bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age, Sex, and BMI Influence on Copper, Zinc, and Their Major Serum Carrier Proteins in a Large European Population Including Nonagenarian Offspring From MARK-AGE Study
Authors: Piacenza Francesco , Giacconi Robertina , Costarelli Laura , Basso Andrea , Bürkle Alexander , Moreno-Villanueva María , Dollé Martijn E T , Jansen Eugène , Grune Tilman , Weber Daniela , Stuetz Wolfgang , Gonos Efstathios S , Schön Christiane , Bernhardt Jürgen , Grubeck-Loebenstein Beatrix , Sikora Ewa , Toussaint Olivier , Debacq-Chainiaux Florence , Franceschi Claudio , Capri Miriam , Hervonen Antti , Hurme Mikko , Slagboom Eline , Breusing Nicolle , Mocchegiani Eugenio , Malavolta Marco 
Published: May 2021

AbstractThe analysis of copper (Cu) and zinc (Zn) along with their major serum carriers, albumin (Alb) and ceruloplasmin (Cp), could provide information on the capacity of humans to maintain homeostasis of metals (metallostasis). However, their relationship with aging, sex, body mass index, as well as with nutritional and inflammatory markers was never investigated in a large-scale study. Here, we report results from the European large-scale cross-sectional study MARK-AGE in which Cu, Zn, Alb, Cp, as well as nutritional and inflammatory parameters were determined in 2424 age-stratified participants (35–75 years), including the general population (RASIG), nonagenarian offspring (GO), a well-studied genetic model of longevity, and spouses of GO (SGO). In RASIG, Cu to Zn ratio and Cp to Alb ratio were higher in women than in men. Both ratios increased with aging because Cu and Cp increased and Alb and Zn decreased. Cu, Zn, Alb, and Cp were found associated with several inflammatory as well as nutritional biomarkers. GO showed higher Zn levels and higher Zn to Alb ratio compared to RASIG, but we did not observe significant differences with SGO, likely as a consequence of the low sample size of SGO and the shared environment. Our results show that aging, sex, body mass index, and GO status are characterized by different levels of Cu, Zn, and their serum carrier proteins. These data and their relationship with inflammatory biomarkers support the concept that loss of metallostasis is a characteristic of inflammaging.
Long-Term Effectiveness of Oral Ferric Maltol vs Intravenous Ferric Carboxymaltose for the Treatment of Iron-Deficiency Anemia in Patients With Inflammatory Bowel Disease: A Randomized Controlled Noninferiority Trial
Authors: Howaldt Stefanie , Domènech Eugeni , Martinez Nicholas , Schmidt Carsten , Bokemeyer Bernd 
Published: May 2021

Abstract

Background
Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability.

Methods
In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, &lt;30 ng/mL/&lt;100 ng/mL with transferrin saturation &lt;20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center’s standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations.

Results
For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively.

Conclusions
Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.
Fecal Diversion for Perianal Crohn Disease in the Era of Biologic Therapies: A Multicenter Study
Authors: McCurdy Jeffrey D , Reid Jacqueline , Yanofsky Russell , Sinnathamby Vigigah , Medawar Edgar , Williams Lara , Bessissow Talat , Rosenfeld Greg 
Published: May 2021

AbstractBackgroundThe natural history of perianal Crohn disease (PCD) after fecal diversion in the era of biologics is poorly understood. We assessed clinical and surgical outcomes after fecal diversion for medically refractory PCD and determined the impact of biologics.MethodsWe performed a retrospective, multicenter study from 1999 to 2020. Patients who underwent fecal diversion for refractory PCD were stratified by diversion type (ostomy with or without proctectomy). Times to clinical and surgical outcomes were estimated using Kaplan-Meier methods, and the association with biologics was assessed using multivariable Cox proportional hazards models.ResultsEighty-two patients, from 3 academic institutions, underwent a total of 97 fecal diversions: 68 diversions without proctectomy and 29 diversions with proctectomy. Perianal healing occurred more commonly after diversion with proctectomy than after diversion without proctectomy (83% vs 53%; P = 0.021). Among the patients who had 68 diversions without proctectomy, with a median follow-up of 4.9 years post-diversion (interquartile range, 1.66-10.19), 37% had sustained healing, 31% underwent surgery to restore bowel continuity, and 22% underwent proctectomy. Ostomy-free survival occurred in 21% of patients. Biologics were independently associated with avoidance of proctectomy (hazard ratio, 0.32; 95% confidence interval, 0.11-0.98) and surgery to restore bowel continuity (hazard ratio, 3.10; 95% confidence interval, 1.02-9.37), but not fistula healing.ConclusionsIn this multicenter study, biologics were associated with bowel restoration and avoidance of proctectomy after fecal diversion without proctectomy for PCD; however, a minority of patients achieved sustained fistula healing after initial fecal diversion or after bowel restoration. These results highlight the refractory nature of PCD.
Russian News Media, Digital Media, Informational Learned Helplessness, and Belief in COVID-19 Misinformation
Authors: Nisbet Erik C , Kamenchuk Olga 
Published: May 2021

AbstractThe COVID-19 pandemic has been paired with a global misinformation “infodemic.” Citizens in authoritarian countries, where most media is state controlled, often do not have access to credible information sources to help combat misinformation. In fact, the news media in these countries may be the primary drivers of misinformation while digital media may be sources of more accurate information. We test how news and digital media in an authoritarian context are associated with endorsing misinformation while introducing the concept of informational learned helplessness as an additional factor driving inaccurate beliefs. We test our hypotheses employing data from a nationally representative telephone survey of the Russian public (N = 1600) and discuss the implications of our findings for Russian attitudes about COVID-19 vaccination.
Error estimate of a decoupled numerical scheme for the Cahn–Hilliard–Stokes–Darcy system
Authors: Chen Wenbin , Wang Shufen , Zhang Yichao , Han Daozhi , Wang Cheng , Wang Xiaoming 
Published: May 2021

Abstract
We analyze a fully discrete finite element numerical scheme for the Cahn–Hilliard–Stokes–Darcy system that models two-phase flows in coupled free flow and porous media. To avoid a well-known difficulty associated with the coupling between the Cahn–Hilliard equation and the fluid motion, we make use of the operator-splitting in the numerical scheme, so that these two solvers are decoupled, which in turn would greatly improve the computational efficiency. The unique solvability and the energy stability have been proved in Chen et al. (2017, Uniquely solvable and energy stable decoupled numerical schemes for the Cahn–Hilliard–Stokes–Darcy system for two-phase flows in karstic geometry. Numer. Math., 137, 229–255). In this work, we carry out a detailed convergence analysis and error estimate for the fully discrete finite element scheme, so that the optimal rate convergence order is established in the energy norm, i.e., in the $\ell ^{\infty } (0, T; H^1) \cap \ell ^2 (0, T; H^2)$ norm for the phase variables, as well as in the $\ell ^{\infty } (0, T; H^1) \cap \ell ^2 (0, T; H^2)$ norm for the velocity variable. Such an energy norm error estimate leads to a cancelation of a nonlinear error term associated with the convection part, which turns out to be a key step to pass through the analysis. In addition, a discrete $\ell ^2 (0;T; H^3)$ bound of the numerical solution for the phase variables plays an important role in the error estimate, which is accomplished via a discrete version of Gagliardo–Nirenberg inequality in the finite element setting.
MicroRNAs: immune modulators in cancer immunotherapy
Authors: Xing Yun , Wang Zhiqiang , Lu Zhou , Xia Jie , Xie Zhangjuan , Jiao Mengxia , Liu Ronghua , Chu Yiwei 
Published: May 2021

Summary
MicroRNA (miRNA) is a class of endogenous small non-coding RNA of 18–25 nucleotides and plays regulatory roles in both physiological and pathological processes. Emerging evidence support that miRNAs function as immune modulators in tumors. MiRNAs as tumor suppressors or oncogenes are also found to be able to modulate anti-tumor immunity or link the crosstalk between tumor cells and immune cells surrounding. Based on the specific regulating function, miRNAs can be used as predictive, prognostic biomarkers, and therapeutic targets in immunotherapy. Here, we review new findings about the role of miRNAs in modulating immune responses, as well as discuss mechanisms underlying their dysregulation, and their clinical potentials as indicators of tumor prognosis or to sensitize cancer immunotherapy.
Targeted ordering of investigations reduces costs of treatment for surgical inpatients
Authors: Adhikari Ashim Nath , Beck Matthew Dylan , Wykes James Justin , Ashford Bruce Graham 
Published: May 2021

Abstract

Background
Laboratory testing forms an important part of diagnostic investigation in modern medicine; however, the overuse of ‘routine blood tests’ can result in significant potential harm and financial cost to the patient and the healthcare system. In 2018, a new protocol targeting the ordering of investigations was implemented within the General Surgical Teams of Wollongong Hospital in New South Wales, an Australian tertiary referral hospital, to reduce the number of ‘routine blood tests’ as a quality improvement initiative.

Objective
To identify whether there was a reduction in the number of ‘routine blood tests’ and associated costs following implementation of the new protocol.

Methods
The protocol involved regular review of the laboratory investigations being ordered for the following day with a senior team member. The medical records of all patients admitted under the general surgery service at Wollongong Hospital were retrospectively reviewed over two 10-week periods in 2017 and 2018 (control and study, respectively). The casemix was categorized into Minor, Intermediate, Major or Unscored, depending on case complexity coding.

Results
A total of 838 patients were identified during the control period (2017) and 805 patients were identified during the study period (2018). Ten thousand and thirty tests were included in the control period, compared to 8610 over the study period, resulting in a 16% (or greater) reduction in ‘routine blood tests’ per patient, per day of admission and a 6% reduction in costs in the study group (P &lt; 0.001).

Conclusion
Targeted ordering of investigations with personalized education and feedback to junior staff during review of clinical status of each patient as a part of normal workflow can reduce inappropriate ordering of ‘routine blood tests’ and associated costs to the patient and the healthcare system.
Beyond Methodological Axioms
Authors: Blum Jason 
Published: May 2021

AbstractSince nearly the field’s birth, religious studies has been plagued by the question of how to deal with claims concerning the supernatural. Strategies for addressing the issue typically take the form of one or another methodological axiom, typically either methodological atheism or methodological agnosticism. Although each axiom answers legitimate concerns about how to address supernatural claims, each is also vulnerable to substantial objections. I therefore argue that these approaches to solving religious studies’ central methodological dilemma is flawed. Eschewing the search for methodological axioms, I advocate that we return to a basic standard of academic work: public evidence. When paired with a distinction between the analytical tasks of interpretation and explanation, this approach resolves the central problems that have vexed both methodological atheism and methodological agnosticism, avoiding the theoretical pitfalls generated by each while providing the necessary guidance and discipline for research on religion.
The use of continuous electronic prescribing data to infer trends in antimicrobial consumption and estimate the impact of stewardship interventions in hospitalized children
Authors: Channon-Wells S. , Kwok M. , Booth J. , Bamford A. , Konstanty P. , Hatcher J. , Dixon G. , Diggle P. J. , Standing J. F. , Irwin A. D. 
Published: May 2021

Abstract

Background
Understanding antimicrobial consumption is essential to mitigate the development of antimicrobial resistance, yet robust data in children are sparse and methodologically limited. Electronic prescribing systems provide an important opportunity to analyse and report antimicrobial consumption in detail.

Objectives
We investigated the value of electronic prescribing data from a tertiary children’s hospital to report temporal trends in antimicrobial consumption in hospitalized children and compare commonly used metrics of antimicrobial consumption.

Methods
Daily measures of antimicrobial consumption [days of therapy (DOT) and DDDs] were derived from the electronic prescribing system between 2010 and 2018. Autoregressive moving-average models were used to infer trends and the estimates were compared with simulated point prevalence surveys (PPSs).

Results
More than 1.3 million antimicrobial administrations were analysed. There was significant daily and seasonal variation in overall consumption, which reduced annually by 1.77% (95% CI 0.50% to 3.02%). Relative consumption of meropenem decreased by 6.6% annually (95% CI −3.5% to 15.8%) following the expansion of the hospital antimicrobial stewardship programme. DOT and DDDs exhibited similar trends for most antimicrobials, though inconsistencies were observed where changes to dosage guidelines altered consumption calculation by DDDs, but not DOT. PPS simulations resulted in estimates of change over time, which converged on the model estimates, but with much less precision.

Conclusions
Electronic prescribing systems offer significant opportunities to better understand and report antimicrobial consumption in children. This approach to modelling administration data overcomes the limitations of using interval data and dispensary data. It provides substantially more detailed inferences on prescribing patterns and the potential impact of stewardship interventions.
Shutting the gate before the horse has bolted: is it time for a conversation about SARS-CoV-2 and antiviral drug resistance?
Authors: Hiscox Julian A. , Khoo Saye H. , Stewart James P. , Owen Andrew 
Published: May 2021

AbstractThis article provides a brief overview of drug resistance to antiviral therapy as well as known and emergent variability in key SARS-CoV-2 viral sequences. The purpose is to stimulate deliberation about the need to consider drug resistance prior to widespread roll-out of antivirals for SARS-CoV-2. Many existing candidate agents have mechanisms of action involving drug targets likely to be critical for future drug development. Resistance emerged quickly with monotherapies deployed for other pulmonary viruses such as influenza virus, and in HIV mutations in key drug targets compromised efficacy of multiple drugs within a class. The potential for drug resistance in SARS-CoV-2 has not yet been rigorously debated or assessed, and we call for more academic and industry research on this potentially important future threat prior to widespread roll-out of monotherapies for COVID-19 treatment and prevention.
Accessibility evaluation of COVID-19 vaccine registration websites across the United States
Authors: Alismail Sarah , Chipidza Wallace 
Published: May 2021

Abstract
This exploratory study investigated the web accessibility of 54 official COVID-19 vaccine registration websites in the US and their concordance with the WCAG 2.0 and 2.1 guidelines. We employed AChecker, WAVE, and SortSite web accessibility evaluation tools to conduct automated analyses of these websites. The results showed suboptimal compliance with WCAG 2.0 and 2.1 guidelines, as determined using the AChecker, WAVE, and SortSite tools. These shortcomings in compliance may pose difficulties to users with disabilities as they access information on the websites. Based on our findings, we offered recommendations for states and other authorities to improve the accessibility of their websites to ensure that users with disabilities can independently schedule vaccination appointments.
Tooth bending strength of gears with a progressive curved path of contact
Authors: Zorko Damijan , Duhovnik Jože , Tavčar Jože 
Published: May 2021

Abstract
The article presents a comprehensive study on the tooth bending strength of spur gears with a progressive curved path of contact, or so-called S-gears. Systematic gear meshing simulations were conducted to study the effects of S-gear geometry parameters on tooth bending strength. Different S-gear geometries were analysed in a systematically organized manner, and a comparison was made against a standard 20° pressure angle involute shape. Furthermore, different material combinations, e.g. polymer/polymer, steel/polymer, and steel/steel, of both drive and driven gear were analysed within a meaningful range of loads. The gear profile shape, material combination of the drive and the driven gear, and the transmitted load were found as the main parameters affecting gear tooth bending stress. Complex, non-linear relations between the recognized effects and the corresponding root stress were observed. Based on the numerical results, a shape factor, which considers the above-mentioned effects, was introduced, and a model for root strength control of S-gears was proposed and verified employing the finite element method (FEM).
Underground heterosis for yield improvement in melon
Authors: Dafna Asaf , Halperin Ilan , Oren Elad , Isaacson Tal , Tzuri Galil , Meir Ayala , Schaffer Arthur A , Burger Joseph , Tadmor Yaakov , Buckler Edward S , Gur Amit 
Published: May 2021

Abstract
Heterosis, the superiority of hybrids over their parents, is a major genetic force associated with plant fitness and crop yield enhancement. We investigated root-mediated yield heterosis in melons (Cucumis melo) by characterizing a common variety grafted onto 190 hybrid rootstocks, resulting from crossing 20 diverse inbreds in a diallel-mating scheme. Hybrid rootstocks improved yield by more than 40% compared with their parents, and the best hybrid yield outperformed the reference commercial variety by 65% under both optimal and minimal irrigation treatments. To characterize the genetics of underground heterosis we conducted whole genome re-sequencing of the 20 founder lines, and showed that parental genetic distance was no predictor for the level of heterosis. Through inference of the 190 hybrid genotypes from their parental genomes, followed by genome-wide association analysis, we mapped multiple quantitative trait loci for root-mediated yield. Yield enhancement of the four best-performing hybrid rootstocks was validated in multiple experiments with four different scion varieties. Our grafting approach is complementary to the common roots genetic approach that focuses mainly on variation in root system architecture, and is a step towards discovery of candidate genes involved in root function and yield enhancement.
Distribution and genotypic analysis of Enterocytozoon bieneusi from wild boars in Korea
Authors: Lee Haeseung , Seo Min-Goo , Lee Seung-Hun , Oem Jae-Ku , Kim Seon-Hee , Jeong Hyesung , Kim Yongkwan , Jheong Weon-Hwa , Kwon Oh-Deog , Kwak Dongmi 
Published: May 2021

Abstract

Enterocytozoon bieneusi, an important microsporidian fungus, causes chronic diarrhea in humans and animals worldwide. Out of the 502 fecal samples from wild boars, 13 were positive for the E. bieneusi internal transcribed spacer region, with a prevalence of 2.6%. Six E. bieneusi genotypes, D, EbpC, and four novel KWB1–KWB4, were identified with zoonotic potential. Genotypes D (subgroup 1a) and EbpC (subgroup 1d) were first reported in Korean swine and Korea, respectively; KWB1–KWB4 (subgroup 1e) were most prevalent in this study. Because zoonotic genotypes have been identified, E. bieneusi transmission through wild boars must be closely monitored for proper prevention and treatment, despite their low prevalence.

Lay Summary
Enterocytozoon bieneusi is an important microsporidian fungus. Its sequences from wild boars were identified with zoonotic potential. Genotypes D and EbpC were first reported in Korean swine and Korea, respectively. E. bieneusi should be closely monitored to properly prevent and treat animals.
Observable spectral and angular distributions of γ-rays from extragalactic ultrahigh energy cosmic ray accelerators: the case of extreme TeV blazars
Authors: Khalikov Emil V , Dzhatdoev Timur A 
Published: May 2021

ABSTRACT
Ultrahigh energy protons and nuclei from extragalactic cosmic ray sources initiate intergalactic electromagnetic cascades, resulting in observable fluxes of γ-rays in the GeV–TeV energy domain. The total spectrum of such cascade γ-rays of hadronic nature is significantly harder than the one usually expected from blazars. The spectra of some sources known as ‘extreme TeV blazars’ could be well-described by this ‘intergalactic hadronic cascade model’ (IHCM). We calculate the shape of the observable point-like spectrum, as well as the observable angular distibution of γ-rays, for the first time taking into account the effect of primary proton deflection in filaments and galaxy clusters of the extragalactic magnetic field assuming the model of Dolag et al. (2005). We present estimates of the width of the observable γ-ray angular distribution derived from simple geometrical considerations. We also employ a hybrid code to compute the observable spectral and angular distributions of γ-rays. The observable point-like spectrum at multi-TeV energies is much softer than the one averaged over all values of the observable angle. The presence of a high-energy cutoff in the observable spectra of extreme TeV blazars in the framework of the IHCM could significantly facilitate future searches of new physics processes that enhance the apparent γ-ray transparency of the Universe (for instance, γ → ALP oscillations). The width of the observable angular distribution is greater than or comparable to the extent of the point spread function of next-generation γ-ray telescopes.