bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise-induced bronchoconstriction: prevalence, pathophysiology, patient impact, diagnosis and management
Authors: Aggarwal Bhumika , Mulgirigama Aruni , Berend Norbert 
Published: August 2018

AbstractExercise-induced bronchoconstriction (EIB) can occur in individuals with and without asthma, and is prevalent among athletes of all levels. In patients with asthma, symptoms of EIB significantly increase the proportion reporting feelings of fearfulness, frustration, isolation, depression and embarrassment compared with those without symptoms. EIB can also prevent patients with asthma from participating in exercise and negatively impact their quality of life. Diagnosis of EIB is based on symptoms and spirometry or bronchial provocation tests; owing to low awareness of EIB and lack of simple, standardised diagnostic methods, under-diagnosis and mis-diagnosis of EIB are common. To improve the rates of diagnosis of EIB in primary care, validated and widely accepted symptom-based questionnaires are needed that can accurately replicate the current diagnostic standards (forced expiratory volume in 1 s reductions observed following exercise or bronchoprovocation challenge) in patients with and without asthma. In patients without asthma, EIB can be managed by various non-pharmacological methods and the use of pre-exercise short-acting β2-agonists (SABAs). In patients with asthma, EIB is often associated with poor asthma control but can also occur in individuals who have good control when not exercising. Inhaled corticosteroids are recommended when asthma control is suboptimal; however, pre-exercise SABAs are also widely used and are recommended as the first-line therapy. This review describes the burden, key features, diagnosis and current treatment approaches for EIB in patients with and without asthma and serves as a call to action for family physicians to be aware of EIB and consider it as a potential diagnosis.
Pressure-driven collapse of the relativistic electronic ground state in a honeycomb iridate
Authors: Clancy J. Patrick , Gretarsson Hlynur , Sears Jennifer A. , Singh Yogesh , Desgreniers Serge , Mehlawat Kavita , Layek Samar , Rozenberg Gregory Kh. , Ding Yang , Upton Mary H. , Casa Diego , Chen Ning , Im Junhyuck , Lee Yongjae , Yadav Ravi , Hozoi Liviu , Efremov Dmitri , van den Brink Jeroen , Kim Young-June 
Published: August 2018

AbstractHoneycomb-lattice quantum magnets with strong spin-orbit coupling are promising candidates for realizing a Kitaev quantum spin liquid. Although iridate materials such as Li2IrO3 and Na2IrO3 have been extensively investigated in this context, there is still considerable debate as to whether a localized relativistic wavefunction (Jeff = 1/2) provides a suitable description for the electronic ground state of these materials. To address this question, we have studied the evolution of the structural and electronic properties of α-Li2IrO3 as a function of applied hydrostatic pressure using a combination of x-ray diffraction and x-ray spectroscopy techniques. We observe striking changes even under the application of only small hydrostatic pressure (P ≤ 0.1 GPa): a distortion of the Ir honeycomb lattice (via X-ray diffraction), a dramatic decrease in the strength of spin-orbit coupling effects (via X-ray absorption spectroscopy), and a significant increase in non-cubic crystal electric field splitting (via resonant inelastic X-ray scattering). Our data indicate that α-Li2IrO3 is best described by a Jeff = 1/2 state at ambient pressure, but demonstrate that this state is extremely fragile and collapses under the influence of applied pressure.
Reduced occupancy of hedgehogs (Erinaceus europaeus) in rural England and Wales: The influence of habitat and an asymmetric intra-guild predator
Authors: Williams Ben M. , Baker Philip J. , Thomas Emily , Wilson Gavin , Judge Johanna , Yarnell Richard W. 
Published: August 2018

AbstractAgricultural landscapes have become increasingly intensively managed resulting in population declines across a broad range of taxa, including insectivores such as the hedgehog (Erinaceus europaeus). Hedgehog declines have also been attributed to an increase in the abundance of badgers (Meles meles), an intra-guild predator. The status of hedgehogs across the rural landscape at large spatial scales is, however, unknown. In this study, we used footprint tracking tunnels to conduct the first national survey of rural hedgehog populations in England and Wales. Single and two-species occupancy modelling was used to quantify hedgehog occupancy in relation to habitat and predator covariates. Hedgehog occupancy was low (22% nationally), and significantly negatively related to badger sett density and positively related to the built environment. Hedgehogs were also absent from 71% of sites that had no badger setts, indicating that large areas of the rural landscape are not occupied by hedgehogs. Our results provide the first field based national survey of hedgehogs, providing a robust baseline for future monitoring. Furthermore, the combined effects of increasing badger abundance and intensive agriculture may have provided a perfect storm for hedgehogs in rural Britain, leading to worryingly low levels of occupancy over large spatial scales.
Engineering of Primary Human B cells with CRISPR/Cas9 Targeted Nuclease
Authors: Johnson Matthew J. , Laoharawee Kanut , Lahr Walker S. , Webber Beau R. , Moriarity Branden S. 
Published: August 2018

AbstractB cells offer unique opportunities for gene therapy because of their ability to secrete large amounts of protein in the form of antibody and persist for the life of the organism as plasma cells. Here, we report optimized CRISPR/Cas9 based genome engineering of primary human B cells. Our procedure involves enrichment of CD19+ B cells from PBMCs followed by activation, expansion, and electroporation of CRISPR/Cas9 reagents. We are able expand total B cells in culture 10-fold and outgrow the IgD+ IgM+ CD27− naïve subset from 35% to over 80% of the culture. B cells are receptive to nucleic acid delivery via electroporation 3 days after stimulation, peaking at Day 7 post stimulation. We tested chemically modified sgRNAs and Alt-R gRNAs targeting CD19 with Cas9 mRNA or Cas9 protein. Using this system, we achieved genetic and protein knockout of CD19 at rates over 70%. Finally, we tested sgRNAs targeting the AAVS1 safe harbor site using Cas9 protein in combination with AAV6 to deliver donor template encoding a splice acceptor-EGFP cassette, which yielded site-specific integration frequencies up to 25%. The development of methods for genetically engineered B cells opens the door to a myriad of applications in basic research, antibody production, and cellular therapeutics.
Seasonal variability of diet and trophic level of the gelatinous predator Pelagia noctiluca (Scyphozoa)
Authors: Milisenda Giacomo , Rossi Sergio , Vizzini Salvatrice , Fuentes Veronica L. , Purcell Jennifer E. , Tilves Uxue , Piraino Stefano 
Published: August 2018

AbstractJellyfish populations apparently have increased in some places around the world and human problems with them also have increased. However, effects of jellyfish outbreaks in the ecosystems remain poorly understood and little or no information is available on their dietary preferences - in relation to the seasonal shifts of prey abundance - and on the potential variability of their impact on marine food webs. The mauve stinger Pelagia noctiluca (Forsskål, 1775) is by far the most common outbreak-forming scyphozoan jellyfish in the Western Mediterranean. By use of a combination of stomach contents, stable isotope (SI) and fatty acid (FA) analyses, we tested the hypothesis that changes in the seasonal dietary sources of P. noctiluca parallel changes in the FA and SI composition. Stomach content and biomarker analyses suggested that P. noctiluca is not a selective predator, cyclically shifting between carnivory and omnivory depending on the seasonality of accessible prey. The combination of SI and FA analyses highlighted the importance of microzooplankton as prey. Specific FA biomarkers showed that the diet of P. noctiluca changed seasonally depending on the availability of living plankton or suspended detritus. This study also revealed significant biochemical differences between jellyfish somatic and gonadal tissues, with total fatty acid concentration in the gonads up to ten times higher than in the somatic tissues.
Gingerol suppresses sepsis-induced acute kidney injury by modulating methylsulfonylmethane and dimethylamine production
Authors: Rodrigues Francisco Adelvane de Paulo , Santos Alan Diego da Conceição , de Medeiros Pedro Henrique Quintela Soares , Prata Mara de Moura Gondim , Santos Tailane Caína de Souza , da Silva James Almada , Brito Gerly Anne de Castro , dos Santos Armênio Aguiar , Silveira Edilberto Rocha , Lima Aldo Ângelo Moreira , Havt Alexandre 
Published: August 2018

AbstractAcute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1β, and transforming growth factor-β. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols.1H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals. Gingerols attenuated septic AKI by decreasing renal disturbances, oxidative stress, and inflammatory response through a mechanism possibly correlated with increased production of dimethylamine and methylsulfonylmethane.
Evidence Based Tailored Parotidectomy in Treating External Auditory Canal Carcinoma
Authors: Lee Jeon Mi , Joo Jin Woo , Kim Sung Huhn , Choi Jae Young , Moon In Seok 
Published: August 2018

AbstractCarcinoma of the external auditory canal (EAC) is a rare tumor and little information is available regarding parotid gland in surgically treating EAC carcinomas. This study aimed to investigate the mode of parotid involvement in EAC carcinoma through staging and histopathological analysis, and to establish surgical guidelines for the parotid gland management when there is no clinical evidence of parotid involvement. Sixty-five patients with EAC carcinoma who underwent temporal bone resection and any type of parotidectomy simultaneously were retrospectively reviewed. The rate of direct parotid invasion and parotid nodal involvement was analyzed according to the stage and histopathological findings. Among the 65 patients, 39 were confirmed to have squamous cell carcinoma (SCC) and 26 were confirmed to have adenoid cystic carcinoma (ACC). Direct parotid invasion occurred in 7 of 39 patients with SCC, only in the advanced stages, and in 15 of 26 patients with ACC, regardless of stage. Metastasis to the parotid node was noted in 6 patients with advanced-stage SCC, whereas no patient with ACC showed parotid nodal metastasis. For adequate tumor control with low risk of surgical complications, evidence based tailored parotidectomy should be applied. With no evidence of parotid involvement, an elective parotidectomy can be excluded in early SCC, whereas a total parotidectomy is recommended for advanced SCC. In ACC, basal resection of the parotid gland rather than a superficial or total parotidectomy should be performed at all disease stages.
Strong beaming of microwave surface waves with complementary split-ring-resonator arrays
Authors: Young Emily , Dockrey Joseph A. , Hibbins Alastair P. , Sambles J. Roy , Lawrence Christopher R. 
Published: August 2018

AbstractA thin copper sheet, populated by an array of complementary split ring resonators, presents strong surface wave beaming in orthogonal directions at two distinct frequencies. This simple array is significantly thinner than existing single frequency beaming surfaces. The observed beaming frequencies are associated with the two lowest resonance modes of the split rings, and the beams are subwavelength in width and approximately non-diverging. The beaming is analysed through comparison of near-field scans of the surface-normal electric fields with numerical simulations.
Keap1–MCM3 interaction is a potential coordinator of molecular machineries of antioxidant response and genomic DNA replication in metazoa
Authors: Tamberg Nele , Tahk Siret , Koit Sandra , Kristjuhan Kersti , Kasvandik Sergo , Kristjuhan Arnold , Ilves Ivar 
Published: August 2018

AbstractCoordination of DNA replication and cellular redox homeostasis mechanisms is essential for the sustained genome stability due to the sensitivity of replicating DNA to oxidation. However, substantial gaps remain in our knowledge of underlying molecular pathways. In this study, we characterise the interaction of Keap1, a central antioxidant response regulator in Metazoa, with the replicative helicase subunit protein MCM3. Our analysis suggests that structural determinants of the interaction of Keap1 with its critical downstream target - Nrf2 master transactivator of oxidative stress response genes – may have evolved in evolution to mimic the conserved helix-2-insert motif of MCM3. We show that this has led to a competition between MCM3 and Nrf2 proteins for Keap1 binding, and likely recruited MCM3 for the competitive binding dependent modulation of Keap1 controlled Nrf2 activities. We hypothesise that such mechanism could help to adjust the Keap1-Nrf2 antioxidant response pathway according to the proliferative and replicative status of the cell, with possible reciprocal implications also for the regulation of cellular functions of MCM3. Altogether this suggests about important role of Keap1-MCM3 interaction in the cross-talk between replisome and redox homeostasis machineries in metazoan cells.
Assessment of candidate elements for development of spectral photon-counting CT specific contrast agents
Authors: Kim Johoon , Bar-Ness Daniel , Si-Mohamed Salim , Coulon Philippe , Blevis Ira , Douek Philippe , Cormode David P. 
Published: August 2018

AbstractSpectral photon-counting computed tomography (SPCCT) is a rapidly emerging imaging modality that provides energy-dependent information on individual x-ray photons, leading to accurate material decomposition and simultaneous quantification of multiple contrast generating materials. Development of SPCCT-specific contrast agents is needed to overcome the issues with currently used iodinated contrast agents, such as difficulty in differentiation from calcified structures, and yield SPCCT’s full promise. In this study, the contrast generation of different elements is investigated using a prototype SPCCT scanner based on a modified clinical CT system and suitable elements for novel contrast agent development for SPCCT imaging are identified. Furthermore, nanoparticles were synthesized from tantalum as a proof of concept spectral photon-counting CT agent and tested for their in vitro cytotoxicity and contrast generation to provide insight into the feasibility of nanoparticle contrast agent development from these elements. We found that gadolinium, ytterbium and tantalum generate high contrast in spectral photon-counting CT imaging and may be suitable elements for contrast agent development for this modality. Our proof of concept results with tantalum-based nanoparticles underscore this conclusion due to their detectability with spectral photon-counting CT, as well as their biocompatibility.
Advancing micro-scale cooling by utilizing liquid-liquid phase separation
Authors: Xing Wei , Ullmann Amos , Brauner Neima , Plawsky Joel , Peles Yoav 
Published: August 2018

AbstractAchieving effective cooling within limited space is one of the key challenges for miniaturized product design. State-of-the-art micro-scale cooling enhancement techniques incorporate flow disturbances and boiling to reach high performance. However, these methods face the inherent issues of extra pressure drop, flow instability and dry-out that limits heat flux. Here we demonstrate that substantial cooling capability enhancement, up to 2.5 times, is realized by introducing the phase separation of a triethylamine (TEA)/water mixture at the micro-scale. Our experiments show that the enhancement behavior is closely related to the system’s initial composition, temperature, and flow conditions. Moreover, the mixture system exhibits reduced pressure drop after separation, which makes it more promising in serving practical applications. The results reveal new possibilities for liquid coolant selection and provide the experimental foundation for further research in this area.
Effectiveness of Z-score of log-transformed A Body Shape Index (LBSIZ) in predicting cardiovascular disease in Korea: the Korean Genome and Epidemiology Study
Authors: Moon Shinje , Park Jung Hwan , Ryu Ohk-Hyun , Chung Wankyo 
Published: August 2018

AbstractBody mass index (BMI) and waist circumference (WC) have limitations in stratifying cardio-metabolic risks. Another obesity measure, A Body Shape Index (ABSI), has been introduced but its applicability remains limited. To address this, the z-score of the log-transformed ABSI (LBSIZ) was recently developed. This study aimed to examine the ability of LBSIZ, compared to that of WC and BMI, to predict cardiovascular disease (CVD) risk. The study included 8,485 participants aged 40–69 years (mean age = 52.1) who were followed for 10 years and recruited from the Korean Genome and Epidemiology Study, a population-based cohort study. The area under the curve was 0.635 (95% confidence interval [CI]: 0.614–0.657) for LBSIZ, 0.604 (95%CI: 0.580–0.627) for WC, and 0.538 (95%CI: 0.514–0.562) for BMI. The AUC of the Framingham risk score (FRS) was 0.680 (95%CI: 0.659–0.701) in comparison. When we added LBSIZ to the model, the integrated AUC significantly improved from 0.680 to 0.692 (95%CI: 0.672–0.713; p value, 0.033), whereas there were no changes with BMI (AUC, 0.678; 95%CI: 0.656–0.699) or WC (AUC, 0.679; 95%CI: 0.658–0.701). In the multivariate Cox regression analysis, LBSIZ but not BMI or WC showed a significant hazard ratio of CVD event compared to 1st decile of each parameter. In the restricted cubic spline regression, BMI and WC showed an overall J-shaped relationship with CVD events whereas LBSIZ showed a linear relationship. LBSIZ is strongly associated with CVD risk and should predict CVD risk better than BMI and WC in the general population.
Sedimentary signals of recent faulting along an old strand of the San Andreas Fault, USA
Authors: Fosdick Julie C. , Blisniuk Kimberly 
Published: August 2018

AbstractContinental transform fault systems are fundamental features in plate tectonics. These complex systems often constitute multiple fault strands with variable spatio-temporal histories. Here, we re-evaluate the complex history of the San Andreas Fault along a restraining bend in southern California (USA). The Mission Creek strand of the San Andreas Fault is a major geologic structure with ~90 km of strike-slip displacement but is currently mapped as inactive. Quaternary deposits record sediment dispersal across the fault from upland catchments and yield key markers of the fault’s displacement history. Our sediment provenance analysis from the Deformed Gravels of Whitewater and the Cabezon Fanglomerate provide detrital geochronologic and lithologic signatures of potential sources within the San Bernardino Mountains and Little San Bernardino Mountains. Statistical analysis shows that the Cabezon Fanglomerate is most compatible with the Mission Creek and Morongo Valley Canyon sources, rather than the Whitewater Canyon as previously suggested. We propose that displacement since deposition ~500–100 ka across the Mission Creek strand has separated these deposits from their original sources. These findings challenge the current paradigm that the Mission Creek strand is inactive and suggest that the fault continues to be a primary structure in accommodating deformation along the Pacific-North American plate boundary.
Dual action of the Gαq-PLCβ-PI(4,5)P2 pathway on TRPC1/4 and TRPC1/5 heterotetramers
Authors: Myeong Jongyun , Ko Juyeon , Kwak Misun , Kim Jinsung , Woo Joohan , Ha Kotdaji , Hong Chansik , Yang Dongki , Kim Hyun Jin , Jeon Ju-Hong , So Insuk 
Published: August 2018

AbstractThe transient receptor potential canonical (TRPC) 1 channel is widely distributed in mammalian cells and is involved in many physiological processes. TRPC1 is primarily considered a regulatory subunit that forms heterotetrameric channels with either TRPC4 or TRPC5 subunits. Here, we suggest that the regulation of TRPC1/4 and TRPC1/5 heterotetrameric channels by the Gαq-PLCβ pathway is self-limited and dynamically mediated by Gαq and PI(4,5)P2. We provide evidence indicating that Gαq protein directly interacts with either TRPC4 or TRPC5 of the heterotetrameric channels to permit activation. Simultaneously, Gαq-coupled PLCβ activation leads to the breakdown of PI(4,5)P2, which inhibits activity of TRPC1/4 and 1/5 channels.
Targeting proinflammatory cytokines ameliorates calcifying phenotype conversion of vascular progenitors under uremic conditions in vitro
Authors: Hegner Björn , Schaub Theres , Janke Daniel , Zickler Daniel , Lange Claudia , Girndt Matthias , Jankowski Joachim , Schindler Ralf , Dragun Duska 
Published: August 2018

AbstractSevere vascular calcification develops almost invariably in chronic kidney patients posing a substantial risk to quality of life and survival. This unmet medical need demands identification of novel therapeutic modalities. We aimed to pinpoint components of the uremic microenvironment triggering differentiation of vascular progenitors to calcifying osteoblast-like cells. In an unbiased approach, assessing the individual potency of 63 uremic retention solutes to enhance calcific phenotype conversion of vascular progenitor cells, the pro-inflammatory cytokines IL-1β and TNF-α were identified as the strongest inducers followed by FGF-2, and PTH. Pharmacologic targeting of these molecules alone or in combination additively antagonized pro-calcifying properties of sera from uremic patients. Our findings stress the importance of pro-inflammatory cytokines above other characteristic components of the uremic microenvironment as key mediators of calcifying osteoblastic differentiation in vascular progenitors. Belonging to the group of “middle-sized molecules”, they are neither effectively removed by conventional dialysis nor influenced by established supportive therapies. Specific pharmacologic interventions or novel extracorporeal approaches may help preserve regenerative capacity and control vascular calcification due to uremic environment.