bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive flexibility and N2/P3 event-related brain potentials
Authors: Kopp Bruno , Steinke Alexander , Visalli Antonino 
Published: June 2020

AbstractTask switching is often considered for evaluating limitations of cognitive flexibility. Switch costs are behavioural indices of limited cognitive flexibility, and switch costs may be decomposable into stimulus- and response-related fractions, as conjectured by the domain hypothesis of cognitive flexibility. According to the domain hypothesis, there exist separable stimulus- and response-related neural networks for cognitive flexibility, which should be discernible as distinct event-related potentials (ERPs). The present card-matching study allowed isolating stimulus- and response-related switch costs, while measuring ERPs evoked by task cues and target stimuli with a focus on the target-locked N2/P3 complex. Behavioural data revealed that both stimulus-task and response-task bindings contribute to switch costs. Cue-locked ERPs yielded larger anterior negativity/posterior positivity in response to switch cues compared to repeat cues. Target-locked ERPs revealed separable ERP correlates of stimulus- and response-related switch costs. P3 waveforms with fronto-central scalp distributions emerged as a corollary of stimulus-related switch costs. Fronto-centrally distributed N2 waveforms occurred when stimulus-task and response-task bindings contributed jointly to switch costs. The reported N2/P3 ERP data are commensurate with the domain hypothesis according to which there exist separable stimulus- and response-related neural networks for cognitive flexibility.
Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo
Authors: Devarasetty Mahesh , Dominijanni Anthony , Herberg Samuel , Shelkey Ethan , Skardal Aleksander , Soker Shay 
Published: June 2020

AbstractThe tumor microenvironment (TME) plays a significant role in cancer progression and thus modeling it will advance our understanding of cancer growth dynamics and response to therapies. Most in vitro models are not exposed to intact body physiology, and at the same time, fail to recapitulate the extensive features of the tumor stroma. Conversely, animal models do not accurately capture the human tumor architecture. We address these deficiencies with biofabricated colorectal cancer (CRC) tissue equivalents, which are built to replicate architectural features of biopsied CRC tissue. Our data shows that tumor-stroma co-cultures consisting of aligned extracellular matrix (ECM) fibers and ordered micro-architecture induced an epithelial phenotype in CRC cells while disordered ECM drove a mesenchymal phenotype, similar to well and poorly differentiated tumors, respectively. Importantly, co-cultures studied in vitro, and upon implantation in mice, revealed similar tumor growth dynamics and retention of architectural features for 28 days. Altogether, these results are the first demonstration of replicating human tumor ECM architecture in ex vivo and in vivo cultures.
PKA and Ube3a regulate SK2 channel trafficking to promote synaptic plasticity in hippocampus: Implications for Angelman Syndrome
Authors: Sun Jiandong , Liu Yan , Zhu Guoqi , Cato Caleb , Hao Xiaoning , Qian Li , Lin Weiju , Adhikari Rachana , Luo Yun , Baudry Michel , Bi Xiaoning 
Published: June 2020

AbstractThe ubiquitin ligase, Ube3a, plays important roles in brain development and functions, since its deficiency results in Angelman Syndrome (AS) while its over-expression increases the risk for autism. We previously showed that the lack of Ube3a-mediated ubiquitination of the Ca2+-activated small conductance potassium channel, SK2, contributes to impairment of synaptic plasticity and learning in AS mice. Synaptic SK2 levels are also regulated by protein kinase A (PKA), which phosphorylates SK2 in its C-terminal domain, facilitating its endocytosis. Here, we report that PKA activation restores theta burst stimulation (TBS)-induced long-term potentiation (LTP) in hippocampal slices from AS mice by enhancing SK2 internalization. While TBS-induced SK2 endocytosis is facilitated by PKA activation, SK2 recycling to synaptic membranes after TBS is inhibited by Ube3a. Molecular and cellular studies confirmed that phosphorylation of SK2 in the C-terminal domain increases its ubiquitination and endocytosis. Finally, PKA activation increases SK2 phosphorylation and ubiquitination in Ube3a-overexpressing mice. Our results indicate that, although both Ube3a-mediated ubiquitination and PKA-induced phosphorylation reduce synaptic SK2 levels, phosphorylation is mainly involved in TBS-induced endocytosis, while ubiquitination predominantly inhibits SK2 recycling. Understanding the complex interactions between PKA and Ube3a in the regulation of SK2 synaptic levels might provide new platforms for developing treatments for AS and various forms of autism.
Alternative catalytic residues in the active site of Esco acetyltransferases
Authors: Ajam Tahereh , De Inessa , Petkau Nikolai , Whelan Gabriela , Pena Vladimir , Eichele Gregor 
Published: June 2020

AbstractCohesin is a protein complex whose core subunits, Smc1, Smc3, Scc1, and SA1/SA2 form a ring-like structure encircling the DNA. Cohesins play a key role in the expression, repair, and segregation of eukaryotic genomes. Following a catalytic mechanism that is insufficiently understood, Esco1 and Esco2 acetyltransferases acetylate the cohesin subunit Smc3, thereby inducing stabilization of cohesin on DNA. As a prerequisite for structure-guided investigation of enzymatic activity, we determine here the crystal structure of the mouse Esco2/CoA complex at 1.8 Å resolution. We reconstitute cohesin as tri- or tetrameric assemblies and use those as physiologically-relevant substrates for enzymatic assays in vitro. Furthermore, we employ cell-based complementation studies in mouse embryonic fibroblast deficient for Esco1 and Esco2, as a means to identify catalytically-important residues in vivo. These analyses demonstrate that D567/S566 and E491/S527, located on opposite sides of the murine Esco2 active site cleft, are critical for catalysis. Our experiments support a catalytic mechanism of acetylation where residues D567 and E491 are general bases that deprotonate the ε-amino group of lysine substrate, also involving two nearby serine residues - S566 and S527- that possess a proton relay function.
Self-organization and multi-line transport of human spermatozoa in rectangular microchannels due to cell-cell interactions
Authors: Bukatin A. , Denissenko P. , Kantsler V. 
Published: June 2020

AbstractThe journey of sperm navigation towards ovum is one of the most important questions in mammalian fertilisation and reproduction. However, we know very little about spermatozoa propagation in a complex fluidic, chemical and topographic environment of a fertility tract. Using microfluidics techniques, we investigate the influence of cell-cell interactions on spermatozoa swimming behavior in constrained environment at different concentrations. Our study shows that at high enough cell concentration the interaction between boundary-following cells leads to formation of areas with preferential direction of cell swimming. In the microchannel of a rectangular cross-section, this leads to formation of a “four-lane” swimming pattern with the asymmetry of the cell distribution of up to 40%. We propose that this is caused by the combination of cell-cell collisions in the corners of the microchannel and the existence of morphologically different spermatozoa: slightly asymmetric cells with trajectories curved left and the symmetric ones, with trajectories curved right. Our findings suggest that cell-cell interactions in highly folded environment of mammalian reproductive tract are important for spermatozoa swimming behavior and play role in selection of highly motile cells.
Alkaline phosphatase affects renal function in never-treated hypertensive patients: effect modification by age
Authors: Sciacqua Angela , Tripepi Giovanni , Perticone Maria , Cassano Velia , Fiorentino Teresa V. , Pititto Gerardo N. , Maio Raffaele , Miceli Sofia , Andreozzi Francesco , Sesti Giorgio , Perticone Francesco 
Published: June 2020

AbstractSeveral studies in patients with chronic kidney disease or normal renal function have shown that high levels of tissue non-specific alkaline phosphatase (ALP) are associated with an increased risk of all cause and cardiovascular (CV) mortality. Considering the independent prognostic role of renal function, we investigated the possible association between ALP levels and estimated glomerular filtration rate (e-GFR) in a large cohort of hypertensive subjects. We enrolled 2157 never-treated uncomplicated hypertensive patients with ALP levels within normal range. In the whole population, e-GFR was strongly related to ALP (r = −0.43, P < 0.0001) with similar magnitude in females and in males, resulting ALP the second independent predictor of renal function. In a multiple linear regression model, both on crude (P < 0.001) and adjusted (P = 0.01) analyses age significantly modified the effect of a fixed increase in ALP (20 UI/L) on renal function so that the reduction in e-GFR associated to a 20 UI/L increase in ALP was of lower magnitude in younger patients and progressively of higher extent from 20 years of age onwards. In conclusion, present data indicate a significant relationship between ALP levels and e-GFR in uncomplicated hypertensive patients that is modulated by age and that persisted after adjusting for several confounders.
Analysis of risk factors for post-bacillus Calmette–Guerin-induced prostatitis in patients with non-muscle invasive bladder cancer
Authors: Kim Tae Jin , Yu Young Dong , Hwang Sung Il , Lee Hak Jong , Hong Sung Kyu , Lee Sang Eun , Oh Jong Jin 
Published: June 2020

AbstractThe objective of this study was to evaluate risk factors for bacillus Calmette–Guerin-induced prostatitis in patients with non-muscle invasive bladder cancer following bacillus Calmette–Guerin therapy. Clinical findings from patients with non-muscle invasive bladder cancer who underwent multi-parametric magnetic resonance imaging before transurethral resection of bladder tumor and post-bacillus Calmette–Guerin therapy from March 2004 to August 2018 were evaluated. The population was grouped into patients with or without newly developed lesions on multi-parametric magnetic resonance imaging performed 3 months after bacillus Calmette–Guerin instillation. Patients with prostate-specific antigen levels ≥ 4 ng/mL or prostate cancer were excluded. Univariable and multivariable analyses were performed to determine the predictors of prostate lesions in patients with prior bacillus Calmette–Guerin exposure. Post bacillus Calmette–Guerin-induced prostatitis was found in 50 of the 194 patients (25.8%). No significant differences were observed between the groups except for prostate volumes (33.8 mL vs. 30.8 mL, P = 0.012) and body mass index (25.2 kg/m2 vs. 24.1 kg/m2, P = 0.044). After bacillus Calmette–Guerin exposure, no significant differences in prostate-specific antigen levels, international prostate symptom scores, or post-voiding residual volume were noted. Multivariable regression analysis showed that body mass index (odds ratio, OR = 1.115, P = 0.038) and prostate volume (OR = 3.080, P = 0.012) were significant predictors of post-bacillus Calmette–Guerin prostate lesions. Body mass index and prostate volume may be clinical predictors of prostate lesions after bacillus Calmette–Guerin exposure. Awareness of potential risk factors for this entity should contribute to the clinical decision-making process for patients following bacillus Calmette–Guerin therapy.
Fatigue-induced Fos immunoreactivity within the lumbar cord and amygdala decreases after С60 fullerene pretreatment
Authors: Maznychenko Andriy V. , Bulgakova Nataliya V. , Sokolowska Inna V. , Butowska Kamila , Borowik Agnieszka , Mankivska Olena P. , Piosik Jacek , Tomiak Tomasz , Gonchar Olga O. , Maisky Volodymyr O. , Kostyukov Alexander I. 
Published: June 2020

AbstractThe fundamental aspects related to the mechanisms of action of C60 fullerene nanoparticles on the level of the central nervous system in different experimental conditions are still unclear. Electrophysiological investigation and immunohistochemical techniques of c-fos expression were combined to determine which neural elements within the lumbar segments and in the central nucleus of the amygdala (CeA) are activated under skeletal muscle fatigue development with prior application of C60 fullerenes (dissolved in dimethyl sulfoxide and in distilled water, FDS). After high-frequency electrical stimulation of the triceps surae muscle, the main fatigue-related increases in the c-Fos expression level were registered ipsilaterally within lamina 1 and 5 of the lumbar segments and within the contralateral capsular part of the CeA. C60 fullerene pretreatment in animals with subsequent electrical stimulation induced a distinct (2–4 times) decrease in the level of Fos immunoreactivity in the observed structures in comparison with only fatigue-induced rats. It can be supposed that FDS, as antioxidant compound, can decrease the concentration of free radicals in fatigued tissue and reduce the transmission intensity of nociceptive information from muscles to the spinal cord and amygdala, thereby changing the level of c-Fos expression within the lumbar segments and CeA.
Design of class‐EM amplifier with consideration of parasitic non‐linear capacitances and on‐state resistance
Authors: Abbasi Hamed , Hayati Mohsen , Kazimierczuk Marian K. , Sekiya Hiroo 
Published: June 2020

In this study, the design of the class‐EM­ power amplifier is presented. In this design, the effects of on‐state resistance and non‐linear parasitic capacitances of the transistors are investigated. Two metal oxide semiconductor field‐effect transistors (MOSFETs) of IRFZ24N and IRF510 with different drain‐source resistances are used in the presented circuits. In the given design, the values of the operational frequency and duty ratio are 3.5 MHz and 0.5, respectively. This study shows the importance of considering non‐linear parasitic elements of MOSFET, especially drain‐source resistance in the designing of the class‐EM power amplifiers. It is shown that the class‐EM power amplifier with high MOSFET drain‐source resistance needs high DC input voltage for both the primary and auxiliary circuits. In the previous works, non‐linear on‐state resistance and non‐linear drain‐source and gate‐drain capacitances have not been included at the same time in the analyses. Two class‐EM amplifiers contain IRF510 and IRFZ24N are designed, simulated, and measured. The efficiency equal to 96.6% with 11.851 W output power at 3.5 MHz and the efficiency equal to 88.4% with 12.361 W output power are achieved for presented class‐EM amplifiers contain IRFZ24N and IRF510, respectively.
Erstlinientherapie des behandlungsbedürftigen Multiplen Myeloms – Aktuelle Empfehlungen
Authors: John Lukas , Goldschmidt Hartmut , Scheid Christof 
Published: June 2020

AbstractDue to the introduction of novel therapeutic agents, the prognosis of Multiple Myeloma has greatly improved over the last decades. The current standard for fit patients is a bortezomib-based induction therapy, followed by high-dose chemotherapy and autologous stem cell transplantation and lenalidomide-based maintenance therapy. For older, non-transplant-eligible patients, daratumumab in combination with bortezomib or lenalidomide offers a well-tolerated, effective treatment option. Despite large improvements, there is still no cure for most myeloma patients, the aim of therapy is therefore to reach a deep remission to prevent lasting damage followed by a continuous maintenance therapy to uphold the remission and prolong overall survival.
Schnittstelle KFO/MKG-Chirurgie –
interdisziplinäre Therapie
Authors: Kirschneck Christian , Proff Peter , Reichert Torsten E. 
Published: June 2020

ZusammenfassungViele kieferorthopädisch relevante Anomalien können nicht
allein durch den Kieferorthopäden behandelt werden, sondern
bedürfen der Unterstützung der weiteren Fachdisziplinen der
Zahnheilkunde, allen voran der Mund-, Kiefer- und Gesichtschirurgie. Die
Schnittstellen beider Disziplinen sind dabei vielfältig und breit
gefächert – sie umfassen nicht allein das Spektrum der
Dysgnathie-Operationen im Erwachsenenalter zur Korrektur skelettaler
transversaler, vertikaler und sagittaler Lageanomalien der Kiefer, dem
natürlich der größte Anteil zukommt, sondern auch
oralchirurgische Eingriffe, welche in Zusammenhang mit
kieferorthopädischen Maßnahmen erforderlich werden. Hierzu
zählen die Entfernung überzähliger und aus
Platzgründen zu extrahierender bleibender Zähne, als auch
die chirurgische Freilegung verlagerter und retinierter Zähne. Im
Rahmen von Nichtanlagen stellen oftmals implantat-prothetische Versorgungen
nach entsprechender Pfeilerverteilung und Lückenöffnung eine
gute Versorgungsmöglichkeit zur oralen Rehabilitation der Patienten
dar, was eine enge interdisziplinäre Planung zur optimalen
Vorbereitung der notwendigen Insertion dentaler Implantate erfordert. Im
folgenden Artikel soll ein Überblick über die
vielfältigen Schnittstellen zwischen der Kieferorthopädie
und der Mund-, Kiefer- und Gesichtschirurgie anhand ausgewählter
Patientenfälle gegeben werden sowie die besonderen Erfordernisse in
der interdisziplinären Therapieplanung.
Bundesteilhabegesetz: Chancen für Menschen mit extremer Adipositas
Authors: Siebert Maxi Florentine , Baumann Alwin , Wabitsch Martin 
Published: June 2020

Abstract
Background Children and adolescents with severe obesity suffer from significant disadvantages in many areas of life. Equal participation in life in society is hardly possible for this group of people. In order to counteract this, it was examined whether children and adolescents with severe obesity are considered disabled under the Social Code.
Results In the context of the revised concept of disability, severe obesity in children and adolescents can be considered a disability. Accordingly, a claim to benefits for participation is possible. Such benefits include special rules and aids that could significantly improve the lives of severe obese children and adolescents.
Conclusion The authors agree that children and adolescents with severe obesity, in the most common cases, qualify to claim benefits.
Klinische Anwendung des digitalen Workflows am Beispiel von
Mini-Implantaten
Authors: Willmann Jan H. , Wilmes Benedict , Chhatwani Sachin , Drescher Dieter 
Published: June 2020

ZusammenfassungDie Nutzung digitaler Technologien erhält zunehmend Einzug in die
Anwendung von Mini-Implantaten und die dazugehörigen
Suprakonstruktionen. Der aktuelle Stand der virtuellen Implantatplatzierung
und die ein- oder 2-zeitigen Workflows werden beleuchtet. Anhand von
Fallbeispielen werden die Workflows, deren klinische Anwendung sowie Vor-
und Nachteile diskutiert.
Surgical Anatomy for Extended Facelift Techniques
Authors: Cakmak Ozcan , Emre Ismet Emrah 
Published: June 2020

AbstractPreservation of the facial nerve is crucial in any type of facial procedure. This is even more important when performing plastic surgery on the face. An intricate knowledge of the course of the facial nerve is a requisite prior to performing facelifts, regardless of the technique used. The complex relationship of the ligaments and the facial nerve may put the nerve at an increased risk of damage, especially if its anatomy is not fully understood. There are several danger zones during dissection where the nerve is more likely to be injured. These include the areas where the nerve branches become more superficial in the dissection plane, and where they traverse between the retaining ligaments of the face. Addressing these ligaments is crucial, as they prevent the transmission of traction during facelifts. Without sufficient release, a satisfying pull on the soft tissues may be limited. Traditional superficial musculoaponeurotic system techniques such as plication or imbrication do not include surgical release of these attachments. Extended facelift techniques include additional dissection to release the retaining ligaments to obtain a more balanced and healthier look. However, these techniques are often the subject of much debate due to the extended dissection that carries a higher risk of nerve complications. In this article we aim to present the relationship of both the nerve and ligaments with an emphasis on the exact location of these structures, both in regard to one another and to their locations within the facial soft tissues, to perform extended techniques safely.
Why general artificial intelligence will not be realized
Authors: Fjelland Ragnar 
Published: June 2020

AbstractThe modern project of creating human-like artificial intelligence (AI) started after World War II, when it was discovered that electronic computers are not just number-crunching machines, but can also manipulate symbols. It is possible to pursue this goal without assuming that machine intelligence is identical to human intelligence. This is known as weak AI. However, many AI researcher have pursued the aim of developing artificial intelligence that is in principle identical to human intelligence, called strong AI. Weak AI is less ambitious than strong AI, and therefore less controversial. However, there are important controversies related to weak AI as well. This paper focuses on the distinction between artificial general intelligence (AGI) and artificial narrow intelligence (ANI). Although AGI may be classified as weak AI, it is close to strong AI because one chief characteristics of human intelligence is its generality. Although AGI is less ambitious than strong AI, there were critics almost from the very beginning. One of the leading critics was the philosopher Hubert Dreyfus, who argued that computers, who have no body, no childhood and no cultural practice, could not acquire intelligence at all. One of Dreyfus’ main arguments was that human knowledge is partly tacit, and therefore cannot be articulated and incorporated in a computer program. However, today one might argue that new approaches to artificial intelligence research have made his arguments obsolete. Deep learning and Big Data are among the latest approaches, and advocates argue that they will be able to realize AGI. A closer look reveals that although development of artificial intelligence for specific purposes (ANI) has been impressive, we have not come much closer to developing artificial general intelligence (AGI). The article further argues that this is in principle impossible, and it revives Hubert Dreyfus’ argument that computers are not in the world.
Blood writing as extraordinary artifact and agent for socioreligious change
Authors: Yu Jimmy 
Published: June 2020

AbstractThis paper explores blood written texts, particularly Buddhist scriptures, as unique artifacts of sanctity. It also examines the extraordinary uses of blood in premodern times and how people have negotiated socioreligious relationships in their production of blood writings, which were seen as a product of meticulous, controlled ritual practice, an act of asceticism par excellence. We typically think of written text as a means to an end, an expression of ideas and knowledge that privilege the written word as the carrier of message, something to be read and understood. However, Buddhist “blood writing” challenges these received notions of how meaning is communicated; blood writings are far more than carriers of a message. When we view these documents, when we experience their material presence and, at the same time, understand their extraordinary mode of production, we have a unique opportunity to appreciate the socioreligious significance of such texts in the premodern world of East Asia.