bluuebunny/crossref_metadata_2025_split huggingface dataset:
A platform for oncogenomic reporting and interpretation
Authors: Reisle Caralyn , Williamson Laura M. , Pleasance Erin , Davies Anna , Pellegrini Brayden , Bleile Dustin W. , Mungall Karen L. , Chuah Eric , Jones Martin R. , Ma Yussanne , Lewis Eleanor , Beckie Isaac , Pham David , Matiello Pletz Raphael , Muhammadzadeh Amir , Pierce Brandon M. , Li Jacky , Stevenson Ross , Wong Hansen , Bailey Lance , Reisle Abbey , Douglas Matthew , Bonakdar Melika , Nelson Jessica M. T. , Grisdale Cameron J. , Krzywinski Martin , Fisic Ana , Mitchell Teresa , Renouf Daniel J. , Yip Stephen , Laskin Janessa , Marra Marco A. , Jones Steven J. M. 
Published: February 2022

AbstractManual interpretation of variants remains rate limiting in precision oncology. The increasing scale and complexity of molecular data generated from comprehensive sequencing of cancer samples requires advanced interpretative platforms as precision oncology expands beyond individual patients to entire populations. To address this unmet need, we introduce a Platform for Oncogenomic Reporting and Interpretation (PORI), comprising an analytic framework that facilitates the interpretation and reporting of somatic variants in cancer. PORI integrates reporting and graph knowledge base tools combined with support for manual curation at the reporting stage. PORI represents an open-source platform alternative to commercial reporting solutions suitable for comprehensive genomic data sets in precision oncology. We demonstrate the utility of PORI by matching 9,961 pan-cancer genome atlas tumours to the graph knowledge base, calculating therapeutically informative alterations, and making available reports describing select individual samples.
The induction of peripheral trained immunity in the pancreas incites anti-tumor activity to control pancreatic cancer progression
Authors: Geller Anne E. , Shrestha Rejeena , Woeste Matthew R. , Guo Haixun , Hu Xiaoling , Ding Chuanlin , Andreeva Kalina , Chariker Julia H. , Zhou Mingqian , Tieri David , Watson Corey T. , Mitchell Robert A. , Zhang Huang-ge , Li Yan , Martin II Robert C. G. , Rouchka Eric C. , Yan Jun 
Published: February 2022

AbstractDespite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate β-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, β-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer.
Chemically Induced Chromosomal Interaction (CICI) method to study chromosome dynamics and its biological roles
Authors: Du Manyu , Zou Fan , Li Yi , Yan Yujie , Bai Lu 
Published: February 2022

AbstractNumerous intra- and inter-chromosomal contacts have been mapped in eukaryotic genomes, but it remains challenging to link these 3D structures to their regulatory functions. To establish the causal relationships between chromosome conformation and genome functions, we develop a method, Chemically Induced Chromosomal Interaction (CICI), to selectively perturb the chromosome conformation at targeted loci. Using this method, long-distance chromosomal interactions can be induced dynamically between intra- or inter-chromosomal loci pairs, including the ones with very low Hi-C contact frequencies. Measurement of CICI formation time allows us to probe chromosome encounter dynamics between different loci pairs across the cell cycle. We also conduct two functional tests of CICI. We perturb the chromosome conformation near a DNA double-strand break and observe altered donor preference in homologous recombination; we force interactions between early and late-firing DNA replication origins and find no significant changes in replication timing. These results suggest that chromosome conformation plays a deterministic role in homology-directed DNA repair, but not in the establishment of replication timing. Overall, our study demonstrates that CICI is a powerful tool to study chromosome dynamics and 3D genome function.
Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection
Authors: Zou Jing , Xia Hongjie , Xie Xuping , Kurhade Chaitanya , Machado Rafael R. G. , Weaver Scott C. , Ren Ping , Shi Pei-Yong 
Published: February 2022

AbstractThe spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We have developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determine the neutralization titers (defined as the maximal serum dilution that inhibited 50% of infectious virus) of patient sera collected at 1- or 6-months after infection with non-Omicron SARS-CoV-2. From 1- to 6-month post-infection, the neutralization titers against USA-WA1/2020 decrease from 601 to 142 (a 4.2-fold reduction), while the neutralization titers against Omicron-spike SARS-CoV-2 remain low at 38 and 32, respectively. Thus, at 1- and 6-months after non-Omicron SARS-CoV-2 infection, the neutralization titers against Omicron are 15.8- and 4.4-fold lower than those against USA-WA1/2020, respectively. The low cross-neutralization against Omicron from previous non-Omicron infection supports vaccination of formerly infected individuals to mitigate the health impact of the ongoing Omicron surge.
Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA
Authors: Bergstrom Erik N. , Luebeck Jens , Petljak Mia , Khandekar Azhar , Barnes Mark , Zhang Tongwu , Steele Christopher D. , Pillay Nischalan , Landi Maria Teresa , Bafna Vineet , Mischel Paul S. , Harris Reuben S. , Alexandrov Ludmil B. 
Published: February 2022

AbstractClustered somatic mutations are common in cancer genomes and previous analyses reveal several types of clustered single-base substitutions, which include doublet- and multi-base substitutions1–5, diffuse hypermutation termed omikli6, and longer strand-coordinated events termed kataegis3,7–9. Here we provide a comprehensive characterization of clustered substitutions and clustered small insertions and deletions (indels) across 2,583 whole-genome-sequenced cancers from 30 types of cancer10. Clustered mutations were highly enriched in driver genes and associated with differential gene expression and changes in overall survival. Several distinct mutational processes gave rise to clustered indels, including signatures that were enriched in tobacco smokers and homologous-recombination-deficient cancers. Doublet-base substitutions were caused by at least 12 mutational processes, whereas most multi-base substitutions were generated by either tobacco smoking or exposure to ultraviolet light. Omikli events, which have previously been attributed to APOBEC3 activity6, accounted for a large proportion of clustered substitutions; however, only 16.2% of omikli matched APOBEC3 patterns. Kataegis was generated by multiple mutational processes, and 76.1% of all kataegic events exhibited mutational patterns that are associated with the activation-induced deaminase (AID) and APOBEC3 family of deaminases. Co-occurrence of APOBEC3 kataegis and extrachromosomal DNA (ecDNA), termed kyklonas (Greek for cyclone), was found in 31% of samples with ecDNA. Multiple distinct kyklonic events were observed on most mutated ecDNA. ecDNA containing known cancer genes exhibited both positive selection and kyklonic hypermutation. Our results reveal the diversity of clustered mutational processes in human cancer and the role of APOBEC3 in recurrently mutating and fuelling the evolution of ecDNA.
Mechanisms of inhibition and activation of extrasynaptic αβ GABAA receptors
Authors: Kasaragod Vikram Babu , Mortensen Martin , Hardwick Steven W. , Wahid Ayla A. , Dorovykh Valentina , Chirgadze Dimitri Y. , Smart Trevor G. , Miller Paul S. 
Published: February 2022

AbstractType A GABA (γ-aminobutyric acid) receptors represent a diverse population in the mammalian brain, forming pentamers from combinations of α-, β-, γ-, δ-, ε-, ρ-, θ- and π-subunits1. αβ, α4βδ, α6βδ and α5βγ receptors favour extrasynaptic localization, and mediate an essential persistent (tonic) inhibitory conductance in many regions of the mammalian brain1,2. Mutations of these receptors in humans are linked to epilepsy and insomnia3,4. Altered extrasynaptic receptor function is implicated in insomnia, stroke and Angelman and Fragile X syndromes1,5, and drugs targeting these receptors are used to treat postpartum depression6. Tonic GABAergic responses are moderated to avoid excessive suppression of neuronal communication, and can exhibit high sensitivity to Zn2+ blockade, in contrast to synapse-preferring α1βγ, α2βγ and α3βγ receptor responses5,7–12. Here, to resolve these distinctive features, we determined structures of the predominantly extrasynaptic αβ GABAA receptor class. An inhibited state bound by both the lethal paralysing agent α-cobratoxin13 and Zn2+ was used in comparisons with GABA–Zn2+ and GABA-bound structures. Zn2+ nullifies the GABA response by non-competitively plugging the extracellular end of the pore to block chloride conductance. In the absence of Zn2+, the GABA signalling response initially follows the canonical route until it reaches the pore. In contrast to synaptic GABAA receptors, expansion of the midway pore activation gate is limited and it remains closed, reflecting the intrinsic low efficacy that characterizes the extrasynaptic receptor. Overall, this study explains distinct traits adopted by αβ receptors that adapt them to a role in tonic signalling.
Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil
Authors: Cerqueira-Silva Thiago , Katikireddi Srinivasa Vittal , de Araujo Oliveira Vinicius , Flores-Ortiz Renzo , Júnior Juracy Bertoldo , Paixão Enny S. , Robertson Chris , Penna Gerson O. , Werneck Guilherme L. , Barreto Maurício L. , Pearce Neil , Sheikh Aziz , Barral-Netto Manoel , Boaventura Viviane S. 
Published: February 2022

AbstractThere is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT–PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14–30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3–55.7) against confirmed infection and 82.1% (95% CI: 81.4–82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1–36.2) against infection and 72.5% (95% CI: 70.9–74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0−94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1−98.1) 14–30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.
Mass cytometric and transcriptomic profiling of epithelial-mesenchymal transitions in human mammary cell lines
Authors: Wagner Johanna , Masek Markus , Jacobs Andrea , Soneson Charlotte , Sivapatham Sujana , Damond Nicolas , de Souza Natalie , Robinson Mark D. , Bodenmiller Bernd 
Published: February 2022

AbstractEpithelial-mesenchymal transition (EMT) equips breast cancer cells for metastasis and treatment resistance. However, detection, inhibition, and elimination of EMT-undergoing cells is challenging due to the intrinsic heterogeneity of cancer cells and the phenotypic diversity of EMT programs. We comprehensively profiled EMT transition phenotypes in four non-cancerous human mammary epithelial cell lines using a flow cytometry surface marker screen, RNA sequencing, and mass cytometry. EMT was induced in the HMLE and MCF10A cell lines and in the HMLE-Twist-ER and HMLE-Snail-ER cell lines by prolonged exposure to TGFβ1 or 4-hydroxytamoxifen, respectively. Each cell line exhibited a spectrum of EMT transition phenotypes, which we compared to the steady-state phenotypes of fifteen luminal, HER2-positive, and basal breast cancer cell lines. Our data provide multiparametric insights at single-cell level into the phenotypic diversity of EMT at different time points and in four human cellular models. These insights are valuable to better understand the complexity of EMT, to compare EMT transitions between the cellular models used here, and for the design of EMT time course experiments.
Natural bio-convective flow of Maxwell nanofluid over an exponentially stretching surface with slip effect and convective boundary condition
Authors: Wang Fuzhang , Ahmad Shafiq , Al Mdallal Qasem , Alammari Maha , Khan Muhammad Naveed , Rehman Aysha 
Published: February 2022

AbstractThe under-consideration article mainly focuses an unsteady three-dimensional Maxwell bio-convective nanomaterial liquid flow towards an exponentially expanding surface with the influence of chemical reaction slip condition. The feature of heat transport is achieving in the existenceof convective boundary condition and variable thermal conductivity. With the help of similarity variables, the flow form of equations is turned into a nonlinear form of coupled ODEs. The numerical solutions are calculated by adopting bvp4c function of MATLAB. Impact of distinct characteristics on the temperature, velocity microorganism and concentration field is graphically evaluated. Moreover, physical quantities are observed via graphs and tabulated data in details. It has been seen by the observation that the involvement of unsteadiness parameter restricts the change of laminar to turbulent flow. Further, for increasing velocity slip parameter velocity component in both directions shows lessening behavior. The Nusselt number exhibits diminishing behavior for larger values of Deborah number, and it shows the opposite behavior for larger values of convective parameter.
Phenylalanine gold nanoclusters as sensing platform for π–π interfering molecules: a case study of iodide
Authors: Amiri-Sadeghan Amir , Dinari Ali , Mohammadi Soheila , Zohrabi Tayebeh , Khodarahmi Reza , Hosseinkhani Saman , Yoon Jungwon 
Published: February 2022

AbstractThe photo-physical properties of metal nano clusters are sensitive to their surrounding medium. Fluorescence enhancement, quenching, and changes in the emitted photon properties are usual events in the sensing applications using these nano materials. Combining this sensitivity with unique properties of self-assembled structures opens new opportunities for sensing applications. Here, we synthesized gold nanoclusters by utilizing phenylalanine amino acid as both capping and reducing molecule. Phenylalanine is able to self-assemble to rod-shaped nano structure in which the π–π interaction between the aromatic rings is a major stabilizing force. Any substance as iodide anion or molecule that is able to weaken this interaction influence the fluorescence of metal nano-clusters. Since the building blocks of the self-assembled structure are made through the reaction of gold ions and phenylalanine, the oxidized products and their effect of sensing features are explored.
Quantitative parameter mapping of contrast agent concentration and relaxivity and brain tumor extracellular pH
Authors: Matsumoto Yuki , Harada Masafumi , Kanazawa Yuki , Taniguchi Yo , Ono Masaharu , Bito Yoshitaka 
Published: February 2022

AbstractIn clinical magnetic resonance imaging, gadolinium-based contrast agents are commonly used for detecting brain tumors and evaluating the extent of malignancy. We present a new method to evaluate relaxivity (r1) and contrast agent concentration separately in contrast-enhanced lesions using quantitative parameter mapping (QPM). Furthermore, we also aimed to estimate the extracellular pH (pHe) of tumor lesions. We demonstrated that it is possible to evaluate pathophysiological tumor changes due to therapeutic efficacy by measuring r1 in contrast-enhanced lesions. In this study, the primary brain tumor group showed significantly higher r1 values than other brain disease groups (P < 0.001). Moreover, mean pHe value showed a trend for tumor malignancy having a lower pHe value and primary brain tumor having a significantly lower pHe than other brain diseases (P < 0.001). Our results might suggest that QPM can separately quantify r1 and CA concentration in brain tumors and that pHe brain tumor mapping could serve as a tumor biomarker. In conclusion, our method has potential clinical applications for assessing the treatment effects.
Clinical and pathological characteristics associated with the presence of the IS6110 Mycobacterim tuberculosis transposon in neoplastic cells from non-small cell lung cancer patients
Authors: Arrieta Oscar , Molina-Romero Camilo , Cornejo-Granados Fernanda , Marquina-Castillo Brenda , Avilés-Salas Alejandro , López-Leal Gamaliel , Cardona Andrés F. , Ortega-Gómez Alette , Orozco-Morales Mario , Ochoa-Leyva Adrián , Hernandez-Pando Rogelio 
Published: February 2022

AbstractLung cancer (LC) and pulmonary tuberculosis (TB) are the deadliest neoplastic and bacterial infectious diseases worldwide, respectively. Clinicians and pathologists have long discussed the co-existence of LC and TB, and several epidemiologic studies have presented evidence indicating that TB could be associated with the development of LC, particularly adenocarcinoma. Nonetheless, this data remains controversial, and the mechanism which could underlie the association remains largely unexplored. Some bioinformatic studies have shown that human cancer biopsies have a very high frequency of bacterial DNA integration; since Mycobacterium Tuberculosis (MTb) is an intracellular pathogen, it could play an active role in the cellular transformation. Our group performed an exploratory study in a cohort of 88 LC patients treated at the Instituto Nacional de Cancelorogía (INCan) of Mexico City to evaluate the presence of MTb DNA in LC tissue specimens. For the first time, our results show the presence of the MTb IS6110 transposon in 40.9% (n = 36/88) of patients with lung adenocarcinomas. Additionally, through in-situ PCR we identified the presence of IS6110 in the nuclei of tumor cells. Furthermore, shotgun sequencing from two samples identified traces of MTb genomes present in tumor tissue, suggesting that similar Mtb strains could be infecting both patients.
A matrix representation for sustainable activities
Authors: Mahmud A. S. , Zachary D. S. 
Published: February 2022

AbstractThe present paper develops a matrix framework to determine the sustainability of multiple activities simultaneously. We define an activity as an action or process involving multiple resources; each activity depends upon other activities at a higher level. First, the problem of sustainability is framed in the context of an input–output model. Later, an infinite layer approach is adopted to represent different sectors of the economy and both renewable and non-renewable resources. Using the infinite layer approach, the concentration of renewable energy usage is calculated for each activity. The conversion to productive use varies from one resource to another. The current endeavor also focuses on enhancing energy efficiency to reduce non-renewable resource dependency.
Classifying neovascular age-related macular degeneration with a deep convolutional neural network based on optical coherence tomography images
Authors: Han Jinyoung , Choi Seong , Park Ji In , Hwang Joon Seo , Han Jeong Mo , Lee Hak Jun , Ko Junseo , Yoon Jeewoo , Hwang Daniel Duck-Jin 
Published: February 2022

AbstractNeovascular age-related macular degeneration (nAMD) is among the main causes of visual impairment worldwide. We built a deep learning model to distinguish the subtypes of nAMD using spectral domain optical coherence tomography (SD-OCT) images. Data from SD-OCT images of nAMD (polypoidal choroidal vasculopathy, retinal angiomatous proliferation, and typical nAMD) and normal healthy patients were analyzed using a convolutional neural network (CNN). The model was trained and validated based on 4749 SD-OCT images from 347 patients and 50 healthy controls. To adopt an accurate and robust image classification architecture, we evaluated three well-known CNN structures (VGG-16, VGG-19, and ResNet) and two customized classification layers (fully connected layer with dropout vs. global average pooling). Following the test set performance, the model with the highest classification accuracy was used. Transfer learning and data augmentation were applied to improve the robustness and accuracy of the model. Our proposed model showed an accuracy of 87.4% on the test data (920 images), scoring higher than ten ophthalmologists, for the same data. Additionally, the part that our model judged to be important in classification was confirmed through Grad-CAM images, and consequently, it has a similar judgment criteria to that of ophthalmologists. Thus, we believe that our model can be used as an auxiliary tool in clinical practice.