bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic signatures define three subtypes of EGFR-mutant stage II–III non-small-cell lung cancer with distinct adjuvant therapy outcomes
Authors: Liu Si-Yang , Bao Hua , Wang Qun , Mao Wei-Min , Chen Yedan , Tong Xiaoling , Xu Song-Tao , Wu Lin , Wei Yu-Cheng , Liu Yong-Yu , Chen Chun , Cheng Ying , Yin Rong , Yang Fan , Ren Sheng-Xiang , Li Xiao-Fei , Li Jian , Huang Cheng , Liu Zhi-Dong , Xu Shun , Chen Ke-Neng , Xu Shi-Dong , Liu Lun-Xu , Yu Ping , Wang Bu-Hai , Ma Hai-Tao , Yan Hong-Hong , Dong Song , Zhang Xu-Chao , Su Jian , Yang Jin-Ji , Yang Xue-Ning , Zhou Qing , Wu Xue , Shao Yang , Zhong Wen-Zhao , Wu Yi-Long 
Published: November 2021

AbstractThe ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II–IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
Operando magnetic resonance imaging for mapping of temperature and redox species in thermo-electrochemical cells
Authors: Gunathilaka Isuru E. , Pringle Jennifer M. , O’Dell Luke A. 
Published: November 2021

AbstractLow-grade waste heat is an abundant and underutilised energy source. In this context, thermo-electrochemical cells (i.e., systems able to harvest heat to generate electricity) are being intensively studied to deliver the promises of efficient and cost-effective energy harvesting and electricity generation. However, despite the advances in performance disclosed in recent years, understanding the internal processes occurring within these devices is challenging. In order to shed light on these mechanisms, here we report an operando magnetic resonance imaging approach that can provide quantitative spatial maps of the electrolyte temperature and redox ion concentrations in functioning thermo-electrochemical cells. Time-resolved images are obtained from liquid and gel electrolytes, allowing the observation of the effects of redox reactions and competing mass transfer processes such as thermophoresis and diffusion. We also correlate the physicochemical properties of the system with the device performance via simultaneous electrochemical measurements.
Transient mTOR inhibition rescues 4-1BB CAR-Tregs from tonic signal-induced dysfunction
Authors: Lamarthée Baptiste , Marchal Armance , Charbonnier Soëli , Blein Tifanie , Leon Juliette , Martin Emmanuel , Rabaux Lucas , Vogt Katrin , Titeux Matthias , Delville Marianne , Vinçon Hélène , Six Emmanuelle , Pallet Nicolas , Michonneau David , Anglicheau Dany , Legendre Christophe , Taupin Jean-Luc , Nemazanyy Ivan , Sawitzki Birgit , Latour Sylvain , Cavazzana Marina , André Isabelle , Zuber Julien 
Published: November 2021

AbstractThe use of chimeric antigen receptor (CAR)-engineered regulatory T cells (Tregs) has emerged as a promising strategy to promote immune tolerance. However, in conventional T cells (Tconvs), CAR expression is often associated with tonic signaling, which can induce CAR-T cell dysfunction. The extent and effects of CAR tonic signaling vary greatly according to the expression intensity and intrinsic properties of the CAR. Here, we show that the 4-1BB CSD-associated tonic signal yields a more dramatic effect in CAR-Tregs than in CAR-Tconvs with respect to activation and proliferation. Compared to CD28 CAR-Tregs, 4-1BB CAR-Tregs exhibit decreased lineage stability and reduced in vivo suppressive capacities. Transient exposure of 4-1BB CAR-Tregs to a Treg stabilizing cocktail, including an mTOR inhibitor and vitamin C, during ex vivo expansion sharply improves their in vivo function and expansion after adoptive transfer. This study demonstrates that the negative effects of 4-1BB tonic signaling in Tregs can be mitigated by transient mTOR inhibition.
Cross-reactivity of antibodies from non-hospitalized COVID-19 positive individuals against the native, B.1.351, B.1.617.2, and P.1 SARS-CoV-2 spike proteins
Authors: Hojjat Jodaylami Maryam , Djaïleb Abdelhadi , Ricard Pierre , Lavallée Étienne , Cellier-Goetghebeur Stella , Parker Megan-Faye , Coutu Julien , Stuible Matthew , Gervais Christian , Durocher Yves , Desautels Florence , Cayer Marie-Pierre , de Grandmont Marie Joëlle , Rochette Samuel , Brouard Danny , Trottier Sylvie , Boudreau Denis , Pelletier Joelle N. , Masson Jean-Francois 
Published: November 2021

AbstractSARS-CoV-2 variants of concern (VOCs) have emerged worldwide, with implications on the spread of the pandemic. Characterizing the cross-reactivity of antibodies against these VOCs is necessary to understand the humoral response of non-hospitalized individuals previously infected with SARS-CoV-2, a population that remains understudied. Thirty-two SARS-CoV-2-positive (PCR-confirmed) and non-hospitalized Canadian adults were enrolled 14–21 days post-diagnosis in 2020, before the emergence of the B.1.351 (also known as Beta), B.1.617.2 (Delta) and P.1 (Gamma) VOCs. Sera were collected 4 and 16 weeks post-diagnosis. Antibody levels and pseudo-neutralization of the ectodomain of SARS-CoV-2 spike protein/human ACE-2 receptor interaction were analyzed with native, B.1.351, B.1.617.2 and P.1 variant spike proteins. Despite a lower response observed for the variant spike proteins, we report evidence of a sustained humoral response against native, B.1.351, B.1.617.2 and P.1 variant spike proteins among non-hospitalized Canadian adults. Furthermore, this response inhibited the interaction between the spike proteins from the different VOCs and ACE-2 receptor for ≥ 16 weeks post-diagnosis, except for individuals aged 18–49 years who showed no inhibition of the interaction between B.1.617.1 or B.1.617.2 spike and ACE-2. Interestingly, the affinity (KD) measured between the spike proteins (native, B.1.351, B.1.617.2 and P.1) and antibodies elicited in sera of infected and vaccinated (BNT162b2 and ChAdOx1 nCoV-19) individuals was invariant. Relative to sera from vaccine-naïve (and previously infected) individuals, sera from vaccinated individuals had higher antibody levels (as measured with label-free SPR) and more efficiently inhibited the spike–ACE-2 interactions, even among individuals aged 18–49 years, showing the effectiveness of vaccination.
Genetic diversity in North American Cercis Canadensis reveals an ancient population bottleneck that originated after the last glacial maximum
Authors: Ony Meher , Klingeman William E. , Zobel John , Trigiano Robert N. , Ginzel Matthew , Nowicki Marcin , Boggess Sarah L. , Everhart Sydney , Hadziabdic Denita 
Published: November 2021

AbstractUnderstanding of the present-day genetic diversity, population structure, and evolutionary history of tree species can inform resource management and conservation activities, including response to pressures presented by a changing climate.Cercis canadensis(Eastern Redbud) is an economically valuable understory tree species native to the United States (U.S.) that is also important for forest ecosystem and wildlife health. Here, we document and explain the population genetics and evolutionary history of this deciduous tree species across its distributed range. In this study, we used twelve microsatellite markers to investigate 691 wild-type trees sampled at 74 collection sites from 23 Eastern U.S. states. High genetic diversity and limited gene flow were revealed in wild, natural stands ofC. canadensiswith populations that are explained by two major genetic clusters. These findings indicate that an ancient population bottleneck occurred coinciding with the last glacial maximum (LGM) in North America. The structure in current populations likely originated from an ancient population in the eastern U.S. that survived LGM and then later diverged into two contemporary clusters. Data suggests that populations have expanded since the last glaciation event from one into several post-glacial refugia that now occupy this species’ current geographic range. Our enhanced understanding benchmarks the genetic variation preserved within this species and can direct future efforts in conservation, and resource utilization of adaptively resilient populations that present the greatest genetic and structural diversity.
Forensic significance of intracardiac heme oxygenase-1 expression in acute myocardial ischemia
Authors: Kuninaka Yumi , Ishida Yuko , Nosaka Mizuho , Ishigami Akiko , Taruya Akira , Shimada Emi , Kimura Akihiko , Yamamoto Hiroki , Ozaki Mitsunori , Furukawa Fukumi , Kondo Toshikazu 
Published: November 2021

AbstractHeme oxygenase-1 (HO-1), an inducible stress-response protein, exerts anti-oxidant and anti-apoptotic effects. However, its significance in forensic diagnosis of acute ischemic heart diseases (AIHD) such as myocardial infarction (MI) is still unknown. We examined the immunohistochemical expression of HO-1 in the heart samples to discuss their forensic significance to determine acute cardiac ischemia. The heart samples were obtained from 23 AIHD cases and 33 non-AIHD cases as controls. HO-1 positive signals in cardiomyocyte nuclear were detected in 78.2% of AIHD cases, however, that were detected in only 24.2% control cases with statistical difference between AIHD and non-AIHD groups. In contrast to HO-1 protein expression, there was no significant difference in the appearance of myoglobin pallor regions and leukocyte infiltration in the hearts between AIHD and non-AIHD groups. From the viewpoints of forensic pathology, intracardiac HO-1 expression would be considered a valuable marker to diagnose AIHD as the cause of death.
Spatiotemporal observation of light propagation in a three-dimensional scattering medium
Authors: Inoue Tomoyoshi , Junpei Yuasa , Itoh Seiya , Okuda Tatsuya , Funahashi Akinori , Takimoto Tetsuya , Kakue Takashi , Nishio Kenzo , Matoba Osamu , Awatsuji Yasuhiro 
Published: November 2021

AbstractSpatiotemporal information about light pulse propagation obtained with femtosecond temporal resolution plays an important role in understanding transient phenomena and light–matter interactions. Although ultrafast optical imaging techniques have been developed, it is still difficult to capture light pulse propagation spatiotemporally. Furthermore, imaging through a three-dimensional (3-D) scattering medium is a longstanding challenge due to the optical scattering caused by the interaction between light pulse and a 3-D scattering medium. Here, we propose a technique for ultrafast optical imaging of light pulses propagating inside a 3D scattering medium. We record an image of the light pulse propagation using the ultrashort light pulse even when the interaction between light pulse and a 3-D scattering medium causes the optical scattering. We demonstrated our proposed technique by recording converging, refracted, and diffracted propagating light for 59 ps with femtosecond temporal resolution.
Toxicity of stainless and mild steel particles generated from gas–metal arc welding in primary human small airway epithelial cells
Authors: Cediel-Ulloa Andrea , Isaxon Christina , Eriksson Axel , Primetzhofer Daniel , Sortica Mauricio A. , Haag Lars , Derr Remco , Hendriks Giel , Löndahl Jakob , Gudmundsson Anders , Broberg Karin , Gliga Anda R. 
Published: November 2021

AbstractWelding fumes induce lung toxicity and are carcinogenic to humans but the molecular mechanisms have yet to be clarified. The aim of this study was to evaluate the toxicity of stainless and mild steel particles generated via gas–metal arc welding using primary human small airway epithelial cells (hSAEC) and ToxTracker reporter murine stem cells, which track activation of six cancer-related pathways. Metal content (Fe, Mn, Ni, Cr) of the particles was relatively homogenous across particle size. The particles were not cytotoxic in reporter stem cells but stainless steel particles activated the Nrf2-dependent oxidative stress pathway. In hSAEC, both particle types induced time- and dose-dependent cytotoxicity, and stainless steel particles also increased generation of reactive oxygen species. The cellular metal content was higher for hSAEC compared to the reporter stem cells exposed to the same nominal dose. This was, in part, related to differences in particle agglomeration/sedimentation in the different cell media. Overall, our study showed differences in cytotoxicity and activation of cancer-related pathways between stainless and mild steel welding particles. Moreover, our data emphasizes the need for careful assessment of the cellular dose when comparing studies using different in vitro models.
Morphological and spectroscopic analysis of snow and glacier algae and their parasitic fungi on different glaciers of Svalbard
Authors: Fiołka Marta J. , Takeuchi Nozomu , Sofińska-Chmiel Weronika , Wójcik-Mieszawska Sylwia , Irvine-Fynn Tristram , Edwards Arwyn 
Published: November 2021

AbstractThe results show the morphological analyses and spectroscopic studies of snow and glacier algae and their parasitic fungi in Svalbard (High Arctic). Fixed algal cells of two species, Sanguina nivaloides and Ancylonema nordenskioeldii, were imaged using light microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). Fluorescence microscopy using Calcofluor white stain supported the observations of parasitic fungi on the algal cells. Images in brightfield microscopy showed chytrid-like fungi penetrating the cells of both algal species. Parasites were found to colonize the cells of A. nordenskioeldii and hypnozygotes of S. nivaloides, while no fungi infected the cyst stages of S. nivaloides. The autofluorescence analysis revealed the ability of S. nivaloides to glow when excited with different wavelengths, while A. nordenskioeldii did not fluoresce. The hypnozygotes of S. nivaloides emitted brighter fluorescence than the cysts, and the most intense luminosity was observed in the UV range. The Fourier-transform infrared spectroscopy (FTIR) and energy-dispersive X-ray spectroscopy (EDS) spectroscopic analysis showed differences in the chemical composition between samples collected from three different sites. Samples dominated by cyst cells were characterized by the presence of an abundant polysaccharide envelope.
Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH
Authors: Kim Won Jung , Kwon Yong-Jin , Cho Chung-Hyun , Ye Sang-Kyu , Kim Kyu Oh 
Published: November 2021

AbstractSelf-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3‐aminophenylboronic acid (APBA) were used to encapsulate insulin (insulin entrapment efficiency: 73.2%) to prepare a fast response, high stability, good distribution, and excellent biocompatible system. Due to the strong hydrophobicity of POSS, the POSS moiety is located at the core in aqueous solution and combines with the boronic group of APBA and the diol generated in PEG-insulin to form a nanomicelle structure, that is, nanoparticles naturally. Micelles self‐assembled from these molecules possess glucose‐responsiveness at varying glucose concentrations. The interaction of the PBA and diol containing insulin via boronate ester bond and its interchange with glucose was investigated by FT-IR, 1H NMR and XPS. Furthermore, the successful glucose-triggered release of insulin from the POSS-APBA micelles was investigated at neutral pH. A linear graph was plotted with the measured released insulin vs glucose concentrations, with a linear correlation coefficient (R2) value close to 1. Circular dichroism (CD) spectroscopy analysis was performed to measure insulin activity by comparing secondary structures of insulin, PEG-Insulin, and POSS-APBA@insulin. When confirming intracellular apoptosis signaling, cleaved caspase 3 and caspase 9 were not increased by 640 μg/ml POSS-APBA and POSS-APBA@insulin in HeLa, HDF and HUVE cells. Application in the biomedical field for controlled delivery of insulin appear to be promising.
Adipose MDM2 regulates systemic insulin sensitivity
Authors: Hallenborg Philip , Jensen Benjamin Anderschou Holbech , Fjære Even , Petersen Rasmus Koefoed , Belmaâti Mohammed-Samir , Rasmussen Sarah Søndergård , Gunnarsson Jon Petur , Lauritzen Pernille , Cheng Kenneth King Yip , Hermansson Martin , Sonne Si Brask , Ejsing Christer S. , Xu Aimin , Kratchmarova Irina , Krüger Marcus , Madsen Lise , Kristiansen Karsten , Blagoev Blagoy 
Published: November 2021

AbstractThe intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53, in their adipose stores suffer from overt obesity, glucose intolerance, and hepatic steatosis. These mice had decreased levels of circulating palmitoleic acid [non-esterified fatty acid (NEFA) 16:1] concomitant with impaired visceral adipose tissue expression of Scd1 and Ffar4. A similar decrease in Scd and Ffar4 expression was found in in vitro differentiated adipocytes with perturbed MDM2 expression. Lowered MDM2 levels led to nuclear exclusion of the transcriptional cofactors, MORC2 and LIPIN1, and thereby possibly hampered adipocyte function by antagonizing LIPIN1-mediated PPARγ coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.
Deep learning for the quality control of thermoforming food packages
Authors: Banús Núria , Boada Imma , Xiberta Pau , Toldrà Pol , Bustins Narcís 
Published: November 2021

AbstractQuality control is a key process designed to ensure that only products satisfying the defined quality requirements reach the end consumer or the next step in a production line. In the food industry, in the packaging step, there are many products that are still evaluated by human operators. To automate the process and improve efficiency and effectiveness, computer vision and artificial intelligence techniques can be applied. This automation is challenging since specific strategies designed according to the application scenario are required. Focusing on the quality control of the sealing and closure of matrix-shaped thermoforming food packages, the aim of the article is to propose a deep-learning-based solution designed to automatically perform the quality control while satisfying production cadence and ensuring 100% inline inspection of the products. Particularly, the designed computer vision system and the image-based criteria defined to determine when a product has to be accepted or rejected are presented. In addition, the vision control software is described with special emphasis on the different convolutional neural network (CNN) architectures that have been considered (ResNet18, ResNet50, Vgg19 and DenseNet161, non-pre-trained and pre-trained on ImageNet) and on the specifically designed dataset. To test the solution, different experiments are carried out in the laboratory and also in a real scenario, concluding that the proposed CNN-based approach improves the efficiency and security of the quality control process. Optimal results are obtained with the pre-trained DenseNet161, achieving false positive rates that range from 0.03 to 0.30% and false negative rates that range from 0 to 0.07%, with a rejection rate between 0.64 and 5.09% of production, and being able to detect at least 99.93% of the sealing defects that occur in any production. The modular design of our solution as well as the provided description allow it to adapt to similar scenarios and to new deep-learning models to prevent the arrival of faulty products to end consumers by removing them from the automated production line.
Catching the Main Ethiopian Rift evolving towards plate divergence
Authors: Nicotra Eugenio , Viccaro Marco , Donato Paola , Acocella Valerio , De Rosa Rosanna 
Published: November 2021

AbstractMagmatism accompanies rifting along divergent plate boundaries, although its role before continental breakup remains poorly understood. For example, the magma-assisted Northern Main Ethiopian Rift (NMER) lacks current volcanism and clear tectono-magmatic relationships with its contiguous rift portions. Here we define its magmatic behaviour, identifying the most recent eruptive fissures (EF) whose aphyric basalts have a higher Ti content than those of older monogenetic scoria cones (MSC), which are porphyritic and plagioclase-dominated. Despite these differences, calculations highlight a similar parental melt for EF and MSC products, suggesting only a different evolutionary history after melt generation. While MSC magmas underwent a further step of storage at intermediate crustal levels, EF magmas rose directly from the base of the crust without contamination, even below older polygenetic volcanoes, suggesting rapid propagation of transcrustal dikes across solidified magma chambers. Whether this recent condition in the NMER is stable or transient, it indicates a transition from central polygenetic to linear fissure volcanism, indicative of increased tensile conditions and volcanism directly fed from the base of the crust, suggesting transition towards mature rifting.
Symmetric resonator based tunable epsilon negative near zero index metamaterial with high effective medium ratio for multiband wireless applications
Authors: Moniruzzaman Md. , Islam Mohammad Tariqul , Hossain Ismail , Soliman Mohamed S. , Samsuzzaman Md , Almalki Sami H. A. 
Published: November 2021

AbstractIn this paper, a tuned metamaterial (MTM) consisting of a symmetric split ring resonator is presented that exhibits epsilon negative (ENG), near zero permeability and refractive index properties for multiband microwave applications. The proposed metamaterial is constituted on a Rogers (RT-5880) substrate with 1.57 mm thickness and the electrical dimension of 0.14λ × 0.14λ, where wavelength, λ is calculated at 4.2 GHz. The symmetric resonating patch is subdivided into four equal and similar quartiles with two interconnecting split rings in each quartile. The quartiles are connected at the center of the substrate with a square metal strip with which four tuning metal strips are attached. These tuning metal strips are acted as spacers between four quartiles of the resonator patch. Numerical simulation of the proposed design is executed in CST microwave studio. The proposed MTM provides four resonances of transmission coefficient (S21) at 4.20 GHz, 10.14 GHz, 13.15 GHz, and 17.1 GHz covering C, X and Ku bands with negative permittivity, near zero permeability and refractive index. The calculated effective medium ratio (EMR) is 7.14 at 4.2 GHz indicates its compactness. The resonance frequencies are selective in nature which can be easily tuned by varying the length of the tuning metal stubs. The equivalent circuit of the proposed MTM is modelled in Advanced Design Software (ADS) that exhibits a similar S21compared with CST simulation. Surface current, electric and magnetic fields are analyzed to explain the frequency tuning property and other performances of the MTM. Compact size, ENG with near zero permeability and refractive index along with frequency selectivity through tuning provides flexibility for frequency selective applications of this MTM in wireless communications.