bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Somatic Mutations and Tumor Mutation Burden in Plasma by CAPP-Seq during Afatinib Treatment in NSCLC Patients Resistance to Osimertinib
Authors: Ishii Hidenobu , Azuma Koichi , Sakai Kazuko , Naito Yoshiko , Matsuo Norikazu , Tokito Takaaki , Yamada Kazuhiko , Hoshino Tomoaki , Nishio Kazuto
Published: January 2020

Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were developed to target the EGFR T790M resistance mutation in non-small cell lung cancer (NSCLC) patients resistant to first- or second-generation EGFR-TKIs. To investigate the efficacy of afatinib treatment for EGFR T790M-positive NSCLC patients showing resistance to osimertinib and alterations in somatic mutations and tumor mutation burden (TMB) in plasma circulating tumor DNA (ctDNA) during afatinib treatment, we conducted a prospective study using Cancer Personalized Profiling by deep Sequencing (CAPP-Seq). Nine NSCLC patients with EGFR T790M mutation who showed resistance to third-generation EGFR-TKIs were enrolled in this study and treated with afatinib. Plasma samples were collected before treatment, 4 weeks after treatment, and at disease progression. The mutation profile and TMB in plasma ctDNA were analyzed by CAPP-Seq. The objective response rate and median progression-free survival associated with afatinib were 0% and 2.0 months, respectively. The C797S mutation-mediated resistance to osimertinib was observed in one patient and following afatinib treatment in two patients; the C797S mutations occurred in the same allele as the T790M mutation. After afatinib treatment, afatinib-sensitive mutant alleles, such as ERBB2, and TMB decreased. We have demonstrated that detection of mutant allele frequency and TMB of ctDNA by CAPP-Seq could help determine the effectiveness of and resistance to afatinib. Although afatinib monotherapy for T790M-positive NSCLC resistant to osimertinib was less effective, the action for multiclonal mutant alleles and TMB might contribute to further treatment strategy.
Significant enhancement of the bias stability of Zn-O-N thin-film transistors via Si doping
Authors: Song Aeran , Park Hyun-Woo , Kim Hyoung-Do , Kim Hyun-Suk , Chung Kwun-Bum
Published: January 2020

Si doping was used to significantly improve the bias stability of ZnON thin-film transistors. Si 3 W (~1%) doped ZnON TFTs showed a saturation mobility of 19.70 cm2/Vs along with remarkable improvements in the threshold voltage shift for negative gate bias stress (NBS) within 1.69 V. The effects of Si doping were interpreted by the experimental correlation between device performance and physical analysis, as well as by the theoretical calculation. Si doping induces the reduction of N-related defects by increasing stoichiometric Zn3N2, and decreasing nonstoichiometric ZnxNy. In addition, Si doping reduces the band edge states below the conduction band. According to density functional theory (DFT) calculations, Si, when it substitutes for Zn, acts as a carrier suppressor in the ZnON matrix.
Prototheca zopfii genotype II induces mitochondrial apoptosis in models of bovine mastitis
Authors: Shahid Muhammad , Cobo Eduardo R. , Chen Liben , Cavalcante Paloma A. , Barkema Herman W. , Gao Jian , Xu Siyu , Liu Yang , Knight Cameron G. , Kastelic John P. , Han Bo
Published: January 2020

Prototheca zopfii is an alga increasingly isolated from bovine mastitis. Of the two genotypes of P. zopfii (genotype I and II (GT-I and -II)), P. zopfii GT-II is the genotype associated with acute mastitis and decreased milk production, although its pathogenesis is not well known. The objective was to determine inflammatory and apoptotic roles of P. zopfii GT-II in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis. Prototheca zopfii GT-II (but not GT-I) invaded bovine and murine mammary epithelial cells (MECs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. This P. zopfii GT-II driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance (ΔΨm) was altered and modulation of mitochondrion-mediated apoptosis regulating genes changed (increased transcriptional Bax, cytochrome-c and Apaf-1 and downregulated Bcl-2), whereas caspase-9 and -3 expression increased. Apoptotic effects by P. zopfii GT-II were more pronounced in macrophages compared to MECs. In a murine mammary infection model, P. zopfii GT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-α, IL-1β and Cxcl-1) and also apoptosis of epithelial cells. Thus, we concluded P. zopfii GT-II is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis.
Choroidoscleral Interface Irregularity Index: A novel optical coherence tomography-based parameter in patients with epiretinal membrane
Authors: Kim Mirinae , Lee Yohan , Kim Rae-Young , Kwak Jae Hyuck , Park Young-Hoon
Published: January 2020

This study aimed to assess the regularity of the choroidoscleral interface (CSI) using a novel parameter, CSI irregularity index, before and after epiretinal membrane (ERM) surgery. This study included 36 patients with idiopathic ERM who underwent pars plana vitrectomy and ERM removal. All subjects underwent ocular examinations at baseline and at 1, 2, 4, and 6 months after surgery. The regular contour of the CSI was found in 14 patients (38.9%); mean CSI irregularity index was 14.84 ± 11.01 in this group. The irregular contour of the CSI was found in 22 patients (61.1%); mean CSI irregularity index was 33.96 ± 20.64 in this group. The CSI irregularity index decreased gradually after ERM surgery, and was correlated with postoperative best-corrected visual acuity. The CSI irregularity index could serve as a surrogate marker to quantitatively represent the CSI morphology. We observed the gradual decrease of the CSI irregularity index after ERM surgery in quantitative manner. This study showed correlations between the CSI irregularity index and visual outcomes after ERM surgery. Our results suggest that the CSI irregularity index might be an intuitive anatomic indicator of the CSI and might be useful as a possible prognostic marker for patients undergoing ERM surgery.
Augmented reality navigation with intraoperative 3D imaging vs fluoroscopy-assisted free-hand surgery for spine fixation surgery: a matched-control study comparing accuracy
Authors: Elmi-Terander Adrian , Burström Gustav , Nachabé Rami , Fagerlund Michael , Ståhl Fredrik , Charalampidis Anastasios , Edström Erik , Gerdhem Paul
Published: January 2020

This study aimed to compare screw placement accuracy and clinical aspects between Augmented Reality Surgical Navigation (ARSN) and free-hand (FH) technique. Twenty patients underwent spine surgery with screw placement using ARSN and were matched retrospectively to a cohort of 20 FH technique cases for comparison. All ARSN and FH cases were performed by the same surgeon. Matching was based on clinical diagnosis and similar proportions of screws placed in the thoracic and lumbosacral vertebrae in both groups. Accuracy of screw placement was assessed on postoperative scans according to the Gertzbein scale and grades 0 and 1 were considered accurate. Procedure time, blood loss and length of hospital stay, were collected as secondary endpoints. A total of 262 and 288 screws were assessed in the ARSN and FH groups, respectively. The share of clinically accurate screws was significantly higher in the ARSN vs FH group (93.9% vs 89.6%, p < 0.05). The proportion of screws placed without a cortical breach was twice as high in the ARSN group compared to the FH group (63.4% vs 30.6%, p < 0.0001). No statistical difference was observed for the secondary endpoints between both groups. This matched-control study demonstrated that ARSN provided higher screw placement accuracy compared to free-hand.
TAK-242, a specific inhibitor of Toll-like receptor 4 signalling, prevents endotoxemia-induced skeletal muscle wasting in mice
Authors: Ono Yuko , Maejima Yuko , Saito Masafumi , Sakamoto Kazuho , Horita Shoichiro , Shimomura Kenju , Inoue Shigeaki , Kotani Joji
Published: January 2020

Circulating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or various endogenous diseases related to bacterial translocation from the gut. Systemic inflammatory responses induced by endotoxemia induce severe involuntary loss of skeletal muscle, termed muscle wasting, which adversely affects the survival and functional outcomes of these patients. Currently, no drugs are available for the treatment of endotoxemia-induced skeletal muscle wasting. Here, we tested the effects of TAK-242, a Toll-like receptor 4 (TLR4)-specific signalling inhibitor, on myotube atrophy in vitro and muscle wasting in vivo induced by endotoxin. LPS treatment of murine C2C12 myotubes induced an inflammatory response (increased nuclear factor-κB activity and interleukin-6 and tumour necrosis factor-α expression) and activated the ubiquitin–proteasome and autophagy proteolytic pathways (increased atrogin-1/MAFbx, MuRF1, and LC-II expression), resulting in myotube atrophy. In mice, LPS injection increased the same inflammatory and proteolytic pathways in skeletal muscle and induced atrophy, resulting in reduced grip strength. Notably, pretreatment of cells or mice with TAK-242 reduced or reversed all the detrimental effects of LPS in vitro and in vivo. Collectively, our results indicate that pharmacological inhibition of TLR4 signalling may be a novel therapeutic intervention for endotoxemia-induced muscle wasting.
Ontology-driven integrative analysis of omics data through Onassis
Authors: Galeota Eugenia , Kishore Kamal , Pelizzola Mattia
Published: January 2020

Public repositories of large-scale omics datasets represent a valuable resource for researchers. In fact, data re-analysis can either answer novel questions or provide critical data able to complement in-house experiments. However, despite the development of standards for the compilation of metadata, the identification and organization of samples still constitutes a major bottleneck hampering data reuse. We introduce Onassis, an R package within the Bioconductor environment providing key functionalities of Natural Language Processing (NLP) tools. Leveraging biomedical ontologies, Onassis greatly simplifies the association of samples from large-scale repositories to their representation in terms of ontology-based annotations. Moreover, through the use of semantic similarity measures, Onassis hierarchically organizes the datasets of interest, thus supporting the semantically aware analysis of the corresponding omics data. In conclusion, Onassis leverages NLP techniques, biomedical ontologies, and the R statistical framework, to identify, relate, and analyze datasets from public repositories. The tool was tested on various large-scale datasets, including compendia of gene expression, histone marks, and DNA methylation, illustrating how it can facilitate the integrative analysis of various omics data.
Evidence of extrinsic factors dominating intrinsic blood host preferences of major African malaria vectors
Authors: Orsborne James , Mohammed Abdul Rahim , Jeffries Claire L. , Kristan Mojca , Afrane Yaw A. , Walker Thomas , Yakob Laith
Published: January 2020

One of the key determinants of a haematophagous vector’s capacity to transmit pathogens is its selection of which host to secure a blood meal from. This choice is influenced by both intrinsic (genetic) and extrinsic (environmental) factors, but little is known of their relative contributions. Blood fed Anopheles mosquitoes were collected from a malaria endemic village in Ghana. Collections were conducted across a range of different host availabilities and from both indoor and outdoor locations. These environmental factors were shown to impact dramatically the host choice of caught malaria vectors: mosquitoes caught indoors were ten-fold more likely to have sourced their blood meal from humans; and a halving in odds of being human-fed was found for mosquitoes caught only 25 m from the centre of the village. For the first time, we demonstrate that anthropophagy was better explained by extrinsic factors (namely, local host availability and indoor/outdoor trapping location) than intrinsic factors (namely, the (sibling) species of the mosquito caught) (respective Akaike information criterion estimates: 243.0 versus 359.8). Instead of characterizing biting behaviour on a taxonomic level, we illustrate the importance of assessing local entomology. Accounting for this behavioural plasticity is important, both in terms of measuring effectiveness of control programmes and in informing optimal disease control strategies.
Mussel-inspired bioadhesives in healthcare: design parameters, current trends, and future perspectives
Authors: Pandey Nikhil , Soto-Garcia Luis F. , Liao Jun , Philippe Zimmern  , Nguyen Kytai T. , Hong Yi
Published: January 2020

Mussel-inspired bioadhesives gain increasing interests in healthcare applications. In this review, adhesive mechanism, mussel-inspired bioadhesive synthesis and applications in healthcare are summarized and discussed.
Bi nanodendrites for efficient electrocatalytic N2 fixation to NH3 under ambient conditions
Authors: Wang Fengyi , Lv Xu , Zhu Xiaojuan , Du Juan , Lu Siyu , Alshehri Abdulmohsen Ali , Alzahrani Khalid Ahmed , Zheng Baozhan , Sun Xuping
Published: January 2020

Bi nanodendrite acts as an efficient electrocatalyst for ambient N2-to-NH3 with NH3 yield rate of 25.86 μg h−1 mg−1cat. and faradaic efficiency of 10.8% at −0.60 V and −0.55 V versus RHE, respectively.
Crystal formation of 1D coordination polymers based on chiral, achiral and racemic 1,2-cyclohexane scaffolds
Authors: Jouaiti Abdelaziz , Grosshans Philippe , Kyritsakas Nathalie , Ferlay Sylvie , Henry Marc , Hosseini Mir Wais
Published: January 2020

Enantiomerically pure ligands (1a and 1b) and meso1c based on trans-1,2-cyclohexanediol and cis-1,2-cyclohexanediol, respectively, were used for the formation of zigzag 1D coordination polymers, when combined with bent HgCl2.
Opportunities for less-explored zeolitic materials in the syngas-to-olefins pathway over nanoarchitectured catalysts: a mini review
Authors: Masudi Ahmad , Jusoh Nurfatehah Wahyuny Che , Muraza Oki
Published: January 2020

The continuous demand for olefins has stimulated recent research to develop appropriate technology to produce olefins from alternative resources.
Structure reconstruction of metal/alloy in reaction conditions: a volcano curve?
Authors: Meng Jun , Zhu Beien , Gao Yi
Published: January 2020

The gas-induced structure reconstruction of metal/alloy evolves like a volcano curve in response to temperature or gas pressure.
Colloidal dispersions of oxide nanoparticles in ionic liquids: elucidating the key parameters
Authors: Riedl J. C. , Akhavan Kazemi M. A. , Cousin F. , Dubois E. , Fantini S. , Loïs S. , Perzynski R. , Peyre V.
Published: January 2020

Key parameters were identified to obtain long-term stable ionic liquid-based colloids.
Unraveling the role of the lacunar Na7PW11O39 catalyst in the oxidation of terpene alcohols with hydrogen peroxide at room temperature
Authors: Vilanculo Castelo B. , Da Silva Márcio J.
Published: January 2020

The Na7PW11O39 lacunar salt was the most active among Keggin lacunar salts (Na8SiW11O39 and Na7PMo11O39), a saturated salt (Na7PW12O40) and heteropolyacid catalysts.
Evaluation of the supramolecular interaction of Congo red with cucurbiturils using mass spectrometry and spectroscopic methods
Authors: Costa Ana L. , Gomes Ana C. , Lopes André D. , Da Silva José P. , Pillinger Martyn , Gonçalves Isabel S. , Seixas de Melo J. Sérgio
Published: January 2020

Cucurbit[n]urils decolourise aqueous solutions of Congo red by forming outer-surface adducts, which are also detected in gas-phase ESI-MS studies.
Improved efficiency of single-component active layer photovoltaics by optimizing conjugated diblock copolymers
Authors: Shi Dengke , Wang Huabin , Sun Hua , Yuan Wenbo , Wang Shifan , Huang Wei
Published: January 2020

Using an A–B type monomer instead of an AA + BB type monomer to synthesise diblock copolymers, the PCE of a single-component photovoltaic device reached 1.22%.
The application of ultrasonic treatment and a bis(2-ethylhexyl)sulfosuccinate-based novel ionic liquid for cadmium extraction
Authors: Guo Junkang , Li Yanping , Ren Xinhao , Xu Huihui , Wei Ting , Jia Honglei , Hua Li , Zhang Yi , Li Yongtao
Published: January 2020

The application of [N4444]AOT can significantly decrease the bioavailability of Cd in soil without changing the soil properties.
Facile synthesis of SnO2@carbon nanocomposites for lithium-ion batteries
Authors: Ambalkar Anuradha A. , Panmand Rajendra P. , Kawade Ujjwala V. , Sethi Yogesh A. , Naik Sonali D. , Kulkarni Milind V. , Adhyapak Parag V. , Kale Bharat B.
Published: January 2020

SnO2@C nanocomposite nanostructure approach is demonstrated, which confers shielding for volume expansion because of carbon. The SnO2@C nanocomposite anode exhibits superior cycling stability and rate capability due to the stable electrode structure.
An optomechanical study of mechanoluminescent elastomeric polyurethanes with different hard segments
Authors: Liu Shuang , Yuan Yuan , Li Junyu , Sun Shuqing , Chen Yulan
Published: January 2020

An optomechanical study of a series of mechanochemiluminescent polyurethanes with different hard segments provides a detailed picture of microphase separation dependent force transduction during their failure process.
13.76% efficiency nonfullerene solar cells enabled by selenophene integrated dithieno[3,2-b:2′,3′-d]pyrrole asymmetric acceptors
Authors: Cao Jinru , Qu Shenya , Yu Jiangsheng , Zhang Zhuohan , Geng Renyong , Yang Linqiang , Wang Hongtao , Du Fuqiang , Tang Weihua
Published: January 2020

An asymmetric heptacyclic electron-donating core, namely DTPPSe, was developed by integrating selenophene and dithieno[3,2-b:2′,3′-d]pyrrole (DTP) building blocks.
Rhodium-catalyzed ene-cycloisomerization of allylic-sulfide-tethered alkylidenecyclopropanes: DFT analysis of origins of regio- and diastereo-selectivities
Authors: Wang Ting , Lv Shuting , Guo Xianming , Li Zhanpeng , Li Juan
Published: January 2020

A unconventional reaction mechanism can be responsible for the regio- and diastereo-selectivities of rhodium-catalyzed ene-cycloisomerization of allylic-sulfide-tethered alkylidenecyclopropanes.
Microstructure and electrochemical performance of 3D hierarchical porous graphene/polyaniline composites
Authors: Hou Zhaoxia , Kong Lingxi , Zou Shengnan , Zhao Lanwei , Yang Lirong
Published: January 2020

3D hierarchical porous graphene/polyaniline composites show outstanding performance in energy storage field due to their unique microstructure and properties.
Efficient syntheses of macrocycles ranging from 22–28 atoms through spontaneous dimerization to yield bis-hydrazones
Authors: Sharma Vishal R. , Mehmood Arshad , Janesko Benjamin G. , Simanek Eric E.
Published: January 2020

Acid treatment of a triazine displaying both a tethered acetal and BOC-protected hydrazine group leads to spontaneous condensation to yield macrocyclic dimers in excellent yields and purity.
Dual responsive PMEEECL–PAE block copolymers: a computational self-assembly and doxorubicin uptake study
Authors: Koochaki Amin , Moghbeli Mohammad Reza , Nikkhah Sousa Javan , Ianiro Alessandro , Tuinier Remco
Published: January 2020

The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the drug doxorubicin is demonstrated using molecular dynamics simulations, coarse-grained force field simulations and self-consistent field theory.
m-s-m cationic gemini and zwitterionic surfactants – a thermodynamic analysis of their mixed micelle formation
Authors: McLachlan Aleisha , Singh Kulbir , McAlduff Michael , Marangoni D. Gerrard , Shortall Samantha , Wettig Shawn D.
Published: January 2020

Excess enthalpies of micelle formation for the ZW3-12/12-s-12 system as a function of the mole fraction of zwittergent (αZW3-12).
Protection of lithium anodes by fibrous silica nanospheres
Authors: Fan Jinxin , Luo Yu , Jiang Keliang , Wang Cheng
Published: January 2020

A fibrous silica nanosphere coating was designed and prepared to protect lithium-metal anodes.
Tuning a surface super-repellent to liquid metal by a femtosecond laser
Authors: Zhang Chengjun , Yang Qing , Shan Chao , Zhang Jingzhou , Yong Jiale , Fang Yao , Hou Xun , Chen Feng
Published: January 2020

Liquid-metal-repellent microstructures were created on various substrates by femtosecond laser ablation, which have important potential applications in preparing flexible circuits.
A microgel-Pickering emulsion route to colloidal molecules with temperature-tunable interaction sites
Authors: Månsson Linda K. , Peng Feifei , Crassous Jérôme J. , Schurtenberger Peter
Published: January 2020

A novel microgel-Pickering emulsion route has been developed for the preparation of colloidal molecules with well-defined, temperature-responsive interaction sites.
A mechanistic study of mesoporous TiO2nanoparticle negative electrode materials with varying crystallinity for lithium ion batteries
Authors: Deng Changjian , Lau Miu Lun , Ma Chunrong , Skinner Paige , Liu Yuzi , Xu Wenqian , Zhou Hua , Zhang Xianghui , Wu Di , Yin Yadong , Ren Yang , Perez Jorge , Jaramillo Diana , Barnes Pete , Hou Dewen , Dahl Michael , Williford Bethany , Zheng Chong , Xiong Hui (Claire)
Published: January 2020

Nanoscale oxide-based negative electrodes are of great interest for lithium ion batteries due to their high energy/power density, and enhanced safety. The crystallinity effect of mesoporous TiO2nanoparticle electrode was investigated in this work.
Sulfide cluster vacancies inducing an electrochemical reversibility improvement of titanium disulfide electrode material
Authors: Lu Jianhao , Lian Fang , Zhang Yuxuan , Chen Ning , Li Yang , Ding Fei , Liu Xingjiang
Published: January 2020

CV–TiS2−x exhibits an extended planar spacing and structural integrity in a process involving more lithium ions due to the presence of abundant S-vacancies.
Sequential delivery of synergistic drugs by silica nanocarriers for enhanced tumour treatment
Authors: Birault Albane , Giret Simon , Théron Christophe , Gallud Audrey , Da Silva Afitz , Durand Denis , Nguyen Christophe , Bettache Nadir , Gary-Bobo Magali , Bartlett John R. , Wong Chi Man Michel , Carcel Carole
Published: January 2020

Environmentally-responsive nanocarriers exhibiting a synergistic effect, where pH-triggered release of the cytotoxic cap followed by diffusion-controlled release of the drug cargo led to essentially complete cell death.
CT/NIRF dual-modal imaging tracking and therapeutic efficacy of transplanted mesenchymal stem cells labeled with Au nanoparticles in silica-induced pulmonary fibrosis
Authors: Huang Jie , Huang Jie , Ning Xinyu , Luo Wei , Chen Mengling , Wang Zhangyan , Zhang Wei , Zhang Zhijun , Chao Jie
Published: January 2020

AA@ICG@PLL NPs, as CT/NIRF dual modal nanotracers, were synthesized to track BMSCs in the treatment of pulmonary fibrosis.
Stimuli-responsive release and efficient siRNA delivery in non-small cell lung cancer by a poly(l-histidine)-based multifunctional nanoplatform
Authors: Shi Menghao , Zhang Jiulong , Huang Ziyuan , Chen Yuying , Pan Shuang , Hu Haiyang , Qiao Mingxi , Chen Dawei , Zhao Xiuli
Published: January 2020

A stimuli-responsive nanoplatform achieves successful intracellular siRNA delivery due to a proton sponge effect based on poly(l-histidine) and effective gene silencing in vivo.
Self-adaptive radiative cooling and solar heating based on a compound metasurface
Authors: Wang Wanlin , Zhao Zhongping , Zou Qixuan , Hong Binbin , Zhang Wang , Wang Guo Ping
Published: January 2020

A conceptive design of self-adaptive photonic thermal management can keep cool under high temperature and keep warm under low temperature with the compound metasurface.
Nickel sulfide nanocrystals for electrochemical and photoelectrochemical hydrogen generation
Authors: Yoo Jisun , Kwak In Hye , Kwon Ik Seon , Park Kidong , Kim Doyeon , Lee Jong Hyun , Lim Soo A , Cha Eun Hee , Park Jeunghee
Published: January 2020

Nickel sulfide nanocrystals act as excellent catalysts for electrocatalytic and photoelectrochemical hydrogen evolution.
H-Bonding on spin centres enhances spin–spin coupling for organic diradicals
Authors: Burnea Francis Kirby B. , Nam Yeonsig , Lee Jin Yong
Published: January 2020

Intramolecular ferromagnetic spin–spin interactions in a nitroxide-based organic diradical is enhanced by hydrogen-bonding interactions through the spin centers.
Reversible photo/thermal stimuli-responsive electrical bistability performance in supramolecular co-crystals accompanied by crystalline-to-amorphous transformations
Authors: Liu Qian , Zhao Liming , Wu Wei , He Yan , Song Kaiyue , Qi Jiayuan , Li Haohong , Chen Zhirong
Published: January 2020

A co-crystal-based device exhibits reversibly stimuli-responsive switchable conductivity states, and its photo/thermal responsive electrically bistable switching mechanism was proposed.
Detection range extended 2D Ruddlesden–Popper perovskite photodetectors
Authors: Pan Yiyi , Wang Haoliang , Li Xiaoguo , Zhang Xin , Liu Fengcai , Peng Meng , Shi Zejiao , Li Chongyuan , Zhang Haijuan , Weng Zhenhua , Gusain Meenakshi , Long Huabao , Li Dapeng , Wang Jiao , Zhan Yiqiang , Zheng Lirong
Published: January 2020

Two-dimensional (2D) perovskite materials are a promising platform to construct high performance photodetectors due to their novel structure, high stability, resistance to ion migration and decent light harvesting ability.
Control of π–π stacking in carbazole-benzimidazo〈1,2-f〉phenanthridines: the design of electron-transporting bipolar hosts for phosphorescent organic light-emitting diodes
Authors: Chen Yu-Hsin , Chen Chia-Hsun , Chang Chun-Ming , Fan Bo-An , Chen Deng-Gao , Lee Jiun-Haw , Chiu Tien-Lung , Chou Pi-Tai , Leung Man-kit
Published: January 2020

The planar benzimidazo〈1,2-f〉phenanthridine moieties form effective electron transport channels through pi-stacking.
Deep learning guided image-based droplet sorting for on-demand selection and analysis of single cells and 3D cell cultures
Authors: Anagnostidis Vasileios , Sherlock Benjamin , Metz Jeremy , Mair Philip , Hollfelder Florian , Gielen Fabrice
Published: January 2020

To uncover the heterogeneity of cellular populations and multicellular constructs we show on-demand isolation of single mammalian cells and 3D cell cultures by coupling bright-field microdroplet imaging with real-time classification and sorting using convolutional neural networks.
Kir6.2-D323 and SUR2A-Q1336: an intersubunit interaction pairing for allosteric information transfer in the KATP channel complex
Authors: Brennan Sean , Rubaiy Hussein N. , Imanzadeh Saba , Reid Ruth , Lodwick David , Norman Robert I. , Rainbow Richard D.
Published: January 2020

ATP-sensitive potassium (KATP) channels are widely expressed and play key roles in many tissues by coupling metabolic state to membrane excitability. The SUR subunits confer drug and enhanced nucleotide sensitivity to the pore-forming Kir6 subunit, and so information transfer between the subunits must occur. In our previous study, we identified an electrostatic interaction between Kir6 and SUR2 subunits that was key for allosteric information transfer between the regulatory and pore-forming subunit. In this study, we demonstrate a second putative interaction between Kir6.2-D323 and SUR2A-Q1336 using patch clamp electrophysiological recording, where charge swap mutation of the residues on either side of the potential interaction compromise normal channel function. The Kir6.2-D323K mutation gave rise to a constitutively active, glibenclamide and ATP-insensitive KATP complex, further confirming the importance of information transfer between the Kir6 and SUR2 subunits. Sensitivity to modulators was restored when Kir6.2-D323K was co-expressed with a reciprocal charge swap mutant, SUR-Q1336E. Importantly, equivalent interactions have been identified in both Kir6.1 and Kir6.2 suggesting this is a second important interaction between Kir6 and the proximal C terminus of SUR.
Lysosomal protein thermal stability does not correlate with cellular half-life: global observations and a case study of tripeptidyl-peptidase 1
Authors: Collier Aaron M. , Nemtsova Yuliya , Kuber Narendra , Banach-Petrosky Whitney , Modak Anurag , Sleat David E. , Nanda Vikas , Lobel Peter
Published: January 2020

Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a neurodegenerative lysosomal storage disorder caused by mutations in the gene encoding the protease tripeptidyl-peptidase 1 (TPP1). Progression of LINCL can be slowed or halted by enzyme replacement therapy, where recombinant human TPP1 is administered to patients. In this study, we utilized protein engineering techniques to increase the stability of recombinant TPP1 with the rationale that this may lengthen its lysosomal half-life, potentially increasing the potency of the therapeutic protein. Utilizing multiple structure-based methods that have been shown to increase the stability of other proteins, we have generated and evaluated over 70 TPP1 variants. The most effective mutation, R465G, increased the melting temperature of TPP1 from 55.6°C to 64.4°C and increased its enzymatic half-life at 60°C from 5.4 min to 21.9 min. However, the intracellular half-life of R465G and all other variants tested in cultured LINCL patient-derived lymphoblasts was similar to that of WT TPP1. These results provide structure/function insights into TPP1 and indicate that improving in vitro thermal stability alone is insufficient to generate TPP1 variants with improved physiological stability. This conclusion is supported by a proteome-wide analysis that indicates that lysosomal proteins have higher melting temperatures but also higher turnover rates than proteins of other organelles. These results have implications for similar efforts where protein engineering approaches, which are frequently evaluated in vitro, may be considered for improving the physiological properties of proteins, particularly those that function in the lysosomal environment.
Isoliquiritigenin inhibits the proliferation, migration and metastasis of Hep3B cells via suppressing cyclin D1 and PI3K/AKT pathway
Authors: Huang Yun , Liu Chen , Zeng Wu-Cha , Xu Guo-Yan , Wu Jian-Min , Li Zhi-Wen , Huang Xuan-Yu , Lin Rong-Jin , Shi Xi
Published: January 2020

The overall survival rate of patients with hepatocellular carcinoma (HCC) has remained unchanged over the last several decades. Therefore, novel drugs and therapies are required for HCC treatment. Isoliquiritigenin (ISL), a natural flavonoid predominantly isolated from the traditional Chinese medicine Glycyrrhizae Radix (Licorice), has a high anticancer potential and broad application value in various cancers. Here, we aimed to investigate the anticancer role of ISL in the HCC cell line Hep3B. Functional analysis revealed that ISL inhibited the proliferation of Hep3B cells by causing G1/S cell cycle arrest in vitro. Meanwhile, the inhibitory effect of ISL on proliferation was also observed in vivo. Further analysis revealed that ISL could suppress the migration and metastasis of Hep3B cells in vitro and in vivo. Mechanistic analysis revealed that ISL inhibited cyclin D1 and up-regulated the proteins P21, P27 that negatively regulate the cell cycle. Furthermore, ISL induced apoptosis while inhibiting cell cycle transition. In addition, phosphatidylinositol 3′-kinase/protein kinase B (PI3K/AKT) signal pathway was suppressed by ISL treatment, and the epithelial marker E-cadherin was up-regulated when the mesenchymal markers Vimentin and N-cadherin were down-regulated. In brief, our findings suggest that ISL could be a promising agent for preventing HCC tumorigenesis and metastasis.
Molecular mechanisms in SUMO conjugation
Authors: Varejão Nathalia , Lascorz Jara , Li Ying , Reverter David
Published: January 2020

The small ubiquitin-like modifier (SUMO) is a post-translational modifier that can regulate the function of hundreds of proteins inside the cell. SUMO belongs to the ubiquitin-like family of proteins that can be attached to target proteins by a dedicated enzymatic cascade pathway formed by E1, E2 and E3 enzymes. SUMOylation is involved in many cellular pathways, having in most instances essential roles for their correct function. In this review, we want to highlight the latest research on the molecular mechanisms that lead to the formation of the isopeptidic bond between the lysine substrate and the C-terminus of SUMO. In particular, we will focus on the recent discoveries on the catalytic function of the SUMO E3 ligases revealed by structural and biochemical approaches. Also, we will discuss important questions regarding specificity in SUMO conjugation, which it still remains as a major issue due to the small number of SUMO E3 ligases discovered so far, in contrast with the large number of SUMO conjugated proteins in the cell.
The ALMA-PILS survey: inventory of complex organic molecules towards IRAS 16293–2422 A
Authors: Manigand S. , Jørgensen J. K. , Calcutt H. , Müller H. S. P. , Ligterink N. F. W. , Coutens A. , Drozdovskaya M. N. , van Dishoeck E. F. , Wampfler S. F.
Published: January 2020

Context.Complex organic molecules are detected in many sources in the warm inner regions of envelopes surrounding deeply embedded protostars. Exactly how these species form remains an open question.

Aims.This study aims to constrain the formation of complex organic molecules through comparisons of their abundances towards the Class 0 protostellar binary IRAS 16293–2422.

Methods.We utilised observations from the ALMA Protostellar Interferometric Line Survey of IRAS 16293–2422. The species identification and the rotational temperature and column density estimation were derived by fitting the extracted spectra towards IRAS 16293–2422 A and IRAS 16293–2422 B with synthetic spectra. The majority of the work in this paper pertains to the analysis of IRAS 16293–2422 A for a comparison with the results from the other binary component, which have already been published.

Results.We detect 15 different complex species, as well as 16 isotopologues towards the most luminous companion protostar IRAS 16293–2422 A. Tentative detections of an additional 11 isotopologues are reported. We also searched for and report on the first detections of methoxymethanol (CH3OCH2OH) and trans-ethyl methyl ether (t-C2H5OCH3) towards IRAS 16293–2422 B and the follow-up detection of deuterated isotopologues of acetaldehyde (CH2DCHO and CH3CDO). Twenty-four lines of doubly-deuterated methanol (CHD2OH) are also identified.

Conclusions.The comparison between the two protostars of the binary system shows significant differences in abundance for some of the species, which are partially correlated to their spatial distribution. The spatial distribution is consistent with the sublimation temperature of the species; those with higher expected sublimation temperatures are located in the most compact region of the hot corino towards IRAS 16293–2422 A. This spatial differentiation is not resolved in IRAS 16293–2422 B and will require observations at a higher angular resolution. In parallel, the list of identified CHD2OH lines shows the need of accurate spectroscopic data including their line strength.
Gravity and limb-darkening coefficients for compact stars: DA, DB, and DBA eclipsing white dwarfs
Authors: Claret A. , Cukanovaite E. , Burdge K. , Tremblay P.-E. , Parsons S. , Marsh T. R.
Published: January 2020

Context. The distribution of the specific intensity over the stellar disk is an essential tool for modeling the light curves in eclipsing binaries, planetary transits, and stellar diameters through interferometric techniques, line profiles in rotating stars, gravitational microlensing, etc. However, the available theoretical calculations are mostly restricted to stars on the main sequence or the giant branch, and very few calculations are available for compact stars.

Aims. The main objective of the present work is to extend these investigations by computing the gravity and limb-darkening coefficients for white dwarf atmosphere models with hydrogen, helium, or mixed compositions (types DA, DB, and DBA).

Methods. We computed gravity and limb-darkening coefficients for DA, DB, and DBA white dwarfs atmosphere models, covering the transmission curves of the Sloan, UBVRI, Kepler, TESS, and Gaia photometric systems. Specific calculations for the HiPERCAM instrument were also carried out. For all calculations of the limb-darkening coefficients we used the least-squares method. Concerning the effects of tidal and rotational distortions, we also computed for the first time the gravity-darkening coefficients y(λ) for white dwarfs using the same models of stellar atmospheres as in the case of limb-darkening. A more general differential equation was introduced to derive these quantities, including the partial derivative (∂ln Io(λ)/∂ln g)Teff.

Results. Six laws were adopted to describe the specific intensity distribution: linear, quadratic, square root, logarithmic, power-2, and a more general one with four coefficients. The computations are presented for the chemical compositions log[H/He] = −10.0 (DB), −2.0 (DBA) and He/H = 0 (DA), with log g varying between 5.0 and 9.5 and effective temperatures between 3750 and 100 000 K. For effective temperatures higher than 40 000 K, the models were also computed adopting nonlocal thermal equilibirum (DA). The adopted mixing-length parameters are ML2/α = 0.8 (DA case) and 1.25 (DB and DBA). The results are presented in the form of 112 tables. Additional calculations, such as for other photometric systems and/or different values of log[H/He], log g, and Teff can be performed upon request.
Therapieresistente und ‑refraktäre Hypertonie
Authors: Düsing Rainer
Published: January 2020

Hypertension is defined as resistant to treatment when treatment fails to lower office systolic and diastolic blood pressure values to < 140/90 mmHg. The treatment strategy should include lifestyle measures and appropriate doses of three or more drugs acting by different mechanisms including a diuretic. An updated definition of treatment resistance includes all patients with ≥ 4 antihypertensive agents of different classes irrespective of their on-treatment blood pressure. The term “refractory” hypertension has been suggested for patients with uncontrolled blood pressure on ≥ 5 antihypertensive drugs including the thiazide-like diuretic chlorthalidone and the mineralocorticoid receptor antagonist spironolactone. “Pseudo resistance” especially due to white coat hypertension and non-adherence with the prescribed medication has to be ruled out to be able to identify patients with “true” treatment resistance. Therefore, before distinguishing true from pseudo resistance, the term “apparent” resistance should be used. While the prevalence of apparent resistance may be in the range of 10–15 % of treated patients, the exact prevalence of true resistance remains unknown due to the lack of appropriate studies but is likely to be rather small including a high proportion of patients with secondary forms of hypertension. Once identified most patients with true treatment resistance should receive intensified drug treatment primarily by expanded diuretic usage. Thus, resistant hypertension is primarily a diagnostic challenge: identifying patients with true resistance and those with secondary hypertension.
Ist die Sarkoidose eine durch Vitamin D getriggerte Krebsabwehr?
Authors: von Helden Raimund , Grant William B. , Moukayed Meis , Becker Bernd
Published: January 2020

Die Ursache der Sarkoidose ist bislang unbekannt. Vitamin D ist zur Behandlung der Erkrankung kontraindiziert. Wir fragen daher, was Sarkoidose verursacht und warum Vitamin D für die Betroffenen gefährlich sein kann und schlagen eine gegenteilige Hypothese vor: Sarkoidose ist ein physiologischer Prozess der Krebsabwehr, der Vitamin D als Substrat benötigt. Zur Prüfung der Hypothese haben wir anhand einer Literaturrecherche zahlreiche Fallberichte über Sarkoidose und Krebs gefunden sowie Fälle von Krebsmimikry durch Sarkoidose. Mehrere Berichte beschreiben Spontanheilungen der Krebserkrankung bei gleichzeitigem Auftreten einer Sarkoidose. Im Zusammenhang mit den Granulomen der Sarkoidose bilden Monozyten den Ort der Vitamin-D-Freisetzung. Darüber hinaus kann aktives Vitamin D Krebszellen mithilfe der Vitamin-D-Rezeptoren des Zellkerns kontrollieren. Dass Granulome „nicht verkäsend“ sind, wird als Resorption von humanen Molekülen der Krebszellen erklärt. Der Umstand, dass in den Granulomen der Sarkoidose meist Krebszellen fehlen, wird als Ergebnis einer gut funktionierenden Sarkoidose interpretiert. Wir betrachten die typische Synthese von aktivem Vitamin D in den Sarkoidose-Monozyten als Krebsabwehr. Die Hypothese muss durch weitere Untersuchungen untermauert werden.
Low Sugar und High Dose Vitamin C
Authors: Holzhauer Peter
Published: January 2020

Die hochdosierte parenterale Applikation von Vitamin C wird häufig als komplementäre Supportivtherapie bei tumorassoziierter Fatigue-Symptomatik eingesetzt 1
3. Die vorgestellte Kasuistik beschreibt eine folgenreiche Wechselwirkung dieser medikamentösen supportiven Therapie mit einem High Tech Medizinprodukt 2. Eine 55-jährige Patientin mit metastasiertem triple negativem Mammakarzinom erhält eine Chemotherapie mit Gemcitabin. Die Auswahl dieses Zytostatikums erfolgte auf dringenden Wunsch der Patientin auf der Basis einer von der Patientin initiierten Liquid Biopsy. Einen Tag nach Applikation der Chemotherapie erhielt die Patientin 7,5 g Vitamin C als Kurzinfusion über 30 Minuten. 3 Stunden später erlitt sie einen generalisierten Krampfanfall und war nicht mehr ansprechbar. Die Messung des Blutzuckers ergab eine Hypoglykämie mit einem Blutzuckerwert von 48 mg/dl. Nach intravenöser Glukosegabe rekompensierte sie schnell. Der kausale Zusammenhang wird beschrieben.
Drug-Induced Liver Injury (DILI) in Patients with Depression Treated with Antidepressants: A Retrospective Multicenter Study
Authors: Ueberberg Bianca , Frommberger Ulrich , Messer Thomas , Zwanzger Peter , Kuhn Jens , Anghelescu Ion , Ackermann Katharina , Assion Hans-Jörg
Published: January 2020

Introduction Drug-induced liver injury (DILI) is the 4th most common cause of liver damage in Western countries and can be caused by antidepressants.

Methods Against the background of increasing antidepressant prescriptions and increasing use of polypharmacy, we analyzed administered antidepressants and other pharmacological substances, liver toxicity, comorbid somatic secondary diseases together with the occurrence of DILI in a patient population of 6 centers throughout Germany.

Results The majority of the enrolled 329 patients received polypharmacological treatment in an inpatient setting. During antidepressant treatment 5.1% of the patients had elevated serum transaminase levels, whereby exactly and not more than 1 criterion proposed to be indicative for DILI, was fulfilled by 3 patients (0.9%).

Discussion During patient characterization it becomes clear that a sensitization for relevant risk constellations causing liver injury in MDD patients is relevant to prevent further serious adverse events.
A Reduction in Match-to-match Variability Using Maximal Mean Analyses in Sub-elite Soccer
Authors: Lord Cameron , Blazevich Anthony John , Abbiss Chris Richard , Maʼayah Fadi
Published: January 2020

The match-to-match variability of external loads in National Premier League soccer competition was determined. Global positioning systems (GPS) data were collected from 20 sub-elite soccer players over 2–10 matches from a single season. Match data were collected from during one season. Twenty-six matches were recorded and 10 were utilised within final match-to-match analysis based on stringent data selection criteria. A symmetric moving average algorithm was applied to GPS data over specific time windows (1, 5, 10, 60, 300 and 600 s), and maximal speed and metabolic power values then calculated at each time interval during each match. Match-to-match coefficients of variation (CV) were greatest for sprint-speed running distance (36.3–43.6%) when comparing 2 vs. 10 matches. CVs for maximal mean speed (4.9–7.0%) and metabolic power (4.4–9.6%) ranged from good to moderate. As the variability of absolute high-speed distance values are greater, and therefore less reliable, their use as indicators of performance is reduced, suggesting that maximal mean analyses could be used as an alternative in the assessment of match running performance during competitive matches.
Angiopoietin 2 and Neuropeptide Y are Associated with Diabetic Kidney
Disease in Type 1 Diabetes Mellitus
Authors: Sokolovska Jelizaveta , Stefanovics Juris , Gersone Gita , Pahirko Leonora , Valeinis Janis , Kalva-Vaivode Sanita , Rovite Vita , Blumfelds Leons , Pirags Valdis , Tretjakovs Peteris
Published: January 2020

Background Serum angiopoietin 2 levels have been associated with
endothelial dysfunction and diabetic kidney disease. Derangements in autonomous
nervous system lead to increased production of vasoconstrictory and angiogenic
mediators such as norepinephrine and neuropeptide Y and are associated with
increased risk of microvascular complications.

Aim To investigate associations between angiopoietin 2, neuropeptide Y
and diabetic kidney disease in patients with type 1 diabetes mellitus.

Methods 289 patients with type 1 diabetes mellitus duration > 1
year were included. Patients were stratified according to presence of diabetic
nephropathy (macroalbuminuria, estimated glomerular filtration
rate<60 ml/min/1.73 m2 or
end-stage renal disease). Angiopoietin 2 was measured by Luminex technology.
Neuropeptide Y was measured by ELISA.

Results Patients with diabetic nephropathy had significantly increased
levels of angiopoietin 2 (4020.5 (2172.4–5778.1) pg/ml
vs. 2001.0 (1326.7–2862.7) pg/ml) and
neuropeptide Y (18.22 (14.85–21.85) ng/ml vs.
12.91 (9.96–17.07) ng/ml). Higher levels of angiopoietin
2 and neuropeptide Y were observed also in patients with arterial hypertension.
Angiopoietin 2 and neuropeptide Y correlated significantly
(ρ=0.245, p<0.001). Both biomarkers were significant
predictors of estimated glomerular filtration rate and diabetic nephropathy in
univariate regression models. In the fully adjusted regression models and after
application of a stepwise selection regression method, angiopoietin 2
demonstrated a stronger predictive power for diabetic nephropathy compared to
neuropeptide Y.

Conclusion Diabetic nephropathy is associated with increased serum
concentrations of angiopoietin 2 (marker of endothelial dysfunction) and
neuropeptide Y (marker of sympathetic activity) in type 1 diabetes. Angiopoietin
2 is a more potent predictor of diabetic nephropathy compared to neuropeptide
Y.