bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteogenomic landscape of squamous cell lung cancer
Authors: Stewart Paul A. , Welsh Eric A. , Slebos Robbert J. C. , Fang Bin , Izumi Victoria , Chambers Matthew , Zhang Guolin , Cen Ling , Pettersson Fredrik , Zhang Yonghong , Chen Zhihua , Cheng Chia-Ho , Thapa Ram , Thompson Zachary , Fellows Katherine M. , Francis Jewel M. , Saller James J. , Mesa Tania , Zhang Chaomei , Yoder Sean , DeNicola Gina M. , Beg Amer A. , Boyle Theresa A. , Teer Jamie K. , Ann Chen Yian , Koomen John M. , Eschrich Steven A. , Haura Eric B. 
Published: August 2019

AbstractHow genomic and transcriptomic alterations affect the functional proteome in lung cancer is not fully understood. Here, we integrate DNA copy number, somatic mutations, RNA-sequencing, and expression proteomics in a cohort of 108 squamous cell lung cancer (SCC) patients. We identify three proteomic subtypes, two of which (Inflamed, Redox) comprise 87% of tumors. The Inflamed subtype is enriched with neutrophils, B-cells, and monocytes and expresses more PD-1. Redox tumours are enriched for oxidation-reduction and glutathione pathways and harbor more NFE2L2/KEAP1 alterations and copy gain in the 3q2 locus. Proteomic subtypes are not associated with patient survival. However, B-cell-rich tertiary lymph node structures, more common in Inflamed, are associated with better survival. We identify metabolic vulnerabilities (TP63, PSAT1, and TFRC) in Redox. Our work provides a powerful resource for lung SCC biology and suggests therapeutic opportunities based on redox metabolism and immune cell infiltrates.
Three-dimensional aromaticity in an antiaromatic cyclophane
Authors: Nozawa Ryo , Kim Jinseok , Oh Juwon , Lamping Anna , Wang Yemei , Shimizu Soji , Hisaki Ichiro , Kowalczyk Tim , Fliegl Heike , Kim Dongho , Shinokubo Hiroshi 
Published: August 2019

AbstractUnderstanding of interactions among molecules is essential to elucidate the binding of pharmaceuticals on receptors, the mechanism of protein folding and self-assembling of organic molecules. While interactions between two aromatic molecules have been examined extensively, little is known about the interactions between two antiaromatic molecules. Theoretical investigations have predicted that antiaromatic molecules should be stabilized when they stack with each other by attractive intermolecular interactions. Here, we report the synthesis of a cyclophane, in which two antiaromatic porphyrin moieties adopt a stacked face-to-face geometry with a distance shorter than the sum of the van der Waals radii of the atoms involved. The aromaticity in this cyclophane has been examined experimentally and theoretically. This cyclophane exhibits three-dimensional spatial current channels between the two subunits, which corroborates the existence of attractive interactions between two antiaromatic π-systems.
Highly efficient dandelion-like near-infrared light photoinitiator for free radical and thiol-ene photopolymerizations
Authors: Li Zhiquan , Zou Xiucheng , Shi Feng , Liu Ren , Yagci Yusuf 
Published: August 2019

AbstractEfficient photopolymerization activated by nonharmful near-infrared (NIR) light is important for various biological applications. Here we propose a NIR light free-radical photoinitiator (PI) fabricated by incorporating oxime-ester coumarin functionality on the surface of upconversion nanoparticles (UCNPs). The coumarin groups of PI absorb the light emitted from the UCNP core, whereas the oxime ester groups undergo cleavage to form radicals. Upon irradiation at 980 nm, the mobile radicals, formed in a manner similar to that of dandelion seed release, initiate both free-radical and thiol-ene photopolymerizations. The superior efficiency of dandelion-like PIs assisted photopolymerizations can be attributed to the reduction of energy loss and increased local PI concentration due to Förster resonance energy transfer process and confinement effect, respectively. Moreover, the proposed PI system can initiate polymerization under low-power NIR laser and reduces the thermal side effects. The possibility of its potential use in deep curing applications was also demonstrated.
Packaging materials with desired mechanical and barrier properties and full chemical recyclability
Authors: Sangroniz Ainara , Zhu Jian-Bo , Tang Xiaoyan , Etxeberria Agustin , Chen Eugene Y.-X. , Sardon Haritz 
Published: August 2019

AbstractPlastics have become indispensable in modern life and the material of choice in packaging applications, but they have also caused increasing plastic waste accumulation in oceans and landfills. Although there have been continuous efforts to develop biodegradable plastics, the mechanical and/or transport properties of these materials still need to be significantly improved to be suitable for replacing conventional plastic packaging materials. Here we report a class of biorenewable and degradable plastics, based on copolymers of γ-butyrolactone and its ring-fused derivative, with competitive permeability and elongation at break compared to commodity polymers and superior mechanical and transport properties to those of most promising biobased plastics. Importantly, these materials are designed with full chemical recyclability built into their performance with desired mechanical and barrier properties, thus representing a circular economy approach to plastic packaging materials.
Saturation mutagenesis of twenty disease-associated regulatory elements at single base-pair resolution
Authors: Kircher Martin , Xiong Chenling , Martin Beth , Schubach Max , Inoue Fumitaka , Bell Robert J. A. , Costello Joseph F. , Shendure Jay , Ahituv Nadav 
Published: August 2019

AbstractThe majority of common variants associated with common diseases, as well as an unknown proportion of causal mutations for rare diseases, fall in noncoding regions of the genome. Although catalogs of noncoding regulatory elements are steadily improving, we have a limited understanding of the functional effects of mutations within them. Here, we perform saturation mutagenesis in conjunction with massively parallel reporter assays on 20 disease-associated gene promoters and enhancers, generating functional measurements for over 30,000 single nucleotide substitutions and deletions. We find that the density of putative transcription factor binding sites varies widely between regulatory elements, as does the extent to which evolutionary conservation or integrative scores predict functional effects. These data provide a powerful resource for interpreting the pathogenicity of clinically observed mutations in these disease-associated regulatory elements, and comprise a rich dataset for the further development of algorithms that aim to predict the regulatory effects of noncoding mutations.
A consensus S. cerevisiae metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism
Authors: Lu Hongzhong , Li Feiran , Sánchez Benjamín J. , Zhu Zhengming , Li Gang , Domenzain Iván , Marcišauskas Simonas , Anton Petre Mihail , Lappa Dimitra , Lieven Christian , Beber Moritz Emanuel , Sonnenschein Nikolaus , Kerkhoven Eduard J. , Nielsen Jens 
Published: August 2019

AbstractGenome-scale metabolic models (GEMs) represent extensive knowledgebases that provide a platform for model simulations and integrative analysis of omics data. This study introduces Yeast8 and an associated ecosystem of models that represent a comprehensive computational resource for performing simulations of the metabolism ofSaccharomyces cerevisiae––an important model organism and widely used cell-factory. Yeast8 tracks community development with version control, setting a standard for how GEMs can be continuously updated in a simple and reproducible way. We use Yeast8 to develop the derived models panYeast8 and coreYeast8, which in turn enable the reconstruction of GEMs for 1,011 different yeast strains. Through integration with enzyme constraints (ecYeast8) and protein 3D structures (proYeast8DB), Yeast8 further facilitates the exploration of yeast metabolism at a multi-scale level, enabling prediction of how single nucleotide variations translate to phenotypic traits.
Brain-targeted drug delivery by manipulating protein corona functions
Authors: Zhang Zui , Guan Juan , Jiang Zhuxuan , Yang Yang , Liu Jican , Hua Wei , Mao Ying , Li Cheng , Lu Weiyue , Qian Jun , Zhan Changyou 
Published: August 2019

AbstractProtein corona presents a major obstacle to bench-to-bedside translation of targeted drug delivery systems, severely affecting targeting yields and directing unfavorable biodistribution. Corona-mediated targeting provides a new impetus for specific drug delivery by precisely manipulating interaction modes of functional plasma proteins on nano-surface. Here bio-inspired liposomes (SP-sLip) were developed by modifying liposomal surface with a short nontoxic peptide derived from Aβ1-42 that specifically interacts with the lipid-binding domain of exchangeable apolipoproteins. SP-sLip absorb plasma apolipoproteins A1, E and J, consequently exposing receptor-binding domain of apolipoproteins to achieve brain-targeted delivery. Doxorubicin loaded SP-sLip (SP-sLip/DOX) show significant enhancement of brain distribution and anti-brain cancer effect in comparison to doxorubicin loaded plain liposomes. SP-sLip preserve functions of the absorbed human plasma ApoE, and the corona-mediated targeting strategy works in SP modified PLGA nanoparticles. The present study may pave a new avenue to facilitate clinical translation of targeted drug delivery systems.
Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy
Authors: Ruzzo Annamaria , Graziano Francesco , Galli Francesca , Galli Fabio , Rulli Eliana , Lonardi Sara , Ronzoni Monica , Massidda Bruno , Zagonel Vittorina , Pella Nicoletta , Mucciarini Claudia , Labianca Roberto , Ionta Maria Teresa , Bagaloni Irene , Veltri Enzo , Sozzi Pietro , Barni Sandro , Ricci Vincenzo , Foltran Luisa , Nicolini Mario , Biondi Edoardo , Bramati Annalisa , Turci Daniele , Lazzarelli Silvia , Verusio Claudio , Bergamo Francesca , Sobrero Alberto , Frontini Luciano , Magnani Mauro 
Published: August 2019

AbstractPolymorphisms contribute to inter-individual differences and show a promising predictive role for chemotherapy-related toxicity in colon cancer (CC). TOSCA is a multicentre, randomized, non-inferiority, phase III study conducted in high-risk stage II/stage III CC patients treated with 6 vs 3 months of FOLFOX-4 or XELOX adjuvant chemotherapy. During this post-hoc analysis, 218 women and 294 men were genotyped for 17 polymorphisms: TYMS (rs34743033, rs2853542, rs11280056), MTHFR (rs1801133, rs1801131), ERCC1 (rs11615), XRCC1 (rs25487), XRCC3 (rs861539), XPD (rs1799793, rs13181), GSTP1 (rs1695), GSTT1/GSTM1 (deletion +/−), ABCC1 (rs2074087), and ABCC2 (rs3740066, rs1885301, rs4148386). The aim was to assess the interaction between these polymorphisms and sex, on safety in terms of time to grade ≥3 haematological (TTH), grade ≥3 gastrointestinal (TTG) and grade ≥2 neurological (TTN) toxicity. Interactions were detected on TTH for rs1801133 and rs1799793, on TTG for rs13181 and on TTN for rs11615. Rs1799793 GA genotype (p = 0.006) and A allele (p = 0.009) shortened TTH in men. In women, the rs11615 CC genotype worsened TTN (co-dominant model p = 0.008, recessive model p = 0.003) and rs13181 G allele improved the TTG (p = 0.039). Differences between the two sexes in genotype distribution of rs1885301 (p = 0.020) and rs4148386 (p = 0.005) were found. We highlight that polymorphisms could be sex-specific biomarkers. These results, however, need to be confirmed in additional series.
Correlation between early dynamics in circulating tumour DNA and outcome from FOLFIRI treatment in metastatic colorectal cancer
Authors: Lyskjær Iben , Kronborg Camilla Skovhus , Rasmussen Mads Heilskov , Sørensen Boe Sandahl , Demuth Christina , Rosenkilde Mona , Johansen Amanda Frydendahl Boll , Knudsen Michael , Vang Søren , Krag Søren Rasmus Palmelund , Spindler Karen-Lise Garm , Andersen Claus Lindbjerg 
Published: August 2019

AbstractChemotherapy resistance remains a challenge in the clinical management of metastatic colorectal cancer (mCRC). Here, early changes in cell-free circulating tumour DNA (ctDNA) levels were explored as a marker of therapeutic efficacy. Twenty-four mCRC patients were enrolled and treated with FOLFIRI based first-line therapy. Blood samples collected pre-treatment, at day 7, 14, 21, 60 and at progression were analysed for cell-free DNA (cfDNA) and ctDNA levels using digital droplet PCR. A subset of samples were additionally analysed by targeted sequencing. Patients with high pre-treatment ctDNA or cfDNA levels (≥75th centile) had significantly shorter progression free survival (PFS) than patients with lower levels. Despite an overall decline in ctDNA levels from pre-treatment to first CT-scan, serial analysis identified seven patients with temporary increases in ctDNA consistent with growth of resistant cells. These patients had shorter PFS and shorter overall survival. Targeted sequencing analyses of cfDNA revealed dramatic changes in the clonal composition in response to treatment. Our study suggests that increasing ctDNA levels during the first cycles of first-line FOLFIRI treatment is a predictor of incipient progressive disease and poorer survival. Thus, we demonstrate the importance of monitoring ctDNA levels as early as one week after treatment onset to enable early detection of treatment failure.
Comparison of Two-Talker Attention Decoding from EEG with Nonlinear Neural Networks and Linear Methods
Authors: Ciccarelli Gregory , Nolan Michael , Perricone Joseph , Calamia Paul T. , Haro Stephanie , O’Sullivan James , Mesgarani Nima , Quatieri Thomas F. , Smalt Christopher J. 
Published: August 2019

AbstractAuditory attention decoding (AAD) through a brain-computer interface has had a flowering of developments since it was first introduced by Mesgarani and Chang (2012) using electrocorticograph recordings. AAD has been pursued for its potential application to hearing-aid design in which an attention-guided algorithm selects, from multiple competing acoustic sources, which should be enhanced for the listener and which should be suppressed. Traditionally, researchers have separated the AAD problem into two stages: reconstruction of a representation of the attended audio from neural signals, followed by determining the similarity between the candidate audio streams and the reconstruction. Here, we compare the traditional two-stage approach with a novel neural-network architecture that subsumes the explicit similarity step. We compare this new architecture against linear and non-linear (neural-network) baselines using both wet and dry electroencephalogram (EEG) systems. Our results indicate that the new architecture outperforms the baseline linear stimulus-reconstruction method, improving decoding accuracy from 66% to 81% using wet EEG and from 59% to 87% for dry EEG. Also of note was the finding that the dry EEG system can deliver comparable or even better results than the wet, despite the latter having one third as many EEG channels as the former. The 11-subject, wet-electrode AAD dataset for two competing, co-located talkers, the 11-subject, dry-electrode AAD dataset, and our software are available for further validation, experimentation, and modification.
Kefir peptides alleviate particulate matter <4 μm (PM4.0)-induced pulmonary inflammation by inhibiting the NF-κB pathway using luciferase transgenic mice
Authors: Chen Hsiao-Ling , Hung Kuan-Fei , Yen Chih-Ching , Laio Chun-Huei , Wang Jiun-Long , Lan Ying-Wei , Chong Kowit-Yu , Fan Hueng-Chuen , Chen Chuan-Mu 
Published: August 2019

AbstractKefir peptides, generated by kefir grain fermentation of milk proteins, showed positive antioxidant effects, lowered blood pressure and modulated the immune response. In this study, kefir peptide was evaluated regarding their anti-inflammatory effects on particulate matter <4 μm (PM4.0)-induced lung inflammation in NF-κB-luciferase+/+ transgenic mice. The lungs of mice under 20 mg/kg or 10 mg/kg PM4.0 treatments, both increased significantly the generation of reactive oxygen species (ROS) and inflammatory cytokines; increased the protein expression levels of p-NF-κB, NLRP3, caspase-1, IL-1β, TNF-α, IL-6, IL-4 and α-SMA. Thus, we choose the 10 mg/kg of PM4.0 for animal trials; the mice were assigned to four treatment groups, including control group (saline treatment), PM4.0 + Mock group (only PM4.0 administration), PM4.0 + KL group (PM4.0 + 150 mg/kg low-dose kefir peptide) and PM4.0 + KH group (PM4.0 + 500 mg/kg high-dose kefir peptide). Data showed that treatment with both doses of kefir peptides decreased the PM4.0-induced inflammatory cell infiltration and the expression of the inflammatory mediators IL-lβ, IL-4 and TNF-α in lung tissue by inactivating NF-κB signaling. The oral administrations of kefir peptides decrease the PM4.0-induced lung inflammation process through the inhibition of NF-κB pathway in transgenic luciferase mice, proposing a new clinical application to particulate matter air pollution-induced pulmonary inflammation.
Incidence, prevalence, and outcome of primary biliary cholangitis in a nationwide Swedish population-based cohort
Authors: Marschall Hanns-Ulrich , Henriksson Ida , Lindberg Sara , Söderdahl Fabian , Thuresson Marcus , Wahlin Staffan , Ludvigsson Jonas F. 
Published: August 2019

AbstractAvailable epidemiological data on primary biliary cholangitis (PBC) in Sweden originate from regional studies in the 1980s and may not reflect modern day PBC. We aimed to estimate incidence and prevalence, survival and death causes, and gender differences in PBC. We used international classification of disease (ICD) codes to identify patients with PBC in inpatient and outpatient registries 1987–2014 who were then linked to the Swedish cause of death, cancer and prescribed drug registries. Each PBC patient was matched with 10 reference individuals from the general population. In sensitivity analyses, we examined PBC patients identified through clinical patient records from Karolinska, Sahlgrenska and Örebro University Hospitals. We identified 5,350 adults with PBC. Prevalence of PBC increased steadily from 5.0 (1987) to 34.6 (2014) per 100,000 inhabitants whereas the yearly incidence rate was relatively constant with a median of 2.6 per 100,000 person-years, with a female:male gender ratio of 4:1. Compared to reference individuals, PBC individuals aged 15–39 years at diagnosis had a substantially higher risk of death (Hazard Ratio [HR] 12.7, 95% Confidence Interval [CI] 8.3–19.5) than those diagnosed between 40–59 (HR 4.1, 95% CI 3.7–4.5) and >60 (HR 3.7, 95% CI 3.5–3.9) years of age. Relative risks of mortality were highest in men. In conclusion, we found that recorded prevalence of PBC in Sweden has increased substantially during the last 30 years although incidence has been stable. Patients diagnosed in young adulthood were at a 12.7-fold increased risk of death, and male PBC patients had worse prognosis.
Stimulation or Cancellation of Ca2+ Influx by Bipolar Nanosecond Pulsed Electric Fields in Adrenal Chromaffin Cells Can Be Achieved by Tuning Pulse Waveform
Authors: Bagalkot Tarique R. , Leblanc Normand , Craviso Gale L. 
Published: August 2019

AbstractExposing adrenal chromaffin cells to single 150 to 400 ns electric pulses triggers a rise in intracellular Ca2+ ([Ca2+]i) that is due to Ca2+ influx through voltage-gated Ca2+ channels (VGCC) and plasma membrane electropores. Immediate delivery of a second pulse of the opposite polarity in which the duration and amplitude were the same as the first pulse (a symmetrical bipolar pulse) or greater than the first pulse (an asymmetrical bipolar pulse) had a stimulatory effect, evoking larger Ca2+ responses than the corresponding unipolar pulse. Progressively decreasing the amplitude of the opposite polarity pulse while also increasing its duration converted stimulation to attenuation, which reached a maximum of 43% when the positive phase was 150 ns at 3.1 kV/cm, and the negative phase was 800 ns at 0.2 kV/cm. When VGCCs were blocked, Ca2+ responses evoked by asymmetrical and even symmetrical bipolar pulses were significantly reduced relative to those evoked by the corresponding unipolar pulse under the same conditions, indicating that attenuation involved mainly the portion of Ca2+ influx attributable to membrane electropermeabilization. Thus, by tuning the shape of the bipolar pulse, Ca2+ entry into chromaffin cells through electropores could be attenuated while preserving Ca2+ influx through VGCCs.
Mating of escaped domestic pigs with wild boar and possibility of their offspring migration after the Fukushima Daiichi Nuclear Power Plant accident
Authors: Anderson Donovan , Toma Rio , Negishi Yuki , Okuda Kei , Ishiniwa Hiroko , Hinton Thomas G. , Nanba Kenji , Tamate Hidetoshi B. , Kaneko Shingo 
Published: August 2019

AbstractThe 2011 Tohoku earthquake drastically changed human activities in some regions of Fukushima Prefecture, Japan. The subsequent tsunami damage and radioactive pollution from the Fukushima Daiichi nuclear power plant resulted in the evacuation of humans, and abandonment of agricultural lands, allowing population expansion of wildlife into areas formally inhabited by domesticated livestock. Unintentional escape of domesticated pigs into wildlife inhabited environments also occurred. In this study, we tested the possibility of introgression between wild boar and domesticated pigs in Fukushima and neighboring prefectures. We analyzed mitochondrial DNA sequences of 338 wild boar collected from populations in the Tohoku region between 2006 and 2018. Although most boar exhibited Asian boar mitochondrial haplotypes, 18 boar, phenotypically identified as wild boar, had a European domesticated pig haplotype. Frequencies of this haplotype have remained stable since first detection in 2015. This result infers ongoing genetic pollution in wild boar populations from released domesticated pigs. In 2018, this haplotype was detected outside of evacuated areas, suggesting migration and successful adaptation. The natural and anthropocentric disasters at Fukushima gave us the rare opportunity to study introgression processes of domestic genes into populations of wild boar. The present findings suggest a need for additional genetic monitoring to document the dispersal of domestic genes within wild boar stock.
KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletion
Authors: Kinoshita Hisanori , Maki Takakuni , Yasuda Ken , Kishida Natsue , Sasaoka Norio , Takagi Yasushi , Kakizuka Akira , Takahashi Ryosuke 
Published: August 2019

AbstractReduced adenosine triphosphate (ATP) levels in ischemic stroke constitute an upstream contributor to neuronal cell death. We have recently created a small chemical, named Kyoto University Substance 121 (KUS121), which can reduce cellular ATP consumption. In this study, we examined whether KUS121 has neuroprotective effects in rodent cerebral ischemia models. We evaluated cell viability and ATP levels in vitro after oxygen glucose deprivation (OGD) in rat cortical primary neuronal cultures incubated with or without KUS121. We found that KUS121 protected neurons from cell death under OGD by preventing ATP depletion. We also used in vivo ischemic stroke models of transient distal middle cerebral artery occlusion in C57BL/6 and B-17 mice. Administration of KUS121 in these models improved functional deficits and reduced brain infarction volume after transient focal cerebral ischemia in both C57BL/6 and B-17 mice. These results indicate that KUS121 could be a novel type of neuroprotective drug for ischemic stroke.