug, reduces fibrosis, alleviates immunosuppression, and significantly enhances the efficacy of immune checkpoint blockers in preclinical models of mBC. Our findings provide a deeper understanding of mechanisms by which desmoplasia promotes immunosuppression in mBC and suggest a clinically translatable approach that can be combined with immunotherapy in patients to enhance therapeutic response.
Knowledge, power and powerful knowledge re‐visited
Authors: Muller Johan , Young Michael
Published: January 2019

This article extends the authors’ earlier work (Young & Muller 2013) exploring the concept of ‘powerful knowledge’. It first examines some of the origins of the concept and goes on to a brief consideration of how sociology, political theory and economics have traditionally represented ‘power’ and ‘knowledge’. Two key senses of power are identified and two difficulties are next identified: how to retain both senses of power in a satisfactory account of ‘powerful knowledge; and how to provide a satisfactory account of the ‘power’ of knowledge in the humanities. By identifying three meanings of ‘powerful knowledge’, and making an argument for their interrelationship, the article aims to put the concept on a firmer footing and point to its potential implications for curriculum theory.
FoxP3 and Ezh2 regulate Tfr cell suppressive function and transcriptional program
Authors: Hou Shenda , Clement Rachel L. , Diallo Alos , Blazar Bruce R. , Rudensky Alexander Y. , Sharpe Arlene H. , Sage Peter T.
Published: January 2019

Follicular regulatory T (Tfr) cells are a regulatory T cell subset that controls antibody production by inhibiting T follicular helper (Tfh)–mediated help to B cells. Tfh and Tfr cells possess opposing functions suggesting unique programming. Here we elucidated the transcriptional program controlling Tfr suppressive function. We found that Tfr cells have a program for suppressive function fine-tuned by tissue microenvironment. The transcription factor FoxP3 and chromatin-modifying enzyme EZH2 are essential for this transcriptional program but regulate the program in distinct ways. FoxP3 modifies the Tfh program to induce a Tfr-like functional state, demonstrating that Tfr cells coopt the Tfh program for suppression. Importantly, we identified a Tfr cell population that loses the Tfr program to become “ex-Tfr” cells with altered functionality. These dysfunctional ex-Tfr cells may have roles in modulating pathogenic antibody responses. Taken together, our studies reveal mechanisms controlling the Tfr transcriptional program and how failure of these mechanisms leads to dysfunctional Tfr cells.
Regulation of myofilament force and loaded shortening by skeletal myosin binding protein C
Authors: Robinett Joel C. , Hanft Laurin M. , Geist Janelle , Kontrogianni-Konstantopoulos Aikaterini , McDonald Kerry S.
Published: January 2019

Myosin binding protein C (MyBP-C) is a 125–140-kD protein located in the C-zone of each half-thick filament. It is thought to be an important regulator of contraction, but its precise role is unclear. Here we investigate mechanisms by which skeletal MyBP-C regulates myofilament function using rat permeabilized skeletal muscle fibers. We mount either slow-twitch or fast-twitch skeletal muscle fibers between a force transducer and motor, use Ca2+ to activate a range of forces, and measure contractile properties including transient force overshoot, rate of force development, and loaded sarcomere shortening. The transient force overshoot is greater in slow-twitch than fast-twitch fibers at all Ca2+ activation levels. In slow-twitch fibers, protein kinase A (PKA) treatment (a) augments phosphorylation of slow skeletal MyBP-C (sMyBP-C), (b) doubles the magnitude of the relative transient force overshoot at low Ca2+ activation levels, and (c) increases force development rates at all Ca2+ activation levels. We also investigate the role that phosphorylated and dephosphorylated sMyBP-C plays in loaded sarcomere shortening. We test the hypothesis that MyBP-C acts as a brake to filament sliding within the myofilament lattice by measuring sarcomere shortening as thin filaments traverse into the C-zone during lightly loaded slow-twitch fiber contractions. Before PKA treatment, shortening velocity decelerates as sarcomeres traverse from ∼3.10 to ∼3.00 µm. After PKA treatment, sarcomeres shorten a greater distance and exhibit less deceleration during similar force clamps. After sMyBP-C dephosphorylation, sarcomere length traces display a brief recoil (i.e., “bump”) that initiates at ∼3.06 µm during loaded shortening. Interestingly, the timing of the bump shifts with changes in load but manifests at the same sarcomere length. Our results suggest that sMyBP-C and its phosphorylation state regulate sarcomere contraction by a combination of cross-bridge recruitment, modification of cross-bridge cycling kinetics, and alteration of drag forces that originate in the C-zone.
Authenticity, Misunderstanding, and Institutional Responsibility in Contemporary Art
Authors: Irvin Sherri
Published: January 2019

This paper addresses two questions about audience misunderstandings of contemporary art. First, what is the institution’s responsibility to prevent predictable misunderstandings about the nature of a contemporary artwork, and how should this responsibility be balanced against other considerations? Second, can an institution ever be justified in intentionally mounting an inauthentic display of an artwork, given that such displays are likely to mislead? I will argue that while the institution has a defeasible responsibility to mount authentic displays, this is not always sufficient to avoid misunderstanding; the institution will sometimes need to supply auxiliary information. And even where competing considerations require mounting an inauthentic display, thoughtful museum practice can promote the audience’s ability to grasp the work. The argument will be developed with consideration of artworks by El Anatsui, Lygia Clark, and Glenn Ligon.
“Effective Disembodiment:” Female Patienthood and Reproductive Health in Elisa Albert’s After Birth and Pamela Erens’s Eleven Hours
Authors: Williams Haleigh R
Published: January 2019

Historically, female patienthood has been defined by an expectation of passivity and the concession of bodily autonomy. After Birth by Elisa Albert (2015) and Eleven Hours by Pamela Erens (2016) shed light on the status of the modern female patient through the lens of her treatment throughout the process of childbirth in a clinical setting. The increasing medicalization of pregnancy and childbirth in the United States has added a compelling layer to the existing tension between women and the institution of medicine. Positioning these texts in conversation with the treatment of women at the hands of healthcare workers allows us to contextualize the fictional narratives, which themselves offer a dialectal framework to facilitate our understanding of female patienthood.
Modeling genotypes in their microenvironment to predict single- and multi-cellular behavior
Authors: Voukantsis Dimitrios , Kahn Kenneth , Hadley Martin , Wilson Rowan , Buffa Francesca M
Published: January 2019

A cell's phenotype is the set of observable characteristics resulting from the interaction of the genotype with the surrounding environment, determining cell behavior. Deciphering genotype-phenotype relationships has been crucial to understanding normal and disease biology. Analysis of molecular pathways has provided an invaluable tool to such understanding; however, typically it does not consider the physical microenvironment, which is a key determinant of phenotype.

In this study, we present a novel modeling framework that enables the study of the link between genotype, signaling networks, and cell behavior in a three-dimensional microenvironment. To achieve this, we bring together Agent-Based Modeling, a powerful computational modeling technique, and gene networks. This combination allows biological hypotheses to be tested in a controlled stepwise fashion, and it lends itself naturally to model a heterogeneous population of cells acting and evolving in a dynamic microenvironment, which is needed to predict the evolution of complex multi-cellular dynamics. Importantly, this enables modeling co-occurring intrinsic perturbations, such as mutations, and extrinsic perturbations, such as nutrient availability, and their interactions.

Using cancer as a model system, we illustrate how this framework delivers a unique opportunity to identify determinants of single-cell behavior, while uncovering emerging properties of multi-cellular growth.

This framework is freely available at http://www.microc.org.
Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24
Authors: Hedberg-Oldfors Carola , Abramsson Alexandra , Osborn Daniel P S , Danielsson Olof , Fazlinezhad Afsoon , Nilipour Yalda , Hübbert Laila , Nennesmo Inger , Visuttijai Kittichate , Bharj Jaipreet , Petropoulou Evmorfia , Shoreim Azza , Vona Barbara , Ahangari Najmeh , López Marcela Dávila , Doosti Mohammad , Banote Rakesh Kumar , Maroofian Reza , Edling Malin , Taherpour Mehdi , Zetterberg Henrik , Karimiani Ehsan Ghayoor , Oldfors Anders , Jamshidi Yalda
Published: January 2019

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.
Electrochemical synthesis of nitric acid from air and ammonia through waste utilization
Authors: Wang Yuting , Yu Yifu , Jia Ranran , Zhang Chao , Zhang Bin
Published: January 2019

Commercial nitric acid (HNO3) and ammonia (NH3) are mostly produced through the Ostwald process and the Haber-Bosch process, respectively. However, high energy demand and enormous greenhouse gas accompy these processes. The development of economical and green ways to synthesize HNO3 and NH3 is highly desirable for solving the global energy and environmental crisis. Here, we present two energy-efficient and environmentally friendly strategies to synthesize HNO3 and NH3 at distributed sources, including the electrocatalytic oxidation of N2 in air to HNO3 and the electrocatalytic reduction of residual ${\rm NO_{3}^{-}}$ contamination in water to NH3. The isotope-labeling studies combined with theoretical calculation reveal the reaction path of the two proposed strategies, confirming the origin of the electrochemical products. Importantly, the electrooxidation-generated ${\rm NO_{3}^{-}}$ ions may also serve as reactants for the electroreduction synthesis of NH3 in the future. Our work may open avenues for energy-efficient and green production of HNO3 and NH3 at distributed sources.
Double-Barrel Extracranial–Intracranial Bypass and Trapping of Dolichoectatic Middle Cerebral Artery Aneurysms: 3-Dimensional Operative Video
Authors: Gandhi Sirin , Rodriguez Ruth Lau , Tabani Halima , Burkhardt Jan-Karl , Benet Arnau , Lawton Michael T
Published: January 2019

A dolichoectatic intracranial vessel with multiple fusiform aneurysms on the same vessel segment is rare, and usually managed with a bypass with aneurysm trapping. This video demonstrates trapping and a double-barrel superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass to treat two fusiform aneurysms in a left dolichoectatic superior MCA trunk. A 46-year-old man with AIDS presented with aphasia and hemiparesis. IRB approval and patient consent were obtained. Both STA branches (frontal and parietal) were harvested. After widely splitting the sylvian fissure from its proximal portion to the angular gyrus, the two fusiform aneurysms on the superior MCA trunk were identified in the insular recess and the circular sulcus. The outflow artery from each aneurysm was identified and prepared for the bypass. The STA was transected, and both limbs were brought down into the fissure. After trapping the distal aneurysm, an end-to-end anastomosis of the parietal STA branch to the M2 MCA was performed. Thereafter, a second bypass was performed in an end-to-side fashion to an M2 branch from the base of the first aneurysm. The second aneurysm was then trapped. Indocyanine green angiography confirmed the patency of both bypasses. Complete aneurysm occlusion and bypass patency were also confirmed with postoperative angiography. The patient recovered from his pre-operative neurological deficits. This case demonstrates the efficacy of double-barrel STA-MCA bypass in combination with aneurysm trapping in a patient with a complex dolichoectatic superior MCA trunk aneurysm. It also highlights the advantage of using end-to-end anastomosis for deep recipients with limited access.
Abandon Ship? An Analysis of Strategic Voting among Liberal Democrat Voters in the 2015 UK Election
Authors: Hale Isaac D
Published: January 2019

Strategic voting occurs when voters make vote choices using their ex ante expectations about the results of an election in addition to their sincere candidate preferences. While there is ample theoretical reason to believe strategic voting should occur under certain electoral conditions and institutional arrangements, the evidence for it in the literature has been mixed. I theorise that the polarisation of the two main British political parties and the highly publicised predictions of defeat for Britain’s primary national third party, the Liberal Democrats, make the 2015 UK election an ideal case for studying strategic voting. I adapt established methods of identifying strategic voting to this election and find evidence that Liberal Democrat voters in the UK voted strategically for Labour and Conservative candidates to maximise their odds of affecting the electoral outcome in their constituency.
Hazardous Air Pollutants and Adverse Birth Outcomes in Portland, OR
Authors: Willis Mary , Hystad Perry
Published: January 2019

Background:

The impact of multiple hazardous air pollutant (HAP) exposures during pregnancy on adverse birth outcomes is unknown. We examined associations between cumulative and individual HAP exposures and adverse birth outcomes in Portland, OR, a region that has exceeded HAP air quality guidelines for decades.

Methods:

We used vital statistics records in the Portland Metropolitan Region from 2000 to 2014 (n = 279,051 births). Prenatal exposure to 19 HAPs was assessed using a dispersion model applied to maternal residential address at delivery. We used linear and logistic multivariate regression models to assess associations between individual and cumulative HAP exposures and preterm term (PTB), term birth weight (TBW), and small for gestational age (SGA), adjusting for several potential individual and neighborhood confounding factors.

Results:

We observed no associations for composite HAP exposure metrics and adverse birth outcomes. Associations were observed in fully adjusted models comparing the highest to lowest quintiles of exposure for certain HAPs including chromium VI and TBW (−12.70; 95% confidence interval [CI]: −23.10, −2.31); 1,3-butadiene and TBW (−16.86; 95% CI: −29.66, −4.06) and SGA (1.18; 95% CI: 1.07, 1.30); and cadmium and TBW (−31.37; 95% CI: −56.20, −.54). For some HAP metrics, we observed higher HAP exposures for minority groups and large unadjusted associations between other HAPs and adverse birth outcomes, but most associations were attenuated in adjusted models.

Conclusions:

Adverse birth outcomes were not consistently associated with most HAP exposures in Portland, OR, although some specific air toxic exposures warrant further attention.
Falsely elevated thyroglobulin and calcitonin due to rheumatoid factor in non-relapsing thyroid carcinoma
Authors: Lupoli Gelsy Arianna , Barba Livia , Liotti Antonietta , La Civita Evelina , Lupoli Roberta , Riccio Enrico , Portella Giuseppe , Formisano Pietro , Beguinot Francesco , Terracciano Daniela
Published: January 2019

Rationale:

Thyroglobulin (Tg) is an accurate indicator of clinical outcome after total thyroidectomy in patients with differentiated thyroid carcinoma. Usually, Tg levels agree with whole body scan. However, in some patient, discordant results were found, often because of Tg immunoassay interference. Several reports indicated that 2-site immunoassay interference with heterophile antibodies (HAb) can lead to misinterpretation of the laboratory test result.

Patient concerns:

We report a case of a 46-year-old woman referred to our endocrine clinic for markedly increased calcitonin (CT) without the associated clinical picture. The measurement was repeated with the same patient sample on a different analytical platform and the result was an undetectable CT level. The measurement of Tg was repeated on 3 different analytical platforms using chemiluminescence and electrochemiluminescence immunoassays and the results were different on each platform. HAb blocking tubes resulted in a different level of both CT and Tg, suggesting the presence of a heterophile substance in the serum sample. Further characterization showed reactivity to several animal species antibodies and an elevated level of the rheumatoid factor (RF).

Diagnoses:

She was diagnosed as papillary thyroid carcinoma.

Interventions:

She had undergone thyroidectomy with lymph node dissection and radioactive therapy.

Outcomes:

She was found not to have recurrence despite a high serum Tg level.

Lessons:

Our report illustrates a rare case of falsely elevated tumor markers levels due to assay interference caused by RF. This finding pointed out the importance of close communication between the clinician and laboratory staff in order to bring to light discordance between laboratory test results and clinical picture and avoid unnecessary diagnostic procedures and overtreatment.
Hepatoid adenocarcinoma in the peritoneal cavity
Authors: Chen Xiao , Li Anqin , Wang Qiuxia , Shen Yaqi , Li Zhen , Peng Jian , Hu Daoyu
Published: January 2019

Rationale:

Hepatoid adenocarcinoma (HAC) is a rare extrahepatic adenocarcinoma that histologically resembles hepatocellular carcinoma (HCC). HAC of peritoneal cavity can present as a solitary mass or disseminated nodules indicating different treatment.

Patient concerns:

In this study, we present the cases of a 29-year-old man and a 64-year-old woman who suffered from HAC.

Diagnosis:

The serum alpha-fetoprotein (AFP) of both patients and ascites of 1 patient were markedly elevated. One patient presented with multiple nodular disseminated in the peritoneal cavity and the other patient has a mass between the left diaphragm and the spleen on computed tomography and magnetic resonance imaging.

Intervention:

The first patient underwent laparoscopic examination and multiple nodules were found in the peritoneal cavity, and only received chemotherapy. The second patient underwent surgery and resected the mass between left diaphragm and the spleen.

Outcome:

Histological examinations showed the nodule of the peritoneal cavity and mass belong to moderately differentiated HCC. HAC has a poor prognosis, but the 2 patients responded well to treatment.

Lesson:

HAC is frequently associated with elevated serum AFP without neoplasm in the liver. Histological and Immunohistochemistry examinations can help differential diagnosis.
Pancreaticopleural and pancreaticomediastinal fistula extending to the cervical region, with dysphagia as initial symptom
Authors: Grudzińska Ewa , Pilch-Kowalczyk Joanna , Kuśnierz Katarzyna
Published: January 2019

Rationale:

Pancreaticopleural and pancreaticomediastinal fistulas are rare complications of pancreatitis. They are often misdiagnosed and there are no strict guidelines of treatment. In this study, we present a brief report of a combined pancreaticopleural and pancreaticomediastinal fistula extending to the cervical region, causing dysphagia and cervical swelling as initial symptoms.

Patient concerns:

A 36-year-old female with history of alcohol abuse and pancreatitis presented progressing dysphagia and mild dyspnea on admission.

Diagnosis:

Chest X-ray and chest and abdominal computed tomography scan (CT) indicated pancreaticopleural fistula combined with pancreaticomediastinal fistula, a diagnosis confirmed by high amylase levels in pleural fluid.

Interventions:

Conservative treatment was administered and ERCP was performed but pancreatic duct stenting was impossible. The patient presented rapid anterior cervical swelling with progressing dysphagia and dyspnea. CT showed fistula penetration to the cervical region. The patient underwent urgent surgery and pancreaticojejunal anastomosis was performed.

Outcomes:

The surgery led to recovery. Six months later, the patient reported good health and weight gain.

Lessons:

Coexistence of pancreaticopleural and pancreaticomediastinal fistula with cervical penetration is an extremely rare pancreatitis complication. It presents with dysphagia and anterior cervical swelling as initial symptoms. It is important to consider this complication in all patients with history of pancreatitis, presenting with dysphagia.
Ramsay Hunt syndrome with pontine lesion
Authors: Ji Ye , Ma Guo-Mei , Kang Zhi-Lei , Zhang Yi , Han Jing-Zhe , Li Jin , Wu Dan-Dan , Wang Jia
Published: January 2019

Rationale:

The coexistence of Ramsay Hunt syndrome (RHS) and varicella-zoster virus (VZV) encephalitis is rare. A patient who developed RHS after being infected with VZV, along with a pontine lesion, is reported in the present study.

Patient concerns:

A 41-year-old male patient presented with his mouth askew for 7 days, and dizziness, accompanied by hearing loss for 3 days.

Diagnoses:

The patient was initially diagnosed with RHS. Brainstem encephalitis was confirmed by lumbar puncture and cerebrospinal fluid. Brain magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) revealed how VZV entered the intracranial space along the vestibulocochlear nerve and facial nerve in the acute period.

Interventions:

Intravenous acyclovir, IV, immunoglobulins (IVIg) and methylprednisolone were administered.

Outcomes:

The herpes was cleared up and left facial nerve palsy was improved, but hearing loss in the left ear did not improve.

Lessons:

An MRI was necessary for some VZV infections limited to the cranial nerve, although there was no evidence of brain stem injury. DWI provided evidence, showing how VZV entered the brain in the early stage. This allowed the doctor to judge the necessity of a lumbar puncture.
The role of the phosphatase and tensin homolog status in predicting pathological complete response to neoadjuvant anti-HER2 therapies in HER2-positive primary breast cancer
Authors: Zhang Chi , Guo Ying , Li Jiyu , Tian Xingsong , Duan Xuening
Published: January 2019

Purpose:

The addition of anti-HER2 therapies to neoadjuvant treatment significantly enhances pathological complete response (PCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Selecting patients unlikely to benefit from neoadjuvant anti-HER2 therapies is increasingly important. In this study, we proposed to assess the role of the phosphatase and tensin homolog (PTEN) as a biomarker in predicting PCR to neoadjuvant anti-HER2 therapies by conducting meta-analysis.

Methods:

Our team searched Embase, Medline, and the Cochrane Library by the end of September 16, 2018, for trials on patients with HER2-positive breast cancer treated with neoadjuvant anti-HER2 therapies. The associations between PTEN expression and PCR rate were then assessed. Odds ratio (ORs) and hazard ratio (HRs) with 95% confidence intervals (CIs) with 2-sided P values were calculated. The Newcastle-Ottawa scale (NOS) was used to estimate the quality of the involved trials.

Results:

A total of 820 patients from 8 trials were included in this meta-analysis. Overall, the PTEN normal tumors was related to a significant increase in PCR rate (OR 0.55; 95% CI = 0.31–0.96; P = .04; I
2 = 54%). In different anti-HER2 agents analysis, the PTEN normal tumors was related to a significant increase in PCR rate in patients treated with trastuzumab alone (OR 0.40; 95% CI = 0.24–0.67; P = .0005; I
2 = 15%). Besides, no significant association between PTEN status and PCR rate was detected in patients treated with lapatinib alone (OR 1.90; 95% CI = 0.78–4.60; P = .16; I
2 = 0%) or trastuzumab plus lapatinib (OR 1.27; 95% CI = 0.27–5.97; P = .76; I
2 = 73%).

Conclusion:

Based on current evidence, PTEN status could be n suitable biomarker in predicting PCR rate to neoadjuvant anti-HER2 therapies, especially in trastuzumab-treated patients.
Catheter ablation of a right posterior accessory pathway in a patient with left ventricular noncompaction
Authors: Cojan-Minzat Bianca Olivia , Boarescu Paul-Mihai , Cismaru Gabriel , Rosu Radu , Cionca Carmen , Pop Dana , Zdrenghea Dumitru , Agoston-Coldea Lucia
Published: January 2019

Rtionale:

Left ventricular noncompaction (LVNC) is a genetic cardiomyopathy characterized by the presence of a thin compacted layer of myocardium and a spongy subendocardial layer with trabeculations and recesses. LVNC associated Wolf–Parkinson–White syndrome is very rare.

Patient concerns:

A 32-year-old male presented with short episodes of palpitations and a syncope 6 months before his hospitalization.

Diagnosis:

His ECG revealed the presence of a right posterior accessory pathway. Echocardiography identified trabeculations of the septal, apical, and lateral wall of the left ventricle, consistent with left ventricular noncompaction. Cardiac MRI confirmed the diagnosis, as the ratio between the noncompacted and compacted myocardial layer was 2.3.

Interventions:

The electrophysiological study revealed a malignant right posterior accessory pathway. Catheter ablation was successfully performed at the level of posterior tricuspid annulus. Programmed ventricular stimulation could not induce any arrhythmia at the end of the procedure.

Outcomes:

During 15 months of follow-up, the patient presented no more episodes of palpitations or syncope.

Lessons:

Left ventricular noncompaction with right accessory pathway is a rare association with genetic basis and gives a higher risk of sudden cardiac death. Catheter ablation of the accessory pathway is a valuable way of treatment in this category of patients, lowering the risk of sudden cardiac death.