bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma
Authors: Manier S. , Park J. , Capelletti M. , Bustoros M. , Freeman S. S. , Ha G. , Rhoades J. , Liu C. J. , Huynh D. , Reed S. C. , Gydush G. , Salem K. Z. , Rotem D. , Freymond C. , Yosef A. , Perilla-Glen A. , Garderet L. , Van Allen E. M. , Kumar S. , Love J. C. , Getz G. , Adalsteinsson V. A. , Ghobrial I. M. 
Published: April 2018

AbstractLiquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM.
Deconvolution of subcellular protrusion heterogeneity and the underlying actin regulator dynamics from live cell imaging
Authors: Wang Chuangqi , Choi Hee June , Kim Sung-Jin , Desai Aesha , Lee Namgyu , Kim Dohoon , Bae Yongho , Lee Kwonmoo 
Published: April 2018

AbstractCell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanism of cell protrusion has been understood based on the ensemble average of actin regulator dynamics. Here, we establish a computational framework called HACKS (deconvolution of heterogeneous activity in coordination of cytoskeleton at the subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion from live cell imaging. HACKS identifies distinct subcellular protrusion phenotypes based on machine-learning algorithms and reveals their underlying actin regulator dynamics at the leading edge. Using our method, we discover “accelerating protrusion”, which is driven by the temporally ordered coordination of Arp2/3 and VASP activities. We validate our finding by pharmacological perturbations and further identify the fine regulation of Arp2/3 and VASP recruitment associated with accelerating protrusion. Our study suggests HACKS can identify specific subcellular protrusion phenotypes susceptible to pharmacological perturbation and reveal how actin regulator dynamics are changed by the perturbation.
Limits on determining the skill of North Atlantic Ocean decadal predictions
Authors: Menary Matthew B. , Hermanson Leon 
Published: April 2018

AbstractThe northern North Atlantic is important globally both through its impact on the Atlantic Meridional Overturning Circulation (AMOC) and through widespread atmospheric teleconnections. The region has been shown to be potentially predictable a decade ahead with the skill of decadal predictions assessed against reanalyses of the ocean state. Here, we show that the prediction skill in this region is strongly dependent on the choice of reanalysis used for validation, and describe the causes. Multiannual skill in key metrics such as Labrador Sea density and the AMOC depends on more than simply the choice of the prediction model. Instead, this skill is related to the similarity between the nature of interannual density variability in the underlying climate model and the chosen reanalysis. The climate models used in these decadal predictions are also used in climate projections, which raises questions about the sensitivity of these projections to the models’ innate North Atlantic density variability.
A cryptic cycle in haematopoietic niches promotes initiation of malaria transmission and evasion of chemotherapy
Authors: Lee Rebecca S. , Waters Andrew P. , Brewer James M. 
Published: April 2018

AbstractBlood stage human malaria parasites may exploit erythropoietic tissue niches and colonise erythroid progenitors; however, the precise influence of the erythropoietic environment on fundamental parasite biology remains unknown. Here we use quantitative approaches to enumerate Plasmodium infected erythropoietic precursor cells using an in vivo rodent model of Plasmodium berghei. We show that parasitised early reticulocytes (ER) in the major sites of haematopoiesis establish a cryptic asexual cycle. Moreover, this cycle is characterised by early preferential commitment to gametocytogenesis, which occurs in sufficient numbers to generate almost all of the initial population of circulating, mature gametocytes. In addition, we show that P. berghei is less sensitive to artemisinin in splenic ER than in blood, which suggests that haematopoietic tissues may enable origins of recrudescent infection and emerging resistance to antimalarials. Continuous propagation in these sites may also provide a mechanism for continuous transmission and infection in malaria endemic regions.
Predictors of next-generation sequencing panel selection using a shared decision-making approach
Authors: Courtney Eliza , Li Shao-Tzu , Shaw Tarryn , Chen Yanni , Allen John Carson , Ngeow Joanne 
Published: April 2018

AbstractThe introduction of next-generation sequencing panels has transformed the approach for genetic testing in cancer patients, however, established guidelines for their use are lacking. A shared decision-making approach has been adopted by our service, where patients play an active role in panel selection and we sought to identify factors associated with panel selection and report testing outcomes. Demographic and clinical data were gathered for female breast and/or ovarian cancer patients aged 21 and over who underwent panel testing. Panel type was classified as ‘breast cancer panel’ (BCP) or ‘multi-cancer panel’ (MCP). Stepwise multiple logistic regression analysis was used to identify clinical factors most predictive of panel selection. Of the 265 included subjects, the vast majority selected a broader MCP (81.5%). Subjects who chose MCPs were significantly more likely to be ≥50 years of age (49 vs. 31%; p < 0.05), Chinese (76 vs. 47%; p < 0.001) and have a personal history of ovarian cancer (41 vs. 8%; p < 0.001) with the latter two identified as the best predictors of panel selection. Family history of cancer was not significantly associated with panel selection. There were no statistically significant differences in result outcomes between the two groups. In summary, our findings demonstrate that the majority of patients have a preference for interrogating a larger number of genes beyond those with established testing guidelines, despite the additional likelihood of uncertainty. Individual factors, including cancer history and ethnicity, are the best predictors of panel selection.
Time efficient whole-brain coverage with MR Fingerprinting using slice-interleaved echo-planar-imaging
Authors: Rieger Benedikt , Akçakaya Mehmet , Pariente José C. , Llufriu Sara , Martinez-Heras Eloy , Weingärtner Sebastian , Schad Lothar R. 
Published: April 2018

AbstractMagnetic resonance fingerprinting (MRF) is a promising method for fast simultaneous quantification of multiple tissue parameters. The objective of this study is to improve the coverage of MRF based on echo-planar imaging (MRF-EPI) by using a slice-interleaved acquisition scheme. For this, the MRF-EPI is modified to acquire several slices in a randomized interleaved manner, increasing the effective repetition time of the spoiled gradient echo readout acquisition in each slice. Per-slice matching of the signal-trace to a precomputed dictionary allows the generation of T1 and T2* maps with integrated B1+ correction. Subsequent compensation for the coil sensitivity profile and normalization to the cerebrospinal fluid additionally allows for quantitative proton density (PD) mapping. Numerical simulations are performed to optimize the number of interleaved slices. Quantification accuracy is validated in phantom scans and feasibility is demonstrated in-vivo. Numerical simulations suggest the acquisition of four slices as a trade-off between quantification precision and scan-time. Phantom results indicate good agreement with reference measurements (Difference T1: −2.4 ± 1.1%, T2*: −0.5 ± 2.5%, PD: −0.5 ± 7.2%). In-vivo whole-brain coverage of T1, T2* and PD with 32 slices was acquired within 3:36 minutes, resulting in parameter maps of high visual quality and comparable performance with single-slice MRF-EPI at 4-fold scan-time reduction.
Multidrug-resistant Pseudomonas aeruginosa aggravates inflammatory responses in murine chronic colitis
Authors: von Klitzing Eliane , Ekmekciu Ira , Kühl Anja A. , Bereswill Stefan , Heimesaat Markus M. 
Published: April 2018

AbstractThe World Health Organization has rated multidrug-resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Psae) as serious threat to human health. We here addressed whether chronic murine gut inflammation facilitates intestinal MDR Psae colonization and whether bacterial infection subsequently worsens colonic immunopathology. Converse to wildtype counterparts, Psae colonized the intestines of IL-10−/− mice with chronic colitis following peroral challenge, but did not lead to changes in intestinal microbiota composition. Psae infection accelerated both macroscopic (i.e. clinical) and microscopic disease (i.e. colonic epithelial apoptosis), that were accompanied by increased intestinal pro-inflammatory immune responses as indicated by elevated colonic numbers of innate and adaptive immune cell subsets and enhanced secretion of pro-inflammatory cytokines such as TNF and IFN-γ in mesenteric lymph nodes of Psae-infected as compared to unchallenged IL-10−/− mice. Remarkably, Psae-induced pro-inflammatory immune responses were not restricted to the gut, but could also be observed systemically as indicated by increased TNF and IFN-γ concentrations in sera upon Psae-infection. Furthermore, viable commensals originating from the intestinal microbiota translocated to extra-intestinal compartments such as liver, kidney and spleen of Psae-infected IL-10−/− mice with chronic colitis only. Hence, peroral MDR Psae-infection results in exacerbated colonic as well as systemic pro-inflammatory immune responses during chronic murine colitis.
Enhancement of UV Second-Harmonic Radiation at Nonlinear Interfaces with Discontinuous Second-order Susceptibilities
Authors: Zhao Xiaohui , Zheng Yuanlin , An Ning , Ren Huaijin , Deng Xuewei , Chen Xianfeng 
Published: April 2018

AbstractWe investigate the generation of ultraviolet (UV) second-harmonic radiation at the boundary of a UV transparent crystal, which is derived from the automatic partial phase matching of the incident wave and the total internal reflection. By adhering to another UV non-transparent crystal with a larger second-order nonlinear coefficient χ(2), a nonlinear interface with large disparity in χ(2) is formed and the enhancement of UV second-harmonic radiation is observed experimentally. The intensity of enhanced second harmonic wave generated at the nonlinear interface is up to 11.6 times that at the crystal boundary. As a tunable phase-matching method, it may suggest potential applications in the UV, and even vacuum-UV region.
Uses of selection strategies in both spectral and sample spaces for classifying hard and soft blueberry using near infrared data
Authors: Hu Menghan , Zhai Guangtao , Zhao Yu , Wang Zhaodi 
Published: April 2018

AbstractIn the current work, we attempt to leverage the fewer wavelengths and samples to develop a classification model for classifying hard and soft blueberries using near infrared (NIR) data. To do this, random frog selection and active learning approaches are used in the spectral space and the sample queue, respectively. To reduce the spectral number, a random frog spectral selection approach was applied to collect wavelengths informative with hardness. Prediction model based on 22 selected spectra gave slightly better results than that based on the full spectra. In terms of the selection operation in the sample space, the query by committee was validated to be suitable for blueberry hardness classification with the accuracy, precision and recall of 78%, 74% and 98% when taking only 25 sample queries. Its standard deviation curves of performance metrics are also located in regions of low values (around 0.05) and fluctuated steadily in shape, winning over those of the other 4 active learning strategies and random method. In summary, the respective uses of random frog and query by committee in the NIR spectral vector and the sample queue showed the considerable potential for establishing a simple but robust classifier for hard and soft blueberries with very low labeling cost.
Effects of litter feeders on the transfer of 137Cs to plants
Authors: Ishii Nobuyoshi , Murakami Masashi , Suzuki Takahiro , Tagami Keiko , Uchida Shigeo , Ohte Nobuhito 
Published: April 2018

AbstractThe effects of the Japanese horned beetle larvae on the transfer of 137Cs from a contaminated leaf litter to the leaf vegetable, komatsuna (Brassica rapa var. perviridis) was studied. Feces of the larvae which were fed 137Cs-contaminated leaf litter were added to a potting mix in which komatsuna plants were cultivated. The presence of feces increased the harvest yield of komatsuna, suggesting that feces provided nutrients for the plant growth. In addition, the amount of exchangeable 137Cs in leaf litter was experimentally confirmed to be enhanced by the presence of feces which were excreted by larvae feeding. However, there was no difference in the soil-to-plant transfer factor of 137Cs for the presence and absence of feces. Interactions between clay minerals and exchangeable 137Cs in the soil beneath the litter layer may diminish the root uptake of 137Cs. From these results, it was concluded that the effect of exchangeable 137Cs released from feces was limited for the transfer of 137Cs to plants if plant roots were not present in litter layers.
60 Jahre Notarztdienst in Köln
Authors: Stangl Robert , Wanke Sebastian , Paul Christian , Adler Christoph 
Published: April 2018

ZusammenfassungBedingt durch die rapide steigenden Verkehrsunfallzahlen im Zuge der zunehmenden Motorisierung ergab sich Ende der 50er-Jahre des 20. Jahrhunderts ein dringender Reformbedarf für das Rettungswesen. In diesem Zusammenhang entstanden ab 1957 die ersten Notarztsysteme in Köln und Heidelberg. Die Entstehung und Entwicklung des Kölner Notarztdienstes seit 1957 kann aufgrund der äußerst günstigen Quellenlage und anhand zahlreicher gut erhaltener Dokumente und lebender Zeitzeugen genauestens dokumentiert und nachvollzogen werden. Zahlreiche grundlegende Organisationsformen und wegweisende Prinzipien des organisierten Notarztdienstes wurden in dieser Zeit entwickelt. Beeindruckend detaillierte statistische Auswertungen wie beispielsweise die erstmalige systematische Analyse präklinischer Reanimationsergebnisse in der deutschen Literatur geben einen interessanten Einblick in die frühen Jahre der deutschen Notfallmedizin.
Clinical Outcomes and Complications after Open Reduction and Internal Fixation Utilizing Conventional Plates in 65 Distal Radial and Ulnar Fractures of Miniature- and Toy-Breed Dogs
Authors: Miyazaki Yuta , Shimatsu Taichi , Iizuka Kyoko , Nishimura Masaaki , Aikawa Takeshi 
Published: April 2018

Objective This article aims to evaluate clinical outcomes and complications of distal radial and ulnar fractures in miniature- and toy-breed dogs treated with conventional bone plate fixation.
Methods Medical records (2001–2010) of miniature- and toy-breed dogs with distal radial and ulnar fractures repaired with open reduction and internal fixation utilizing conventional plates were reviewed. The inclusion criteria were body weight of <7 kg, fracture located in the distal antebrachium (distal-to-total radial length ratio < 0.4) and follow-up radiographs available.
Results All 65 fractures healed without developing non-union, and had a successful return to normal function (median follow-up: 73 months; range: 2–149 months). Minor complication in seven fractures and major complication in four fractures were identified.
Clinical Significance Open reduction and conventional plate fixation of distal radial and ulnar fractures in miniature- and toy-breed dogs are effective means of fixation that result in normal functional outcome without developing non-union.
Prävention und Diagnostik multiresistenter Erreger
Authors: Scheithauer Simone , Kaase Martin 
Published: April 2018

AbstractPatients colonized or infected by multidrug-resistant bacteria (MDR) are entitled to the same medical treatment as other patients and infection control measures based on the current evidence are not in conflict with this aim. Recent studies indicate that the correct sampling technique is of utmost importance when screening for MRSA and usage of certain swabs might reduce the sensitivity considerably. Despite improvements in diagnostic strategies for direct MRSA detection by PCR, false positive results cannot be totally excluded. With regard to multidrug-resistant gramnegative bacteria differences between species should be emphasized to tailor infection control measures. E. g. easier transmissibility has been shown for K. pneumoniae compared to E. coli. Hospitals in Germany should strictly employ screening for carbapenemase-producing Enterobacterales as well as A. baumannii in all patients hospitalized abroad within the previous year. To avoid unnecessary social exclusion of MDR patients it must be emphasized that contact precautions are recommended for hospitals and not for long-time care facilities.
Genetic instrumental variable regression: Explaining socioeconomic and health outcomes in nonexperimental data
Authors: DiPrete Thomas A. , Burik Casper A. P. , Koellinger Philipp D. 
Published: April 2018

Significance
We propose genetic instrumental variable (GIV) regression—a method that controls for pleiotropic effects of genes on two variables. GIV regression is broadly applicable to study outcomes for which polygenic scores from large-scale genome-wide association studies are available. We explore the performance of GIV regression in the presence of pleiotropy across a range of scenarios and find that it yields more accurate estimates than alternative approaches such as ordinary least-squares regression or Mendelian randomization. When GIV regression is combined with proper controls for purely environmental sources of bias (e.g., using control variables and sibling fixed effects), it improves our understanding of the causal relationships between genetically correlated variables.
Status threat, not economic hardship, explains the 2016 presidential vote
Authors: Mutz Diana C. 
Published: April 2018

Significance
Support for Donald J. Trump in the 2016 election was widely attributed to citizens who were “left behind” economically. These claims were based on the strong cross-sectional relationship between Trump support and lacking a college education. Using a representative panel from 2012 to 2016, I find that change in financial wellbeing had little impact on candidate preference. Instead, changing preferences were related to changes in the party’s positions on issues related to American global dominance and the rise of a majority–minority America: issues that threaten white Americans’ sense of dominant group status. Results highlight the importance of looking beyond theories emphasizing changes in issue salience to better understand the meaning of election outcomes when public preferences and candidates’ positions are changing.
Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion
Authors: Bänfer Sebastian , Schneider Dominik , Dewes Jenny , Strauss Maximilian T. , Freibert Sven-A. , Heimerl Thomas , Maier Uwe G. , Elsässer Hans-Peter , Jungmann Ralf , Jacob Ralf 
Published: April 2018

Significance
Lacking a canonical signal peptide for translocation into the endoplasmic reticulum, galectin-3 (Gal3) is exported by unconventional secretion to play key roles in various cellular processes of fundamental importance. However, molecular details about the sorting components, the signals involved, and the underlying mechanism have remained elusive. Here, we identify a highly conserved tetrapeptide motif P(S/T)AP in the amino-terminal domain of Gal3 that directly interacts with the endosomal sorting complex required for transport (ESCRT) component Tsg101, resulting in exosomal release. This study thus defines a unique molecular mechanism based on a late domain-like motif known from many viruses by which an endogenous non-ESCRT protein is secreted in exosomes.
Cryptographic hashing using chaotic hydrodynamics
Authors: Gilpin William 
Published: April 2018

Significance
An essential component of digital communication is hashing, in which a complex piece of information (a document, video, etc.) is mathematically transformed into a unique signature that can later be used to identify the original piece of data. Here, we show that this process bears strong similarity to the chaotic behavior of certain types of flows observed when ordinary fluids mix, such as the stirring of dye into water. We use this analogy between rearranging information and stirring a fluid to construct a fluid-based hash function with comparable properties to traditional algorithms. Our work bears direct relevance to cases in which the physical representation of information affects its transmission, including in microfluidic self-assembly schemes and characterizing complex natural flows.
Iron promotes oxidative cell death caused by bisretinoids of retina
Authors: Ueda Keiko , Kim Hye Jin , Zhao Jin , Song Ying , Dunaief Joshua L. , Sparrow Janet R. 
Published: April 2018

Significance
Cells are subject to metabolic sources of oxidizing species and to the need to regulate Fe, a redox-active metal. Retinal pigment epithelial (RPE) cells have to contend with an additional, unique source of oxidative stress: photooxidative insult from bisretinoids that accumulate as lipofuscin. Here we report that Fe can interact with bisretinoids in RPE to promote cell damage. These findings inform disease processes in both Fe-related and bisretinoid-associated retinal degeneration. The link between Fe and bisretinoid oxidation also highlights opportunities for repurposed and combination therapies. This could include visual cycle inhibitors as a treatment for maculopathy associated with elevated retinal Fe, and Fe chelation to aid in suppressing the damaging effects of bisretinoids in juvenile and age-related macular degeneration.
Dome-headed, small-brained island mammal from the Late Cretaceous of Romania
Authors: Csiki-Sava Zoltán , Vremir Mátyás , Meng Jin , Brusatte Stephen L. , Norell Mark A. 
Published: April 2018

SignificanceIsland-living animals often differ from close relatives and mainland contemporaries in unusual ways, as best demonstrated by modern and Cenozoic mammals that are dwarfed or evolved aberrant anatomical features. However, it is unclear whether mammals from the Age of Dinosaurs followed this same pattern. We describe the fossil skeleton of a previously undiscovered peculiar Cretaceous island-dwelling mammal from Romania, which has a domed skull and one of the smallest brains (proportional to body size) of any mammal, living or extinct, but retains enlarged regions of the brain related to sensory processing. These unusual features were probably related to the species’ island habitat and demonstrate that the ability to adapt to island environments developed early in mammalian history.