bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of loan covenants on audit delays and audit fees
Authors: Parkash Mohinder , Singhal Rajeev , Zhu Yun (Ellen) 
Published: May 2022

AbstractWe provide evidence on the impact of loan covenants on audit delays and audit fees. We find that for most covenants, firms with a particular covenant have longer audit delays than firms without that covenant. On average, we observe that adding one more loan covenant will delay the audit report by at least 1 day. We also found that adding one more loan covenant increases audit fees by 1.2%.
Contagion of credit risk: Comparative analysis before and after the pandemic of COVID‐19
Authors: Ito Takayasu 
Published: May 2022

AbstractThe spreads of credit default swaps (CDS) in Germany, Japan, United Kingdom, and United States move together before the COVID‐19 pandemic with few mutual causalities. However, they do not move together after the pandemic and have more mutual causalities. The credit risk of four major countries—Germany, Japan, United Kingdom, and United States are connected due to their relative stability before the pandemic. However, they are not connected in terms of the differences in public spending between the countries during COVID‐19. This makes the CDS market more sensitive to credit risk in each nation, resulting in the independent move of credit risk among the four countries.
A promoter variant in theOTCgene associated with late and variable age of onset hyperammonemia
Authors: Han Sangwoo T. , Anderson Katherine J. , Bjornsson Hans T. , Longo Nicola , Valle David 
Published: May 2022

AbstractOrnithine transcarbamylase deficiency (OTCD) is an X‐linked inborn error caused by loss of function variants in theOTCgene typically associated with severe neonatal hyperammonemia. Rare examples of late‐onset OTCD have also been described. Here, we describe anOTCpromoter variant, c.‐106C>A, in a conserved HNF4a binding site, identified in two male siblings in Family 1 whose first and only recognized episodes of severe hyperammonemia occurred at ages 14 and 39 years, respectively. We identified the sameOTCvariant segregating in a large family with late‐onset OTCD with variable expressivity (Family 2). We show that thisOTCpromoter variant reduces expression >5‐fold in a dual‐luciferase assay that tests promoter function. Addition of an upstreamOTCenhancer increases expression of both the wild type and the c.‐106C>A variant promoter constructs >5‐fold with the mutant promoter still about fourfold lower than the wild type. Thus, in both contexts, the promoter variant results in substantially lowerOTCexpression. Under normal demand on urea cycle function,OTCexpression in hemizygous males, although reduced, is sufficient to meet the demand for waste nitrogen excretion. However, in response to severe metabolic stress with attendant increased requirements on urea cycle function, the impaired promoter function results in inadequateOTCexpression with resultant hyperammonemia. In the absence of precipitating events, hemizygotes with this allele are asymptomatic, explaining the late age of onset of hyperammonemia in affected individuals and the incomplete penetrance observed in some individuals in Family 2.
Sophoridine inhibits endotoxin-induced acute lung injury by enhancing autophagy of macrophage and reducing inflammation
Authors: Liang Jinping , Liu Juntong , Tang Yezhen , Peng Qian , Zhang Ling , Ma Xiaoxia , Xu Nan , Wei Jun , Han Huaiqin 
Published: May 2022

AbstractAcute lung injury (ALI) is characterized by uncontrolled inflammation, which can lead to respiratory distress syndrome and cause patient death. In this study, we sought to determine the role of sophoridine, a compound purified from sophora, in ALI. A mouse model of ALI was established by treating mice with LPS through nonexposed tracheal instillation. After LPS-induced mice were treated with sophoridine, LPS-induced alveolar wall thickening, alveolar interstitial inflammatory exudation and thickening, and the degree of pulmonary edema were found to be inhibited. Macrophages play an important role in inflammation, and in vitro experiments have demonstrated that sophoridine reduces the LPS-induced expression of inflammatory factors by macrophages, suggesting that sophoridine may inhibit lung inflammation in LPS-treated mice through reduces the secretion of inflammatory factors. Further, treatment with sophoridine up-regulated autophagy in macrophage cells in vitro and mouse lung tissues in vivo. LPS can bind to TLRs and activate the MyD88/NF-κB pathways, leading to increased inflammation in the pathogenesis of ALI. Our findings revealed that sophoridine down-regulated the expression of TLR4/MyD88/NF-κB and mTOR mRNA and protein in mouse pulmonary tissue. Collectively, these findings indicate that sophoridine may inhibit LPS-induced ALI by enhancing autophagy of macrophages and reducing inflammation.
Changes in the peripheral and central auditory performance in the elderly—A cross‐sectional study
Authors: Pürner Dominik , Schirkonyer Volker , Janssen Thomas 
Published: May 2022

AbstractAge‐related hearing loss (ARHL, formerly presbycusis) is due to a variety of lifetime damages to the auditory system and is characterized by bilateral sensorineural hearing loss, impaired speech understanding in noise and central sound processing deficits. Despite its commonness, the pathogenesis has not been completely clarified yet; especially the existence of an independent central ARHL component still remains controversial. We present the results of a cross‐sectional topodiagnostic test battery study which aimed at separating aging‐ and hearing loss‐related effects on all parts of the auditory system by current test procedures. Three groups of 30 participants each underwent extensive topodiagnostic test procedures (otoscopy, tympanometry, questionnaires, pure‐tone audiometry, DPOAE threshold measurements, auditory brainstem response, central auditory discrimination tests, and speech‐in‐noise test). By comparing the results of the normally hearing young (18–26 years) and healthy control group, the normally hearing elderly group (60–80 years) and the hearing‐impaired elderly group (60–80 years), we deduced aging and hearing loss‐related effects on auditory performance. All measurements indicated a significant deterioration of auditory performance in the elderly, partly associated with aging and partly with age‐related hearing loss. Our study thereby contributes to a multifocal concept of ARHL. All parts of the auditory system are impaired by aging, age‐related hearing loss, or a combination of both. Further evidence for an independent central ARHL component, not attributable to peripheral hearing loss, is provided by the results of the central auditory discrimination test.
New improved Brazilian daily weather gridded data (1961–2020)
Authors: Xavier Alexandre C. , Scanlon Bridget R. , King Carey W. , Alves Aline I. 
Published: May 2022

AbstractThe demand for meteorological gridded datasets has increased within the last few years to inform studies such those in climate, weather, and agriculture. These studies require those data to be readily usable in standard formats with continuous spatial and temporal coverage. Since 2016, Brazil has a daily gridded meteorological data set with spatial resolution of 0.25° × 0.25° from January 1, 1980 to December 31, 2013 which was well received by the community. The main objective of this work is to improve the Brazilian meteorological data set. We do this by increasing the resolution of the minimum and maximum temperature (Tmax and Tmin) gridded interpolations from 0.25° × 0.25° to 0.1° × 0.1° by incorporating data on topographic relief, and increasing the time period covered (January 1, 1961–July 31, 2020). Besides Tmax and Tmin, we also gridded precipitation (pr), solar radiation (Rs), wind speed (u2), and relative humidity (RH) using observed data from 11,473 rain gauges and 1,252 weather stations. By means of ranked cross‐validation statistics, we selected the best interpolation among inverse distance weighting and angular distance weighting methods. We determined that interpolations for Tmax and Tmin are improved by using the elevation of a query point, that accounts for topographic relief, and a temperature lapse rate. Even though this new version has ≈25 years more data relative to the previous one, statistics from cross‐validation were similar. To allow researchers to assess the performance of the interpolation relative to station data in the area, we provide two types of gridded controls.
Modelling of hydrological and environmental flow dynamics over a central Himalayan river basin through satellite altimetry and recent climate projections
Authors: Kumar Nirmal , Dubey Amit Kumar , Goswami Uttam Puri , Singh Sudhir Kumar 
Published: May 2022

AbstractThe Himalayan region is vulnerable to climate change, which is triggering extreme hydrological events. To understand the impact of climate emission scenarios on different hydrological flow dynamics of the Himalayan region, a thorough hydrological investigation is needed for improved water resource management. Hence, this research exemplifies the use of remote sensing, modelling techniques, and recent climate projections (CMIP5 and CMIP6) for the assessment of hydrological flow dynamics in the central Himalayan catchment. The SWAT model is calibrated/validated using gauge observation and satellite altimetry‐derived river discharge and used for long‐term hydrological simulations (1979–2100). CMIP6 models predicted that there would be a steady rise in high flows in all the projected scenarios. Flow duration curve for CMIP5 and CMIP6 models depicted that high flow of short duration would be frequent in future. The environmental flow components (EFCs) were calculated using the indicator of hydrologic alteration tool. The SWAT model simulations of hydrological and EFCs under CMIP6 climate projections are found to be significantly more vulnerable to climate warming than CMIP5, which could be due to socioeconomic pathway emission scenarios.
LC–MS/MS‐based metabolomics approach revealed novel phytocompounds from sugarcane rind with promising pharmacological value
Authors: Rao Muhammad Junaid , Duan Mingzheng , Wei Xiaoshuang , Zuo Hou , Ma Li , Tahir ul Qamar Muhammad , Li Min , Han Shijian , Hu Lihua , Wang Lingqiang 
Published: May 2022

AbstractBACKGROUNDSugarcane provides many secondary metabolites for the pharmacological and cosmetic industries. Secondary metabolites, such as phenolic compounds, flavonoids, and anthocyanins, have been studied, but few reports focus on the identification of alkaloid and non‐alkaloid phytocompounds in sugarcane.RESULTSIn this study, we identified 40 compounds in total from the rinds of cultivated sugarcane varieties (including eight alkaloids, 24 non‐alkaloids, and eight others) by using the liquid chromatography–tandem mass spectrometry (LC–MS/MS) approach. Among these compounds, 31 were novel and are reported for the first time in sugarcane. Some alkaloids such as 3‐indoleacrylic acid,N,N‐dimethyl‐5‐methoxytryptamine, tryptamine, 6‐hydroxynicotinic acid, and 6‐deoxyfagomine are identified the first time in sugarcane rind. Four alkaloids such as trigonelline, piperidine, 3‐indoleacrylic acid, and 6‐deoxyfagomine are found abundantly in sugarcane rind and these compounds have promising pharmaceutical value. Some phytocompounds such as choline and acetylcholine (non‐alkaloid compounds) were most common in the rind of ROC22 and Yuetang93/159 (YT93/159). Hierarchical cluster analysis and principal component analysis revealed that the ROC22, Taitang172 (F172), and Yuetang71/210 (YT71/210) varieties were quite similar in alkaloid composition when compared with other sugarcane varieties. We have also characterized the biosynthesis pathway of sugarcane alkaloids. The rind of F172, ROC22, and YT71/210 showed the highest total alkaloid content, whereas the rind of ROC16 revealed a minimum level. Interestingly, the rind extract from YT71/210 and F172 showed maximum antioxidant activity, followed by ROC22.CONCLUSIONOur results showed the diversity of alkaloid and non‐alkaloid compounds in the rind of six cultivated sugarcanes and highlighted the promising phytocompounds that can be extracted, isolated, and utilized by the pharmacological industry. © 2022 Society of Chemical Industry.
Osteogenic activities of four calcium‐chelating microalgae peptides
Authors: Yu Huilin , Chen Yixuan , Zhu Jiajin 
Published: May 2022

AbstractBACKGROUNDAdequate calcium intake is necessary to prevent osteoporosis, which poses significant public health challenges. The natural bioactive peptide calcium chelates have been regarded as superior calcium supplements. Microalgae peptides are regarded as potential candidates for protection from bone loss in osteoporosis. This study aimed to prepare microalgae calcium‐chelating peptides from four microalgae proteins and assess their osteogenic activities in osteoporosis‐like zebrafish.RESULTSAfter in vitro gastrointestinal digestion, 4.42% Chlorella pyrenoidosa protein, 2.74% Nannochloropsis oceanica protein, 6.07% Arthospira platensis protein and 10.47% Dunaliella salina protein were retained. The calcium‐chelating capacities of four microalgae protein hydrolysates (MPHs) ranged from 14.10 ± 7.16% to 34.11 ± 9.34%. CaCl2 addition increased the maximum absorption peaks, absorption intensities and particle sizes of MPHs. Calcium‐chelating MPHs showed stronger osteogenic activities than MPHs in the osteoporosis‐like zebrafish model, with significantly increased mineralized tissue area and integrated optical density.CONCLUSIONMicroalgae proteins have favorable digestibilities. Among the four MPHs, Nannochloropsis oceanica protein hydrolysates showed the highest calcium‐chelating capacity, which might be due to its high degree of hydrolysis after in vitro digestion and high content of Ser, Tyr, Thr, Asp and Glu. The absorption intensities and particle sizes of MPHs both increased after calcium addition. MPH treatment could reverse dexamethasone‐induced osteoporosis of zebrafish, and MPHs‐Ca chelates showed higher osteogenic activities in osteoporosis‐like phenotype zebrafish. © 2022 Society of Chemical Industry.
Unraveling the Photovoltaic, Mechanical, and Microstructural Properties and Their Correlations in Simple Poly(3‐pentylthiophene) Solar Cells
Authors: Yang Xuantong , Gao Mengyuan , Bi Zhaozhao , Liu Yang , Xian Kaihu , Peng Zhongxiang , Qi Qingchun , Li Saimeng , Song Jinsheng , Ma Wei , Ye Long 
Published: May 2022

AbstractThe power conversion efficiency of polythiophene organic solar cells is constantly refreshed. Despite the renewed device efficiency, very few efforts have been devoted to understanding how the type of electron acceptor alters the photovoltaic and mechanical properties of these low‐cost solar cells. Herein, the authors conduct a thorough investigation of photovoltaic and mechanical characteristics of a simple yet less‐explored polythiophene, namely poly(3‐pentylthiophene) (P3PT), in three different types of organic solar cells, where ZY‐4Cl, PC71BM, and N2200 are employed as three representative acceptors, respectively. Compared with the reference poly(3‐hexylthiophene) (P3HT)‐based solar cells, P3PT‐based devices, all perform more efficiently. Particularly, the P3PT:ZY‐4Cl blend exhibits the highest efficiency (ca. 10%) among the six combinations and outperforms the prior top‐performance system P3HT:ZY‐4Cl. Furthermore, the blend films based on N2200 exhibit a high crack‐onset strain of ∼38% on average, which is approximately 15‐ and 17‐times higher than those of ZY‐4Cl and PC71BM, respectively. The microstructural origins for the above difference are well elucidated by detailed grazing incidence X‐ray scattering and microscopy analysis. This work not only underlines the potential of P3PT in prolific solar cell research but also demonstrates the superior tensile properties of polythiophene‐based all‐polymer blends for the preparation of stretchable solar cells.
Input layer regularization for magnetic resonance relaxometry biexponential parameter estimation
Authors: Rozowski Michael , Palumbo Jonathan , Bisen Jay , Bi Chuan , Bouhrara Mustapha , Czaja Wojciech , Spencer Richard G. 
Published: May 2022

AbstractMany methods have been developed for estimating the parameters of biexponential decay signals, which arise throughout magnetic resonance relaxometry (MRR) and the physical sciences. This is an intrinsically ill‐posed problem so that estimates can depend strongly on noise and underlying parameter values. Regularization has proven to be a remarkably efficient procedure for providing more reliable solutions to ill‐posed problems, while, more recently, neural networks have been used for parameter estimation. We re‐address the problem of parameter estimation in biexponential models by introducing a novel form of neural network regularization which we call input layer regularization (ILR). Here, inputs to the neural network are composed of a biexponential decay signal augmented by signals constructed from parameters obtained from a regularized nonlinear least‐squares estimate of the two decay time constants. We find that ILR results in a reduction in the error of time constant estimates on the order of 15%–50% or more, depending on the metric used and signal‐to‐noise level, with greater improvement seen for the time constant of the more rapidly decaying component. ILR is compatible with existing regularization techniques and should be applicable to a wide range of parameter estimation problems.
Diet of the Chanyu and his people: Stable isotope analysis of the human remains from Xiongnu burials in western and northern Mongolia
Authors: Zhou Ligang , Mijiddorj Enkhbayar , Erdenebaatar Diimaajav , Lan Wanli , Liu Bin , Iderkhangai Tumur‐Ochir , Ulziibayar Sodnom , Galbadrakh Baatar 
Published: May 2022

AbstractThis study was designed to study the effect of social stratification on human diet in the Xiongnu society. Human remains unearthed from three different sites in western and northern Mongolia were analyzed for stable carbon and nitrogen isotope values. The results demonstrate that a certain amount of C4 component was consumed by people of different social levels. The three noble individuals from terrace tombs at the Gol Mod 2 site ate a similar diet to most of the burial followers buried in satellite tombs, indicating similar lifestyle or a close relationship between them. Commoners from the Ereen Hailaas were very close to the nobles in isotopic features; this might indicate dietary similarity or could be related to the environment factors. The Salkhitiin Am commoners were lower in both carbon and nitrogen isotope values compared with other Xiongnu people analyzed before; it is likely that they had a quite different diet featuring less C4 plant and animal protein. If such dietary variation was not related to social stratification, possible differences in subsistence strategies or dietary traditions should be considered. These results provide an important window into the social structure and subsistence strategies of the Xiongnu people and will facilitate future study on cultural communication and material exchange across the Eurasian continent.
Factors influencing outcomes of older children with medulloblastoma over 15 years in Peru, a resource‐limited setting
Authors: Diaz‐Coronado Rosdali Y. , Reinecke James Brandon , Stanek Joseph R. , Finlay Jonathan L. , Hernández Broncano Eddy , Chávez Paredes Sharon , Tunque Yesenia Miranda , Heredia Zelaya Adela , Casavilca Zambrano Sandro , García‐Corrochano Medina Pamela , Ojeda Medina Luis , Orrego Puelles Enrique , Torres Malca Ebert , Sernaque Quintana Raymundo , Quispe Valverde William , García León Juan L. , Osorio Diana S. 
Published: May 2022

AbstractBackgroundMedulloblastoma is the most common malignant brain tumor in children. While survival has improved in high‐income countries (HIC), the outcomes for patients in low‐to‐middle‐income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru.MethodsBetween 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997–2008 and 2009–2013, corresponding with chemotherapy regimen changes. Event‐free (EFS) and overall survival (OS) were calculated using the Kaplan–Meier method, whereas prognostic factors were determined by univariate analysis (log‐rank test).ResultsEighty‐nine patients were included; median age was 8.1 years (range: 3–13.9 years). The 5‐year OS was 62% (95% CI: 53%–74%), while EFS was 57% (95% CI: 48%–69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31–60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009–2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03).ConclusionsOutcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009–2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco‐regional groups and colleagues in HIC is likely beneficial.
Distribution and frequency of tyrosine kinase inhibitor‐associated long‐term complications in children with chronic myeloid leukemia
Authors: Dong Elizabeth E. , Bruno Michael A. , Kim Jeffrey J. , Bernhardt Melanie B. , Brown Austin L. , Gramatges Maria M. 
Published: May 2022

AbstractBackgroundTyrosine kinase inhibitors (TKIs) improve outcomes for pediatric malignancies characterized by specific gene rearrangements and mutations; however, little is known about the long‐term impact of TKI exposure. Our objective was to assess the incidence and type of late‐onset TKI‐related toxicities in children with chronic myeloid leukemia (CML).MethodsWe reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21 years of age and prescribed one or more TKIs. Patients treated with stem cell transplant were excluded. Outcomes were captured beginning at 1 year after CML diagnosis. Outcome incidence was described overall and stratified by TKI exposure during the data‐capture period.ResultsTwenty‐two eligible TKI‐exposed patients with CML were identified. The median follow‐up was 6.0 years (range: 2.2–14.3). All pericardial (n = 3) or pleural (n = 3) effusion outcomes occurred in patients treated with TKIs during the data‐capture period. Other outcomes included hypertension (n = 2), ectopy on electrocardiogram (n = 2), and gastrointestinal bleed (n = 1). All outcomes were graded as mild to moderate: some resulted in a temporary discontinuation of TKI, but none led to a change in TKI. No differences were noted in outcome incidence by type of TKI exposure.ConclusionsTKIs have substantially improved prognosis for subsets of childhood leukemia, but there are limited long‐term data to inform exposure‐based risk for late‐onset complications and screening. Our results suggest that TKI‐exposed survivors may be at risk for long‐term outcomes that extend well into survivorship.
Molecular targeted therapies for pediatric atypical teratoid/rhabdoid tumors
Authors: Zhang Chang , Li Hao 
Published: May 2022

ABSTRACTAtypical teratoid/rhabdoid tumors (AT/RTs) are lethal central nervous system tumors, which are primarily diagnosed in infants. Current treatments for AT/RTs include surgery, radiotherapy, and chemotherapy; these treatments have poor prognoses and challenging side effects. The pivotal genetic event in AT/RT pathogenesis comprises the inactivation of SMARCB1 or SMARCA4. Recent epigenetic studies have demonstrated mutual and subtype‐specific epigenetic derangements that drive tumorigenesis; the exploitation of these potential targets might improve the dismal treatment outcomes of AT/RTs. This review aims to summarize the literature concerning targeted molecular therapies for pediatric AT/RTs.