bluuebunny/crossref_metadata_2025 huggingface dataset:
Amorphous solid dispersions of enzalutamide and novel polysaccharide derivatives: investigation of relationships between polymer structure and performance
Authors: Wilson Venecia R. , Lou Xiaochun , Osterling Donald J. , Stolarik DeAnne F. , Jenkins Gary J. , Nichols Brittany L. B. , Dong Yifan , Edgar Kevin J. , Zhang Geoff G. Z. , Taylor Lynne S.
Published: October 2020

Amorphous solid dispersion (ASD) is a widely employed formulation technique for drugs with poor aqueous solubility. Polymers are integral components of ASDs, but mechanisms by which polymers lead to the generation and maintenance of supersaturated solutions, which enhance oral absorption in vivo, are poorly understood. Herein, a diverse group of newly synthesized cellulose derivatives was evaluated for their ability to inhibit crystallization of enzalutamide, a poorly soluble compound used to treat prostate cancer. ASDs were prepared from selected polymers, specifically a somewhat hydrophobic polymer that was extremely effective at inhibiting drug crystallization, and a less effective, but more hydrophilic, crystallization inhibitor, that might afford better release. Drug membrane transport rate was evaluated in vitro and compared to in vivo performance, following oral dosing in rats. Good correlation was noted between the in vitro diffusion cell studies and the in vivo data. The ASD formulated with the less effective crystallization inhibitor outperformed the ASD prepared with the highly effective crystallization inhibitor in terms of the amount and rate of drug absorbed in vivo. This study provides valuable insight into key factors impacting oral absorption from enabling ASD formulations, and how best to evaluate such formulations using in vitro approaches.
Lithium containing layered high entropy oxide structures
Authors: Wang Junbo , Cui Yanyan , Wang Qingsong , Wang Kai , Huang Xiaohui , Stenzel David , Sarkar Abhishek , Azmi Raheleh , Bergfeldt Thomas , Bhattacharya Subramshu S. , Kruk Robert , Hahn Horst , Schweidler Simon , Brezesinski Torsten , Breitung Ben
Published: October 2020

Layered Delafossite-type Lix(M1M2M3M4M5…Mn)O2 materials, a new class of high-entropy oxides, were synthesized by nebulized spray pyrolysis and subsequent high-temperature annealing. Various metal species (M = Ni, Co, Mn, Al, Fe, Zn, Cr, Ti, Zr, Cu) could be incorporated into this structure type, and in most cases, single-phase oxides were obtained. Delafossite structures are well known and the related materials are used in different fields of application, especially in electrochemical energy storage (e.g., LiNixCoyMnzO2 [NCM]). The transfer of the high-entropy concept to this type of materials and the successful structural replication enabled the preparation of novel compounds with unprecedented properties. Here, we report on the characterization of a series of Delafossite-type high-entropy oxides by means of TEM, SEM, XPS, ICP-OES, Mössbauer spectroscopy, XRD including Rietveld refinement analysis, SAED and STEM mapping and discuss about the role of entropy stabilization. Our experimental data indicate the formation of uniform solid-solution structures with some Li/M mixing.
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

The 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

In 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

We 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

Epidemiological 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

The 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

The 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

Tropical 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

Paediatric 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

Inhibition 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

Accurate 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

Declining 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

Abnormal 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

Cholangiocarcinoma (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.
Custom extraction of macular ganglion cell-inner plexiform layer thickness more precisely co-localizes structural measurements with visual fields test grids
Authors: Tong Janelle , Alonso-Caneiro David , Yoshioka Nayuta , Kalloniatis Michael , Zangerl Barbara
Published: October 2020

We aimed to evaluate methods of extracting optical coherence tomography (OCT)-derived macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements over retinal locations corresponding to standard visual field (VF) test grids. A custom algorithm was developed to automatically extract GCIPL thickness measurements from locations corresponding to Humphrey Field Analyser 10-2 and 30-2 test grids over Goldmann II, III and V stimulus sizes from a healthy cohort of 478 participants. Differences between GCIPL thickness measurements based on VF test grids (VF-based paradigms) and the 8 × 8 grid, as per instrument review software, were analyzed, as were impacts of fovea to optic disc tilt and areas over which GCIPL thickness measurements were extracted. Significant differences between the VF-based paradigms and the 8 × 8 grid were observed at up to 55% of locations across the macula, with the greatest deviations at the fovea (median 25.5 μm, 95% CI 25.24–25.72 μm, P < .0001). While significant correlations with fovea to optic disc tilt were noted at up to 33% of locations distributed 6°–8° from the foveal center, there were no marked differences in GCIPL thickness measurements between VF-based paradigms using different stimulus sizes. As such, standard high-density OCT measurement paradigms do not adequately reflect GCIPL measurements at retinal locations tested with standard VF patterns, with the central macular region contributing most to the observed differences and with further correction required for fovea to optic disc tilt. Spatial direction of GCIPL thickness measurements will improve future comparisons of structure and function, thereby improving methods designed to detect pathology affecting the inner retina.
Inclusion of endophenotypes in a standard GWAS facilitate a detailed mechanistic understanding of genetic elements that control blood lipid levels
Authors: Zhang Qianqian , Cai Zexi , Lhomme Marie , Sahana Goutam , Lesnik Philippe , Guerin Maryse , Fredholm Merete , Karlskov-Mortensen Peter
Published: October 2020

Dyslipidemia is the primary cause of cardiovascular disease, which is a serious human health problem in large parts of the world. Therefore, it is important to understand the genetic and molecular mechanisms that regulate blood levels of cholesterol and other lipids. Discovery of genetic elements in the regulatory machinery is often based on genome wide associations studies (GWAS) focused on end-point phenotypes such as total cholesterol level or a disease diagnosis. In the present study, we add endophenotypes, such as serum levels of intermediate metabolites in the cholesterol synthesis pathways, to a GWAS analysis and use the pig as an animal model. We do this to increase statistical power and to facilitate biological interpretation of results. Although the study population was limited to ~ 300 individuals, we identify two genome-wide significant associations and ten suggestive associations. Furthermore, we identify 28 tentative associations to loci previously associated with blood lipids or dyslipidemia associated diseases. The associations with endophenotypes may inspire future studies that can dissect the biological mechanisms underlying these previously identified associations and add a new level of understanding to previously identified associations.
Diamond step-index nanowaveguide to structure light efficiently in near and deep ultraviolet regimes
Authors: Mahmood Nasir , Mehmood Muhammad Qasim , Tahir Farooq Ahmad
Published: October 2020

Two-dimensional metamaterials, consisting of an array of ultrathin building blocks, offer a versatile and compact platform for tailoring the properties of the electromagnetic waves. Such flat metasurfaces provide a unique solution to circumvent the limitations imposed by their three-dimensional counterparts. Albeit several successful demonstrations of metasurfaces have been presented in the visible, infrared, and terahertz regimes, etc., there is hardly any demonstration for ultraviolet wavelengths due to the unavailability of the appropriate lossless materials. Here, we present diamond as an ultra-low loss material for the near and deep ultraviolet (UV) light and engineer diamond step-index nanowaveguides (DSINs) to achieve full control over the phase and amplitude of the incident wave. A comprehensive analytical solution of step-index nanowaveguides (supported by the numerical study) is provided to describe the underlying mechanism of such controlled wavefront shaping. Due to the ultra-low loss nature of diamond in near and deep UV regimes, our DSINs and metasurfaces designed (from them) exhibit a decent efficiency of ≈ 84% over the entire spectrum of interest. To verify this high efficiency and absolute control over wavefront, we have designed polarization-insensitive meta-holograms through optimized DSINs for operational wavelength λ = 250 nm.
Publisher Correction: Genome analysis of deep sea piezotolerant Nesiotobacter exalbescens COD22 and toluene degradation studies under high pressure condition
Authors: Ganesh Kumar A. , Mathew Noelin Chinnu , Sujitha K. , Kirubagaran R. , Dharani G.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Plasma Electrolytic Oxidation as a Feasible Surface Treatment for Biomedical Applications: an in vivo study
Authors: Polo Tárik Ocon Braga , Silva William Phillip Pereira , Momesso Gustavo Antonio Correa , Lima-Neto Tiburtino José , Barbosa Stéfany , Cordeiro Jairo Matozinho , Hassumi Jaqueline Suemi , da Cruz Nilson Cristino , Okamoto Roberta , Barão Valentim A. R. , Faverani Leonardo P.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A mix-and-detect method based on colloidal gold immunochromatographic assay for on-site detection of zearalenone in edible oils
Authors: Mao Xinyi , Wu Yuxiang , Chen Huitian , Wang Yifan , Yu Binger , Shi Guoqing
Published: October 2020

A very simple sample pretreatment method was developed for the detection of zearalenone in edible oil by using an immunochromatography strip.
A strategy to construct uniform MOFs/PAN nanowire derived bead-like Co3O4 for VOC catalytic combustion
Authors: Han Weigao , Dong Fang , Han Weiliang , Tang Zhicheng
Published: October 2020

An effective strategy was developed to construct uniform MOFs/PAN nanowires and the derived bead-like dodecahedron Co3O4 is effective for the catalytic combustion of VOCs.
Characterization of heterogeneous aryl–Pd(ii)–oxo clusters as active species for C–H arylation
Authors: Shin Taeil , Kim Minjun , Jung Younjae , Cho Sung June , Kim Hyunwoo , Song Hyunjoon
Published: October 2020

The surface oxidation of Pd nanoparticles with [Ph2I]BF4 resulted in the generation of Pd(ii)–aryl–oxo clusters, which led to C–H arylation in high yields and regioselectivity.
Four octamolybdate complexes constructed from a quinoline–imidazole–monoamide ligand: structures and electrochemical, photocatalytic and magnetic properties
Authors: Li Lei , Wang Xiang , Xu Na , Chang Zhihan , Liu Guocheng , Lin Hongyan , Wang Xiuli
Published: October 2020

Four octamolybdate-based complexes synthesized by employing N-(quinoline-5-yl)-1H-imidazole-4-carboxamide as a ligand exhibit excellent electrocatalytic activities, photocatalytic properties and antiferromagnetic behavior.
Photoluminescence property of Cr-doped β-Ga2O3 nanorods synthesized by a hydrothermal method
Authors: Shi Feng , Qiao Hengyang
Published: October 2020

Cr-Doped β-Ga2O3 nanorods were synthesized by a hydrothermal method and were characterized in detail so as to analyze the effects of Cr3+ doping on their crystalline quality and photoluminescence property.
Thermochemical energy storage performance of zinc destabilized calcium hydride at high-temperatures
Authors: Balakrishnan Sruthy , Sofianos M. Veronica , Humphries Terry D. , Paskevicius Mark , Buckley Craig E.
Published: October 2020

The thermodynamic destabilisation of CaH2 with Zn reduces the decomposition temperature of CaH2 (1100 °C at 1 bar of H2 pressure) to 597 °C at 1 bar of H2 pressure, creating a viable thermal energy storage material for third generation CSP plants.
Photoluminescence of diamond containing nitrogen vacancy defects as a sensor of temperature upon exposure to vacuum- and extreme-ultraviolet radiation
Authors: Lu Hsiao-Chi , Lo Jen-Iu , Peng Yu-Chain , Cheng Bing-Ming
Published: October 2020

Upon excitation with vacuum-ultraviolet (VUV) and extreme-ultraviolet (EUV) radiation, diamond with nitrogen vacancies (DNV) emits strong photoluminescence (PL) in the wavelength region of 550–800 nm.
Rapid survey of nuclear quadrupole resonance by broadband excitation with comb modulation and dual-mode acquisition
Authors: Hibe Yuta , Noda Yasuto , Takegoshi K. , Takeda Kazuyuki
Published: October 2020

A rapid-scan with gapped excitation with dual-mode operation (RASGADO) scheme allows rapid survey of nuclear quadrupole resonance (NQR) signals.
Internal catalysis for dynamic covalent chemistry applications and polymer science
Authors: Van Lijsebetten Filip , Holloway Joshua O. , Winne Johan M. , Du Prez Filip E.
Published: October 2020

In this review, we provide a concise analysis of internal catalysis as an attractive design principle to combine chemical robustness with reactivity in dynamic covalent chemistry applications and a material context.
Assembling two Dy2 single-molecule magnets with different energy barriers via fine-tuning the geometries of DyIII sites
Authors: Li Dawei , Ding Man-Man , Ge Yu , Tello Yepes David Felipe , Sun Mingyuan , Najib Muhammad Saleem , Li Yahong , Zhang Yi-Quan , Yao Jin-lei
Published: October 2020

Two Dy2 single-molecule magnets are prepared. The energy barrier of 2 is slightly enhanced by adjusting the geometries of DyIII centers.
A biomimetic nanoenzyme for starvation therapy enhanced photothermal and chemodynamic tumor therapy
Authors: Xu Keqiang , Wu Xiaqing , Cheng Yan , Yan Jiao , Feng Yanlin , Chen Rui , Zheng Runxiao , Li Xi , Song Panpan , Wang Yanjing , Zhang Haiyuan
Published: October 2020

Glucose oxidase decorated N-doped carbon nanoparticles have been designed as a biomimetic nanoenzyme, which present prominent synergistic effects of starvation therapy enhancing photothermal therapy and chemodynamic therapy against tumors.
Thermal stability of self-assembled ordered three-phase Au–BaTiO3–ZnO nanocomposite thin films via in situ heating in TEM
Authors: Misra Shikhar , Zhang Di , Lu Ping , Wang Haiyan
Published: October 2020

Thermal stability of an ordered three-phase Au–BaTiO3–ZnO vertically aligned nanostructure by both ex situ annealing under air and vacuum conditions, and in situ heating in TEM in vacuum has been demonstrated.
Understanding metal organic chemical vapour deposition of monolayer WS2: the enhancing role of Au substrate for simple organosulfur precursors
Authors: Fan Ye , Nakanishi Kenichi , Veigang-Radulescu Vlad P. , Mizuta Ryo , Stewart J. Callum , Swallow Jack E. N. , Dearle Alice E. , Burton Oliver J. , Alexander-Webber Jack A. , Ferrer Pilar , Held Georg , Brennan Barry , Pollard Andrew J. , Weatherup Robert S. , Hofmann Stephan
Published: October 2020

A deconstructed MOCVD model process allows in-operando fingerprinting of the chemical reactions that underpin WS2 monolayer crystal growth, and highlights the enhancing role of Au support in conjunction with simple organosulfide precursors.
Coenzyme-dependent nanozymes playing dual roles in oxidase and reductase mimics with enhanced electron transport
Authors: Chen Jinxing , Ma Qian , Li Minghua , Wu Weiwei , Huang Liang , Liu Ling , Fang Youxing , Dong Shaojun
Published: October 2020

PEI/ZIF-FMN mediated the electron transfer from NADH to cytochrome c.
Multi-stimuli controlled release of a transmembrane chloride ion carrier from a sulfonium-linked procarrier
Authors: Das Sribash , Biswas Oindrila , Akhtar Nasim , Patel Anjali , Manna Debasis
Published: October 2020

We demonstrated the development of a multi-stimuli activatable anion transport approach to induce regulated transport of Cl− ion across the membranes under specific conditions.
TPE-containing amphiphilic block copolymers: synthesis and application in the detection of nitroaromatic pollutants
Authors: Zhou Shiyuan , Gu Peiyang , Wan Haibo , Zhu Yutao , Wang Anna , Shi Haibin , Xu Qingfeng , Lu Jianmei
Published: October 2020

Two AIE block copolymers termed P1 and P2 bearing TPE and PEG-based chains were synthesized with moderate molecular weights and narrow PDIs via RAFT polymerization. Both P1 and P2 can be used in the fluorescence detection of nitroaromatic compounds (NACs) and cell images.
Investigation on nanostructured Cu-based electrocatalysts for improvising water splitting: a review
Authors: Kannimuthu Karthick , Sangeetha Kumaravel , Sam Sankar Selvasundarasekar , Karmakar Arun , Madhu Ragunath , Kundu Subrata
Published: October 2020

In this review, various forms of Cu based nanostructures have been explored in terms of improvise and enhancing their activity and durability with vast investigation for OER, HER and TWS applications.
Organ-on-a-chip: the next generation platform for risk assessment of radiobiology
Authors: Quan Yi , Sun Miao , Tan Zhaoyi , Eijkel Jan C. T. , van den Berg Albert , van der Meer Andries , Xie Yanbo
Published: October 2020

Organ-on-a-chip technology has great potential for the next generation risk estimation of low dose internal irradiation, due to its success in mimicking human organs/tissues, which possibly can significantly improve on current animal models.
Cellulose hydrolysis using ionic liquids and inorganic acids under dilute conditions: morphological comparison of nanocellulose
Authors: Jordan Jacobs H. , Easson Michael W. , Condon Brian D.
Published: October 2020

Cellulose nanocrystals prepared with 1-butyl-3-methylimidazolium chloride ([BMIm]Cl) and HCl, H2SO4, or H3PO4in a one-pot process under dilute conditions are investigated for changes in CNC dimensions, crystallinity, and thermal stability.
Nitroacetonitrile as a versatile precursor in energetic materials synthesis
Authors: Creegan Shannon E. , Piercey Davin G.
Published: October 2020

Nitroacetonitrile is a useful synthetic precursor capable of participating in a wide range of reactions and enables the simple synthesis of annulated heterocyclic systems which are rapidly becoming promising new energetic materials.
Kinetics enhanced hierarchical Ni2P1−xSx/Ni@carbon/graphene yolk–shell microspheres boosting advanced sodium/potassium storage
Authors: Zhao Xiaojun , Song Yizhuo , Liu Zhi-Hong
Published: October 2020

Design and fabrication of yolk–shell Ni2P1−xSx/Ni with a porous carbon/graphene coating (YS Ni2P1−xSx/Ni@C/G) exhibits superior electrochemical performances of sodium/potassium storages due to unique morphology and electronic structure.
Scalable open-air deposition of compact ETL TiOxon perovskite for fullerene-free solar cells
Authors: Chen Justin P. , Hilt Florian , Rolston Nicholas , Dauskardt Reinhold H.
Published: October 2020

Low-temperature TiOxelectron transport layer (ETL) with improved fracture energy and barrier properties to environmental species compared to organic ETLs.
Erwartungen an eine Volltextdatenbank für Abschlussarbeiten aus den Therapiewissenschaften – Eine Online-Befragung
Authors: Griefahn Annika , Lüken Nele , Möller Dirk , Zalpour Christoff
Published: October 2020

Hintergrund Das Bundesministerium für Bildung und Forschung (BMBF) initiierte 2016 die Open-Access-Initiative. Open Access bedeutet, Wissen online kostenlos freizugänglich zu machen. Dieser Anspruch setzt eine Digitalisierung voraus, die hochschulübergreifend professionelles Wissen öffentlich macht. Dazu passt die Etablierung einer entsprechenden Online-Datenbank.

Ziel Mithilfe einer Online-Befragung die Erwartungen potentieller Nutzer an eine Volltextdatenbank zu untersuchen. Mittels eines Fragebogens sollen Nutzerverhalten, Bedürfnisse, Notwendigkeiten erforscht sowie Ideen, Anregungen, persönliche Einschätzungen und mögliche Vor- und Nachteile erfasst werden.

Methode Durchführung einer Online-Befragung mit 20 Fragen, welche in vier Abschnitte eingeteilt wurden. Geschlossene Fragen wurden deskriptiv ausgewertet, offene Fragen wurden mit der Kernsatzmethode nach Leithäuser und Volmerg (1988) ausgewertet.

Ergebnisse Insgesamt 84,87 % der 337 Befragten zeigten Interesse an einer Volltextdatenbank für Abschlussarbeiten aus den Therapiewissenschaften. Wünsche der Befragten konnten in den Anforderungskatalog für die zu entwickelnde Volltextdatenbank aufgenommen werden. 67,95 % der Befragten würden sich ein Profil in einer Volltextdatenbank anlegen. Die Vorstellung, eine Abschlussarbeit in einem Videoporträt anzulegen, wurde hingegen von 36,50 % als nicht nützlich bewertet.

Schlussfolgerung Anhand der Online-Befragung konnten die Rechercheaktivität und die Wünsche an eine Volltextdatenbank abgefragt werden. Die Nutzerakzeptanz kann erst zu einem späteren Zeitpunkt hinreichend bewertet werden, mithilfe einer Evaluationsstudie.
Versorgung per- und subtrochantärer Frakturen mit dem Gamma-Nagel
Authors: Klöffel Maike , Völk Michael
Published: October 2020

Per- und subtrochantäre Frakturen sind typische Verletzungen bei älteren Patienten. Da sie häufig an Osteoporose leiden, ist ihre Versorgung herausfordernd. Ein OP-Team des Leopoldina-Krankenhauses Schweinfurt schildert die intramedulläre Osteosynthese mittels Gamma-Nagel.
Synthesis and Crystal Engineering of Rubrene and Its Derivatives
Authors: Douglas Christopher J. , Clapham Margaret L. , Murphy Emma C.
Published: October 2020

Rubrene (5,6,11,12-tetraphenyltetracene) is a polyacene material that has been well studied throughout its nearly one-hundred year history. Originally found fascinating for its luminescent properties, it has emerged at the forefront for organic electronics due to its particularly high charge carrier mobility for an organic crystal. Despite great interest and its explosion in the literature over the past two decades, the commercial synthesis of rubrene has remained relatively unchanged since its initial discovery in 1926. Several recent studies have reported alternate routes to the rubrene structure with substitutions on the peripheral­ aromatic rings and tetracene core. Substituting in this manner has the potential to improve upon rubrene’s electronic properties. We review the various routes to rubrene and its derivatives and provide a brief overview of the solid-state library available for study. The information gained by comparing the solid-state properties between derivatives offers insight into unpredictable crystallization and polymorphism – complicated issues – which have hindered research into materials applications­ of rubrene. We hope that these insights inspire work in application­-driven synthetic chemistry for future rubrene derivatives.

1 Introduction

2 Synthesis

2.1 Traditional Rubrene Synthesis

2.1.1 Recent Applications

2.2 Multi-Step Synthesis

2.2.1 Historical Routes

2.2.2 Diels–Alder Approaches

2.2.3 Cross-Coupling Approaches

2.2.4 Comparative Synthesis of Perfluororubrene

3 Crystal Engineering

4 Conclusions and Outlook
Recent Progress towards Organocatalyzed Asymmetric (Hetero)Arene Formation
Authors: Zhu Tingshun , Xu Ke , Wang Ziyuan
Published: October 2020

Owing to the importance of arene moieties in organic chemistry, methods for arene construction attract great attention. Besides the traditional substitution strategy from pre-existing arenes, the straightforward formation of arene cores can also provide significant shortcuts towards a wide array of target molecules with different substitution patterns. Among direct arene formation reactions, applying environmentally benign organocatalysis to access arene moieties continues to attract increasing attention. This short review provides a brief summary of recent progress on organocatalyzed de novo (hetero)arene formation and applications in enantioselective synthesis.

1 Introduction

2 Arene Formation with Non-Covalent Organocatalysts

2.1 Arene Formation with Acid Organocatalysts

2.2 Arene Formation with Base Organocatalysts

2.3 Arene Formation with Hydrogen-Bonding Organocatalysts

3 Arene Formation with Covalent Organocatalysts

3.1 Arene Formation with Lewis Base Organocatalysts

3.1.1 Arene Formation with Secondary Amine Organocatalysts

3.1.2 Arene Formation with Tertiary Amine, Tertiary Phosphine and Sulfide Organocatalysts

3.1.3 Arene Formation with N-Heterocyclic Carbene Organocatalysts

3.2 Arene Formation with Lewis Acid Organocatalysts

4 Conclusion
Posterior Tibial Slope Increases Anterior Cruciate Ligament Stress in Bi-Cruciate Retaining Total Knee Arthroplasty: In Vivo Kinematic Analysis
Authors: Klemt Christian , Bounajem Georges , Tirumala Venkatsaiakhil , Xiong Liang , Oganesyan Ruben , Kwon Young-Min
Published: October 2020

The study design involved here is experimental in nature. The resection of the anterior cruciate ligament (ACL) during conventional total knee arthroplasty (TKA) has been considered a potential factor leading to abnormal in vivo knee kinematics. Bi-cruciate retaining (BCR) TKA designs allow the preservation of the ACL with the potential to restore native knee kinematics. This study aimed to investigate the effect of posterior tibial slope (PTS) on stress experienced by the ACL during weight bearing sit-to-stand (STS) and single-leg deep lunge. The ACL elongation patterns were measured in 30 unilateral BCR TKA patients during weight-bearing STS and single-leg deep lunge using a validated dual fluoroscopic tracking technique. The minimum normalized stress within the anteromedial (AM) and posterolateral (PL) bundle of the ACL during weight-bearing STS and single-leg deep lunge was found at a PTS of 3.7 degrees. The maximum AM and PL bundle stresses were observed at a PTS of 8.5 and 9.3 degrees, respectively during STS and at 8.4, and 9.1 degrees, respectively during single-leg deep lunge. There was a significant positive correlation between PTS and stress observed within the AM and PL bundle of the ACL during weight-bearing STS (R
2 = 0.37; p < 0.01; R2
 = 0.36; p = 0.01) and single-leg deep lunge (R
2 = 0.42; p < 0.01; R
2 = 0.40; p < 0.01). The study demonstrates that PTS of operated BCR TKA knees has a significant impact on the stress experienced by the preserved ACL during weight-bearing STS and single-leg deep lunge. This suggests that avoiding excessive PTS may be one of the surgical implant alignment factors to consider during surgery to minimize increased loading of the preserved ACL.