bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolite-cycled density-weighted concentric rings k-space trajectory (DW-CRT) enables high-resolution 1 H magnetic resonance spectroscopic imaging at 3-Tesla
Authors: Steel Adam , Chiew Mark , Jezzard Peter , Voets Natalie L. , Plaha Puneet , Thomas Michael Albert , Stagg Charlotte J. , Emir Uzay E. 
Published: May 2018

AbstractMagnetic resonance spectroscopic imaging (MRSI) is a promising technique in both experimental and clinical settings. However, to date, MRSI has been hampered by prohibitively long acquisition times and artifacts caused by subject motion and hardware-related frequency drift. In the present study, we demonstrate that density weighted concentric ring trajectory (DW-CRT) k-space sampling in combination with semi-LASER excitation and metabolite-cycling enables high-resolution MRSI data to be rapidly acquired at 3 Tesla. Single-slice full-intensity MRSI data (short echo time (TE) semi-LASER TE = 32 ms) were acquired from 6 healthy volunteers with an in-plane resolution of 5 × 5 mm in 13 min 30 sec using this approach. Using LCModel analysis, we found that the acquired spectra allowed for the mapping of total N-acetylaspartate (median Cramer-Rao Lower Bound [CRLB] = 3%), glutamate+glutamine (8%), and glutathione (13%). In addition, we demonstrate potential clinical utility of this technique by optimizing the TE to detect 2-hydroxyglutarate (long TE semi-LASER, TE = 110 ms), to produce relevant high-resolution metabolite maps of grade III IDH-mutant oligodendroglioma in a single patient. This study demonstrates the potential utility of MRSI in the clinical setting at 3 Tesla.
Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation
Authors: Chobanyan-Jürgens Kristine , Heusser Karsten , Duncker David , Veltmann Christian , May Marcus , Mehling Heidrun , Luft Friedrich C. , Schröder Christoph , Jordan Jens , Tank Jens 
Published: May 2018

AbstractClinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test influences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine. Subjects underwent combined head up tilt plus lower body negative pressure testing followed by rapid return to the supine position. In the current secondary analysis with predefined endpoints before data unblinding, continuous finger blood pressure and ECG recordings were analyzed by two experienced cardiac electrophysiologists and a physician, blinded for treatment assignment. The total atrial premature activity (referred to as atrial events) at baseline did not differ between treatments. After backwards tilting, atrial events were significantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. The model in addition to providing insight in the role of HCN4 in human atrial arrhythmogenesis may have utility in gauging potential atrial pro-arrhythmic drug properties.
AICAR inhibits NFκB DNA binding independently of AMPK to attenuate LPS-triggered inflammatory responses in human macrophages
Authors: Kirchner Johannes , Brüne Bernhard , Namgaladze Dmitry 
Published: May 2018

Abstract5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an established pharmacological activator of AMP-activated protein kinase (AMPK). Both, AICAR and AMPK were reported to attenuate inflammation. However, AICAR is known for many AMPK-independent effects, although the mechanisms remain incompletely understood. Here we report a potent suppression of lipopolysaccharide (LPS)-induced inflammatory gene expression by AICAR in primary human macrophages, which occurred independently of its conversion to AMPK-activating 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate. Although AICAR did not interfere with activation of cytosolic signalling cascades and nuclear translocation of nuclear factor - κB (NFκB) by LPS, it prevented the recruitment of NFκB and RNA polymerase II to target gene promoters. AICAR also inhibited signal transducer and activator of transcription 3 (STAT3)-dependent induction of interleukin (IL) IL-6 and IL-10 targets, while leaving STAT6 and HIF1α-dependent gene expression in IL-4 and dimethyloxalylgylcine-treated macrophages intact. This points to a transcription factor-specific mode of action. Attenuated gene expression correlated with impaired NFκB and STAT3, but not HIF-binding in electrophoretic mobility shift assays in vitro. Conclusively, AICAR interferes with DNA binding of NFκB and STAT3 to modulate inflammatory responses.
Genome-wide haplotype association analysis of primary biliary cholangitis risk in Japanese
Authors: Im Cindy , Sapkota Yadav , Moon Wonjong , Kawashima Minae , Nakamura Minoru , Tokunaga Katsushi , Yasui Yutaka 
Published: May 2018

AbstractPrimary biliary cholangitis (PBC) susceptibility loci have largely been discovered through single SNP association testing. In this study, we report genic haplotype patterns associated with PBC risk genome-wide in two Japanese cohorts. Among the 74 genic PBC risk haplotype candidates we detected with a novel methodological approach in a discovery cohort of 1,937 Japanese, nearly two-thirds were replicated (49 haplotypes, Bonferroni-corrected P < 6.8 × 10−4) in an independent Japanese cohort (N = 949). Along with corroborating known PBC-associated loci (TNFSF15, HLA-DRA), risk haplotypes may potentially model cis-interactions that regulate gene expression. For example, one replicated haplotype association (9q32–9q33.1, OR = 1.7, P = 3.0 × 10−21) consists of intergenic SNPs outside of the human leukocyte antigen (HLA) region that overlap regulatory histone mark peaks in liver and blood cells, and are significantly associated with TNFSF8 expression in whole blood. We also replicated a novel haplotype association involving non-HLA SNPs mapped to UMAD1 (7p21.3; OR = 15.2, P = 3.9 × 10−9) that overlap enhancer peaks in liver and memory Th cells. Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci.
Recording animal vocalizations from a UAV: bat echolocation during roost re-entry
Authors: Kloepper Laura N. , Kinniry Morgan 
Published: May 2018

AbstractUnmanned aerial vehicles (UAVs) are rising in popularity for wildlife monitoring, but direct recordings of animal vocalizations have not yet been accomplished, likely due to the noise generated by the UAV. Echolocating bats, especially Tadarida brasiliensis, are good candidates for UAV recording due to their high-speed, high-altitude flight. Here, we use a UAV to record the signals of bats during morning roost re-entry. We designed a UAV to block the noise of the propellers from the receiving microphone, and report on the characteristics of bioacoustic recordings from a UAV. We report the first published characteristics of echolocation signals from bats during group flight and cave re-entry. We found changes in inter-individual time-frequency shape, suggesting that bats may use differences in call design when sensing in complex groups. Furthermore, our first documented successful recordings of animals in their natural habitat demonstrate that UAVs can be important tools for bioacoustic monitoring, and we discuss the ethical considerations for such monitoring.
Searching for a compromise between biological and economic demands to protect vulnerable habitats
Authors: Pennino M. Grazia , Rufener Marie-Christine , Thomé-Souza Mario J. F. , Carvalho Adriana R. , Lopes Priscila F. M. , Sumaila U. Rashid 
Published: May 2018

AbstractIdentifying vulnerable habitats is necessary to designing and prioritizing efficient marine protected areas (MPAs) to sustain the renewal of living marine resources. However, vulnerable habitats rarely become MPAs due to conflicting interests such as fishing. We propose a spatial framework to help researchers and managers determine optimal conservation areas in a multi-species fishery, while also considering the economic relevance these species may have in a given society, even in data poor situations. We first set different ecological criteria (i.e. species resilience, vulnerability and trophic level) to identify optimal areas for conservation and restoration efforts, which was based on a traditional conservationist approach. We then identified the most economically relevant sites, where the bulk of fishery profits come from. We overlapped the ecologically and economically relevant areas using different thresholds. By ranking the level of overlap between the sites, representing different levels of conflicts between traditional conservation and fishing interests, we suggest alternatives that could increase fishers’ acceptance of protected areas. The introduction of some flexibility in the way conservation targets are established could contribute to reaching a middle ground where biological concerns are integrated with economic demands from the fishing sector.
RNase H-assisted RNA-primed rolling circle amplification for targeted RNA sequence detection
Authors: Takahashi Hirokazu , Ohkawachi Masahiko , Horio Kyohei , Kobori Toshiro , Aki Tsunehiro , Matsumura Yukihiko , Nakashimada Yutaka , Okamura Yoshiko 
Published: May 2018

AbstractRNA-primed rolling circle amplification (RPRCA) is a useful laboratory method for RNA detection; however, the detection of RNA is limited by the lack of information on 3′-terminal sequences. We uncovered that conventional RPRCA using pre-circularized probes could potentially detect the internal sequence of target RNA molecules in combination with RNase H. However, the specificity for mRNA detection was low, presumably due to non-specific hybridization of non-target RNA with the circular probe. To overcome this technical problem, we developed a method for detecting a sequence of interest in target RNA molecules via RNase H-assisted RPRCA using padlocked probes. When padlock probes are hybridized to the target RNA molecule, they are converted to the circular form by SplintR ligase. Subsequently, RNase H creates nick sites only in the hybridized RNA sequence, and single-stranded DNA is finally synthesized from the nick site by phi29 DNA polymerase. This method could specifically detect at least 10 fmol of the target RNA molecule without reverse transcription. Moreover, this method detected GFP mRNA present in 10 ng of total RNA isolated from Escherichia coli without background DNA amplification. Therefore, this method can potentially detect almost all types of RNA molecules without reverse transcription and reveal full-length sequence information.
A comprehensive study on microstructure and tensile behaviour of a selectively laser melted stainless steel
Authors: Qiu Chunlei , Kindi Mohammed Al , Aladawi Aiman Salim , Hatmi Issa Al 
Published: May 2018

Abstract316L stainless steel samples have been prepared by selective laser melting (SLM) using a pulsed laser mode and different laser powers and scanning patterns. The as-fabricated samples were found to be dominated by clusters of nano-sized γ needles or cells. TEM imaging shows that these needles contain a high population of dislocations while TEM-EDX analysis reveals high chemical homogeneity throughout the as-fabricated samples as evidenced by the fact that there is even no micro-/nano-segregation at interfaces between neighbouring γ needles. The good chemical homogeneity is attributed to the extremely high cooling rate after SLM (>106 °C/s) and the formation of Si- and Mn-oxides that distribute randomly in the current samples. The laser-processed samples show both superior strength and ductility as compared with conventionally manufactured counterparts. TEM examination on the deformed specimens reveals a significantly high density of dislocations and a great number of twinning within nano-needles, suggesting that the plastic deformation has been governed by both gliding of dislocations and twinning deformation, which is believed to be responsible for the simultaneous acquisition of superior strength and ductility. Finally, laser power shows a much more dominant role than laser scanning pattern in porosity and grain size development for the SLM-processed 316L stainless steel samples.
Co-cultivation of fungal-microalgal strains in biogas slurry and biogas purification under different initial CO2 concentrations
Authors: Zhou Kai , Zhang Yuejin , Jia Xiaobo 
Published: May 2018

AbstractThe effects of five different microalgae-fungi on nutrient removal and CO2 removal were investigated under three different CO2 contents (35%, 45% and 55%). The results showed that the highest nutrient and CO2 removal efficiency were found at 55% CO2 by cocultivation of different microalgae and fungi. The effect of different initial CO2 concentration on the removal of CO2 from microalgae was significant, and the order of CO2 removal efficiency was 55% (v/v) >45% (v/v) >35% (v/v). The best nutrient removal and biogas purification could be achieved by co-cultivation of C. vulgaris and G. lucidum with 55% initial CO2 content. The maximum mean COD, TN, TP and CO2 removal efficiency can reach 68.29%, 61.75%, 64.21% and 64.68%, respectively under this condition. All highest COD, TN, TP and CO2 removal efficiency were more than 85%. The analysis of energy consumption economic efficiency revealed that this strategy resulted in the highest economic efficiency. The results of this work can promote simultaneously biological purification of wastewater and biogas using microalgal-fungal symbiosis.
Risk factors for severe hypocalcemia after parathyroidectomy in dialysis patients with secondary hyperparathyroidism
Authors: Sun Xiaoliang , Zhang Xiaoqing , Lu Yao , Zhang Ling , Yang Meng 
Published: May 2018

AbstractSevere hypocalcemia (SH) is a common and serious complication in dialysis patients with secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX). The aim is to explore the risk predictors of SH in post-PTX dialysis ESRD patients with SHPT. 129 consecutive dialysis patients with SHPT underwent PTX were retrospectively reviewed. A total of 22 clinical parameters were included in the study. SH was defined as the minimum values of serum calcium lower than 1.875 mmol/L (7.5 mg/dL) after surgery. Univariate analysis showed that pruritus, lumbar X-ray changes of renal osteodystrophy, pre- and post-operative intact parathyroid hormone (iPTH), Calcium, alkaline phosphatase, and gland mass were significantly different between SH and non-SH groups. In the multivariate logistic regression model, the pre-operative serum iPTH, calcium, and pruritus were independent risk predictors of SH. AUCs for pre-operative serum iPTH, calcium and pruritus were 0.810, 0.714 and 0.591, respectively. Patients with higher level of pre-operative serum iPTH, lower level of serum calcium and with no/mild symptoms of pruritus are at greater risk of developing SH after PTX.
Ocular Counter Rolling in Astronauts After Short- and Long-Duration Spaceflight
Authors: Reschke Millard F. , Wood Scott J. , Clément Gilles 
Published: May 2018

AbstractOcular counter-rolling (OCR) is a reflex generated by the activation of the gravity sensors in the inner ear that stabilizes gaze and posture during head tilt. We compared the OCR measures that were obtained in 6 astronauts before, during, and after a spaceflight lasting 4–6 days with the OCR measures obtained from 6 astronauts before and after a spaceflight lasting 4–9 months. OCR in the short-duration fliers was measured using the afterimage method during head tilt at 15°, 30°, and 45°. OCR in the long-duration fliers was measured using video-oculography during whole body tilt at 25°. A control group of 7 subjects was used to compare OCR measures during head tilt and whole body tilt. No OCR occurred during head tilt in microgravity, and the response returned to normal within 2 hours of return from short-duration spaceflight. However, the amplitude of OCR was reduced for several days after return from long-duration spaceflight. This decrease in amplitude was not accompanied by changes in the asymmetry of OCR between right and left head tilt. These results indicate that the adaptation of otolith-driven reflexes to microgravity is a long-duration process.
Systemic Vascular Risk Factors for Multiple Retinal Nerve Fiber Layer Defects
Authors: Jung Kyoung In , Kim Seon Joo , Park Chan Kee 
Published: May 2018

AbstractMultiple retinal nerve fiber layer (RNFL) defects develop uncommonly, even though glaucomatous RNFL loss is typically observed as one RNFL defect in each quadrant. We investigated the risk factors associated with multiple RNFL defects to increase our understanding of the nature and pathogenesis of various RNFL defect patterns. Data from subjects with multiple RNFL defects (28 patients) and glaucoma patients without multiple RNFL defects (194 patients) were analyzed. The term “multiple RNFL defects” refers to three or more isolated defects separated by a comparatively normal area. Patients with multiple RNFL defects showed a higher prevalence of hypertension, end-stage renal disease, and cerebrovascular disease than those without multiple RNFL defects, both before and after propensity score matching for age and mean deviation (all P < 0.05). The number of patients with parafoveal visual field points depressed <5% on pattern deviation plots was higher in subjects with multiple RNFL defects than in those without multiple RNFL defects (P = 0.048). In conclusion, the presence of multiple RNFL defects had clinical relevance for systemic vascular risk factors and a higher risk of parafoveal scotoma. Clinicians should be aware of the possibility of concomitant systemic vascular disease when evaluating patients with multiple RNFL defects.
Assessing the Feasibility of Neutralizing Osteopontin with Various Therapeutic Antibody Modalities
Authors: Farrokhi Vahid , Chabot Jeffrey R. , Neubert Hendrik , Yang Zhiyong 
Published: May 2018

AbstractOsteopontin is a secreted glycophosphoprotein that is highly implicated in many physiological and pathological processes such as biomineralization, cell-mediated immunity, inflammation, fibrosis, cell survival, tumorigenesis and metastasis. Antibodies against osteopontin have been actively pursued as potential therapeutics for various diseases by pharmaceutical companies and academic laboratories. Many studies have demonstrated the efficacy of osteopontin inhibition in a variety of preclinical models of diseases such as rheumatoid arthritis, cancer, nonalcoholic steatohepatitis, but clinical utility has not yet been demonstrated. To evaluate the feasibility of osteopontin neutralization with antibodies in a clinical setting, we measured its physiological turnover rate in humans, a sensitive parameter required for mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Results from a stable isotope-labelled amino acid pulse-chase study in healthy human subjects followed by mass spectrometry showed that osteopontin undergoes very rapid turnover. PK/PD modeling and simulation of different theoretical scenarios reveal that achieving sufficient target coverage using antibodies can be very challenging mostly due to osteopontin’s fast turnover, as well as its relatively high plasma concentrations in human. Therapeutic antibodies against osteopontin would need to be engineered to have much extended PK than conventional antibodies, and be administered at high doses and with short dosing intervals.
Intraperitoneal administration of the anti-IL-23 antibody prevents the establishment of intestinal nematodes in mice
Authors: Gomez-Samblas M. , Bernal D. , Bolado-Ortiz A. , Vilchez S. , Bolás-Fernández F. , Espino A. M. , Trelis M. , Osuna A. 
Published: May 2018

AbstractPrevious studies have established that an increased Th-9 response creates a hostile environment for nematode parasites. Given that IL-23, a cytokine required for maintenance of the IL-17–secreting phenotype, has inhibitory effects on IL-9 production, we hypothesized that reducing circulating IL-23 by treatment with anti-IL-23 antibodies would reduce the establishment and development of parasitic intestinal nematodes. In this study, we show that animals treated with anti-IL-23 monoclonal antibodies showed a drastic reduction in the number of mouse pinworms (Aspiculuris tetraptera)recovered from the intestine (p < 0.001) at 23 days post-infection compared to the untreated animals. The cytokine levels in Peyer’s patches (PP) in treated and infected animals increase the expression of interleukins such as IL-25, IL-21, and IL-9, augmenting mucus production in the crypts, and boosting chemokines, such as OX40 and CCL20 in the mucosa. Our results suggest that the Th17/Th2 regulatory mechanism provoked by the administration of the anti-IL-23 antibody prevents the implantation of the intestinal nematode in mice. The diminished inflammatory IL-17 levels alter the Th9 environment perhaps as a consequence of IL-17 inhibiting IL-9 expression. These Th9 conditions may explain the successful treatment against Inflammatory Bowel Disease (IBD) both with antibodies against IL-23 or through parasitization with nematodes.
Protective Effects of Intraoperative Nerve Monitoring (IONM) for Recurrent Laryngeal Nerve Injury in Thyroidectomy: Meta-analysis
Authors: Bai Binglong , Chen Wuzhen 
Published: May 2018

AbstractRecurrent laryngeal nerve (RLN) injury is an intractable complication of thyroidectomy. Intraoperative nerve monitoring (IONM) was designed to prevent RLN injury. However, the results concerning the protective effect of IONM on RLN injury are still controversial. We searched all eligible databases from 1980 to 2017. Meta-analysis was performed to evaluate the effect of IONM on RLN injury. Sensitivity analysis was also conducted to check the stability of our results. There were 34 studies included in the analysis. Overall analysis found a significant decrease in total injury (RR = 0.68, 95%CI: 0.55 to 0.83), transient injury (RR = 0.71, 95%CI: 0.57 to 0.88), and permanent injury (RD = −0.0026, 95%CI: −0.0039 to −0.0012) with IONM. Subgroup analysis found IONM played a preventive role of total, transient and permanent injury in patients undergoing bilateral thyroidectomy. IONM also reduced the incidence of total and transient injury for malignancy cases. Operations with IONM were associated with fewer total and transient RLN injuries in operation volume < 300 NARs per year and fewer total and permanent RLN injuries in operation volume ≥ 300 NARs per year. The application of IONM could reduce the RLN injury of thyroidectomy. Particularly, we recommend routine IONM for use in bilateral operations and malignancy operations.