bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypotension associated with azithromycin infusion in children with heart failure: a case report
Authors: Zanaboni Dominic , Vitale Carolyn 
Published: March 2022

AbstractWe report two cases of acute hypotension after intravenous azithromycin administration in children with acute, decompensated heart failure. In each of our reported cases, azithromycin was being used to treat possible Mycoplasma myocarditis. In this report, we aim to describe hypotension as a potentially rare adverse reaction to intravenous azithromycin and encourage judicious use in patients with cardiac dysfunction.
High variability in cardiac education and experiences during United States paediatric critical care fellowships
Authors: Hanson Amy E. , Mastropietro Christopher W. , Murphy Lee D. , Rowan Courtney M. 
Published: March 2022

AbstractBackground:Paediatric cardiac critical care continues to become more sub-specialised, and many institutions have transitioned to dedicated cardiac ICUs. Literature regarding the effects of these changes on paediatric critical care medicine fellowship training is limited.Objective:To describe the current landscape of cardiac critical care education during paediatric critical care medicine fellowship in the United States and demonstrate its variability.Methods:A review of publicly available information in 2021 was completed. A supplemental REDCap survey focusing on cardiac ICU experiences during paediatric critical care medicine fellowships was e-mailed to all United States Accreditation Council of Graduate Medical Education-accredited paediatric critical care medicine fellowship programme coordinators/directors. Results are reported using inferential statistics.Results:Data from 71 paediatric critical care medicine fellowship programme websites and 41 leadership responses were included. Median fellow complement was 8 (interquartile range: 6, 12). The majority (76%, 31/41) of programmes had a designated cardiac ICU. Median percentage of paediatric critical care medicine attending physicians with cardiac training was 25% (interquartile range: 0%, 69%). Mandatory cardiac ICU time was 16 weeks (interquartile range: 13, 20) with variability in night coverage and number of other learners present. A minority of programmes (29%, 12/41) mandated other cardiac experiences. Median CHD surgical cases per year were 215 (interquartile range: 132, 338). When considering the number of annual cases per fellow, programmes with higher case volume were not always associated with the highest case number per fellow.Conclusions:There is a continued trend toward dedicated cardiac ICUs in the United States, with significant variability in cardiac training during paediatric critical care medicine fellowship. As the trend toward dedicated cardiac ICUs continues and practices become more standardised, so should the education.
The impact of an employer match and automatic enrollment on the savings behavior of public-sector workers
Authors: Falk Justin , Karamcheva Nadia S. 
Published: March 2022

AbstractWe use administrative data on federal civilian workers' accounts in their employer-provided defined contribution plan, called the thrift savings plan (TSP), to provide new evidence on the effects of employer matching and defaults on workers' savings behavior. The empirical analysis relies on exogenous variation stemming from two natural experiments caused by policy changes to the TSP: the establishment of an employer match for workers hired after 1983 and the introduction of automatic enrollment for workers hired after July 2010. We find that the introduction of the employer match lead to a higher increase in both participation and contribution rates compared to the subsequent switch to automatic enrollment. In terms of portfolio allocations, we find that matching and automatic enrollment had small and minimal effects, respectively.
Cultural evolution: Protecting “digital cultural property” in armed conflict
Authors: Alcala Ronald 
Published: March 2022

AbstractAs an emerging and largely unfamiliar form of cultural heritage, digital cultural property remains something of an enigma. Under the law of armed conflict, States are bound to protect cultural property from harm, yet the rules applicable to traditional cultural property do not transfer neatly to digital works. It is unclear, for example, how the twin obligations to safeguard and respect cultural property, as outlined in the 1954 Hague Cultural Property Convention, should apply to digital creations – or even what digital material appropriately qualifies as cultural property. Can only new digital creations, otherwise known as “born-digital” material, be cultural property? What about high-quality copies of existing works, such as an extremely high-resolution image of the Mona Lisa? Does it matter whether a digital work has been reproduced in large quantities? Given the ubiquity of digital media and the growing popularity of digital art and other works, protecting digital cultural property in the event of armed conflict will require States to consider and resolve as-yet undecided questions concerning the nature of digital creations and the reasons why certain works should be preserved.
Hallett‐Mossop Rime Splintering Dims Cumulus Clouds Over the Southern Ocean: New Insight From Nudged Global Storm‐Resolving Simulations
Authors: Atlas R. L. , Bretherton C. S. , Khairoutdinov M. F. , Blossey P. N. 
Published: March 2022

AbstractIn clouds containing both liquid and ice with temperatures between −3°C and −8°C, liquid droplets collide with large ice crystals, freeze, and shatter, producing a plethora of small ice splinters. This process, known as Hallett‐Mossop rime splintering, and other forms of secondary ice production, can cause clouds to reflect less sunlight and to have shorter lifetimes. We show its impact on Southern Ocean shallow cumuli using a novel suite of five global storm‐resolving simulations, which partition the Earth's atmosphere into 2–4 km wide columns. We evaluate simulated clouds and radiation over the Southern Ocean with aircraft observations from the Southern Ocean Clouds, Radiation, Aerosol Transport Experimental Study (SOCRATES), and satellite observations from Clouds and the Earth's Radiant Energy System (CERES) and Himawari. Simulations with large concentrations of ice crystals in boundary layer clouds, which agree better with SOCRATES observations, have reduced mixed‐phase cumulus cloud cover and weaker shortwave cloud radiative effects (CREs) that are less biased compared with CERES. Using a pair of simulations differing only in their treatment of Hallett‐Mossop rime splintering, we show that including this process increases ice crystal concentrations in cumulus clouds and weakens shortwave CREs over the Southern Ocean by 10 W m−2. We also demonstrate the key role that global storm‐resolving models can play in detangling the effects of clouds on Earth's climate across scales, making it possible to trace the impact of changes in individual cumulus cloud anvils (10 km2) on the radiative budget of the massive Southern Ocean basin (107 km2).
Assimilative Mapping of Auroral Electron Energy Flux Using SSUSI Lyman‐Birge‐Hopfield (LBH) Emissions
Authors: Li J. , Matsuo T. , Kilcommons L. M. 
Published: March 2022

AbstractFar ultraviolet (FUV) imaging of the aurora from space provides great insight into the dynamic coupling of the atmosphere, ionosphere, and magnetosphere on global scales. To gain a quantitative understanding of these coupling processes, the global distribution of auroral energy flux is required, but the inversion of FUV emission to derive precipitating auroral particles' energy flux is not straightforward. Furthermore, the spatial coverage of FUV imaging from Low Earth Orbit (LEO) altitudes is often insufficient to achieve global mapping of this important parameter. This study seeks to fill these gaps left by the current geospace observing system using a combination of data assimilation and machine learning techniques. Specifically, this paper presents a new data‐driven modeling approach to create instantaneous, global assimilative mappings of auroral electron total energy flux from Lyman‐Birge‐Hopfield (LBH) emission data from the Defense Meteorological System Program (DMSP) Special Sensor Ultraviolet Spectrographic Imager (SSUSI). We take a two‐step approach; the creation of assimilative maps of LBH emission using optimal interpolation, followed by the conversion to energy flux using a neural network model trained with conjunction observations of in‐situ auroral particles and LBH emission from the DMSP Special Sensor J and SSUSI instruments. The paper demonstrates the feasibility of this approach with a model prototype built with DMSP data from 17 February 2014 to 23 February 2014. This study serves as a blueprint for a future comprehensive data‐driven model of auroral energy flux that is complementary to traditional inversion techniques to take advantage of FUV imaging from LEO platforms for global assimilative mapping of auroral energy flux.
Hybrid Physically Based and Deep Learning Modeling of a Snow Dominated, Mountainous, Karst Watershed
Authors: Xu Tianfang , Longyang Qianqiu , Tyson Conor , Zeng Ruijie , Neilson Bethany T. 
Published: March 2022

AbstractSnow dominated mountainous karst watersheds are the primary source of water supply in many areas in the western U.S. and worldwide. These watersheds are typically characterized by complex terrain, spatiotemporally varying snow accumulation and melt processes, and duality of flow and storage dynamics because of the juxtaposition of matrix (micropores and small fissures) and karst conduits. As a result, predicting streamflow from meteorological inputs has been challenging due to the inability of physically based or conceptual hydrologic models to represent these unique characteristics. We present a hybrid modeling approach that integrates a physically based, spatially distributed, snow model with a deep learning karst model. More specifically, the high‐resolution snow model captures spatiotemporal variability in snowmelt, and the deep learning model simulates the corresponding response of streamflow as influenced by complex surface and subsurface properties. The deep learning model is based on the Convolutional Long Short‐Term Memory (ConvLSTM) architecture capable of handling spatiotemporal recharge patterns and watershed storage dynamics. The hybrid modeling approach is tested on a watershed in northern Utah with seasonal snow cover and variably karstified carbonate bedrock. The hybrid models were able to simulate streamflow at the watershed outlet with high accuracy. The spatial and temporal recharge and discharge patterns learned by the ConvLSTM model were then examined and compared with known hydrogeologic information. Results suggest that ConvLSTM simulates streamflow with higher accuracy than reference models for the study area and provides insight into spatially influenced hydrologic responses that are unavailable within lumped modeling approaches.
General dental practitioner views on the current and future provision of advanced NHS restorative dentistry services: a cross-sectional survey in England
Authors: O´Connor Christopher , Bridges-Smith Francis , Docherty Ciara , Research Network Northern Dental Practice Based , Holliday Richard 
Published: March 2022

AbstractIntroduction Advanced NHS restorative dentistry services are an important aspect of patient care. Managed clinical networks (MCNs) have been proposed as a future model of care.Aim To assess general dental practitioners' (GDPs') satisfaction with the current provision of advanced NHS restorative dentistry services and assess their views on MCNs.Methods A self-administered, online survey was distributed by the Northern Dental Practice Based Research Network and was shared on social media.Results In total, 108 responses were received from GDPs working in England; 55% in the North East. GDPs felt current services for periodontics, endodontics, tooth surface loss and temporomandibular disorders were the most important and were most unsatisfied with periodontics, endodontics and tooth surface loss. The most important barriers to current referral practice were previous referral rejections and the return of costly treatment plans. Opinions were favourable towards the proposed MCNs, with one-third of participants feeling they were already suitable to apply to deliver Level 2 services. There was a notable imbalance between sexes, with fewer female dentists (57%) registering interest in joining an MCN compared to their male counterparts (76%) and female dentists also identifying more barriers to join MCNs, including access to suitable training. Recent graduates were least likely to cite a lack of time as a barrier to engaging with MCNs.Conclusions GDPs are currently unsatisfied with advanced NHS restorative dentistry services but appear keen to engage with MCNs. The survey identified important insights which may help healthcare planners develop services.
The mmu_circRNA_37492/hsa_circ_0012138 function as potential ceRNA to attenuate obstructive renal fibrosis
Authors: Cheng Xu , Ai Kai , Yi Lei , Liu Wentao , Li Yijian , Wang Yinhuai , Zhang Dongshan 
Published: March 2022

AbstractCircular RNAs (circRNAs) are involved in the pathogenesis of certain renal diseases, however, the function and mechanism of them in renal fibrosis remains largely unknown. In the present study, RNA expression data in unilateral ureteral obstruction (UUO) kidneys was obtained from our previous circRNA Microarray and public Gene Expression Omnibus datasets to construct a ceRNA network. The effects of target circRNA as long as the homologous human circRNA on renal fibrosis was examined in vitro and in vivo. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was further performed among genes regulated by the human circRNA. We found that circRNA_37492, showing well connection degree in the ceRNA network, was abundant expression and high sequence conservation. We observed that the expression of circRNA_37492 was induced by the TGF-β1 or UUO in BUMPT cells and C57BL/6 mice, respectively. In vitro, cytoplasmic circRNA_37492 inhibited type I, III collagen and fibronectin deposition by sponging miR-7682-3p and then upregulated its downstream target Fgb. In vivo, overexpression of circRNA_37492 attenuated fibrotic lesions in the kidneys of UUO mice via targeting miR-7682-3p/Fgb axis. Furthermore, hsa_circ_0012138, homologous with circRNA_37492, may potentially target miR-651-5p/FGB axis in human renal fibrosis. Not only that, GO and KEGG enrichment revealed that hsa_circ_0012138-regulated genes were previously demonstrated to related to the fibrosis. In conclusion, we for the first time demonstrated that circRNA_37492 attenuated renal fibrosis via targeting miR-7682-3p/Fgb axis, and the homologous hsa_circRNA_0012138 was speculated as a possible ceRNA to regulate multiple gene expressions and involve in human renal fibrosis, suggesting that circRNA_37492/hsa_circ_0012138 may serve as potent therapy target for obstructive renal fibrosis disease.
The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma
Authors: Yin De-Pei , Zheng Yu-Fan , Sun Peng , Yao Ming-Yu , Xie Li-xiao , Dou Xun-Wu , Tian Ye , Liu Ji-Sheng 
Published: March 2022

AbstractIt is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.
A drug repurposing strategy for overcoming human multiple myeloma resistance to standard-of-care treatment
Authors: Chroma Katarina , Skrott Zdenek , Gursky Jan , Bacovsky Jaroslav , Moudry Pavel , Buchtova Tereza , Mistrik Martin , Bartek Jiri 
Published: March 2022

AbstractDespite several approved therapeutic modalities, multiple myeloma (MM) remains an incurable blood malignancy and only a small fraction of patients achieves prolonged disease control. The common anti-MM treatment targets proteasome with specific inhibitors (PI). The resulting interference with protein degradation is particularly toxic to MM cells as they typically accumulate large amounts of toxic proteins. However, MM cells often acquire resistance to PIs through aberrant expression or mutations of proteasome subunits such as PSMB5, resulting in disease recurrence and further treatment failure. Here we propose CuET—a proteasome-like inhibitor agent that is spontaneously formed in-vivo and in-vitro from the approved alcohol-abuse drug disulfiram (DSF), as a readily available treatment effective against diverse resistant forms of MM. We show that CuET efficiently kills also resistant MM cells adapted to proliferate under exposure to common anti-myeloma drugs such as bortezomib and carfilzomib used as the first-line therapy, as well as to other experimental drugs targeting protein degradation upstream of the proteasome. Furthermore, CuET can overcome also the adaptation mechanism based on reduced proteasome load, another clinically relevant form of treatment resistance. Data obtained from experimental treatment-resistant cellular models of human MM are further corroborated using rather unique advanced cytotoxicity experiments on myeloma and normal blood cells obtained from fresh patient biopsies including newly diagnosed as well as relapsed and treatment-resistant MM. Overall our findings suggest that disulfiram repurposing particularly if combined with copper supplementation may offer a promising and readily available treatment option for patients suffering from relapsed and/or therapy-resistant multiple myeloma.
Elevated nuclear localization of glycolytic enzyme TPI1 promotes lung adenocarcinoma and enhances chemoresistance
Authors: Liu Peng , Sun Si-Jia , Ai Ying-Jie , Feng Xu , Zheng Yi-Min , Gao Yun , Zhang Jin-Ye , Zhang Lei , Sun Yi-Ping , Xiong Yue , Lin Miao , Yuan Hai-Xin 
Published: March 2022

AbstractIncreased glycolysis is a hallmark of tumor, which can provide tumor cells with energy and building blocks to promote cell proliferation. Recent studies have shown that not only the expression of glycolytic genes but also their subcellular localization undergoes a variety of changes to promote development of different types of tumors. In this study, we performed a comprehensive analysis of glycolysis and gluconeogenesis genes based on data from TCGA to identify those with significant tumor-promoting potential across 14 types of tumors. This analysis not only confirms genes that are known to be involved in tumorigenesis, but also reveals a significant correlation of triosephosphate isomerase 1 (TPI1) with poor prognosis, especially in lung adenocarcinoma (LUAD). TPI1 is a glycolytic enzyme that interconverts dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (GAP). We confirm the upregulation of TPI1 expression in clinical LUAD samples and an inverse correlation with the overall patient survival. Knocking down of TPI1 in lung cancer cells significantly reduced cell migration, colony formation, and xenograft tumor growth. Surprisingly, we found that the oncogenic function of TPI1 depends on its translocation to cell nucleus rather than its catalytic activity. Significant accumulation of TPI1 in cell nucleus was observed in LUAD tumor tissues compared with the cytoplasm localization in adjacent normal tissues. Moreover, nuclear translocation of TPI1 is induced by extracellular stress (such as chemotherapy agents and peroxide), which facilitates the chemoresistance of cancer cells. Our study uncovers a novel function of the glycolytic enzyme TPI1 in the LUAD.
Leptin secreted from testicular microenvironment modulates hedgehog signaling to augment the endogenous function of Leydig cells
Authors: Arora Himanshu , Qureshi Rehana , Khodamoradi Kajal , Seetharam Deepa , Parmar Madhumita , Van Booven Derek J. , Issa Isabelle Catherine , Sackstein Robert , Lamb Dolores , Hare Joshua M. , Ramasamy Ranjith 
Published: March 2022

AbstractAlthough testosterone deficiency (TD) may be present in one out of five men 40 years or older, the factors responsible for TD remain largely unknown. Leydig stem cells (LSCs) differentiate into adult Leydig cells (ALC) and produce testosterone in the testes under the pulsatile control of luteinizing hormone (LH) from the pituitary gland. However, recent studies have suggested that the testicular microenvironment (TME), which is comprised of Sertoli and peritubular myoid cells (PMC), plays an instrumental role in LSC differentiation and testosterone production under the regulation of the desert hedgehog signaling pathway (DHH). It was hypothesized that the TME releases paracrine factors to modulate LSC differentiation. For this purpose, cells (Sertoli, PMCs, LSCs, and ALCs) were extracted from men undergoing testis biopsies for sperm retrieval and were evaluated for the paracrine factors in the presence or absence of the TME (Sertoli and PMC). The results demonstrated that TME secretes leptin, which induces LSC differentiation and increases testosterone production. Leptin’s effects on LSC differentiation and testosterone production, however, are inversely concentration-dependent: positive at low doses and negative at higher doses. Mechanistically, leptin binds to the leptin receptor on LSCs and induces DHH signaling to modulate LSC differentiation. Leptin-DHH regulation functions unidirectionally insofar as DHH gain or loss of function has no effect on leptin levels. Taken together, these findings identify leptin as a key paracrine factor released by cells within the TME that modulates LSC differentiation and testosterone release from mature Leydig cells, a finding with important clinical implications for TD.