bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shift-&-Persist and discrimination predicting depression across the life course: An accelerated longitudinal design using MIDUSI-III
Authors: Christophe N. Keita , Stein Gabriela L. 
Published: April 2021

AbstractLife course theorists posit that sensitive periods exist during life span development where risk and protective factors may be particularly predictive of psychological outcomes relative to other periods in life. While there have been between-cohort studies trying to examine differences in discrimination and depressive symptoms, these studies have not been designed to identify these sensitive periods, which are best modeled by examining intra-individual change across time. To identify sensitive periods where discrimination and shift-&-persist (S&P) – a coping strategy that may protect against the negative impact of discrimination – are most strongly predictive of depressive symptoms, we employed latent growth curve modeling using an accelerated longitudinal design to track intra-individual change in depressive symptoms from ages 20–69. Participants were 3,685 adults measured at three time points ~10 years apart from the Midlife in the United States study (Mage = 37.93, SD = 6.948 at Wave I). Results identified two sensitive periods in development where high levels of S&P interacted with discrimination to protect against depressive symptoms; during the 30s and a lagged effect where 40's S&P protected against depressive symptoms when participants were in their 50s. Implications for the life course study of discrimination, coping, and depression are discussed.
Normalization Method and Application for MODIS TEB Assessments Using Earth Scene Measurements
Authors: Chang Tiejun , Xiong Xiaoxiong , Shrestha Ashish , Diaz Carlos Perez 
Published: April 2021

AbstractSelected Earth targets are commonly used for satellite sensor calibration assessments (e.g., sensor stability and inter‐comparisons). Moreover, typical scenes used for the calibration assessment of the thermal emissive bands (TEBs) include Dome Concordia (Dome‐C), ocean, desert, and deep convective clouds (DCC). Reference data used for these calibration assessments can come from another band, another instrument, or ground measurements. The Dome‐C site, covered with uniformly distributed permanent snow, is normally used for the assessment of the TEBs at cold temperatures. Furthermore, ocean and desert measurements prove useful for scenes with higher temperatures. The DCC, one of the most consistent and coldest targets, can be used for the TEBs calibration and product stability assessments. Moderate Resolution Imaging Spectroradiometer (MODIS) band 31 (∼11 μm) can be used as a reference for these scenes. However, measurements over these scenes have seasonal variations, and the DCC brightness temperatures (BTs) have asymmetrical distributions. These features can introduce additional uncertainty to the stability assessments. A normalization method is applied by using an empirical model to derive reference‐dependent BTs. Using the developed empirical model, measurements can be normalized to a reference BT in order to enhance the calibration assessment's accuracy. This method is evaluated using all four scene types (i.e., ocean, desert, snow (Dome‐C), and DCC) and applied to all the Terra and Aqua MODIS TEBs. Stability assessments over the instruments' entire data records are presented and discussed. The technique can be applied in future efforts to support MODIS TEBs calibration assessments.
A Comparison of the CIR‐ and CME‐Induced Geomagnetic Activity Effects on Mesosphere and Lower Thermospheric Temperature
Authors: Wang Ningchao , Yue Jia , Wang Wenbin , Qian Liying , Jian Lan , Zhang Jie 
Published: April 2021

AbstractNeutral temperature responses in the mesosphere and lower thermosphere (MLT) to severe geomagnetic storms induced by coronal mass ejections (CMEs) are of growing interest to the space science research community. Recently, it was found that geomagnetic activities produced by the corotating interaction regions (CIRs) caused comparable effects on the Earth's upper atmosphere. In this work, we carried out a comparative study of the temperature responses in the MLT region to these two types of geomagnetic activities, using the temperature measured by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instruments onboard the Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics (TIMED) satellite. Our results demonstrate that CIR‐induced geomagnetic activity produced temperature variations in the MLT region and that this effect can penetrate downward to ∼100 km at high latitudes in both hemispheres. Temperature enhancements penetrated deeper during CME‐induced geomagnetic activities, but the heating effects lasted longer during CIR‐induced geomagnetic activities. There is a hemispherical asymmetry in the geomagnetical activity induced temperature changes in the MLT region. The temperature enhancements are stronger in the southern hemisphere than in the northern hemisphere during CME events.
Fault‐Valve Behavior Estimated From Intensive Foreshocks and Aftershocks of the 2017 M 5.3 Kagoshima Bay Earthquake Sequence, Kyushu, Southern Japan
Authors: Matsumoto Yoshiaki , Yoshida Keisuke , Matsuzawa Toru , Hasegawa Akira 
Published: April 2021

AbstractDetermining fluid migration and pore pressure change within the Earth is key to understand earthquake occurrences. We investigated the spatiotemporal characteristics of the intense foreshocks and aftershocks of the 2017 ML 5.3 earthquake in Kagoshima Bay, Kyushu, southern Japan, to examine the physical processes governing this earthquake sequence. Our relocated hypocenters show the foreshocks moved on a sharply defined plane with a steep dip. The mainshock rupture initiated at the edge of the foreshock seismic gap. The size of the foreshock seismic gap is comparable to that of the mainshock estimated from the source corner frequency, suggesting this seismic gap corresponds to the large slip region of the mainshock. The aftershocks migrated upward along several steeply dipped planes with a seismicity pattern that deviated from the typical mainshock–aftershock type. This deviation of seismicity pattern, together with the hypocenter migrations, suggests aseismic processes, such as pore pressure migration and aseismic slip, affected this earthquake sequence. We established the following hypothesis. First, fluids originating from the subducting slab migrated upward and intruded into the fault plane, reducing the fault strength and causing the foreshock sequence and potentially aseismic slip. Second, the mainshock rupture occurred due to the decreased fault strength and the increased shear stress in an area with relatively high strength. Third, pore pressure increase associated with post‐failure fluid discharge caused the upward aftershock migration. These observations are consistent with the fault‐valve model and show the importance of fluid movement at depth not only in earthquake swarms but also in foreshock–mainshock–aftershock sequences.
The Shelf Circulation of the Bellingshausen Sea
Authors: Schulze Chretien L. M. , Thompson A. F. , Flexas M. M. , Speer K. , Swaim N. , Oelerich R. , Ruan X. , Schubert R. , LoBuglio C. 
Published: April 2021

AbstractOver recent decades, the West Antarctic Ice Sheet has experienced rapid thinning of its floating ice shelves as well as grounding line retreat across its marine‐terminating glaciers. The transport of warm Modified Circumpolar Deep Water (MCDW) onto the continental shelf, extensively documented along the West Antarctic Peninsula (WAP), and in the Amundsen Sea, has been identified as the key process for inducing these changes. The Bellingshausen Sea sits between the Amundsen Sea and the northern part of the WAP, but its oceanic properties remain remarkably under‐studied compared to surrounding regions. Here, we present observations collected from a hydrographic survey of the Bellingshausen Sea continental shelf in austral summer 2019. Using a combination of ship‐based and glider‐based CTD and lowered ADCP observations, we show that submarine troughs provide topographically steered pathways for MCDW from the shelf break toward deep embayments and ultimately under floating ice shelves. Warm MCDW enters the continental shelf at the deepest part of the Belgica Trough and flows onshore along the eastern side of the trough. Modification of these shoreward‐flowing waters by glacial melt is estimated by calculating meltwater fractions using an optimal multiparameter analysis. Meltwater is found to be elevated at the western edge of both the Latady and Belgica troughs. Meltwater distributions, consistent with other diagnostics, suggest a recirculation in each trough with modified waters eventually flowing westward upon leaving the Belgica Trough. Our results show that the Bellingshausen Sea is a critical part of the larger West Antarctic circulation system, linking the WAP and the Amundsen Sea.
Ocean Variability at Greenland's Largest Glacier Tongue Linked to Continental Shelf Circulation
Authors: von Albedyll Luisa , Schaffer Janin , Kanzow Torsten 
Published: April 2021

AbstractIncreased ocean‐to‐ice heat fluxes play a key role in the accelerated mass loss of Greenland’s marine‐terminating glaciers. Ocean current variability leads to variations in this heat flux. A year‐long time series of ocean currents at all gateways to the ocean cavity under Greenland’s largest remaining floating ice tongue at the Nioghalvfjerdsfjorden Glacier (79NG) was analyzed. The variability of the exchange flow at intra‐annual to near‐daily timescales was characterized. The currents exhibit considerable variability with standard deviations exceeding the time mean flow strength by a factor of 2. The inflow of warm Atlantic Intermediate Water into the cavity and the outflow via the northernmost calving front were directly coupled on intra‐annual timescales (periods, T > 30 days) with enhanced fluctuations in the winter months. A strong correlation between the variability of the deep inflow and currents in the subsurface boundary current on the continental shelf suggests a link between cavity and continental shelf circulation. Variability on higher frequencies (T < 30 days) in the outflow was only partly induced by the inflow variability. Two export branches of the cavity circulation were identified, which were potentially constrained by subglacial meltwater channels. The relative importance of the two export branches varies on monthly time scales. This research has provided evidence that the large intra‐annual ocean current variability at the 79NG is strongly influenced by the continental shelf circulation. Temporally varying preferred export routes increase the complexity of the cavity circulation.
Origin and Fate of the Chukchi Slope Current Using a Numerical Model and In‐Situ Data
Authors: Leng Hengling , Spall Michael A. , Pickart Robert S. , Lin Peigen , Bai Xuezhi 
Published: April 2021

AbstractA regional coupled sea ice‐ocean model and mooring/shipboard measurements are used to investigate the origins, seasonality, and downstream fate of the Chukchi Slope Current (CSC). Three years (2013–2015) of model integration indicates that, in the mean, the model slope current transports ∼0.45 Sv of Pacific water northwestward along the Chukchi continental slope. Only 62% of this water emanates from Barrow Canyon, while the rest (38%) is fed by a westward jet extending from the southern Beaufort Sea. The jet merges with the outflow from the canyon, forming the CSC. Due to these two distinct origins, the slope current in the model has a double velocity core at times. This is consistent with the double‐core structure of the slope current seen in ship‐based observations. Seasonal changes in the volume, heat, and freshwater transports by the slope current appear to be related to the changes in the upstream flows. A tracer diagnostic in the model suggests that the part of the slope current over the upper continental slope continues westward toward the East Siberian Sea, while the portion of the current overlying deeper isobaths flows northward into the Chukchi Borderland, where it ultimately gets entrained into the Beaufort Gyre. Our study provides a detailed and complete picture of the slope current.
MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner
Authors: Wang Yen-Yun , Chen Yuk-Kwan , Lo Steven , Chi Tsung-Chen , Chen Yi-Hua , Hu Stephen Chu-Sung , Chen Ya-Wen , Jiang Shih Sheng , Tsai Fang-Yu , Liu Wangta , Li Ruei-Nian , Hsieh Ya-Ching , Huang Chih-Jen , Yuan Shyng-Shiou F. 
Published: April 2021

AbstractMRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment.
The role of chemotaxis and efflux pumps on nitrate reduction in the toxic regions of a ciprofloxacin concentration gradient
Authors: Alcalde Reinaldo E , Dundas Christopher M , Dong Yiran , Sanford Robert A , Keitz Benjamin Keith , Fouke Bruce W , Werth Charles J 
Published: April 2021

Abstract
Spatial concentration gradients of antibiotics are prevalent in the natural environment. Yet, the microbial response in these heterogeneous systems remains poorly understood. We used a microfluidic reactor to create an artificial microscopic ecosystem that generates diffusive gradients of solutes across interconnected microenvironments. With this reactor, we showed that chemotaxis toward a soluble electron acceptor (nitrate) allowed Shewanella oneidensis MR-1 to inhabit and sustain metabolic activity in highly toxic regions of the antibiotic ciprofloxacin (&gt;80× minimum inhibitory concentration, MIC). Acquired antibiotic resistance was not observed for cells extracted from the reactor, so we explored the role of transient adaptive resistance by probing multidrug resistance (MDR) efflux pumps, ancient elements that are important for bacterial physiology and virulence. Accordingly, we constructed an efflux pump deficient mutant (∆mexF) and used resistance-nodulation-division (RND) efflux pump inhibitors (EPIs). While batch results showed the importance of RND efflux pumps for microbial survival, microfluidic studies indicated that these pumps were not necessary for survival in antibiotic gradients. Our work contributes to an emerging body of knowledge deciphering the effects of antibiotic spatial heterogeneity on microorganisms and highlights differences of microbial response in these systems versus well-mixed batch conditions.
Ibrutinib combinations in CLL therapy: scientific rationale and clinical results
Authors: Timofeeva Natalia , Gandhi Varsha 
Published: April 2021

AbstractIbrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL). This drug irreversibly inhibits Bruton tyrosine kinase (BTK) by covalently binding to the C481 residue in the BTK kinase domain. BTK is a pivotal protein for B cell receptor signaling and tissue homing of CLL cells. Preclinical investigations have established the importance of the B cell receptor pathway in the maintenance and survival of normal and malignant B cells, underscoring the importance of targeting this axis for CLL. Clinical trials demonstrated overall and progression-free survival benefit with ibrutinib in multiple CLL subgroups, including patients with relapsed or refractory disease, patients with 17p deletion, elderly patients, and treatment-naïve patients. Consequently, ibrutinib was approved by the US Food and Drug Administration for newly diagnosed and relapsed disease. Ibrutinib has transformed the treatment of CLL; however, several limitations have been identified, including low complete remission rates, development of resistance, and uncommon substantial toxicities. Further, ibrutinib must be used until disease progression, which imposes a financial burden on patients and society. These limitations were the impetus for the development of ibrutinib combinations. Four strategies have been tested in recent years: combinations of ibrutinib with immunotherapy, chemoimmunotherapy, cell therapy, and other targeted therapy. Here, we review the scientific rationale for and clinical outcome of each strategy. Among these strategies, ibrutinib with targeted agent venetoclax results in high complete response rates and, importantly, high rates of undetectable minimal residual disease. Although we concentrate here on ibrutinib, similar combinations are expected or ongoing with acalabrutinib, tirabrutinib, and zanubrutinib, second-generation BTK inhibitors. Future investigations will focus on the feasibility of discontinuing ibrutinib combinations after a defined time; the therapeutic benefit of adding a third agent to ibrutinib-containing combinations; and profiling of resistant clones that develop after combination treatment. A new standard of care for CLL is expected to emerge from these investigations.
A deep convolutional neural network for segmentation of whole-slide pathology images identifies novel tumour cell-perivascular niche interactions that are associated with poor survival in glioblastoma
Authors: Zadeh Shirazi Amin , McDonnell Mark D. , Fornaciari Eric , Bagherian Narjes Sadat , Scheer Kaitlin G. , Samuel Michael S. , Yaghoobi Mahdi , Ormsby Rebecca J. , Poonnoose Santosh , Tumes Damon J. , Gomez Guillermo A. 
Published: April 2021

AbstractBackgroundGlioblastoma is the most aggressive type of brain cancer with high-levels of intra- and inter-tumour heterogeneity that contribute to its rapid growth and invasion within the brain. However, a spatial characterisation of gene signatures and the cell types expressing these in different tumour locations is still lacking.MethodsWe have used a deep convolutional neural network (DCNN) as a semantic segmentation model to segment seven different tumour regions including leading edge (LE), infiltrating tumour (IT), cellular tumour (CT), cellular tumour microvascular proliferation (CTmvp), cellular tumour pseudopalisading region around necrosis (CTpan), cellular tumour perinecrotic zones (CTpnz) and cellular tumour necrosis (CTne) in digitised glioblastoma histopathological slides from The Cancer Genome Atlas (TCGA). Correlation analysis between segmentation results from tumour images together with matched RNA expression data was performed to identify genetic signatures that are specific to different tumour regions.ResultsWe found that spatially resolved gene signatures were strongly correlated with survival in patients with defined genetic mutations. Further in silico cell ontology analysis along with single-cell RNA sequencing data from resected glioblastoma tissue samples showed that these tumour regions had different gene signatures, whose expression was driven by different cell types in the regional tumour microenvironment. Our results further pointed to a key role for interactions between microglia/pericytes/monocytes and tumour cells that occur in the IT and CTmvp regions, which may contribute to poor patient survival.ConclusionsThis work identified key histopathological features that correlate with patient survival and detected spatially associated genetic signatures that contribute to tumour-stroma interactions and which should be investigated as new targets in glioblastoma. The source codes and datasets used are available in GitHub:https://github.com/amin20/GBM_WSSM.
A review of acquired blepharoptosis: prevalence, diagnosis, and current treatment options
Authors: Bacharach Jason , Lee Wendy W. , Harrison Andrew R. , Freddo Thomas F. 
Published: April 2021

AbstractBlepharoptosis (ptosis) is among the most common disorders of the upper eyelid encountered in both optometric and ophthalmic practice. The unilateral or bilateral drooping of the upper eyelid that characterises ptosis can affect appearance and impair visual function, both of which can negatively impact quality of life. While there are several known forms of congenital ptosis, acquired ptosis (appearing later in life, due to a variety of causes) is the predominant form of the condition. This review summarises the prevalence, causes, identification, differential diagnosis, and treatment of acquired ptosis. Particular attention is paid to the differential diagnosis of acquired ptosis and emerging treatment options, including surgical and pharmacologic approaches.
Genetic and spatial organization of the unusual chromosomes of the dinoflagellate Symbiodinium microadriaticum
Authors: Nand Ankita , Zhan Ye , Salazar Octavio R. , Aranda Manuel , Voolstra Christian R. , Dekker Job 
Published: April 2021

AbstractDinoflagellates are main primary producers in the oceans, the cause of algal blooms and endosymbionts of marine invertebrates. Much remains to be understood about their biology, including their peculiar crystalline chromosomes. We assembled 94 chromosome-scale scaffolds of the genome of the coral endosymbiont Symbiodinium microadriaticum and analyzed their organization. Genes are enriched towards the ends of chromosomes and are arranged in alternating unidirectional blocks. Some chromosomes are enriched for genes involved in specific biological processes. The chromosomes fold as linear rods and each is composed of a series of structural domains separated by boundaries. Domain boundaries are positioned at sites where transcription of two gene blocks converges and disappear when cells are treated with chemicals that block transcription, indicating correlations between gene orientation, transcription and chromosome folding. The description of the genetic and spatial organization of the S. microadriaticum genome provides a foundation for deeper exploration of the extraordinary biology of dinoflagellates and their chromosomes.