bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute myeloid leukemia: current progress and future directions
Authors: Kantarjian Hagop , Kadia Tapan , DiNardo Courtney , Daver Naval , Borthakur Gautam , Jabbour Elias , Garcia-Manero Guillermo , Konopleva Marina , Ravandi Farhad 
Published: February 2021

AbstractProgress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various indications in AML. These included several targeted therapies like venetoclax, FLT3 inhibitors, IDH inhibitors, and others. The management of AML is complicated, highlighting the need for expertise in order to deliver optimal therapy and achieve optimal outcomes. The multiple subentities in AML require very different therapies. In this review, we summarize the important pathophysiologies driving AML, review current therapies in standard practice, and address present and future research directions.
Use of CRISPR/Cas9-mediated disruption of CNS cell type genes to profile transduction of AAV by neonatal intracerebroventricular delivery in mice
Authors: Torregrosa Tess , Lehman Sydney , Hana Sam , Marsh Galina , Xu Shanqin , Koszka Kathryn , Mastrangelo Nicole , McCampbell Alexander , Henderson Christopher E. , Lo Shih-Ching 
Published: February 2021

AbstractAdeno-associated virus (AAV) transduction efficiency and tropism are conventionally determined by high expression of a fluorescent reporter gene. Emerging data has suggested that such conventional methods may underestimate AAV transduction for cells in which reporter expression from AAV vectors is undetectable. To explore an alternative method that captures AAV transduction in cells in which low expression of a cargo is sufficient for the intended activity, we sought after CRISPR/Cas9-mediated gene disruption. In this study, we use AAV to deliver CRISPR/guide RNA designed to abolish the genes NeuN, GFAP, or MOG expressed specifically in neurons, astrocytes, or oligodendrocytes respectively in the central nervous system (CNS) of mice. Abrogated expression of these cell-type-specific genes can be measured biochemically in CNS subregions and provides quantitative assessment of AAV transduction in these CNS cell types. By using this method, we compared CNS transduction of AAV9, AAV-PHP.B, and AAV-PHP.eB delivered via intracerebroventricular injection (ICV) in neonatal mice. We found both AAV-PHP.B and AAV-PHP.eB resulted in marked disruption of the NeuN gene by CRISPR/Cas9, significantly greater than AAV9 in several brain regions and spinal cord. In contrast, only modest disruption of the GFAP gene and the MOG gene was observed by all three AAV variants. Since the procedure of ICV circumvents the blood–brain barrier, our data suggests that, independent of their ability to cross the blood–brain barrier, AAV-PHP.B variants also exhibit remarkably improved neuronal transduction in the CNS. We anticipate this approach will facilitate profiling of AAV cellular tropism in murine CNS.
Uniform genomic data analysis in the NCI Genomic Data Commons
Authors: Zhang Zhenyu , Hernandez Kyle , Savage Jeremiah , Li Shenglai , Miller Dan , Agrawal Stuti , Ortuno Francisco , Staudt Louis M. , Heath Allison , Grossman Robert L. 
Published: February 2021

AbstractThe goal of the National Cancer Institute’s (NCI’s) Genomic Data Commons (GDC) is to provide the cancer research community with a data repository of uniformly processed genomic and associated clinical data that enables data sharing and collaborative analysis in the support of precision medicine. The initial GDC dataset include genomic, epigenomic, proteomic, clinical and other data from the NCI TCGA and TARGET programs. Data production for the GDC started in June, 2015 using an OpenStack-based private cloud. By June of 2016, the GDC had analyzed more than 50,000 raw sequencing data inputs, as well as multiple other data types. Using the latest human genome reference build GRCh38, the GDC generated a variety of data types from aligned reads to somatic mutations, gene expression, miRNA expression, DNA methylation status, and copy number variation. In this paper, we describe the pipelines and workflows used to process and harmonize the data in the GDC. The generated data, as well as the original input files from TCGA and TARGET, are available for download and exploratory analysis at the GDC Data Portal and Legacy Archive (https://gdc.cancer.gov/).
Computation and data driven discovery of topological phononic materials
Authors: Li Jiangxu , Liu Jiaxi , Baronett Stanley A. , Liu Mingfeng , Wang Lei , Li Ronghan , Chen Yun , Li Dianzhong , Zhu Qiang , Chen Xing-Qiu 
Published: February 2021

AbstractThe discovery of topological quantum states marks a new chapter in both condensed matter physics and materials sciences. By analogy to spin electronic system, topological concepts have been extended into phonons, boosting the birth of topological phononics (TPs). Here, we present a high-throughput screening and data-driven approach to compute and evaluate TPs among over 10,000 real materials. We have discovered 5014 TP materials and grouped them into two main classes of Weyl and nodal-line (ring) TPs. We have clarified the physical mechanism for the occurrence of single Weyl, high degenerate Weyl, individual nodal-line (ring), nodal-link, nodal-chain, and nodal-net TPs in various materials and their mutual correlations. Among the phononic systems, we have predicted the hourglass nodal net TPs in TeO3, as well as the clean and single type-I Weyl TPs between the acoustic and optical branches in half-Heusler LiCaAs. In addition, we found that different types of TPs can coexist in many materials (such as ScZn). Their potential applications and experimental detections have been discussed. This work substantially increases the amount of TP materials, which enables an in-depth investigation of their structure-property relations and opens new avenues for future device design related to TPs.
Coupled nitrification and N2 gas production as a cryptic process in oxic riverbeds
Authors: Ouyang Liao , Thamdrup Bo , Trimmer Mark 
Published: February 2021

AbstractThe coupling between nitrification and N2 gas production to recycle ammonia back to the atmosphere is a key step in the nitrogen cycle that has been researched widely. An assumption for such research is that the products of nitrification (nitrite or nitrate) mix freely in the environment before reduction to N2 gas. Here we show, in oxic riverbeds, that the pattern of N2 gas production from ammonia deviates by ~3- to 16-fold from that predicted for denitrification or anammox involving nitrite or nitrate as free porewater intermediates. Rather, the patterns match that for a coupling through a cryptic pool, isolated from the porewater. A cryptic pool challenges our understanding of a key step in the nitrogen cycle and masks our ability to distinguish between sources of N2 gas that 20 years’ research has sought to identify. Our reasoning suggests a new pathway or a new type of coupling between known pathways in the nitrogen cycle.
Chromosomally unstable tumor cells specifically require KIF18A for proliferation
Authors: Marquis Carolyn , Fonseca Cindy L. , Queen Katelyn A. , Wood Lisa , Vandal Sarah E. , Malaby Heidi L. H. , Clayton Joseph E. , Stumpff Jason 
Published: February 2021

AbstractChromosomal instability (CIN) is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that compromise the mitotic spindle. Thus, CIN cells may respond differently than diploid cells to treatments that target mitotic spindle regulation. Here, we test this idea by inhibiting a subset of kinesin motor proteins involved in mitotic spindle control. KIF18A is required for proliferation of CIN cells derived from triple negative breast cancer or colorectal cancer tumors but is not required in near-diploid cells. Following KIF18A inhibition, CIN tumor cells exhibit mitotic delays, multipolar spindles, and increased cell death. Sensitivity to KIF18A knockdown is strongly correlated with centrosome fragmentation, which requires dynamic microtubules but does not depend on bipolar spindle formation or mitotic arrest. Our results indicate the altered spindle microtubule dynamics characteristic of CIN tumor cells can be exploited to reduce the proliferative capacity of CIN cells.
Unravelling the structural complexity of glycolipids with cryogenic infrared spectroscopy
Authors: Kirschbaum Carla , Greis Kim , Mucha Eike , Kain Lisa , Deng Shenglou , Zappe Andreas , Gewinner Sandy , Schöllkopf Wieland , von Helden Gert , Meijer Gerard , Savage Paul B. , Marianski Mateusz , Teyton Luc , Pagel Kevin 
Published: February 2021

AbstractGlycolipids are complex glycoconjugates composed of a glycan headgroup and a lipid moiety. Their modular biosynthesis creates a vast amount of diverse and often isomeric structures, which fulfill highly specific biological functions. To date, no gold-standard analytical technique can provide a comprehensive structural elucidation of complex glycolipids, and insufficient tools for isomer distinction can lead to wrong assignments. Herein we use cryogenic gas-phase infrared spectroscopy to systematically investigate different kinds of isomerism in immunologically relevant glycolipids. We show that all structural features, including isomeric glycan headgroups, anomeric configurations and different lipid moieties, can be unambiguously resolved by diagnostic spectroscopic fingerprints in a narrow spectral range. The results allow for the characterization of isomeric glycolipid mixtures and biological applications.
Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis
Authors: Hovaguimian Frédérique , Günthard Huldrych F. , Hauser Christoph , Conen Anna , Bernasconi Enos , Calmy Alexandra , Cavassini Matthias , Seneghini Marco , Marzel Alex , Heinrich Henriette , Scherrer Alexandra , Riou Julien , Spoerri Adrian , Schmidlin Kurt , Balakrishna Suraj , Braun Dominique L. , Rampini Silvana K. , Fehr Jan S. , Kouyos Roger D. ,   the Swiss HIV Cohort Study, Aebi-Popp K. , Anagnostopoulos A. , Battegay M. , Bernasconi E. , Böni J. , Braun D. L. , Bucher H. C. , Calmy A. , Cavassini M. , Ciuffi A. , Dollenmaier G. , Egger M. , Elzi L. , Fehr J. , Fellay J. , Furrer H. , Fux C. A. , Günthard H. F. , Haerry D. , Hasse B. , Hirsch H. H. , Hoffmann M. , Hösli I. , Huber M. , Kahlert C. R. , Kaiser L. , Keiser O. , Klimkait T. , Kouyos R. D. , Kovari H. , Ledergerber B. , Martinetti G. , Martinez de Tejada B. , Marzolini C. , Metzner K. J. , Müller N. , Nicca D. , Paioni P. , Pantaleo G. , Perreau M. , Rauch A. , Rudin C. , Scherrer A. U. , Schmid P. , Speck R. , Stöckle M. , Tarr P. , Trkola A. , Vernazza P. , Wandeler G. , Weber R. , Yerly S. 
Published: February 2021

AbstractEvidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.
Longitudinal and multi-tissue molecular diagnostics track somatic BRCA2 reversion mutations that correct the open reading frame of germline alteration upon clinical relapse
Authors: Sorrells Shelly , McKinnon Kelly E. , McBratney Ashleigh , Sumey Christopher 
Published: February 2021

AbstractBRCA-mutant cancers often develop therapeutic resistance through several mechanisms. Here, we report a case of pathogenic germline BRCA2-driven breast cancer monitored for disease progression and acquired resistance using longitudinal multi-tissue genomic testing. Briefly, genomic testing was performed throughout the course of disease on tumor tissue from multiple sites, circulating tumor DNA from blood plasma, and matched normal tissue. Genomic analyses identified actionable variants for targeted therapies, as well as emerging resistance mutations over time. Two unique BRCA2 somatic alterations (p.N255fs and p.D252fs) were identified upon resistance to PARP inhibitor and platinum treatment, respectively. Both alterations restored the open reading frame of the original germline alteration, likely accounting for acquired resistance. This case exemplifies the evolution of multiple subclonal BRCA reversion alterations over time and demonstrates the value of longitudinal multi-tissue genomic testing for monitoring disease progression, predicting measures of response, and evaluating treatment outcomes in oncology patients.
SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates
Authors: Kyriakidis Nikolaos C. , López-Cortés Andrés , González Eduardo Vásconez , Grimaldos Alejandra Barreto , Prado Esteban Ortiz 
Published: February 2021

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.
A prognostic model for colorectal cancer based on CEA and a 48-multiplex serum biomarker panel
Authors: Björkman Kajsa , Jalkanen Sirpa , Salmi Marko , Mustonen Harri , Kaprio Tuomas , Kekki Henna , Pettersson Kim , Böckelman Camilla , Haglund Caj 
Published: February 2021

AbstractMortality in colorectal cancer (CRC) remains high, resulting in 860,000 deaths annually. Carcinoembryonic antigen is widely used in clinics for CRC patient follow-up, despite carrying a limited prognostic value. Thus, an obvious need exists for multivariate prognostic models. We analyzed 48 biomarkers using a multiplex immunoassay panel in preoperative serum samples from 328 CRC patients who underwent surgery at Helsinki University Hospital between 1998 and 2003. We performed a multivariate prognostic forward-stepping background model based on basic clinicopathological data, and a multivariate machine-learned prognostic model based on clinicopathological data and biomarker variables, calculating the disease-free survival using the value of importance score. From the 48 analyzed biomarkers, only IL-8 emerged as a significant prognostic factor for CRC patients in univariate analysis (HR 4.88; 95% CI 2.00–11.92;p = 0.024) after correcting for multiple comparisons. We also developed a multivariate model based on all 48 biomarkers using a random survival forest analysis. Variable selection based on a minimal depth and the value of importance yielded two tentative candidate CRC prognostic markers: IL-2Ra and IL-8. A multivariate prognostic model using machine-learning technologies improves the prognostic assessment of survival among surgically treated CRC patients.
Evaluation of Antarctic Ozone Profiles derived from OMPS-LP by using Balloon-borne Ozonesondes
Authors: Sepúlveda Edgardo , Cordero Raul R. , Damiani Alessandro , Feron Sarah , Pizarro Jaime , Zamorano Felix , Kivi Rigel , Sánchez Ricardo , Yela Margarita , Jumelet Julien , Godoy Alejandro , Carrasco Jorge , Crespo Juan S. , Seckmeyer Gunther , Jorquera Jose A. , Carrera Juan M. , Valdevenito Braulio , Cabrera Sergio , Redondas Alberto , Rowe Penny M. 
Published: February 2021

AbstractPredicting radiative forcing due to Antarctic stratospheric ozone recovery requires detecting changes in the ozone vertical distribution. In this endeavor, the Limb Profiler of the Ozone Mapping and Profiler Suite (OMPS-LP), aboard the Suomi NPP satellite, has played a key role providing ozone profiles over Antarctica since 2011. Here, we compare ozone profiles derived from OMPS-LP data (version 2.5 algorithm) with balloon-borne ozonesondes launched from 8 Antarctic stations over the period 2012–2020. Comparisons focus on the layer from 12.5 to 27.5 km and include ozone profiles retrieved during the Sudden Stratospheric Warming (SSW) event registered in Spring 2019. We found that, over the period December-January–February-March, the root mean square error (RMSE) tends to be larger (about 20%) in the lower stratosphere (12.5–17.5 km) and smaller (about 10%) within higher layers (17.5–27.5 km). During the ozone hole season (September–October–November), RMSE values rise up to 40% within the layer from 12.5 to 22 km. Nevertheless, relative to balloon-borne measurements, the mean bias error of OMPS-derived Antarctic ozone profiles is generally lower than 0.3 ppmv, regardless of the season.
Changes in surface characteristics and adsorption properties of 2,4,6-trichlorophenol following Fenton-like aging of biochar
Authors: Cui Liqiang , Fan Qinya , Sun Jianxiong , Quan Guixiang , Yan Jinlong , Hina Kiran , Wang Hui , Zhang Zhiqiang , Hussain Qaiser 
Published: February 2021

AbstractFenton-like system formed in a natural soil environment deemed to be significant in the aging process of biochar. Aged biochars have distinct physico-chemical and surface properties compared to non-aged biochar. The aged biochar proved to be useful soil amendment due to its improved elements contents and surface properties. The biochar aging process resulted in increased surface area and pore volume, as well as carbon and oxygen-containing functional groups (such as C=O, –COOH, O–C=O etc.) on its surface, which were also associated with the adsorption behavior of 2,4,6-trichlorophenol (2,4,6-TCP). The biochar aging increased the adsorption capacity of 2,4,6-TCP, which was maximum at pH 3.0. The 2,4,6-TCP adsorption capacity of aged-bush biochar (ABB) and aged-peanut shell biochar (APB) was increased by 1.0–11.0% and 7.4–38.8%, respectively compared with bush biochar (BB) and peanut shell biochar (PB) at the same initial concentration of 2,4,6-TCP. All biochars had similar 2,4,6-TCP desorption rates ranging from 33.2 to 73.3% at different sorption temperatures and times. The desorbed components were mainly 2,4,6-TCP and other degraded components, which were low in concentration with small molecule substance. The results indicated that the aged-biochar could be effective for the long-term remediation of naturally organic polluted soils.
Human brain activity reflecting facial attractiveness from skin reflection
Authors: Sakano Yuichi , Wada Atsushi , Ikeda Hanako , Saheki Yuriko , Tagai Keiko , Ando Hiroshi 
Published: February 2021

AbstractFacial attraction has a great influence on our daily social interactions. Previous studies have mainly focused on the attraction from facial shape and expression. We recently found that faces with radiant skin appear to be more attractive than those with oily-shiny or matte skin. In the present study, we conducted functional magnetic resonance imaging (fMRI) and psychological experiments to determine the human brain activity that reflects facial attractiveness modulated by these skin reflection types. In the fMRI experiment, female subjects were shown successive images of unfamiliar female faces with matte, oily-shiny, or radiant skin. The subjects compared each face with the immediately preceding face in terms of attractiveness, age, and skin reflection, all based on the skin. The medial part of the orbitofrontal cortex (mOFC) was significantly more active when comparing attractiveness than when comparing skin reflection, suggesting that the mOFC is involved in processing facial attractiveness from skin reflection. In the psychological experiment, attractiveness rating was highest for radiant skin, followed by oily-shiny, and then matte skin. Comparison of the results of these experiments showed that mOFC activation level increased with attractiveness rating. These results suggest that the activation level of the mOFC reflects facial attractiveness from skin reflection.
Audiovisual structural connectivity in musicians and non-musicians: a cortical thickness and diffusion tensor imaging study
Authors: Møller Cecilie , Garza-Villarreal Eduardo A. , Hansen Niels Chr. , Højlund Andreas , Bærentsen Klaus B. , Chakravarty M. Mallar , Vuust Peter 
Published: February 2021

AbstractOur sensory systems provide complementary information about the multimodal objects and events that are the target of perception in everyday life. Professional musicians’ specialization in the auditory domain is reflected in the morphology of their brains, which has distinctive characteristics, particularly in areas related to auditory and audio-motor activity. Here, we combineddiffusion tensor imaging(DTI) with a behavioral measure of visually induced gain in pitch discrimination, and we used measures ofcortical thickness(CT) correlations to assess how auditory specialization and musical expertise are reflected in the structural architecture of white and grey matter relevant to audiovisual processing. Across all participants (n = 45), we found a correlation (p < 0.001) between reliance on visual cues in pitch discrimination and thefractional anisotropy(FA) in the leftinferior fronto-occipital fasciculus(IFOF), a structure connecting visual and auditory brain areas. Group analyses also revealed greater cortical thickness correlation between visual and auditory areas in non-musicians (n = 28) compared to musicians (n = 17), possibly reflecting musicians’ auditory specialization (FDR < 10%). Our results corroborate and expand current knowledge of functional specialization with a specific focus on audition, and highlight the fact that perception is essentially multimodal while uni-sensory processing is a specialized task.