bluuebunny/crossref_metadata_2025_split huggingface dataset:
Horizontal Stirring Over the Northeast U.S. Continental Shelf: The Spatial and Temporal Evolution of Surface Eddy Kinetic Energy
Authors: Kirincich Anthony , Hodges Ben , Flament Pierre , Futch Victoria 
Published: May 2022

AbstractThis study examines the spatial and temporal variability of eddy kinetic energy over the Northeast Shelf using observations of surface currents from a unique array of six high frequency radar systems. Collected during summer and winter conditions over three consecutive years, the horizontal scales present were examined in the context of local wind and hydrographic variability, which were sampled concurrently from moorings and autonomous surface vehicles. While area‐averaged mean kinetic energy at the surface was tightly coupled to wind forcing, eddy kinetic energy was not, and was lower in magnitude in winter than summer in all areas. Kinetic energy wavenumber spectral slopes were generally near k−5/3, but varied seasonally, spatially, and between years. In contrast, wavenumber spectra of surface temperature and salinity along repeat transect lines had sharp k−3 spectral slopes with little seasonal or inter‐annual variability. Radar‐based estimates of spectral kinetic energy fluxes revealed a mean transition scale of energy near 18 km during stratified months, but suggested much longer scales during winter. Overall, eddy kinetic energy was unrelated to local winds, but the up‐ or down‐scale flux of kinetic energy was tied to wind events and, more weakly, to local density gradients.
Evaluating the Impact of Chemical Complexity and Horizontal Resolution on Tropospheric Ozone Over the Conterminous US With a Global Variable Resolution Chemistry Model
Authors: Schwantes Rebecca H. , Lacey Forrest G. , Tilmes Simone , Emmons Louisa K. , Lauritzen Peter H. , Walters Stacy , Callaghan Patrick , Zarzycki Colin M. , Barth Mary C. , Jo Duseong S. , Bacmeister Julio T. , Neale Richard B. , Vitt Francis , Kluzek Erik , Roozitalab Behrooz , Hall Samuel R. , Ullmann Kirk , Warneke Carsten , Peischl Jeff , Pollack Ilana B. , Flocke Frank , Wolfe Glenn M. , Hanisco Thomas F. , Keutsch Frank N. , Kaiser Jennifer , Bui Thao Paul V. , Jimenez Jose L. , Campuzano‐Jost Pedro , Apel Eric C. , Hornbrook Rebecca S. , Hills Alan J. , Yuan Bin , Wisthaler Armin 
Published: May 2022

AbstractA new configuration of the Community Earth System Model (CESM)/Community Atmosphere Model with full chemistry (CAM‐chem) supporting the capability of horizontal mesh refinement through the use of the spectral element (SE) dynamical core is developed and called CESM/CAM‐chem‐SE. Horizontal mesh refinement in CESM/CAM‐chem‐SE is unique and novel in that pollutants such as ozone are accurately represented at human exposure relevant scales while also directly including global feedbacks. CESM/CAM‐chem‐SE with mesh refinement down to ∼14 km over the conterminous US (CONUS) is the beginning of the Multi‐Scale Infrastructure for Chemistry and Aerosols (MUSICAv0). Here, MUSICAv0 is evaluated and used to better understand how horizontal resolution and chemical complexity impact ozone and ozone precursors over CONUS as compared to measurements from five aircraft campaigns, which occurred in 2013. This field campaign analysis demonstrates the importance of using finer horizontal resolution to accurately simulate ozone precursors such as nitrogen oxides and carbon monoxide. In general, the impact of using more complex chemistry on ozone and other oxidation products is more pronounced when using finer horizontal resolution where a larger number of chemical regimes are resolved. Large model biases for ozone near the surface remain in the Southeast US as compared to the aircraft observations even with updated chemistry and finer horizontal resolution. This suggests a need for adding the capability of replacing sections of global emission inventories with regional inventories, increasing the vertical resolution in the planetary boundary layer, and reducing model biases in meteorological variables such as temperature and clouds.
TXN inhibitor impedes radioresistance of colorectal cancer cells with decreased ALDH1L2 expression via TXN/NF-κB signaling pathway
Authors: Yu Lu , Guo Qiqing , Luo Ziqian , Wang Yongjia , Weng Jiawen , Chen Yuchuan , Liang Weijie , Li Yiyi , Zhang Yuqin , Chen Keli , Chen Zhenhui , Ding Yi , Zhang Yaowei 
Published: May 2022

Abstract
Background
Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC.

Methods
Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance.

Results
Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2.

Conclusions
Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.
Modelling immune cytotoxicity for cholangiocarcinoma with tumour-derived organoids and effector T cells
Authors: Zhou Guoying , Lieshout Ruby , van Tienderen Gilles S. , de Ruiter Valeska , van Royen Martin E. , Boor Patrick P. C. , Magré Luc , Desai Jyaysi , Köten Kübra , Kan Yik Yang , Ge Zhouhong , Campos Carrascosa Lucia , Geuijen Cecile , Sprengers Dave , van der Laan Luc J. W. , Verstegen Monique M. A. , Kwekkeboom Jaap 
Published: May 2022

Abstract
Background
Immunotherapy with immune checkpoint inhibitors (ICIs) is being explored to improve cholangiocarcinoma (CCA) therapy. However, it remains difficult to predict which ICI will be effective for individual patients. Therefore, the aim of this study is to develop a co-culture method with patient-derived CCA organoids and immune cells, which could represent anti-cancer immunity in vitro.

Methods
CCA organoids were co-cultured with peripheral blood mononuclear cells or T cells. Flow cytometry, time-lapse confocal imaging for apoptosis, and quantification of cytokeratin 19 fragment (CYFRA) release were applied to analyse organoid and immune cell behaviour. CCA organoids were also cultured in immune cell-conditioned media to analyse the effect of soluble factors.

Results
The co-culture system demonstrated an effective anti-tumour organoid immune response by a decrease in live organoid cells and an increase in apoptosis and CYFRA release. Interpatient heterogeneity was observed. The cytotoxic effects could be mediated by direct cell–cell contact and by release of soluble factors, although soluble factors only decreased viability in one organoid line.

Conclusions
In this proof-of-concept study, a novel CCA organoid and immune cell co-culture method was established. This can be the first step towards personalised immunotherapy for CCA by predicting which ICIs are most effective for individual patients.
Overall survival of patients with metastatic breast cancer in Sweden: a nationwide study
Authors: Valachis Antonis , Carlqvist Peter , Ma Yuanjun , Szilcz Máté , Freilich Jonatan , Vertuani Simona , Holm Barbro , Lindman Henrik 
Published: May 2022

Abstract
Background
Breast cancer is the most common cancer among women in Sweden. Whereas survival for the overall breast cancer population is well-documented, survival of patients with metastatic breast cancer (MBC) is harder to quantify due to the lack of reliable data on disease recurrence in national cancer registers.

Methods
This study used machine learning to classify the total MBC population in Sweden diagnosed between 2009 and 2016 using national registers, with the aim to estimate overall survival (OS).

Results
The total population consisted of 13,832 patients—2528 (18.3%) had de novo MBC whereas 11,304 (81.7%) were classed as having a recurrent MBC. Median OS for patients with MBC was found to be 29.8 months 95% confidence interval (CI) [28.9, 30.6]. Hormone-receptor (HR)-positive MBC had a median OS of 37.0 months 95% CI [35.9, 38.3] compared to 9.9 months 95% CI [9.1, 11.0] for patients with HR-negative MBC.

Conclusion
This study covered the entire MBC population in Sweden during the study time and may serve as a baseline for assessing the effect of new treatment strategies in MBC introduced after the study period.
PHF13 epigenetically activates TGFβ driven epithelial to mesenchymal transition
Authors: Sun Yating , Li Dan , Liu Hongmei , Huang Yongye , Meng Fanyu , Tang Jiahao , Li Zhanjun , Xie Wanhua 
Published: May 2022

AbstractEpigenetic alteration is a pivotal factor in tumor metastasis. PHD finger protein 13 (PHF13) is a recently identified epigenetic reader of H3K4me2/3 that functions as a transcriptional co-regulator. In this study, we demonstrate that PHF13 is required for pancreatic-cancer-cell growth and metastasis. Integrative analysis of transcriptome and epigenetic profiles provide further mechanistic insights into the epigenetic regulation of genes associated with cell metastasis during the epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor β (TGFβ). Our data suggest PHF13 depletion impairs activation of TGFβ stimulated genes and correlates with a loss of active epigenetic marks (H3K4me3 and H3K27ac) at these genomic regions. These observations argue for a dependency of TGFβ target activation on PHF13. Furthermore, PHF13-dependent chromatin regions are enriched in broad H3K4me3 domains and super-enhancers, which control genes critical to cancer-cell migration and invasion, such as SNAI1 and SOX9. Overall, our data indicate a functional and mechanistic correlation between PHF13 and EMT.
m6Am methyltransferase PCIF1 is essential for aggressiveness of gastric cancer cells by inhibiting TM9SF1 mRNA translation
Authors: Zhuo Wei , Sun Meng , Wang Kun , Zhang Lu , Li Kai , Yi Danyang , Li Mengjie , Sun Qiang , Ma Xixi , Liu Wei , Teng Lisong , Yi Chengqi , Zhou Tianhua 
Published: May 2022

AbstractPCIF1 (phosphorylated CTD interacting factor 1) is the first reported RNA N6,2′-O-dimethyladenosine (m6Am) methyltransferase. However, the pathological significance of PCIF1 and m6Am modification remains unknown. Here we find that both PCIF1 expression and m6Am modification are significantly elevated in gastric cancer tissues. Increased PCIF1 is associated with gastric cancer progression, and predicts poor prognosis. Silence of PCIF1 inhibits the proliferation and invasion of gastric cancer cells, and suppresses tumor growth and metastasis in mouse model. m6Am-seq analysis reveals TM9SF1 (transmembrane 9 superfamily member 1) as a target of PCIF1. PCIF1 modifies TM9SF1 mRNA with m6Am leading to decreased TM9SF1 translation. TM9SF1 reverses the effects of PCIF1 on gastric cancer cell aggressiveness. Collectively, our work uncovers an oncogenic function of PCIF1, providing insights into the critical role of m6Am modification in cancer progression.
Efficacy and safety of brolucizumab versus aflibercept in eyes with early persistent retinal fluid: 96-week outcomes from the HAWK and HARRIER studies
Authors: Lally David R. , Loewenstein Anat , Arnold Jennifer J. , Yang Yit C. , Gedif Kinfemichael , Best Catherine , Patel Hersh , Tadayoni Ramin , Heier Jeffrey S. 
Published: May 2022

AbstractObjectivePost-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER.MethodsAfter 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12.ResultsA lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: −202 µm vs. −145 µm;p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm.ConclusionIn this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.
Effect of electrochemical oxidation and drug loading on the antibacterial properties and cell biocompatibility of titanium substrates
Authors: Nowruzi Fateme , Imani Rana , Faghihi Shahab 
Published: May 2022

AbstractA combination of $${\text{ TiO}}_{2}$$

TiO

2

nanotube array (TON) and controlled drug release system is employed to provide enhanced surface properties of titanium implants. Electrochemical anodization process is used to generate TON for introducing, vancomycin, an effective antibacterial drug against Staphylococcusaureus. TON loaded vancomycin is then coated with a number of layers of 10% gelatin using spin coating technique. The gelatin film is reinforced with graphene oxide (GO) nanoparticles to improve the surface bioactivity. The surface of the samples is characterized by field emission electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), and contact angle measurement. The results illustrate that the TON was constructed and vancomycin molecules are successfully loaded. The drug release study shows that the amount of released vancomycin is controlled by the thickness of gelatin layers. With an increase in gelatin film layers from 3 to 7, the release of vancomycin in the burst release phase decreased from 58 to 31%, and sustained release extended from 10 to 17 days. The addition of GO nanoparticles seems to reduce drug release in from 31 to 22% (burst release phase) and prolonged drug release (from 17 to 19 days). MTT assay indicates that samples show no cytotoxicity, and combination of GO nanoparticles with gelatin coating could highly promote MG63 cell proliferation. Soaking the samples in SBF solution after 3 and 7 days demonstrates that hydroxy apatite crystals were deposited on the TON surface with GO-gelatin coating more than surface of TON with gelatin. Moreover, based on the results of disc diffusion assay, both samples (loaded with Vancomycin and coated with gelatin and gelatin-GO) with the inhibition zones equaled to 20 mm show effective antibacterial properties against S. aureus. The evidence demonstrates that titania nanotube loaded with vancomycin and coated with gelatin-GO has a great potential for general applicability to the orthopedic implant field.
Projected U.S. drought extremes through the twenty-first century with vapor pressure deficit
Authors: Gamelin Brandi L. , Feinstein Jeremy , Wang Jiali , Bessac Julie , Yan Eugene , Kotamarthi Veerabhadra R. 
Published: May 2022

AbstractGlobal warming is expected to enhance drought extremes in the United States throughout the twenty-first century. Projecting these changes can be complex in regions with large variability in atmospheric and soil moisture on small spatial scales. Vapor Pressure Deficit (VPD) is a valuable measure of evaporative demand as moisture moves from the surface into the atmosphere and a dynamic measure of drought. Here, VPD is used to identify short-term drought with the Standardized VPD Drought Index (SVDI); and used to characterize future extreme droughts using grid dependent stationary and non-stationary generalized extreme value (GEV) models, and a random sampling technique is developed to quantify multimodel uncertainties. The GEV analysis was performed with projections using the Weather Research and Forecasting model, downscaled from three Global Climate Models based on the Representative Concentration Pathway 8.5 for present, mid-century and late-century. Results show the VPD based index (SVDI) accurately identifies the timing and magnitude short-term droughts, and extreme VPD is increasing across the United States and by the end of the twenty-first century. The number of days VPD is above 9 kPa increases by 10 days along California’s coastline, 30–40 days in the northwest and Midwest, and 100 days in California’s Central Valley.
Rising surface pressure over Tibetan Plateau strengthens indian summer monsoon rainfall over northwestern India
Authors: Singh Randhir , Jaiswal Neeru , Kishtawal C. M. 
Published: May 2022

AbstractThe dipole pattern (wetting over northwestern India and drying over the Indo-Gangetic plains and northeast India) in the rainfall trends is reported in many earlier studies. The exact cause of the rainfall trends’ asymmetry remains unclear. We show that increasing trends over the northwestern parts are closely associated with the rise in surface pressure over the Tibetan Plateau. The surface pressure over Tibetan Plateau shows increasing trends (0.23 hPa decade−1, p < 0.01) during 1979–2020. Easterlies across northwest India and southerlies over east India show rises of − 0.26 ms−1 decade−1 and 0.15 ms−1 decade−1, respectively, in line with Tibetan surface pressure trends. Water vapour transfer across northwest India has increased as a result of these changes in circulation. Increased lower-level easterlies carried more water vapour from the Bay of Bengal over northwest India. At the same time, stronger mid-level southerlies drove extratropical dry air out of India, strengthening the rainfall generating mechanism. Rising easterlies in northwest India also enhance vorticity along the monsoon trough, which promotes rainfall generation. Concurrently, because of the high surface pressure over Tibet, the circulation intensity of the mid-tropospheric cyclone over East India was weakened, resulting in less rain in the Indo-Gangetic region. The present study proposes that an increase in the surface pressure over Tibetan Plateau is an important factor contributing to the dipole pattern in the ISMR trends, particularly upward trends in rainfall over northwest India
FAM83B is involved in thyroid cancer cell differentiation and migration
Authors: Cirello Valentina , Grassi Elisa Stellaria , Pogliaghi Gabriele , Ghiandai Viola , Ermellino Laura , Muzza Marina , Gazzano Giacomo , Persani Luca , Colombo Carla , Fugazzola Laura 
Published: May 2022

AbstractFAM83B has been recently identified as an oncogene, but its role in thyroid cancers (TC) is still unclear. We examined the expression of FAM83B and its possible involvement in cell migration and differentiation, in neoplastic/normal thyroid tissues and in TC human cell lines. FAM83B expression in TC varies according to the tumor histotype, being significantly downregulated in more aggressive and metastatic tissues. FAM83B levels in cell lines recapitulate patients’ samples variations, and its total and cytoplasmic levels decrease upon the induction of migration, together with an increase in its nuclear localization. Similar variations were detected in the primary tumor and in the metastatic tissues from a follicular TC. FAM83B knock down experiments confirmed its role in thyroid differentiation and cell migration, as demonstrated by the reduction of markers of thyroid differentiation and the increase of the mesenchymal marker vimentin. Moreover, the silencing of FAM83B significantly increased cells migration abilities, while not affecting the oncogenic RAS/MAPK/PI3K pathways. Our data indicate for the first time a role for FAM83B in TC cell differentiation and migration. Its expression is reduced in dedifferentiated tumors and its nuclear re-localization could favour distant migration, suggesting that FAM83B should be considered a possible diagnostic and prognostic biomarker.
Demographic and clinical parameters are comparable across different types of pediatric feeding disorder
Authors: Galai Tut , Friedman Gal , Moses Michal , Shemer Kim , Gal Dana L. , Yerushalmy-Feler Anat , Lubetzky Ronit , Cohen Shlomi , Moran-Lev Hadar 
Published: May 2022

AbstractKnowledge and understanding of risk mechanisms associated with pediatric feeding disorder (PFD) remain limited. We aimed to investigate factors associated with PFD and their relation to specific PFD types according to the recent consensus WHO-based definition. We retrospectively reviewed the medical records of children with PFD and retrieved their demographic and clinical characteristics. Healthy age- and sex-matched children served as controls. Included were 254 children with PFD [median (interquartile range) age 16.4 (9.5–33) months at diagnosis] and 108 children in the control group [median age 24.85 (14.5–28.5) months]. According to the WHO-based definition, disturbances in oral intake were predominantly related to nutritional dysfunction in 118 (46.6%), feeding skill dysfunction in 83 (32.3%), medical conditions in 42 (16.7%) and psychosocial dysfunction in 11 (4.4%). In multivariate analysis, children with PFD had a higher risk for lower socioeconomic background (P < 0.01) and low birth weight (26.8% compared to 7.4%,P < 0.001). Moreover, significantly fewer children in the PFD group were breastfed (75% versus 89%,P = 0.003). There were no significant differences in any of those variables between PFD types. In conclusion, low socioeconomic status, lack of breastfeeding, and low birth weight were significantly more frequent in children with PFD. PDF manifest as multiple dysfunctions, thus highlighting the need to offer these children and their families multidisciplinary care.