bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and biological evaluation of salophen nickel(II) and cobalt(III) complexes as potential anticancer compounds
Authors: Ma Benjamin N. , Baecker Daniel , Descher Hubert , Brandstaetter Philipp , Hermann Martin , Kircher Brigitte , Gust Ronald
Published: February 2023

Recent in vitro investigations of N,N′‐bis(salicylidene)‐1,2‐phenylenediamine (SAP) iron(III) complexes substituted with alkyl (ethyl, propyl, butyl) carboxylates at position 4 in tumor and leukemia cells revealed strong cytotoxic activity. In continuation of this study, analogous nickel(II) and cobalt(III) complexes were synthesized and tested in HL‐60 leukemia, and cisplatin‐sensitive and ‐resistant A2780 ovarian cancer cell lines. The biological activity depended on the extent of cellular uptake and the formation of reactive oxygen species (ROS). Inactive [(Ni(II)SAP] complexes (1−3) only marginally accumulated in tumor cells and did not induce ROS. The cellular uptake of [Co(III)SAP]Cl complexes (4−6) into the cells depended on the length of the ester alkyl chain (ethyl, 4 < propyl, 5 < butyl, 6). The cytotoxicity correlated with the presence of ROS. The low cytotoxic complex 4 induced only few ROS, while 5 and 6 caused a good to outstanding antiproliferative activity, exerted high ROS generation, and induced cell death after 48 h. Necrostatin‐1 prevented the biological effects, proving necroptosis as part of the mode of action. Interestingly, the effects of 5 and 6 were not reversed by Ferrostatin‐1, but even enhanced upon simultaneous application to the tumor cells.
Reactivity of Oxygen‐Bridged Geminal Al/P and Si/P Frustrated Lewis Pairs towards Heterocumulenes
Authors: Wickemeyer Lucas , Trapp Pia C. , Aders Niklas , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W.
Published: February 2023

The two oxygen‐bridged geminal frustrated Lewis pairs (FLP) tBu2P−O−AlBis2 (Bis=CH(SiMe3)2; 1) and tBu2P−O−Si(C2F5)3 (2) were reacted with the heterocumulenes PhNCO, PhOCN, PhNCS, CS2 and PhNSO as well as SO2. With isocyanate and cyanate, both 1 and 2, form addition products under formation of five‐membered rings. With CS2, isothiocyanate and sulfinylaniline, only 1 forms stable adducts, whereas 2 shows reactivity towards sulfinylaniline, but the product decomposed after a few minutes. The reaction of 1 with SO2 led to partial cleavage of the P−O−Al and Al−C units, as confirmed by X‐ray diffraction studies of a complex aggregate. The reaction of 2 with SO2 affords the 1,2‐addition product. All adducts were characterized by means of multinuclear NMR spectroscopy, X‐ray crystallography and CHN analyses.
Bringing Machine‐Learning Enhanced Quantum Chemistry and Microwave Spectroscopy to Conformational Landscape Exploration: the Paradigmatic Case of 4‐Fluoro‐Threonine
Authors: Barone V. , Fusè M. , Aguado R. , Potenti S. , León I. , Alonso E. R. , Mata S. , Lazzari F. , Mancini G. , Spada L. , Gualandi A. , Cozzi P. G. , Puzzarini C. , Alonso J. L.
Published: February 2023

A combined experimental and theoretical study has been carried out on 4‐fluoro‐threonine, the only naturally occurring fluorinated amino acid. Fluorination of the methyl group significantly increases the conformational complexity with respect to the parent amino acid threonine. The conformational landscape has been characterized in great detail, with special attention given to the inter‐conversion pathways between different conformers. This led to the identification of 13 stable low‐energy minima. The equilibrium population of so many conformers produces a very complicated and congested rotational spectrum that could be assigned through a strategy that combines several levels of quantum chemical calculations with the principles of machine learning. Twelve conformers out of 13 could be experimentally characterized. The results obtained from the analysis of the intra‐molecular interactions can be exploited to accurately model fluorine‐substitution effects in biomolecules.
Near‐Infrared Piezochromism from an o‐Carborane Dyad: Boron Clusters Facilitating a Wide‐Range Redshift and High Sensitivity
Authors: Lv Chunyan , Shen Yunxia , Cao Feng , Zhang Qing , Wang Kai , Zhang Yujian
Published: February 2023

Piezochromic materials, which exhibit a fluorescence response with large emission spectral shifts and high sensitivity, may be useful in important applications, but there have been few reports of such organic luminophores. Herein, we report a new high‐sensitivity piezochromic material based on the incorporation of an o‐carborane unit, which exhibits aggregation‐induced emission properties. In a high‐pressure experiment, compared to carborane‐free MTY, which exhibits an emission spectral shift of 75 nm and a sensitivity of 19.1 nm ⋅ GPa−1, the o‐carborane dyad MTCb shows a larger emission wavelength difference of 131 nm and a higher sensitivity of 32.8 nm ⋅ GPa−1, demonstrating a performance that ranks among the best of organic piezochromic materials reported thus far. MTCb molecules adopt a J‐aggregated pattern and have relatively loose molecular packing in the crystalline state. Interestingly, nonconjugated spherical carborane can disrupt the π‐π interactions between adjacent molecules during compression, which results in excellent piezochromic performance.
Cation Co‐intercalation in Potassium Copper(II) Hexacyanoferrates
Authors: Doménech‐Carbó Antonio , López Silvana , Chandía Bastián , Cáceres Gustavo , Muñoz Eduardo
Published: February 2023

The cation‐insertion solid state electrochemistry of a potassium copper(II) hexacyanoferrate in contact with LiClO4/DMSO, NaPF6/DMSO, and KPF6/DMSO electrolytes has been theoretically and experimentally studied using the voltammetry of immobilized particles methodology. Voltammetric data, combined with SEM/EDS analysis permit to determine a K0.876CuII1.328FeIII0.049[FeIII0.318FeII0.682(CN)6] stoichiometry for the synthesized solid. Separation of electronic and ionic contributions to Gibbs energy changes can be made based on cyclic voltammetric and open circuit potential measurements. These parameters can be combined to measure values of the Gibbs energy of cation‐independent electron transfer of 7.2±0.4 (K+), 7.1±0.5 (Na+) kJ mol−1, in close agreement with the expected independence of this parameter on the electrolyte cation. The reduction Fe(III) centers bound to cyano groups exhibit a cation‐dependent, essentially Nernstian character which can be described in terms of Na+and K+insertion/deinsertion while in the case of Li+electrolytes there is significant co‐cation diffusion. Chronoamperometric data provide estimates of the diffusion coefficients of Na+, and K+ions through the solid around 10−9 cm2 s−1.
Rural residence across the life course and late‐life cognitive decline in KHANDLE: A causal inference study
Authors: Peterson Rachel L. , Gilsanz Paola , Lor Yi , George Kristen M. , Ko Michelle , Wagner Jenny , Soh Yenee , Meyer Oanh L. , Glymour M. Maria , Whitmer Rachel A.
Published: February 2023

Background

Modifiable risks for dementia are more prevalent in rural populations, yet there is a dearth of research examining life course rural residence on late‐life cognitive decline.

Methods

The association of rural residence and socioeconomic status (SES) in childhood and adulthood with late‐life cognitive domains (verbal episodic memory, executive function, and semantic memory) and cognitive decline in the Kaiser Healthy Aging and Diverse Life Experiences cohort was estimated using marginal structural models with stabilized inverse probability weights.

Results

After adjusting for time‐varying SES, the estimated marginal effect of rural residence in childhood was harmful for both executive function (β = −0.19, 95% confidence interval [CI] = −0.32, −0.06) and verbal episodic memory (β = −0.22, 95% CI = −0.35, −0.08). Effects of adult rural residence were imprecisely estimated with beneficial point estimates for both executive function (β = 0.19; 95% CI = −0.07, 0.44) and verbal episodic memory (β = 0.24, 95% CI = −0.07, 0.55).

Conclusions

Childhood rurality is associated with poorer late‐life cognition independent of SES.
Measurement of actual evapotranspiration in a páramo ecosystem using portable closed chambers: Comparison between giant rosettes, tussock grasses and shrubs
Authors: Meyers Barbara , Gutiérrez‐Lagoueyte María Elena , Tobón Conrado
Published: February 2023

The páramos are Neotropical alpine tundra‐like ecosystems that play a crucial role as biodiversity hotspots and also act as water sources for the inter‐Andean regions and cities. Improving our understanding of hydrological processes, here evapotranspiration, is crucial, especially in the context of global changes. In páramos, most research have focused on estimating potential evapotranspiration (ETo) using the Penman–Monteith method. Only a few studies have quantified actual evapotranspiration using mostly the Eddy covariance method (EC) or volumetric lysimeters. Importantly, these studies focused only on tussock grass communities, and none have addressed the effect of other plant communities specific to páramos on the actual evapotranspiration of this ecosystem. In this research, portable closed chambers were installed for the first time in a páramo (in Los Nevados National Park, between 3900 and 4100 masl) to quantify actual evapotranspration (ETa) in March and May 2019 in three representative plant communities of the páramo (giant rosettes, shrubs and tussock grasses). The ETa rates measured were then compared with ETo estimated using the Penman–Monteith method. Also, environmental factors of solar radiation, temperature and relative humidity were recorded and their influence on ETa variation was analysed. Our results indicate that ETa daily rates were very low with a high daily variation (0.290 ± 0.266 mm day−1). The shrubs showed higher ETa rates even though differences among communities were not significant. ETo rates calculated via the Penman–Monteith method were significantly higher (1.017 ± 0.468 mm day−1) than those measured using the portable chambers. Portable closed chamber is a promising method to assess ETa at small spatial and time scales and under controlled environment; however, they should be improved to enable ETa measurements on longer time periods. This study confirms the highly variable and low evapotranspiration rate of the páramo vegetation, here confirmed across different plant communities and underlines the importance of solar radiation and temperature, which were positively correlated with evapotranspiration rates.
What Changes in Topochemistry when Going from Small Molecule Dimerizations to Polymerizations in Single Crystals?
Authors: Salzillo Tommaso , Brillante Aldo , Weber Thomas , Schlüter A. Dieter
Published: February 2023

This publication promotes the increased necessity for strain management in topochemical reactions with an enlarged structural extension of the molecular products formed,i. e., when going from small molecule dimerizations, through linear polymerizations to the formation of 2D polymers. Further, it promotes to combine the trap model for photon absorption with concrete molecular scale consequences of this absorption on topochemical transformations and briefly discusses the expected consequences topological dimensionality of the forming (macro)molecular products has on trap location. The time appears ripe for going in this direction because local information concerning structural changes within single crystals is now accessible by the 3D‐ΔPDF method. This method greatly facilitates the analysis of diffuse X‐ray scattering providing access to concrete values of pair distribution functions and, thus, factual information on which and how distances change near a reaction site. Although only based on a first case where distance changes could be quantified in a lateral polymerization, the thoughts put forward may ignite more research towards a full understanding of all the action that occurs when a photochemically triggered topochemical reaction takes place. The 3D‐ΔPDF method is so attractive for this purpose because it provides otherwise inaccessible local information in pair correlation functions rather than average structure information, which is used through the ubiquitousBraggscattering.
HBsAg (−)/HBsAb (−)/HBeAg (−)/HBeAb (+)/HBcAb (+) predicts a high risk of hepatitis B reactivation in patients with B‐cell lymphoma receiving rituximab based immunochemotherapy
Authors: Shui Li‐Ping , Zhu Yan , Duan Xiao‐Qin , Chen Yu‐Ting , Yang Li , Tang Xiao‐Qiong , Zhang Hong‐Bin , Xiao Qing , Wang Li , Liu Lin , Luo Xiao‐Hua
Published: February 2023

Patterns of hepatitis B virus reactivation (HBV‐R) in HBsAg (−)/HBcAb (+) patients with B‐cell non‐Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. The retrospective study included 222 HBsAg (−)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV‐R in HBsAg (−)/HBcAb (+) B‐cell NHL patients was 6.3% (14/222), of which that in HBsAg (−)/HBsAb (−)/HBeAg (−)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (‐)/HBsAb (−)/HBeAg (−)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV‐R in B‐cell lymphoma patients (training phase hazard ratio [HR], 10.123; 95% confidence interval [CI], 3.389–30.239; p < 0.001; validation phase HR, 18.619; 95% CI, 1.684–205.906; p = 0.017; combined HR, 12.264; 95% CI, 4.529–33.207; p < 0.001). In the training cohort, the mortality rate of HBsAg (−)/HBcAb (+) B‐cell NHL caused by HBV‐R was 14.3% (2/14) while that for HBV reactivated HBsAg (‐)/HBsAb (−)/HBeAg (−)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV‐R and high mortality after HBV‐R was found in HBsAg (−)/HBsAb (−)/HBcAb (+)/HBeAg (−)/HBeAb (+) patients with B‐cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients.
AdpAlin regulates lincomycin and melanin biosynthesis by modulating precursors flux in Streptomyces lincolnensis
Authors: Kang Yajing , Wu Wei , Zhang Feixue , Chen Lei , Wang Ruida , Ye Jiang , Wu Haizhen , Zhang Huizhan
Published: February 2023

Lincomycin is one of the most important antibiotics. However, transcriptional regulation network of secondary metabolism in Streptomyces lincolnensis, the lincomycin producer, remained obscure. AdpA from S. lincolnensis (namely AdpAlin) has been proved to activate lincomycin biosynthesis. Here we found that both lincomycin and melanin took l‐tyrosine as precursor, and AdpAlin activated melanin biosynthesis as well. Three tyrosinases, MelC2, MelD2, and MelE, and one tyrosine peroxygenase, LmbB2, participated in lincomycin and melanin biosynthesis in different ways. For melanin biosynthesis, MelC2 was the only key enzyme required. For lincomycin biosynthesis, MelD2 and LmbB2 were positive factors and were suggested to convert l‐tyrosine to l‐dihydroxyphenylalanine (l‐DOPA). Otherwise, MelC2 and MelE were negative factors for lincomycin biosynthesis and they were supposed to oxidize l‐DOPA to generate melanin and certain unknown metabolite, respectively. Based on in silico analysis combined with electrophoretic mobility shift assays (EMSAs), we proved that AdpAlin directly interacted with promoters of melC, melD, and melE by binding to putative AdpA‐binding sites in vitro. Moreover, in vivo experiments revealed that AdpAlin positively regulated the transcription of melC and melE, but negatively regulated melD. In conclusion, AdpAlin was the switch of secondary metabolism in S. lincolnensis, and it modulated precursor flux of lincomycin and melanin biosynthesis by directly activating melC, melE, and lmbB1/lmbB2 or repressing melD.
Application of a new spectral deconvolution method for in vitro dosimetry in assessment of targeted alpha therapy
Authors: Doudard Alexis , Corroyer‐Dulmont Aurélien , Jaudet Cyril , Bernaudin Myriam , Valable Samuel , Ledoux Xavier , Frelin‐Labalme Anne‐Marie
Published: February 2023

Background

The improvement of in vitro assessment of targeted alpha therapy (reproducibility, comparability of experiments…) requires precise evaluation of the dose delivered to the cells. To answer this need, a previous study proposed an innovative dosimetry method based on α‐spectroscopy and a specific deconvolution process to recover the spatial distribution of 212Pb isotopes inside in vitro culture wells. Nevertheless, although promising, the deconvolution method was time consuming and only tested for a simple isotope decay chain.

Purpose

The purpose of this work is to propose a new matrix deconvolution method of α spectra based on a constrained‐non‐negative‐maximum‐likelihood decomposition, both faster and offering a greater modelling flexibility, allowing to study independently the kinetics of each of the daughter nuclides of complex decay chains (illustrated here with 223Ra) in in vitro culture wells.

Methods

Firstly, the performance of the new method was fully evaluated through Monte Carlo simulations of in vitro irradiations. Different spatial distributions of 212Pb and 223Ra, the corresponding α spectra measured by a silicon detector and the doses delivered to the cells were simulated with Geant4. The deconvolution results were then compared to the simulation results. Secondly, measurements were carried out in culture wells without cells containing 15 kBq of 212Pb or 9.3 kBq of 223Ra, placed above silicon detectors recording α spectra in real time. The matrix deconvolution was then applied to determine the spatial and temporal distribution of all α‐emitting daughters of studied isotopes.

Results

The matrix deconvolution was proved to recover the simulated distribution gradients, ensuring simulated doses within 3 % for both tested radionuclides, with errors on dose normally distributed around the reference value (consequently not exhibiting any bias), even in the case of complex decay chains as 223Ra. The experimental study of 212Pb and 223Ra showed highly inhomogeneous distributions and time evolution of the concentration gradients, consistent with the previous study. Furthermore, it highlighted the complex kinetics of 223Ra with different distributions of its α‐emitting daughters (219Rn, 215Po, 215At, 211Bi, 211Po).

Conclusions

This study validates a new deconvolution method, fast and flexible, that proved to be accurate and reliable. This method allowed to reveal the complexity of isotopes kinetics in in vitro experiments, especially with complex decay chains. Experimental dosimetry, necessary to improve reliability of in vitro studies in targeted alpha therapy, is demonstrated to be feasible with the proposed method.
A novel combinatorial testing approach with fuzzing strategy
Authors: Chen Jinfu , Chen Jingyi , Cai Saihua , Chen Haibo , Zhang Chi
Published: February 2023

Combinatorial testing (CT) is considered as a practical approach to detect software faults, which has arisen from the interaction between factors affecting the software behavior. However, most of the traditional algorithms on CT generation did not take advantage of the execution results of the earlier test cases, as well as neglect the impact of the nonequilibrium input parameter model (NE‐IPM) effect on redundant test cases, which bring a deleterious effect to the detection accuracy of the software faults. To solve these problems, we propose a novel CT approach with fuzzing strategy called CTAF. Based on the idea that fuzzing is performed during execution, CTAF exploits the execution results of earlier tests to provide guidance for subsequent test generation thereby reducing the redundant test cases without compromising the diversity of test cases. And then, we designed three experiments on real subjects of six open source software systems, and the experimental results show that the proposed CTAF approach can effectively improve the NE‐IPM effect and enhance the detection accuracy of software faults.
Helping the animals that protect all our lives
Authors: Mills Georgina
Published: February 2023

Georgina Mills sits down with Lady Bathurst, the founder of the National Foundation for Retired Service Animals, to discuss the charity's aims and the reasons behind its inception.
Ensuring both quality and quantity of EMS
Authors: Richards Kate
Published: February 2023

In this latest article from the RCVS about the forthcoming changes to its policy on extramural studies (EMS), senior vice president and chair of the RCVS education committee Kate Richards describes how a new balance is being sought between the number of EMS weeks veterinary students are required to undertake and the quality of the placements.
Charles McKinnon Robertson
Authors: Grant Lewis G.
Published: February 2023

Vet, family man, DJ, music lover, raconteur and tennis player.
Policy position on non‐traditional companion animals published
Authors: Findon Amelia
Published: February 2023

BVA policy and governance director Amelia Findon talks through BVA's latest policy position.
Shaping the Field of Open, Distance, and Digital Education
Authors: Zawacki-Richter Olaf , Jung Insung
Published: February 2023

This chapter provides a brief overview of the overall structure by the Chief Editors of the Handbook of Open, Distance, and Digital Education (ODDE) published in Springer’s Major Reference Series. The handbook is organized along the lines of the 3M-Framework covering all important issues related to ODDE at the macro- (ODDE systems, theories, and methods), meso- (ODDE educational management and institutions), and micro- (teaching and learning) levels. Each level is addressed in one volume with two sections. Informed by the historical roots of ODDE, the editors and authors of this handbook are shaping the field of ODDE scholarship, theory, and practice.
A theory of National Development Bank: long-term investment and the agency problem
Authors: Jiang Shenzhe , Xia Junjie , Xu Jiajun , Yan Jianye
Published: February 2023

This paper applies the contract theory to study the role of National Development Bank (NDB) in financing infrastructure investment. We first show that to mitigate overrun issues resulting from the agency problem during the infrastructure construction, the government uses mixed financing strategy combining fiscal funding with NDB loans. We then endogenize the NDB investment strategy to study the determinants of NDB profit and use cross-country panel data to empirically test our model predictions.
The recycled content of plastic products: estimating the impact of a recycling law on the input mix
Authors: Kumamaru Hirotaka , Takeuchi Kenji
Published: February 2023

The use of recycled material is a key building block for the circular economy. In this study, we explore the impact of recycling laws in Japan on the use of recycled materials in the production process of intermediate plastics. Using a difference-in-differences approach, we investigate whether the input share of recycled plastics in intermediate plastic products increased after the Container and Packaging Recycling Law (CPR Law) was enforced in 1997 in Japan. Results indicate that the input share of recycled plastics increased by 1 percentage point after the law’s implementation. Meanwhile, the input share of virgin plastic materials, such as polyethylene, polypropylene, and vinyl chloride, per plastic product decreased by 3 percentage points on average. These results suggest that the CPR law helped shift inputs from virgin plastics to recycled plastic materials even though the impact size has been small. To further encourage the use of recycled plastic materials, policy interventions should directly incentivize producers to increase the use of recycled plastics.
A phase I/II study of preoperative letrozole, everolimus, and carotuximab in stage 2 and 3 hormone receptor-positive and Her2-negative breast cancer
Authors: Vaklavas Christos , Stringer-Reasor Erica M. , Elkhanany Ahmed M. , Ryan Kevin J. , Li Yufeng , Theuer Charles P. , Acosta Edward P. , Wei Shi , Yang Eddy S. , Grizzle William E. , Forero-Torres Andres
Published: February 2023

Purpose

In nonmetastatic hormone receptor-positive and Her2-negative breast cancer, preoperative endocrine therapies can yield outcomes similar with chemotherapy. We evaluated the tolerability and preliminary antitumor activity of preoperative letrozole, everolimus, and carotuximab, a monoclonal antibody targeting endoglin, in nonmetastatic breast cancer.

Methods

Eligible patients had newly diagnosed, stage 2 or 3, hormone receptor-positive and Her2/neu-negative breast cancer. Patients received escalating doses of everolimus; the dose of letrozole and carotuximab were fixed at 2.5 mg PO daily and 15 mg/kg intravenously every 2 weeks, respectively. The primary objective was to determine the safety and tolerability of the combination. Secondary objectives included pharmacokinetic and pharmacodynamic studies and assessments of antitumor activity.

Results

Fifteen patients enrolled. The recommended phase 2 dose of everolimus in combination with letrozole and carotuximab was 10 mg PO daily. The most frequent adverse events were headache (67%), fatigue (47%), facial flushing and swelling (47%), gingival hemorrhage (40%), epistaxis (33%), nausea and vomiting (27%). Headache constituted a dose-limiting toxicity. At least two signs of mucocutaneous telangiectasia developed in 92% of patients. Carotuximab accumulated in the extravascular space and accelerated the biodistribution and clearance of everolimus. All patients had residual disease. Gene expression analyses were consistent with downregulation of genes involved in proliferation and DNA repair. Among 6 patients with luminal B breast cancer, 5 converted to luminal A after one cycle of therapy.

Conclusion

Letrozole, everolimus, and carotuximab were tolerated in combination at their single-agent doses. Pharmacokinetic studies revealed an interaction between everolimus and carotuximab.

Trial registration

This trial is registered with ClinicalTrials.gov (Identifier: NCT02520063), first posted on August 11, 2015, and is active, not recruiting.
Radial Orbit Errors of Contemporary Altimetry Satellite Orbits
Authors: Rudenko Sergei , Dettmering Denise , Zeitlhöfler Julian , Alkahal Riva , Upadhyay Dhruv , Bloßfeld Mathis
Published: February 2023

Precise orbits of altimetry satellites are a prerequisite for the investigation of global, regional, and coastal sea levels together with their changes, since accurate satellite positions in the radial direction are required for the reliable determination of the water surface height (distance between the altimeter position in space and the water surface). Significant progress in the improvement of altimetry satellite orbit quality has been achieved in the last 30 years increasing the orbit accuracy in the radial direction from decimeter to centimeter and even sub-centimeter level. That was possible due to the improvements in the modeling of Earth’s time variable gravity field, ocean tides, terrestrial and celestial reference frames, but also due to the accomplishments reached in the observation methods used for altimetry satellites, namely Satellite Laser Ranging (SLR), Doppler Orbitography and Radiopositioning Integrated by Satellite (DORIS), and Global Positioning System (GPS—used for some satellites). In this paper, we review the main improvements in the models used for the determination of orbits of altimetry satellites, namely, in so called Geophysical Data Records (GDR) orbit standards from GDR-C to Precise Orbit Ephemeris-F (POE-F), illustrate the impact of the improvements in precise orbit determination of these satellites on the orbit accuracy in the radial direction. Additionally we investigate orbit differences in the radial direction, single-satellite crossover differences, radial, and geographically correlated orbit errors of contemporary orbits of various altimetry satellites namely Cryosat-2, Envisat, ERS-1, ERS-2, Jason-1, Jason-2, Jason-3, SARAL, Sentinel-3A, Sentinel-3B, and TOPEX/Poseidon derived by different institutions.
Impacts of heatwaves and cold spells on glaucoma in rural China: a national cross-sectional study
Authors: Zhang Ai , Wang Qihua , Yang Xueli , Liu Yuanyuan , He Jiayu , Shan Anqi , Sun Naixiu , Liu Qianfeng , Yao Baoqun , Liang Fengchao , Yang Ze , Yan Xiaochang , Bo Shaoye , Liu Yang , Mao Hongjun , Chen Xi , Tang Nai-jun , Yan Hua
Published: February 2023

China faces increasing health risks from climate change. The structure and function of the eye and vision were affected by extreme heat and cold. The study aimed to evaluate the impacts of heatwaves and cold spells on glaucoma. A national cross-sectional study of the Rural Epidemiology for Glaucoma (REG-China) was conducted in ten provinces of China, and 36,081 adults aged 40 years or more were included. Glaucoma signs were assessed via a standard examination. A total of 15 heatwave definitions, based on intensity (95th to 99th percentiles of temperature distribution) and duration (≥2 days, 3 days, and 4 days), were used to quantify heatwave effects, and 6 cold spell definitions were defined based on threshold temperature percentile (5th and 10th) and duration (3 days, 5 days, and 9 days). Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the impacts of heatwaves and cold spells on glaucoma, and the dose-response relationships were assessed using a restricted cubic spline (RCS) model. Subgroup analysis was conducted stratified by gender, age, smoking status, occupation, and family history of glaucoma. The overall prevalence of glaucoma was 2.1% (95% CI 1.94–2.25%). Higher heatwaves were significantly correlated with higher OR of glaucoma, with the OR (95% CI) ranging from 1.014 (1.009, 1.018) to 1.090 (1.065, 1.115) by different definitions. Glaucoma was affected by heatwaves more strongly than by cold spells. The effects of both heatwaves and cold spells were higher in males than females and in smokers than nonsmokers. These results of the present study evoked the attention of prospective research to elucidate the relationship between extreme temperatures and eye diseases.
Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence
Authors: Melton Phillip E. , Burton M. A. , Lillycrop K. A. , Godfrey K. M. , Rauschert S. , Anderson D. , Burdge G. C. , Mori T. A. , Beilin L. J. , Ayonrinde O. T. , Craig J. M. , Olynyk J. K. , Holbrook J. D. , Pennell C. E. , Oddy W. H. , Moses E. K. , Adams L. A. , Huang R. C.
Published: February 2023

Background and aims

Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.

Approach and results

We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10–3).

Conclusions

We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

Graphical abstract
Cybercriminal networks in the UK and Beyond: Network structure, criminal cooperation and external interactions
Authors: Lusthaus Jonathan , Kleemans Edward , Leukfeldt Rutger , Levi Michael , Holt Thomas
Published: February 2023

This article examines the network structure, criminal cooperation, and external interactions of cybercriminal networks. Its contribution is empirical and inductive. The core of this study involved carrying out 10 case analyses on closed cybercrime investigations – all with financial motivations on the part of the offenders - in the UK and beyond. Each analysis involved investigator interview and access to unpublished law enforcement files. The comparison of these cases resulted in a wide range of findings on these cybercriminal networks, including: a common division between the scam/attack components and the money components; the presence of offline/local elements; a broad, and sometimes blurred, spectrum of cybercriminal behaviour and organisation. An overarching theme across the cases that we observe is that cybercriminal business models are relatively stable.
Determining basil production functions under simultaneous water, salinity, and nitrogen stresses
Authors: Farahbakhsh Mahshad , Sarai Tabrizi Mahdi , Babazadeh Hossein
Published: February 2023

One of the priorities in the management of agricultural inputs, such as water and fertilizers, involves investigating the variations in the crop yields under actual field conditions, subjected to the effects of various simultaneous stresses. The current study is mainly aimed at investigating the simultaneous effects of triple water, salinity, and nitrogen stresses on basil, Mazandaran mass cultivar, and determining its production functions in such situations. The study was conducted at Doshan Tappeh Agricultural Experiment Station with an area of one ha in Tehran, Iran. A factorial experiment was conducted in the form of a randomized complete block design with different irrigation levels as the main treatment. In addition, two sub-treatments, i.e., salinity and fertilization, were conducted in three replications by a water and soil laboratory in 2016 and 2017. The irrigation treatments included full irrigation (FI) in 100% (W1) and deficit irrigation (DI) in 80% (W2), 60% (W3), and 40% (W4) of crop water requirements. The salinity treatment involved 1.175 ds m−1 (S1) (control treatment), 3 ds/m (S2), and 5 ds/m (S3), while the fertilization treatment involved 100% (F1) (control treatment), 75% (F2), and 50% (F3) of the recommended fertilizer requirement. Overall, results indicated that under a constant fertilizer treatment, the rise in the salinity and water stress reduced the basil yield, while under the water-fertilizer double stress, the basil yield rate first decreased and then had a notable increase. By applying water and salinity stresses, the crop yield experienced a steeper reduction under the water stress than the salinity stress. Contrary to expectations, fertilization reduced basil yield under these conditions.
Modeling triangular, rectangular, and parabolic weirs using weighted robust extreme learning machine
Authors: Mahmoudian Alireza , Yosefvand Fariborz , Shabanlou Saeid , Izadbakhsh Mohammad Ali , Rajabi Ahmad
Published: February 2023

In this study, dimensionless parameters influencing the coefficient of discharge (COD) are found and four different WRELM models are developed. After that, a dataset is created for verifying the WRELM models in which 70% of the data are employed to train learning machine models and the remaining 30% to test them. For the mentioned algorithm, the optimal number of hidden layer neurons along with the best activation function is chosen. Additionally, the best value for the regularization parameter of the WRELM algorithm is computed. By analyzing the simulation results, the superior WRELM model and the variables impacting the COD are detected. The superior WRELM model approximates COD values with the minimum error and the highest correlation with laboratory values. For the superior model, the values of the R, MAE and VAF statistical indices are computed to be 0.994, 0.0004 and 98.662, respectively. The analysis of the simulation results indicates that the dimensionless parameters α and T/B are the most influencing input parameters. The superior WRELM model results are compared with the algorithm, and it is concluded that the WRELM model is noticeably more efficient. For the superior WRELM model, a partial derivative sensitivity analysis (PDSA) is conducted in which as the input parameter α increases, the PSDA value increases as well. Finally, an equation is suggested for estimating COD values.
Occurrence, origin, and risk assessment of metals in drinking water from a tropical suburban area (Jengka, Malaysia)
Authors: Sulaiman Fazrul Razman , Mohamed Noorfazira , Aris Ahmad Zaharin
Published: February 2023

Information about metal contamination in drinking water remains inadequate, especially for semi-urban areas. This study determines the concentrations of metals in drinking water in Jengka, Pahang, Malaysia. It also attempts to assess the potential health risks and to identify the possible sources of metal contamination. Metal concentration was analysed using inductively coupled plasma optical emission spectrometry. The results included the mean concentrations of Zn (1.7 × 10–1 mg/L), Pb (2.4 × 10–2 mg/L), and Cr (1.75 × 10–3 mg/L). In general, the concentration of metals was below the drinking water limitation standards set by the Malaysia Ministry of Health and the World Health Organization, except for Pb. This work estimates low potential non-cancer (HQ < 1) and low cancer risks (LCR < 1) from metal exposure. However, children appear to be more susceptible to metal exposure via drinking water than adults. Based on multivariate analysis, metal in drinking water could come from two sources. The findings suggest comprehensive continuous monitoring of metal concentrations from potable water, especially for semi-urban regions, to minimise health risks.
MxA for differentiating viral and bacterial infections in adults: a prospective, exploratory study
Authors: Metz Matthäus , Gualdoni Guido A. , Winkler Heide-Maria , Warenits Alexandra-Maria , Stöckl Johannes , Burgmann Heinz , Winkler Stefan , Oesterreicher Zoe Anne
Published: February 2023

Purpose

Inappropriate antibiotic prescription in patients with viral infections contributes to the surge of antibiotic resistance. Viral infections induce the expression of the antiviral protein MxA in monocytes, which is a promising biomarker to differentiate between viral and bacterial diseases. In this prospective, exploratory study, we aimed to determine the diagnostic value of monocyte MxA expression in adults with viral, bacterial or co-infections.

Methods

We measured monocyte MxA expression using flow cytometry in a cohort of 61 adults with various viral, bacterial and co-infections including patients receiving immunosuppressive therapy.

Results

Monocyte MxA expression in virus-infected patients was significantly higher compared to bacterial infections (83.3 [66.8, 109.4] vs. 33.8 [29.3, 47.8] mean fluorescence intensity [MFI]; p < 0.0001) but not co-infections (53.1 [33.9, 88.9] MFI). At a threshold of 62.2 MFI, the area under the ROC curve (AUC) to differentiate between viral and bacterial infections was 0.9, with a sensitivity and specificity of 92.3% and 84.6%, respectively. Immunosuppressive therapy did not affect monocyte MxA expression in virus-infected patients.

Conclusion

Our findings corroborate the diagnostic performance of MxA in differentiating viral and bacterial infections but also point to an important caveat of MxA in viral-bacterial co-infections. This study extends previous reports and indicates that MxA is also a useful biomarker in immunocompromised patients.
Characterization of the tribologically relevant cover layers formed on copper in oxygen and oxygen-free conditions
Authors: Raumel Selina , Barienti Khemais , Luu Hoang-Thien , Merkert Nina , Dencker Folke , Nürnberger Florian , Maier Hans Jürgen , Wurz Marc Christopher
Published: February 2023

Engineering in vacuum or under a protective atmosphere permits the production of materials, wherever the absence of oxygen is an essential demand for a successful processing. However, very few studies have provided quantitative evidence of the effect of oxidized surfaces to tribological properties. In the current study on 99.99% pure copper, it is revealed that tribo-oxidation and the resulting increased abrasive wear can be suppressed by processing in an extreme high vacuum (XHV) adequate environment. The XHV adequate atmosphere was realized by using a silane-doped shielding gas (1.5 vol% SiH4 in argon). To analyse the influence of the ambient atmosphere on the tribological and mechanical properties, a ball—disk tribometer and a nanoindenter were used in air, argon, and silane-doped argon atmosphere for temperatures up to 800 °C. Resistance measurements of the resulting coatings were carried out. To characterize the microstructures and the chemical compositions of the samples, the scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) were used. The investigations have revealed a formation of η-Cu3Si in silane-doped atmosphere at 300 °C, as well as various intermediate stages of copper silicides. At temperatures above 300 °C, the formation of γ-Cu5Si were detected. The formation was linked to an increase in hardness from 1.95 to 5.44 GPa, while the Young’s modulus increased by 46% to 178 GPa, with the significant reduction of the wear volume by a factor of 4.5 and the suppression of further oxidation and susceptibility of chemical wear. In addition, the relevant diffusion processes were identified using molecular dynamics (MD) simulations.
Adaptive Color Quantization Method with Multi-level Thresholding
Authors: Kılıçaslan Mahmut , İncetaş Mürsel Ozan
Published: February 2023

In this study, a novel color quantization approach which automatically estimates the number of colors by multi-level thresholding based on the histogram is proposed. The method consists of three stages. First, red–green–blue is clustered by threshold values. Thus, the pixels are positioned in a cluster or sub-prism. Second, the color palette is produced by determining the centroids of the clusters. Finally, the pixels are reassigned to clusters based on their distance from each centroid. The average of the pixels included in each cluster also represents the color of that cluster. While conventional methods are user-dependent, the proposed algorithm automatically generates the number of colors by considering the pixels assigned to the clusters. Additionally, the multi-level thresholding approach is also a solution to the initialization problem, which is another important issue for quantization. Consequently, the experimental results of the method tested with various images show better performance than many frequently used quantization techniques.
Characteristics of pivotal clinical trials of FDA-approved endovascular devices between 2000 and 2018: An interrupted time series analysis
Authors: Moon John T. , Konstantinidis Menelaos , Song Nevon , Nezami Nariman , Majdalany Bill S. , Herr Allen , Siskin Gary
Published: February 2023

Background:

The Food and Drug Administration (FDA) reviews safety, efficacy, and the quality of medical devices through its regulatory process. The FDA Safety and Innovation Act (FDASIA) of 2012 was aimed at accelerating the regulatory process for medical devices.

Objectives:

The purpose of our study was to (1) quantify characteristics of pivotal clinical trials (PCTs) supporting the premarket approval of endovascular medical devices and (2) analyze trends over the last two decades in light of the FDASIA.

Methods:

We surveyed the study designs of endovascular devices with PCTs from the US FDA pre-market approval medical devices database. The effect of FDASIA on key design parameters (e.g., randomization, masking, and number of enrolled patients) was estimated using an interrupted time series analysis (segmented regression).

Results:

We identified 117 devices between 2000–2018. FDASIA was associated with a decrease in double blinding (p < 0.0001) and a decrease in historical comparators (p < 0.0001).

Discussion:

Our results reveal an overall trend of decreased regulatory requirements as it relates to clinical trial characteristics, but a compensatory increased rate of post-approval across device classes. Furthermore, there was an emphasis on proving equivalence or non-inferiority rather than more use of active comparators in clinical trials. Medical device stakeholders, notably clinicians, must be aware of the shifting regulatory landscape in order to play an active role in promoting patient safety.
Ability, Knowledge, and Non-paradigmatic Testimony
Authors: Harris Keith Raymond
Published: February 2023

Critics of virtue reliabilism allege that the view cannot account for testimonial knowledge, as the acquisition of such knowledge is creditable to the testifier, not the recipient's cognitive abilities. I defend virtue reliabilism by attending to empirical work concerning human abilities to detect sincerity, certainty, and seriousness through bodily cues and properties of utterances. Then, I consider forms of testimony involving books, newspapers, and online social networks. I argue that, while discriminatory abilities directed at bodily cues and properties of utterances are impotent in the face of such testimony, alternative abilities facilitate the acquisition of knowledge from these sources.
Subcritical crack propagation in glacial quarrying during subglacial water pressure variation
Authors: Li Lin , Huang Yipeng , Su Ningchuan
Published: February 2023

Glacial quarrying stems from the fracturing of subglacial bedrock. Much evidence shows that subcritical crack propagation of bedrock is closely related to subglacial water pressure fluctuations. Here we employ a model that assesses the impact of subglacial water pressure fluctuation on cavity length and subcritical crack propagation, while analyzing the effect of a pre-existing crack location using a phase-field model (PFM). Our results indicate that the cavity length is reduced during diurnal fluctuations in water pressure. There are two patterns of subcritical crack propagation on the corner of the step. The first stems from a rapid drop in water pressure. The second occurs after the water pressure recovers from the fluctuation to the initial steady state. This pattern is a consequence of enhanced stress concentration on the step since the modeled cavity length exceeds its steady value and has higher efficiency in promoting subcritical crack propagation. Additionally, based on the PFM results, we speculate that the subcritical crack initiation and propagation happen on a broader scale, including the ice-bed contact region and its adjacent region. Our findings imply that the duration of subcritical crack propagation is short and typically ceases once the cavity length adjusts to reduced water pressure levels.
REVERSED HARDY–LITTLEWOOD–PÓLYA INEQUALITIES WITH FINITE TERMS
Authors: HAN HAIYAN , LEI YUTIAN
Published: February 2023

We prove a reversed Hardy–Littlewood–Pólya inequality with finite terms. We also give the limit of the best constant.