bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower neck organs at risk sparing in nasopharyngeal carcinoma using hybrid volumetric-modulated arc therapy (hybrid-VMAT): a case report
Authors: Yuen Adams Hei Long , Li Alex Kai Leung , Mak Philip Chung Yin 
Published: April 2021

AbstractIntroduction:Nasopharyngeal carcinoma (NPC) is a prevalent disease in Southern China. Radiation therapy remains the primary treatment modality for NPC due to its high radiation sensitivity. Conventional volumetric-modulated arc therapy (VMAT) can achieve excellent target volume coverage and superior conformal dose distributions while sparing organs at risk (OARs). However, VMAT may also produce substantial volume of low-dose region in the surrounding normal tissue. Our oncology centre has incorporated the concept of anterior cervical field with VMAT in clinical practice of NPC treatment planning. The purpose of this treatment-comparison case study is to demonstrate the lower neck OARs sparing ability of hybrid volumetric-modulated arc therapy (hybrid-VMAT) over conventional VMAT for NPC.Methods:Four patients diagnosed with NPC of different clinical lymph node staging (N staging) were enrolled for this treatment-comparison case study. Planning target volumes and OARs were delineated with reference to Radiation Therapy Oncology Group (RTOG) 0225/0615. Additional OARs from lower neck region, including thyroid, trachea, cervical spine and pharyngeal constrictor muscles (PCMs), were also delineated. Two treatment techniques, hybrid-VMAT and VMAT, were created for each patient’s dataset.Results and findings:Both treatment techniques produced adequate target coverage and reduced radiation dose to the OARs as suggested in RTOG 0225/0615. Hybrid-VMAT plans achieved superior dose reduction in larynx, oesophagus, middle PCM, inferior PCM, cervical spine and trachea comparing with VMAT plans. Hence, the clinical usability and functional outcome of hybrid-VMAT should be further investigated for NPC radiation therapy.
A lifespan approach to understanding family caregiver experiences of a blood cancer diagnosis
Authors: Kastrinos Amanda L. , Fisher Carla L. , Mullis Michaela D. , Wollney Easton , Sae-Hau Maria , Weiss Elisa S. , Bylund Carma L. 
Published: April 2021

AbstractObjectivesThe study examined the diagnosis experience of midlife family caregivers of a patient with a blood cancer, exploring similarities and differences between parent caregivers and adult-child caregivers.MethodsParticipants were between 30 and 65 years old and were family caregivers of a living patient with acute myeloid leukemia, acute lymphoblastic leukemia, or lymphoma. We conducted semi-structured interviews with parent caregivers (n = 20) and adult-child caregivers (n = 19) and a thematic analysis of the interview data.ResultsBoth types of caregivers report the patient experiencing (1) mis- and missed diagnosis (facing delayed diagnosis or treatment and having symptoms dismissed or overlooked) and (2) emotional distress (being in shock and survival mode, struggling with uncertainty, and confronting mortality). Adult-child caregivers also experienced relational shifts in assuming control of their parent's care, sometimes despite geographic distance, and struggled to distribute the care burden among family members.Significance of resultsDifferences between the caregivers’ experiences emerged based on the relational role and the patient's place in the lifespan. Findings can be used to inform the development of support resources to address the needs of each group.
Exhuming theNahualli:Shapeshifting, Idolatry, and Orthodoxy in Colonial Mexico
Authors: Hagler Anderson 
Published: April 2021

AbstractThis article examines the relationship between ritual specialists,nanahualtinornahualistas(pl.) andnahualliornahual(sing.), and healing practices, adding context to the social roles they fulfilled and the range of feats they performed. The cases examined here reveal that nanahualtin operated as intellectuals in their communities because of their ability to control animals, prognosticate, and heal or harm individuals at will. Some nanahualtin shapeshifted from humans to animals while others possessed animal companions. The elevated status of nanahualtin led commoners to seek their advice, which conflicted with the established orthodoxy of the Catholic Church. Because clergymen championed the sacraments as the best way to access the divine, non-orthodox rituals performed in mountains, rivers, and caves were derided as idolatrous devil worship.The 11 criminal and Mexican Inquisition cases examined here range from 1599 to 1801. Two seventeenth-century cases (1678 and 1685) and one eighteenth-century case (1701) contain Nahuatl phrases and testimonies from Chiapas and Tlaxcala, respectively. The cases from Chiapas demonstrate the use of Nahuatl as a vehicular language outside the central valley of Mexico. This article examines the gender of the animals into which ritual specialists transformed as an emergent category from trial records, which provides insight into Catholic officials’ understanding of the nahualli. Last, this study notes social divisions between rural and urban clergy regarding the power of nanahualtin and the efficacy of their magic.
Ice Age‐Holocene Similarity of Foraminifera‐Bound Nitrogen Isotope Ratios in the Eastern Equatorial Pacific
Authors: Studer Anja S. , Mekik Figen , Ren Haojia , Hain Mathis P. , Oleynik Sergey , Martínez‐García Alfredo , Haug Gerald H. , Sigman Daniel M. 
Published: April 2021

AbstractBulk sediment δ15N records from the eastern tropical Pacific (ETP) extending back to the last ice age most often show low glacial δ15N, then a deglacial δ15N maximum, followed by a gradual decline to a late Holocene δ15N that is typically higher than that of the Last Glacial Maximum (LGM). The lower δ15N of the LGM has been interpreted to reflect an ice age reduction in water column denitrification. We report foraminifera shell‐bound nitrogen isotope (FB‐δ15N) measurements for the two species Neogloboquadrina dutertrei and Neogloboquadrina incompta over the last 35 ka in two sediment cores from the eastern equatorial Pacific (EEP), both of which have the typical LGM‐to‐Holocene increase in bulk sediment δ15N. FB‐δ15N contrasts with bulk sediment δ15N by not indicating a lower δ15N during the LGM. Instead, the FB‐δ15N records are dominated by a deglacial δ15N maximum, with comparable LGM and Holocene values. The lower LGM δ15N of the bulk sediment records may be an artifact, possibly related to greater exogenous N inputs and/or weaker sedimentary diagenesis during the LGM. The new data raise the possibility that the previously inferred glacial reduction in ETP water column denitrification was incorrect. A review of reconstructed ice age conditions and geochemical box model output provides mechanistic support for this possibility. However, equatorial ocean circulation and nitrate‐rich surface water overlying both core sites allow for other possible interpretations, calling for replication at non‐equatorial ETP sites.
Increasing the Physical Representation of Forest‐Snow Processes in Coarse‐Resolution Models: Lessons Learned From Upscaling Hyper‐Resolution Simulations
Authors: Mazzotti Giulia , Webster Clare , Essery Richard , Jonas Tobias 
Published: April 2021

AbstractProcesses shaping forest snow cover evolution often vary at small spatial scales, which are not resolved by most model applications. Representing this variability at larger scales and coarser model resolutions constitutes a major challenge for model developers. In this study, we use a well‐validated hyper‐resolution forest snow model that explicitly resolves the spatial variability of canopy‐snow interactions at the meter scale to explore adequate representation of forest‐snow processes at coarser resolutions (50 m). For this purpose, we assess coarser‐resolution runs against spatially averaged results from corresponding hyper‐resolution simulations over a 150,000 m2 model domain. For the coarser‐resolution simulations, we tested alternative upscaling strategies. Our results reveal considerable discrepancies between strategies that utilize generalized canopy metrics versus strategies that apply a more detailed set of process‐specific canopy descriptors. Particularly, the inclusion of canopy descriptors that represent the various scales and perspectives relevant to the individual processes leads to accurate simulation of forest snow cover dynamics at coarse resolutions. Our results further demonstrate that a realistic representation of snow‐covered fraction in snowmelt calculations is important even for relatively small (∼50 m) grid cells. Ultimately, this work provides recommendations for modeling forest‐snow processes in large‐scale applications, which allow coarse resolution simulations to approximate spatially averaged results of corresponding hyper‐resolution simulations.
Statistical Emulation of Winter Ambient Fine Particulate Matter Concentrations From Emission Changes in China
Authors: Conibear Luke , Reddington Carly L. , Silver Ben J. , Chen Ying , Knote Christoph , Arnold Stephen R. , Spracklen Dominick V. 
Published: April 2021

AbstractAir pollution exposure remains a leading public health problem in China. The use of chemical transport models to quantify the impacts of various emission changes on air quality is limited by their large computational demands. Machine learning models can emulate chemical transport models to provide computationally efficient predictions of outputs based on statistical associations with inputs. We developed novel emulators relating emission changes in five key anthropogenic sectors (residential, industry, land transport, agriculture, and power generation) to winter ambient fine particulate matter (PM2.5) concentrations across China. The emulators were optimized based on Gaussian process regressors with Matern kernels. The emulators predicted 99.9% of the variance in PM2.5 concentrations for a given input configuration of emission changes. PM2.5 concentrations are primarily sensitive to residential (51%–94% of first‐order sensitivity index), industrial (7%–31%), and agricultural emissions (0%–24%). Sensitivities of PM2.5 concentrations to land transport and power generation emissions are all under 5%, except in South West China where land transport emissions contributed 13%. The largest reduction in winter PM2.5 exposure for changes in the five emission sectors is by 68%–81%, down to 15.3–25.9 μg m−3, remaining above the World Health Organization annual guideline of 10 μg m−3. The greatest reductions in PM2.5 exposure are driven by reducing residential and industrial emissions, emphasizing the importance of emission reductions in these key sectors. We show that the annual National Air Quality Target of 35 μg m−3 is unlikely to be achieved during winter without strong emission reductions from the residential and industrial sectors.
CRISPR-Cas9 cytidine and adenosine base editing of splice-sites mediates highly-efficient disruption of proteins in primary and immortalized cells
Authors: Kluesner Mitchell G. , Lahr Walker S. , Lonetree Cara-lin , Smeester Branden A. , Qiu Xiaohong , Slipek Nicholas J. , Claudio Vázquez Patricia N. , Pitzen Samuel P. , Pomeroy Emily J. , Vignes Madison J. , Lee Samantha C. , Bingea Samuel P. , Andrew Aneesha A. , Webber Beau R. , Moriarity Branden S. 
Published: April 2021

AbstractCRISPR-Cas9 cytidine and adenosine base editors (CBEs and ABEs) can disrupt genes without introducing double-stranded breaks by inactivating splice sites (BE-splice) or by introducing premature stop (pmSTOP) codons. However, no in-depth comparison of these methods or a modular tool for designing BE-splice sgRNAs exists. To address these needs, we develop SpliceR (http://z.umn.edu/spliceR) to design and rank BE-splice sgRNAs for any Ensembl annotated genome, and compared disruption approaches in T cells using a screen against the TCR-CD3 MHC Class I immune synapse. Among the targeted genes, we find that targeting splice-donors is the most reliable disruption method, followed by targeting splice-acceptors, and introducing pmSTOPs. Further, the CBE BE4 is more effective for disruption than the ABE ABE7.10, however this disparity is eliminated by employing ABE8e. Collectively, we demonstrate a robust method for gene disruption, accompanied by a modular design tool that is of use to basic and translational researchers alike.
Active discovery of organic semiconductors
Authors: Kunkel Christian , Margraf Johannes T. , Chen Ke , Oberhofer Harald , Reuter Karsten 
Published: April 2021

AbstractThe versatility of organic molecules generates a rich design space for organic semiconductors (OSCs) considered for electronics applications. Offering unparalleled promise for materials discovery, the vastness of this design space also dictates efficient search strategies. Here, we present an active machine learning (AML) approach that explores an unlimited search space through consecutive application of molecular morphing operations. Evaluating the suitability of OSC candidates on the basis of charge injection and mobility descriptors, the approach successively queries predictive-quality first-principles calculations to build a refining surrogate model. The AML approach is optimized in a truncated test space, providing deep methodological insight by visualizing it as a chemical space network. Significantly outperforming a conventional computational funnel, the optimized AML approach rapidly identifies well-known and hitherto unknown molecular OSC candidates with superior charge conduction properties. Most importantly, it constantly finds further candidates with highest efficiency while continuing its exploration of the endless design space.
MicroRNA-146a limits tumorigenic inflammation in colorectal cancer
Authors: Garo Lucien P. , Ajay Amrendra K. , Fujiwara Mai , Gabriely Galina , Raheja Radhika , Kuhn Chantal , Kenyon Brendan , Skillin Nathaniel , Kadowaki-Saga Ryoko , Saxena Shrishti , Murugaiyan Gopal 
Published: April 2021

AbstractChronic inflammation can drive tumor development. Here, we have identified microRNA-146a (miR-146a) as a major negative regulator of colonic inflammation and associated tumorigenesis by modulating IL-17 responses. MiR-146a-deficient mice are susceptible to both colitis-associated and sporadic colorectal cancer (CRC), presenting with enhanced tumorigenic IL-17 signaling. Within myeloid cells, miR-146a targets RIPK2, a NOD2 signaling intermediate, to limit myeloid cell-derived IL-17-inducing cytokines and restrict colonic IL-17. Accordingly, myeloid-specific miR-146a deletion promotes CRC. Moreover, within intestinal epithelial cells (IECs), miR-146a targets TRAF6, an IL-17R signaling intermediate, to restrict IEC responsiveness to IL-17. MiR-146a within IECs further suppresses CRC by targeting PTGES2, a PGE2 synthesis enzyme. IEC-specific miR-146a deletion therefore promotes CRC. Importantly, preclinical administration of miR-146a mimic, or small molecule inhibition of the miR-146a targets, TRAF6 and RIPK2, ameliorates colonic inflammation and CRC. MiR-146a overexpression or miR-146a target inhibition represent therapeutic approaches that limit pathways converging on tumorigenic IL-17 signaling in CRC.
Sub-second and ppm-level optical sensing of hydrogen using templated control of nano-hydride geometry and composition
Authors: Luong Hoang Mai , Pham Minh Thien , Guin Tyler , Madhogaria Richa Pokharel , Phan Manh-Huong , Larsen George Keefe , Nguyen Tho Duc 
Published: April 2021

AbstractThe use of hydrogen as a clean and renewable alternative to fossil fuels requires a suite of flammability mitigating technologies, particularly robust sensors for hydrogen leak detection and concentration monitoring. To this end, we have developed a class of lightweight optical hydrogen sensors based on a metasurface of Pd nano-patchy particle arrays, which fulfills the increasing requirements of a safe hydrogen fuel sensing system with no risk of sparking. The structure of the optical sensor is readily nano-engineered to yield extraordinarily rapid response to hydrogen gas (<3 s at 1 mbar H2) with a high degree of accuracy (<5%). By incorporating 20% Ag, Au or Co, the sensing performances of the Pd-alloy sensor are significantly enhanced, especially for the Pd80Co20sensor whose optical response time at 1 mbar of H2is just ~0.85 s, while preserving the excellent accuracy (<2.5%), limit of detection (2.5 ppm), and robustness against aging, temperature, and interfering gases. The superior performance of our sensor places it among the fastest and most sensitive optical hydrogen sensors.
Proton-assisted calcium-ion storage in aromatic organic molecular crystal with coplanar stacked structure
Authors: Han Cuiping , Li Hongfei , Li Yu , Zhu Jiaxiong , Zhi Chunyi 
Published: April 2021

AbstractRechargeable calcium-ion batteries are intriguing alternatives for use as post-lithium-ion batteries. However, the high charge density of divalent Ca2+ establishes a strong electrostatic interaction with the hosting lattice, which results in low-capacity Ca-ion storage. The ionic radius of Ca2+ further leads to sluggish ionic diffusion, hindering high-rate capability performances. Here, we report 5,7,12,14-pentacenetetrone (PT) as an organic crystal electrode active material for aqueous Ca-ion storage. The weak π-π stacked layers of the PT molecules render a flexible and robust structure suitable for Ca-ion storage. In addition, the channels within the PT crystal provide efficient pathways for fast ionic diffusion. The PT anode exhibits large specific capacity (150.5 mAh g-1 at 5 A g-1), high-rate capability (86.1 mAh g-1 at 100 A g-1) and favorable low-temperature performances. A mechanistic study identifies proton-assisted uptake/removal of Ca2+ in PT during cycling. First principle calculations suggest that the Ca ions tend to stay in the interstitial space of the PT channels and are stabilized by carbonyls from adjacent PT molecules. Finally, pairing with a high-voltage positive electrode, a full aqueous Ca-ion cell is assembled and tested.
COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
Authors: Rysz Susanne , Al-Saadi Jonathan , Sjöström Anna , Farm Maria , Campoccia Jalde Francesca , Plattén Michael , Eriksson Helen , Klein Margareta , Vargas-Paris Roberto , Nyrén Sven , Abdula Goran , Ouellette Russell , Granberg Tobias , Jonsson Fagerlund Malin , Lundberg Johan 
Published: April 2021

AbstractSARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
Full recovery of ultrafast waveforms lost under noise
Authors: Crockett Benjamin , Romero Cortés Luis , Konatham Saikrishna Reddy , Azaña José 
Published: April 2021

AbstractThe ability to detect ultrafast waveforms arising from randomly occurring events is essential to such diverse fields as bioimaging, spectroscopy, radio-astronomy, sensing and telecommunications. However, noise remains a significant challenge to recover the information carried by such waveforms, which are often too weak for detection. The key issue is that most of the undesired noise is contained within the broad frequency band of the ultrafast waveform, such that it cannot be alleviated through conventional methods. In spite of intensive research efforts, no technique can retrieve the complete description of a noise-dominated ultrafast waveform of unknown parameters. Here, we propose a signal denoising concept involving passive enhancement of the coherent content of the signal frequency spectrum, which enables the full recovery of arbitrary ultrafast waveforms buried under noise, in a real-time and single-shot fashion. We experimentally demonstrate the retrieval of picosecond-resolution waveforms that are over an order of magnitude weaker than the in-band noise. By granting access to previously undetectable information, this concept shows promise for advancing various fields dealing with weak or noise-dominated broadband waveforms.
A heterocyte glycolipid-based calibration to reconstruct past continental climate change
Authors: Bauersachs Thorsten , Russell James M. , Evans Thomas W. , Schwalb Antje , Schwark Lorenz 
Published: April 2021

AbstractUnderstanding Earth’s response to climate forcing in the geological past is essential to reliably predict future climate change. The reconstruction of continental climates, however, is hampered by the scarcity of universally applicable temperature proxies. Here, we show that heterocyte glycolipids (HGs) of diazotrophic heterocytous cyanobacteria occur ubiquitously in equatorial East African lakes as well as polar to tropical freshwater environments. The relative abundance of HG26 diols and keto-ols, quantified by the heterocyte diol index (HDI26), is significantly correlated with surface water temperature (SWT). The first application of the HDI26 to a ~37,000 year-long sediment record from Lake Tanganyika provides evidence for a ~4.1 °C warming in tropical East Africa from the last glacial to the beginning of the industrial period. Given the worldwide distribution of HGs in lake sediments, the HDI26 may allow reconstructing SWT variations in polar to tropical freshwater environments and thereby quantifying past continental climate change.
Forecasting the dissemination of antibiotic resistance genes across bacterial genomes
Authors: Ellabaan Mostafa M. H. , Munck Christian , Porse Andreas , Imamovic Lejla , Sommer Morten O. A. 
Published: April 2021

AbstractAntibiotic resistance spreads among bacteria through horizontal transfer of antibiotic resistance genes (ARGs). Here, we set out to determine predictive features of ARG transfer among bacterial clades. We use a statistical framework to identify putative horizontally transferred ARGs and the groups of bacteria that disseminate them. We identify 152 gene exchange networks containing 22,963 bacterial genomes. Analysis of ARG-surrounding sequences identify genes encoding putative mobilisation elements such as transposases and integrases that may be involved in gene transfer between genomes. Certain ARGs appear to be frequently mobilised by different mobile genetic elements. We characterise the phylogenetic reach of these mobilisation elements to predict the potential future dissemination of known ARGs. Using a separate database with 472,798 genomes from Streptococcaceae, Staphylococcaceae and Enterobacteriaceae, we confirm 34 of 94 predicted mobilisations. We explore transfer barriers beyond mobilisation and show experimentally that physiological constraints of the host can explain why specific genes are largely confined to Gram-negative bacteria although their mobile elements support dissemination to Gram-positive bacteria. Our approach may potentially enable better risk assessment of future resistance gene dissemination.