bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Witch-Hunting Magistrate? Brian Darcy and the St Osyth Witchcraft Cases of 1582
Authors: Durrant Jonathan 
Published: December 2020

Abstract
In just a few short weeks, between 19 February and 26 March 1582, the small coastal town of St Osyth, Essex, became the centre of an outbreak of witch-hunting that saw fifteen suspected witches investigated, two of whom, Ursley Kempe and Elizabeth Bennet, were hanged. Almost immediately, some of the pre-trial materials were published in the pamphlet A True and Just Recorde (1582). These materials have been used to argue that Brian Darcy, the investigating magistrate, hunted witches out of godly zeal, perhaps as part of the earl of Leicester’s campaign against seditious Catholics in the county. Yet, as this article shows, he was neither a ‘contentious person’ nor a witch-hunter. There were genuine reasons why people felt compelled to accuse their neighbours of witchcraft that were rooted in a short-term mortality crisis in and around St Osyth, and fragile personal relationships which made Darcy receptive to their anxieties. Darcy was certainly credulous and played an important role in the examination of the alleged witches who came to his attention, but he did not hunt them out. He was a willing magistrate who reacted to a situation that arose because there existed authentic suspects, accusers with genuine fears and grievances, and local problems which made accusations of witchcraft seems plausible. The St Osyth witchcraft episode was not the product of one man’s actions.
Immediate and long-term health impact of exposure to gas-mining induced earthquakes and related environmental stressors
Authors: Dückers Michel L A , Baliatsas Christos , Spreeuwenberg Peter , Verheij Robert A , Reifels Lennart , Yzermans C Joris 
Published: December 2020

Abstract

Background
Little is known about the public health impact of chronic exposure to physical and social stressors in the human environment. Objective of this study was to investigate the immediate and long-term health effects of living in an environment with gas-mining induced earthquakes and related stressors in the Netherlands.

Methods
Data on psychological, somatic and social problems recorded routinely in electronic health records by general practitioners during a 6-year period (2010–2015) were combined with socioeconomic status and seismicity data. To assess immediate health effects of exposure to ML≥1.5 earthquakes, relative risk ratios were calculated for patients in the week of an earthquake and the week afterwards, and compared to the week before the earthquake. To analyse long-term health effects, relative risks of different groups, adjusted for age, sex and socioeconomic status, were computed per year and compared.

Results
Apart from an increase in suicidality, few immediate health changes were found in an earthquake week or week afterwards. Generally, the prevalence of health problems was higher in the mining province in the first years, but dropped to levels equal to or even below the control group in subsequent years, with lower relative risks observed in more frequently exposed patients.

Conclusions
From a public health perspective, the findings are fascinating. Contrary to our expectation, health problems presented in general practice in the earthquake province decreased during the study period. More frequently exposed populations reported fewer health issues to general practitioners, which might point at health adaptation to chronic exposure to stressors.
Metabolomics of ginger based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology
Authors: Yan Hui , Zou Dongqian , Zhou Guisheng , Yu Hanwen , Li Penghui , Wang Tianshu , Bao Beihua , Guo Sheng , Duan Jinao 
Published: December 2020

Abstract

Objectives
Dried ginger and ginger are the same type of medicine and food. The differential components of ginger and dried ginger, dried ginger and ginger charcoal were investigated.

Materials and Methods
The experimental materials were divided into three sample groups: the ginger group, dried ginger group, and ginger charcoal group. The ginger group, dried ginger group, and ginger charcoal group were qualitatively analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The data were processed by Marker View Software. Principal component analysis and orthogonal partial least-square discriminant analysis were performed with SIMCA 13.0 Software. The differential components of the ginger and dried ginger groups as well as the dried ginger and ginger charcoal groups with a variable importance in the projection &gt; 2 (P &lt; 0.05) were identified with PeakView 1.2 Software.

Results
Ten differential components, including 6-gingerol, 8-gingerol, and 10-gingerol, were identified between the ginger group and dried ginger group; 13 differential components, including 6-shogaol, 10-gingerol, and zingiberone, were identified between the dried ginger group and ginger charcoal group.

Conclusions
The main differential components between the ginger and dried ginger groups and the dried ginger and ginger charcoal groups were gingerols and diphenylheptanes. Based on metabolomics analysis of the chemical composition of ginger’s medicinal materials, effects, and other related factors, it is recommended that 6-gingerol, 6-shogaol, and zingiberone should be used as indicative components for the respective quality evaluation of ginger, dried ginger and ginger charcoal. The results of this study may provide a basis for the reasonable quality evaluation of ginger medicinal materials.
Collagenous Colitis Mucosa Is Characterized by an Expansion of Nonsuppressive FoxP3+ T Helper Cells
Authors: Daferera Niki , Escudero-Hernández Celia , Nyström Sofia , Jenmalm Maria C , Hjortswang Henrik , Ignatova Simone , Ström Magnus , Münch Andreas 
Published: December 2020

Abstract

Background and Aim
Increased frequencies of T regulatory (Treg) cells, key players in immune regulation, have been reported in inflammatory bowel diseases, including collagenous colitis (CC). However, traditional Treg identification techniques might have misinterpreted the frequencies of Treg cells in CC. Thus, we investigated the presence of genuine Treg cells in CC.

Methods
Treg cells were analyzed in mucosal and peripheral blood samples of CC patients before and during treatment with the corticosteroid drug budesonide and in healthy controls. Samples were analyzed by flow cytometry by classifying CD3+CD4+ cells as activated FoxP3highCD45RA- Treg cells, resting FoxP3dimCD45RA+ Treg cells, and nonsuppressive FoxP3dimCD45RA- T helper cells. Traditional gating strategies that classified Treg cells as CD25highCD127low, FoxP3+CD127low, and CD4+CD25+FoxP3+ were also used to facilitate comparison with previous studies.

Results
Activated and resting Treg cell frequencies did not change in active CC mucosa or peripheral blood and were not affected by budesonide treatment. Instead, nonsuppressive FoxP3dimCD45RA- T helper cells were increased in active CC mucosa, and budesonide helped restore them to normal levels. In contrast, traditional Treg cell gating strategies resulted in increased Treg cell frequencies in active CC mucosa. No alterations were found in peripheral blood samples, independently of patient treatment or gating techniques.

Conclusion
Previously reported increase of Treg cells is a result of incomplete Treg phenotyping, which included nonsuppressive FoxP3dimCD45RA- T helper cells. Because budesonide did not affect Treg percentage, its therapeutic effect in CC might involve alternative mechanisms.
A variational approach to the sum splitting scheme
Authors: Eisenmann Monika , Hansen Eskil 
Published: December 2020

AbstractNonlinear parabolic equations are frequently encountered in applications and efficient approximating techniques for their solution are of great importance. In order to provide an effective scheme for the temporal approximation of such equations, we present a sum splitting scheme that comes with a straightforward parallelization strategy. The convergence analysis is carried out in a variational framework that allows for a general setting and, in particular, nontrivial temporal coefficients. The aim of this work is to illustrate the significant advantages of a variational framework for operator splittings and to use this to extend semigroup-based theory for this type of scheme.
Singularities of Non-ℚ-Gorenstein Varieties Admitting a Polarized Endomorphism
Authors: Yoshikawa Shou 
Published: December 2020

Abstract
In this paper, we introduce a new generalization of log canonical singularities for non-$\mathbb{Q}$-Gorenstein varieties. We prove that if a normal complex projective variety has a non-invertible polarized endomorphism, then it has log canonical singularities in our sense. As a corollary, we give an affirmative answer to a conjecture of Broustet and Höring [ 6].
Low rate of oseltamivir prescription among adults and children with confirmed influenza illness in France during the 2018–19 influenza season
Authors: Cizeron Alexandra , Saunier Florian , Gagneux-Brunon Amandine , Pillet Sylvie , Cantais Aymeric , Botelho-Nevers Elisabeth 
Published: December 2020

Abstract

Background
Oseltamivir shows effectiveness in reducing influenza-related symptoms, morbidity and mortality. Its prescription remains suboptimal.

Objectives
We aim to describe oseltamivir prescription in confirmed cases of influenza and to identify associated factors.

Methods
A prospective monocentric observational study was conducted between 1 December 2018 and 30 April 2019. All patients with a virologically confirmed influenza diagnosis were included. Factors associated with oseltamivir prescription were studied.

Results
Influenza was confirmed in 755 patients (483 children and 272 adults), of which 188 (25.1%) were hospitalized and 86 (11.4%) had signs of severity. Oseltamivir was prescribed for 452 patients (59.9%), more frequently in children than in adults [329/483 (68.1%) versus 123/272 (45.2%), P &lt; 0.001]. Factors associated with oseltamivir prescription were evaluated in 729 patients (246 adults and 483 children). Patients with at least one risk factor for severe influenza received oseltamivir less frequently (50%, 137/274) than those without risk factors (70%, 315/452) (P &lt; 0.001). Pregnant women received oseltamivir in 81% of cases (17/21). Severe influenza cases were treated with oseltamivir in only 45.3% (39/86). The median duration of symptoms was 24 h (IQR 12–48) in treated patients versus 72 h (IQR 48–120) in untreated patients (P &lt; 0.01).

Conclusions
Oseltamivir should be administered as early as possible, preferably within 24–48 h after illness onset, for the best benefits. It is, however, very important to promote the use of neuraminidase inhibitor (‘NAI’) treatment beyond 48 h in some specific patient populations.
Effect of a novel animal milk oligosaccharide biosimilar on macronutrient digestibility and gastrointestinal tolerance, fecal metabolites, and fecal microbiota of healthy adult cats
Authors: Oba Patrícia M , Lee Anne H , Vidal Sara , Wyss Romain , Miao Yong , Adesokan Yemi , Swanson Kelly S 
Published: December 2020

Abstract
GNU100 is a novel animal milk oligosaccharide (AMO) biosimilar. In a recent in vitro fermentation study, GNU100 was shown to be fermentable by feline gastrointestinal microbiota and lead to increased short-chain fatty acid production. Our objectives herein were to evaluate the palatability, safety, and gastrointestinal tolerance of GNU100 in healthy adult cats. Exploratory end-points were measured to assess utility. In study 1, 20 adult cats were used to test the palatability of diets containing 0% or 1% GNU100. In study 2, 32 (mean age = 1.9 yr; mean body weight = 4.6 kg) male (n = 12) and female (n = 20) adult cats were used in a completely randomized design. After a 2-wk baseline, cats were assigned to one of the following treatment groups and fed for 26 wk: control (CT, no GNU100), low dose (LD, 0.5% GNU100), medium dose (MD, 1.0% GNU100), and high dose (HD, 1.5% GNU100). On weeks 2, 4, and 26, fresh fecal samples were collected for the measurement of stool quality and immune and inflammatory markers and on weeks 2 and 4 for microbiota and metabolites. On week 4, total feces were collected to measure apparent total tract macronutrient digestibility. On weeks 2, 4, and 26, blood samples were collected for serum chemistry, hematology, and inflammatory marker measurement. The palatability test showed that 1% GNU100 was strongly preferred (P &lt; 0.05), with GNU100 having a 17.6:1 consumption ratio compared with control. In the long-term study, all cats remained healthy, without any signs of gastrointestinal intolerance or illness. All diets were well accepted, resulting in similar (P &gt; 0.05) food intake, fecal characteristics, immunoglobulin A, and calprotectin, and dry matter, organic matter, fat, and crude protein digestibilities. Fecal butyrate was greater (P = 0.02) in cats fed HD than cats fed LD or MD. Fecal indole was lower (P = 0.02) in cats fed HD than cats fed LD. Cats fed CT had a higher (P = 0.003) relative abundance of Actinobacteria than cats fed LD. The relative abundance of Peptococcus was impacted by diet and time. At 4 wk, Campylobacter was lower in fecal samples of cats fed HD. Overall, the data suggest that dietary GNU100 supplementation was highly palatable, well tolerated, did not cause detrimental effects on fecal quality or nutrient digestibility, increased fecal butyrate concentrations, and reduced fecal indole concentrations, supporting the safety of GNU100 for inclusion in feline diets and suggesting potential benefits on gastrointestinal health of cats.
Kavain Interference with Amphetamine Immunoassay
Authors: Madhavaram H , Patel T , Kyle C 
Published: December 2020

Abstract
We encountered unexpected false-positive urine results in three patients for amphetamine-type substances by immunoassay (IA), measured as part of community drug prevention programs. Kavain was identified in all three urine samples by gas chromatography-mass spectrometry (GC--MS). No other potential cross-reactants were found. Kavain is a kava-lactone present in kava, a ceremonial and recreational drink derived from the roots and stems of the plant Piper methysticum. It is consumed regularly by many indigenous Pacific and Australian Aboriginal communities.
Urine IA was performed on a Beckman Coulter AU480 Analyzer using cloned enzyme donor immunoassay (CEDIA) amphetamine-type substance reagent and DRI ethanol reagent. We purchased three different kava powders from local kava clubs and dissolved in ethanol, then evaporated and reconstituted in blank urine and analyzed by IA, GC--MS for amphetamine-type substances. Additionally, authentic kavain standard was also tested for cross-reactivity by IA and analyzed by GC--MS to compare the mass fragmentation pattern and retention time with the kava powder and patient specimens. The patient urine samples tested positive by CEDIA IA for amphetamines. However, when analyzed by GC--MS, they were negative for amphetamine-type but contained kavain. The kava powders and kavain standard all cross-reacted with the amphetamine IA to give falsely detected results. GC--MS did not identify any amphetamine-type compounds in any of the kava powders nor in the kavain standard. To our knowledge, this is the first report of false-positive amphetamine measurements due to kavain, a component of the kava drink, widely consumed in Oceania and Australasia.
Association Between Susceptibility of Thrips palmi to Spinetoram and Frequency of G275E Mutation Provides Basis for Molecular Quantification of Field-Evolved Resistance
Authors: Shi Pan , Guo Shao-Kun , Gao Yong-Fu , Chen Jin-Cui , Gong Ya-Jun , Tang Meng-Qing , Cao Li-Jun , Li Hu , Hoffmann Ary Anthony , Wei Shu-Jun 
Published: December 2020

Abstract
Putative mechanisms underlying spinosyn resistance have been identified in controlled studies on many species; however, mechanisms underlying field-evolved resistance and the development of a molecular diagnostic method for monitoring field resistance have lagged behind. Here, we examined levels of resistance of melon thrips, Thrips palmi Karny (Thysanoptera:Thripidae), to spinetoram as well as target site mutations in field populations across China to identify potential mechanisms and useful molecular markers for diagnostic and quantifying purposes. In resistant populations, we identified the G275E mutation, which has previously been linked to spinosyns resistance, and F314V mutation, both located in the α6 subunit of the nicotinic acetylcholine receptor. There was a strong correlation between levels of spinetoram resistance and allele frequency of G275E mutation in field-collected populations (r2 = 0.84) and those reared under laboratory conditions for two to five generations (r2 = 0.91). LC50 ranged from 0.12 to 0.66 mg/liter in populations without G275E mutation, whereas it ranged from 33.12 to 39.91 mg/liter in most populations with a G275E mutation frequency more than 90%. Our results indicate that the field-evolved resistance of T. palmi to spinetoram in China is mainly conferred by the G275E mutation. The frequency of the G275E mutation provides a useful diagnostic for quantifying resistance levels in field populations of T. palmi.
Leaf apoplastic alkalization promotes transcription of the ABA-synthesizing enzyme Vp14 and stomatal closure in Zea mays
Authors: Geilfus Christoph-Martin , Zhang Xudong , Mithöfer Axel , Burgel Lisa , Bárdos Gyöngyi , Zörb Christian 
Published: December 2020

Abstract
The chloride component of NaCl salinity causes the leaf apoplast to transiently alkalinize. This transition in pH reduces stomatal aperture. However, whether this apoplastic pH (pHapo) transient initiates stomatal closure by interacting with other chloride stress-induced responses or whether the pH transient alone initiates stomatal closure is unknown. To clarify the problem, the transient alkalinization of the leaf apoplast was mimicked in intact maize (Zea mays L.) by infiltrating near-neutral pH buffers into the leaf apoplast. Effects of the pHapo transient could thus be investigated independently from other chloride stress-derived effects. Microscopy-based ratiometric live pHapo imaging was used to monitor pHapoin planta. LC-MS/MS and real-time quantitative reverse transcription–PCR leaf analyses showed that the artificially induced pHapo transient led to an increase in the concentrations of the stomata-regulating plant hormone abscisic acid (ABA) and in transcripts of the key ABA-synthesizing gene ZmVp14 in the leaf. Since stomatal aperture and stomatal conductance decreased according to pHapo, we conclude that the pHapo transient alone initiates stomatal closure. Therefore, the functionality does not depend on interactions with other compounds induced by chloride stress. Overall, our data indicate that the pH of the leaf apoplast links chloride salinity with the control of stomatal aperture via effects exerted on the transcription of ABA.
The American Paddlefish Genome Provides Novel Insights into Chromosomal Evolution and Bone Mineralization in Early Vertebrates
Authors: Cheng Peilin , Huang Yu , Lv Yunyun , Du Hao , Ruan Zhiqiang , Li Chuangju , Ye Huan , Zhang Hui , Wu Jinming , Wang Chengyou , Ruan Rui , Li Yanping , Bian Chao , You Xinxin , Shi Chengcheng , Han Kai , Xu Junming , Shi Qiong , Wei Qiwei 
Published: December 2020

Abstract
Sturgeons and paddlefishes (Acipenseriformes) occupy the basal position of ray-finned fishes, although they have cartilaginous skeletons as in Chondrichthyes. This evolutionary status and their morphological specializations make them a research focus, but their complex genomes (polyploidy and the presence of microchromosomes) bring obstacles and challenges to molecular studies. Here, we generated the first high-quality genome assembly of the American paddlefish (Polyodon spathula) at a chromosome level. Comparative genomic analyses revealed a recent species-specific whole-genome duplication event, and extensive chromosomal changes, including head-to-head fusions of pairs of intact, large ancestral chromosomes within the paddlefish. We also provide an overview of the paddlefish SCPP (secretory calcium-binding phosphoprotein) repertoire that is responsible for tissue mineralization, demonstrating that the earliest flourishing of SCPP members occurred at least before the split between Acipenseriformes and teleosts. In summary, this genome assembly provides a genetic resource for understanding chromosomal evolution in polyploid nonteleost fishes and bone mineralization in early vertebrates.
Structural basis for inhibition of the type I-F CRISPR–Cas surveillance complex by AcrIF4, AcrIF7 and AcrIF14
Authors: Gabel Clinton , Li Zhuang , Zhang Heng , Chang Leifu 
Published: December 2020

Abstract
CRISPR–Cas systems are adaptive immune systems in bacteria and archaea to defend against mobile genetic elements (MGEs) and have been repurposed as genome editing tools. Anti-CRISPR (Acr) proteins are produced by MGEs to counteract CRISPR–Cas systems and can be used to regulate genome editing by CRISPR techniques. Here, we report the cryo-EM structures of three type I-F Acr proteins, AcrIF4, AcrIF7 and AcrIF14, bound to the type I-F CRISPR–Cas surveillance complex (the Csy complex) from Pseudomonas aeruginosa. AcrIF4 binds to an unprecedented site on the C-terminal helical bundle of Cas8f subunit, precluding conformational changes required for activation of the Csy complex. AcrIF7 mimics the PAM duplex of target DNA and is bound to the N-terminal DNA vise of Cas8f. Two copies of AcrIF14 bind to the thumb domains of Cas7.4f and Cas7.6f, preventing hybridization between target DNA and the crRNA. Our results reveal structural detail of three AcrIF proteins, each binding to a different site on the Csy complex for inhibiting degradation of MGEs.
A hotspot for enhancing insulin receptor activation revealed by a conformation-specific allosteric aptamer
Authors: Yunn Na-Oh , Park Mangeun , Park Seongeun , Lee Jimin , Noh Jeongeun , Shin Euisu , Ryu Sung Ho 
Published: December 2020

Abstract
Aptamers are single-stranded oligonucleotides that bind to a specific target with high affinity, and are widely applied in biomedical diagnostics and drug development. However, the use of aptamers has largely been limited to simple binders or inhibitors that interfere with the function of a target protein. Here, we show that an aptamer can also act as a positive allosteric modulator that enhances the activation of a receptor by stabilizing the binding of a ligand to that receptor. We developed an aptamer, named IR-A43, which binds to the insulin receptor, and confirmed that IR-A43 and insulin bind to the insulin receptor with mutual positive cooperativity. IR-A43 alone is inactive, but, in the presence of insulin, it potentiates autophosphorylation and downstream signaling of the insulin receptor. By using the species-specific activity of IR-A43 at the human insulin receptor, we demonstrate that residue Q272 in the cysteine-rich domain is directly involved in the insulin-enhancing activity of IR-A43. Therefore, we propose that the region containing residue Q272 is a hotspot that can be used to enhance insulin receptor activation. Moreover, our study implies that aptamers are promising reagents for the development of allosteric modulators that discriminate a specific conformation of a target receptor.