bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra rapid lispro (URLi) shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early‐phase study
Authors: Leohr Jennifer , Kazda Christof , Liu Rong , Reddy Shobha , Dellva Mary Anne , Matzopoulos Mark , Loh Mei Teng , Hardy Thomas , Klein Oliver , Kapitza Christoph 
Published: October 2021

AbstractAimsTo compare the pharmacokinetics (PK), glucodynamics (GD) and tolerability following single and multiple daily subcutaneous doses of ultra rapid lispro (URLi) and Humalog® in patients with type 2 diabetes mellitus (T2D).Materials and MethodsThis was a two‐part, randomized, double‐blind Phase 1b study. Part A used a six‐period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15 minutes before, immediately before, or 15 minutes after the start of the meal. Part B evaluated URLi or Humalog during 2 weeks of multiple daily dosing with a parallel design. The PK and GD were assessed following MMTTs at the beginning and end of the 2 weeks when insulins were administered immediately before the start of the meal.ResultsURLi increased the insulin exposure within the first 30 minutes postdose by 2.2‐fold and reduced the time to the early half‐maximal drug concentration by 22.6% compared with Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal. In comparing the same meal‐to‐dose timing between the insulins, the postprandial glucose excursion over 5 hours was significantly reduced by 29%‐105% for all three dose timings (−15, 0 and +15 minutes) with URLi. The PK and GD were sustained after daily subcutaneous dosing for 2 weeks in patients with T2D. URLi had more hypoglycaemic events during the MMTTs; few events occurred for both treatments during the 2 weeks of outpatient dosing.ConclusionsURLi demonstrated accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal‐to‐dose timings compared with Humalog and was well tolerated in patients with T2D.
A novel hypothesis linking low‐grade ketonaemia to cardio‐renal benefits with sodium‐glucose cotransporter‐2 inhibitors
Authors: Ekanayake Preethika , Mudaliar Sunder 
Published: October 2021

AbstractThe cardio‐renal benefits of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are well established. In 2016, we postulated that these benefits are attributable, in part, to the occurrence of chronic low‐grade ketonaemia and a shift in myocardial and renal fuel metabolism away from fat oxidation, which is energy inefficient, towards ketone oxidation, which is more energy efficient. This shift improves myocardial and renal function and can potentially translate into lower rates of progression to heart failure and end‐stage kidney disease in patients with and without diabetes. There is now evidence that, in addition to being an efficient fuel substrate, ketones also have antiinflammatory and antioxidative benefits on the heart and the kidney. In addition, ketones have positive effects on mitochondrial biogenesis and function, and on erythropoiesis, and thereby are potentially able to further ameliorate the proinflammatory and hypoxic milieu in those with heart and kidney failure, independent of hyperglycaemia. In the present review, we propose a novel hypothesis to link the pleiotropic effects of low‐grade ketonaemia to the cardio‐renal benefits seen with SGLT2 inhibitors.
Heritage practices as development's blind spot: A case study of Coptic tattooing in Libya and Egypt
Authors: Tadros Mariz 
Published: October 2021

SummaryMotivationThe relationship between heritage and international development has been understudied despite more recent attempts to highlight the role of culture, and heritage as an element of it, for holistic and sustainable conceptions of development.PurposeThe article explores the relationship between heritage practices and inclusive development through the exploration of the role of Coptic tattooing in shaping the experiences of Coptic men as migrant workers in Libya and as job‐seekers in Egypt, and of Coptic women in Egypt.Methods and approachThe methodology combined primary and secondary data and is informed by a grounded theory approach; 20 in‐depth interviews with Coptic migrants who had worked in Libya and returned to Egypt is complemented by over 80 interviews with Coptic women and men across different generations living in southern Egypt who have imprinted religious tattoos.FindingsThe main findings are that the presence of a tattoo, an embodied form of religious heritage practice, contributed to exposing Coptic Egyptian migrant men to religious profiling and targeting, to the point of putting their lives in danger. The prohibition of Egyptian labour migration to Libya would not remove the susceptibility of these Coptic men to economic exclusion and discrimination since employers in Egypt also vetted them out in the labour force.Policy implicationsPolicy‐making can enable more “heritage‐aware development” by undertaking situational and context analysis that takes into account the full spectrum of the sources and drivers of inequality and exclusion; by considering ways in which experiences and responses to heritage practices can shed light on exclusion and developing policies that take into account the immateriality of “otherization” and are designed to be purposely inclusive.
A prevalence survey of Wolbachia in butterflies from southern China
Authors: Zhu Dao‐Hong , Gao Shuo 
Published: October 2021

AbstractWolbachia is a maternally inherited endosymbiont of the phylum α‐Proteobacteria that is found widely in arthropods and nematodes. Wolbachia is the most common endosymbiont in butterflies (Lepidoptera) and it manipulates host reproduction mainly by inducing cytoplasmic incompatibility, male killing, and feminization. We studied the prevalence patterns of Wolbachia in 52 butterfly species from five families collected in southern China. A substantial infection incidence was determined in the study region, where 18 out of the 52 butterfly species (35%) were infected, including members of the families Hesperiidae, Lycaenidae, Nymphalidae, Papilionidae, and Pieridae. Based on multi‐locus sequence typing (MLST) and Wolbachia cell surface protein (WSP) profiles, seven unique sequence types (STs) and six wsp alleles were detected. One MLST haplotype was detected for the first time (ST‐wPcau). Most of the identified Wolbachia STs belonged to supergroup B, those found in two Ypthima spp. belonged to supergroup A. Many STs were shared among various insect species; the most widespread strain in our samples, ST‐41, was detected in seven butterfly species from four families. We discuss the potential horizontal transmission routes of Wolbachia, as well as the suitability of the Wolbachia strain typing method.
Predator life history and prey ontogeny limit natural selection on the major armour gene,Eda, in threespine stickleback
Authors: Wasserman Ben A. , Reid Kerry , Arredondo Olivia M. , Osterback Ann‐Marie K. , Kern Cynthia H. , Kiernan Joseph D. , Palkovacs Eric P. 
Published: October 2021

AbstractNatural selection shapes the evolution of antipredator traits in prey. However, selection in the wild depends on ecological context, including features of predator and prey populations, making field studies of selection critical to understanding how predators shape selection on prey defences. Threespine stickleback (Gasterosteus aculeatus) is a classic system to study the effects of predators on the natural selection of prey. In lakes and rivers, fish predators have been shown to impose selection against low plated adult stickleback phenotypes and genotypes. We directly measured selection by predatory salmonids on theEctodysplasin‐A(Eda) gene in estuary stickleback from California. Despite previous studies showing a positive correlation between predator presence and frequency of theEda“complete” allele in estuary populations, we found thatEda“low” genotypes were not significantly more frequent in salmonid predator diets. Further, we found no evidence of changes inEdagenotype frequencies across generations that would suggest directional selection driven by predators. Prior selection studies have examined the effects of large resident trout on adult stickleback. In contrast, predators in this study were juvenile anadromous salmonids, which only ate juvenile stickleback whose plate phenotypes had not fully developed. Thus, in this case, predator life history and stickleback ontogeny may preclude strong selection on stickleback armour. Our results underscore the importance of selection studies in the wild for understanding the context‐dependent nature of selection in natural populations.
Phenological trends in the pre‐ and post‐breeding migration of long‐distance migratory birds
Authors: Lawrence Kieran B. , Barlow Clive R. , Bensusan Keith , Perez Charles , Willis Stephen G. 
Published: October 2021

AbstractPhenological mismatch is often cited as a putative driver of population declines in long‐distance migratory birds. The mechanisms and cues utilized to advance breeding ground arrival will impact the adaptability of species to further warming. Furthermore, timing of post‐breeding migration potentially faces diverging selective pressures, with earlier onset of tropical dry seasons favouring migration advancement, while longer growing seasons in temperate areas could facilitate delayed departures. Despite this, few studies exist of migration phenology on the non‐breeding grounds or on post‐breeding passage. Here, we use first arrival and last departure dates of 20 species of trans‐Saharan migratory birds from tropical non‐breeding grounds (The Gambia), between 1964 and 2019. Additionally, we use first arrival and last departure dates, as well as median arrival and departure dates, at an entry/departure site to/from Europe (Gibraltar), between 1991 and 2018. We assess phenological trends in pre‐ and post‐breeding migration, as well as individual species’ durations of stay in breeding and non‐breeding areas. Furthermore, we assess the extent to which inter‐annual variation in these timings may be explained by meteorological and ecological variables. We find significant advances in pre‐breeding migration at both locations, while post‐breeding migration is delayed. At Gibraltar, these trends do not differ between first/last and median dates of migration. The combination of these trends suggests substantial changes in the temporal usage of the two continents by migratory birds. Duration of stay (of species, not individuals) within Europe increased by 16 days, on average, over the 27‐year monitoring period. By contrast, duration of species’ stays on the non‐breeding range declined by 63 days, on average, over the 56‐year monitoring period. Taken together these changes suggest substantial, previously unreported alterations to annual routines in Afro‐Palaearctic migrants.
Efficacy of mirabegron, a β3‐adrenoreceptor agonist, in Japanese women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence: Post‐hoc analysis of pooled data from two randomized, placebo‐controlled, double‐blind studies
Authors: Takahashi Satoru , Mishima Yuji , Kuroishi Kentaro , Ukai Masashi 
Published: October 2021

ObjectiveTo confirm if mirabegron 50 mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo.MethodsPost‐hoc analyses were carried out using pooled data from a Japanese phase IIb and a phase III study. The primary efficacy end‐point was baseline to end‐of‐treatment change in the mean number of micturitions/24 h. The secondary end‐points were changes in the mean voided volume/micturition, mean number of urgency and incontinence episodes/24 h, and mean number of nocturia episodes/night. Other end‐points were quality of life and incontinence normalization rates.ResultsWomen with urgency urinary incontinence (placebo n  = 204, mirabegron n = 214) and mixed urinary incontinence (placebo n = 122, mirabegron n = 139) were included. Change in mean micturitions/24 h at end‐of‐treatment for mirabegron was statistically significant versus placebo in both populations; the effect size increased over time. For all secondary end‐points, median changes for mirabegron were statistically significant versus placebo at end‐of‐treatment, except for nocturia for the urgency urinary incontinence population and urgency for the mixed urinary incontinence population. Mirabegron showed larger improvements versus placebo in all quality‐of‐life domains, except for general health perception in the urgency urinary incontinence population. Incontinence normalization rates for mirabegron were 47.2% and 49.6% in the urgency urinary incontinence and mixed urinary incontinence populations, respectively, versus 42.6% and 39.3% for placebo.ConclusionsMirabegron 50 mg significantly improved key overactive bladder symptoms versus placebo in women with urgency urinary incontinence, and it also improved most overactive bladder symptoms, including micturition frequency, in patients with mixed urinary incontinence. These findings support the benefits of using mirabegron in the female overactive bladder wet population.
Application of credit‐scoring methods in a decision support system of investment for peer‐to‐peer lending
Authors: Babaei Golnoosh , Bamdad Shahrooz 
Published: October 2021

AbstractPeer‐to‐peer lending, as a novel lending model, has challenged investors to make effective investment decisions. Issued loans are grouped into default and nondefault. Therefore, different classification methods can be utilized to predict the status of loans in the future. Our study aim is to propose an investment decision model based on the nondefault loans predicted using three different classifiers, including random forest (RF) that is a multitude of decision trees, support vector machine, and naïve Bayes. In fact, we combine each of these classifiers with the portfolio optimization problem to understand which combination leads to the best portfolio concerning the risk and return. In order to find the best combined model, numerical studies are conducted based on real‐world data. In addition, the performances of these classifiers are evaluated based on different performance measures using the 10‐fold cross‐validation method. The results indicate that combining the RF algorithm and portfolio optimization problem leads to the least level of risk. Moreover, it is concluded that RF is the best classifier in terms of performance analysis.
Mechanism and function of phasic firing in vasopressin‐releasing magnocellular neurosecretory cells
Authors: Thirouin Zahra S. , Bourque Charles W. 
Published: October 2021

AbstractMagnocellular neurosecretory cells that release vasopressin (MNCVP) from axon terminals in the neurohypophysis display a unique pattern of action potential firing termed phasic firing. Under basal conditions, only a small proportion of MNCVP display spontaneous phasic firing. However, acute and chronic conditions that stimulate vasopressin release, such as hemorrhage and dehydration, greatly enhance the number of MNCVP that fire phasically. Phasic firing optimizes VP neurosecretion at axon terminals by allowing action potential broadening to promote calcium‐dependent frequency‐facilitation, at the same time as preventing the secretory fatigue caused by spike inactivation that occurs during prolonged continuous stimulation. This review provides an update on our mechanistic understanding of these processes and highlights important gaps in our knowledge that must be addressed in future experiments.
A combination of garlic oil and cooked chilli oil could be effective and efficient for pigeon production
Authors: Du Jian , Bao Tianchao , Wang Zhongyu , Sun Jinhua 
Published: October 2021

AbstractThis study was conducted to investigate whether the combination of garlic oil and cooked chilli oil is worth using for pigeon production in the context of a total ban on antibiotics in feed additives in China. Two hundred female white king pigeons aged 23 days were randomly divided into five groups with ten replicates (four birds each). In the 47 days trial, the control group was fed with a basal diet, treatment groups were given a basal diet supplemented with 20 mg/kg neomycin sulphate or 2 g/kg corresponding oil (garlic oil or cooked chilli oil or their mixture) respectively. The mixed oil showed obvious antibacterial activity against gram‐positive bacterium and its minimal bactericidal concentration against St. aureus, Salmonella and Escherichia coli were all no more than 1.0 mg/ml. In the feeding experiment, pigeons feed with garlic oil with strong bacteriostatic activity had lower FCR and better protein metabolism, and chilli oil showed strong effects of promoting feed intake and weight gain on pigeons but increased serum glucose and lipid content. Compared with the control and the antibiotic group, the mixed oil got increased growth performance, less drip loss of meat, better protein metabolism promoting, and more complete intestinal structure of pigeon. In addition, the breast meat in the mixed oil group had higher total points in the sensory test. The mixed oil combined the strong bacteriostasis of garlic oil with the feeding promotion effect of cooked chilli oil, it improved the comprehensive performance of pigeons and had the feasibility to be popularized as a non‐antibiotic strategy in pigeon production.
Current review of hemp‐based medicines in dogs
Authors: R. C. Coelho Maria Paula , de O. P. Leme Fabiola , A. Moreira Fabricio , E. M. T. Branco Stephanie , M. Melo Marilia , G. de Melo Eliane 
Published: October 2021

AbstractMedical use of Cannabis (or hemp) began thousands of years ago. In the 20th century, mechanisms of action were demonstrated with the discovery of its active substances, the phytocannabinoids, and its pharmacological targets, the endocannabinoid system. This system is composed of receptors, endogenous substances, and enzymes, and it participates in the modulation of physiological mechanisms in several species, including dogs. Studies indicate that changes in this system may contribute to the genesis of some diseases. Therefore, the use of substances that act on its components may help in the treatment of these diseases. The main phytocannabinoids described are Δ9−tetrahydrocannabinol (THC) and cannabidiol (CBD). In humans, the benefits of using CBD in several diseases have been demonstrated. The popularization of this type of treatment has also reached veterinary medicine, which on one hand was related to an increase in adverse event records, but on the other also allowed reports of anecdotal evidences of its effectiveness and safety in animals. Clinical studies published so far indicate that the use of CBD in dogs can be safe at given doses and can contribute to osteoarthritis and idiopathic epilepsy treatments. Clinical and pre‐clinical studies and case reports were reviewed in this report to identify the main characteristics of hemp‐based therapies in dogs, including its pharmacokinetics, pharmacodynamics, safety, and efficacy in the treatment of diseases.
Phytophthora infestans Ago1‐associated miRNA promotes potato late blight disease
Authors: Hu Xinyi , Persson Hodén Kristian , Liao Zhen , Åsman Anna , Dixelius Christina 
Published: October 2021

Summary

Phytophthora spp. cause serious damage to plants by exploiting a large number of effector proteins and small RNAs (sRNAs). Several reports have described modulation of host RNA biogenesis and defence gene expression. Here, we analysed Phytophthora infestans Argonaute (Ago) 1 associated small RNAs during potato leaf infection.

Small RNAs were co‐immunoprecipitated, deep sequenced and analysed against the P. infestans and potato genomes, followed by transcript analyses and transgenic assays on a predicted target.

Extensive targeting of potato and pathogen‐derived sRNAs to a range of mRNAs was observed, including 638 sequences coding for resistance (R) proteins in the host genome. The single miRNA encoded by P. infestans (miR8788) was found to target a potato alpha/beta hydrolase‐type encoding gene (StABH1), a protein localized to the plasma membrane. Analyses of stable transgenic potato lines harbouring overexpressed StABH1 or artificial miRNA gene constructs demonstrated the importance of StABH1 during infection by P. infestans. miR8788 knock‐down strains showed reduced growth on potato, and elevated StABH1 expression levels were observed when plants were inoculated with the two knock‐down strains compared to the wild‐type strain 88069.

The findings of our study suggest that sRNA encoded by P. infestans can affect potato mRNA, thereby expanding our knowledge of the multifaceted strategies this species uses to facilitate infection.
Shear wave velocity measurements obtained in different regions are repeatable for presumed normal canine lymph nodes: A pilot study
Authors: Favril Sophie , de Rooster Hilde , Broeckx Bart J.G. , Stock Emmelie , Vanderperren Katrien 
Published: October 2021

AbstractShear wave elastography (SWE) has been applied as a noninvasive method for predicting regional lymph node (LN) metastases in human and veterinary patients. However, published studies describing standardized protocols and repeatability of this technique are currently lacking. The objective of this prospective, pilot, observer agreement study was to determine whether different shear wave velocity (SWV) measurements obtained in different regions of presumed normal canine LNs would be repeatable. Two imagers consecutively performed shear wave elastography of submandibular, superficial inguinal, and popliteal LNs in 10, clinically healthy adult dogs. Ten elastograms of each LN were acquired by each imager. In each adequate elastogram, three regions of interest (ROIs) were placed in the softest and stiffest region of the LN. Additionally, one ROI was drawn covering the entire LN. In each ROI, mean, median, and maximum SWVs were calculated. Mean values for the mean, median, and maximum SWVs varied from 2.33 to 3.10 m/s, 2.32 to 3.10 m/s, and 2.61 to 4.09 m/s, respectively. Intra‐ and interobserver agreements were acceptable. Superficial inguinal LNs demonstrated the highest intra‐ and interobserver agreement, followed by the popliteal and the submandibular LNs, respectively. Using the different measurements (mean, median, or maximum SWVs) had no significant effect on the intra‐ and interobserver variability, neither did the region (softest, stiffest, or entire LN). Findings indicated that all evaluated measurements and regions could be used to obtain reliable elastography data of presumed normal canine LNs. Clinical trials in dogs with cancer are necessary to compare SWVs of metastatic LNs with the reported SWVs and evaluate whether various measurements and regions can also be used in metastatic LNs.