bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omicron – The new SARS‐CoV‐2 challenge?
Authors: Lino A. , Cardoso M. A. , Martins‐Lopes P. , Gonçalves H. M. R. 
Published: April 2022

AbstractSARS‐CoV‐2 virus has infected nearly 300 M people worldwide and has been associated with over 6 M deaths by March 2022. Since the virus emergence in December 2019 in Wuhan, several new mutations have been described. The World Health Organization has developed a working name for these emerging variants according to their impact on the worldwide population. In this context a high alert has been paid to variants of concern (VOC) due to their high infectiousness and transmissibility patterns. The most recent VOC, Omicron (B.1.1.529), has become dominant in the shortest time ever and has placed Europe under an overwhelming and unprecedented number of new cases. This variant has numerous mutations in regions that are associated with higher transmissibility, stronger viral binding, affinity and antibody escape. Moreover, the mutations and deletions present in the spike protein suggest that the SARS‐CoV‐2 specific attachment inhibitors may not be the best option for Omicron therapy. Omicron is the dominant variant circulating worldwide and, at the end of February 2022, it was responsible for nearly all sequences reported to GISAID. Omicron is made up of several sublineages, where the most common are BA.1 and BA.2 (or Nextstrain clade 21K and 21L, respectively). At a global level, it is possible to say that the proportion of BA.2 has been increasing relative to BA.1 and in some countries it has been replacing it at high rates. In order to better assess the Omicron effectiveness on antibody escape, spread and infectious ability it is of the highest relevance to maintain a worldwide tight surveillance. Even though this variant has been associated with a lower death rate, it is important to highlight that the number of people becoming infected is concerning and that further unpredictable mutations may emerge as the number of infected people rises.
Bisphosphonates on Smooth TiO2: Modeling and Characterization
Authors: Dias Leonardo F. G. , Rheinheimer João P. C. , Gomes Orisson P. , Noeske Michael , Stamboroski Stephani , Bronze‐Uhle Erika S. , Mainardi Maria C. , Cavalcanti Welchy L. , Neto Augusto B. , Lisboa‐Filho Paulo N. 
Published: April 2022

AbstractThis paper presents insights into surfaces properties of sputter‐deposited titania modified with bisphosphonates, including zeta potential measurements in a pH range. Functionalization was investigated through simulation and experimental approaches to model the adsorbate and evaluate structure‐response relationships. Molecules of etidronic, alendronic, and risedronic acids were investigated through density functional theory. The molecules vary their reactivity through similar structures considering different scenarios. X‐ray photoelectron spectroscopy of titania/BP systems demonstrated that functionalization occurs in a short time and resulted in a predominantly “side‐on” adsorbate configuration after two hours of immersion. Zeta potential showed the predominancy of negative charges deprotonated free phosphonates. Water contact angle demonstrated that titania surfaces are hydrophilic after overnight functionalization. Atomic force measurements of bisphosphonates layers suggested that the molecular anions follow the surface topography, unchanging the surface roughness.
Detection of L‐Aspartic Acid and L‐Glutamic Acid in Water Using a Fluorescent Nanoparticle Constructed by Pillar[5]arene‐Based Molecular Recognition
Authors: Shi Bingbing , Zhao Xing‐Xing , Chai Yongping , Qin Peng , Qu Wen‐Juan , Lin Qi , Zhang You‐Ming 
Published: April 2022

AbstractAspartic acid and glutamic acid show critical impact in the central nervous system as excitatory neurotransmitters. The selective detection of aspartic acid and glutamic acid has a wide range of potential applications in the field of biomedicine. In this work, we report the highly selective detection of L‐Aspartic acid (L‐Asp) and L‐Glutamic acid (L‐Glu) in water is achieved by using a fluorescent nanoparticle constructed by a water‐soluble pillar[5]arene‐based host‐guest interactions. These nanoparticles show strong fluorescent emission in water. After the addition of L‐Asp or L‐Glu to a solution of the fluorescent nanoparticles, these nanoparticles transformed to nanosheets with weak fluorescent emission, resulting the highly selective detection of aspartic acid and glutamic acid in water. The detection limits of the fluorescent nanoparticles toward L‐Asp and L‐Glu were calculated to be 2.09×10−7 M and 4.03×10−7 M, respectively. This work provide an efficiency way for highly sensitive detection of L‐Asp and L‐Glu in water.
A comparison of integrated and designated ELD models on second and third graders' oral English language proficiency
Authors: Edelman Emily R. , Amirazizi Samira A. , Feinberg Daniel K. , Quirk Matthew , Scheller Jennifer , Pagán Carlos R. , Persoon Jamie 
Published: April 2022

This article reports on a longitudinal, quasi‐experimental comparison of two English language development (ELD) models implemented from kindergarten through Grade 3 to support oral English language development among Spanish‐speaking English language learners (ELLs). Specifically, the study examined oral English language proficiency among students who received only integrated English language development (I‐ELD; n = 39) and students who received I‐ELD with 30 minutes of daily designated ELD (D‐ELD) entailing four specific routines and strategies (n = 65). The study also compared oral proficiency with English‐only speakers (EO) from the same school (n = 47). Oral language proficiency was measured by the IDEA Proficiency Test (IPT I‐Oral; Ballard & Tighe, 2017). A repeated‐measures analysis of variance (ANOVA) across Grades 2 and 3 indicated significant (p < .001; η2 = 0.53) increases in oral proficiency for ELL students who received D‐ELD. A follow‐up analysis of covariance (ANCOVA) indicated significant positive effects (p < .001; η2 = 0.19) of the D‐ELD approach on ELL students' oral proficiency compared to only I‐ELD in Grade 3. The ANCOVA also found no significant (p > .05) differences in oral proficiency between ELL students who received D‐ELD and EO students in Grade 3, indicating similar oral English skills. The D‐ELD model's instructional strategies and practical implications are discussed.
Protective effect of lupeol on arthritis induced by type II collagen via the suppression of P13K/AKT signaling pathway in Sprague dawley rats
Authors: Song Tiebing , Shi Renhong , Vijayalakshmi Annamalai , Lei Bin 
Published: April 2022

AbstractTo explore the therapeutic value of lupeol on collagen‐induced arthritis (CIA) in rats, a rheumatoid arthritis model. Lupeol is well known pentacyclic triterpene found in various plant sources, which possess anti‐inflammatory and antioxidant actions. The current study was assessed the anti‐arthritic potential of lupeol and its molecular mechanisms as compared with indomethacin (Indo) in collagen‐induced arthritis CIA rats. The rats were randomly alienated into five groups: Control, CIA alone, CIA + lupeol (10 mg/kg bw), CIA + Indomethacin (3 mg/kg bw), and lupeol (10 mg/kg bw) alone. The paw volume, biochemical, hematological parameters, inflammatory enzymes, and cytokines were measured. As well protein expression of apoptotic proteins, and histopathological of ankle joint were examined. Inflammatory markers, cytokines, histological changes, paw volume, and inflammation were intensely reduced and enhanced apoptosis by lupeol. Alterations in hematological parameters, rheumatoid factor, C‐reactive protein, and ceruloplasmin in arthritis were reverted by lupeol. Protein expressions of Bcl‐2, and P13K/Akt signaling were declined, whereas the Bax, caspssae‐3, and caspase‐9 were elevated. These results highlighted that lupeol suppresses P13K/Akt signaling and has a promising anti‐arthritic potential for collagen‐induced rheumatic arthritis treatment. Hence lupeol would be suggested as an alternative natural source with potent anti‐inflammatory and apoptotic actions for chronic inflammatory disorders.
Deltamethrin induces apoptosis in cerebrum neurons of quail via promoting endoplasmic reticulum stress and mitochondrial dysfunction
Authors: Li Siyu , Wu Pengfei , Han Bing , Yang Qingyue , Wang Xiaoqiao , Li Jiayi , Deng Ning , Han Biqi , Liao Yuge , Liu Yan , Zhang Zhigang 
Published: April 2022

AbstractDeltamethrin (DLM) is a widely used and highly effective insecticide. DLM exposure is harmful to animal and human. Quail, as a bird model, has been widely used in the field of toxicology. However, there is little information available in the literature about quail cerebrum damage caused by DLM. Here, we investigated the effect of DLM on quail cerebrum neurons. Four groups of healthy quails were assigned (10 quails in each group), respectively given 0, 15, 30, and 45 mg/kg DLM by gavage for 12 weeks. Through the measurements of quail cerebrum, it was found that DLM exposure induced obvious histological changes, oxidative stress, and neurons apoptosis. To further explore the possible molecular mechanisms, we performed real‐time quantitative PCR to detect the expression of endoplasmic reticulum (ER) stress‐related mRNA such as glucose regulated protein 78 kD, activating transcription factor 6, inositol requiring enzyme, and protein kinase RNA (PKR)‐like ER kinase. In addition, we detected ATP content in quail cerebrum to evaluate the functional status of mitochondria. The study showed that DLM exposure significantly increased the expression of ER stress‐related mRNA and decreased ATP content in quail cerebrum tissues. These results suggest that chronic exposure to DLM induces apoptosis of quail cerebrum neurons via promoting ER stress and mitochondrial dysfunction. Furthermore, our results provide a novel explanation for DLM‐induced apoptosis of avian cerebrum neurons.
A novel approach to consider triaxial tensile stresses within the framework of a failure criterion
Authors: Roetsch Karl , Horst Thomas 
Published: April 2022

AbstractFor use in micromechanical simulations of continuous fiber reinforced polymers, a more general form of the paraboloid failure criterion by Stassi‐D'Alia for matrix failure was developed with explicit consideration of the hydrostatic tension strength. Regarding polymers, limits for hydrostatic tensile strength based on isotropic linear elasticity could be derived. The comparison of the newly developed extended paraboloid criterion with experimental data for yielding as well as for material separation (fracture) shows good agreement.
Socio-Technical Innovation Bundles Tailored to Distinct Agri-Food Systems
Authors: Barrett Christopher B. , Benton Tim , Fanzo Jessica , Herrero Mario , Nelson Rebecca J. , Bageant Elizabeth , Buckler Edward , Cooper Karen , Culotta Isabella , Fan Shenggen , Gandhi Rikin , James Steven , Kahn Mark , Lawson-Lartego Laté , Liu Jiali , Marshall Quinn , Mason-D’Croz Daniel , Mathys Alexander , Mathys Cynthia , Mazariegos-Anastassiou Veronica , Miller Alesha , Misra Kamakhya , Mude Andrew , Shen Jianbo , Sibanda Lindiwe Majele , Song Claire , Steiner Roy , Thornton Philip , Wood Stephen 
Published: April 2022

AbstractScientific discovery is neither linear nor predictable. The time it takes to develop breakthrough technologies varies enormously among application domains. Some basic scientific discoveries remain elusive and will need continued, concerted funding and attention in the years and decades ahead. In some cases, the stumbling block is the scientific advancement per se, when important discoveries along the path towards technological readiness have not yet been made.
Artificial Intelligence in Education and Ethics
Authors: du Boulay Benedict 
Published: April 2022

AbstractThis chapter traces the ethical issues around applying artificial intelligence (AI) in education from the early days of artificial intelligence in education in the 1970s to the current state of this field, including the increasing sophistication of the system interfaces and the rise in data use and misuse. While in the early days most tools were largely learner-facing, now there are tools that are teacher-facing, supporting their management of the classroom, and administrator-facing, assisting in their management of cohorts of students. Learner-facing tools now take into account the affective and motivational aspects of learning as well as the cognitive. The rise of data collection and its associated analytic tools has enabled the development of dashboards for the dynamic management and reflective understanding of learners, teachers, and administrators. Ethical issues hardly figured in the early days of the field but now they loom large. This is because of the legitimate fears that learners’ and teachers’ autonomy will be compromised, that learner data will be collected and potentially misappropriated for other purposes, and that AI will introduce extra biases into educational decisions and increase existing inequity and also because of the scary reputation that AI has in general.
Impact of phosphorylation of heat shock protein 27 on the expression profile of periodontal ligament fibroblasts during mechanical strain
Authors: Schröder Agnes , Wagner Kathrin , Cieplik Fabian , Spanier Gerrit , Proff Peter , Kirschneck Christian 
Published: April 2022

Abstract
Purpose
Orthodontic tooth movement is a complex process involving the remodeling of extracellular matrix and bone as well as inflammatory processes. During orthodontic treatment, sterile inflammation and mechanical loading favor the production of receptor activator of NF-κB ligand (RANKL). Simultaneously, expression of osteoprotegerin (OPG) is inhibited. This stimulates bone resorption on the pressure side. Recently, heat shock protein 27 (HSP27) was shown to be expressed in the periodontal ligament after force application and to interfere with inflammatory processes.

Methods
We investigated the effects of phosphorylated HSP27 on collagen synthesis (COL1A2 mRNA), inflammation (IL1B mRNA, IL6 mRNA, PTGS2 protein) and bone remodeling (RANKL protein, OPG protein) in human periodontal ligament fibroblasts (PDLF) without and with transfection of a plasmid mimicking permanent phosphorylation of HSP27 using real-time quantitative polymerase chain reaction (RT-qPCR), western blot and enzyme-linked immunosorbent assays (ELISAs). Furthermore, we investigated PDLF-induced osteoclastogenesis after compressive strain in a co-culture model with human macrophages.

Results
In particular, phosphorylated HSP27 increased gene expression of COL1A2 and protein expression of PTGS2, while IL6 mRNA levels were reduced. Furthermore, we observed an increasing effect on the RANKL/OPG ratio and osteoclastogenesis mediated by PDLF.

Conclusion
Phosphorylation of HSP27 may therefore be involved in the regulation of orthodontic tooth movement by impairment of the sterile inflammation response and osteoclastogenesis.
Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial
Authors: Waijer Simke W. , Vart Priya , Cherney David Z. I. , Chertow Glenn M. , Jongs Niels , Langkilde Anna Maria , Mann Johannes F. E. , Mosenzon Ofri , McMurray John J. V. , Rossing Peter , Correa-Rotter Ricardo , Stefansson Bergur V. , Toto Robert D. , Wheeler David C. , Heerspink Hiddo J. L. 
Published: April 2022

Abstract
Aims/hypothesis
In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin reduced the risks of progressive kidney disease, hospitalised heart failure or cardiovascular death, and death from all causes in patients with chronic kidney disease (CKD) with or without type 2 diabetes. Patients with more severe CKD are at higher risk of kidney failure, cardiovascular events and all-cause mortality. In this post hoc analysis, we assessed the efficacy and safety of dapagliflozin according to baseline Kidney Disease Improving Global Outcomes (KDIGO) risk categories.

Methods
DAPA-CKD was a double-blind, placebo-controlled trial that randomised patients with an eGFR of 25–75 ml min−1 [1.73 m]−2 and urinary albumin/creatinine ratio (UACR) of ≥22.6 and <565.0 mg/mmol (200–5000 mg/g) to dapagliflozin 10 mg/day or placebo. The primary endpoint was a composite of ≥50% reduction in eGFR, end-stage kidney disease (ESKD), and death from a kidney or cardiovascular cause. Secondary endpoints included a kidney composite (≥50% reduction in eGFR, ESKD and death from a kidney cause), a cardiovascular composite (heart failure hospitalisation or cardiovascular death), and death from all causes. We used Cox proportional hazards regression analyses to assess relative and absolute effects of dapagliflozin across KDIGO risk categories.

Results
Of the 4304 participants in the DAPA-CKD study, 619 (14.4%) were moderately high risk, 1349 (31.3%) were high risk and 2336 (54.3%) were very high risk when categorised by KDIGO risk categories at baseline. Dapagliflozin reduced the hazard of the primary composite (HR 0.61; 95% CI 0.51, 0.72) and secondary endpoints consistently across KDIGO risk categories (all p for interaction >0.09). Absolute risk reductions for the primary outcome were also consistent irrespective of KDIGO risk category (p for interaction 0.26). Analysing patients with and without type 2 diabetes separately, the relative risk reduction with dapagliflozin in terms of the primary outcome was consistent across subgroups of KDIGO risk categories. The relative frequencies of adverse events and serious adverse events were also similar across KDIGO risk categories.

Conclusion/interpretations
The consistent benefits of dapagliflozin on kidney and cardiovascular outcomes across KDIGO risk categories indicate that dapagliflozin is efficacious and safe across a wide spectrum of kidney disease severity.

Trial registration
ClinicalTrials.gov NCT03036150.

Funding
The study was funded by AstraZeneca.

Graphical abstract
Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia
Authors: Meyhöfer Svenja , Dembinski Katharina , Schultes Bernd , Born Jan , Wilms Britta , Lehnert Hendrik , Hallschmid Manfred , Meyhöfer Sebastian M. 
Published: April 2022

Abstract
Aims/hypothesis
Attenuated counterregulation after recurrent hypoglycaemia is a major complication of diabetes treatment. As there is previous evidence for the relevance of sleep in metabolic control, we assessed the acute contribution of sleep to the counterregulatory adaptation to recurrent hypoglycaemia.

Methods
Within a balanced crossover design, 15 healthy, normal-weight male participants aged 18–35 years underwent three hyperinsulinaemic–hypoglycaemic clamps with a glucose nadir of 2.5 mmol/l, under two experimental conditions, sleep and sleep deprivation. Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8 h sleep vs sleep deprivation. The counterregulatory response of relevant hormones (glucagon, growth hormone [GH], ACTH, cortisol, adrenaline [epinephrine] and noradrenaline [norepinephrine]) was measured, and autonomic and neuroglycopenic symptoms were assessed.

Results
Sleep deprivation compared with sleep dampened the adaptation to recurrent hypoglycaemia for adrenaline (p=0.004), and this pattern also emerged in an overall analysis including adrenaline, GH and glucagon (p=0.064). After regular sleep, the counterregulatory responses of adrenaline (p=0.005), GH (p=0.029) and glucagon (p=0.009) were attenuated during the 3rd clamp compared with the 1st clamp, but were preserved after sleep deprivation (all p>0.225). Neuroglycopenic and autonomic symptoms during the 3rd clamp compared with the 1st clamp were likewise reduced after sleep (p=0.005 and p=0.019, respectively). In sleep deprivation, neuroglycopenic symptoms increased (p=0.014) and autonomic symptoms were unchanged (p=0.859).

Conclusions/interpretation
The counterregulatory adaptation to recurrent hypoglycaemia is compromised by sleep deprivation between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neurometabolic memory, and may be a potential target of interventions to treat hypoglycaemia unawareness syndrome.

Graphical abstract
Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application
Authors: Kuo Byron , Beal Marc A. , Wills John W. , White Paul A. , Marchetti Francesco , Nong Andy , Barton-Maclaren Tara S. , Houck Keith , Yauk Carole L. 
Published: April 2022

AbstractRisk assessments are increasingly reliant on information from in vitro assays. The in vitro micronucleus test (MNvit) is a genotoxicity test that detects chromosomal abnormalities, including chromosome breakage (clastogenicity) and/or whole chromosome loss (aneugenicity). In this study, MNvit datasets for 292 chemicals, generated by the US EPA’s ToxCast program, were evaluated using a decision tree-based pipeline for hazard identification. Chemicals were tested with 19 concentrations (n = 1) up to 200 µM, in the presence and absence of Aroclor 1254-induced rat liver S9. To identify clastogenic chemicals, %MN values at each concentration were compared to a distribution of batch-specific solvent controls; this was followed by cytotoxicity assessment and benchmark concentration (BMC) analyses. The approach classified 157 substances as positives, 25 as negatives, and 110 as inconclusive. Using the approach described in Bryce et al. (Environ Mol Mutagen 52:280–286, 2011), we identified 15 (5%) aneugens. IVIVE (in vitro to in vivo extrapolation) was employed to convert BMCs into administered equivalent doses (AEDs). Where possible, AEDs were compared to points of departure (PODs) for traditional genotoxicity endpoints; AEDs were generally lower than PODs based on in vivo endpoints. To facilitate interpretation of in vitro MN assay concentration–response data for risk assessment, exposure estimates were utilized to calculate bioactivity exposure ratio (BER) values. BERs for 50 clastogens and two aneugens had AEDs that approached exposure estimates (i.e., BER < 100); these chemicals might be considered priorities for additional testing. This work provides a framework for the use of high-throughput in vitro genotoxicity testing for priority setting and chemical risk assessment.
An Automaton Group with PSPACE-Complete Word Problem
Authors: Wächter Jan Philipp , Weiß Armin 
Published: April 2022

AbstractWe construct an automaton group with a -complete word problem, proving a conjecture due to Steinberg. Additionally, the constructed group has a provably more difficult, namely -complete, compressed word problem and acts over a binary alphabet. Thus, it is optimal in terms of the alphabet size. Our construction directly simulates the computation of a Turing machine in an automaton group and, therefore, seems to be quite versatile. It combines two ideas: the first one is a construction used by D’Angeli, Rodaro and the first author to obtain an inverse automaton semigroup with a -complete word problem and the second one is to utilize a construction used by Barrington to simulate Boolean circuits of bounded degree and logarithmic depth in the group of even permutations over five elements.
A (2,3)-complete intersection fourfold with no decomposition of the diagonal
Authors: Skauli Bjørn 
Published: April 2022

AbstractWe apply the specialization technique based on the decomposition of the diagonal to the intersection of a quadric and cubic hypersurface in $$\mathbb {P}^6$$

P

6

. We find an explicit example defined over $$\mathbb {Q}$$
Q
that is smooth, and does not admit a decomposition of the diagonal, and is therefore not retract rational. The proof uses the specialization of Nicaise and Ottem (Tropical degenerations and stable rationality, 2020), who proved that the very general complete intersection of this type is stably irrational using the motivic volume.