bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme Low Flows in Rivers of the East European Plain in the 19th–21st Centuries
Authors: Georgiadi A G , Borodin O O 
Published: May 2022

Abstract
This study is focused on extreme low flows in rivers (when water flow is less than or equal to 75 and 90% exceedance probability) in the East European Plain (Volga, Don, Dnieper, Western Dvina, and Northern Dvina) in the 19th–21st centuries. It is shown that the proportion of years in which an extreme low flow is observed in one or more seasons of the year or in the year as a whole during the entire observation period varies from 46 to 57%. In 30 years, a low flow formed only in one basin under consideration, and in 50 years, it was observed in several (from 2 to 5) basins simultaneously. In seven years, an extreme low flow was observed in different hydrological seasons and during the entire years simultaneously in all the rivers and, in nine cases, in four basins. Modern global warming leads to a significant decrease in the number of low-flow years in the winter and summer-autumn low-water seasons and the year as a whole for all the rivers under consideration. In years when severe draughts were recorded in the territories of all river basins under consideration, low flows were recorded only in 1921 and 1972.
Experimental investigation on mechanical behavior of as cast Zn-Al-Cu/SiC/TiB2 hybrid metal matrix composite by ultrasonic assisted stir casting technique
Authors: Chebolu Rohinikumar , Nallu Ramanaiah , Chanamala Ratnam 
Published: May 2022

Abstract
Now a days, the Zn-Al-Cu alloy-based composites have great impact on modern trends for bearing applications because of its reliable mechanical performance. In this paper the mechanical characteristics of as cast Zn-Al-Cu alloy-based hybrid metal matrix composites have been investigated, as well as the influence of reinforcements Silicon Carbide (SiC) and Titanium Diboride (TiB2) on the composite. The ultrasonic assisted stir casting technique has been adopted for fabricating the composites with the addition of dual reinforcements like 5 wt% of SiC as constant and by varying the wt% of TiB2 as 0 wt%, 5 wt% and 10 wt%. The ceramic particles SiC and TiB2 are taken with 20 and 30 microns in size. The ASTM standards were used to conduct the different tests, and the findings demonstrate the significance of adding reinforcements to alloy and also noticeable increase in mechanical performance in terms of hardness, tensile strength, young’s modulus and impact strength. As cast Zn-Al-Cu/5 wt.% of SiC/10 wt.% of TiB2 hybrid composite gives the minimum density as 4.79 g cc−1 and maximum hardness as 156Hv.
Examining clustered somatic mutations with SigProfilerClusters
Authors: Bergstrom Erik N , Kundu Mousumy , Tbeileh Noura , Alexandrov Ludmil B 
Published: May 2022

AbstractMotivationClustered mutations are found in the human germline as well as in the genomes of cancer and normal somatic cells. Clustered events can be imprinted by a multitude of mutational processes, and they have been implicated in both cancer evolution and development disorders. Existing tools for identifying clustered mutations have been optimized for a particular subtype of clustered event and, in most cases, relied on a predefined inter-mutational distance (IMD) cutoff combined with a piecewise linear regression analysis.ResultsHere, we present SigProfilerClusters, an automated tool for detecting all types of clustered mutations by calculating a sample-dependent IMD threshold using a simulated background model that takes into account extended sequence context, transcriptional strand asymmetries and regional mutation densities. SigProfilerClusters disentangles all types of clustered events from non-clustered mutations and annotates each clustered event into an established subclass, including the widely used classes of doublet-base substitutions, multi-base substitutions, omikli and kataegis. SigProfilerClusters outputs non-clustered mutations and clustered events using standard data formats as well as provides multiple visualizations for exploring the distributions and patterns of clustered mutations across the genome.Availability and implementationSigProfilerClusters is supported across most operating systems and made freely available at https://github.com/AlexandrovLab/SigProfilerClusters with an extensive documentation located at https://osf.io/qpmzw/wiki/home/.Supplementary informationSupplementary data are available at Bioinformatics online.
Simultaneous Determination of Cortisol and 6β-Hydroxycortisol in Human Plasma by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Sun Lu-Ning , Shen Ye , Yang Yu-Qing , Chen Xiang-Long , Huang Feng-Ru , Wang Dun-Jian , Zhang Ye , Wang Da-Wei , Wang Yong-Qing 
Published: May 2022

Abstract
The feasibility of taking the ratio of 6β-hydroxycortisol (6β-OHCOR) to cortisol (COR) in plasma as a biomarker to reflect CYP3A4 activity needs to be verified, but the low concentration of 6β-OHCOR which is an endogenous substance in plasma presents a challenge for determination. In this study, a Liquid chromatography with tandem mass spectrometry (LC–MS/MS) method was established to simultaneously quantify the COR and 6β-OHCOR in plasma with COR-d4 and 6β-OHCOR-d4 as internal standards (ISs). Plasma samples were treated by protein precipitation using acetonitrile. Separation with a gradient elution within 5 min was achieved on C18+ column utilizing 5 mM ammonium formate and methanol. An API 4,000 MS in multiple reaction monitoring mode with transitions of 407.1 → 361.1 and 423.1 → 347.1 was utilized. Albumin solution was used as a surrogate matrix, with good linearities over the concentration of 1.20–300 ng/mL for COR and 0.0400–10.0 ng/mL for 6β-OHCOR. The precisions for intrarun and interrun were &lt; 6.8%, and the accuracy was fell in the interval of −5.2 to 3.5%. Matrix effect was not found. Recovery was close to 100.0%. Stability was confirmed under the storage and processing conditions. The validated method was applied to evaluate the inhibitory effect of voriconazole to CYP3A by the ratio of 6β-OHCOR to COR.
Repurposing drugs for highly prevalent diseases: pentoxifylline, an old drug and a new opportunity for diabetic kidney disease
Authors: Donate-Correa Javier , Sanchez-Niño María Dolores , González-Luis Ainhoa , Ferri Carla , Martín-Olivera Alberto , Martín-Núñez Ernesto , Fernandez-Fernandez Beatriz , Tagua Víctor G , Mora-Fernández Carmen , Ortiz Alberto , Navarro-González Juan F 
Published: May 2022

ABSTRACT
Diabetic kidney disease is one of the most frequent complications in patients with diabetes and constitutes a major cause of end-stage kidney disease. The prevalence of diabetic kidney disease continues to increase as a result of the growing epidemic of diabetes and obesity. Therefore, there is mounting urgency to design and optimize novel strategies and drugs that delay the progression of this pathology and contain this trend. The new approaches should go beyond the current therapy focussed on the control of traditional risk factors such as hyperglycaemia and hypertension. In this scenario, drug repurposing constitutes an economic and feasible approach based on the discovery of useful activities for old drugs. Pentoxifylline is a nonselective phosphodiesterase inhibitor currently indicated for peripheral artery disease. Clinical trials and meta-analyses have shown renoprotection secondary to anti-inflammatory and antifibrotic effects in diabetic patients treated with this old known drug, which makes pentoxifylline a candidate for repurposing in diabetic kidney disease.
Electrocardiography: an usefull tool for prediction of the diagnosis and severity of pulmonary embolism
Authors: Couto Pereira S , Valente Silva B , Silverio Antonio P , Brito J , Alves Da Silva P , Simoes De Oliveira C , Beatriz Garcia A , Martins M , Nobre Menezes M , Garcia L , Jorge C , Cortez-Dias N , Pinto FJ 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Pulmonary embolism (PE) is associated with morbidity and mortality. Immediate recognition of this condition is critical to commencement of early and appropriate therapy which could be lifesaving. Particularly in patients with suspected PE in which computed tomography pulmonary angiography (CTPA) is not promptly available or is contra-indicated, an electrocardiographic (ECG) score could serve as a ubiquitously available test to raise suspicion of PE. This study aimed to evaluate the diagnostic value of an ECG score for PE diagnosis.

Methods
Retrospective study of consecutive patients who performed CTPA in Emergency Department due to PE suspicion. All ECG were scored according to the previous published Daniel’s ECG score, by an investigator blinded for the CTPA result.

Results
The most common ECG findings in patients with PE were incomplete right-brand bock (48%), T wave inversion in DIII (48%), sinus tachycardia (41%) and Q wave in DII (31%). The S1Q3T3 sign was documented in 20% of patients.
The ECG score was significantly higher in patients with PE compared to those without PE (5.06 vs 3.70, p=0.005). ECG score showed moderate accuracy to detect PE (AUC: 0.60; 95%CI: 0.53-0.67; p=0.004), but it is of a particular value because of very high specificity: an ECG score &gt; 12 identified PE with a specificity of 96% (95% CI 91.93 – 98.38).
The ECG score significantly increased the diagnostic accuracy of the diagnostic algorithm based on pretest clinical probability evaluated by Wells score combined with D-Dimer measurement (Wells & DD). In comparison to patients in which clinical pretest probability combined with D-dimer measurement considers PE excluded (Wells & ECG -), PE was 6.3 times more frequent in patients with Wells & DD +/ECG- (95% 2.7- 14.5) and 14.6 times more prevalent in the ones with Wells & DD +/ECG+ (95%CI: 4.1-51.3; p&lt;0.001) – Figure 1.

Conclusion
In patients with clininal suspition of PE, na ECG score (Daniel’s score) &gt;12 predicts PE with 96% specificity and could be used to increase the suspicion and define therapeutic strategy in patients in whom CTPA could not be immediately performed or is contra-indicated.
Selective epicardial pulsed field ablation of atrial ganglionated plexi causes anti-arrhythmic prolongation of refractoriness: demonstration of feasibility in cardiac surgery patients
Authors: De Groot JR , Shaburishvili T , Skalsky I , Van Zyl M , O Brien B , Reilly J , Coffey K , Neuzil P , Reddy VY 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020 SME Instrument.

Background
Epicardial ganglionated plexi (GP) play a significant role in the initiation and maintenance of atrial fibrillation. However, modulation of this effect, through GP ablation, has had limited success; outcomes being confounded by unnecessary atrial tissue ablation and inability to access and ablate all of the atrial GPs. Selective pulsed field ablation (PFA) of GPs, using epicardial access, provides the opportunity to better identify the role of GP ablation in the treatment of atrial fibrillation.

Purpose
This study aimed to assess the safety and feasibility of selective GP ablation in patients undergoing elective coronary artery bypass grafting (CABG). It was hypothesized that GP ablation would provide an acute extension of atrial tissue refractoriness, which constitutes its antiarrhythmic effect.

Methods
Using a monopolar, monophasic PFA system, atrial GPs were ablated in nineteen patients with or without atrial fibrillation, undergoing CABG. The Oblique Sinus GP, Right Superior GP, Transverse Sinus GP, Left Superior GP and Ligament of Marshall GP were each ablated with up to sixty PFA pulses of 1000 V amplitude and 100 µs pulse width. Atrial Effective Refractory Period (AERP) was measured before and after all GP ablations, at the left atrial appendage (LAA) and on the right atrium (RA). Patients were monitored through to discharge for post-operative atrial fibrillation (POAF).

Results
Complete ablation of the GPs was performed in nineteen patients (aged 63.4 ± 6.6 years, 63.1% male) immediately after sternotomy. Electric field pulses were ECG-gated, with energy delivery during the ventricular refractory period. All GP sites were successfully accessed and ablated; all patients progressed immediately to their planned elective surgery and were discharged on schedule. Procedure time, for all GP ablations and AERP measurements was in the range 35-45 minutes. Thirteen valid pre- and post-ablation datasets were obtained. AERP (LAA and RA combined) increased upon GP ablation on average by 23% (220 ± 46 ms pre-ablation versus 269 ± 59 ms post-ablation, p = 0.002). Four patients experienced POAF; there was no evident correlation between POAF and AERP data. Only three of the enrolled patients had a prior history of AF; none of these exhibited AF on 24-hour Holter monitoring at 3-month follow-up.

Conclusions
Selective epicardial PFA of GPs is feasible and safe. An acute increase in atrial tissue refractoriness is promising but further studies are required to see how this translates to longer term outcomes in symptomatic AF patients and in a percutaneous epicardial access setting.
Management of conduction disorders after transcatheter aortic valve implantation: results of an EHRA survey
Authors: Badertscher P , Knecht S , Zeljkovic I , Sticherling C , De Asmundis C , Conte G , Kuehne M , Boveda S 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Left bundle branch block (LBBB) is common after transcatheter aortic valve implantation (TAVI) and is an indicator of subsequent high-grade atrioventricular block. Consensus regarding a reasonable strategy to manage cardiac conduction disturbances after TAVI has been elusive

Methods
The European Heart Rhythm Association (EHRA) conducted a survey to capture contemporary clinical practice for conduction disorders after TAVI. A 25-item online questionnaire was developed and distributed among the EHRA electrophysiology research network centres.

Results
Of 117 respondents, 44% were affiliated with university hospitals. This survey has revealed that a standardized management protocol for advanced conduction disorders such as LBBB or AVB after TAVR is available in 63% of participating centres. Telemetry was chosen by most participants as the most frequent management strategy for patients with new or preexisting LBBB after TAVI (79%, 70%, respectively, Figure 1). Duration of telemetry in patients with new LBBB varied: 18% chose 24 hours, 35% 48 hours, 27% 72 hours and 20% ≥ 72 hours. Similarly, in patients with new LBBB after TAVI undergoing EP study, the cut-off for a prolonged HV interval for PM implantation was heterogenous among European centers (7.4% ≥ 55ms and 44% ≥ 75ms). Conduction system pacing was chosen as preferred device therapy in patients with LBBB and normal LVEF in 3.7% and in patients with LBBB and reduced LVEF in 5.6%.

Conclusions
The management of conduction disorders after TAVI is very heterogeneous across European centres. Risk stratification strategies vary substantially. The role of conduction system pacing in patients with LBBB after TAVI needs to be defined. There is a considerable room for better uniformity in clinical practice.
Biological units of antimicrobial resistance and strategies for their containment in animal production
Authors: Muurinen Johanna , Cairns Johannes , Ekakoro John Eddie , Wickware Carmen L , Ruple Audrey , Johnson Timothy A 
Published: May 2022

Abstract
The increasing prevalence of antimicrobial-resistant bacterial infections has ushered in a major global public health crisis. Judicious or restricted antimicrobial use in animal agriculture, aiming to confine the use for the treatment of infections, is the most commonly proposed solution to reduce selection pressure for resistant bacterial strains and resistance genes. However, a multifaceted solution will likely be required to make acceptable progress in reducing antimicrobial resistance, due to other common environmental conditions maintaining antimicrobial resistance and limited executionary potential as human healthcare and agriculture will continue to rely heavily on antimicrobials in the foreseeable future. Drawing parallels from systematic approaches to the management of infectious disease agents and biodiversity loss, we provide examples that a more comprehensive approach is required, targeting antimicrobial resistance in agroecosystems on multiple fronts simultaneously. We present one such framework, based on nested biological units of antimicrobial resistance, and describe established or innovative strategies targeting units. Some of the proposed strategies are already in use or ready to be implemented, while some require further research and discussion among scientists and policymakers. We envision that antimicrobial resistance mitigation strategies for animal agriculture combining multiple tools would constitute powerful ecosystem-level interventions necessary to mitigate antimicrobial resistance.
Genetic background and mistranslation frequency determine the impact of mistranslating tRNASerUGG
Authors: Berg Matthew D , Zhu Yanrui , Loll-Krippleber Raphaël , San Luis Bryan-Joseph , Genereaux Julie , Boone Charles , Villén Judit , Brown Grant W , Brandl Christopher J 
Published: May 2022

Abstract
Transfer RNA variants increase the frequency of mistranslation, the misincorporation of an amino acid not specified by the “standard” genetic code, to frequencies approaching 10% in yeast and bacteria. Cells cope with these variants by having multiple copies of each tRNA isodecoder and through pathways that deal with proteotoxic stress. In this study, we define the genetic interactions of the gene encoding tRNASerUGG,G26A, which mistranslates serine at proline codons. Using a collection of yeast temperature-sensitive alleles, we identify negative synthetic genetic interactions between the mistranslating tRNA and 109 alleles representing 91 genes, with nearly half of the genes having roles in RNA processing or protein folding and turnover. By regulating tRNA expression, we then compare the strength of the negative genetic interaction for a subset of identified alleles under differing amounts of mistranslation. The frequency of mistranslation correlated with the impact on cell growth for all strains analyzed; however, there were notable differences in the extent of the synthetic interaction at different frequencies of mistranslation depending on the genetic background. For many of the strains, the extent of the negative interaction with tRNASerUGG,G26A was proportional to the frequency of mistranslation or only observed at intermediate or high frequencies. For others, the synthetic interaction was approximately equivalent at all frequencies of mistranslation. As humans contain similar mistranslating tRNAs, these results are important when analyzing the impact of tRNA variants on disease, where both the individual’s genetic background and the expression of the mistranslating tRNA variant need to be considered.
JiangShi(僵尸): a widely distributed Mucin-like protein essential for Drosophila development
Authors: Huang Yueping , Li LingLing , Rong Yikang S 
Published: May 2022

Abstract
Epithelia exposed to elements of the environment are protected by a mucus barrier in mammals. This barrier also serves to lubricate during organ movements and to mediate substance exchanges between the environmental milieu and internal organs. A major component of the mucus barrier is a class of glycosylated proteins called Mucin. Mucin and mucin-related proteins are widely present in the animal kingdom. Mucin mis-regulation has been reported in many diseases such as cancers and ones involving the digestive and respiratory tracts. Although the biophysical properties of isolated Mucins have been extensively studied, in vivo models remain scarce for the study of their functions and regulations. Here, we characterize the Mucin-like JiangShi protein and its mutations in the fruit fly Drosophila. JiangShi is an extracellular glycoprotein with domain features reminiscent of mammalian nonmembranous Mucins, and one of the most widely distributed Mucin-like proteins studied in Drosophila. Both loss and over-production of JiangShi lead to terminal defects in adult structures and organismal death. Although the physiological function of JiangShi remains poorly defined, we present a genetically tractable model system for the in vivo studies of Mucin-like molecules.
Decreased EMILIN2 correlates to metabolism phenotype and poor prognosis of ovarian cancer
Authors: Tang Xiaojian , Li Fengli 
Published: May 2022

Abstract
This study aimed to explore the function and related mechanisms of elastin microfibril interfacer 2 (EMILIN2) in ovarian cancer. First, the expression level of EMILIN2 was detected in patient tissues and its correlation with overall survival rate was analysed. Then, EMILIN2 was overexpressed in ovarian cancer cell lines to observe its function and effect on Warburg effect. By detecting its promoter region methylation, the epigenetic regulatory role was explored. Finally, through the luciferase reporter assay and siRNA tools, the regulatory mechanism of p53 on EMILIN2 was investigated. It was detected in clinical samples that down-regulated EMILIN2 was associated with poor prognosis of ovarian cancer. It was further found that EMILIN2 regulated the metabolic phenotype of ovarian cancer cells. The expression of EMILIN2 was epigenetically regulated by its promoter methylation. Also, it was found that p53 regulated the expression of EMILIN2 and the p53/EMILIN2 axis regulated the Warburg effect in ovarian cancer cells. EMILIN2 was inhibited by methylation in ovarian cancer. In summary, p53 can promote and regulate its transcription by binding to the promoter region of EMILIN2, thereby affecting the Warburg effect and inhibiting tumours. Therefore, EMILIN2 might be a potential target for clinical diagnosis and treatment of ovarian cancer.
Business and Investment in Brazil
Authors: Sester Peter 
Published: May 2022

Abstract
This book provides a thorough analysis of Brazilian business law for investors and their legal advisers, focusing on topics relevant to business transactions and disputes that can arise in the aftermath of the signing or performance of deals. The essence of investment and negotiation processes is risk evaluation and allocation. Examining Brazilian law, the book focuses on the legal risks, which are higher in Brazilian law than elsewhere, particularly in comparison with contract, partnership, and company (LLC) laws governing international business transactions in the US and UK. However, whilst Brazilian contract law remains a risk factor as a result of its over-ambitious and consequently interventionist approach, Brazilian law in the areas of stock corporation, capital market, antitrust, and public procurement are state-of-the-art when compared to the US and leading European laws in Germany, Switzerland, and France. The book is divided into eight chapters: the introduction provides an overview of the economic and legal framework for doing business in Brazil, focusing on features of the Brazilian legal and economic order that are unusual to international practitioners from a comparative perspective. The other seven chapters analyze those fields of substantive law that impact most investments and cross-border transactions in Brazil. The book focuses on the interpretation of statutory law by the Brazilian Superior Court of Justice and regulatory agencies, and also provides insights into the economic and business rationale of some of the legal solutions offered.