bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of VigiBase reports on tinnitus associated with bisoprolol—An exploratory and descriptive study
Authors: Watson Sarah , Taavola Henric , Attalla Marian , Kaminsky Elenor , Yue Quin‐Ying 
Published: May 2021

AbstractThe aim of this descriptive and explorative study was to assess individual case safety reports of bisoprolol associated with tinnitus and investigate their added value in information about adverse drug reactions (ADRs) in relation to information provided in medicine labels. The global reports from VigiBase, the WHO database of individual case safety reports, as of May 3, 2020, were analyzed for information about bisoprolol associated with tinnitus as an ADR affecting the quality of life of the patients. There were 123 reports of the ADR tinnitus reported with intake of bisoprolol in VigiBase. These described experiences of tinnitus and how this impacted on patients’ daily life, for example, it could be long‐lasting and may have negative impact on sleeping, and even ability to work and keep a job. There were also reports describing the management of the reaction, for example, recovery upon stopping the treatment, and improvement of the symptoms following a decreased dose or change of medicine batch. Based on reports in VigiBase, the ADR tinnitus associated with bisoprolol suggests vigilance for the onset of the event and that, if it occurs, a dose reduction or stopping the treatment could be necessary. The information provided in the reports shows the value of individual case safety reports collected post marketing, in providing descriptive information of the experience and management of the ADR.
A phase I, single and continuous dose administration study on the safety, tolerability, and pharmacokinetics of neorudin, a novel recombinant anticoagulant protein, in healthy subjects
Authors: Liu Yubin , Wang Meixia , Dong Xiaona , He Jia , Zhang Lin , Zhou Ying , Xia Xia , Dou Guifang , Wu Chu‐tse , Jin Jide 
Published: May 2021

AbstractThe aim of this study was to evaluate the tolerability, safety, and pharmacokinetics of single and continuous dose administration of recombinant neorudin (EPR‐hirudin, EH) by intravenous administration in healthy subjects, and to provide a safe dosage range for phase II clinical research. Forty‐four subjects received EH as a single dose of between 0.2 and 2.0 mg/kg by intravenous bolus and drip infusion. In addition, 18 healthy subjects were randomly divided into three dose groups (0.15, 0.30, and 0.45 mg/kg/h) with 6 subjects in each group for the continuous administration trial. Single or continuous doses of neorudin were generally well tolerated by healthy adult subjects. There were no serious adverse events (SAEs), and all adverse events (AEs) were mild to moderate. Moreover, no subjects withdrew from the trial because of AEs. There were no clinically relevant changes in physical examination results, clinical chemistry, urinalysis, or vital signs. The incidence of adverse events was not significantly related to drug dose or systemic exposure. After single‐dose and continuous administration, the serum EH concentration reached its peak at 5 min, and the exposure increased with the increase in the administered dose. The mean half‐life (T1/2), clearance (Cl), and apparent volume of distribution (Vd) of EH ranged from 1.7 to 2.5 h, 123.9 to 179.7 ml/h/kg, and 402.7 to 615.2 ml/kg, respectively. The demonstrated safety, tolerability, and pharmacokinetic characteristics of EH can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies.Clinical trial registration: Chinadrugtrials.org identifier: CTR20160444.
Pharmacokinetic/pharmacodynamic modeling of drug interactions at the P2Y12 receptor between selatogrel and oral P2Y12 antagonists
Authors: Henrich Andrea , Claussen Christian Hove , Dingemanse Jasper , Krause Andreas 
Published: May 2021

AbstractSelatogrel is a potent and reversible P2Y12 receptor antagonist developed for subcutaneous self‐administration by patients with suspected acute myocardial infarction. After single‐dose emergency treatment with selatogrel, patients are switched to long‐term treatment with oral P2Y12 receptor antagonists. Selatogrel shows rapid onset and offset of inhibition of platelet aggregation (IPA) to overcome the critical initial time after acute myocardial infarction. Long‐term benefit is provided by oral P2Y12 receptor antagonists such as clopidogrel, prasugrel, and ticagrelor. A population pharmacokinetic (PK)/pharmacodynamic (PD) model based on data from 545 subjects in 4 phase I and 2 phase II studies well described the effect of selatogrel on IPA alone and in combination with clopidogrel, prasugrel, and ticagrelor. The PK of selatogrel were described by a three‐compartment model. The PD model included a receptor‐pool compartment to which all drugs can bind concurrently, reversibly or irreversibly, depending on their mode of action. Furthermore, ticagrelor and its active metabolite can bind to the selatogrel‐receptor complex allosterically, releasing selatogrel from the binding site. The model provided a framework for predicting the effect on IPA of selatogrel followed by reversibly and irreversibly binding oral P2Y12 receptor antagonists for sustained effects. Determining the timepoint for switching from emergency to maintenance treatment is critical to achieve sufficient IPA at all times. Simulations based on the interaction model showed that loading doses of clopidogrel and prasugrel administered 15 h and 4.5 h after selatogrel, respectively, provide sustained IPA with clinically negligible drug interaction.
Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Selatogrel is a potent reversible P2Y12 receptor antagonist developed for subcutaneous self‐administration by patients in case of suspected acute myocardial infarction. Transition to oral P2Y12 receptor antagonists without drug interaction and sufficient inhibition of platelet aggregation must be assured at all times.

WHAT QUESTION DID THIS STUDY ADDRESS?
The pharmacokinetic/pharmacodynamic model semimechanistically describes the effect of selatogrel on platelet inhibition alone and in combination with the oral P2Y12 receptor antagonists clopidogrel, prasugrel, and ticagrelor.

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
Model‐based simulations showed that loading doses of clopidogrel and prasugrel can be administered from 15 h and 4.5 h after selatogrel, respectively.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
These results support guiding the clinical transition from selatogrel emergency treatment to oral maintenance therapy in a safe and efficacious way.
A wavefunction model to chemical bonding
Authors: Náray‐Szabó Gábor , Mezey Paul G. 
Published: May 2021

AbstractIn this paper we give a brief survey on some specific aspects of a wavefunction model for chemical bonding which are connected to or have been motivated in part by the work of the late István Mayer and colleagues. After a brief description of the early wavefunction models as reflected in Mayer's works, naturally leading to electron densities, we discuss localized molecular orbitals, and summarize some of the early initiatives and applications. The concept of the Chemical Hamiltonian, as introduced by Mayer, its extensions and some classical and some more advanced connections will be discussed. The twofold motivating role of Mayer in the development of the earliest, ab initio level macromolecular linear scaling methods, giving proven “ab initio quality” protein energy results by the adjustable density matrix assembler method, and in some other molecular fragment advances will be also pointed out.
Current and future deep learning algorithms for tandem mass spectrometry (MS/MS)‐based small molecule structure elucidation
Authors: Liu Youzhong , De Vijlder Thomas , Bittremieux Wout , Laukens Kris , Heyndrickx Wouter 
Published: May 2021

RationaleStructure elucidation of small molecules has been one of the cornerstone applications of mass spectrometry for decades. Despite the increasing availability of software tools, structure elucidation from tandem mass spectrometry (MS/MS) data remains a challenging task, leaving many spectra unidentified. However, as an increasing number of reference MS/MS spectra are being curated at a repository scale and shared on public servers, there is an exciting opportunity to develop powerful new deep learning (DL) models for automated structure elucidation.ArchitecturesRecent early‐stage DL frameworks mostly follow a “two‐step approach” that translates MS/MS spectra to database structures after first predicting molecular descriptors. The related architectures could suffer from: (1) computational complexity because of the separate training of descriptor‐specific classifiers, (2) the high dimensional nature of mass spectral data and information loss due to data preprocessing, (3) low substructure coverage and class imbalance problem of predefined molecular fingerprints. Inspired by successful DL frameworks employed in drug discovery fields, we have conceptualized and designed hypothetical DL architectures to tackle the above issues. For (1), we recommend multitask learning to achieve better performance with fewer classifiers by grouping structurally related descriptors. For (2) and (3), we introduce feature engineering to extract condensed and higher‐order information from spectra and structure data. For instance, encoding spectra with subtrees and pre‐calculated spectral patterns add peak interactions to the model input. Encoding structures with graph convolutional networks incorporates connectivity within a molecule. The joint embedding of spectra and structures can enable simultaneous spectral library and molecular database search.ConclusionsIn principle, given enough training data, adapted DL architectures, optimal hyperparameters and computing power, DL frameworks can predict small molecule structures, completely or at least partially, from MS/MS spectra. However, their performance and general applicability should be fairly evaluated against classical machine learning frameworks.
From Water Solutions to Ionic Liquids with Solid State Nanopores as a Perspective to Study Transport and Translocation Phenomena
Authors: Marion Sanjin , Vučemilović‐Alagić Nataša , Špadina Mario , Radenović Aleksandra , Smith Ana‐Sunčana 
Published: May 2021

AbstractSolid state nanopores are single‐molecular devices governed by nanoscale physics with a broad potential for technological applications. However, the control of translocation speed in these systems is still limited. Ionic liquids are molten salts which are commonly used as alternate solvents enabling the regulation of the chemical and physical interactions on solid–liquid interfaces. While their combination can be challenging to the understanding of nanoscopic processes, there has been limited attempts on bringing these two together. While summarizing the state of the art and open questions in these fields, several major advances are presented with a perspective on the next steps in the investigations of ionic‐liquid filled nanopores, both from a theoretical and experimental standpoint. By analogy to aqueous solutions, it is argued that ionic liquids and nanopores can be combined to provide new nanofluidic functionalities, as well as to help resolve some of the pertinent problems in understanding transport phenomena in confined ionic liquids and providing better control of the speed of translocating analytes.
Typification of Dactylis ibizensis (Poaceae) and inference of the ploidy level of the type specimen
Authors: Rosselló Josep A. , Maravilla Alexis J. , Rosato Marcela , Torres Nèstor , Ferrer‐Gallego P. Pablo 
Published: May 2021

AbstractDactylis ibizensis (Poaceae) is lectotypified based on a specimen at W. Anatomical and macromorphological data from karyologically verified individuals strongly support that the lectotype comprises exclusively diploid plants. This allows for preservation of the name in current use for the Balearic cocksfoot restricted to the islands of Formentera and Ibiza.
A novel (ATC)n microsatellite locus is associated with litter size in an indigenous Chinese pig
Authors: Wu Guofang , Shen Wenjuan , Xue Xingxing , Wang Lei , Ma Yuhong , Zhou Jiping 
Published: May 2021

AbstractSimple sequence repeats (SSRs) are an important part of the genome and have become powerful auxiliary DNA markers in animal breeding using marker‐assisted selection (MAS). Based on previous sequencing data of Qinghai Bamei pigs, a total of three novel candidate SSR loci were analysed in this study. Time‐of‐flight mass spectrometry (TOF‐MS) was used for SSR genotyping, and association analyses between SSRs and the litter size of Qinghai Bamei sows was also performed. The results of genotyping showed that the (ATC)n‐P1, (AC)n‐P2 and (AC)n‐P3 loci had 2, 3 and 18 genotypes, respectively; 2, 3 and 8 alleles were also identified at these loci. Except for the (AC)n‐P2 locus, the polymorphism information content (PIC) values of other loci were greater than 0.25. Association analyses indicated that only the (ATC)n‐P1 locus was significantly associated with the litter size of Qinghai Bamei sows (p = .047). Compared to 189‐/189‐ genotype, individuals with the 189‐/195‐ genotype had the senior litter size, which was 9.04 ± 0.21. Our results enrich the data on SSRs in Qinghai Bamei pigs and indicate that (ATC)n‐P1 is a candidate locus for MAS in the pig industry.
Seroprevalence of Coxiella burnetii in patients presenting with acute febrile illness at Marigat District Hospital, Baringo County, Kenya
Authors: Lemtudo Allan P. , Mutai Beth K. , Mwamburi Lizzy , Waitumbi John N. 
Published: May 2021

AbstractQ fever is not routinely diagnosed in Kenyan hospitals. This study reports on Q fever in patients presenting at Marigat District Hospital, Kenya, with febrile illness. ELISA was used to detect Coxiella burnetii phase antigens. Of 406 patients, 45 (11.1%) were judged to have acute disease (phase II IgM or IgG > phase I IgG), 2 (0.5%) were chronic (phase I IgG titer >800 or phase I IgG > phase II IgG), while 26 (6.4%) had previous exposure (phase I IgG titer <800). Age (6–10 years, p = 0.002) and contact with goats (p = 0.014) were significant risk factors. Compared to immunofluorescence antibody test, the sensitivity and specificity for phase I IgG were 84% and 98%, respectfully, 46% and 100% for phase II IgG and 35% and 89% for phase II IgM. It is concluded that the low sensitivity of phase II ELISA underestimated the true burden of acute Q fever in the study population.
Bacterial pathogens identified from houseflies in different human and animal settings: A systematic review and meta‐analysis
Authors: Monyama Maropeng C. , Onyiche Emmanuel T. , Taioe Moeti O. , Nkhebenyane Jane S. , Thekisoe Oriel M. M. 
Published: May 2021

AbstractHousefly (Musca domestica) is an excellent candidate for the distribution of susceptible and resistant bacterial strains that potentially threaten public health. To date, there is a paucity of information on the global distribution of pathogenic bacteria of medical and veterinary importance from diverse environmental settings. Therefore, this study was undertaken to conduct a systemic review and meta‐analysis to estimate occurrence of various bacterial species of medical and veterinary importance harboured by houseflies around the world. Published articles from 1980 to 2020 were retrieved from electronic databases and assessed for eligibility according to Preferred Reporting Items for Systemic Reviews and Meta‐Analysis guidelines. Seventy‐eight studies were included in the review with only 44 studies being eligible for meta‐analysis. Results indicated that eligible studies used in this review were from four continents, i.e., Asia (47.4%) America (23.1%), Africa (20.5%) and Europe (8.9%). The majority of the studies (56.4%) used the culture method for the identification of bacterial pathogens, while 30.7% used both culture and PCR techniques. For meta‐analysis, we focused on five pathogenic bacterial species including Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. High heterogeneity was found among studies investigating different pathogens including E. coli (Q = 10,739.55; I2 = 99.60; Q‐p 0.0001), E. faecium (Q = 317.61; I2 = 86.46; Q‐p < 0.0001), K. pneumonia (Q = 1,576.61; I2 = 97.27; Q‐p < 0.0001), S. aureus (Q = 2,439.12; I2 = 98.24; Q‐p < 0.0001) and P. aeruginosa (Q = 1,283.0; I2 = 96.65; Q‐p < 0.0001). Furthermore, it was observed that houseflies carried a considerable number of susceptible and antibiotic‐resistant bacterial strains that pose considerable threats to public health. Findings from this study have provided more insight on the vectoral potential of houseflies in the transmission of significant bacterial pathogens from different regions across the world. Further investigation is required to quantify the bacterial contamination and dissemination by houseflies.
Prevalence, aetiology and risk factors of mastitis of dairy cows kept under extensive management system in west Wollega, western Oromia, Ethiopia
Authors: Kitila Gutu , Kebede Bedaso , Wakgari Moti 
Published: May 2021

AbstractIntroductionMastitis is an inflammation of the mammary gland that could either be clinical or subclinical, and can be caused by infectious agents. It has different aetiological pathogens such as Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli that pose different economic and health impacts. In Ethiopia, previous studies on mastitis have been focused on semi‐intensive and intensive dairy production system. The objectives of this study were therefore to estimate prevalence, aetiology of causative pathogens and identify different risk factors of mastitis in extensive management systems. A total of 532 lactating cows were randomly selected for a cross‐sectional study carried out in four districts of west Wollega, western Oromia, Ethiopia.ResultBased on the clinical examination and California mastitis test, 39.67% overall prevalence of mastitis on cow level was recorded. Of them, 16.70% and 22.70% were clinical and subclinical mastitis, respectively. Among 2,128 quarters examined 210 were blind teats. The associated risk factors age ≥8 years (16.35%), parity 1–3 calving (27.63%), milk yield 1–2 litres (21.98%), lactation stage <4 months (18.04%) and tick infestation (26.70%) were significantly associated in the occurrence of mastitis. Staphylococcus spp. (15.60%) were the dominant bacteria isolated from collected mastitic milk.ConclusionMastitis is an important disease for dairy cows kept under an extensive management system. Its occurrence is determined by risk factors like age, parity, milk yield, lactation stage and tick infestation. This study is indicated Staphylococcus species as the major bacteria isolated from mastitic milk. This study warrants further study on the prevalence, aetiology, economic impact and potential risk factors of mastitis in dairy cows kept in extensive production system.
Introduction: Citizens, Markets, and Turkey
Authors: Ark-Yıldırım Ceren , Smyrl Marc 
Published: May 2021

AbstractThe concept of citizenship is typically divided into distinct components. Following the pioneering work of T.H. Marshall, we focus on social and economic citizenship. We ask in particular whether the “basic equality of membership” at the heart of Marshall’s definition of citizenship can be advanced by market-centered policies such as social cash transfer, even in cases such as that of forced migrants in which political or civil elements of citizenship are not present. Contemporary Turkey provides an ideal setting in which to investigate this question.
The Turkish Context
Authors: Ark-Yıldırım Ceren , Smyrl Marc 
Published: May 2021

AbstractIn Chap. 2, we traced the emergence of a new and controversial model of citizenship centered on the market. We turn now to the national case that is the focus of this book, Turkey. The central question of this chapter is whether the transition to a market-based model of citizenship much studied in Europe and North America can be applied to countries like Turkey, typified by late industrialization and a distinct social welfare model. To this end, we consider the evolution of the operational content and context of social and economic citizenship in Turkey. In a final section, we expand the scope of reflection to discuss the situation of migrants, and the evolution of the Turkish “incorporation regime.”
Cash Transfer with Turkish Characteristics: Two Local Examples
Authors: Ark-Yıldırım Ceren , Smyrl Marc 
Published: May 2021

AbstractHaving discussed the emergence of cash transfer (CT) as an instrument not only for economic assistance but potentially for inclusion in a market-centered society, and the policy environment of contemporary Turkey, we now bring these together through examination of two case studies of CT programs designed and implemented at the local level. By proceeding in this way, we are explicitly eschewing any claim to providing a universal treatment of social policy, or even of CT programs, in contemporary Turkey. Rather, we consider these cases with a view to highlighting the elements that seem most closely tied to particular outcomes, and then to generalizing these in the form of hypotheses applicable beyond Turkey.
Cash Transfer and Humanitarian Assistance
Authors: Ark-Yıldırım Ceren , Smyrl Marc 
Published: May 2021

AbstractIn this chapter, we turn our attention to cash transfer (CT) as an instrument of humanitarian assistance for forced migrants in Turkey. We first consider the emergence of CT as a priority instrument for humanitarian assistance in the twenty-first century. We then sketch the political background of humanitarian assistance in Turkey for persons displaced by internal conflicts in Syria focusing in particular on the EU–Turkey agreements that led to the establishment of the Facility for Refugees in Turkey (FRiT) in 2016. In a final section we focus on the establishment as part of FRiT of the Emergency Social Safety Net (ESSN), the largest humanitarian CT program ever established by the European Union. We discuss in particular the program’s institutional complexity and the resulting risk of ambiguous consensus and conflicts of interest among the agencies involved in its design and implementation.
The Consequences of Ambiguity: Designing and Implementing the ESSN
Authors: Ark-Yıldırım Ceren , Smyrl Marc 
Published: May 2021

AbstractThe stated purpose of the Emergency Social Safety Net (ESSN) was to contribute to meeting the basic needs of the most vulnerable refugees in Turkey. In the context of this book’s argument, we ask whether it achieved this goal but also whether and to what extent it contributed to extending elements of market citizenship to forced migrants. We conclude that while the ESSN’s CT program made a limited contribution to meeting basic needs and empowering displaced persons as consumers, other elements of market citizenship, or even “denizenship,” are lacking. With regard to its explicit targets, the effectiveness of ESSN was limited by the ambiguities of its design, linked to the different priorities of the agencies involved, which exclude some vulnerable persons from the program. More broadly, very limited access to the formal labor market remained an obstacle to fuller market citizenship.