bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response
Authors: Jia Qi , Sieburth Derek 
Published: April 2021

AbstractMitochondria play a pivotal role in the generation of signals coupling metabolism with neurotransmitter release, but a role for mitochondrial-produced ROS in regulating neurosecretion has not been described. Here we show that endogenously produced hydrogen peroxide originating from axonal mitochondria (mtH2O2) functions as a signaling cue to selectively regulate the secretion of a FMRFamide-related neuropeptide (FLP-1) from a pair of interneurons (AIY) in C. elegans. We show that pharmacological or genetic manipulations that increase mtH2O2 levels lead to increased FLP-1 secretion that is dependent upon ROS dismutation, mitochondrial calcium influx, and cysteine sulfenylation of the calcium-independent PKC family member PKC-1. mtH2O2-induced FLP-1 secretion activates the oxidative stress response transcription factor SKN-1/Nrf2 in distal tissues and protects animals from ROS-mediated toxicity. mtH2O2 levels in AIY neurons, FLP-1 secretion and SKN-1 activity are rapidly and reversibly regulated by exposing animals to different bacterial food sources. These results reveal a previously unreported role for mtH2O2 in linking diet-induced changes in mitochondrial homeostasis with neuropeptide secretion.
Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1
Authors: Vuorela A. , Freitag T. L. , Leskinen K. , Pessa H. , Härkönen T. , Stracenski I. , Kirjavainen T. , Olsen P. , Saarenpää-Heikkilä O. , Ilonen J. , Knip M. , Vaheri A. , Partinen M. , Saavalainen P. , Meri S. , Vaarala O. 
Published: April 2021

AbstractNarcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175–189 (NA175–189) and nucleoprotein 214–228 (NP214–228), but also respond to a NA175–189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675–689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175–189 or POMT1675–689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.
Deletion of Mfsd2b impairs thrombotic functions of platelets
Authors: Chandrakanthan Madhuvanthi , Nguyen Toan Quoc , Hasan Zafrul , Muralidharan Sneha , Vu Thiet Minh , Li Aaron Wei Liang , Le Uyen Thanh Nha , Thi Thuy Ha Hoa , Baik Sang-Ha , Tan Sock Hwee , Foo Juat Chin , Wenk Markus R. , Cazenave-Gassiot Amaury , Torta Federico , Ong Wei Yi , Chan Mark Yan Yee , Nguyen Long N. 
Published: April 2021

AbstractWe recently discovered that Mfsd2b, which is the S1P exporter found in blood cells. Here, we report that Mfsd2b is critical for the release of all S1P species in both resting and activated platelets. We show that resting platelets store S1P in the cytoplasm. After activation, this S1P pool is delivered to the plasma membrane, where Mfsd2b is predominantly localized for export. Employing knockout mice of Mfsd2b, we reveal that platelets contribute a minor amount of plasma S1P. Nevertheless, Mfsd2b deletion in whole body or platelets impairs platelet morphology and functions. In particular, Mfsd2b knockout mice show significantly reduced thrombus formation. We show that loss of Mfsd2b affects intrinsic platelet functions as part of remarkable sphingolipid accumulation. These findings indicate that accumulation of sphingolipids including S1P by deletion of Mfsd2b strongly impairs platelet functions, which suggests that the transporter may be a target for the prevention of thrombotic disorders.
Experimental parameters defining ultra-low biomass bioaerosol analysis
Authors: Luhung Irvan , Uchida Akira , Lim Serene B. Y. , Gaultier Nicolas E. , Kee Carmon , Lau Kenny J. X. , Gusareva Elena S. , Heinle Cassie E. , Wong Anthony , Premkrishnan Balakrishnan N. V. , Purbojati Rikky W. , Acerbi Enzo , Kim Hie Lim , Junqueira Ana C. M. , Longford Sharon , Lohar Sachin R. , Yap Zhei Hwee , Panicker Deepa , Koh Yanqing , Kushwaha Kavita K. , Ang Poh Nee , Putra Alexander , Drautz-Moses Daniela I. , Schuster Stephan C. 
Published: April 2021

AbstractInvestigation of the microbial ecology of terrestrial, aquatic and atmospheric ecosystems requires specific sampling and analytical technologies, owing to vastly different biomass densities typically encountered. In particular, the ultra-low biomass nature of air presents an inherent analytical challenge that is confounded by temporal fluctuations in community structure. Our ultra-low biomass pipeline advances the field of bioaerosol research by significantly reducing sampling times from days/weeks/months to minutes/hours, while maintaining the ability to perform species-level identification through direct metagenomic sequencing. The study further addresses all experimental factors contributing to analysis outcome, such as amassment, storage and extraction, as well as factors that impact on nucleic acid analysis. Quantity and quality of nucleic acid extracts from each optimisation step are evaluated using fluorometry, qPCR and sequencing. Both metagenomics and marker gene amplification-based (16S and ITS) sequencing are assessed with regard to their taxonomic resolution and inter-comparability. The pipeline is robust across a wide range of climatic settings, ranging from arctic to desert to tropical environments. Ultimately, the pipeline can be adapted to environmental settings, such as dust and surfaces, which also require ultra-low biomass analytics.
TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer
Authors: da Silva Edaise M. , Selenica Pier , Vahdatinia Mahsa , Pareja Fresia , Da Cruz Paula Arnaud , Ferrando Lorenzo , Gazzo Andrea M. , Dopeso Higinio , Ross Dara S. , Bakhteri Ariya , Riaz Nadeem , Chandarlapaty Sarat , Razavi Pedram , Norton Larry , Wen Hannah Y. , Brogi Edi , Weigelt Britta , Zhang Hong , Reis-Filho Jorge S. 
Published: April 2021

AbstractMetaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Forty-four MBCs were subjected to: whole-exome sequencing (WES; n = 27) or targeted sequencing of 341-468 cancer-related genes (n = 17); 16 MBCs were subjected to Sanger sequencing of the TERT promoter, TP53 and selected exons of PIK3CA, HRAS, and BRAF. TERT promoter hotspot mutations (n = 9) and TERT gene amplification (n = 1) were found in 10 of the 60 MBCs analyzed, respectively. These TERT alterations were less frequently found in MBCs with predominant chondroid differentiation than in other MBC subtypes (p = 0.01, Fisher’s exact test) and were mutually exclusive with TP53 mutations (p < 0.001, CoMEt). In addition, a comparative analysis of the MBCs subjected to WES or targeted cancer gene sequencing (n = 44) revealed that MBCs harboring TERT promoter hotspot mutations or gene amplification (n = 6) more frequently harbored PIK3CA than TERT wild-type MBCs (n = 38; p = 0.001; Fisher’s exact test). In conclusion, TERT somatic genetic alterations are found in a subset of TP53 wild-type MBCs with squamous/spindle differentiation, highlighting the genetic diversity of these cancers.
Machine learning augmented predictive and generative model for rupture life in ferritic and austenitic steels
Authors: Mamun Osman , Wenzlick Madison , Sathanur Arun , Hawk Jeffrey , Devanathan Ram 
Published: April 2021

AbstractThe Larson–Miller parameter (LMP) offers an efficient and fast scheme to estimate the creep rupture life of alloy materials for high-temperature applications; however, poor generalizability and dependence on the constant C often result in sub-optimal performance. In this work, we show that the direct rupture life parameterization without intermediate LMP parameterization, using a gradient boosting algorithm, can be used to train ML models for very accurate prediction of rupture life in a variety of alloys (Pearson correlation coefficient >0.9 for 9–12% Cr and >0.8 for austenitic stainless steels). In addition, the Shapley value was used to quantify feature importance, making the model interpretable by identifying the effect of various features on the model performance. Finally, a variational autoencoder-based generative model was built by conditioning on the experimental dataset to sample hypothetical synthetic candidate alloys from the learnt joint distribution not existing in both 9–12% Cr ferritic–martensitic alloys and austenitic stainless steel datasets.
mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents
Authors: Rauch Susanne , Roth Nicole , Schwendt Kim , Fotin-Mleczek Mariola , Mueller Stefan O. , Petsch Benjamin 
Published: April 2021

AbstractmRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle-encapsulated mRNA vaccine that encodes full-length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Immunisation with CVnCoV induced strong humoral responses with high titres of virus-neutralising antibodies and robust T-cell responses. CVnCoV vaccination protected hamsters from challenge with wild-type SARS-CoV-2, demonstrated by the absence of viral replication in the lungs. Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine-enhanced disease. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.
Modeling vaccination rollouts, SARS-CoV-2 variants and the requirement for non-pharmaceutical interventions in Italy
Authors: Giordano Giulia , Colaneri Marta , Di Filippo Alessandro , Blanchini Franco , Bolzern Paolo , De Nicolao Giuseppe , Sacchi Paolo , Colaneri Patrizio , Bruno Raffaele 
Published: April 2021

AbstractDespite progress in clinical care for patients with coronavirus disease 2019 (COVID-19)1, population-wide interventions are still crucial to manage the pandemic, which has been aggravated by the emergence of new, highly transmissible variants. In this study, we combined the SIDARTHE model2, which predicts the spread of SARS-CoV-2 infections, with a new data-based model that projects new cases onto casualties and healthcare system costs. Based on the Italian case study, we outline several scenarios: mass vaccination campaigns with different paces, different transmission rates due to new variants and different enforced countermeasures, including the alternation of opening and closure phases. Our results demonstrate that non-pharmaceutical interventions (NPIs) have a higher effect on the epidemic evolution than vaccination alone, advocating for the need to keep NPIs in place during the first phase of the vaccination campaign. Our model predicts that, from April 2021 to January 2022, in a scenario with no vaccine rollout and weak NPIs ($${\cal{R}}_0$$

R

0

= 1.27), as many as 298,000 deaths associated with COVID-19 could occur. However, fast vaccination rollouts could reduce mortality to as few as 51,000 deaths. Implementation of restrictive NPIs ($${\cal{R}}_0$$

R

0

= 0.9) could reduce COVID-19 deaths to 30,000 without vaccinating the population and to 18,000 with a fast rollout of vaccines. We also show that, if intermittent open–close strategies are adopted, implementing a closing phase first could reduce deaths (from 47,000 to 27,000 with slow vaccine rollout) and healthcare system costs, without substantive aggravation of socioeconomic losses.
High spatial resolution global ocean metagenomes from Bio-GO-SHIP repeat hydrography transects
Authors: Larkin Alyse A. , Garcia Catherine A. , Garcia Nathan , Brock Melissa L. , Lee Jenna A. , Ustick Lucas J. , Barbero Leticia , Carter Brendan R. , Sonnerup Rolf E. , Talley Lynne D. , Tarran Glen A. , Volkov Denis L. , Martiny Adam C. 
Published: April 2021

AbstractDetailed descriptions of microbial communities have lagged far behind physical and chemical measurements in the marine environment. Here, we present 971 globally distributed surface ocean metagenomes collected at high spatio-temporal resolution. Our low-cost metagenomic sequencing protocol produced 3.65 terabases of data, where the median number of base pairs per sample was 3.41 billion. The median distance between sampling stations was 26 km. The metagenomic libraries described here were collected as a part of a biological initiative for the Global Ocean Ship-based Hydrographic Investigations Program, or “Bio-GO-SHIP.” One of the primary aims of GO-SHIP is to produce high spatial and vertical resolution measurements of key state variables to directly quantify climate change impacts on ocean environments. By similarly collecting marine metagenomes at high spatiotemporal resolution, we expect that this dataset will help answer questions about the link between microbial communities and biogeochemical fluxes in a changing ocean.
Effect of perioperative bronchodilator therapy on postoperative pulmonary function among lung cancer patients with COPD
Authors: Shin Sun Hye , Shin Sumin , Im Yunjoo , Lee Genehee , Jeong Byeong-Ho , Lee Kyungjong , Um Sang-Won , Kim Hojoong , Kwon O. Jung , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Kim Jhingook , Zo Jae Ill , Shim Young Mog , Cho Juhee , Kang Danbee , Park Hye Yun 
Published: April 2021

AbstractChronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; − 161.1 mL [− 240.2, − 82.0], − 179.2 mL [− 252.1, − 106.3], − 128.8 mL [− 193.2, − 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.
Molecular features of tumor-derived genetic alterations in circulating cell-free DNA in virtue of autopsy analysis
Authors: Koba Hayato , Kimura Hideharu , Yoneda Taro , Sone Takashi , Ohkura Noriyuki , Hara Johsuke , Hosomichi Kazuyoshi , Tajima Atsushi , Kasahara Kazuo 
Published: April 2021

AbstractIn cancer patients, circulating cell-free DNA (cfDNA) includes tumor-derived DNA (tDNA). cfDNA has been used clinically for non-invasive gene mutation testing. The aim of this study was to characterize the features of the genetic alterations detected in cfDNA. This study included 6 patients with primary lung cancer who died due to cancer progression. Tumors were biopsied at autopsy. Genetic alteration profiles were obtained using next generation sequencing. The features of the tDNA genetic alterations detected in cfDNA included a higher frequency of being present in multiple tumors (67% truncal mutations, 36% shared mutations, and 4% individual mutations) and a higher variant allele frequency (VAF; 47.6% versus 4.1% for tDNA alterations detected in cfDNA versus not detected in cfDNA, respectively). The data revealed that the tumor-derived genetic alterations most easily detected in cfDNA were truncal mutations with a high VAF. These results showed that essential genetic alterations enriched in cfDNA could help to characterize cancer cells and that genetic testing using cfDNA has advantages in the detection of fundamental regulatory aberrations occurring during tumorigenesis.
Optimisation of the coalescent hyperbolic embedding of complex networks
Authors: Kovács Bianka , Palla Gergely 
Published: April 2021

AbstractSeveral observations indicate the existence of a latent hyperbolic space behind real networks that makes their structure very intuitive in the sense that the probability for a connection is decreasing with the hyperbolic distance between the nodes. A remarkable network model generating random graphs along this line is the popularity-similarity optimisation (PSO) model, offering a scale-free degree distribution, high clustering and the small-world property at the same time. These results provide a strong motivation for the development of hyperbolic embedding algorithms, that tackle the problem of finding the optimal hyperbolic coordinates of the nodes based on the network structure. A very promising recent approach for hyperbolic embedding is provided by the noncentered minimum curvilinear embedding (ncMCE) method, belonging to the family of coalescent embedding algorithms. This approach offers a high-quality embedding at a low running time. In the present work we propose a further optimisation of the angular coordinates in this framework that seems to reduce the logarithmic loss and increase the greedy routing score of the embedding compared to the original version, thereby adding an extra improvement to the quality of the inferred hyperbolic coordinates.
Low serum iron is associated with anemia in CKD stage 1–4 patients with normal transferrin saturations
Authors: Yu Pei-Hua , Lin Ming-Yen , Chiu Yi-Wen , Lee Jia-Jung , Hwang Shang-Jyh , Hung Chi-Chih , Chen Hung-Chun 
Published: April 2021

AbstractLow transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1–4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (< 200 μg/dL) was associated with hypoalbuminemia and high C-reactive protein. In fully-adjusted logistic regression, both “normal TSAT low iron” and “low TSAT low iron” groups were associated with baseline anemia (hemoglobin < 11 g/dL) (odds ratios (OR) 1.56; 95% confidence interval (CI) 1.13–2.16 and OR 2.36; 95% CI 1.76–3.18, respectively) compared with the reference group (normal TSAT normal iron). Sensitivity tests with different cutoffs for TSAT and iron also showed similar results. In patients without anemia, both groups were associated with anemia after 1 year (OR 1.69; 95% CI 1.00–2.83 and OR 1.94; 95% CI 1.11–3.40, respectively). In conclusion, CKD stage 1–4 patients with normal TSAT but low serum iron are still at risk for anemia.
The non-indigenous Oithona davisae in a Mediterranean transitional environment: coexistence patterns with competing species
Authors: Pansera Marco , Camatti Elisa , Schroeder Anna , Zagami Giacomo , Bergamasco Alessandro 
Published: April 2021

AbstractThe Venice lagoon (VL) has been recognized as a hot spot of introduction of non-indigenous species (NIS), due to several anthropogenic factors and environmental stressors that combined may facilitate NIS invasions. In the last decades an increasing number of zooplankton NIS have been observed in the VL. This work aims to provide a picture of the annual cycle and distribution of the recently recorded non-indigenous copepod Oithona davisae, considering the coexistence patterns with the congeneric resident Oithona nana. Therefore, zooplankton samplings were carried out monthly from August 2016 to July 2017 at five Long-Term Ecological Research LTER stations in the VL. Oithona davisae showed a persistent occurrence throughout the year with the highest abundances in the warm season and in the inner areas, while the congeneric O. nana, showing a different distribution pattern, resulted more abundant near the inlets of the Lagoon, where O. davisae reached the minimum density. Oithona davisae seems to find local conditions that promote its settlement and distribution, especially in the inner and more trophic lagoon sites. In other European coastal embayments or transitional waters, O. davisae occupied the niche left by the indigenous O. nana or can replace this congeneric species through competitive exclusion mechanisms. Our data indicate that, for now, such species replacement has not occurred in the VL. One of the causes is the extreme variety of habitats and niches offered by this environment allowing a balanced coexistence with O. nana and in general with the resident copepod community.