bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular immune responses in the pathophysiology of preeclampsia
Authors: Miller Derek , Motomura Kenichiro , Galaz Jose , Gershater Meyer , Lee Eun D , Romero Roberto , Gomez-Lopez Nardhy
Published: April 2021

Preeclampsia, defined as new-onset hypertension accompanied by proteinuria occurring at 20 weeks of gestation or later, is a leading cause of perinatal morbidity and mortality worldwide. The pathophysiology of this major multi-systemic syndrome includes defective deep placentation, oxidative stress, endothelial dysfunction, the presence of an anti-angiogenic state, and intravascular inflammation, among others. In this review, we provide a comprehensive overview of the cellular immune responses involved in the pathogenesis of preeclampsia. Specifically, we summarize the role of innate and adaptive immune cells in the maternal circulation, reproductive tissues, and at the maternal-fetal interface of women affected by this pregnancy complication. The major cellular subsets involved in the pathogenesis of preeclampsia are regulatory T cells, effector T cells, NK cells, monocytes, macrophages, and neutrophils. We also summarize the literature on those immune cells that have been less characterized in this clinical condition, such as γδ T cells, invariant natural killer T cells, dendritic cells, mast cells, and B cells. Moreover, we discuss in vivo studies utilizing a variety of animal models of preeclampsia to further support the role of immune cells in this disease. Finally, we highlight the existing gaps in knowledge of the immunobiology of preeclampsia that require further investigation. The goal of this review is to promote translational research leading to clinically relevant strategies that can improve adverse perinatal outcomes resulting from the obstetrical syndrome of preeclampsia.
TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID-19 patients
Authors: Assmann Jorn LJC , Kolijn P Martijn , Schrijver Benjamin , van Gammeren Adriaan J , Loth Daan W , Ermens Ton AAM , Dik Willem A , van der Velden Vincent HJ , Langerak Anton W
Published: April 2021

The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T lymphocyte response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 781 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 158 SARS-CoV-2 specific TRB sequences belonging to 134 clusters in our COVID-19 patients. Next, we investigated 113 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences toward the nonstructural proteins (NSPs) encoded within ORF1a/b of the SARS-CoV-2 genome was observed in clusters associated with critical disease course when compared to COVID-19 clusters associated with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from NSPs of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.
Prevalence and genotype distribution of high‐risk HPV infection among women in Beijing, China
Authors: Zhu Xiaoyan , Wang Yaxuan , Lv Zhi , Su Jianrong
Published: April 2021

Cervical cancer (CC) is highly associated with high‐risk human papillomavirus (HPV) infection and genotype distribution of high‐risk HPV (HR‐HPV) infection varies greatly in different regions. Clinical specimens were collected from 46 365 patients at Beijing Friendship Hospital, Capital Medical University from January 2017 to December 2020. HPV DNA genotype testing was performed using real‐time PCR. The infection rates based on disease group were compared using the χ
2 test. The linear‐by‐linear association test and gamma value were used to assess the changes in HPV prevalence over calendar year and age group. A total of 10 514 women were infected with HR‐HPV, with an overall positive rate of 22.7%. The most prevalent HR‐HPV types were HPV52, 58, 16, 51, and 66, and HPV59 had a higher prevalence except for HPV16, 58, and 52 in the CC group. Single infection of HR‐HPV was dominant among different disease groups. The infection rate of HR‐HPV decreased first and then increased from below 20 years old to over 60 years old. There were significant differences in the HR‐HPV infection rates among the age and disease groups. Our findings demonstrate that the genotype distribution of HR‐HPV varied with age and diseases. The HR‐HPV genotypes prevalence was found to be directly useful for local governments to promote HPV targeted vaccination in the study region.
Tillage erosion as an important driver of in‐field biomass patterns in an intensively used hummocky landscape
Authors: Öttl Lena Katharina , Wilken Florian , Auerswald Karl , Sommer Michael , Wehrhan Marc , Fiener Peter
Published: April 2021

Tillage erosion causes substantial soil redistribution that can exceed water erosion especially in hummocky landscapes under highly mechanized large field agriculture. Consequently, truncated soil profiles can be found on hill shoulders and top slopes, whereas colluvial material is accumulated at footslopes, in depressions, and along downslope field borders. We tested the hypothesis that soil erosion substantially affects in‐field patterns of the enhanced vegetation index (EVI) of different crop types on landscape scale. The interrelation between the EVI (RAPIDEYE satellite data; 5 m spatial resolution) as a proxy for crop biomass and modeled total soil erosion (tillage and water erosion modeled using SPEROS‐C) was analyzed for the Quillow catchment (size: 196 km2) in Northeast Germany in a wet versus normal year for four crop types (winter wheat, maize, winter rapeseed, winter barley). Our findings clearly indicate that eroded areas had the lowest EVI values, while the highest EVI values were found in depositional areas. The differences in the EVI between erosional and depositional sites are more pronounced in the analyzed normal year. The net effect of total erosion on the EVI compared to areas without pronounced erosion or deposition ranged from −10.2% for maize in the normal year to +3.7% for winter barley in the wet year. Tillage erosion has been identified as an important driver of soil degradation affecting in‐field crop biomass patterns in a hummocky ground moraine landscape. While soil erosion estimates are to be made, more attention should be given toward tillage erosion.
Photobiomodulation Therapy on Myocardial Infarction in Rats: Transcriptional and Posttranscriptional Implications to Cardiac Remodeling
Authors: Feliciano Regiane dos Santos , Atum Allan Luís Barboza , Ruiz Érico Gustavo da Silva , Serra Andrey Jorge , Antônio Ednei Luiz , Manchini Martha Trindade , Silva Jairo Montemor Augusto , Tucci Paulo José Ferreira , Nathanson Lubov , Morris Mariana , Chavantes Maria Cristina , Silva Júnior José Antônio
Published: April 2021

Background and Objectives: Induction of myocardial infarction (MI) in rats by occlusion of the left anterior descending coronary artery is an experimental model used in research to elucidate functional, structural, and molecular modifications associated with ischemic heart disease. Photobiomodulation therapy (PBMT) has become a therapeutic alternative by modulating various biological processes eliciting several effects, including anti‐inflammatory and pro‐proliferative actions. The main objective of this work was to evaluate the effect of PBMT in the modulation of transcriptional and post‐transcriptional changes that occurred in myocardium signal transduction pathways after MI. Study Design/Materials and Methods: Continuous wave (CW) non‐thermal laser parameters were: 660 nm wavelength, power 15 mW, with a total energy of 0.9 J, fluence of 1.15 J/cm2, spot size of 0.785 cm2, and time of 60 seconds. Using in silico analysis, we selected and then, quantified the expression of messenger RNA (mRNA) of 47 genes of 9 signaling pathways associated with MI (angiogenesis, cell survival, hypertrophy, oxidative stress, apoptosis, extracellular matrix, calcium kinetics, cell metabolism, and inflammation). Messenger RNA expression quantification was performed in myocardial samples by polymerase chain reaction real‐time array using TaqMan customized plates. Results: Our results evidenced that MI modified mRNA expression of several well‐known biomarkers related to detrimental cardiac activity in almost all signaling pathways analyzed. However, PBMT reverted most of these transcriptional changes. More expressively, PBMT provoked a robust decrease in mRNA expression of molecules that participate in post‐MI inflammation and ECM composition, such as IL‐6, TNF receptor, TGFb1, and collagen I and III. Global microRNA (miRNA) expression analysis revealed that PBMT decreased miR‐221, miR‐34c, and miR‐93 expressions post‐MI, which are related to deleterious effects in cardiac remodeling.

Conclusion: Thus, the identification of transcriptional and post‐transcriptional changes induced by PBMT may be used to interfere in the molecular dynamics of cardiac remodeling post‐MI.
Nonstandard solutions for a perturbed nonlinear Schrödinger system with small coupling coefficients
Authors: An Xiaoming , Wang Chunhua
Published: April 2021

In this paper, we consider the following weakly coupled nonlinear Schrödinger system
where , is a coupling constant, with if and if , V1 and V2 belong to .

When and is suitably small, we show that the problem has a family of nonstandard solutions concentrating synchronously at the common local minimum of V1 and V2. All decay rates of are admissible and we can allow that is close to 0 in this paper. Moreover, the location of concentration points is given by local Pohozaev identities. Our proofs are based on variational methods and the penalized technique.
Isolation, chemistry, and biology of pyrrolo[1,4]benzodiazepine natural products
Authors: Sakaine Guna , Ture Anastasija , Pedroni Julia , Smits Gints
Published: April 2021

The isolation of the antitumor antibiotic anthramycin in the 1960s prompted extensive research into pyrrolo[1,4]benzodiazepines (PBD) as potential therapeutics for the treatment of cancers. Since then, nearly 60 PBD natural products have been isolated and evaluated with regard to their biological activity. Synthetic studies and total syntheses have enabled access to PBD analogues, culminating in the development of highly potent anticancer agents. This review provides a summary of the occurrence and biological activity of PBD natural products and covers the strategies employed for their total syntheses.
A low‐profile high‐gain multi‐beam antenna based on 3D‐printed cylindrical Luneburg lens
Authors: Cao Yuanxi , Yan Sen
Published: April 2021

In this article, a low‐profile and high‐gain multi‐beam antenna is proposed. The antenna consists of a cylindrical Luneburg lens based planar beamforming network, a folded double‐layer guided‐wave structure, and a leaky wave antenna (LWA) array. All the three parts are manufactured by 3D printing technology. The lens is realized by an n‐shaped gradual thickness unit to realize the refractive index variation of Luneburg lens in a parallel plate waveguide. The lens and the LWA array are folded into a double‐layer guided wave structure, which transforms the planar wave from the flat Luneburg lens to the LWA array to realize the antenna miniaturization. The antenna is excited by a radially placed microstrip antenna array at the focal plane of the lens. The proposed antenna has seven beams with minimum −2.5 dB crossover level, and the scanning range is ±29°. The broadside gain is 19.8 dB, and the gain variation in scan range is 2.7 dB. The proposed antenna is fabricated and tested, and the measured results agree well with the simulated ones. Due to the advantages including low‐profile, high aperture efficiency, high radiation efficiency, and low cost, the proposed design can find its applications in multi‐beam radar and communication systems.
A standard system phantom for magnetic resonance imaging
Authors: Stupic Karl F. , Ainslie Maureen , Boss Michael A. , Charles Cecil , Dienstfrey Andrew M. , Evelhoch Jeffrey L. , Finn Paul , Gimbutas Zydrunas , Gunter Jeffrey L. , Hill Derek L. G. , Jack Clifford R. , Jackson Edward F. , Karaulanov Todor , Keenan Kathryn E. , Liu Guoying , Martin Michele N. , Prasad Pottumarthi V. , Rentz Nikki S. , Yuan Chun , Russek Stephen E.
Published: April 2021

Purpose

A standard MRI system phantom has been designed and fabricated to assess scanner performance, stability, comparability and assess the accuracy of quantitative relaxation time imaging. The phantom is unique in having traceability to the International System of Units, a high level of precision, and monitoring by a national metrology institute. Here, we describe the phantom design, construction, imaging protocols, and measurement of geometric distortion, resolution, slice profile, signal‐to‐noise ratio (SNR), proton‐spin relaxation times, image uniformity and proton density.

Methods

The system phantom, designed by the International Society of Magnetic Resonance in Medicine ad hoc committee on Standards for Quantitative MR, is a 200 mm spherical structure that contains a 57‐element fiducial array; two relaxation time arrays; a proton density/SNR array; resolution and slice‐profile insets. Standard imaging protocols are presented, which provide rapid assessment of geometric distortion, image uniformity, T1 and T2 mapping, image resolution, slice profile, and SNR.

Results

Fiducial array analysis gives assessment of intrinsic geometric distortions, which can vary considerably between scanners and correction techniques. This analysis also measures scanner/coil image uniformity, spatial calibration accuracy, and local volume distortion. An advanced resolution analysis gives both scanner and protocol contributions. SNR analysis gives both temporal and spatial contributions.

Conclusions

A standard system phantom is useful for characterization of scanner performance, monitoring a scanner over time, and to compare different scanners. This type of calibration structure is useful for quality assurance, benchmarking quantitative MRI protocols, and to transition MRI from a qualitative imaging technique to a precise metrology with documented accuracy and uncertainty.
The Effects of Employment Counseling on Labor Market Outcomes for Adults and Dislocated Workers: Evidence from a Nationally Representative Experiment
Authors: McConnell Sheena , Schochet Peter Z. , Rotz Dana , Fortson Ken , Burkander Paul , Mastri Annalisa
Published: April 2021

This article examines the effects of “intensive services” provided by the Adult and Dislocated Worker programs, two of the largest employment service programs in the United States. Intensive services include one‐on‐one staff assistance—assessments, coaching, career counseling, and service referrals. The study was a randomized controlled trial conducted in 28 randomly selected sites, with the randomization of job seekers to research groups with or without access to intensive services, yielding study findings with both internal and external validity. Using survey and administrative earnings data, we find that access to intensive services increased earnings by between 7 and 20 percent over a three‐year follow‐up period; these benefits exceed program costs from the perspective of both taxpayers and society as a whole. Although impacts were larger for more educated job seekers and in areas with higher rates of unemployment, impacts were similar across many other subgroups, including for adults compared with dislocated workers.
Hypoxia‐sensitive micelles based on amphiphilic chitosan derivatives for drug‐controlled release
Authors: Chen Zhiming , Wen Weiqiu , Guo Jianwei
Published: April 2021

Natural chitosan (CS) is composed of a larger hydrophilic skeleton with great biocompatibility. A hypoxia sensitive amphiphilic conjugate (CS‐NBCF) was synthesized by conjugating CS with nitrobenzyl chloroformate (NBCF). Subsequently, nano micelles with high stability (CMC = 0.0030 mg/ml) were formed by self‐assembly of the polymers in deionized water. The hypoxia‐responsive function was demonstrated by examining the size variations of polymeric micelles under the hypoxia conditions. Doxorubicin (DOX) was encapsulated into the micellar core, the drug loading and encapsulation efficiency of DOX were 15.0% and 52.6%, respectively. The in vitro release experiments showed that DOX could be released rapidly in hypoxic environment, and the release amount was up to 68% in 24 h. It was found from the cytotoxicity experiment that that the toxicity of the blank micelles was low, while DOX‐loaded micelles exhibited a good anti‐cancer effect under hypoxic conditions, and the cell inhibition rate of MCF‐7 was high up to 63%. As a result, the demonstrated properties endowed as‐developed polymeric micelles with promising application as drug delivery system in tumor treatment.
Microenvironmental regulation of tumour immunity and response to immunotherapy
Authors: Kockx Mark M , McCleland Mark , Koeppen Hartmut
Published: April 2021

The confluence of immunology and oncology has led to a lot of uncertainty and questions about relevant biomarkers. Despite the complexity of the tumour microenvironment, most clinical studies have relied on a single‐parameter immunohistochemical assay to prospectively select patients for checkpoint inhibitor therapy; the results of this strategy have been highly variable and often less than optimal. While great efforts have been made to identify additional or alternative biomarkers, pathologists, drug developers, and clinicians alike have faced technical, logistical, and regulatory challenges on how to implement them successfully. In this review, we will discuss these challenges; we will also highlight recent advances in dissecting the functional diversity of immune cell populations within the tumour microenvironment and their potential for improved, biomarker‐driven therapeutic strategies. The dynamic nature and cellular diversity of the tumour microenvironment may challenge past models of a single biomarker predicting patient response and clinical outcome. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Through the self to music: The self as the creative origin for composing in time frames
Authors: Hamel Peter Michael
Published: April 2021

Since childhood, the composer Peter Michael Hamel has been embedded in a musical environment. Here he describes a new experience leading to some new insight when he was confronted with some results in brain science. Although he has always been interested in the scientific basis of sound and music, certain characteristics of temporal information processing in the brain were new to him. In particular, the time window of some 3 s fascinated him. As an immediate reaction, he decided to compose a string quartet, which he called The Time Frame. This time window, which is an anthropological universal, provides an operative basis for effortless communication, empathic relationships to others, and it is the brain's way to integrate continuity and simultaneity of what is experienced in a complementary mode. This time window is also a temporal platform for self‐awareness. This suggests a reflection of the concept of the “self” as it has been conceived since antiquity and in different cultural environments. This reflection has motivated the title of his report, “Through the Self to Music.” This appears to be contradictory to the internationally well‐received title of his book, Through Music to the Self. However, it can be interpreted as complementary. As the composer says: the “self” is a creative starting point for composing and listening “in” time windows.
Electron beam irradiation on monolayer plastic packaging films: Studies on physico‐mechanical and thermal properties
Authors: Pramanik Nilay K. , Katamgari Irmia , Dey Ayan , Bhardwaj Yatender K. , Alam Tanweer , Chattopadhyay Sanjay K. , Saha Narayan C.
Published: April 2021

Linear low‐density polyethylene (LLDPE), biaxially oriented polypropylene (BOPP), polyethylene terephthalate (PET) and Nylon 6 films used for food packaging application were subjected to e‐beam (EB) irradiation at different doses in the range of 0 to 80 kGy. The mechanical, barrier, optical and thermal properties of the irradiated films were evaluated and compared with the non‐irradiated films. A notable decrease in oxygen transmission rate (OTR) was observed for BOPP and Nylon 6 specimens after irradiation, whereas for PET samples, no significant change was noticed. Water vapour transmission rate (WVTR) was found to exhibit a decreasing trend for PET and Nylon 6 samples but remains unchanged for BOPP after EB irradiation. Tensile strength (TS) of Nylon 6 and LLDPE films was found to increase upon irradiation up to 20 kGy, whereas for BOPP, a clear decreasing trend was observed. No significant change in TS and elongation at break was observed for PET film after irradiation. The melting temperature (Tm) and enthalpy of melting (ΔHm) were decreased with EB dose as revealed by differential scanning calorimetry (DSC) studies.
History of otorhinolaryngology in Germany before 1921
Authors: Mudry Albert , Mlynski Robert , Kramp Burkhard
Published: April 2021

In 2021, the German Society of Otorhinolaryngology, Head and Neck Surgery is celebrating the 100th anniversary of its foundation. The aim of this article is to present the main inventions and progress made in Germany before 1921, the date the society was founded. Three chronological periods are discernible: the history of otorhinolaryngology (ORL) in Germany until the beginning of the 19th century, focusing mainly on the development of scattered knowledge; the birth of the sub-specialties otology, laryngology (pharyngo-laryngology and endoscopy), and rhinology in the 19th century, combining advances in knowledge and implementation of academic structures; and the creation of the ORL specialty at the turn of the 20th century, mainly concentrating on academic organization and expansion. This period was crucial and allowed for the foundation of the German Society of Otorhinolaryngology, Head and Neck Surgery on solid ground. Germany played an important role in the development and progress of ORL internationally in the 19th century with such great contributors as Anton von Tröltsch, Hermann Schwartze, Otto Körner, Rudolf Voltolini, and Gustav Killian to mention a few.
Influence of compounding conditions, treatment of wood particles with fire-retardants and artificial weathering on properties of wood-polymer composites for façade applications
Authors: Schirp Arne , Schwarz Benjamin
Published: April 2021

Various fire-retardants (FR) for the pre-treatment of wood flour, for example, ammonium polyphosphate and different formulations based on phosphorus- and nitrogen-compounds, as well as for application during compounding were tested for their effectiveness in injection-molded and extruded composites based on high-density polyethylene and polypropylene. Small-scale tests for flammability of polymeric materials and for determination of the limiting oxygen index were used to characterize the composite materials. Differences pertaining to the applied compounding conditions, i.e., underwater granulation versus air granulation, were determined. The amount of phosphorus leached from FR during underwater granulation was analyzed. Artificial weathering trials were performed and reaction-to-fire performance and color changes of FR-composites were evaluated. Tensile strength properties of the composites and results for cold water immersion tests are also reported. An optimized formulation based on pre-treated wood flour was developed and extruded into façade profiles for the single burning item test according to DIN EN 13823. The test showed that classification C-s3, d0 according to DIN EN 13501-1 can be achieved if pre-treated wood flour is used. The use of untreated wood flour leads to a lower classification (D-s2, d0). Fire performance of extruded façade profiles can be improved by the use of pre-treated wood flour and enables new applications in the building sector.
Time-dependent modeling and experimental characterization of foamed EPDM rubber
Authors: Buchen Stefan , Kröger Nils Hendrik , Reppel Thomas , Weinberg Kerstin
Published: April 2021

Foamed rubber with a mixed cellular microstructure is a compressible material used for various sealing applications in the automotive industry. For technical optimization, a sufficiently precise material model is required. Here a material description for the porous elastic and viscoelastic response of low density foamed rubber is proposed and adapted to ethylene propylene diene monomer (EPDM)-based rubber. The elastic description is based on a spherical shell model which is homogenized in an analytical and also in a numerical manner. A viscoelastic contribution accounts for the time-dependence of the material’s response. The derived constitutive model is implemented in a finite element software and calibrated experimentally with multi-step relaxation tensile tests of foamed EPDM rubber.
Observable quality assessment of broadband very long baseline interferometry system
Authors: Xu Ming H. , Anderson James M. , Heinkelmann Robert , Lunz Susanne , Schuh Harald , Wang Guangli
Published: April 2021

The next-generation, broadband geodetic very long baseline interferometry system, named VGOS, is developing its global network, and VGOS networks with a small size of 3–7 stations have already made broadband observations from 2017 to 2019. We made quality assessments for two kinds of observables in the 21 VGOS sessions currently available: group delay and differential total electron content ($$\delta $$
δ
TEC). Our study reveals that the random measurement noise of VGOS group delays is at the level of less than 2 ps ($$1\,\hbox {ps}\,=\,10^{-12}$$

1

ps

=

10

-
12

 s), while the contributions from systematic error sources, mainly source structure related, are at the level of 20 ps. Due to the significant improvement in measurement noise, source structure effects with relatively small magnitudes that are not overwhelming in the S/X VLBI system, for instance 10 ps, are clearly visible in VGOS observations. Another critical error source in VGOS observations is discrete delay jumps, for instance, a systematic offset of about 310 ps or integer multiples of that. The predominant causative factor is found to be related to source structure. The measurement noise level of $$\delta $$
δ
TEC observables is about 0.07 TECU, but the systematic effects are five times larger than that. A strong correlation between group delay and $$\delta $$
δ
TEC observables is discovered with a trend of 40 ps/TECU for observations with large structure effects; there is a second trend in the range 60–70 ps/TECU when the measurement noise is dominant.
Current EU regulatory requirements for the assessment of chemicals and cosmetic products: challenges and opportunities for introducing new approach methodologies
Authors: Pistollato Francesca , Madia Federica , Corvi Raffaella , Munn Sharon , Grignard Elise , Paini Alicia , Worth Andrew , Bal-Price Anna , Prieto Pilar , Casati Silvia , Berggren Elisabet , Bopp Stephanie K , Zuang Valérie
Published: April 2021

The EU Directive 2010/63/EU   on the protection of animals used for scientific purposes and other EU regulations, such as REACH and the Cosmetic Products Regulation advocate for a change in the way toxicity testing is conducted. Whilst the Cosmetic Products Regulation bans animal testing altogether, REACH aims for a progressive shift from in vivo testing towards quantitative in vitro and computational approaches. Several endpoints can already be addressed using non-animal approaches including skin corrosion and irritation, serious eye damage and irritation, skin sensitisation, and mutagenicity and genotoxicity. However, for systemic effects such as acute toxicity, repeated dose toxicity and reproductive and developmental toxicity, evaluation of chemicals under REACH still heavily relies on animal tests. Here we summarise current EU regulatory requirements for the human health assessment of chemicals under REACH and the Cosmetic Products Regulation, considering the more critical endpoints and identifying the main challenges in introducing alternative methods into regulatory testing practice. This supports a recent initiative taken by the International Cooperation on Alternative Test Methods (ICATM) to summarise current regulatory requirements specific for the assessment of chemicals and cosmetic products for several human health-related endpoints, with the aim of comparing different jurisdictions and coordinating the promotion and ultimately the implementation of non-animal approaches worldwide. Recent initiatives undertaken at European level to promote the 3Rs and the use of alternative methods in current regulatory practice are also discussed.
Mass spectrometric identification and quantification of the antibiotic clavulanic acid in broiler chicken plasma and meat as a necessary analytical tool in finding ways to increase the effectiveness of currently used antibiotics in the treatment of broiler chickens
Authors: Putecova Kristina , Nedbalcova Katerina , Bartejsova Iva , Zouharova Monika , Matiaskova Katarina , Stastny Kamil
Published: April 2021

Clavulanic acid is a molecule with antimicrobial effect used in several livestock species treatment. Its inclusion in the treatment of infectious diseases of broilers requires determination of pharmacokinetic and pharmacodynamic parameters in order to determine the appropriate dosage for broilers and ensure safety of chicken products for human health. The present study describes the optimisation of analytical LC-MS/MS method for identification and quantification of clavulanic acid in broiler chicken plasma and meat. The limit of detection and the limit of quantification for the developed method were 3.09 μg·L−1 and 10.21 μg·L−1 for plasma and 2.57 μg·kg−1 and 8.47 μg·kg−1 for meat. The recoveries of the developed plasma and tissue extraction procedure were > 105.7% and > 95.6%, respectively. The achieved coefficient of variation of within-run precision ranged from 2.8 to 10.9% for plasma and from 6.5 to 8.5% for meat. The pharmacokinetic experiment was performed in 112 Ross broiler chickens assigned into time interval groups ranging from 10 min to 24 h in accredited animal facilities. Administered dose of clavulanic acid was 2.5 mg·kg−1 according to the manufacturer’s recommendations. The pharmacokinetic parameters obtained from the experiment are as follows: Cmax = 1.82 ± 0.91 mg·L−1, Tmax = 0.25 h, T1/2 = 0.87 h, Kel = 0.80 ± 0.04 h−1, AUC0-∞ = 2.17 mg·h ·L−1.
Striking a balance: outcomes of short-term Mono-J placement following ureterorenoscopy
Authors: Reicherz Alina , Maas Verena , Reike Moritz , Brehmer Mirco , Noldus Joachim , Bach Peter
Published: April 2021

To evaluate factors affecting the outcomes of short-term Mono-J insertion for 6 h following ureteroscopic stone removal. Patients treated with a Mono-J for 6 h after ureterorenoscopy and stone removal were analysed. FaST 1 and 2 (Fast Track Stent Studies), two consecutive single academic centre studies, were conducted between August 2014 and April 2018. In each study, we randomized patients with renal or ureteral calculi to two groups before ureterorenoscopy. FaST 1 compared a Mono-J insertion for 6 h versus Double-J insertion for 3–5 days after ureterorenoscopy. FaST 2 compared a Mono-J insertion to a tubeless procedure in the same clinical setting. All patients were pre-stented for 3–5 days before URS. The study endpoint was stent-related symptoms as assessed by a validated questionnaire (USSQ). Results were stratified by clinical parameters, stone characteristics and operation details. 108 of 156 initially randomized patients undergoing ureterorenoscopy were included. USSQ scores covering the time 3–5 weeks after stone removal showed a significantly reduced urinary symptoms and pain index compared to the scores before ureterorenoscopy. USSQ results before and after stone removal did not correlate with stone size or operation time and did not differ significantly depending on stone localization, the treating endourologist, or ureterorenoscopic device used (p > 0.05). Six patients (5%) required reintervention. Following secondary ureterorenoscopy and ureteral drainage with a Mono-J for 6 h, quality of life is independent of stone size and localization, operation time, the treating endourologist, and the URS device used.
Validating scoring systems for fracture healing in infants and young children: pilot study
Authors: Crompton Samuel , Messina Fabrizio , Klafkowski Gillian , Hall Christine , Offiah Amaka C.
Published: April 2021

Background

Recent studies have analysed birth-related clavicular fractures to propose time frames for healing that could be applied to dating of all fractures in cases of suspected child abuse.

Objective

To assess differences in healing rates between femoral fractures and birth-related clavicular fractures in infants and young children.

Materials and methods

A retrospective 5-year pilot study of femoral fractures in children younger than 3 years of age was performed. Anonymised radiographs were independently scored by two radiologists for stages of fracture healing. In cases of reader disagreement, radiographs were independently scored by a third radiologist.

Results

In total, 74 radiographs (30 children) met the inclusion criteria. Fracture healing evolved over time with subperiosteal new bone formation (SPNBF) appearing first, followed by callus then remodelling. A power calculation for a single proportion, with a level of confidence of 95% and a margin of error of 5%, showed that in a definitive study, 359 radiographs would be required.

Conclusion

Although the overall pattern of healing is similar, in this small pilot study, the earliest times for SPNBF and callus formation in femoral fractures appeared to lag behind healing of birth-related clavicular fractures. Remodelling appeared earlier than remodelling of clavicular fractures. A power calculation has determined numbers of femoral radiographs (359) required for a definitive study.
Natural language processing of radiology reports to investigate the effects of the COVID-19 pandemic on the incidence and age distribution of fractures
Authors: Jungmann Florian , Kämpgen B. , Hahn F. , Wagner D. , Mildenberger P. , Düber C. , Kloeckner R.
Published: April 2021

Objective

During the COVID-19 pandemic, the number of patients presenting in hospitals because of emergency conditions decreased. Radiology is thus confronted with the effects of the pandemic. The aim of this study was to use natural language processing (NLP) to automatically analyze the number and distribution of fractures during the pandemic and in the 5 years before the pandemic.

Materials and methods

We used a pre-trained commercially available NLP engine to automatically categorize 5397 radiological reports of radiographs (hand/wrist, elbow, shoulder, ankle, knee, pelvis/hip) within a 6-week period from March to April in 2015–2020 into “fracture affirmed” or “fracture not affirmed.” The NLP engine achieved an F1 score of 0.81 compared to human annotators.

Results

In 2020, we found a significant decrease of fractures in general (p < 0.001); the average number of fractures in 2015–2019 was 295, whereas it was 233 in 2020. In children and adolescents (p < 0.001), and in adults up to 65 years (p = 0.006), significantly fewer fractures were reported in 2020. The number of fractures in the elderly did not change (p = 0.15). The number of hand/wrist fractures (p < 0.001) and fractures of the elbow (p < 0.001) was significantly lower in 2020 compared with the average in the years 2015–2019.

Conclusion

NLP can be used to identify relevant changes in the number of pathologies as shown here for the use case fracture detection. This may trigger root cause analysis and enable automated real-time monitoring in radiology.
Quantitative X-ray phase contrast computed tomography with grating interferometry
Authors: Birnbacher Lorenz , Braig Eva-Maria , Pfeiffer Daniela , Pfeiffer Franz , Herzen Julia
Published: April 2021

The ability of biomedical imaging data to be of quantitative nature is getting increasingly important with the ongoing developments in data science. In contrast to conventional attenuation-based X-ray imaging, grating-based phase contrast computed tomography (GBPC-CT) is a phase contrast micro-CT imaging technique that can provide high soft tissue contrast at high spatial resolution. While there is a variety of different phase contrast imaging techniques, GBPC-CT can be applied with laboratory X-ray sources and enables quantitative determination of electron density and effective atomic number. In this review article, we present quantitative GBPC-CT with the focus on biomedical applications.
Feasibility and safety of a new endoscopic synthetic sealant nebulizing device over gastric endoscopic submucosal dissections
Authors: Boškoski Ivo , Hamanaka Jun , Barbaro Federico , Arena Vincenzo , Mascagni Pietro , Caristo Maria Emiliana , De Siena Martina , Gallo Camilla , Costamagna Guido
Published: April 2021

Background

Endoscopic Submucosal Dissection (ESD) is the treatment of choice of superficial neoplastic gastrointestinal lesions. Delayed bleedings and perforations are still current clinical concerns. Glubran 2 is a synthetic cyanoacrylate-derived glue nowadays already widely used as an effective tissue adhesive. ENDONEB is a novel device thought for enabling the sealant nebulization over a specific targeted surface during laparotomy, laparoscopy, and thoracotomy. The aim of this single-center preclinical animal trial is to evaluate the feasibility and safety of the same nebulization technique during ESD in the perspective that further clinical studies would demonstrate the efficacy of Glubran 2 in preventing post-ESD adverse events.

Methods

Four live Landrace pigs were enrolled. Two approximately 30-mm-wide gastric ESDs were performed in each pig (experimental ESD and control ESD). About 0.5 mL of Glubran 2 was nebulized on the experimental ESDs. Subjective perception of the feasibility of the Glubran 2 nebulization was reported. Pigs were clinically monitored at follow-up and upper GI endoscopy was performed at 24 and 48 hours, when animals were euthanized to perform a macroscopic and histological analysis of the specimens.

Results

No peri-procedural adverse events were reported. Glubran 2 nebulization over experimental ESDs showed to be technically easy and time-effective. Clinical and endoscopic animal monitoring was negative at follow-up. At 24 hours, the Glubran 2 film was clearly visible on the eschar of the ESDs and signs of initial hydrolysis were discernable at 48 hours. No signs of peritoneal reaction were observed at the macroscopic examination. Equal transmural inflammation was described at the histological examination of both types of ESDs.

Conclusions

Safety and feasibility profiles of Glubran 2 nebulizing ENDONEB device over ESD surfaces were excellent. Further evidences and human trials are needed to investigate its effectiveness in ESDs’ eschars sealing and, thus, in delayed micro-perforations and bleedings prevention and treatment.
Identifying classes of the pain, fatigue, and depression symptom cluster in long-term prostate cancer survivors—results from the multi-regional Prostate Cancer Survivorship Study in Switzerland (PROCAS)
Authors: Adam Salome , Thong Melissa S. Y. , Martin-Diener Eva , Camey Bertrand , Egger Hayoz Céline , Konzelmann Isabelle , Mousavi Seyed Mohsen , Herrmann Christian , Rohrmann Sabine , Wanner Miriam , Staehelin Katharina , Strebel Räto T. , Randazzo Marco , John Hubert , Schmid Hans-Peter , Feller Anita , Arndt Volker
Published: April 2021

Purpose

Aside from urological and sexual problems, long-term (≥5 years after initial diagnosis) prostate cancer (PC) survivors might suffer from pain, fatigue, and depression. These concurrent symptoms can form a cluster. In this study, we aimed to investigate classes of this symptom cluster in long-term PC survivors, to classify PC survivors accordingly, and to explore associations between classes of this cluster and health-related quality of life (HRQoL).

Methods

Six hundred fifty-three stage T1-T3N0M0 survivors were identified from the Prostate Cancer Survivorship in Switzerland (PROCAS) study. Fatigue was assessed with the EORTC QLQ-FA12, depressive symptoms with the MHI-5, and pain with the EORTC QLQ-C30 questionnaire. Latent class analysis was used to derive cluster classes. Factors associated with the derived classes were determined using multinomial logistic regression analysis.

Results

Three classes were identified: class 1 (61.4%) – “low pain, low physical and emotional fatigue, moderate depressive symptoms”; class 2 (15.1%) – “low physical fatigue and pain, moderate emotional fatigue, high depressive symptoms”; class 3 (23.5%) – high scores for all symptoms. Survivors in classes 2 and 3 were more likely to be physically inactive, report a history of depression or some other specific comorbidity, be treated with radiation therapy, and have worse HRQoL outcomes compared to class 1.

Conclusion

Three distinct classes of the pain, fatigue, and depression cluster were identified, which are associated with treatment, comorbidities, lifestyle factors, and HRQoL outcomes. Improving classification of PC survivors according to severity of multiple symptoms could assist in developing interventions tailored to survivors’ needs.
Anti-mitochondrial autoantibodies are associated with cardiomyopathy, dysphagia, and features of more severe disease in adult-onset myositis
Authors: Sabbagh Sara E. , Pinal-Fernandez Iago , Casal-Dominguez Maria , Albayda Jemima , Paik Julie J. , Miller Frederick W. , Rider Lisa G. , Mammen Andrew L. , Christopher-Stine Lisa ,   for the Johns Hopkins Myositis Center Group, Michelle Harlan , Tiniakou Eleni , Danoff Sonye K. , Lloyd Tom
Published: April 2021

We analyzed the prevalence of anti-mitochondrial autoantibodies (AMA) in adult- and juvenile-onset myositis longitudinal cohorts and investigated phenotypic differences in myositis patients with AMA. We screened sera from myositis patients including 619 adult- and 371 juvenile-onset dermatomyositis (DM, JDM), polymyositis (PM, JPM), inclusion body myositis (IBM), or amyopathic DM patients and from healthy controls, including 164 adults and 92 children, for AMA by ELISA. Clinical characteristics were compared between myositis patients with and without AMA. AMA were present in 5% of adult myositis patients (16 of 216 DM, 10 of 222 PM, 4 of 140 IBM, 1 of 19 amyopathic DM), 1% of juvenile myositis patients (3 of 302 JDM, 1 of 25 JPM), and 1% of both adult and juvenile healthy controls. In patients with adult-onset myositis, AMA were associated with persistent muscle weakness, Raynaud’s phenomenon, dysphagia, and cardiomyopathy. Adult myositis patients with AMA may have more severe or treatment refractory disease, as they more frequently received glucocorticoids and intravenous immunoglobulin. In juvenile myositis, children with AMA often had falling episodes and dysphagia, but no other clinical features or medications were significantly associated with AMA. AMA are present in 5% of adult myositis patients and associated with cardiomyopathy, dysphagia, and other signs of severe disease. The prevalence of AMA is not increased in patients with juvenile myositis compared to age-matched healthy controls. Our data suggest that the presence of AMA in adult myositis patients should prompt screening for cardiac and swallowing involvement.

Key Points• Approximately 5% of a large North American cohort of adult myositis patients have anti-mitochondrial autoantibodies.• Adults with anti-mitochondrial autoantibodies often have chronic weakness, Raynaud’s, dysphagia, cardiomyopathy, and more severe disease.• Anti-mitochondrial autoantibodies are rare in juvenile myositis and not associated with a specific clinical phenotype.
New insight into the stability and dynamics of fluid-conveying supported pipes with small geometric imperfections
Authors: Zhou Kun , Ni Qiao , Chen Wei , Dai Huliang , Peng Zerui , Wang Lin
Published: April 2021

In several previous studies, it was reported that a supported pipe with small geometric imperfections would lose stability when the internal flow velocity became sufficiently high. Recently, however, it has become clear that this conclusion may be at best incomplete. A reevaluation of the problem is undertaken here by essentially considering the flow-induced static deformation of a pipe. With the aid of the absolute nodal coordinate formulation (ANCF) and the extended Lagrange equations for dynamical systems containing non-material volumes, the nonlinear governing equations of a pipe with three different geometric imperfections are introduced and formulated. Based on extensive numerical calculations, the static equilibrium configuration, the stability, and the nonlinear dynamics of the considered pipe system are determined and analyzed. The results show that for a supported pipe with the geometric imperfection of a half sinusoidal wave, the dynamical system could not lose stability even if the flow velocity reaches an extremely high value of 40. However, for a supported pipe with the geometric imperfection of one or one and a half sinusoidal waves, the first-mode buckling instability would take place at high flow velocity. Moreover, based on a further parametric analysis, the effects of the amplitude of the geometric imperfection and the aspect ratio of the pipe on the static deformation, the critical flow velocity for buckling instability, and the nonlinear responses of the supported pipes with geometric imperfections are analyzed.
Thermal Stability of Ru–Re NPs in H2 and O2 Atmosphere and Their Activity in VOCs Oxidation: Effect of Ru Precursor
Authors: Okal Janina , Adamska Katarzyna
Published: April 2021

The thermal stability of Ru–Re NPs on γ-alumina support was studied in hydrogen at 800 °C and in air at 250–400 °C. The catalysts were synthesized using Cl-free and Cl-containing Ru precursors and NH4ReO4. Very high sintering resistance of Ru–Re NPs was found in hydrogen atmosphere and independent of Ru precursors and Re loading, the size of them was below 2–3 nm. In air, metal segregation occurred at 250 °C, leading to formation of RuO2 and highly dispersed ReOx species. Ruthenium agglomeration was hindered at higher Re loading and in presence of residual Cl species. Propane oxidation rate was higher with the Ru(N)–Re catalysts than with Ru(N) and that containing Cl species. The Ru(N)–Re (3:1) catalyst exhibited the highest activity and the lowest activation energy (91.6 kJ mol−1) what is in contrast to Ru(Cl)–Re (3:1) which had the lowest activity and the highest activation energy (119.3 kJ mol−1). Thus, the synergy effect was not observed in Cl-containing catalysts.

Graphic Abstract