bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Litigants, Trials and Precedents Vanishing After All?
Authors: Mulcahy Linda , Teeder Wendy
Published: October 2021

In recent years scholars have become increasingly concerned with the ‘vanishing trial’, and its impact on common law civil justice systems that rely on precedent. This article updates previous accounts of the vanishing trial in England and Wales, showing that the rapid decline which prompted earlier debate has levelled off. Against this backdrop the article goes on to discuss the production of precedent and, drawing on an analysis of seventy years of government data on civil litigation cases, contests the assumption that vanishing trials lead to a decline in precedent. It shows that, despite contra‐predictions, the number of appellate court judgments has increased while cases coming into the system and proceeding to trial have decreased. Further, it considers what House of Lords and Supreme Court data reveal about demand for precedent and the sort of cases that are taking up a greater proportion of Supreme Court time in the twenty‐first century.
Comparison of thermal variations in post‐retrieval graft conditioning on rat livers
Authors: von Horn Charlotte , Zlatev Hristo , Pletz Jessica , Lüer Bastian , Minor Thomas
Published: October 2021

Background

Machine perfusion was found an effective tool to recover organ grafts from ischemic insults during preservation. It could be observed that organ integrity is significantly affected by abrupt temperature shifts during hypothermic storage and implantation periods. Studies showed that a gentle and controlled rise of the temperature during oxygenated machine perfusion prior to implantation can protect the tissue from reperfusion injury. Now, the possible role of temperature kinetics upon retrieval of the graft and prior to later cold storage should be investigated.

Methods

Rat livers were retrieved after cardiac arrest and subjected to a brief ex situ machine perfusion with either hypothermic resuscitation (HR) at 8°C, near‐normothermic resuscitation (NR) at 30°C or progressive resuscitation with lowering the temperature in a controlled fashion from 30°C to 8°C (PR). After cold storage (CS), liver functional parameters were evaluated by an established ex vivo reperfusion system.

Results

NR and PR resulted in significantly lower release of hepatic enzymes and less production of tumor necrosis factor upon reperfusion compared to CS while HR had a far less protective effect. An increase in bile production was only observed in the PR group, which also significantly increased the recovery of tissue adenosine triphosphate, the amount of which was, however, nearly paralleled by the NR protocol.

Conclusion

Within the limitations of this model, it seems that normothermic recirculation appears to be a superior approach for the restitution of warm‐ischemically injured liver grafts than immediate hypothermic machine perfusion.
Primary therapy and relative survival in patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia: a population‐based study in the Netherlands, 1989–2018
Authors: Amaador Karima , Kersten Marie José , Visser Otto , Brink Mirian , Posthuma Eduardus F. M. , Minnema Monique C. , Vos Josephine M. I. , Dinmohamed Avinash G.
Published: October 2021

It is unclear how treatment advances impacted the population‐level survival of patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia (LPL/WM). Therefore, we assessed trends in first‐line therapy and relative survival (RS) among patients with LPL/WM diagnosed in the Netherlands between 1989 and 2018 (N = 6232; median age, 70 years; 61% males) using data from the nationwide Netherlands Cancer Registry. Patients were grouped into three age groups (<65, 66–75 and >75 years) and four calendar periods. Overall, treatment with anti‐neoplastic agents within 1 year post‐diagnosis gradually decreased over time, following a broader application of an initial watch‐and‐wait approach. Approximately 40% of patients received anti‐neoplastic therapy during 2011–2018. Furthermore, use of chemotherapy alone decreased over time, following an increased application of chemoimmunotherapy. Detailed data among 1596 patients diagnosed during 2014–2018 revealed that dexamethasone‐rituximab‐cyclophosphamide was the most frequently applied regimen; its use increased from 14% to 39% between 2014 and 2018. The 5‐year RS increased significantly over time, particularly since the introduction of rituximab in the early–mid 2000s. The 5‐year RS during 1989–1995 was 75%, 65%, and 46% across the age groups compared to 93%, 85%, and 79% during 2011–2018. However, the survival improvement was less pronounced after 2011. Collectively, the impressive survival improvement may be accounted for by broader application of rituximab‐containing therapy. The lack of survival improvement in the post‐rituximab era warrants studies across multiple lines of therapy to further improve survival in LPL/WM.
Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real‐world setting
Authors: Torrecillas Vanessa , Sharma Anu , Neuberger Kaden , Abraham Dev
Published: October 2021

Objective

American Thyroid Association (ATAn) 2015 guidelines recommend repeat fine‐needle aspiration with molecular marker profiling (MMP) or diagnostic lobectomy in thyroid nodules yielding atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology. Our objective is to describe the molecular profiles and histological correlates of these cytologically indeterminate nodules (CIN) to aid risk stratification.

Design

Retrospective chart review.

Patients

Adults with CIN that underwent MMP from 2017 to 2020.

Measurements

Pearsons' χ2, Fisher's exact test, nonparametric testing and multiple regression analysis were performed.

Results

A total of 89 CIN underwent mutational analysis. Of 55% (n = 49) were Bethesda class III AUS/FLUS and 45% (n = 40) were Bethesda class IV FN/SFN. The US phenotype of a CIN was isoechoic (53%) or hypoechoic (32%) with well‐defined margins (98%), absence of calcifications (75%) and mildly increased internal vascularity (70%). A total of 84% and 87% of nodules were classified as mild/moderate or low/intermediate risk per the Thyroid Imaging Reporting and Data System and ATA classifications, respectively. Based on the Thyroseq patient management resource, 6.7% (n = 6) of nodules had a high predicted probability of cancer (≥95%), 41.6% (n = 37) were intermediate probability (40%–94%) and 51.7% (n = 46) were low probability (<40%). MMP revealed positive mutations in 45% (n = 40) of nodules, with 71% demonstrating RAS mutations. Of the nodules that underwent resection (n = 38), 39% (n = 15) had malignant pathology. Increasing the threshold to recommend surgical resection to a Thyroseq predicted probability of cancer to ≥50%, had a 100% sensitivity and 65% specificity for detecting malignant nodules (area under the ROC curve: 0.86). The positive predictive value was 37% and the negative predictive value was 100%.

Conclusion

US phenotypes of CIN nodules were variable and did not aid in differentiating malignant from benign nodules. Of the CIN nodules with a positive MMP, most were RAS and had a benign pathology. With the exception of high‐risk genetic markers for malignancy, the threshold to recommend surgical resection should be raised for CIN. Further studies to improve risk stratification in these nodules are required.
Phylogenomics of Northeast AsianPungitiussticklebacks
Authors: Wang Yingnan , Wang Yu , Zhao Yahui , Kravchenko Alexandra Yu , Merilä Juha , Guo Baocheng
Published: October 2021

Aim

Understanding the phylogeography of a species complex can provide important insights into its evolutionary history. However, phylogeographic inference often faces the dilemma of regionally inadequate sampling.Pungitiussticklebacks are a case in point: although the highest species diversity is found in Northeast Asia, their phylogeography in this region is still poorly understood.

Location

Northeast Asia.

Methods

With the aid of whole‐genome resequencing data, we investigated the phylogeography of Northeast AsianPungitiussticklebacks, with newly sampled 83 worldwidePungitiusindividuals from 11 locations including eight Chinese locations reported to host onlyP. sinensis.

Results

We discovered that three of the eight Chinese locations hosted populations ofP. kaibarae andP. bussei, species new to the fauna of China. Phylogeographic analyses further clarified the sequence and timing of colonization of Northeast Asia by differentPungitiusspecies, shedding new light on their origins and current distribution ranges. Colonization of inland Northeast Asia byPungitiussticklebacks occurred in multiple waves, and the widespreadP. sinensisexpanded its range relatively late in the Pleistocene.

Main conclusions

This study complements our understanding of the phylogeography ofPungitiussticklebacks by extending sampling to cover an area that comprises nearly half of the known distribution area of this genus in Northeast Asia. The discovery of threePungitusspecies from China is of particular interest, as translocations to support locally declining populations have occurred under the assumption that all sticklebacks in China—except the endangeredP. stenurus—areP. sinensis, raising conservation concerns associated with unintentional translocations and possible admixture.
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

Aims

To 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 Methods

This 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.

Results

URLi 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.

Conclusions

URLi 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

The 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

Motivation

The 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.

Purpose

The 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 approach

The 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.

Findings

The 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 implications

Policy‐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

Wolbachia 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

Natural 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

Phenological 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

Objective

To confirm if mirabegron 50 mg shows efficacy in women with overactive bladder and either urgency urinary incontinence or mixed urinary incontinence versus placebo.

Methods

Post‐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.

Results

Women 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.

Conclusions

Mirabegron 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

Peer‐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

Magnocellular 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.
An Intersectional Approach to Understanding the Academic and Health Effects of Policing Among Urban Adolescents
Authors: Del Toro Juan , Wang Ming‐Te , Thomas Alvin , Hughes Diane
Published: October 2021

This brief report examines whether the effects of direct and vicarious police stops on adolescents’ academic adjustment via their psychological and physical well‐being differ across ethnic–racial and gender groups. Using national and longitudinal survey data from Black, Latinx, and White adolescents (N = 3004; 49% girls), we found that the police stopped more Black boys and Black girls than their ethnic–racial peers. Vicarious stops were prevalent among all groups. The effects of police stops on adolescents’ adjustment outcomes were more detrimental for adolescents of color and particularly Black boys relative to their White peers. Implications are discussed regarding how law enforcement shapes disparities that disadvantage particular adolescents at the intersections of their ethnicity–race and gender.
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

This 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

Medical 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

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

Shear 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.
Short‐term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross‐over trial
Authors: Walsh Jeremy J. , Caldwell Hannah G. , Neudorf Helena , Ainslie Philip N. , Little Jonathan P.
Published: October 2021

Adults with obesity are at increased risk of neurocognitive impairments, partly as a result of reduced cerebral blood flow and brain‐derived neurotrophic factor (BDNF). Ketone supplements containing β‐hydroxybutyrate (β‐OHB) are a purported therapeutic strategy for improving brain health in at‐risk populations. We tested the hypothesis that short‐term β‐OHB supplementation will elevate cerebral blood flow and BDNF, as well as improve cognition in adults with obesity. In a placebo‐controlled double‐blind, cross‐over design, 14 adults with obesity (10 females; aged 56 ± 12 years; body mass index = 33.8 ± 6.9 kg m–2) consumed 30 mL (12 g) of β‐OHB or placebo thrice‐daily for 14 days. Blood flow (Q) and cerebrovascular conductance (CVC) were measured in the common carotid (CCA), internal carotid (ICA) and vertebral (VA) arteries by duplex ultrasound. BDNF was measured by an enzyme‐linked immunosorbent assay. Cognition was assessed by the digit‐symbol substitution (DSST), Stroop and task‐switching tests. Following 14 days of ketone supplementation, we observed significant improvements in cerebrovascular outcomes including QCCA (+12%), QVA (+11%), VACVC (+12%) and VA shear rate (+10%). DSST performance significantly improved following ketone supplementation (+2.7 correct responses) and improved DSST performance was positively associated improvements in cerebrovascular outcomes including QCCA, CCACVC, QVA and VACVC. By contrast to one hypothesis, β‐OHB did not impact fasting serum and plasma BDNF. β‐OHB supplementation improved cognition in adults with obesity, which may be partly facilitated by improvements in cerebral blood flow. β‐OHB supplementation was well‐tolerated and appears to be safe for cerebrovascular health, suggesting potential therapeutic benefits of β‐OHB in a population at risk of neurocognitive impairment.

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Key points

People with obesity are at increased risk of neurocognitive dysfunction, partly as a result of ‐induced reductions in cerebral blood flow (CBF) and brain‐derived neurotrophic factor (BDNF).

Ketone supplements containing β‐hydroxybutyrate (β‐OHB) reduce postprandial hyperglycaemia, which may increase CBF and BDNF, thereby protecting against obesity‐related cognitive dysfunction.

We show for the first time that 14 days of thrice‐daily β‐OHB supplementation improves aspects of cognition and increases cerebrovascular flow, conductance and shear rate in the extracranial arteries of adults with obesity.

Our preliminary data indicate a significant positive relationship between elevated CBF and improved cognition following β‐OHB supplementation.

This trial provides a foundation for the potential non‐pharmacological therapeutic application of β‐OHB supplementation in patient groups at risk of hyperglycaemic cerebrovascular disease and cognitive dysfunction.
Non-native English listeners' adaptation to native English speakers
Authors: Lee Dae-yong , Baese-Berk Melissa M.
Published: October 2021

Listeners often have difficulty understanding unfamiliar speech (e.g., non-native speech), but they are able to adapt to or improve their ability to understand unfamiliar speech. However, it is unclear whether non-native listeners demonstrate adaptation to novel native English speech broadly with relatively limited exposure. Thus, this study examines non-native English listeners' adaptation to native English speakers and whether talker variability affects adaptation. Results suggest that while greater variability initially disrupts non-native English listeners' perception of native English speakers, listeners are able to rapidly adapt to novel speakers and exposure to greater variability could result in cross-talker generalization.
Return to Play for Exertional Rhabdomyolysis in Korea National Rugby Player
Authors: Kim Jaehong , Yeol Jeong Jeung , Kim, Daeho
Published: October 2021

This case report describes the process of returning to play as a case of exertional rhabdomyolysis caused by excessive training by a national rugby player. The authors reported the serum analysis, urinalysis, visual analog scale for pain, and lower-extremity functional scale. The aspartate aminotransferase, alanine transaminase, and myoglobin levels in the serum analysis decreased normally during the eighth day, and creatine phosphokinase levels decreased to normal levels by the 15th day. The maximal scale of visual analog scale for pain was 10 from the third day to the fifth day, and gradually decreased from the sixth day (scale = 6.6) to the 13th day (scale = 0.9). The lower-extremity functional scale scores after the diagnosis of exertional rhabdomyolysis were 0 at the third day, 47 at the 10th day, and 80 at the 24th day. A moderate increase in water intake could help the player recover faster. To restore overall body condition for rugby performance, specific athletic therapy and training should be provided at a predetermined specific time.
Astaxanthin Supplementation Increases Glutathione Concentrations but Does Not Impact Fat Oxidation During Exercise in Active Young Men
Authors: McAllister Matthew J. , Mettler Joni A. , Patek Kyle , Butawan Matthew , Bloomer Richard J.
Published: October 2021

This study investigated the effects of 6 mg/day of astaxanthin supplementation on markers of oxidative stress and substrate metabolism during a graded exercise test in active young men. A double-blind, randomized, counterbalanced, cross-over design was used. Fourteen men (age = 23 ± 2 years) supplemented with 6 mg/day of astaxanthin and a placebo for 4 weeks, with a 1 week washout period between treatments. Following each supplementation period, a fasting blood sample was obtained to measure markers of oxidative stress: glutathione, hydrogen peroxide, advanced oxidation protein products, and malondialdehyde. Participants also completed a graded exercise test after each treatment to determine substrate utilization during exercise at increasing levels of intensity. Glutathione was ∼7% higher following astaxanthin compared with placebo (1,233 ± 133 vs. 1,156 ± 185 μM, respectively; p = .02, d = 0.48). Plasma hydrogen peroxide and malondialdehyde were not different between treatments (p > .05). Although not statistically significant (p = .45), advanced oxidation protein products were reduced by ∼28%. During the graded exercise test, mean fat oxidation rates were not different between treatments (p > .05); however, fat oxidation decreased from 50 to 120 W (p < .001) and from 85 to 120 W (p = .004) in both conditions. Astaxanthin supplementation of 6 mg/day for 4 weeks increased whole blood levels of the antioxidant glutathione in active young men but did not affect oxidative stress markers or substrate utilization during exercise. Astaxanthin appears to be an effective agent to increase endogenous antioxidant status.
Exploring Shared Effects of Multisensory Impairment, Physical Dysfunction, and Cognitive Impairment on Physical Activity: An Observational Study in a National Sample
Authors: Huisingh-Scheetz Megan J. , Li Li , Wroblewski Kristen E. , Schumm L. Philip , McClintock Martha K. , Pinto Jayant M.
Published: October 2021

Multisensory, physical, and cognitive dysfunction share age-related physiologic disturbances and may have common health effects. We determined whether the effect of multisensory impairment on physical activity (PA) is explained by physical (timed up and go) or cognitive (Short Portable Mental Status Questionnaire) dysfunction. A National Social Life, Health, and Aging Project participant subset (n = 507) underwent objective sensory testing in 2005–2006 and wrist accelerometry in 2010–2011. We related multisensory impairment to PA using multivariate mixed-effects linear regression and compared the effect magnitude after adjusting for physical then cognitive dysfunction. Worse multisensory impairment predicted lower PA across three scales (Global Sensory Impairment: β = −0.04, 95% confidence interval [−0.07, −0.02]; Total Sensory Burden: β = −0.01, 95% confidence interval [−0.03, −0.003]; and Number of Impaired Senses: β = −0.02, 95% confidence interval [−0.04, −0.004]). Effects were similar after accounting for physical and cognitive dysfunction. Findings suggest that sensory, physical, and cognitive dysfunction have unique mechanisms underlying their PA effects.
No One Is on an Island: Connecting, Collaborating, and Coping During the Pandemic
Authors: Carpenter Paul , Stylianides Karen , Weiler-Timmins Rebecca , Randolph-Krisova Andrea , Sprinkle Kelly , Angulo-Barrosso Rosa
Published: October 2021

The onset and spread of COVID-19 forced an accelerated shift to remote communication and online teaching, generating new challenges and opportunities for kinesiology. As a result of the pandemic situation, redefined collaborative models independently emerged among kinesiology departments in two systems, California State University and the Pennsylvania State University. These models built community; addressed geographic and size challenges associated with meeting in-person; empowered sharing of ideas, resources, best practices, and emotional support; and guided our campus communities to success. We suggest that these collaborative models can be used in the future as platforms to improve kinesiology student’s success by facilitating professional development, integration, sharing, problem solving, and social support.
Toxoplasma gondii-Induced Neutrophil Extracellular Traps Amplify the Innate and Adaptive Response
Authors: Miranda Farlen J. B. , Rocha Bruno C. , Pereira Milton C. A. , Pereira Larissa M. N. , de Souza Erikson H. M. , Marino Ana P. , Costa Pedro A. C. , Vasconcelos-Santos Daniel V. , Antonelli Lis R. V. , Gazzinelli Ricardo T.
Published: October 2021

Approximately one-third of the human population is estimated to be chronically infected with the obligate intracellular parasiteToxoplasma gondii. Humans are accidental hosts that are infected withT. gondiiafter consumption of undercooked meat or contaminated water.
Foraging Signals Promote Swarming in Starving Pseudomonas aeruginosa
Authors: Badal Divakar , Jayarani Abhijith Vimal , Kollaran Mohammad Ameen , Prakash Deep , P Monisha , Singh Varsha
Published: October 2021

P. aeruginosa
, a Gram-negative opportunistic pathogen, can adapt to diverse ecological niches and exhibits several forms of social behavior. Swarming (flagellum-driven collective motility) is a collective behavior of
P. aeruginosa
exclusively over semisolid surfaces.
Para-Aminobenzoic Acid, Calcium, and c-di-GMP Induce Formation of Cohesive, Syp-Polysaccharide-Dependent Biofilms in Vibrio fischeri
Authors: Dial Courtney N. , Speare Lauren , Sharpe Garrett C. , Gifford Scott M. , Septer Alecia N. , Visick Karen L.
Published: October 2021

Bacteria integrate environmental signals to regulate gene expression and protein production to adapt to their surroundings. One such behavioral adaptation is the formation of a biofilm, which can promote adherence and colonization and provide protection against antimicrobials.
Isolation and Analysis of the Nisin Biosynthesis Complex NisBTC: further Insights into Their Cooperative Action
Authors: Chen Jingqi , Kuipers Oscar P.
Published: October 2021

Lantibiotics are ribosomally synthesized and posttranslationally modified peptide antibiotics. Although the membrane-associated lantibiotic biosynthesis machinery has long been proposed to exist, the isolation of such a complex has not been reported yet, which limits the elucidation of the processive mechanism of lantibiotic biosynthesis.
Predicting Microbiome Metabolism and Interactions through Integrating Multidisciplinary Principles
Authors: Schmidt Caleb M. , Ghadermazi Parsa , Chan Siu Hung Joshua
Published: October 2021

In this Commentary, we will discuss some of the current trends and challenges in modeling microbiome metabolism. A focus will be the state of the art in the integration of metabolic networks, ecological and evolutionary principles, and spatiotemporal considerations, followed by envisioning integrated frameworks incorporating different principles and data to generate predictive models in the future.
Novel Drivers of Virulence in Clostridioides difficile Identified via Context-Specific Metabolic Network Analysis
Authors: Jenior Matthew L. , Leslie Jhansi L. , Powers Deborah A. , Garrett Elizabeth M. , Walker Kimberly A. , Dickenson Mary E. , Petri William A. , Tamayo Rita , Papin Jason A.
Published: October 2021

Clostridioides difficile
has become the leading single cause of hospital-acquired infections. Numerous studies have demonstrated the importance of specific metabolic pathways in aspects of
C. difficile
pathophysiology, from initial colonization to regulation of virulence factors.
Primary synchronous malignancies of the breast and the kidney
Authors: Khan Rehan Nasir , Kazmi Zehra , Vohra Lubna Mushtaque , Uddin Zeeshan
Published: October 2021

Synchronous primary malignancies are most frequently seen with cancers of the stomach and oesophagus, mainly attributed to the similar genetic mutations. Most of these multiple malignancies turn out to be metastatic or metachronous lesions. Multiple synchronous malignancies are rarer than metachronous ones. Primary synchronous breast and renal cancer is even rare. These patients require extensive workup to exclude all possible metastases. The nature of the primary tumours must also be confirmed, prior to any treatment strategy. We report the case of a healthy, middle-aged woman who initially presented with a lesion suspicious for breast carcinoma, and further workup revealed the presence of an asymptomatic, synchronous primary renal cell cancer, which is a very rare presentation.