bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThis 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

AbstractPatterns 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

AbstractLincomycin 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

AbstractBackgroundThe 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.PurposeThe 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.MethodsFirstly, 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.ResultsThe 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).ConclusionsThis 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

SummaryCombinatorial 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.
Shaping the Field of Open, Distance, and Digital Education
Authors: Zawacki-Richter Olaf , Jung Insung 
Published: February 2023

AbstractThis 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

AbstractThis 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

AbstractThe 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

Abstract
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

AbstractPrecise 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

AbstractChina 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

Abstract
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

AbstractThis 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

AbstractOne 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.