bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of Ranolazine on E1784K is altered by temperature and calcium
Authors: Abdelsayed Mena , Ruprai Manpreet , Ruben Peter C. 
Published: February 2018

AbstractE1784K is the most common mixed syndrome SCN5a mutation underpinning both Brugada syndrome type 1 (BrS1) and Long-QT syndrome type 3 (LQT3). The charge reversal mutant enhances the late sodium current (INa) passed by the cardiac voltage-gated sodium channel (NaV1.5), delaying cardiac repolarization. Exercise-induced triggers, like elevated temperature and cytosolic calcium, exacerbate E1784K late INa. In this study, we tested the effects of Ranolazine, the late INa blocker, on voltage-dependent and kinetic properties of E1784K at elevated temperature and cytosolic calcium. We used whole-cell patch clamp to measure INa from wild type and E1784K channels expressed in HEK293 cells. At elevated temperature, Ranolazine attenuated gain-of-function in E1784K by decreasing late INa, hyperpolarizing steady-state fast inactivation, and increasing use-dependent inactivation. Both elevated temperature and cytosolic calcium hampered the capacity of Ranolazine to suppress E1784K late INa. In-silico action potential (AP) simulations were done using a modified O’Hara Rudy (ORd) cardiac model. Simulations showed that Ranolazine failed to shorten AP duration, an effect augmented at febrile temperatures. The drug-channel interaction is clearly affected by external triggers, as reported previously with ischemia. Determining drug efficacy under various physiological states in SCN5a cohorts is crucial for accurate management of arrhythmias.
HIF1α-dependent glycolysis promotes macrophage functional activities in protecting against bacterial and fungal infection
Authors: Li Chunxiao , Wang Yu , Li Yan , Yu Qing , Jin Xi , Wang Xiao , Jia Anna , Hu Ying , Han Linian , Wang Jian , Yang Hui , Yan Dapeng , Bi Yujing , Liu Guangwei 
Published: February 2018

AbstractMacrophages are important innate immune defense system cells in the fight against bacterial and fungal pathogenic infections. They exhibit significant plasticity, particularly with their ability to undergo functional differentiation. Additionally, HIF1α is critically involved in the functional differentiation of macrophages during inflammation. However, the role of macrophage HIF1α in protecting against different pathogenic infections remains unclear. In this study, we investigated and compared the roles of HIF1α in different macrophage functional effects of bacterial and fungal infectionsin vitroandin vivo. We found that bacterial and fungal infections produced similar effects on macrophage functional differentiation. HIF1α deficiency inhibited pro-inflammatory macrophage functional activities when cells were stimulated with LPS or curdlanin vitroor when mice were infected withL. monocytogenesorC. albicans in vivo, thus decreasing pro-inflammatory TNFα and IL-6 secretion associated with pathogenic microorganism survival. Alteration of glycolytic pathway activation was required for the functional differentiation of pro-inflammatory macrophages in protecting against bacterial and fungal infections. Thus, the HIF1α-dependent glycolytic pathway is essential for pro-inflammatory macrophage functional differentiation in protecting against bacterial and fungal infections.
Protective humoral and CD4+ T cellular immune responses of Staphylococcus aureus vaccine MntC in a murine peritonitis model
Authors: Yu Wei , Yao Di , Yu Simiao , Wang Xintong , Li Xiaoting , Wang Mengyao , Liu Shuo , Feng Zhenyue , Chen Xiaoting , Li Wanyu , Wang Lizi , Liu Wei , Ma Jinzhu , Yu Liquan , Tong Chunyu , Song Baifen , Cui Yudong 
Published: February 2018

AbstractStaphylococcus aureus can cause different types of diseases from mild skin infections to life-threatening sepsis worldwide. Owing to the emergence and transmission of multidrug-resistant strains, developing an impactful immunotherapy especially vaccine control approach against S. aureus infections is increasingly encouraged and supported. S. aureus manganese transport protein C (MntC), which is a highly-conserved cell surface protein, can elicit protective immunity against S. aureus and Staphylococcus epidermidis. In this study, we evaluated the humoral immune response and CD4+ T cell-mediated immune responses in a mouse peritonitis model. The results showed that MntC-specific antibodies conferred an essential protection for mice to reduce invasion of S. aureus, which was corroborated via the opsonophagocytic killing assay and passive immunization experiment in mice, and moreover MntC-induced Th17 played a remarkable part in preventing S. aureus infection since the MntC-induced protective immunity decreased after neutralization of IL-17 by antibody in vivo and the Th17 adoptive transferred-mice could partly resist S. aureus challenge. In conclusion, we considered that the MntC-specific antibodies and MntC-specific Th17 cells play cooperative roles in the prevention of S. aureus infection.
Strength of tremor patches along deep transition zone of a megathrust
Authors: Kano Masayuki , Kato Aitaro , Ando Ryosuke , Obara Kazushige 
Published: February 2018

AbstractDeep low frequency tremors are indicators of slow slip transients in the brittle-ductile transition zone along subducting plates. Investigation of comprehensive tremor activities is therefore an important issue for understanding the seismic/aseismic characteristics in transition zones. Here, we focus on the radiated energy from tremors to reveal the along-strike heterogeneity in the strength of tremor patches. Based on a tremor catalog that more accurately evaluates radiated energy, we examine the spatio-temporal activity of tremors accompanied by slow slip events (SSEs) in western Shikoku, southwestern Japan. The new finding of this study is that the energy radiated from tremors is positively correlated with the speed of tremor migration front and the slip rate along the plate interface during a SSE. This can be qualitatively explained by a stress diffusion model, which consists of along-strike heterogeneities in the effective strength of tremor patches embedded in a ductile shear zone. This effective strength heterogeneity is supported by a lateral variation in the stress drop of a SSE; it is consistent with the fluid pressure distribution along the plate boundary fault and the tidal sensitivity of tremors. Accurate evaluation of tremor activities, especially the radiated energy, can be used to infer the spatial distribution of the strength of tremor patches in transition zones worldwide.
Targeted Mutation of NGN3 Gene Disrupts Pancreatic Endocrine Cell Development in Pigs
Authors: Sheets Timothy P. , Park Ki-Eun , Park Chi-Hun , Swift Steven M. , Powell Anne , Donovan David M. , Telugu Bhanu P. 
Published: February 2018

AbstractThe domestic pig is an attractive model for biomedical research because of similarities in anatomy and physiology to humans. However, key gaps remain in our understanding of the role of developmental genes in pig, limiting its full potential. In this publication, the role of NEUROGENIN 3 (NGN3), a transcription factor involved in endocrine pancreas development has been investigated by CRISPR/Cas9 gene ablation. Precomplexed Cas9 ribonucleoproteins targeting NGN3 were injected into in vivo derived porcine embryos, and transferred into surrogate females. On day 60 of pregnancy, nine fetuses were collected for genotypic and phenotypic analysis. One of the piglets was identified as an in-frame biallelic knockout (Δ2/Δ2), which showed a loss of putative NGN3-downstream target genes: NEUROD1 and PAX4, as well as insulin, glucagon, somatostatin and pancreatic polypeptide-Y. Fibroblasts from this fetus were used in somatic cell nuclear transfer to generate clonal animals to qualify the effect of mutation on embryonic lethality. Three live piglets were born, received colostrum and suckled normally, but experienced extreme weight loss over a 24 to 36-hour period requiring humane euthanasia. Expression of pancreatic endocrine hormones: insulin, glucagon, and somatostatin were lost. The data support a critical role of NGN3 in porcine endocrine pancreas development.
Morphological evidence of telocytes in human synovium
Authors: Rosa Irene , Marini Mirca , Guasti Daniele , Ibba-Manneschi Lidia , Manetti Mirko 
Published: February 2018

AbstractA new cell type named telocyte (i.e. cell with distinctive prolongations called telopodes) has recently been identified in the stroma of various organs in humans. However, no study has yet reported the existence of telocytes in the synovial membrane of diarthrodial joints. This work was therefore undertaken to search for telocytes in the normal human synovium using transmission electron microscopy, immunohistochemistry and immunofluorescence. Ultrastructural analyses demonstrated the presence of numerous spindle-shaped telocytes in the whole synovial sublining layer. Synovial telocytes exhibited very long and thin moniliform telopodes and were particularly concentrated at the boundary between the lining and sublining layers and around blood vessels. Light microscopy confirmed the presence of CD34-positive telocytes in the aforementioned locations. Moreover, synovial telocytes coexpressed CD34 and platelet-derived growth factor receptor α. Double immunostaining further allowed to unequivocally differentiate synovial telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). The in vitro examination of fibroblast-like synoviocyte primary cultures revealed the coexistence of different cell types, including CD34-positive telocytes projecting typical moniliform telopodes. In conclusion, our work provides the first evidence that telocytes do exist in the human synovium and lays the groundwork for future studies on synovial telocytes in a variety of degenerative and destructive joint diseases.
Development of a numerical model to predict physiological strain of firefighter in fire hazard
Authors: Su Yun , Yang Jie , Song Guowen , Li Rui , Xiang Chunhui , Li Jun 
Published: February 2018

AbstractThis paper aims to develop a numerical model to predict heat stress of firefighter under low-level thermal radiation. The model integrated a modified multi-layer clothing model with a human thermoregulation model. We took the coupled radiative and conductive heat transfer in the clothing, the size-dependent heat transfer in the air gaps, and the controlling active and controlled passive thermal regulation in human body into consideration. The predicted core temperature and mean skin temperature from the model showed a good agreement with the experimental results. Parametric study was conducted and the result demonstrated that the radiative intensity had a significant influence on the physiological heat strain. The existence of air gap showed positive effect on the physiological heat strain when air gap size is small. However, when the size of air gap exceeds 6 mm, a different trend was observed due to the occurrence of natural convection. Additionally, the time length for the existence of the physiological heat strain was greater than the existence of the skin burn under various heat exposures. The findings obtained in this study provide a better understanding of the physiological strain of firefighter and shed light on textile material engineering for achieving higher protective performance.
Time‐domain virtual EMI receiver model algorithm for corona‐originated electromagnetic interference of dc transmission line
Authors: Yi Yong , Chen Zhengying , Wang Liming 
Published: February 2018

A time‐domain virtual electromagnetic interference (EMI) receiver model algorithm for corona‐originated EMI of dc transmission line is proposed. The presented model is based on short‐time fast Fourier transform (FFT) and digital quasi‐peak, peak and average detector algorithms together with the measured corona current. The virtual EMI receiver model algorithm is verified by comparing with measurement results of conducted interference of the three regular waveforms. The influences of computational accuracy on the conducted interference are discussed. Through utilising the laboratory‐scale corona cage to generate corona current, the 0.5 MHz excitation current is calculated by using short‐time FFT and excitation function theory. The measured and computational average value, root mean square value, quasi‐peak value and peak value of EMI receiver response to corona current sequence are obtained. It is found that computations of radio interference have a good agreement with the measured results.
Longitudinal Stent Elongation of a Tapered Lesion during Percutaneous Coronary Intervention: A Case Report
Authors: Matsumoto Sen , Sakakibara Masayuki , Nishikawa Nagahiro 
Published: February 2018

AbstractThe therapeutic strategy for percutaneous coronary intervention (PCI) of a tapered lesion is still being developed. Herein, we describe a 67-year-old man with stable angina who underwent elective PCI of a tapered lesion. The coronary angiogram showed diffuse, severe stenosis in the tapered left anterior descending artery. A third-generation sirolimus-eluting stent (2.5 × 24-mm Ultimaster, Terumo, Tokyo, Japan) was deployed, and the distal side was selected as the reference. Postdilatation with a balloon diameter 2.0 mm larger than the stent was needed because of the tapered lesion. We performed postdilatation from the distal side to the proximal side of the stent with a noncompliant balloon (4.5 × 8-mm Powered Lacrosse2, Goodman, Aichi, Japan). The final angiogram showed that the total stent length was 6 mm longer than the original length. Therefore, physicians should be aware of longitudinal stent elongation of a tapered lesion during PCI to ensure appropriate treatment.
Die erste Bluttransfusion beim Menschen durch Jean-Baptiste Denis im Jahre 1667 aus medizinhistorischer Perspektive
Authors: Bauer Axel 
Published: February 2018

ZusammenfassungIm Juni 1667 gelang dem französischen Arzt Jean-Baptiste Denis (ca. 1635 – 1704) in Paris die erste erfolgreiche Transfusion von Lammblut auf einen Menschen. Die Auswahl des Spendertieres erfolgte gemäß der antiken Theorie der Humoralpathologie, wonach die physischen und psychischen Eigenschaften des als friedfertig geltenden Lammes auf den Empfänger übergehen sollten. Denis zog insbesondere einen Analogieschluss von der menschlichen Ernährung mit tierischem Fleisch auf die Transfusion tierischen Blutes. Das gelungene Experiment führte in den folgenden Monaten zu einem heftigen Gelehrtenstreit, der vor allem in der englischen Zeitschrift „Philosophical Transactions“ der Londoner „Royal Society“ ausgetragen wurde. Hierbei spielte der aus Deutschland stammende Herausgeber Henry Oldenburg (1618 – 1677) eine führende Rolle, indem er die angebliche historische Priorität englischer Wissenschaftler bei der Bluttransfusion hervorhob. Durch ein Verbot des Pariser Kriminalgerichts endete diese erste Phase der Übertragung von Tierblut auf den Menschen jedoch bereits im April 1668.
Psychologische Optionen zur Reaktivierung und Bindung von Blutspendern
Authors: Greffin Klara , Muehlan Holger , Sümnig Ariane , Schmidt Silke , Greinacher Andreas 
Published: February 2018

ZusammenfassungDas derzeitige Verhältnis von Vollblutspendern und -empfängern
1
wird in Zukunft weiter aus dem Gleichgewicht geraten: Der demografische Wandel und die Zunahme von Spenderausschlusskriterien führen zu einer Reduktion potenzieller Vollblutspender, während der Bedarf an Blutprodukten weiterhin steigt. Aus diesem Grund wird die Rekrutierung von Neuspendern allein nicht ausreichend sein, um einen stabilen Spenderpool zu erhalten. Um die Versorgung mit Blutprodukten zukünftig trotzdem gewährleisten zu können, rücken alternative Interventionsoptionen zunehmend in den Vordergrund. Der vorliegende Artikel zeigt psychologische Optionen auf, die auf die Begrenzung des drohenden Blutkonservenmangels abzielen, und richtet dabei den Fokus auf die wichtigste Ressource
2
– den Blutspender. Dafür sollen ergänzende Reaktivierungsmaßnahmen, die der Initiierung eines erneuten Blutspendeversuchs dienen, erläutert und diskutiert werden. Anschließend wird das Konstrukt der Spenderloyalität als eine aussichtsreiche Möglichkeit der langfristigen Spenderbindung vorgestellt.
Hereditäre Hämochromatose und Blutspende: Patient oder Spender?
Authors: Deitenbeck Robert , Zeiler Thomas 
Published: February 2018

ZusammenfassungBei der hereditären Hämochromatose (HH) handelt es sich um eine genetisch bedingte Störung des Eisenstoffwechsels, die bei der Mehrzahl der Betroffenen zu einer Verminderung von Hepcidin führt, das durch Bindung an Ferroportin im Darm die Resorption von Eisen hemmt. Hieraus resultieren Eisenablagerungen in verschiedenen Organen. Die Therapie besteht in der Entfernung von in Hämoglobin gebundenem Eisen durch regelmäßigen Aderlass, weshalb Blutspenden den Krankheitsverlauf positiv beeinflussen.
Entzündungssignal RANTES / CCL5 aus dem Kieferknochen
Authors: Lechner Johann , von Baehr Volker 
Published: February 2018

Summary
Hintergrund: Diese Studie behandelt die Frage, ob allgemeine und weit verbreitete zahnärztliche Eingriffe, wie Zahnextraktionen und operative Entfernung von Weisheitszähnen, zu chronischer Kieferknochenentzündung führen. Eine mangelhafte Wundheilung im Kieferknochen kann über Entzündungsmediatoren eine versteckte Ursache chronischer Erkrankungen sein.
Materialien und Methoden: Mittels Mutliplexanalyse untersuchen wir fettig-degenerativ osteonekrotisch / osteolytisch veränderten Kieferknochen (FDOK) in zwei Gruppen auf sieben Zytokine: 16 FDOK-Präparate postoperativ in Bereichen der retromolaren Weisheitszahngebiete und 19 Präparate von gesundem Kieferknochen.
Ergebnisse: Alle FDOK-Proben zeigen RANTES / CCL5 (R / C) und den Fibroblastenwachstumsfaktor (FGF)-2 als einzige stark überexprimierte Botenstoffe. Die FDOK-Proben zeigen im Mittel einen 30-fachen Überschuss von R / C und einen 20-fachen Überschuss von FGF-2 im Vergleich zu gesunden Kontrollgruppen.
Schlussfolgerungen: Da R / C in der Literatur als wichtiger Treiber von entzündlichen Erkrankungen diskutiert wird und onkogene Wirkung haben kann, verfolgen wir die Hypothese, dass FDOK infolge mangelhafter oder unvollständiger Wundheilung im Kieferknochen eine Quelle hyperaktivierter Signalwege ist. Dabei wirkt das FDOK-Areal als unentdeckter Herd einer „stillen Entzündung“. Aufgrund der R / C-Beteiligungen bei vielen Immunerkrankungen kann die chirurgische Beseitigung einer FDOK potenzielle Entwicklungen von entzündlich systemischen Erkrankungen positiv beeinflussen.
Traumatisch bedingter Kreislaufstillstand
Authors: Kreimeier Uwe , Bogner-Flatz Viktoria 
Published: February 2018

ZusammenfassungEin schweres Trauma mit Kreislaufstillstand ist eine interdisziplinäre Herausforderung. Eine verbesserte Struktur durch das TraumaNetzwerk, die Entwicklung der S3-Leitlinie für die Schwerverletztenversorgung und die optimierte Ausbildung aller Beteiligten bilden die wichtigsten aktuellen Entwicklungen.Der Refresher fasst kompakt den aktuellen Stand der Basismaßnahmen zur Wiederbelebung, die Priorisierung der lebensrettenden Maßnahmen auf Basis der aktuellen Leitlinie zusammen und gibt einen Ausblick auf die Prognose und das mögliche Potenzial einer guten Erstversorgung.
Die Digitalisierung der Arzt-Patienten Beziehung in
Deutschland: Ein Discrete Choice Experiment zur Analyse der Patientenpräferenzen
bezüglich digitaler Gesundheitsleistungen
Authors: von Wedel Philip , Hagist Christian , Saunders Katharina 
Published: February 2018

Zusammenfassung
Ziel Das deutsche E-Health Gesetz soll Effizienz, Qualität und
Zugänglichkeit des deutschen Gesundheitssystems positiv beeinflussen. Diese
Studie untersucht die Präferenzen der Patienten bezüglich digitaler
Gesundheitsleistungen und vergleicht diese mit den Prioritäten des
Gesetzgebers.
Methodik Zwei Discrete Choice Experimente (DCE) wurden durchgeführt um
Präferenzen und auch die Zahlungsbereitschaft von Patienten bezüglich digitaler
Gesundheitsinformationen und Telemedizin zu erfassen.
Ergebnisse Patienten in Deutschland bevorzugen die Speicherung einer
allumfassenden Patientenakte gefolgt von Notfalldaten auf ihrer
Versichertenkarte. Einem Medikationsplan wird eine klare Absage erteilt. In
Bezug auf eine telemedizinische Betreuung ziehen Patienten die Kommunikation via
E-Mail einer Videosprechstunde oder Text-Chats vor.
Schlussfolgerung Die Ergebnisse dieser Studie lassen zum Teil erhebliche
Diskrepanzen zwischen den Prioritäten des E-Health Gesetzes und den Präferenzen
der Patienten erkennen. Dies stellt die Adaption von Patientenseite und damit
die Effektivität des Gesetzes in Frage.
Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion
Authors: Avery Lyndsay , Filderman Jessica , Szymczak-Workman Andrea L. , Kane Lawrence P. 
Published: February 2018

Significance
During a chronic viral infection, prolonged exposure to viral antigens leads to dysfunction or “exhaustion” of T cells specific to the virus, a condition also observed in T cells that infiltrate tumors. The exhausted state is associated with poor T cell memory and expression of specific cell-surface proteins, some of which may inhibit T cell activation. Expression of Tim-3 is associated with acquisition of T cell exhaustion, although it is also expressed transiently during acute infection. We have found that a major function of Tim-3 is to enhance T cell activation during either acute or chronic viral infection, and that Tim-3 is not required for the development of T cell exhaustion.
Fundamental limits on dynamic inference from single-cell snapshots
Authors: Weinreb Caleb , Wolock Samuel , Tusi Betsabeh K. , Socolovsky Merav , Klein Allon M. 
Published: February 2018

Significance
Seeing a snapshot of individuals at different stages of a dynamic process can reveal what the process would look like for a single individual over time. Biologists apply this principle to infer temporal sequences of gene expression states in cells from measurements made at a single moment in time. However, the sparsity and high dimensionality of single-cell data have made inference difficult using formal approaches. Here, we apply recent innovations in spectral graph theory to devise a simple and asymptotically exact algorithm for inferring the unique dynamic solution under defined approximations and apply it to data from bone marrow stem cells.
Algorithms in the historical emergence of word senses
Authors: Ramiro Christian , Srinivasan Mahesh , Malt Barbara C. , Xu Yang 
Published: February 2018

SignificanceHow do words develop new senses? Unlike changes in sound or grammar where there are rich formal characterizations, semantic change is poorly understood. Changes in meaning are often considered intractable, with sparse attempts at formalizing and evaluating the principles against historical data at scale. We present a data-enriched formal approach that explores the time-varying lexicon. Motivated by prominent work in cognitive science and linguistics, we develop computational algorithms that predict the historical order in which the senses of a word have emerged, and we test these predictions against records of English over the past millennium. Our findings suggest that word senses emerge in ways that minimize cognitive costs, providing an efficient mechanism for expressing new ideas via a compact lexicon.