bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innate local response and tissue recovery following application of high density microarray patches to human skin
Authors: Muller David A. , Henricson Joakim , Baker S. Ben , Togö Totte , Jayashi Flores Cesar M. , Lemaire Pierre A. , Forster Angus , Anderson Chris D. 
Published: October 2020

AbstractThe development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. Microarray patches (MAP) reduce risks of needle stick injury, do not require reconstitution and have the potential to enhance immune responses using a fractional vaccine dose. To date, the majority of research has focused on vaccine delivery with little characterisation of local skin response and recovery. Here we study in detail the immediate local skin response and recovery of the skin post high density MAP application in 12 individuals receiving 3 MAPs randomly assigned to the forearm and upper arm. Responses were characterised by clinical scoring, dermatoscopy, evaporimetry and tissue viability imaging (TiVi). MAP application resulted in punctures in the epidermis, a significant transepidermal water loss (TEWL), the peak TEWL being concomitant with peak erythema responses visualised by TiVi. TEWL and TiVi responses reduced over time, with TEWL returning to baseline by 48 h and erythema fading over the course of a 7 day period. As MAPs for vaccination move into larger clinical studies more variation of individual subject phenotypic or disease propensity will be encountered which will require consideration both in regard to reliability of dose delivery and degree of inherent skin response.
A proof-of principal study using phase-contrast imaging for the detection of large airway pathologies after lung transplantation
Authors: Umkehrer Stephan , Morrone Carmela , Dinkel Julien , Aigner Laura , Reiser Maximilian F. , Herzen Julia , Yildirim Ali Ö. , Pfeiffer Franz , Hellbach Katharina 
Published: October 2020

AbstractIn this study we aim to evaluate the assessment of bronchial pathologies in a murine model of lung transplantation with grating-based X-ray interferometry in vivo. Imaging was performed using a dedicated grating-based small-animal X-ray dark-field and phase-contrast scanner. While the contrast modality of the dark-field signal already showed several promising applications for diagnosing various types of pulmonary diseases, the phase-shifting contrast mechanism of the phase contrast has not yet been evaluated in vivo. For this purpose, qualitative analysis of phase-contrast images was performed and revealed pathologies due to previous lung transplantation, such as unilateral bronchial stenosis or bronchial truncation. Dependent lung parenchyma showed a strong loss in dark-field and absorption signal intensity, possibly caused by several post transplantational pathologies such as atelectasis, pleural effusion, or pulmonary infiltrates. With this study, we are able to show that bronchial pathologies can be visualized in vivo using conventional X-ray imaging when phase-contrast information is analysed. Absorption and dark-field images can be used to quantify the severity of lack of ventilation in the affected lung.
Plane photoacoustic wave generation in liquid water using irradiation of terahertz pulses
Authors: Tsubouchi Masaaki , Hoshina Hiromichi , Nagai Masaya , Isoyama Goro 
Published: October 2020

AbstractWe demonstrate photoacoustic wave propagation with a plane wavefront in liquid water using a terahertz (THz) laser pulse. The THz light can effectively generate the photoacoustic wave in water because of strong absorption via a stretching vibration mode of the hydrogen bonding network. The excitation of a large-area water surface irradiated by loosely focused THz light produces a plane photoacoustic wave. This is in contrast with conventional methods using absorbers or plasma generation using near-infrared laser light. The photoacoustic wave generation and plane wave propagation are observed using a system with a THz free-electron laser and shadowgraph imaging. The plane photoacoustic wave is generated by incident THz light with a small radiant exposure of < 1 mJ/cm2 and delivered 600 times deeper than the penetration depth of THz light for water. The THz-light-induced plane photoacoustic wave offers great advantages to non-invasive operations for industrial and biological applications as demonstrated in our previous report (Yamazaki et al. in Sci Rep 10:9008, 2020).
Synergistic association of high-sensitivity C-reactive protein and body mass index with insulin resistance in non-diabetic adults
Authors: Kim Gyu Ri , Choi Dong-Woo , Nam Chung Mo , Jang Sung-In , Park Eun-Cheol 
Published: October 2020

AbstractEpidemiological evidence has indicated that inflammatory markers and obesity are strongly correlated with insulin resistance (IR). However, there is a paucity of studies assessing the complex interaction between elevated hs-CRP and body mass index (BMI), particularly among Asians. This study investigated the additive interaction between hs-CRP and BMI on IR, using cross-sectional data from the 7th Korea National Health and Nutrition Examination Survey (2016–2018). A total of 5706 men and 6707 women aged 20 years or older were evaluated, and a multiple logistic regression analysis was used to assess the association of serum hs-CRP and BMI with IR, as measured by the triglyceride-glucose index (TyG index). Sex-specific median values were used to dichotomise the continuous TyG index variable into insulin-sensitive and IR categories. Biological interaction was evaluated using the Relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). The joint effects of high hs-CRP and overweight/obesity on IR were greater than would be expected from the effects of the individual exposures alone. Relative to those with low hs-CRP and BMI < 23, having both exposures was related to increased IR with an adjusted OR of 2.97 (95% CI 2.50–3.52) in men and 3.08 (95% CI 2.67–3.56) in women with significant additive interactions. These findings demonstrate that IR prevention strategies that reduce both systematic inflammation and BMI may exceed the expected benefits based on targeting these risk factors separately.
Conservation of vegetable genetic diversity in Transylvania-Romania
Authors: Maxim Aurel , Străjeru Silvia , Albu Cristian , Sandor Mignon , Mihalescu Lucia , Pauliuc Sînziana Ecaterina 
Published: October 2020

AbstractThe conservation of plant and animal genetic heritage is not a purpose in itself, but it represents the sine qua non condition for practicing a sustainable agriculture and to ensure nutrition and food security on long-term. Our research focused on identifying the areas with the richest genetic diversity of vegetables in Transylvania, Romania, as well as the main vulnerabilities related to seed production for the local vegetables. Our trips included 210 locations where 338 small seed producers were surveyed. The questionnaire method with fixed questions and undisguised multiple-choices was used. A number of 316 out of 565 cultivars taken into study have been proven to be authentic and valuable landraces, meaning 55.9%. In Transylvania, the richest genetic diversity of vegetables is found in the counties of Maramures, Bistrita-Nasaud and Hunedoara—where the cooperativization was lower before the year 1989. The most important risk in losing vegetable landraces is the old age of small growers (68.4%). However, it is encouraging that many NGOs interested in identifying, conserving and promoting local varieties have emerged in the last decade. Therefore, so-called "seed houses" have been set up to facilitate the exchange of seeds, and on the other hand, the expansion of organic farming requires local varieties that are better adapted to harsh environmental conditions.
The Fuchs corneal dystrophy-associated CTG repeat expansion in the TCF4 gene affects transcription from its alternative promoters
Authors: Sirp Alex , Leite Kristian , Tuvikene Jürgen , Nurm Kaja , Sepp Mari , Timmusk Tõnis 
Published: October 2020

AbstractThe CTG trinucleotide repeat (TNR) expansion in Transcription factor 4 (TCF4) intron 3 is the main cause of Fuchs’ endothelial corneal dystrophy (FECD) and may confer an increased risk of developing bipolar disorder (BD). Usage of alternative 5′ exons for transcribing the human TCF4 gene results in numerous TCF4 transcripts which encode for at least 18 N-terminally different protein isoforms that vary in their function and transactivation capability. Here we studied the TCF4 region containing the CTG TNR and characterized the transcription initiation sites of the nearby downstream 5′ exons 4a, 4b and 4c. We demonstrate that these exons are linked to alternative promoters and show that the CTG TNR expansion decreases the activity of the nearby downstream TCF4 promoters in primary cultured neurons. We confirm this finding using two RNA sequencing (RNA-seq) datasets of corneal endothelium from FECD patients with expanded CTG TNR in the TCF4 gene. Furthermore, we report an increase in the expression of various other TCF4 transcripts in FECD, possibly indicating a compensatory mechanism. We conclude that the CTG TNR affects TCF4 expression in a transcript-specific manner both in neurons and in the cornea.
Drivers of tropical soil invertebrate community composition and richness across tropical secondary forests using DNA metasystematics
Authors: McGee Katie M. , Porter Teresita M. , Wright Michael , Hajibabaei Mehrdad 
Published: October 2020

AbstractTropical forests are fundamental ecosystems, essential for providing terrestrial primary productivity, global nutrient cycling, and biodiversity. Despite their importance, tropical forests are currently threatened by deforestation and associated activities. Moreover, tropical regions are now mostly represented by secondary forest regrowth, with half of the remaining tropical forests as secondary forest. Soil invertebrates are an important component to the functioning and biodiversity of these soil ecosystems. However, it remains unclear how these past land-use activities and subsequent secondary forest developments have altered the soil invertebrate communities and any potential ecological consequences associated with this. DNA metabarcoding offers an effective approach to rapidly monitor soil invertebrate communities under different land-use practices and within secondary forests. In this study, we used DNA metabarcoding to detect community-based patterns of soil invertebrate composition across a primary forest, a 23-year-old secondary forest, and a 33-year-old secondary forest and the associated soil environmental drivers of the soil invertebrate community structure in the Maquenque National Wildlife Refuge of Costa Rica (MNWR). We also used a species contribution analysis (SIMPER) to determine which soil invertebrate groups may be an indication of these soils reaching a pre-disturbed state such as a primary forest. We found that the soil invertebrate community composition at class, order, family, and ESV level were mostly significantly different across that habitats. We also found that the primary forest had a greater richness of soil invertebrates compared to the 23-year-old and 33-year-old secondary forest. Moreover, a redundancy analysis indicated that soil moisture influenced soil invertebrate community structure and explained up to 22% of the total variation observed in the community composition across the habitats; whereas soil invertebrate richness was structured by soil microbial biomass carbon (C) (Cmic) and explained up to 52% of the invertebrate richness across the primary and secondary forests. Lastly, the SIMPER analysis revealed that Naididae, Entomobryidae, and Elateridae could be important indicators of soil and forest recuperation in the MNWR. This study adds to the increasing evidence that soil invertebrates are intimately linked with the soil microbial biomass carbon (Cmic) and that even after 33 years of natural regrowth of a forest, these land use activities can still have persisting effects on the overall composition and richness of the soil invertebrate communities.
A compound combination screening approach with potential to identify new treatment options for paediatric acute myeloid leukaemia
Authors: Lappin Katrina M. , Davis Lindsay , Matchett Kyle B. , Ge Yubin , Mills Ken I. , Blayney Jaine K. 
Published: October 2020

AbstractPaediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by genetics and morphology. The introduction of intensive chemotherapy treatments together with patient stratification and supportive therapy has resulted in a moderate improvement in patient prognosis. However, overall survival rates remain unacceptably poor, with only 65% of patients surviving longer than 5 years. Recently age-specific differences in AML have been identified, highlighting the need for tailored treatments for paediatric patients. Combination therapies have the potential to improve patient prognosis, while minimising harmful side-effects. In the laboratory setting, identifying key combinations from large drug libraries can be resource-intensive, prohibiting discovery and translation into the clinic. To minimise redundancy and maximise discovery, we undertook a multiplex screen of 80 apoptotic-inducing agents in paediatric AML pre-clinical models. The screen was designed using an all-pairs testing algorithm, which ensured that all pairs of compounds could be tested, while minimising the number of wells used. We identified a combination of ABT-737, a Bcl-2 family inhibitor and Purvalanol A, a CDK inhibitor, as a potential targeted therapy for AML patients with an MLL rearrangement and an FLT3-ITD. Our approach has the potential to reduce resource-intensity and time associated with the identification of novel combination therapies.
Conformational gating, dynamics and allostery in human monoacylglycerol lipase
Authors: Tyukhtenko Sergiy , Ma Xiaoyu , Rajarshi Girija , Karageorgos Ioannis , Anderson Kyle W. , Hudgens Jeffrey W. , Guo Jason J. , Nasr Mahmoud L. , Zvonok Nikolai , Vemuri Kiran , Wagner Gerhard , Makriyannis Alexandros 
Published: October 2020

AbstractInhibition of human Monoacylglycerol Lipase (hMGL) offers a novel approach for treating neurological diseases. The design of inhibitors, targeting active-inactive conformational transitions of the enzyme, can be aided by understanding the interplay between structure and dynamics. Here, we report the effects of mutations within the catalytic triad on structure, conformational gating and dynamics of hMGL by combining kinetics, NMR, and HDX-MS data with metadynamics simulations. We found that point mutations alter delicate conformational equilibria between active and inactive states. HDX-MS reveals regions of the hMGL that become substantially more dynamic upon substitution of catalytic acid Asp-239 by alanine. These regions, located far from the catalytic triad, include not only loops but also rigid α-helixes and β-strands, suggesting their involvement in allosteric regulation as channels for long-range signal transmission. The results identify the existence of a preorganized global communication network comprising of tertiary (residue-residue contacts) and quaternary (rigid-body contacts) networks that mediate robust, rapid intraprotein signal transmission. Catalytic Asp-239 controls hMGL allosteric communications and may be considered as an essential residue for the integration and transmission of information to enzymes’ remote regions, in addition to its well-known role to facilitate Ser-122 activation. Our findings may assist in the identification of new druggable sites in hMGL.
Cardiac motion estimation from medical images: a regularisation framework applied on pairwise image registration displacement fields
Authors: Wiputra Hadi , Chan Wei Xuan , Foo Yoke Yin , Ho Sheldon , Yap Choon Hwai 
Published: October 2020

AbstractAccurate cardiac motion estimation from medical images such as ultrasound is important for clinical evaluation. We present a novel regularisation layer for cardiac motion estimation that will be applied after image registration and demonstrate its effectiveness. The regularisation utilises a spatio-temporal model of motion, b-splines of Fourier, to fit to displacement fields from pairwise image registration. In the process, it enforces spatial and temporal smoothness and consistency, cyclic nature of cardiac motion, and better adherence to the stroke volume of the heart. Flexibility is further given for inclusion of any set of registration displacement fields. The approach gave high accuracy. When applied to human adult Ultrasound data from a Cardiac Motion Analysis Challenge (CMAC), the proposed method is found to have 10% lower tracking error over CMAC participants. Satisfactory cardiac motion estimation is also demonstrated on other data sets, including human fetal echocardiography, chick embryonic heart ultrasound images, and zebrafish embryonic microscope images, with the average Dice coefficient between estimation motion and manual segmentation at 0.82–0.87. The approach of performing regularisation as an add-on layer after the completion of image registration is thus a viable option for cardiac motion estimation that can still have good accuracy. Since motion estimation algorithms are complex, dividing up regularisation and registration can simplify the process and provide flexibility. Further, owing to a large variety of existing registration algorithms, such an approach that is usable on any algorithm may be useful.
Organic nitrogen steadily increasing in Norwegian rivers draining to the Skagerrak coast
Authors: Deininger A. , Kaste Ø. , Frigstad H. , Austnes K. 
Published: October 2020

AbstractDeclining atmospheric nitrogen (N) deposition, through reduction in the direct input of inorganic N, may result in less inorganic N being leached from soils to freshwaters (dissolved inorganic N = DIN). Declining sulphur deposition, through reducing the ionic strength in soil water, increases the solubility and mobility of organic soil compounds and may result in increased leaching of organically bound N to freshwaters (total organic N = TON). It is unknown to which extent these two independents and opposing trends, i.e. DIN decline versus TON increase, may affect the nutrient balance (load, stoichiometry) of river water draining into coastal zones. By combining long-term atmospheric and riverine monitoring data of the five major Norwegian rivers draining to the Skagerrak coast, we show that over the past 27 years (1990–2017) river water nutrient composition, and specifically N stoichiometry has been steadily shifting from inorganic to organic fractions, with correlations to changes in human pressures (air pollution), but especially climate (precipitation, temperature, discharge). This shift in nutrient quality may have large consequences on the nutrient cycling in both freshwater and coastal ecosystems and illustrates the complex interactions of multiple stressors (here: N deposition, S deposition, and climate change) on aquatic ecosystems.
Enhanced FGFR3 activity in postmitotic principal neurons during brain development results in cortical dysplasia and axonal tract abnormality
Authors: Huang Jui-Yen , Krebs Bruna Baumgarten , Miskus Marisha Lynn , Russell May Lin , Duffy Eamonn Patrick , Graf Jason Michael , Lu Hui-Chen 
Published: October 2020

AbstractAbnormal levels of fibroblast growth factors (FGFs) and FGF receptors (FGFRs) have been detected in various neurological disorders. The potent impact of FGF-FGFR in multiple embryonic developmental processes makes it challenging to elucidate their roles in postmitotic neurons. Taking an alternative approach to examine the impact of aberrant FGFR function on glutamatergic neurons, we generated a FGFR gain-of-function (GOF) transgenic mouse, which expresses constitutively activated FGFR3 (FGFR3K650E) in postmitotic glutamatergic neurons. We found that GOF disrupts mitosis of radial-glia neural progenitors (RGCs), inside-out radial migration of post-mitotic glutamatergic neurons, and axonal tract projections. In particular, late-born CUX1-positive neurons are widely dispersed throughout the GOF cortex. Such a cortical migration deficit is likely caused, at least in part, by a significant reduction of the radial processes projecting from RGCs. RNA-sequencing analysis of the GOF embryonic cortex reveals significant alterations in several pathways involved in cell cycle regulation and axonal pathfinding. Collectively, our data suggest that FGFR3 GOF in postmitotic neurons not only alters axonal growth of postmitotic neurons but also impairs RGC neurogenesis and radial glia processes.
Dinaciclib, a cyclin-dependent kinase inhibitor, suppresses cholangiocarcinoma growth by targeting CDK2/5/9
Authors: Saqub Hera , Proetsch-Gugerbauer Hannah , Bezrookove Vladimir , Nosrati Mehdi , Vaquero Edith M. , de Semir David , Ice Ryan J. , McAllister Sean , Soroceanu Liliana , Kashani-Sabet Mohammed , Osorio Robert , Dar Altaf A. 
Published: October 2020

AbstractCholangiocarcinoma (CCA) is a highly invasive cancer, diagnosed at an advanced stage, and refractory to surgical intervention and chemotherapy. Cyclin-dependent kinases (CDKs) regulate cell cycle progression and transcriptional processes, and are considered potential therapeutic targets for cancer. Dinaciclib is a small molecule multi-CDK inhibitor targeting CDK 2/5/9. In this study, the therapeutic efficacy of dinaciclib was assessed using patient-derived xenograft cells (PDXC) and CCA cell lines. Treatment with dinaciclib significantly suppressed cell proliferation, induced caspase 3/7 levels and apoptotic activity in PDXC and CCA cell lines. Dinaciclib suppressed expression of its molecular targets CDK2/5/9, and anti-apoptotic BCL-XL and BCL2 proteins. Despite the presence of cyclin D1 amplification in the PDXC line, palbociclib treatment had no effect on cell proliferation, cell cycle or apoptosis in the PDXC as well as other CCA cell lines. Importantly, dinaciclib, in combination with gemcitabine, produced a robust and sustained inhibition of tumor progression in vivo in a PDX mouse model, greater than either of the treatments alone. Expression levels of two proliferative markers, phospho-histone H3 and Ki-67, were substantially suppressed in samples treated with the combination regimen. Our results identify dinaciclib as a novel and potent therapeutic agent alone or in combination with gemcitabine for the treatment of CCA.