bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety in s-t Paths, Trails and Walks
Authors: Cairo Massimo , Khan Shahbaz , Rizzi Romeo , Schmidt Sebastian , Tomescu Alexandru I.
Published: October 2021

Given a directed graphGand a pair of nodessandt, ans-tbridgeofGis an edge whose removal breaks alls-tpaths ofG(and thus appears in alls-tpaths). Computing alls-tbridges ofGis a basic graph problem, solvable in linear time. In this paper, we consider a natural generalisation of this problem, with the notion of “safety” from bioinformatics. We say that a walkWissafewith respect to a set$${\mathcal {W}}$$Wofs-twalks, ifWis a subwalk of all walks in$${\mathcal {W}}$$W. We start by considering the maximal safe walks when$${\mathcal {W}}$$Wconsists of: alls-tpaths, alls-ttrails, or alls-twalks ofG. We show that the solutions for the first two problems immediately follow from finding alls-tbridges after incorporating simple characterisations. However, solving the third problem requires non-trivial techniques for incorporating its characterisation. In particular, we show that there exists a compact representation computable in linear time, that allows outputting all maximal safe walks in time linear in their length. Our solutions also directly extend to multigraphs, except for the second problem, which requires a more involved approach. We further generalise these problems, by assuming that safety is defined only with respect to a subset ofvisibleedges. Here we prove a dichotomy between thes-tpaths ands-ttrails cases, and thes-twalks case: the former two are NP-hard, while the latter is solvable with the same complexity as when all edges are visible. We also show that the same complexity results hold for the analogous generalisations ofs-tarticulation points(nodes appearing in alls-tpaths). We thus obtain the best possible results for natural “safety”-generalisations of these two fundamental graph problems. Moreover, our algorithms are simple and do not employ any complex data structures, making them ideal for use in practice.
Speech and Swallowing Outcomes Following Surgical Resection with Immediate Free Tissue Transfer Reconstruction for Advanced Osteoradionecrosis of the Mandible Following Radiation Treatment for Head and Neck Cancer
Authors: Brady Grainne , Leigh-Doyle Lauren , Riva Francesco Mattia Giovanni , Kerawala Cyrus , Roe Justin
Published: October 2021

Despite recent advances in the radiation techniques used for the treatment of head and neck cancer (HNC) including intensity-modulated radiotherapy (IMRT), mandibular osteoradionecrosis (ORN) remains a significant complication. Advanced stage ORN is managed surgically with resection and immediate free tissue transfer reconstruction. An evaluation of the functional speech and swallowing outcomes was undertaken for patients undergoing surgical management of advanced ORN. We retrospectively reviewed consecutive patients, at a single, tertiary cancer centre, who underwent surgical resection for advanced Notani grade III ORN. Outcomes investigated included use and duration of tracheostomy and swallowing and speech status using Performance Status Scale for Head and Neck Cancer Normalcy of Diet (PSS-NOD) and Understandability of Speech (PSS-Speech) at baseline and 3 months following surgery. Ten patients underwent surgical resection with free tissue transfer reconstruction between January 2014 and December 2019. Two patients required supplemental nutrition via a gastrostomy at three months post surgery. As per the PSS-NOD data half of the patients’ (n = 5) diet remained stable (n = 2) or improved (n = 3) and half of the participants experienced a decline in diet (n = 5). The majority of patients had no speech difficulties at baseline (n = 8). The majority of patients’ speech remained stable (n = 8) with two patients experiencing a deterioration in speech clarity following surgery. Well-designed studies with robust, sensitive multidimensional dysphagia and communication assessments are required to fully understand the impact of surgical management of advanced ORN using resection with free tissue transfer reconstruction.
The role of dual energy computed tomography in the differentiation of acute gout flares and acute calcium pyrophosphate crystal arthritis
Authors: Kravchenko Dmitrij , Karakostas Pantelis , Kuetting Daniel , Meyer Carsten , Brossart Peter , Behning Charlotte , Schäfer Valentin S.
Published: October 2021

Objectives

To analyse the diagnostic impact of dual energy computed tomography (DECT) in acute gout flares and acute calcium pyrophosphate (CPP) crystal arthritis when compared to the gold standard of arthrocentesis with compensated polarised light microscopy. Microscopy results were also compared to musculoskeletal ultrasound (MUS), conventional radiographs, and the suspected clinical diagnosis (SCD).

Methods

Thirty-six patients with a suspected gout flare (n = 24) or acute CPP crystal arthritis (n = 11, n = 1 suffered from neither) who received a DECT and underwent arthrocentesis were included. Two independent readers assessed DECT images for signs of monosodium urate crystals or calcium pyrophosphate deposition.

Results

Sensitivity of DECT for gout was 63% (95% CI 0.41–0.81) with a specificity of 92% (0.41–0.81) while sensitivity and specificity for acute CPP arthritis were 55% (0.23–0.83) and 92% (0.74–0.99), respectively. MUS had the highest sensitivity of all imaging modalities with 92% (0.73–0.99) and a specificity of 83% (0.52–0.98) for gout, while sensitivity and specificity for acute CPP crystal arthritis were 91% (0.59–1.00) and 92% (0.74–0.99), respectively.

Conclusion

DECT is an adequate non-invasive diagnostic tool for acute gout flares but might have a lower sensitivity than described by previous studies. Both MUS and SCD had higher sensitivities than DECT for acute gout flares and acute CPP crystal arthritis.

Key Points• DECT offers a lower sensitivity for acute gout flares than previously described.• DECT sensitivity for acute CPP crystal arthritis is less than the already validated ultrasound.
From differential equation solvers to accelerated first-order methods for convex optimization
Authors: Luo Hao , Chen Long
Published: October 2021

Convergence analysis of accelerated first-order methods for convex optimization problems are developed from the point of view of ordinary differential equation solvers. A new dynamical system, called Nesterov accelerated gradient (NAG) flow, is derived from the connection between acceleration mechanism and A-stability of ODE solvers, and the exponential decay of a tailored Lyapunov function along with the solution trajectory is proved. Numerical discretizations of NAG flow are then considered and convergence rates are established via a discrete Lyapunov function. The proposed differential equation solver approach can not only cover existing accelerated methods, such as FISTA, Güler’s proximal algorithm and Nesterov’s accelerated gradient method, but also produce new algorithms for composite convex optimization that possess accelerated convergence rates. Both the convex and the strongly convex cases are handled in a unified way in our approach.
The effect of mental and physical health problems on sickness absence
Authors: Bryan Mark L. , Bryce Andrew M. , Roberts Jennifer
Published: October 2021

Absenteeism is an important feature of the labour market, imposing significant costs on employers and the economy as a whole. This paper is the first to use a large labour force survey sample to investigate how different physical and mental health conditions affect absence rates among prime age workers in the UK. A pooled time series/cross-section analysis reveals that people with a chronic health condition are more likely to be absent from work, and mental health has a significantly larger effect than physical health. From a longitudinal perspective, we find that a change in mental health has an effect on absenteeism more than three times greater than a change in physical health. These findings imply that the prevention and alleviation of chronic health conditions, particularly common mental disorders such as depression and anxiety that are highly prevalent in prime age workers, will deliver significant benefits to the UK economy due to reduced absenteeism. Further, there is significant heterogeneity between different health conditions, with some having no effect at all on absenteeism having controlled for other factors.
Correlating Lévy processes with self-decomposability: applications to energy markets
Authors: Gardini Matteo , Sabino Piergiacomo , Sasso Emanuela
Published: October 2021

Based on the concept of self-decomposability, we extend some recent multidimensional Lévy models built using multivariate subordination. Our aim is to construct multivariate Lévy processes that can model the propagation of the systematic risk in dependent markets with some stochastic delay instead of affecting all the markets at the same time. To this end, we extend some known approaches keeping their mathematical tractability, study the properties of the new processes, derive closed-form expressions for their characteristic functions and detail how Monte Carlo schemes can be implemented. We illustrate the applicability of our approach in the context of gas, power and emission markets focusing on the calibration and on the pricing of spread options written on different underlying commodities.
SENTiVENT: enabling supervised information extraction of company-specific events in economic and financial news
Authors: Jacobs Gilles , Hoste Véronique
Published: October 2021

We present SENTiVENT, a corpus of fine-grained company-specific events in English economic news articles. The domain of event processing is highly productive and various general domain, fine-grained event extraction corpora are freely available but economically-focused resources are lacking. This work fills a large need for a manually annotated dataset for economic and financial text mining applications. A representative corpus of business news is crawled and an annotation scheme developed with an iteratively refined economic event typology. The annotations are compatible with benchmark datasets (ACE/ERE) so state-of-the-art event extraction systems can be readily applied. This results in a gold-standard dataset annotated with event triggers, participant arguments, event co-reference, and event attributes such as type, subtype, negation, and modality. An adjudicated reference test set is created for use in annotator and system evaluation. Agreement scores are substantial and annotator performance adequate, indicating that the annotation scheme produces consistent event annotations of high quality. In an event detection pilot study, satisfactory results were obtained with a macro-averaged$$F_1$$F1-score of$$59\%$$59%validating the dataset for machine learning purposes. This dataset thus provides a rich resource on events as training data for supervised machine learning for economic and financial applications. The dataset and related source code is made available athttps://osf.io/8jec2/.
What’s Worrying Our Students? Increasing Worry Levels over Two Decades and a New Measure of Student Worry Frequency and Domains
Authors: Davey Graham C. L. , Meeten Frances , Field Andy P.
Published: October 2021

Background

The frequency and severity of mental health problems in student populations have been a growing cause for concern worldwide, and studies have identified measures of a number of mental health symptoms that have been steadily increasing in frequency and intensity over the past 20–25 years.

Methods

In two studies we investigate the levels and domains of pathological worrying in university student participants. Study 1 is a retrospective study of Penn State Worry Questionnaire (PSWQ) data collected between 2001 and 2019. Study 2 describes the development of the Student Worry Questionnaire, a short and easily delivered measure of student worrying that identifies both frequency of worry as well as the student-relevant domains across which worrying occurs.

Results

Study 1 revealed a steady increase in student worry scores of around 20% between 2001 and 2019, with a significant positive correlation between year of data collection and mean PSWQ score. The domain scores in Study 2 indicated that academic work was a significantly higher worry than any of the other domains, and worries about intimate relationships and ‘what people think of me’ were also worries that scored higher than either financial or health worries.

Conclusions

The present studies indicate that pathological worrying can be added to the list of anxiety- and stress-related symptoms that have been shown to be on the increase in student populations in recent decades, and we discuss whether these increases represent a greater willingness to report symptoms or a genuine increase in experienced symptoms over time.
The Dark Side of Mobile Learning via Social Media: How Bad Can It Get?
Authors: Loh Xiu-Kin , Lee Voon-Hsien , Loh Xiu-Ming , Tan Garry Wei-Han , Ooi Keng-Boon , Dwivedi Yogesh K.
Published: October 2021

As the COVID-19 pandemic continues to spread at an unprecedented rate, many universities around the world halted physical forms of teaching and learning to stop the spread of the virus. As a result, many university students were forced to utilize online learning through channels such as mobile social media. Due to the novelty of this situation, there are many unknowns particularly with the negative influences of mobile learning via social media on university students. Thus, this study looks to examine this subject matter from the perspective of the stimulus–organism–response theory. The uniquely developed research model included four stimuli (i.e., social overload, information overload, life invasion, and privacy invasion), two organisms (i.e., technostress and exhaustion) as well as a response in terms of reduced intention to use mobile learning via social media. The responses were collected from 384 university students via an online survey and analyzed with the Partial-Least-Square-Structural-Equation-Modelling. It was found that the antecedents for both technostress and exhaustion were able to account for more than half of their respective variances. Furthermore, technostress and exhaustion were significant facilitators of the students’ reduced intention to use mobile learning via social media. In addition to the practical insights for stakeholders in the education industry, this study also posited several theoretical implications for researchers.
On the NS-DSSB unidirectional estimates in the SAMPL6 SAMPLing challenge
Authors: Procacci Piero , Macchiagodena Marina
Published: October 2021

In the context of the recent SAMPL6 SAMPLing challenge (Rizzi et al. 2020 in J Comput Aided Mol Des 34:601–633) aimed at assessing convergence properties and reproducibility of molecular dynamics binding free energy methodologies, we propose a simple explanation of the severe errors observed in the nonequilibrium switch double-system-single-box (NS-DSSB) approach when using unidirectional estimates. At the same time, we suggest a straightforward and minimal modification of the NS-DSSB protocol for obtaining reliable unidirectional estimates for the process where the ligand is decoupled in the bound state and recoupled in the bulk.
Electrospun fibre diameter and its effects on vascular smooth muscle cells
Authors: Reid James Alexander , McDonald Alison , Callanan Anthony
Published: October 2021

Bypass grafting is a technique used in the treatment of vascular disease, which is currently the leading cause of mortality worldwide. While technology has moved forward over the years, synthetic grafts still show significantly lower rates of patency in small diameter bypass operations compared to the gold standard (autologous vessel grafts). Scaffold morphology plays an important role in vascular smooth muscle cell (VSMC) performance, with studies showing how fibre alignment and surface roughness can modulate phenotypic and genotypic changes. Herein, this study has looked at how the fibre diameter of electrospun polymer scaffolds can affect the performance of seeded VSMCs. Four different scaffolds were electrospun with increasing fibre sizes ranging from 0.75 to 6 µm. Culturing VSMCs on the smallest fibre diameter (0.75 µm) lead to a significant increase in cell viability after 12 days of culture. Furthermore, interesting trends were noted in the expression of two key phenotypic genes associated with mature smooth muscle cell contractility (myocardin and smooth muscle alpha-actin 1), whereby reducing the fibre diameter lead to relative upregulations compared to the larger fibre diameters. These results showed that the smallest (0.75 µm) fibre diameter may be best suited for the culture of VSMCs with the aim of increasing cell proliferation and aiding cell maturity.
Physical Activity Advice for Prevention and Rehabilitation of Low Back Pain- Same or Different? A Study on Device-Measured Physical Activity and Register-Based Sickness Absence
Authors: Gupta Nidhi , Rasmussen Charlotte Lund , Hartvigsen Jan , Mortensen Ole Steen , Clays Els , Bültmann Ute , Holtermann Andreas
Published: October 2021

Purpose We lack knowledge on whether the advice of “being physically active” should be the same for prevention and rehabilitation of low back pain (LBP). Sickness absence is a key outcome for LBP prevention and rehabilitation. We investigated the associations between physical activity and long-term sickness absence (LTSA) among employees with and without LBP. Methods Between 2011 and 2013, 925 Danish employees wore a Actigraph GTX3 accelerometer for 1–5 workdays to measure physical activity and reported LBP in past 7 days. Employees were followed for 4 years to determine their first register-based LTSA event (≥ 6 consecutive weeks). Results Among employees with LBP, increasing moderate-to-vigorous-intensity physical activity at work by 20 min and decreasing the remaining behaviors at work (ie., sitting, standing and light-intensity activity) by 20 min was associated with 38% (95% CI 17%; 63%) higher LTSA risk. Increasing light-intensity activity at work by 20 min and decreasing 20 min from the remaining behaviors was associated with 18% (95% CI 4%; 30%) lower risk. During leisure, increasing moderate-to-vigorous-intensity activity by 20 min or standing by 40 min was associated with 26% (95% CI 3%; 43%) lower and 37% (95% CI 0%; 87%) higher risk, respectively. Among employees without LBP, we found no such associations. Conclusions The physical activity advice ought to be different for LBP prevention and rehabilitation to reduce LTSA risk, and specified by domain and activity intensity. At work, employees with LBP should be advised to spend time on light-intensity physical activity and limit their time on moderate-to-vigorous-intensity physical activity. During leisure, employees should spend time on moderate-to-vigorous-intensity physical activity.
Highly stretchable, compressible, adhesive hydrogels with double network
Authors: Guo Cuiping , Zeng Zhiwen , Yu Shan , Zhou Xiaoyan , Liu Qunfeng , Pei Dating , Lu Daohuan , Geng Zhijie
Published: October 2021

In this work, a double network bovine serum albumin-polyacrylamide (BSA-PAM) adhesive hydrogel was fabricated, in which combination of physical interactions including hydrogen bonds and chain entanglements, and chemical covalent photo-crosslinking. The BSA-PAM hydrogel exhibited excellent mechanical and adhesive properties. The composite hydrogel not only demonstrated excellent tensile properties (maximum force elongation 1552%~2037%), but also displayed extremely high fatigue resistance even when subjected to compress strains of up to 85%. More importantly, the BSA-PAM hydrogel showed excellent adhesiveness to various substrates (90 kPa~150 kPa for glass and 9.74 kPa~35.09 kPa for pigskin). This work provided a facile way of fabricating tough, stretchable and adhesive BSA-PAM hydrogels.
Evaluation of a sensitive, reasonable, and fast detection method for 55Fe in steel
Authors: Merchel Silke , Rugel Georg , Lachner Johannes , Wallner Anton , Walther Diana , Ziegenrücker René
Published: October 2021

A pilot study to quantify 55Fe in steel from a reactor vessel of a nuclear power plant by accelerator mass spectrometry (AMS) without any chemical sample preparation was validated by liquid scintillation counting (LSC) and AMS after radiochemical separation. AMS reaches an uncertainty < 10% at the 1 kBq gFe−1 level within less than 10 min measuring time. The background was < 3 Bq gFe−1, presently limited by the short measurement time. The new instrumental AMS method for analysing 55Fe from neutron capture production is reasonable and fast compared to other analytical methods.
Silicone pressure-sensitive adhesives with increased thermal resistance
Authors: Antosik Adrian Krzysztof , Mozelewska Karolina , Piątek-Hnat Marta , Czech Zbigniew , Bartkowiak Marcin
Published: October 2021

The purpose of this work was to obtain single-sided tapes with different concentrations of kaolin and to check its impact on the self-adhesive properties of commercial adhesives. The most important self-adhesive properties were examined, such as tack, peel adhesion, shear strength, shrinkage, and thermal resistance. Tapes based on silicone PSAs with kaolin can be used in many branches of industry to bond elements operating at elevated temperatures, i.e., in aeronautics, aerospace including solar cells for satellites and space stations. There are few reports on one-sided adhesive tapes based on silicones with the addition of kaolin. However, taking into account the number of their potential applications, we did self-adhesive tests and explained how kaolin affects them. In addition, the reactivity of the crosslinking compound and silicone adhesive during the crosslinking process and the thermal effects of this process were also examined. In connection with the various applications of the obtained tapes, also the flammability and heat of combustion were tested, in accordance with applicable standards. As a result of the tests, one-sided self-adhesive tapes with new properties (increased temperature resistance, less shrinkage, and increased resistance to flammability) were obtained.
Butterfly biodiversity in the city is driven by the interaction of the urban landscape and species traits: a call for contextualised management
Authors: Pla-Narbona Clàudia , Stefanescu Constantí , Pino Joan , Cabrero-Sañudo Francisco J. , García-Barros Enrique , Munguira Miguel L. , Melero Yolanda
Published: October 2021

Context

Urbanisation is an environmental filter for many species that leads to community homogenisation, with a few species inhabiting isolated patches (e.g. public and private gardens and parks) embedded within the urban landscape. Promoting biodiversity in urban areas requires understanding which species traits allow species to survive the urban landscape.

Objectives

The objective of this study was to assess how species traits and landscape factors combine to allow species functional groups to live in the city.

Methods

We used butterfly count data collected by volunteers in 24 gardens of Barcelona city, during 2018 and 2019. Species were clustered in functional groups according to their traits. We applied a multinomial choice model to test for the effect of the landscape on the different functional groups.

Results

Three functional groups became prevalent in the city while a fourth, containing most sedentary specialist species, was filtered out. Although the observed groups had similar species richness, abundances varied depending on urban landscape characteristics. Specialist sedentary specialists and medium mobile species were all favoured by patch connectivity; while the presence of mobile generalist species was only enhanced by habitat quality. Our results indicate that butterfly communities are more diverse in highly connected gardens.

Conclusions

Our study highlights the need of contextualised management with actions accounting for the species functional groups, rather than a management focused on general species richness. It demonstrates that urban landscape planning must focus on improving connectivity inside the city in order to diversify the community composition.
The effect of competition on product removal
Authors: Barriola Xabier
Published: October 2021

The relationship between innovation and competition has been vastly studied over the past fifty years. However, one piece of the puzzle that has not been studied in detail is how in certain industries competition has an effect in the number of products that are removed from the market. That is why in this paper, I use scanner data to analyze the effect of competition on product removal. In particular, I track sales in the beer industry across a set of 1107 over a period of four years. Following previous studies, I use the merger between SABMiller and Molson Coors as an unexpected change in the industry to estimate future market concentration. I find that there is a negative relationship between removal and concentration. Therefore, retailers decide to remove products from their shelves in a faster way when the market is more competitive to open the gates for a more dynamic assortment.
The Risk Atlas of Mexico City, Mexico: a tool for decision-making and disaster prevention
Authors: Novelo-Casanova David A. , Suárez Gerardo , Cabral-Cano Enrique , Fernández-Torres Enrique A. , Fuentes-Mariles Oscar A. , Havazli Emre , Jaimes Miguel Á. , López-Espinoza Erika D. , Martin-Del Pozzo Ana Lillian , Morales-Barrera Wendy V. , Morales-Rodríguez Hipólito L. , Nieto-Torres Amiel , Rodríguez-Elizarrarás Sergio R. , Solano-Rojas Darío , Velasco-Herrera Victor M.
Published: October 2021

We present a Risk Atlas of Mexico City based on a Geographical Information System (RA-GIS). We identified the prevalent social risk to the more relevant hazards in Mexico City (CDMX): earthquakes, volcanic eruptions, floods, landslides, forest fires, and land subsidence. A total of 274 shape-file maps were generated in this project. Seismic hazard was estimated for return periods (RP) of 20, 125, 250, and 475 years. Three areas in central and northwestern CDMX were identified along the Younger Chichinautzin Monogenetic Volcanic Field with a high probability of forming a new volcano. Subsidence is concentrated to the east and southeast of CDMX, where subsidence rates are among the highest worldwide. Flooding events were estimated for RP of 2, 5, 10, 50, and 100 years, and most of them are concentrated in the central and northern sectors of the city. During the dry season (December–April), southern CDMX has very high probability of forest fire occurrence. There is high susceptibility of landslides on the west and southwest of the city. The goals of this RA-GIS are to provide a tool to the local and federal authorities and all organizations responsible for disaster prevention and mitigation to: (1) improve the knowledge of the potential physical and social impact of local hazards; (2) provide elements for disaster prevention, mitigation, preparedness, and response; (3) benefit decision-makers with robust risk data; (4) provide information for land-use planning; and (5) support further research to reduce the impact of disasters caused by natural phenomena.
Mapping the impact of papers on various status groups in excellencemapping.net: a new release of the excellence mapping tool based on citation and reader scores
Authors: Bornmann Lutz , Mutz Rüdiger , Haunschild Robin , de Moya-Anegon Felix , de Almeida Madeira Clemente Mirko , Stefaner Moritz
Published: October 2021

In over five years, Bornmann, Stefaner, de Moya Anegon, and Mutz (2014b) and Bornmann, Stefaner, de Moya Anegón, and Mutz (2014c, 2015) have published several releases of thewww.excellencemapping.nettool revealing (clusters of) excellent institutions worldwide based on citation data. With the new release, a completely revised tool has been published. It is not only based on citation data (bibliometrics), but also Mendeley data (altmetrics). Thus, the institutional impact measurement of the tool has been expanded by focusing on additional status groups besides researchers such as students and librarians. Furthermore, the visualization of the data has been completely updated by improving the operability for the user and including new features such as institutional profile pages. In this paper, we describe the datasets for the current excellencemapping.net tool and the indicators applied. Furthermore, the underlying statistics for the tool and the use of the web application are explained.
Use of pooled serum samples to assess herd disease status using commercially available ELISAs
Authors: Hernandez-Medrano Juan Heberth , Espinosa-Castillo Luis Fernando , Rodriguez Ana D. , Gutierrez Carlos G. , Wapenaar Wendela
Published: October 2021

Pooled samples are used in veterinary and human medicine as a cost-effective approach to monitor disease prevalence. Nonetheless, there is limited information on the effect of pooling on test performance, and research is required to determine the appropriate number of samples which can be pooled. Therefore, this study aimed to evaluate the use of pooled serum samples as a herd-level surveillance tool for infectious production-limiting diseases: bovine viral diarrhoea (BVD), infectious bovine rhinotracheitis (IBR), enzootic bovine leukosis (EBL) andNeospora caninum(NC), by investigating the maximum number of samples one can pool to identify one positive animal, using commercial antibody-detection ELISAs. Four positive field standards (PFS), one for each disease, were prepared by pooling highly positive herd-level samples diagnosed using commercially available ELISA tests. These PFS were used to simulate 18 pooled samples ranging from undiluted PFS to a dilution representing 1 positive in 1,000 animals using phosphate-buffered saline as diluent. A 1:10 dilution of the PFS resulted in positive results for IBR, BVD and EBL. Moreover, for IBR and BVD, results were still positive at 1:100 and 1:30 dilutions, respectively. However, for NC, a lower dilution (8:10) was required for a seropositive result. This study indicates that, at herd-level, the use of pooled serum is a useful strategy for monitoring infectious diseases (BVD, IBR and EBL) but not NC, using readily available diagnostic assays.
Jagd auf den Adlermörder — Entdeckung eines neuen Cyanotoxins
Authors: Breinlinger Steffen , Niedermeyer Timo H. J.
Published: October 2021

Hunting down the eagle killer: Vacuolar myelinopathy is a neurological disease affecting wildlife — including the iconic bald eagle — in the United States. Its cause has been elusive for decades, but its occurrence has been linked to the cyanobacterium Aetokthonos hydrillicola colonizing the invasive aquatic plant Hydrilla verticillata. In a recent study, we found that A. hydrillicola produces a novel highly toxic biindole alkaloid (aetokthonotoxin), and proved that it is causing the disease.
Von Genen zu Chromosomen: Pflanzenzüchtung mit CRISPR-CAS
Authors: Wetzel Rebecca , Schindele Patrick , Puchta Holger
Published: October 2021

Using the CRISPR-Cas system, it has been possible to introduce different kinds of mutations in single or multiple genes for trait improvement in crops. Last year, for the first time, the CRISPR-Cas-mediated induction of different kinds of targeted heritable chromosomal rearrangements has been achieved in plants. This novel application has the potential to revolutionize plant breeding as genetic exchange and linkage drag are now becoming controllable in a targeted manner.
Analyse von Zellfunktionen mit Hochdurchsatz-Mikroskopie und KI
Authors: Scheeder Christian , Heigwer Florian , Boutros Michael
Published: October 2021

Genes that share a distinct phenotype often share biological functions. A principle that is used in genetic screens and that provides the basis for our understanding of key biological processes. Traditionally, individual phenotypes were used to group mutant alleles into cellular pathways. Today, high-throughput technologies allow the screening of thousands of perturbations. Using computational methods and machine learning, millions of images are profiled to assign biological effects to genes and drugs.
Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP)
Authors: Horn A. , Krist L. , Lieb W. , Montellano F. A. , Kohls M. , Haas K. , Gelbrich G. , Bolay-Gehrig S. J. , Morbach C. , Reese J. P. , Störk S. , Fricke J. , Zoller T. , Schmidt S. , Triller P. , Kretzler L. , Rönnefarth M. , Von Kalle C. , Willich S. N. , Kurth F. , Steinbeis F. , Witzenrath M. , Bahmer T. , Hermes A. , Krawczak M. , Reinke L. , Maetzler C. , Franzenburg J. , Enderle J. , Flinspach A. , Vehreschild J. , Schons M. , Illig T. , Anton G. , Ungethüm K. , Finkenberg B. C. , Gehrig M. T. , Savaskan N. , Heuschmann P. U. , Keil T. , Schreiber S.
Published: October 2021

Purpose

Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany.

Methods

The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained.

Results

As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once.

Conclusion

NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity.

Trial registration

Registered at the German registry for clinical studies (DRKS00023742).
A new spectrofluorimetric method for the determination of ascorbic acid with bromocresol purple in pharmaceutical samples
Authors: Klepo L. , Ascalic M. , Medunjanin D. , Copra-Janicijevic A.
Published: October 2021

Based on the interaction between ascorbic acid and bromocresol purple, a new simple, straightforward, and quick method for the quantification of ascorbic acid is proposed. The procedure is based on the determined quenching effect of ascorbic acid on the natural fluorescence signal of bromocresol purple in the reaction between ascorbic acid and bromocresol purple in phosphate buffer solution (pH 6). The reduction of bromocresol purple fluorescence intensity is detected at 641 nm, while excitation occurs at 318 nm. The linear relationship between the reduced fluorescence intensity of bromocresol purple and the concentration of ascorbic acid is in the range 4.65 × 10–5 to 4.65 × 10–6 mol L−1 (R2 = 0.9964), with the detection limit of 8.77 × 10–7 mol L−1 and quantification limit of 2.35 × 10–5 mol L−1. The findings in this study further show that the new method provides good precision and repeatability, as well as satisfactory recovery values in terms of accuracy. The new method is tested on fifteen samples with different amounts of ascorbic acid and additional components. The effects of interfering components such as citrus bioflavonoids, citric acid, folic acid, paracetamol, calcium, and magnesium carbonate on the intensity of fluorescence of bromocresol purple are also investigated. The effects of interfering components such as citrus bioflavonoids (routine and hesperidin), citric acid, folic acid, paracetamol, calcium, and magnesium carbonate on the intensity of fluorescence of bromocresol purple are also investigated. The results of iodometric titration point out that the new method is effective for the determination of ascorbic acid in pharmaceutical samples.

Article Highlights

A new spectrofluorimetric method for determination of ascorbic acid in pharmaceutical samples using bromocresol purple.

Determination of optimal parameters for ascorbic acid determination in a variety of pharmaceutical samples.

Examination of the influence of additional substances in the pharmaceutical samples on the analysis.
A novel amplification gene PCI domain containing 2 (PCID2) promotes colorectal cancer through directly degrading a tumor suppressor promyelocytic leukemia (PML)
Authors: Zhang Jingwan , Zhai Jianning , Wong Chi Chun , Chen Huarong , Wang Xiaohong , Ji Jiafu , Yu Jun
Published: October 2021

Using whole genome sequencing, PCI Domain Containing 2 (PCID2) was identified to be amplified in colorectal cancer (CRC). In this study, we investigated the expression, biological function, molecular mechanism, and clinical implication of PCID2 in CRC. PCID2 mRNA and protein expression were higher in CRC cells and tumor tissues compared to healthy colonic tissues. The copy number of PCID2 was positively correlated with its mRNA expression. Multivariate analysis revealed that PCID2 is an independent prognostic factor for CRC recurrence. Functional studies showed that PCID2 promoted cell growth, cell cycle progression, and cell migration/invasion, while apoptosis was suppressed. Moreover, PCID2 promoted xenograft growth and lung metastasis in nude mice. Using co-immunoprecipitation and mass spectroscopy, we showed that PCID2 binds to promyelocytic leukemia (PML), a tumor suppressor involved in non-canonical β-catenin signaling. PCID2 promoted the degradation of PML via poly-ubiquitination, which in turn, induced Wnt/β-catenin signaling while simultaneously repressing ARF-p53 pathway. Thus, these results demonstrated that PCID2 functions as an oncogene in CRC by enhancing canonical Wnt/β-catenin signaling and inhibition of CTNNB1-ARF-p53 axis. PCID2 promoted canonical Wnt/β-catenin signaling in CRC via degradation of PML. PCID2 may serve as an independent prediction marker for CRC recurrence.
Increasing awareness of degenerative cervical myelopathy: a preventative cause of non-traumatic spinal cord injury
Authors: Zipser Carl M. , Margetis Konstantinos , Pedro Karlo M. , Curt Armin , Fehlings Michael , Sadler Iwan , Tetreault Lindsay , Davies Benjamin M. ,   On behalf of the AO Spine RECODE DCM Steering Committee, Kotter Mark , Davies Benjamin , Kwon Brian , Zipser Carl , Kurpad Shekar , Rahimi-Movaghar Vafa , Aarabi Bizhan , Harrop James , Guest James , Kalsi-Ryan Sukhvinder , McNair Angus , Furlan Julio , Sadler Iwan , Houghton Delphine , Sarewitz Ellen , Carter Julia , Miller Margot , Boerger Timothy , Howard Paige , Widdop Shirley , Salzman Carla , Milligan Jamie , Merli Geno J. , Chen Robert , Wilson Jefferson R. , Rodrigues-Pinto Ricardo ,   Members of the Diagnostic Criteria Working Group, Rodrigues-Pinto Ricardo , Wilson Jamie R. F. , Kimmatkar Nitin , Milligan Jamie , Davies Benjamin , Yurac Ratko , Cameron Lucy , Zipser Carl , Abdel-Wanis Mohamed , Sarewitz Ellen , Costa Bruno Lourenço , Widdop Shirley , Betz Michael , Obadaseraye Oke , Pedro Karlo , Wood Lianne
Published: October 2021

Degenerative cervical myelopathy (DCM) is a common non-traumatic spinal cord disorder and characterized by progressive neurological impairment. Generally, it is still underdiagnosed and referral to spine specialists is often late, when patients already present with incomplete cervical spinal cord injury (SCI). To improve early diagnosis and accelerate referral, diagnostic criteria for DCM are required. Recently, AO Spine RECODE- DCM (REsearch Objectives and Common Data Elements for Degenerative Cervical Myelopathy) (aospine.org/recode), an international, interdisciplinary and interprofessional initiative, including patients with DCM, was funded with the aim to accelerate knowledge discovery that can change outcomes. In this perspective we advocate for the participation of SCI specialists in this process, where the expertise and perspective on this disorder and requirements for the diagnostic and therapeutic work up is well developed.
The tertiary structure of the human Xkr8–Basigin complex that scrambles phospholipids at plasma membranes
Authors: Sakuragi Takaharu , Kanai Ryuta , Tsutsumi Akihisa , Narita Hirotaka , Onishi Eriko , Nishino Kohei , Miyazaki Takuya , Baba Takeshi , Kosako Hidetaka , Nakagawa Atsushi , Kikkawa Masahide , Toyoshima Chikashi , Nagata Shigekazu
Published: October 2021

Xkr8–Basigin is a plasma membrane phospholipid scramblase activated by kinases or caspases. We combined cryo-EM and X-ray crystallography to investigate its structure at an overall resolution of 3.8 Å. Its membrane-spanning region carrying 22 charged amino acids adopts a cuboid-like structure stabilized by salt bridges between hydrophilic residues in transmembrane helices. Phosphatidylcholine binding was observed in a hydrophobic cleft on the surface exposed to the outer leaflet of the plasma membrane. Six charged residues placed from top to bottom inside the molecule were essential for scrambling phospholipids in inward and outward directions, apparently providing a pathway for their translocation. A tryptophan residue was present between the head group of phosphatidylcholine and the extracellular end of the path. Its mutation to alanine made the Xkr8–Basigin complex constitutively active, indicating that it plays a vital role in regulating its scramblase activity. The structure of Xkr8–Basigin provides insights into the molecular mechanisms underlying phospholipid scrambling.
Targeting small GTPases and their downstream pathways with intracellular macromolecule binders to define alternative therapeutic strategies in cancer
Authors: Sorbara Marie , Bery Nicolas
Published: October 2021

The RAS superfamily of small GTPases regulates major physiological cellular processes. Mutation or deregulation of these small GTPases, their regulators and/or their effectors are associated with many diseases including cancer. Hence, targeting these classes of proteins is an important therapeutic strategy in cancer. This has been recently achieved with the approval of the first KRASG12C covalent inhibitors for the clinic. However, many other mutants and small GTPases are still considered as ‘undruggable' with small molecule inhibitors because of a lack of well-defined pocket(s) at their surface. Therefore, alternative therapeutic strategies have been developed to target these proteins. In this review, we discuss the use of intracellular antibodies and derivatives — reagents that bind their antigen inside the cells — for the discovery of novel inhibitory mechanisms, targetable features and therapeutic strategies to inhibit small GTPases and their downstream pathways. These reagents are also versatile tools used to better understand the biological mechanisms regulated by small GTPases and to accelerate the drug discovery process.
Controlled metabolic cascades for protein synthesis in an artificial cell
Authors: Nguyen Huong Thanh , Lee Sungwoo , Shin Kwanwoo
Published: October 2021

In recent years, researchers have been pursuing a method to design and to construct life forms from scratch — in other words, to create artificial cells. In many studies, artificial cellular membranes have been successfully fabricated, allowing the research field to grow by leaps and bounds. Moreover, in addition to lipid bilayer membranes, proteins are essential factors required to construct any cellular metabolic reaction; for that reason, different cell-free expression systems under various conditions to achieve the goal of controlling the synthetic cascades of proteins in a confined area have been reported. Thus, in this review, we will discuss recent issues and strategies, enabling to control protein synthesis cascades that are being used, particularly in research on artificial cells.
Red-Light-Induced N,N′-Dipropyl-1,13-dimethoxyquinacridinium-Catalyzed [3+2] Cycloaddition of Cyclopropylamines with Alkenes or Alkynes
Authors: Gianetti Thomas L. , Stull Savannah M. , Mei Liangyong
Published: October 2021

A red-light-mediated [3+2] annulation of cyclopropylamines with akenes or alkynes in the presence of N,N′-dipropyl-1,13-dimethoxyquinacridinium is reported. An array of cyclopentane or cyclopentene derivatives with diverse functional groups have been obtained in moderate to excellent yields under mild conditions.
Cardiovascular Mortality after Venous Thromboembolism: A Meta-Analysis of Prospective Cohort Studies
Authors: Noumegni Steve Raoul , Grangereau Thomas , Demir Arzu , Bressollette Luc , Couturaud Francis , Hoffmann Clément
Published: October 2021

Many studies from current literature show that cardiovascular diseases in patients with venous thromboembolism (VTE) are more frequent than in the general population without VTE. However, data summarizing the impact of cardiovascular diseases on mortality of patients with VTE are lacking. In this systematic review and meta-analysis, we aimed to determine the frequency and incidence rate of cardiovascular death in patients with VTE. MEDLINE and EMBASE were searched from January 1, 2000 to February 28, 2021. Eligible studies were observational prospective cohort studies including patients with VTE and reporting all causes of death. Cardiovascular death was defined as deaths that result from new or recurrent pulmonary embolism, death due to acute myocardial infarction, sudden cardiac death or heart failure, death due to stroke, death due to cardiovascular procedures or hemorrhage, death due to ruptured aortic aneurysm or aortic dissection and death due to other cardiovascular causes. Random-effect models meta-analysis served to determine all pooled effect size of interest with their 95% confidence interval (CI). Thirteen observational studies enrolling 22,251 patients were identified and included. The mean/median age varied between 49 and 75 years. The proportion of men ranged from 38.3 to 53.2%. The overall pooled frequency of cardiovascular death in patients with VTE was 3.9% (95% CI: 2.5–5.6%), while the overall pooled frequency of all-cause mortality was 12.0% (95% CI: 9.1–15.4%). The pooled proportion of cardiovascular death among all causes of deaths in patients with VTE was 35.2% (95% CI: 22.2–49.3%). The pooled incidence rate of cardiovascular death was 1.92 per 100 patient-years (95% CI: 0–4.1). The frequency of cardiovascular death in patients with VTE was significantly higher than in patients without VTE (risk ratio: 3.85, 95% CI: 2.75–5.39). Based on this updated meta-analysis from 13 prospective cohort studies, cardiovascular death in patients with VTE is more frequent than in the general population without VTE.