bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing health technology assessment in Kuwait: a qualitative study of perceived barriers and facilitators
Authors: Darawsheh Basshar , Germeni Evi 
Published: November 2019

AbstractObjectivesThis study sought to explore main barriers and facilitators to implementing health technology assessment (HTA) in Kuwait from the perspective of key stakeholders.MethodsSemi-structured qualitative interviews were conducted with ten key stakeholders: seven healthcare providers working at various departments of the Kuwaiti Ministry of Health (MOH), and three academics with substantial experience in teaching HTA or related fields. Interviews were conducted face-to-face, audio-recorded, and transcribed verbatim. Data were analyzed using an inductive thematic approach.ResultsParticipating stakeholders reported several factors that might act as a barrier to building HTA in Kuwait: minimal awareness of HTA, lack of institutional and human capacity, a fragmented healthcare system, poor communication between researchers and policy makers, the country's wealth, politics, as well as data quality, availability, and sharing. Institutionalizing HTA as a politically empowered body, enforcing its recommendation by law, and benefiting from neighboring countries' experiences were suggested as possible ways to move forward.ConclusionStudies exploring the unique challenges that high-income developing countries may face in implementing HTA are still scarce. The results of this study are consistent with evidence coming from other developing countries, while also suggesting that the abundance of financial resources in the country is a double-edged sword; it has the potential to facilitate the development of HTA capacity, but also hinders recognizing the need for it.
Heart failure biomarker levels correlate with invasive haemodynamics in pulmonary valve replacement
Authors: Zegelbone Phillip M. , Ringel Richard E. , Coulson John D. , Nies Melanie K. , Stabler Meagan E. , Brown Jeremiah R. , Everett Allen D. 
Published: November 2019

AbstractBackground:Although widely used in cardiology, relation of heart failure biomarkers to cardiac haemodynamics in patients with CHD (and in particular with pulmonary insufficiency undergoing pulmonary valve replacement) remains unclear. We hypothesised that the cardiac function biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity 2, and galectin-3 would have significant associations to right ventricular haemodynamic derangements.Methods:Consecutive patients ( n = 16) undergoing cardiac catheterisation for transcatheter pulmonary valve replacement were studied. NT-proBNP, soluble suppressor of tumorigenicity 2, and galectin-3 levels were measured using a multiplex enzyme-linked immunosorbent assay from a pre-intervention blood sample obtained after sheath placement. Spearman correlation was used to identify significant correlations (p ≤ 0.05) of biomarkers with baseline cardiac haemodynamics. Cardiac MRI data (indexed right ventricular and left ventricular end-diastolic volumes and ejection fraction) prior to device placement were also compared to biomarker levels.Results:NT-proBNP and soluble suppressor of tumorigenicity 2 were significantly correlated (p < 0.01) with baseline mean right atrial pressure and right ventricular end-diastolic pressure. Only NT-proBNP was significantly correlated with age. Galectin-3 did not have significant associations in this cohort. Cardiac MRI measures of right ventricular function and volume were not correlated to biomarker levels or right heart haemodynamics.Conclusions:NT-proBNP and soluble suppressor of tumorigenicity 2, biomarkers of myocardial strain, significantly correlated to invasive pressure haemodynamics in transcatheter pulmonary valve replacement patients. Serial determination of soluble suppressor of tumorigenicity 2, as it was not associated with age, may be superior to serial measurement of NT-proBNP as an indicator for timing of pulmonary valve replacement.
A New Method for Distinguishing Unactivated Particles in Cloud Condensation Nuclei Measurements: Implications for Aerosol Indirect Effect Evaluation
Authors: Wang Yuan , Niu Shengjie , Lv Jingjing , Lu Chunsong , Xu Xiaoqi , Wang Yuying , Ding Jie , Zhang Hongwei , Wang Tianshu , Kang Boshi 
Published: November 2019

AbstractAn ongoing challenge for cloud condensation nuclei (CCN) measurements is the inclusion of unactivated particles, which affects droplet activation parameterizations and aerosol indirect effects in models. For the first time, a reciprocal relationship between the critical diameter and critical supersaturation of activated droplets from the κ‐Köhler theory is derived to accurately count unactivated particles in CCN measurements. We conducted 4‐day continuous observations to simultaneously measure the number concentration of CCN (NCCN) and aerosol. The results show that as supersaturation (SS) decreases from 0.186% at 25 °C, the proportion of the unactivated particles in the CCN measurements increases, reaching 88% at SS of 0.07%. Owing to the NCCN overestimation caused by NCCN‐SS parameterizations with uncorrected NCCN, there is significant overestimation of aerosol indirect effects, especially under low SS conditions. After removing unactivated particles, NCCN‐SS parameterizations are adjusted accordingly, which can improve simulations of aerosol‐cloud‐radiation interactions in models.
Paleoenvironmental Changes at ODP Site 702 (South Atlantic): Anatomy of the Middle Eocene Climatic Optimum
Authors: Rivero‐Cuesta L. , Westerhold T. , Agnini C. , Dallanave E. , Wilkens R. H. , Alegret L. 
Published: November 2019

AbstractThe Middle Eocene Climatic Optimum (MECO) was an unusual global warming event that interrupted the long‐term Eocene cooling trend ca. 40 Ma. Here we present new high‐resolution bulk and benthic isotope records from South Atlantic ODP Site 702 to characterize the MECO at a high latitude setting. The MECO event, including early and peak warming as well as recovery to background levels, had an estimated ~300 Kyr duration (~40.51 to ~40.21 Ma). Cross‐plots (δ18O vs. δ13C) suggest that the mechanisms driving coupled changes in O and C isotope values across the MECO were weaker or absent before the event. The paleoecological response has been evaluated by quantitative analysis of calcareous nannofossils and benthic foraminifera assemblages. We document a shift in the biogeographical distribution of warm and temperate calcareous nannoplankton taxa, which migrated toward higher latitudes due to increased temperatures during the MECO. Conversely, changes in the organic matter flux to the seafloor appear to have controlled benthic foraminifera dynamics at Site 702. Benthic phytodetritus exploiting taxa increased in abundance coinciding with a positive δ13C excursion, ~150 Kyr before the start of the δ18O negative excursion that marks the start of MECO warming. Our data suggest that paleoecological disturbance in the deep sea predates MECO δ18O excursion and that it was driven by changes in the type and/or amount of organic matter reaching the seafloor rather than by increased temperature.
Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment
Authors: Caye Aurélie , Rouault-Pierre Kevin , Strullu Marion , Lainey Elodie , Abarrategi Ander , Fenneteau Odile , Arfeuille Chloé , Osman Jennifer , Cassinat Bruno , Pereira Sabrina , Anjos-Afonso Fernando , Currie Erin , Ariza-McNaughton Linda , Barlogis Vincent , Dalle Jean-Hugues , Baruchel André , Chomienne Christine , Cavé Hélène , Bonnet Dominique 
Published: November 2019

Abstract
Juvenile myelomonocytic leukemia (JMML) is a rare aggressive myelodysplastic/myeloproliferative neoplasm of early childhood, initiated by RAS-activating mutations. Genomic analyses have recently described JMML mutational landscape; however, the nature of JMML-propagating cells (JMML-PCs) and the clonal architecture of the disease remained until now elusive. Combining genomic (exome, RNA-seq), Colony forming assay and xenograft studies, we detect the presence of JMML-PCs that faithfully reproduce JMML features including the complex/nonlinear organization of dominant/minor clones, both at diagnosis and relapse. Further integrated analysis also reveals that although the mutations are acquired in hematopoietic stem cells, JMML-PCs are not always restricted to this compartment, highlighting the heterogeneity of the disease during the initiation steps. We show that the hematopoietic stem/progenitor cell phenotype is globally maintained in JMML despite overexpression of CD90/THY-1 in a subset of patients. This study shed new lights into the ontogeny of JMML, and the identity of JMML-PCs, and provides robust models to monitor the disease and test novel therapeutic approaches.
Protrudin modulates seizure activity through GABAA receptor regulation
Authors: Lu Xi , Yang Yong , Zhou Ruijiao , Li Yun , Yang Yi , Wang Xuefeng 
Published: November 2019

AbstractEpilepsy is a serious neurological disease characterized by recurrent unprovoked seizures. The exact etiology of epilepsy is not fully understood. Protrudin is a neural membrane protein and is found to be mutated in hereditary spastic paraplegia that characterized by symptoms like seizures. Here, we reported that the expression of protrudin was downregulated in the temporal neocortex of epileptic patients and in the hippocampus and cortex of pentylenetetrazol and kainic acid-kindled epileptic mouse models. Behavioral and electroencephalogram analyses indicated that overexpression of protrudin in the mouse hippocampus increased the latency of the seizure and decreased the frequency and duration of seizure activity. Using whole-cell patch clamp, overexpression of protrudin in the mouse hippocampus resulted in a reduction in action potential frequency and an increase in gamma-aminobutyric acid (GABA)ergic inhibitory current amplitude. Moreover, western blot analysis showed that the membrane expression of the GABA A receptor β2/3 subunit was also upregulated after protrudin overexpression, and coimmunoprecipitation resulted in a protein–protein interaction between protrudin, GABAARβ2/3 and GABA receptor-associated protein in the hippocampus of epileptic mice. These findings suggest that protrudin probably inhibits the occurrence and development of epilepsy through the regulation of GABAA receptor-mediated synaptic transmission, and protrudin might be a promising target for the treatment of epilepsy.
The preponderance of nonsynonymous A-to-I RNA editing in coleoids is nonadaptive
Authors: Jiang Daohan , Zhang Jianzhi 
Published: November 2019

AbstractA-to-I editing enzymatically converts the base adenosine (A) in RNA molecules to inosine (I), which is recognized as guanine (G) in translation. Exceptionally abundant A-to-I editing was recently discovered in the neural tissues of coleoids (octopuses, squids, and cuttlefishes), with a greater fraction of nonsynonymous sites than synonymous sites subject to high levels of editing. Although this phenomenon is thought to indicate widespread adaptive editing, its potential advantage is unknown. Here we propose an alternative, nonadaptive explanation. Specifically, increasing the cellular editing activity permits some otherwise harmful G-to-A nonsynonymous substitutions, because the As are edited to Is at sufficiently high levels. These high editing levels are constrained upon substitutions, resulting in the predominance of nonsynonymous editing at highly edited sites. Our evidence for this explanation suggests that the prevalent nonsynonymous editing in coleoids is generally nonadaptive, as in species with much lower editing activities.
Cytoplasmic glycoengineering enables biosynthesis of nanoscale glycoprotein assemblies
Authors: Tytgat Hanne L. P. , Lin Chia-wei , Levasseur Mikail D. , Tomek Markus B. , Rutschmann Christoph , Mock Jacqueline , Liebscher Nora , Terasaka Naohiro , Azuma Yusuke , Wetter Michael , Bachmann Martin F. , Hilvert Donald , Aebi Markus , Keys Timothy G. 
Published: November 2019

AbstractGlycosylation of proteins profoundly impacts their physical and biological properties. Yet our ability to engineer novel glycoprotein structures remains limited. Established bacterial glycoengineering platforms require secretion of the acceptor protein to the periplasmic space and preassembly of the oligosaccharide substrate as a lipid-linked precursor, limiting access to protein and glycan substrates respectively. Here, we circumvent these bottlenecks by developing a facile glycoengineering platform that operates in the bacterial cytoplasm. The Glycoli platform leverages a recently discovered site-specific polypeptide glycosyltransferase together with variable glycosyltransferase modules to synthesize defined glycans, of bacterial or mammalian origin, directly onto recombinant proteins in the E. coli cytoplasm. We exploit the cytoplasmic localization of this glycoengineering platform to generate a variety of multivalent glycostructures, including self-assembling nanomaterials bearing hundreds of copies of the glycan epitope. This work establishes cytoplasmic glycoengineering as a powerful platform for producing glycoprotein structures with diverse future biomedical applications.
Engineering dendritic cell vaccines to improve cancer immunotherapy
Authors: Perez Caleb R. , De Palma Michele 
Published: November 2019

AbstractAt the interface between the innate and adaptive immune system, dendritic cells (DCs) play key roles in tumour immunity and hold a hitherto unrealized potential for cancer immunotherapy. Here we review the role of distinct DC subsets in the tumour microenvironment, with special emphasis on conventional type 1 DCs. Integrating new knowledge of DC biology and advancements in cell engineering, we provide a blueprint for the rational design of optimized DC vaccines for personalized cancer medicine.
Impact of transport electrification on critical metal sustainability with a focus on the heavy-duty segment
Authors: Hao Han , Geng Yong , Tate James E. , Liu Feiqi , Chen Kangda , Sun Xin , Liu Zongwei , Zhao Fuquan 
Published: November 2019

AbstractThe majority of transport electrification studies, examining the demand and sustainability of critical metals, have focused on light-duty vehicles. Heavy-duty vehicles have often been excluded from the research scope due to their smaller vehicle stock and slower pace of electrification. This study fills this research gap by evaluating the lithium resource impacts from electrification of the heavy-duty segment at the global level. Our results show that a mass electrification of the heavy-duty segment on top of the light-duty segment would substantially increase the lithium demand and impose further strain on the global lithium supply. The significant impact is attributed to the large single-vehicle battery capacity required by heavy-duty vehicles and the expected battery replacement needed within the lifetime of heavy-duty vehicles. We suggest that the ambition of mass electrification in the heavy-duty segment should be treated with cautions for both policy makers and entrepreneurs.
Release factor-dependent ribosome rescue by BrfA in the Gram-positive bacterium Bacillus subtilis
Authors: Shimokawa-Chiba Naomi , Müller Claudia , Fujiwara Keigo , Beckert Bertrand , Ito Koreaki , Wilson Daniel N. , Chiba Shinobu 
Published: November 2019

AbstractRescue of the ribosomes from dead-end translation complexes, such as those on truncated (non-stop) mRNA, is essential for the cell. Whereas bacteria use trans-translation for ribosome rescue, some Gram-negative species possess alternative and release factor (RF)-dependent rescue factors, which enable an RF to catalyze stop-codon-independent polypeptide release. We now discover that the Gram-positive Bacillus subtilis has an evolutionarily distinct ribosome rescue factor named BrfA. Genetic analysis shows that B. subtilis requires the function of either trans-translation or BrfA for growth, even in the absence of proteotoxic stresses. Biochemical and cryo-electron microscopy (cryo-EM) characterization demonstrates that BrfA binds to non-stop stalled ribosomes, recruits homologous RF2, but not RF1, and induces its transition into an open active conformation. Although BrfA is distinct from E. coli ArfA, they use convergent strategies in terms of mode of action and expression regulation, indicating that many bacteria may have evolved as yet unidentified ribosome rescue systems.
Applications of the European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS)
Authors: Balestrino Roberta , Hurtado-Gonzalez Carlos Alberto , Stocchi Fabrizio , Radicati Fabiana Giada , Chaudhuri K. Ray , Rodriguez-Blazquez Carmen , Martinez-Martin Pablo ,   The PDCS European Study Group, Adarmes Astrid D. , Méndez-del-Barrio Carlota , Ariadne Vakirli , Aschermann Zsuzsanna , Juhász Annamária , Harmat Márk , Bostantjopoulou Sevasti , Corbo Massimo , Grassi Andrea , Dellaporta Dionysia , Falup-Pecurariu Cristian , Diaconu Ştefania , Giagkou Nikolaos , Guekht Alla , Popov Georgy , Gurevich Tanya , Johansson Anders , Sundgren Mathias , Kefalopoulou Zinovia , Ellul John , Kostić Vladimir S. , Kovacs Norbert , Marti Maria J. , Planelles Lluis , Migirov-Sanderovich Angel , Ezra Adi , Minar Michal , Mir Pablo , Jan Necpal  , Popovici Maria , Simitsi Athima , Stefanis Leonidas , Simu Mihaela , Rosca Cecilia , Skorvanek Matej , Stefani Alessandro , Cerroni Rocco , Stamelou Maria , Tsolaki Magda , Vuletic Vladimira , Katsarou Zoe 
Published: November 2019

AbstractThis study was addressed to determine the presence of Parkinson disease (PD) manifestations, their distribution according to motor subtypes, and the relationships with health-related quality of life (QoL) using the recently validated European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS). Frequency of symptoms was determined by the scores of items (present if >0). Using ROC analysis and Youden method, MDS-UPDRS motor subtypes were projected on the PDCS to achieve a comparable classification based on the PDCS scores. The same method was used to estimate severity levels from other measures in the study. The association between the PDCS and QoL (PDQ-39) was analyzed by correlation and multiple linear regression. The sample consisted of 776 PD patients. We found that the frequency of PD manifestations with PDCS and MDS-UPDRS were overlapping, the average difference between scales being 5.5% only. Using the MDS-UPDRS subtyping, 215 patients (27.7%) were assigned as Tremor Dominant (TD), 60 (7.7%) Indeterminate, and 501 (64.6%) Postural Instability and Gait Difficulty (PIGD) in this cohort. With this classification as criterion, the analogous PDCS-based ratio provided these cut-off values: TD subtype, ≥1.06; Indeterminate, <1.06 but >0.65; and PIGD, <0.65. The agreement between the two scales on this classification was substantial (87.6%; kappa = 0.69). PDCS total score cut-offs for PD severity were: 23/24 for mild/moderate and 41/42 for moderate/severe. Moderate to high correlations (r = 0.35–0.80) between PDCS and PDQ-39 were obtained, and the four PDCS domains showed a significant independent influence on QoL. The conclusions are: (1) the PDCS assessed the frequency of PD symptoms analogous to the MDS-UPDRS; (2) motor subtypes and severity levels can be determined with the PDCS; (3) a significant association between PDCS and QoL scores exists.
IL-23 induces regulatory T cell plasticity with implications for inflammatory skin diseases
Authors: Kannan Arun K. , Su Zhi , Gauvin Donna M. , Paulsboe Stephanie E. , Duggan Ryan , Lasko Loren M. , Honore Prisca , Kort Michael E. , McGaraughty Steve P. , Scott Victoria E. , Gauld Stephen B. 
Published: November 2019

AbstractFoxp3+ regulatory T cells (Tregs) represent a major fraction of skin resident T cells. Although normally protective, Tregs have been shown to produce pro-inflammatory cytokines in human diseases, including psoriasis. A significant hurdle in the Treg field has been the identification, or development, of model systems to study this Treg plasticity. To overcome this gap, we analyzed skin resident Tregs in a mouse model of IL-23 mediated psoriasiform dermatitis. Our results demonstrate that IL-23 drove the accumulation of Tregs; including a subpopulation that co-expressed RORγt and produced IL-17A. Genesis of this population was attenuated by a RORγt inverse agonist compound and clinically relevant therapeutics. In vitro, IL-23 drove the generation of CD4+Foxp3+RORγt+IL-17A+ cells from Treg cells. Collectively, our data shows that IL-23 drives Treg plasticity by inducing a population of CD4+Foxp3+RORγt+IL-17A+ cells that could play a role in the disease pathogenesis. Through this work, we define an in vitro system and a pre-clinical in vivo mouse model that can be used to further study Treg homeostasis and plasticity in the context of psoriasis.
Projected impacts of climate change on functional diversity of frugivorous birds along a tropical elevational gradient
Authors: Bender Irene M. A. , Kissling W. Daniel , Böhning-Gaese Katrin , Hensen Isabell , Kühn Ingolf , Nowak Larissa , Töpfer Till , Wiegand Thorsten , Dehling D. Matthias , Schleuning Matthias 
Published: November 2019

AbstractClimate change forces many species to move their ranges to higher latitudes or elevations. Resulting immigration or emigration of species might lead to functional changes,e.g., in the trait distribution and composition of ecological assemblages. Here, we combined approaches from biogeography (species distribution models; SDMs) and community ecology (functional diversity) to investigate potential effects of climate-driven range changes on frugivorous bird assemblages along a 3000 m elevational gradient in the tropical Andes. We used SDMs to model current and projected future occurrence probabilities of frugivorous bird species from the lowlands to the tree line. SDM-derived probabilities of occurrence were combined with traits relevant for seed dispersal of fleshy-fruited plants to calculate functional dispersion (FDis; a measure of functional diversity) for current and future bird assemblages. Comparisons of FDis between current and projected future assemblages showed consistent results across four dispersal scenarios, five climate models and two representative concentration pathways. Projections indicated a decrease of FDis in the lowlands, an increase of FDis at lower mid-elevations and little changes at high elevations. This suggests that functional dispersion responds differently to global warming at different elevational levels, likely modifying avian seed dispersal functions and plant regeneration in forest ecosystems along tropical mountains.
Organic Molecule Detection Based on SERS in Microfluidics
Authors: Zhang Xin , Zhang Haiyan , Yan Sheng , Zeng Zugang , Huang Anshou , Liu Anping , Yuan Yuan , Huang Yingzhou 
Published: November 2019

AbstractSensitive in situ detection of organic molecules is highly demanded in environmental monitoring. In this work, the surface enhanced Raman spectroscopy (SERS) is adopted in microfluidics to detect the organic molecules with high accuracy and high sensitivity. Here the SERS substrate in microchannel consists of Ag nanoparticles synthesized by chemical reduction. The data indicates the fabrication conditions have great influence on the sizes and distributions of Ag nanoparticles, which play an important role on the SERS enhancement. This result is further confirmed by the simulation of electromagnetic field distributions based on finite difference time domain (FDTD) method. Furthermore, the SERS spectra of organic molecule (methylene blue) obtained in this plasmonic microfluidic system exhibit good reproducibility with high sensitivity. By a combination of SERS and microfluidics, our work not only explores the research field of plasmonics but also has broad application prospects in environmental monitoring.