bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrrolidine in Drug Discovery: A Versatile Scaffold for Novel Biologically Active Compounds
Authors: Li Petri Giovanna , Raimondi Maria Valeria , Spanò Virginia , Holl Ralph , Barraja Paola , Montalbano Alessandra 
Published: August 2021

AbstractThe five-membered pyrrolidine ring is one of the nitrogen heterocycles used widely by medicinal chemists to obtain compounds for the treatment of human diseases. The great interest in this saturated scaffold is enhanced by (1) the possibility to efficiently explore the pharmacophore space due to sp3-hybridization, (2) the contribution to the stereochemistry of the molecule, (3) and the increased three-dimensional (3D) coverage due to the non-planarity of the ring—a phenomenon called “pseudorotation”. In this review, we report bioactive molecules with target selectivity characterized by the pyrrolidine ring and its derivatives, including pyrrolizines, pyrrolidine-2-one, pyrrolidine-2,5-diones and prolinol described in the literature from 2015 to date. After a comparison of the physicochemical parameters of pyrrolidine with the parent aromatic pyrrole and cyclopentane, we investigate the influence of steric factors on biological activity, also describing the structure–activity relationship (SAR) of the studied compounds. To aid the reader’s approach to reading the manuscript, we have planned the review on the basis of the synthetic strategies used: (1) ring construction from different cyclic or acyclic precursors, reporting the synthesis and the reaction conditions, or (2) functionalization of preformed pyrrolidine rings, e.g., proline derivatives. Since one of the most significant features of the pyrrolidine ring is the stereogenicity of carbons, we highlight how the different stereoisomers and the spatial orientation of substituents can lead to a different biological profile of drug candidates, due to the different binding mode to enantioselective proteins. We believe that this work can guide medicinal chemists to the best approach in the design of new pyrrolidine compounds with different biological profiles.
The effect of heat treatment and impact angle on the erosion behavior of nickel-tungsten carbide cold spray coating using response surface methodology
Authors: Kazasidis Marios , Verna Elisa , Yin Shuo , Lupoi Rocco 
Published: August 2021

AbstractThis study elucidates the performance of cold-sprayed tungsten carbide-nickel coating against solid particle impingement erosion using alumina (corundum) particles. After the coating fabrication, part of the specimens followed two different annealing heat treatment cycles with peak temperatures of 600 °C and 800 °C. The coatings were examined in terms of microstructure in the as-sprayed (AS) and the two heat-treated conditions (HT1, HT2). Subsequently, the erosion tests were carried out using design of experiments with two control factors and two replicate measurements in each case. The effect of the heat treatment on the mass loss of the coatings was investigated at the three levels (AS, HT1, HT2), as well as the impact angle of the erodents (30°, 60°, 90°). Finally, the response surface methodology (RSM) was applied to analyze and optimize the results, building the mathematical models that relate the significant variables and their interactions to the output response (mass loss) for each coating condition. The obtained results demonstrated that erosion minimization was achieved when the coating was heat treated at 600 °C and the angle was 90°.
Scale-Dependent Point Selection Methods for Web Maps
Authors: Gröbe Mathias , Burghardt Dirk 
Published: August 2021

AbstractIn cartographic generalization, the selection is an often-used method to adjust information density in a map. This paper deals with methods for selecting point features for a specific scale with numerical attributes, such as population, elevation, or visitors. With the Label Grid approach and the method of Functional Importance, two existing approaches are described, which have not been published in the scientific literature so far. They are explained and illustrated in the method chapter for better understanding. Furthermore, a new approach based on the Discrete Isolation measure is introduced. It combines the spatial position and the attribute's value and is defined as the minimum distance to the nearest point with a higher value. All described selection methods are implemented and made available as Plugins named “Point selection algorithms” for QGIS. Based on this implementation, the three methods are compared regarding runtime, parameterization, legibility, and generalization degree. Finally, recommendations are given on which data and use cases the approaches are suitable. We see digital maps with multiple scales as the main application of those methods. The possibilities of labeling the selected points are not considered within the scope of this work.
Enhanced chemoselectivity of a plant cytochrome P450 through protein engineering of surface and catalytic residues
Authors: Zhang Xiaopeng , Luo Wei , Yao Yinying , Luo Xuming , Han Chao , Zhong Yang , Zhang Bo , Li Dawei , Han Lida , Huang Sanwen , Greisen Per , Shang Yi 
Published: August 2021

AbstractCytochrome P450s (P450s) are the most versatile catalysts utilized by plants to produce structurally and functionally diverse metabolites. Given the high degree of gene redundancy and challenge to functionally characterize plant P450s, protein engineering is used as a complementary strategy to study the mechanisms of P450-mediated reactions, or to alter their functions. We previously proposed an approach of engineering plant P450s based on combining high-accuracy homology models generated by Rosetta combined with data-driven design using evolutionary information of these enzymes. With this strategy, we repurposed a multi-functional P450 (CYP87D20) into a monooxygenase after redesigning its active site. Since most plant P450s are membrane-anchored proteins that are adapted to the micro-environments of plant cells, expressing them in heterologous hosts usually results in problems of expression or activity. Here, we applied computational design to tackle these issues by simultaneous optimization of the protein surface and active site. After screening 17 variants, effective substitutions of surface residues were observed to improve both expression and activity of CYP87D20. In addition, the identified substitutions were additive and by combining them a highly efficient C11 hydroxylase of cucurbitadienol was created to participate in the mogrol biosynthesis. This study shows the importance of considering the interplay between surface and active site residues for P450 engineering. Our integrated strategy also opens an avenue to create more tailoring enzymes with desired functions for the metabolic engineering of high-valued compounds like mogrol, the precursor of natural sweetener mogrosides.
Examining NEET situations in Spain: Labour Market, Discourses and Policies
Authors: Strecker Tanja , López Joffre , Cabasés M. Àngels 
Published: August 2021

AbstractNot in Education, Employment, or Training (NEET) and its Spanish equivalent ‘nini’ (Ni estudia, Ni trabaja) have dominated youth policy discourses in recent years. Within the European Union, Spain is one of the countries with the highest proportion of young people in NEET situations. In this article, it is argued that the idea of NEET has been weaponised to stigmatise youth, by evoking the phantom of a demotivated young person with scarce training. This stigmatisation has little to do with the reality of many young Spaniards who can find themselves in different situations, such as unemployment, precarious employment, training and education in a matter of days. Thus, there is a need to consider the different experiences and structural circumstances of so-called NEETs rather than viewing them as a homogenous and static group. Using documentary analysis and secondary data, this article examines the diversity of NEET situations for the youth in Spain, which is generally not captured in large national statistics data-sets and policies. Furthermore, it analyses the EU Youth Guarantee and its application in Spain, highlighting where official objectives have not been met, and includes an overview of the current effects of the coronavirus crisis. Ultimately, the paper shows that public discourses centred on an artificially created social group (NEET) legitimise and produce policies that do not respond to young people’s actual needs and problems, especially for the most vulnerable among them.
Trauma and self‐harming behaviors in high school students: The mediating role of identity formation
Authors: Raemen Leni , Luyckx Koen , Palmeroni Nina , Verschueren Margaux , Gandhi Amarendra , Grobler Adelene , Claes Laurence 
Published: August 2021

AbstractIntroductionThis study investigated the link between trauma and self‐harming behaviors in South African high school students, and examined the mediating role of identity formation. Traumatic experiences have been commonly associated with self‐harming behaviors in adolescents. However, research addressing this association in non‐Western countries is limited.MethodsA total of 552 South African high school students aged 13–21 (60.4% female; Mage = 16 years) were included in the study. Students completed self‐report questionnaires on traumatic experiences, identity formation, and self‐harming behaviors (disturbed eating behaviors and suicidal thoughts and behaviors).ResultsStructural equation modelling indicated that the association between traumatic experiences and self‐harming behaviors was partially mediated by identity formation. Traumatic experiences were associated with more identity diffusion, bulimia, and suicidal thoughts and behaviors. Identity diffusion, in turn, was associated with more drive for thinness, bulimia, body dissatisfaction, and suicidal thoughts and behaviors. Identity consolidation was positively associated with drive for thinness and negatively with body dissatisfaction and suicidal thoughts and behaviors. No moderation effects by gender or age were found.ConclusionsTraumatic experiences were associated with higher levels of identity diffusion, which, in turn, were associated with more self‐harming behaviors in South African high school students. These findings suggest the importance of focusing on identity diffusion in prevention and intervention programs targeting self‐harming behaviors.
Evaluation of clinical manifestation and risk factors of idiopathic granulomatous mastitis
Authors: Pak Haleh , Maghsoudi Leila Haji , Soltanian Ali , Jafarinia Sepideh 
Published: August 2021

ABSTRACT

Background:
Idiopathic granulomatous mastitis is a rare inflammatory breast pathology that, due to its rarity, remain challengeable for diagnosis. The disease has been suggested to have multiple etiologies. In this study the clinical manifestations and risk factors of idiopathic granulomatous mastitis (IGM) were assessed.

Methods and materials:
In this case-control study 30 cases with idiopathic granulomatous mastitis and 60 control subjects in clinical centers in (XXX) in 2020 were enrolled and clinical manifestations and risk factors were determined and compared across the groups.

Results:
The breast mass (40%), pain (23.3%), and discharge (36.7%) were significantly higher in idiopathic granulomatous mastitis versus control subjects (P = 0.001). Passive smoking was seen in 3 cases (10%) and none of the subjects in case and control groups, with significant difference (P = 0.035). Age, contraceptive use, tuberculosis, malignancy, family history, breastfeeding duration, child count, and gravid were significantly different between the groups (P > 0.05).

Conclusions:
Our study showed that breast mass, pain, and discharge are main clinical manifestations in idiopathic granulomatous mastitis cases and passive smoking is the main risk factor for this disease. The role of pregnancy, lactation, smoking and use of oral contraceptive in the etiology of the disease still remains unclear.

Highlights
Thymectomy for non-thymomatous myasthenia gravis: Short and long term outcomes, a single-center 10 years' experience
Authors: Baram Aram , AbdullahSalih Kizhan H. , Saqat Bashar Hana 
Published: August 2021

ABSTRACT

Background:
Myasthenia gravis (MG) is an auto-immune disorder characterized by the production of abnormal antibodies to the acetylcholine receptors at the neuromuscular junction. Radical thymectomy in many forms of MG may lead to clinical improvement in 70–80% of cases. Our objectives were to demonstrate our short and long-term results of radical trans-sternal thymectomy.

Patients and methods:
Retrospective analysis of prospectively collected data from 48 consecutive patients with non-thymomatous MG, managed over 10 years. All patients with thymomatous MG were excluded. The myasthenia gravis activities of daily living (MG-ADL) scoring performed for all patients and the stage of disease determined by the Myasthenia Gravis Foundation of America (MGFA) classification. The primary endpoint of this study was to evaluate early first 30 days postoperative outcomes and the secondary endpoint was to determine complete stable remission, time of pharmacological remission, and decreasing MG-ADL scoring over 5 years follow-up.

Results:
Totally, 48 patients included: 41 females (85.4%) and 7 males (14.5%). Generalized muscle weakness, shortness of breath, and easy fatigability were the most common presenting features. During 5 years follow up, 38 patients (79.1%) had decreased their medication dose. Time of pharmacological remission started (6–60) months. Complete stable remission (CSR) achieved in 44 patients (91.6%) over 60 months. Post-operative MG-ADL levels ranged between (12–24) scores, at the end of the follow-up period decrease to less than 10 scores.

Conclusion:
Radical trans-sternal thymectomy for non-thymomatous MG is an effective and well-tolerated procedure that is associated with significant clinical improvement in the majority of patients.

Highlights
‘Sich ausgehen’:On modalizinggoconstructions in Austrian German
Authors: Gergel Remus , Kopf-Giammanco Martin 
Published: August 2021

AbstractThe goal of this article is to diagnose a verbal construction which has made it to common use in Austrian German and is typically unknown to many speakers of Federal German who have not been exposed to Austrian German. This construction is based on the verbgehen(‘go’) conjoined by a particle and the reflexive. An argument for its analysis as a degree-based sufficiency construction is developed, which is constructed by extending existing approaches in the literature onenoughconstructions and suggesting a meaning of the construction at hand, which is presuppositional in multiple respects. The results of diachronic corpus searches as well as the significance of the results of this work for the space of possibilities of the semantic change of motion verbs are discussed.
Renaming and Reclaiming Urban Spaces in Ukraine: The Perspective of Internally Displaced People
Authors: Lazarenko Valeria 
Published: August 2021

AbstractFor more than six years, Ukrainian society has been constantly searching for ideas as to how to write a new “national biography.” In a society divided by armed conflict, the so-called decommunization process is considered to be an idea capable of uniting a nation. This process started back in 2015, with the passing of a specific law that required not only the deconstruction of Soviet-time monuments in public spaces, but also a huge decommunization of place names. The article will explore the main practices of place (re-)naming during the different stages of the decommunization (but not de-ideologization) of spaces, as well as describing the problems that may emerge in society as a result of a rapid transition from one narrative to another. Based on a case study of spatial identities of internally displaced people, I am going to answer the question of how people perceive renamed spaces, and how they reclaim and re-appropriate these spaces in the midst of an identity crisis.
Identification of bovine mastitis pathogens using MALDI-TOF mass spectrometry in Brazil
Authors: Oliveira Thais Cristina de Assis , Brito Maria Aparecida Vasconcelos Paiva , Giambiagi-de Marval Marcia , Vicentini Nívea Maria , Lange Carla Christine 
Published: August 2021

AbstractIn this Research Communication we evaluate the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify 380 bacteria isolated from cases of bovine mastitis in Brazil. MALDI-TOF MS identifications were compared to previous identifications by biochemical tests and 16S rRNA sequencing. MALDI-TOF MS achieved a typeability of 95.5%. The accuracy of MALDI-TOF MS for the identification of Staphylococcus isolates was 93.2%. The agreement between MALDI-TOF MS and biochemical identification of Streptococcus agalactiae was 96%, however, the agreement between these techniques for identifying other catalase-negative, Gram-positive cocci was lower. Agreement in identifying Gram-negative bacteria at the genus level was 90.5%. Our findings corroborate that MALDI-TOF MS is an accurate, rapid and simple technique for identifying bovine mastitis pathogens. The availability of this methodology in some research institutions would represent a significant step toward increasing the diagnosis and epidemiological studies of bovine mastitis and other animal infectious diseases in Brazil.
Why Are Bidder Termination Provisions Included in Takeovers?
Authors: Chen Zhiyao , Mahmudi Hamed , Virani Aazam , Zhao Xiaofei 
Published: August 2021

AbstractWe present a rationale for bidder termination provisions that considers their effect on bidders’ and targets’ joint takeover gains. The provision’s inclusion can create value by enabling termination when the target becomes less valuable to the bidder than on its own, but creates a trade-off because termination may also occur when the target is more valuable to the bidder than on its own. This trade-off explains why the provision is included in only some deals, and explains variation in termination fees. Inclusion of the provision is associated with larger combined announcement returns, provided that the termination fee is priced appropriately.
Epidemiological investigations identified an outbreak of Shiga toxin-producing Escherichia coli serotype O26:H11 associated with pre-packed sandwiches
Authors: Butt Saira , Allison Lesley , Vishram Bhavita , Greig David R. , Aird Heather , McDonald Eisin , Drennan Genna , Jenkins Claire , Byrne Lisa , Licence Kirsty , Smith-Palmer Alison 
Published: August 2021

Abstract
In October 2019, public health surveillance systems in Scotland identified an increase in the number of reported infections of Shiga toxin-producing Escherichia coli (STEC) O26:H11 involving bloody diarrhoea. Ultimately, across the United Kingdom (UK) 32 cases of STEC O26:H11 stx1a were identified, with the median age of 27 years and 64% were male; six cases were hospitalised. Among food exposures there was an association with consuming pre-packed sandwiches purchased at outlets belonging to a national food chain franchise (food outlet A) [odds ratio (OR) = 183.89, P < 0.001]. The common ingredient identified as a component of the majority of the sandwiches sold at food outlet A was a mixed salad of Apollo and Iceberg lettuce and spinach leaves. Microbiological testing of food and environmental samples were negative for STEC O26:H11, although STEC O36:H19 was isolated from a mixed salad sample taken from premises owned by food outlet A. Contamination of fresh produce is often due to a transient event and detection of the aetiological agent in food that has a short-shelf life is challenging. Robust, statistically significant epidemiological analysis should be sufficient evidence to direct timely and targeted on-farm investigations. A shift in focus from testing the microbiological quality of the produce to investigating the processes and practices through the supply chain and sampling the farm environment is recommended.
Serological and molecular detection of pathogenic Leptospira in domestic and stray cats on Reunion Island, French Indies
Authors: Holzapfel M. , Taraveau F. , Djelouadji Z. 
Published: August 2021

Abstract
Indian Ocean islands are endemic areas for human and animal leptospirosis. Maintenance host species for Leptospira spp. have still not been completely elucidated, and recently the role of cats (Felis catus) has been questioned. This cross-sectional study aims to determine whether cats are part of the maintenance community of different strains of Leptospira spp. in Reunion Island. The prevalence of Leptospira infection in an opportunistic sample of stray and domestic cats (n = 92) from Reunion Island has been studied using serological (microagglutination test) and molecular detection (polymerase chain reaction (PCR)). The results revealed a seroprevalence of 37.0% (34/92) (cut-off 1:40) without a significant difference in the living conditions of animals. The predominant serogroup was Icterohaemorrhagiae, but Ballum, Cynopteri and Australis were also detected. Using PCR, 28.6% (12/42) of stray cats were tested positive. Leptospiral DNA was detected in renal tissue, urine and blood of respectively 14.3% (6/42), 10.3% (4/39) and 11.9% (5/42) of stray cats, but 0% (0/3), 0% (0/50) and 0% (0/36) of domestic cats (P = non-applicable, P = 0,038, P = 0,058 respectively). Partial rrs gene (16S rRNA) sequencing identified Leptospira interrogans in all PCR-positive samples. Our study confirms that renal carriage and urinary shedding are possible, positioning cats, and especially stray cats as potential actors within the maintenance community of L. interrogans in Reunion Island.
Changes in COVID-19-related outcomes, potential risk factors and disparities over time
Authors: Yu Youfei , Gu Tian , Valley Thomas S. , Mukherjee Bhramar , Fritsche Lars G. 
Published: August 2021

Abstract
To investigate temporal trends in coronavirus disease 2019 (COVID-19)-related outcomes and to evaluate whether the impacts of potential risk factors and disparities changed over time, we conducted a retrospective cohort study with 249 075 patients tested or treated for COVID-19 at Michigan Medicine (MM), from 10 March 2020 to 3 May 2021. Among these patients, 26 289 were diagnosed with COVID-19. According to the calendar time in which they first tested positive, the COVID-19-positive cohort were stratified into three-time segments (T1: March–June, 2020; T2: July–December, 2020; T3: January–May, 2021). Potential risk factors that we examined included demographics, residential-level socioeconomic characteristics and preexisting comorbidities. The main outcomes included COVID-19-related hospitalisation and intensive care unit (ICU) admission. The hospitalisation rate for COVID-positive patients decreased from 36.2% in T1 to 14.2% in T3, and the ICU admission rate decreased from 16.9% to 2.9% from T1 to T3. These findings confirm that COVID-19-related hospitalisation and ICU admission rates were decreasing throughout the pandemic from March 2020 to May 2021. Black patients had significantly higher (compared to White patients) hospitalisation rates (19.6% vs. 11.0%) and ICU admission rates (6.3% vs. 2.8%) in the full COVID-19-positive cohort. A time-stratified analysis showed that racial disparities in hospitalisation rates persisted over time and the estimates of the odds ratios (ORs) stayed above unity in both unadjusted [full cohort: OR = 1.98, 95% confidence interval (CI) (1.79, 2.19); T1: OR = 1.70, 95% CI (1.36, 2.12); T2: OR = 1.40, 95% CI (1.17, 1.68); T3: OR = 1.55, 95% CI (1.29, 1.86)] and adjusted analysis, accounting for differences in demographics, socioeconomic status, and preexisting comorbid conditions (full cohort: OR = 1.45, 95% CI (1.25, 1.68); T1: OR = 1.26, 95% CI (0.90, 1.76); T2: OR = 1.29, 95% CI (1.01, 1.64); T3: OR = 1.29, 95% CI (1.00, 1.67)).