bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generalized kernel regularized least squares estimator with parametric error covariance
Authors: Dang Justin , Ullah Aman 
Published: April 2023

AbstractA two-step estimator of a nonparametric regression function via Kernel regularized least squares (KRLS) with parametric error covariance is proposed. The KRLS, not considering any information in the error covariance, is improved by incorporating a parametric error covariance, allowing for both heteroskedasticity and autocorrelation, in estimating the regression function. A two step procedure is used, where in the first step, a parametric error covariance is estimated by using KRLS residuals and in the second step, a transformed model using the error covariance is estimated by KRLS. Theoretical results including bias, variance, and asymptotics are derived. Simulation results show that the proposed estimator outperforms the KRLS in both heteroskedastic errors and autocorrelated errors cases. An empirical example is illustrated with estimating an airline cost function under a random effects model with heteroskedastic and correlated errors. The derivatives are evaluated, and the average partial effects of the inputs are determined in the application.
Metabolomics-based strategy to assess drug hepatotoxicity and uncover the mechanisms of hepatotoxicity involved
Authors: Martínez-Sena Teresa , Moro Erika , Moreno-Torres Marta , Quintás Guillermo , Hengstler Jan , Castell José V. 
Published: April 2023

AbstractToxicity studies, among them hepatotoxicity, are key throughout preclinical stages of drug development to minimise undesired toxic effects that might eventually appear in the course of the clinical use of the new drug. Understanding the mechanism of injury of hepatotoxins is essential to efficiently anticipate their potential risk of toxicity in humans. The use of in vitro models and particularly cultured hepatocytes represents an easy and robust alternative to animal drug hepatotoxicity testing for predicting human risk. Here, we envisage an innovative strategy to identify potential hepatotoxic drugs, quantify the magnitude of the alterations caused, and uncover the mechanisms of toxicity. This strategy is based on the comparative analysis of metabolome changes induced by hepatotoxic and non-hepatotoxic compounds on HepG2 cells, assessed by untargeted mass spectrometry. As a training set, we used 25 hepatotoxic and 4 non-hepatotoxic compounds and incubated HepG2 cells for 24 h at a low and a high concentration (IC10 and IC50) to identify mechanism-related and cytotoxicity related metabolomic biomarkers and to elaborate prediction models accounting for global hepatotoxicity and mechanisms-related toxicity. Thereafter, a second set of 69 chemicals with known predominant mechanisms of toxicity and 18 non-hepatotoxic compounds were analysed at 1, 10, 100 and 1000 µM concentrations from which and based on the magnitude of the alterations caused as compared with non-toxic compounds, we defined a “toxicity index” for each compound. In addition, we extracted from the metabolome data the characteristic signatures for each mechanism of hepatotoxicity. The integration of all this information allowed us to identify specific metabolic patterns and, based on the occurrence of that specific metabolome changes, the models predicted the likeliness of a compound to behave as hepatotoxic and to act through a given toxicity mechanism (i.e., oxidative stress, mitochondrial disruption, apoptosis and steatosis) for each compound and concentration.
An active new formulation of iron carried by aspartyl casein for iron-deficiency anemia: results of the ACCESS trial
Authors: Tsilika Maria , Mitrou John , Antonakos Nikolaos , Tseti Ioulia K. , Damoraki Georgia , Leventogiannis Konstantinos , Giamarellos-Bourboulis Evangelos J. 
Published: April 2023

AbstractOral iron supplementation is the cornerstone for the management of iron-deficiency anemia. A new oral formulation of iron conjugated with N-aspartyl-casein (Fe-ASP) (Omalin®, Uni-Pharma) is studied in the ACCESS double-blind, double-dummy randomized clinical trial; 60 patients were randomized to 12-week oral treatment twice every day either with oral ferrous sulfate (FeSO4) delivering 47 mg elementary iron or oral Fe-ASP delivering 40 mg elementary iron. Participants had hemoglobin less than 10 g/dl, decreased red blood cell (RBC) count, and ferritin lower than 30 ng/ml; patients with a medical history of malignancy were excluded. The primary endpoint was the increase of Hb in the first 4 weeks of treatment, and the study was powered for non-inferiority. A new score of global improvement was introduced where all participants were given one point for any at least 10% increase of Hb, RBC, and reticulocytes. At week 4, the mean (SE) change of Hb was 0.76 g/dl in the FeSO4 group and 0.83 g/dl in the Fe-ASP group (p: 0.876). The odds for worse allocation of the global score were 0.35 in the Fe-ASP group compared to the FeSO4 group. Patients in the Fe-ASP group experienced a significant decrease in the number of IDA-related physical signs by week 4. No differences were found between the two groups in any of the patient-reported outcomes of fatigue and of gastrointestinal adverse events either at week 4 or at week 12. ACCESS is the most recent clinical trial showing the non-inferiority of Fe-ASP to FeSO4 for the primary endpoint of the Hb change.
Gut Microbiota Dysbiosis and Increased NLRP3 Levels in Patients with Pregnancy-Induced Hypertension
Authors: Wu Jingjing , Zhang Dongmei , Zhao Meijing , Zheng Xiaowei 
Published: April 2023

AbstractPregnancy-induced hypertension (PIH) is one of the most common diseases, causing high maternal morbidity and mortality. However, the correlation of gut microbiota in PIH has not been reported. Our aim was to characterize the intestinal microbiota of patients with PIH compared with healthy people. We analyzed and compared the gut microbiota communities in the feces of 28 PIH patients with pregnancy(not pre-pregnancy) body mass index (including height and weight)-matched healthy controls using 16S rRNA gene sequencing and then investigate the relationships among gut microbiota, cytokines, and PIH. Compared with the healthy group, microbial α diversity was lower in the PIH group, but not statistically significant different. At the phylum level, Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria exhibited obvious differences between the PIH and control groups. LEfSe analysis found 33 differentially abundant taxa between the two groups. The production of pro-inflammatory cytokines in PIH serum or placenta tissues was higher than that of the control group. In addition to alterations in gut microbiota composition, we also found that the Bac_Prevotellaceae, Pre_Prevotella bacteria were positively correlated with NLRP3 level, but negatively correlated with Bac_Bacteroidaceae, Bac_Bacteroides. PIH patients had gut microbiota dysbiosis and increased NLRP3 levels, which will lead to a better understanding of the relationship between the gut microbiota and PIH.
Synthesis and cytotoxic activities of selenium nanoparticles incorporated nano-chitosan
Authors: Abdelhamid Ahmed E. , Ahmed Eman H. , Awad Hanem M. , Ayoub Magdy M. H. 
Published: April 2023

AbstractNew system compromising of chitosan nanoparticles encapsulated pre-synthesized selenium nanoparticles in the presence of 5-fluorouracil was successfully prepared and used for cancer antiproliferation. Selenium nanoparticles were synthesized using ascorbic acid as reducing agent under mild condition. Chitosan nanoparticles were prepared via ionic gelation technique using sodium tri-polyphosphate. Characterization of the prepared nanoparticles was carried out using FTIR, TEM, XRD, TGA and dynamic light scattering (DLS). The results displayed the formation of selenium nanoparticles with an average size 20 nm and chitosan nanoparticles with an average size 207 and 250 nm for neat nano-chitosan and chitosan incorporated 5-fluorouracil/selenium nanoparticles, respectively. The encapsulated nanocomposites were tested for treatment of cancer cell of human colorectal carcinoma (HCT-116), human liver carcinoma (HepG-2), and human breast adenocarcinoma MCF-7. The results indicated the potent cytotoxic activities of all nanocomposite toward the tested cells with enhanced anticancer activity rather than the single drug or neat selenium nanoparticle. All composites were tested against non-tumor fibroblast-derived cell line (BJ) and demonstrated very low cytotoxicity.
Outcomes of a radiation sparing approach in medulloblastoma by subgroup in young children: an institutional review
Authors: Ronsley Rebecca , Triscott Joanna , Stanek Joseph , Rassekh S. Rod , Lum Amy , Cheng Sylvia , Goddard Karen , McConnell Dina , Strahlendorf Caron , Singhal Ash , Finlay Jonathan L. , Yip Stephen , Dunham Christopher , Hukin Juliette 
Published: April 2023

Abstract
Objective
To describe disease outcomes including overall survival and relapse patterns by subgroup in young pediatric patients treated for medulloblastoma with a radiation-sparing approach.

Methods
Retrospective analysis of clinical outcomes includes treatment, relapse, and salvage therapy and late effects in children treated for medulloblastoma with a radiation-sparing approach at British Columbia Children’s Hospital (BCCH) between 2000 and 2020.

Results
There were 30 patients (median age 2.8 years, 60% male) treated for medulloblastoma with a radiation-sparing approach at BCCH. Subgroups included Sonic Hedgehog (SHH) (n = 14), group 3 (n = 7), group 4 (n = 6), and indeterminate status (n = 3). Three- and 5-year event-free survival (EFS) were 49.0% (30.2–65.4%) and 42.0% (24.2–58.9%) and overall survival (OS) 66.0% (95% CI 46.0–80.1%) and 62.5% (95% CI 42.5 and 77.2%), respectively, with a median follow-up of 9.5 years. Relapse occurred in 12/25 patients following a complete response, of whom six (group 4: n = 4; group 3: n = 1; unknown: n = 1) were successfully salvaged with craniospinal axis (CSA) RT and remain alive at a median follow-up of 7 years. Disease/treatment-related morbidity included endocrinopathies (n = 8), hearing loss n = 16), and neurocognitive abnormalities (n = 9).

Conclusions
This radiation sparing treatment approach for young patients with medulloblastoma resulted in a durable cure in most patients with SHH subgroup medulloblastoma. In those patients with groups 3 and 4 medulloblastoma, relapse rates were high; however, most group 4 patients were salvaged with RT.
Cytokeratin 6 identifies basal-like subtypes of pancreatic ductal adenocarcinoma with decreased survival
Authors: Lyu Su Ir , Krey Thaddaeus , Damanakis Alexander I. , Zhao Yue , Bruns Christiane J. , Schmidt Thomas , Popp Felix C. , Quaas Alexander , Knipper Karl ,   the PANCALYZE Study Group, Heise Michael , Marusch Frank , Siech Marco , Mosa Tawfik , Schniewind Bodo , Tepel Jürgen , Hartwig Werner , Prinz Christoph , Rau Bettina M. , Niedergethmann Marco , Kube Rainer , Saada George , Hiller Wolfgang , Settmacher Utz 
Published: April 2023

Abstract
Purpose
Rising incidence of pancreatic ductal adenocarcinoma (PDAC) bind with insufficient therapy options showcases a great medical challenge. Further biomarkers are required to identify patients, who will benefit from more aggressive therapy.

Methods
320 patients were included by the PANCALYZE study group. Cytokeratin 6 (CK6) immunohistochemical staining as a putative marker for the basal-like subtype of PDAC was performed. The correlation between CK6 expression patterns and survival data, as well as various markers of the (inflammatory) tumor microenvironment, were analyzed.

Results
We divided the study population based on the expression pattern of CK6. Patients with a high CK6 tumor expression had a significantly shorter survival (p = 0.013), confirmed in a multivariate cox regression model. CK6-expression is an independent marker for a decreased overall survival (HR = 1.655, 95% CI 1.158–2.365, p = 0.006). In addition, the CK6-positive tumors showed significantly less plasma cell infiltration and more cancer-associated fibroblasts (CAFs) expressing Periostin and SMA.

Conclusions
CK6 could be considered as an independent biomarker for a shorter overall survival. CK6 is a clinically easily accessible biomarker for the identification of the basal-like subtype of PDAC. Therefore, it could be taken into consideration in deciding for the more aggressive therapy regimes. Prospectively, studies addressing the chemosensitive characteristics of this subtype are required.
Modified orca predation algorithm: developments and perspectives on global optimization and hybrid energy systems
Authors: Emam Marwa M. , El-Sattar Hoda Abd , Houssein Essam H. , Kamel Salah 
Published: April 2023

AbstractThis paper provides a novel, unique, and improved optimization algorithm called the modified Orca Predation Algorithm (mOPA). The mOPA is based on the original Orca Predation Algorithm (OPA), which combines two enhancing strategies: Lévy flight and opposition-based learning. The mOPA method is proposed to enhance search efficiency and avoid the limitations of the original OPA. This mOPA method sets up to solve the global optimization issues. Additionally, its effectiveness is compared with various well-known metaheuristic methods, and the CEC’20 test suite challenges are used to illustrate how well the mOPA performs. Case analysis demonstrates that the proposed mOPA method outperforms the benchmark regarding computational speed and yields substantially higher performance than other methods. The mOPA is applied to ensure that all load demand is met with high reliability and the lowest energy cost of an isolated hybrid system. The optimal size of this hybrid system is determined through simulation and analysis in order to service a tiny distant location in Egypt while reducing costs. Photovoltaic panels, biomass gasifier, and fuel cell units compose the majority of this hybrid system’s configuration. To confirm the mOPA technique’s superiority, its outcomes have been compared with the original OPA and other well-known metaheuristic algorithms.
Carbon nanomaterial-based membranes in solid-phase extraction
Authors: Bosco Chiara Dal , De Cesaris Massimo Giuseppe , Felli Nina , Lucci Elena , Fanali Salvatore , Gentili Alessandra 
Published: April 2023

AbstractCarbon nanomaterials (CNMs) have some excellent properties that make them ideal candidates as sorbents for solid-phase extraction (SPE). However, practical difficulties related to their handling (dispersion in the atmosphere, bundling phenomena, reduced adsorption capability, sorbent loss in cartridge/column format, etc.) have hindered their direct use for conventional SPE modes. Therefore, researchers working in the field of extraction science have looked for new solutions to avoid the above-mentioned problems. One of these is the design of CNM-based membranes. These devices can be of two different types: membranes that are exclusively composed of CNMs (i.e. buckypaper and graphene oxide paper) and polysaccharide membranes containing dispersed CNMs. A membrane can be used either as a filter, operating under flow-through mode, or as a rotating device, operating under the action of magnetic stirring. In both cases, the main advantages arising from the use of membranes are excellent results in terms of transport rates, adsorption capability, high throughput, and ease of employment. This review covers the preparation/synthesis procedures of such membranes and their potential in SPE applications, highlighting benefits and shortcomings in comparison with conventional SPE materials (especially, microparticles carbonaceous sorbents) and devices. Further challenges and expected improvements are addressed too.
Graphical Abstract
Exploring the longer-term impact of the COVID-19 pandemic on physical and mental health of people with inflammatory rheumatic diseases: a cross-sectional survey
Authors: Hider Samantha , Muller Sara , Gray Lauren , Manning Fay , Brooks Mike , Heining Dominic , Menon Ajit , Packham Jonathan , Roddy Edward , Ryan Sarah , Scott Ian C. , Paskins Zoe 
Published: April 2023

Abstract

Objective

To assess the longer term impact of the COVID-19 pandemic on the self-reported physical and mental health of people with inflammatory rheumatic diseases (IRDs).

Methods
Two thousand twenty-four patients with IRDs were randomly selected from electronic health records. Survey invitations were sent (August 2021 coinciding with relaxation of UK COVID-19 restrictions) using SMS and postal approaches. Self-reported data included demographics, shielding status and physical (MSK-HQ) and mental health (PHQ8 and GAD7).

Results
Six hundred thirty-nine people completed the survey (mean (SD) age 64.5 (13.1) years, 384 (60%) female). Moderate/severe impact of the pandemic on physical and mental health was reported by 250 (41%) and 241 (39%) respectively. One hundred seventy-two (29%) reported moderate/severe depression (PHQ8 ≥ 10) and 135 (22%) moderate/severe anxiety (GAD7 ≥ 10). Females reported greater impacts of the pandemic on physical health (44% vs 34%), mental health (44% vs 34%), arthritis symptoms (49% vs 36%) and lifestyle factors (weight gain and reduced exercise and physical activity) than males. The physical and mental impacts were less in people with RA compared with other IRDs. Physical health impacts did not differ between age groups, but younger patients reported greater impacts on mental health.

Conclusion
The COVID-19 pandemic has had a significant impact on the physical and mental health of people with IRDs. These effects were greatest in females. Recovery needs to address the negative impact of the pandemic on lifestyle factors to minimise the long-term impacts for people with IRDs.

Key Points• The pandemic had a significant impact on long term physical and mental health in almost 40% of people with IRDs.• The impact of the pandemic was greater in women for physical health, mental health and arthritis symptoms.• Many people reported negative pandemic impacts on lifestyle factors including weight and physical activity.
Negative ANA-IIF in SLE patients: what is beyond?
Authors: Abozaid Hanan Sayed M. , Hefny Hesham M. , Abualfadl Esam M. , Ismail Mohamad A. , Noreldin Amal K. , Eldin Ahmed N. Nour , Goda Asmaa M. , Ali Amal H. 
Published: April 2023

AbstractThe antinuclear antibody (ANA) test has high sensitivity in diagnosing and classifying systemic lupus erythematosus (SLE).ObjectivesTo describe the immunological pattern of SLE patients through investigating specific antinuclear autoantibodies by enzyme dot immunoassay and studying their frequency in both positive and negative ANA indirect immunofluorescence assay (IIF) cases.MethodsIn a cross-sectional study, blood samples from 393 newly diagnosed SLE patients were analyzed using (IIF) on HEp-2 cells and ANA dot immunoassay by automated enzyme immunoassay (EIA) to detect 19 antibodies.ResultsNinety-one percent of the patients are females; their mean age was 37 ± 12.28. Antinuclear antibody (ANA) was detected by IIF in 82.4% of cases, with 181 (46.1%) speckled and 167 (42.4%) homogeneous ANA patterns. The majority of patients (96%) demonstrated autoantibodies via EIA. Among the ANA-IIF-negative patients, 97.2% demonstrated autoantibodies. There was a significant difference in the frequency of certain autoantibodies between SLE patients with negative and positive ANA-IIF (1.44 0.73, 3.12 2.09,p = 0.00) respectively.ConclusionThe results of analyzing 19 autoantibodies with the ANA staining pattern increased the significance of analyzing the immune profile even if IIF is negative when clinical symptoms strongly suggest SLE diagnosis. Certain autoantibodies may evade staining by the IFA approach while they are present in the patient’s serum, and they may not be detected by the ANA EIA profile if it does not contain that antigenic substrate.Key Points•Indirect immunofluorescence on Hep-2 is the conventional method for ANA detection and is regarded as the “gold standard” for testing in clinical practice for SLE.•In our study, ANA profile dot enzyme immunoassay (EIA)-based test was performed to evaluate 19 autoantibodies in SLE patients either positive or negative for ANA-IIF.•The presence of anti-dsDNA with ANA-IIF-negative serum in 32.4% of SLE patients provides evidence that not all anti-dsDNA antibodies are identified on standard HEp-2 substrates.•certain autoantibodies can evade staining by the ANA-IIF method despite being present in the SLE patient’s blood; this supports the ANA profile enzyme dot immunoassay as a more sensitive test.
Investigating language and religiosity in Brunei
Authors: Sharbawi Salbrina 
Published: April 2023

AbstractThe inexplicable link between the Malay language and Islam has been well-documented in Malaysia. In Brunei, however, this association has not been made explicit and could only be inferred through the state’s stance of utilising only the Malay language for Islamic-related matters, most conspicuously in the Islamic education curriculum. While this practice has been in place since the early days of Islamic education in the country, the changing linguistic situation in Brunei, where English is now more popular than Malay among the younger generation, may require some rethinking of this practice. An earlier study investigating the issues of language and religion in Brunei has found that those who are more English-inclined do not identify strongly with the Muslim identity as their Malay-leaning counterparts. Taking its cue from those findings, the present study extends the investigation in two ways: one, by adding the social variables age, gender and educational background in its analysis; and two, by focusing on the notion of religiosity rather than on religious identity alone. The findings show that age and language proclivity are both predictors of religiosity with older Bruneians displaying greater religiosity than the younger ones. Language also plays a factor such that those who are predisposed to using more English than Malay have fewer manifestations of practices aligned to the Islamic teaching. Gender and educational level, however, have low factor loadings and are not contributory to the measurement of religiosity.
Sample average approximation of conditional value-at-risk based variational inequalities
Authors: Cherukuri Ashish 
Published: April 2023

AbstractThis paper focuses on a class of variational inequalities (VIs), where the map defining the VI is given by the component-wise conditional value-at-risk (CVaR) of a random function. We focus on solving the VI using sample average approximation, where solutions of the VI are estimated with solutions of a sample average VI that uses empirical estimates of the CVaRs. We establish two properties for this scheme. First, under continuity of the random map and the uncertainty taking values in a bounded set, we prove asymptotic consistency, establishing almost sure convergence of the solution of the sample average problem to the true solution. Second, under the additional assumption of random functions being Lipschitz, we prove exponential convergence where the probability of the distance between an approximate solution and the true solution being smaller than any constant approaches unity exponentially fast. The exponential decay bound is refined for the case where random functions have a specific separable form in the decision variable and uncertainty. We adapt these results to the case of uncertain routing games and derive explicit sample guarantees for obtaining a CVaR-based Wardrop equilibria using the sample average procedure. We illustrate our theoretical findings by approximating the CVaR-based Wardrop equilibria for a modified Sioux Falls network.