bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
Authors: Järver Peter , Dondalska Aleksandra , Poux Candice , Sandberg AnnSofi , Bergenstråhle Joseph , Sköld Annette E. , Dereuddre-Bosquet Nathalie , Martinon Fréderic , Pålsson Sandra , Zaghloul Eman , Brodin David , Sander Birgitta , Lennox Kim A. , Behlke Mark A. , EL-Andaloussi Samir , Lehtiö Janne , Lundeberg Joakim , LeGrand Roger , Spetz Anna-Lena 
Published: October 2018

AbstractRecognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream of TLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
High resolution laboratory grating-based X-ray phase-contrast CT
Authors: Viermetz Manuel , Birnbacher Lorenz , Willner Marian , Achterhold Klaus , Pfeiffer Franz , Herzen Julia 
Published: October 2018

AbstractThe conventional form of computed tomography using X-ray attenuation without any contrast agents is of limited use for the characterization of soft tissue in many fields of medical and biological studies. Grating-based phase-contrast computed tomography (gbPC-CT) is a promising alternative imaging method solving the low soft tissue contrast without the need of any contrast agent. While highly sensitive measurements are possible using conventional X-ray sources the spatial resolution does often not fulfill the requirements for specific imaging tasks, such as visualization of pathologies. The focus of this study is the increase in spatial resolution without loss of sensitivity. To overcome this limitation a super-resolution reconstruction based on sub-pixel shifts involving a deconvolution of the image data during each iteration is applied. In our study we achieve an effective pixel size of 28 μm with a conventional rotating anode tube and a photon-counting detector. We also demonstrate that the method can upgrade existing setups to measure tomographies with higher resolution. The results show the increase in resolution at high sensitivity and with the ability to make quantitative measurements. The combination of sparse sampling and statistical iterative reconstruction may be used to reduce the total measurement time. In conclusion, we present high-quality and high-resolution tomographic images of biological samples to demonstrate the experimental feasibility of super-resolution reconstruction.
Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status
Authors: Hasegawa Yu , Curtis Britni , Yutuc Vernon , Rulien Megan , Morrisroe Kelly , Watkins Kristin , Ferrier Clayton , English Chris , Hewitson Laura , Slupsky Carolyn M. 
Published: October 2018

AbstractAlthough thimerosal, an ethylmercury-based preservative, has been removed from most pediatric vaccines in the United States, some multidose vaccines, such as influenza vaccines, still contain thimerosal. Considering that a growing number of studies indicate involvement of the gut microbiome in infant immune development and vaccine responses, it is important to elucidate the impact of pediatric vaccines, including thimerosal-containing vaccines, on gut microbial structure and function. Here, a non-human primate model was utilized to assess how two vaccine schedules affect the gut microbiome in infants (5–9 days old) and juveniles (77–88 weeks old) through 16S ribosomal RNA sequencing and metabolomics analyses of the fecal samples. Two treatment groups (n = 12/group) followed either the vaccine schedule that was in place during the 1990s (intensive exposure to thimerosal) or an expanded schedule administered in 2008 (prenatal and postnatal exposure to thimerosal mainly via influenza vaccines), and were compared with a control group (n = 16) that received saline injections. The primary impact on gut microbial structure and function was age. Although a few statistically significant impacts of the two common pediatric vaccine schedules were observed when confounding factors were considered, the magnitude of the differences was small, and appeared to be positive with vaccination.
Effects of UV for Cycloaliphatic Epoxy Resin via Thermokinetic Models, Novel Calorimetric Technology, and Thermogravimetric Analysis
Authors: Laiwang Bin , Liu Shang-Hao , Tsai Yun-Ting , Deng Jun , Jiang Hui-Chun , Li Bei , Shu Chi-Min 
Published: October 2018

AbstractThe cycloaliphatic epoxy resin selected for this study was 3,4-epoxycyclohexane methyl-3′4′-epoxycyclohexyl-carboxylate (EEC). Epoxy resin has numerous applications, such as varnishes, tires, and electronic materials. However, the extensive used of chlorofluorocarbon (CFC) compounds in the last century has resulted in the formation of a hole in the ozone layer. As a consequence, solar radiation is intensifying gradually; therefore, continuous irradiation by sunlight should be avoided. The results of solar radiation can exacerbate the deterioration and photolysis of compounds. Through thermogravimetry and differential scanning calorimetry, the apparent onset temperature of EEC and EEC was analyzed under UV radiation for different durations. Thermokinetic data were used to determine the parameters of thermal decomposition characteristics through simulation to assess the reaction of EEC and EEC under UV radiation for different durations. The goal of the study was to establish the parameters of thermal decomposition characteristics for the effects of UV on EEC, as well as the probability of severity of thermal catastrophe.
The pattern of gestational weight gains among Chinese women: a repeated measure analysis
Authors: Tan Jing , Ren Yan , Qi Yana , Chen Peng , Tang Li , He Guolin , Li Sheyu , Sun Xin , Liu Xinghui 
Published: October 2018

AbstractThis study aimed to investigate the pattern of gestational weight gain (GWG) among Chinese women. We included pregnant women, who delivered at a referral medical center in China and had no pre-specified adverse pregnancy outcomes. We collected weight data across all pregnancy visits, and used the two-level spline linear model to fit for the pattern of GWG according to pre-pregnancy BMI categories. In total, 4,567 pregnant women with 47,699 repeated measures were eligible. For those who were underweight, normal and overweight before pregnancy, the interquartile ranges (25th to 75th quartiles) of GWG between 14 and 36 gestational weeks were 12.9–17.7 kg, 12.6–17.3 kg and 11.7–16.8 kg, and the corresponding rates of GWG were 2.62 kg/month, 2.56 kg/month and 2.37 kg/month. For underweight and normal women, the rates of GWG were similar before 14 weeks (0.57 and 0.58 kg/month) and after 36 weeks (1.69 and 1.70 kg/month); however, the rates of GWG were higher for overweight women (0.66 kg/month before 14 weeks and 1.89 kg/month after 36 weeks). In summary, the pattern of GWG among Chinese pregnant women is generally consistent with the IOM recommendation, particularly for those who are normal or underweight. Modifications are, however, warranted for overweight pregnant women.
Mortality induced by PM2.5 exposure following the 1783 Laki eruption using reconstructed meteorological fields
Authors: Balkanski Y. , Menut L. , Garnier E. , Wang R. , Evangeliou N. , Jourdain S. , Eschstruth C. , Vrac M. , Yiou P. 
Published: October 2018

AbstractThe 1783–1784 Laki eruption provides a natural experiment to evaluate the performance of chemistry-transport models in predicting the health impact of air particulate pollution. There are few existing daily meteorological observations during the second part of the 18th century. Hence, creating reasonable climatological conditions for such events constitutes a major challenge. We reconstructed meteorological fields for the period 1783–1784 based on a technique of analogues described in the Methods. Using these fields and including detailed chemistry we describe the concentrations of sulphur (SO2/SO4) that prevail over the North Atlantic, the adjoining seas and Western Europe during these 2 years. To evaluate the model, we analyse these results through the prism of two datasets contemporary to the Laki period: • The date of the first appearance of ‘dry fogs’ over Europe, • The excess mortality recorded in French parishes over the period June–September 1783. The sequence of appearances of the dry fogs is reproduced with a very-high degree of agreement to the first dataset. High concentrations of SO2/SO4 are simulated in June 1783 that coincide with a rapid rise of the number of deceased in French parishes records. We show that only a small part of the deceased of the summer of 1783 can be explained by the present-day relationships between PM2.5 and relative risk. The implication of this result is that other external factors such as the particularly warm summer of 1783, and the lack of health care at the time, must have contributed to the sharp increase in mortality over France recorded from June to September 1783.
DNA repair protein Rad18 restricts LINE-1 mobility
Authors: Ariumi Yasuo , Kawano Koudai , Yasuda-Inoue Mariko , Kuroki Misao , Fukuda Hiroyuki , Siddiqui Rokeya , Turelli Priscilla , Tateishi Satoshi 
Published: October 2018

AbstractLong interspersed element-1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome. L1 utilizes an endonuclease to insert L1 cDNA into the target genomic DNA, which induces double-strand DNA breaks in the human genome and activates the DNA damage signaling pathway, resulting in the recruitment of DNA-repair proteins. This may facilitate or protect L1 integration into the human genome. Therefore, the host DNA repair machinery has pivotal roles in L1 mobility. In this study, we have, for the first time, demonstrated that the DNA repair protein, Rad18, restricts L1 mobility. Notably, overexpression of Rad18 strongly suppressed L1 retrotransposition as well as L1-mediated Alu retrotransposition. In contrast, L1 retrotransposition was enhanced in Rad18-deficient or knockdown cells. Furthermore, the Rad6 (E2 ubiquitin-conjugated enzyme)-binding domain, but not the Polη-binding domain, was required for the inhibition of L1 retrotransposition, suggesting that the E3 ubiquitin ligase activity of Rad18 is important in regulating L1 mobility. Accordingly, wild-type, but not the mutant Rad18-lacking Rad6-binding domain, bound with L1 ORF1p and sequestered with L1 ORF1p into the Rad18-nuclear foci. Altogether, Rad18 restricts L1 and Alu retrotransposition as a guardian of the human genome against endogenous retroelements.
Covert Stuttering: Investigation of the Paradigm Shift From Covertly Stuttering to Overtly Stuttering
Authors: Douglass Jill E. , Schwab Maria , Alvarado Jacqueline 
Published: October 2018

Purpose
Covert stuttering is a type of stuttering experience that occurs when a person who stutters conceals his or her stutter from others, attempting to be perceived as a nonstuttering individual. A person who covertly stutters experiences the cognitive and emotional elements of stuttering with minimum overt behavioral symptoms. Individuals who covertly stutter are able to provide insight into their experiences in attempting to be perceived as nonstuttering individuals. Covert stuttering is a topic that continues to be in need of a formal definition. The current investigation is utilizing thematic analysis to provide a detail-rich investigation of the paradigm shift from covertly stuttering to overtly stuttering.

Method
The current investigation is a qualitative analysis of individuals' transition process from covertly stuttering to overtly stuttering. Real-time video interviews were conducted with the use of open-ended phenomenological interview questions. Interviews were transcribed, and thematic analysis of interview transcripts was conducted to investigate the covertly to overtly stuttering process for participants.

Results
The findings provide insight into a paradigm shift that occurs when individuals who covertly stutter begin to outwardly identify themselves and allow for overt stuttering. The primary theme was a paradigm shift in the 6 participants' mindset regarding stuttering; additional details are provided in the subthemes: attending speech therapy, meeting other people who stutter, and a psychological low point. The details of the covert-to-overt stuttering conversion are documented with the use of direct quotations.

Conclusion
The evidence suggests the various intricacies of the experiences of persons who are covert. Clinical implications of these findings for assessing and treating individuals who covertly stutter are discussed.
Evolution of protoplanetary disks from their taxonomy in scattered light: spirals, rings, cavities, and shadows
Authors: Garufi A. , Benisty M. , Pinilla P. , Tazzari M. , Dominik C. , Ginski C. , Henning Th. , Kral Q. , Langlois M. , Ménard F. , Stolker T. , Szulagyi J. , Villenave M. , van der Plas G. 
Published: October 2018

Context.Dozens of protoplanetary disks have been imaged in scattered light during the last decade.Aims.The variety of brightness, extension, and morphology from this census motivates a taxonomical study of protoplanetary disks in polarimetric light to constrain their evolution and establish the current framework of this type of observation.Methods.We classified 58 disks with available polarimetric observations into six major categories (Ring, Spiral, Giant, Rim, Faint, and Small disks) based on their appearance in scattered light. We re-calculated the stellar and disk properties from the newly availableGaiaDR2 and related these properties with the disk categories.Results.More than half of our sample shows disk substructures. For the remaining sources, the absence of detected features is due to their faintness, their small size, or the disk geometry. Faint disks are typically found around young stars and typically host no cavity. There is a possible dichotomy in the near-infrared (NIR) excess of sources with spiral-disks (high) and ring-disks (low). Like spirals, shadows are associated with a high NIR excess. If we account for the pre-main sequence evolutionary timescale of stars with different mass, spiral arms are likely associated with old disks. We also found a loose, shallow declining trend for the disk dust mass with time.Conclusions.Protoplanetary disks may form substructures like rings very early in their evolution but their detectability in scattered light is limited to relatively old sources ( ≳5 Myr) where the recurrently detected disk cavities cause the outer disk to be illuminate. The shallow decrease of disk mass with time might be due to a selection effect, where disks observed thus far in scattered light are typically massive, bright transition disks with longer lifetimes than most disks. Our study points toward spirals and shadows being generated by planets of a fraction of a Jupiter mass to a few Jupiter masses in size that leave their (observed) imprint on both the inner disk near the star and the outer disk cavity.
Krankengymnastische Haltungskorrektur mittels Fazilitation über die Hände „Hands Induced Posture“ (HIP) – eine Einführung
Authors: Best Norman , Schildt-Rudloff Karla , Strohbach Dorit , Derlien Steffen , Loudovici-Krug Dana , Bocker Barbara , Anders Christoph , Best Stefanie 
Published: October 2018

Zusammenfassung
Hintergrund Die propriozeptive sensomotorische Fazilitation (PSF) nach Janda stellt eine anerkannte Methode zur Verbesserung der sensomotorischen Kompetenz dar. Allerdings sind Menschen davon ausgeschlossen, denen es nicht möglich ist, die Fußmuskulatur zu aktivieren.
Konzeptvorstellung Über die Fazilitation der Handmuskulatur und distoproximaler Stützmuster gelingt es die Rücken- und Bauchmuskulatur anzusprechen und damit die posturale Muskulatur zu beüben.
Pilotstudie Im Rahmen einer Pilotstudie konnten eine Änderung der Skapulaposition und eine Bauchumfangsminderung eruiert werden. Weitere Parameter zeigten nicht die vermuteten Änderungen.
Konsequenz und Fazit Über eine Oberflächen-EMG-Studie sollen Muskelgruppen gefunden werden, die durch die „HIP“–Übung angesprochen werden.
Phytotherapie bei obstruktiven Atemwegserkrankungen
Authors: Gündling Peter W. 
Published: October 2018

ZusammenfassungObgleich Phytotherapeutika bei Asthma und COPD nicht an erster Stelle stehen, weisen sie doch Wirkungen auf, die sowohl für das akute als auch das chronische
entzündliche Geschehen obstruktiver Atemwegserkrankungen eine wichtige Rolle spielen: Schutz vor Infekten, antiinflammatorische und antivirale Wirkung,
Verbesserung der mukoziliären Clearance, antitussive Wirkung, Immunmodulation, Schutz vor bakterieller Superinfektion.Bei Beachtung der Grenzen dieser Therapierichtung stehen dem Therapeuten in der Praxis bewährte und wirksame Optionen zur Verfügung.
Complicaciones de las derivaciones urinarias heterópicas no continentes: Ureterostomías cutáneas vs conducto ileal
Authors: Franco Diana Carolina , Ramirez Rodolfo Varela , de Mesa Byron Lopez , Fierro Marino Cabrera , Madarriaga Yesica Yasmín Quiroz 
Published: October 2018

Introducción Y Objetivos Las derivaciones del tracto urinario abarcan una amplia gama de técnicas quirúrgicas, siendo la causa más frecuente para su uso la patología urotelial maligna. De las derivaciones urinarias no continentes heterótopicas las más utilizadas son el conducto ileal y las ureterostomias cutáneas. La elección de la técnica dependerá de la patología de base, las condiciones del paciente y la experiencia del cirujano. El objetivo de este trabajo es determinar las complicaciones tempranas (≤30 días) y tardías (>30 días) de derivaciones urinarias heterópicas no continentes (DUHNC) tipo conducto ileal (CI) vs ureterostomias cutáneas (UC).
Métodos Se realizó un estudio descriptivo retrospectivo de los pacientes llevados a DUHNC tipo CI o UC, desde enero del 2008 a julio del 2016, en un centro de referencia para patología oncológica. Se evaluó: edad, género, comorbilidades, escala de Karnofsky, patología quirúrgica, sangrado, ASA, tiempo quirúrgico, estancia hospitalaria, complicaciones tempranas y tardías.
Resultados De los 70 pacientes incluidos, 26 con UC y 44 con CI, prevaleciendo el género masculino en ambos grupos. El promedio de edad fue de 66 y 63 años respectivamente y el indice Karnofsky en todos los pacientes fue superior al 90%. La causa más frecuente fue patología maligna de vejiga. El tiempo quirúrgico fue mayor en los pacientes del CI, siendo estadísticamente significativo (p = 0.000). El sangrado fue similar en ambas técnicas quirúrgicas requiriendo transfusión de hemoderivados el 92,3% de los pacientes con UC y 88,6% de los CI. La estancia hospitalaria no tuvo diferencias. En cuanto a las complicaciones tempranas, la más frecuente en ambos grupos fue el choque hipovolémico (61% UC y 58% CI). De las complicaciones tardías la sepsis urinaria prevaleció en ambos grupos (34% y 18% respectivamente) y la estrechez del estoma y la anastomosis ureteroileal se presentaron en las UC y en los CI respectivamente. La mortalidad en el transoperatorio fue del 12,8%.
Conclusiones Las DUHNC como las ureterostomias cutáneas o el conducto ileal son técnicas quirúrgicas con tasas de sangrado, transfusión y estancia hospitalaria similares, pero con una menor proporción de complicaciones tanto tempranas como tardías en los pacientes llevados a conducto ileal.
Harms and Benefits of Using Aspirin for Primary Prevention of Cardiovascular Disease: A Narrative Overview
Authors: Danese Elisa , Favaloro Emmanuel , Lippi Giuseppe 
Published: October 2018

AbstractAspirin is one of the most often used drugs for prevention and treatment of a variety of thrombotic disorders. This narrative review aims to provide an overview of evidence highlighting potential benefits and relative harms of aspirin in primary prevention of cardiovascular disease. The authors summarize key findings of the ASPirin in Reducing Events in the Elderly (ASPREE) Investigator Group randomized trial and also provide a comparative overview of recent meta-analyses. Overall, all-cause mortality was largely heterogeneous, with some meta-analyses showing a modestly decreased risk in patients taking aspirin, with others reporting no effects, but the ASPREE Investigator Group trial evidencing 14% higher risk. Regarding cardiovascular disease, the most favorable impact could be noted for major adverse cardiovascular events, with most meta-analyses reporting a decreased risk in people receiving aspirin. Conversely, the ASPREE Investigator Group trial demonstrated no significant impact of aspirin on risk of cardiovascular mortality or ischemic stroke. A modest favorable effect of aspirin in decreasing the risk of myocardial infarction was noted in two meta-analyses, but not in other reports or in the ASPREE Investigator Group trial. Furthermore, one meta-analysis reported a lower risk of future cancer, others failed to report a significant effect, and the ASPREE Investigator Group trial reported a 31% increased risk. Unlike these conflicting outcomes, the bleeding risk of patients receiving aspirin was found to be consistently enhanced in all reports reviewed. These recent findings would lead us to conclude that the harms of aspirin in primary prevention of cardiovascular disease may be larger than the benefits, especially in the elderly general population.
SHOC2–MRAS–PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis
Authors: Young Lucy C. , Hartig Nicole , Boned del Río Isabel , Sari Sibel , Ringham-Terry Benjamin , Wainwright Joshua R. , Jones Greg G. , McCormick Frank , Rodriguez-Viciana Pablo 
Published: October 2018

Significance
We demonstrate a mechanism whereby germline mutations in MRAS, SHOC2, and PPP1CB contribute directly to Noonan syndrome by enhancing formation of a ternary complex, which specifically dephosphorylates an inhibitory site on RAF kinases, activating downstream signaling. SHOC2 is required for tumorigenic properties of tumor-derived cell lines with RAS mutations and has more recently been identified by others in a synthetic lethal screen as a gene essential for viability of RAS mutant but not RAS wild-type cells. A thorough analysis of this complex at the biochemical and structural level has demonstrated the remarkable ability of this complex to dictate specificity for RAF and suggests possible strategies to inhibit the complex as a way of targeting the RAS–ERK pathway.
Hominoid intraspecific cranial variation mirrors neutral genetic diversity
Authors: Zichello Julia M. , Baab Karen L. , McNulty Kieran P. , Raxworthy Christopher J. , Steiper Michael E. 
Published: October 2018

SignificanceIn humans, patterns of cranial variation mirror genetic diversity globally, implicating population history as a key driver of cranial disparity. Here, we demonstrate that the magnitude of genetic diversity within 12 extant ape taxa explains a large proportion of cranial shape variation. Taxa that are more genetically diverse tend to be more cranially diverse also. Our results suggest that neutral evolutionary processes such as mutation, genetic drift, and gene flow are reflected in both genetic and cranial diversity in apes. This work provides a perspective on intraspecific cranial variation in apes which has important implications for interpreting selective and developmental pressures on the cranium and for understanding shape variation in fossil hominin crania.