bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing animal personhood in compassionate conservation
Authors: Wallach Arian D. , Batavia Chelsea , Bekoff Marc , Alexander Shelley , Baker Liv , Ben‐Ami Dror , Boronyak Louise , Cardilin Adam P. A. , Carmel Yohay , Celermajer Danielle , Coghlan Simon , Dahdal Yara , Gomez Jonatan J. , Kaplan Gisela , Keynan Oded , Khalilieh Anton , Kopnina Helen , Lynn William S. , Narayanan Yamini , Riley Sophie , Santiago‐Ávila Francisco J. , Yanco Esty , Zemanova Miriam A. , Ramp Daniel
Published: March 2020

Compassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space.
12‐year data on skin diseases in the Finnish Register of Occupational Diseases II: Risk occupations with special reference to allergic contact dermatitis
Authors: Aalto‐Korte Kristiina , Koskela Kirsi , Pesonen Maria
Published: March 2020

Background

Detailed epidemiological studies on occupational skin diseases (OSDs) are scarce.

Objectives

To analyze risk occupations for OSDs in the Finnish Register of Occupational Diseases (FROD).

Methods

We retrieved numbers of OSD cases (excluding skin infections) for different occupations from the FROD in 2005‐2016. In the FROD, Finnish ISCO‐08–based classification of occupations was used since 2011, and the preceding ISCO‐88–based version until 2010. We combined cases from the earlier and the later period using conversion tables provided by Statistics Finland. We included occupations with at least five cases and analyzed them in detail. We calculated incidence rates for OSDs and separately for allergic contact dermatitis (ACD) in different risk occupations using national labor force statistics. We also studied causes of ACD in these occupations.

Results

Risk occupations with the largest number of OSD cases included farmers, hairdressers, assistant nurses, cooks, cleaners, machinists, and nurses. Occupations with the highest incidences of OSDs comprised spray painters (23.8/10 000 person years), bakers (20.4), and dental technicians (19.0). Epoxy compounds and acrylates were prominent causes of ACD in occupations with the highest incidences of ACD.

Conclusions

Uniform use of International Standard Classification of Occupations (ISCO) would facilitate comparisons of OSD figures in different countries.
Occupational contact dermatitis in Triveneto: Analysis of patch test data of the North Eastern Italian Database from 1996 to 2016
Authors: Santarossa Monica , Mauro Marcella , Belloni Fortina Anna , Corradin Maria T. , Larese Filon Francesca
Published: March 2020

Background

Occupational contact dermatitis (OCD) is frequent in the workplace.

Objectives

To provide recent data on the epidemiology of OCD in Italy.

Methods

This multicenter retrospective study, conducted from 1996 to 2016, included patients with suspected allergic contact dermatitis (ACD) patch tested in the departments comprising the North‐East Italy Contact Dermatitis Group.

Results

We studied 18 859 workers with a diagnosis of contact dermatitis (CD), of which 10.4% were recognized as being of professional origin. OCD declined from 1996 to 2011–2013 and increased in 2014–2016. The overall prevalence of both CD and OCD was higher in women compared to men, but the share of OCD of the total CD was greater for men compared to women. A history of atopic dermatitis was less frequent in workers with OCD than in non‐OCD patients (5.8% vs 8.6%). Hairdressers were the youngest profession (27.1 ± 11.7 years). Hands were the primary site of involvement in patients with OCD (76.6%). The five highest risk occupations for OCD were hairdressers, cooks, metalworkers, chemical industry workers, and construction workers.

Conclusions

OCDs have a relevant impact in our region, mainly for five job categories, and the increase in the last 3 years suggests the need to improve preventive measures.
Marine spatial planning on the Caribbean island of Montserrat: Lessons for data‐limited small islands
Authors: Flower Jason , Ramdeen Robin , Estep Andy , Thomas Lennon R. , Francis Sarita , Goldberg Grace , Johnson Ayana E. , McClintock Will , Mendes Stephen R. , Mengerink Kathryn , O'Garro Melissa , Rogers Lavern , Zischka Ute , Lester Sarah E.
Published: March 2020

As human use of the oceans increases, marine spatial planning (MSP) is being more widely adopted to achieve improved environmental, economic, and social outcomes. However, there is a lack of practical guidance for stakeholder driven, scientifically informed MSP processes in small island and data‐limited contexts. Here, we present an overview of MSP on the Caribbean island of Montserrat, with a focus on the scientific and technical input that helped inform the process. Montserrat presents an interesting case study of MSP in the small island context as it has ocean uses that are common to many islands, namely small‐scale fisheries and tourism, but the marine environment has been heavily impacted due to volcanic activity. We detail the methods for data collection and analysis and the decision‐making process that contributed to a marine spatial plan. We highlight aspects of the process that may be useful for other small islands embarking on MSP, and lessons learned regarding scientific support, including the need for on‐site scientific support and guidance throughout MSP, the importance of setting clear objectives, working within data limitations and making data accessible, and choosing and using appropriate decision support tools.
Is seabird light‐induced mortality explained by the visual system development?
Authors: Atchoi Elizabeth , Mitkus Mindaugas , Rodríguez Airam
Published: March 2020

Seabirds are impacted by coastal light pollution, leading to massive mortality events. Juveniles comprise the majority of affected individuals, while adults are only seldom grounded and reported in rescue programs. We propose a connection between visual system development of burrow nesting seabirds and the observed higher vulnerability to light pollution by a specific age group. We illustrate the need for multidisciplinary research to better understand and further mitigate light‐induced mortality.
No QTc Prolongation With Zanubrutinib: Results of Concentration‐QTc Analysis From a Thorough QT Study in Healthy Subjects
Authors: Mu Song , Darpo Borje , Tang Zhiyu , Novotny William , Tawashi Manal , Xue Hongqi , Willett Michael , Lin Leo , Sahasranaman Sri , Ou Ying C.
Published: March 2020

This thorough QT (TQT) study evaluated the effect of zanubrutinib on electrocardiogram (ECG) parameters by using concentration‐QTc (C‐QTc) analysis as the primary analysis for this study. Part A of the study determined the safety and tolerability of a single supratherapeutic dose of zanubrutinib (480 mg) in healthy volunteers. Part B was a randomized, blinded, placebo‐controlled and positive‐controlled, four‐way crossover, TQT study of single therapeutic (160 mg) and supratherapeutic (480 mg) doses of zanubrutinib, placebo, and open‐label moxifloxacin 400 mg. Thirty‐two participants received at least 1 dose of zanubrutinib, and 26 participants completed all 4 periods. Zanubrutinib did not have any effect on heart rate or cardiac conduction (pulse rate, QRS interval, or T‐wave morphology) and was generally well‐tolerated. Using C‐QTc analysis, the predicted placebo‐corrected change‐from‐baseline QT interval using Fridericia’s formula (ΔΔQTcF) was −3.4 msec (90% confidence interval: −4.9 to −1.9 msec) at peak concentrations of the 480 mg dose. A QT effect (ΔΔQTcF) exceeding 10 msec could be excluded within the observed concentration range at 160 and 480 mg doses. Assay sensitivity was established by moxifloxacin with 90% lower bound exceeding 5 msec. Implementing a C‐QTc analysis prospectively in this TQT study resulted in a substantially smaller sample size to maintain a similar study power as shown in the traditional time‐point analysis. A single 160‐mg or 480‐mg zanubrutinib dose did not prolong the QTc interval or have any other clinically relevant effects on ECG parameters.
Endoscopic ultrasound guided hepatic interventions
Authors: Hashimoto Rintaro , Chang Kenneth J.
Published: March 2020

Intervention for liver disease has predominantly been performed through the percutaneous approach. However, as endoscopic ultrasound (EUS) applications have expanded, there have emerged various EUS‐guided interventions for liver disease, a space we call “Endo‐Hepatology”. EUS‐guided liver biopsy can be considered the “forerunner” of Endo‐Hepatology and has become a clinical option for patients requiring histologic diagnosis and staging of their liver disease. EUS also enables direct access to the portal vein. Subsequently, many procedures are being explored, such as angiography, measurement of the portosystemic pressure gradient, portal vein sampling to detect cancer cell or DNA, and EUS‐guided transhepatic intrahepatic portosystemic shunt creation. Since the transducer is close to the liver, especially the left and caudate lobes, EUS can be used as a rescue when the percutaneous approach is not favorable and EUS‐guided treatments of liver tumor, cyst and abscess have been reported. This review summarizes the available studies of EUS‐guided intervention in the liver.
One language or two? Navigating cross‐language conflict in statistical word segmentation
Authors: Antovich Dylan M. , Graf Estes Katharine
Published: March 2020

Bilingual infants must navigate the similarities and differences between their languages to achieve native proficiency in childhood. Bilinguals learning to find individual words in fluent speech face the possibility of conflicting cues to word boundaries across their languages. Despite this challenge, bilingual infants typically begin to segment and learn words in both languages around the same time as monolinguals. It is possible that early bilingual experience may support infants’ abilities to track regularities relevant for word segmentation separately across their languages. In a dual speech stream statistical word segmentation task, we assessed whether 16‐month‐old infants could track syllable co‐occurrence regularities in two artificial languages despite conflicting information across the languages. We found that bilingual, but not monolingual, infants were able to segment the dual speech streams using statistical regularities. Although the two language groups did not differ on secondary measures of cognitive and linguistic development, bilingual infants’ real‐world experience with bilingual speakers was predictive of their performance in the dual language statistical segmentation task.
Barriers to completing oral glucose tolerance testing in women at risk of gestational diabetes
Authors: Lachmann E. H. , Fox R. A. , Dennison R. A. , Usher‐Smith J. A. , Meek C. L. , Aiken C. E.
Published: March 2020

Aim

Complications of gestational diabetes (GDM) can be mitigated if the diagnosis is recognized. However, some at‐risk women do not complete antenatal diagnostic oral glucose tolerance testing (OGTT). We aimed to understand reasons contributing to non‐completion, particularly to identify modifiable factors.

Methods

Some 1906 women attending a tertiary UK obstetrics centre (2018–2019) were invited for OGTT based on risk‐factor assessment. Demographic information, test results and reasons for non‐completion were collected from the medical record. Logistic regression was used to analyse factors associated with non‐completion.

Results

Some 242 women (12.3%) did not complete at least one OGTT, of whom 32.2% (n = 78) never completed testing. In adjusted analysis, any non‐completion was associated with younger maternal age [≤ 30 years; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6–3.4; P < 0.001], Black African ethnicity (OR 2.7, 95% CI 1.2–5.5; P = 0.011), lower socio‐economic status (OR 0.9, 95% CI 0.8–1.0; P = 0.021) and higher parity (≥ 2; OR 1.8, 95% CI 1.1–2.8; P = 0.013). Non‐completion was more likely if testing indications included BMI ≥ 30 kg/m2 (OR 1.7, 95% CI 1.1–2.4; P = 0.009) or family history of diabetes (OR 2.2, 95% CI 1.5–3.3; P < 0.001) and less likely if the indication was an ultrasound finding (OR 0.4, 95% CI 0.2–0.9; P = 0.035). We identified a common overlapping cluster of reasons for non‐completion, including inability to tolerate test protocol (21%), social/mental health issues (22%), and difficulty keeping track of multiple antenatal appointments (15%).

Conclusions

There is a need to investigate methods of testing that are easier for high‐risk groups to schedule and tolerate, with fuller explanation of test indications and additional support for vulnerable groups.
Changes in incidence of severe hypoglycaemia in people with type 2 diabetes from 2006 to 2016: analysis based on health insurance data in Germany considering the anti‐hyperglycaemic medication
Authors: Müller N. , Lehmann T. , Klöss A. , Günster C. , Kloos C. , Müller U. A.
Published: March 2020

Aim

To investigate the incidence of severe hypoglycaemia over the past 10 years, taking into account changes in anti‐hyperglycaemic therapy.

Methods

This retrospective population‐based study used German health insurance data. All adults diagnosed with documented type 2 diabetes (extrapolated to the German population: 6.6 million in 2006; 7.9 million in 2011; 8.86 million in 2016) were screened for severe hypoglycaemia. Anti‐hyperglycaemic agents were identified by Anatomical Therapeutic Chemical (ATC) code.

Results

The event rate for severe hypoglycaemia was 460 per 100 000 people in 2006, 490 per 100 000 in 2011 and 360 per 100 000 in 2016. The proportion of people with severe hypoglycaemia receiving sulfonylureas, as well as receiving combination therapy of metformin and sulfonylureas decreased from 2006 to 2016 (23.6% vs. 6.2%) Among those with severe hypoglycaemia in 2006, there were no prescriptions for dipeptidyl peptidase‐4 (DPP‐4) inhibitors, glucagon‐like peptide‐1 (GLP‐1) receptor agonists or sodium–glucose co‐transporter 2 (SGLT2) agonists. The proportions of people with severe hypoglycaemia receiving DPP‐4 inhibitors, GLP‐1 receptor agonists or SGLT2 agonists in 2011 and 2016 were low. The proportion of people receiving human insulin also decreased (from 11.3% in 2006 to 10.3% in 2011 and 4.3% in 2016); the proportion of people receiving insulin analogues increased from 5.4% in 2006 to 11.5% in 2016. Therapy with mixed insulins was used by 19.7% of people with severe hypoglycaemia in 2006, by 14.0% in 2011 and by 7.3% in 2016. People undergoing therapy with insulin analogues have the highest risk of severe hypoglycaemia adjusted by age, gender, nephropathy diagnosis and year of survey [odds ratio (OR) 14.4, 95% confidence interval (95% CI) 13.5–15.5].

Conclusion

The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, and decreased in 2016.
Empathy of dental students towards children after behaviour guidance lectures and clinical experience
Authors: Souror Yasser R. , Aljehani Dareen K. , Alshaikh Malath H.
Published: March 2020

Introduction

The empathetic behaviour of dentists is essential for perfect patient care. Because the behaviour of child patients in a dental clinic differs from that exhibited by the adults, knowing of empathy of dental students towards the child in the dental clinic is an important concern.

Methods

We distributed a modified form of the Health Professions Student version (HPS‐version) of the Jefferson Scale of Empathy (JSE) to dental students in two rounds: (R1) before and (R2) after introducing behaviour guidance subcourse and exposure to 3 clinical experiences with children to measure changes in empathy of dental students towards child patients. The modifications include replacing the “patient” words with “child patients” and translation into Arabic. We checked the internal consistency of the modified form of HPS‐version by Cronbach's coefficient alpha test. The significance level was set at 0.05 for all statistical analyses.

Results

Out of eighty‐one, sixty‐five dental students completed the survey and attended a behaviour guidance course and three clinical sessions. The questionnaire showed accepted reliability. There was a significant decrease in the empathy of dental students in R2 than R1 (P < .05). The level of empathy for males was less than female students in both rounds (P < .05).

Conclusions

The clinical interaction of children by dental students inhibits their empathy towards child patients, and a specific training course is needed to improve dental students’ empathy towards children since learning behaviour guidance may not sufficient.
Network meta‐analysis of first‐line treatments in transplant‐ineligible multiple myeloma patients
Authors: Gil‐Sierra Manuel David , Gimeno‐Ballester Vicente , Fenix‐Caballero Silvia , Alegre‐Del Rey Emilio Jesus
Published: March 2020

Objectives

Multiple myeloma (MM) is a complex disease. Lack of direct comparisons among treatments and incorporation of new alternatives make it necessary to perform studies that allow for clinical decision‐making. A network meta‐analysis (NMA) was developed to evaluate the comparative efficacy among different therapeutic alternatives in newly diagnosed transplant‐ineligible MM patients.

Methods

MEDLINE® and EMBASE® were systematically searched up for these drugs: lenalidomide, thalidomide, bortezomib, and daratumumab. Comparative phase II‐III randomized clinical trials (RCTs) were included. Progression‐free survival (PFS) was selected as efficacy outcome. The NMA was developed using Bayesian methods. Fixed‐ and random‐effects models were assessed using deviance information criteria.

Results

The systematic search yielded 593 results. Ten RCTs were included. No differences were observed between fixed‐ and random‐effects models. The combination of daratumumab, bortezomib, melphalan, and prednisone showed the best HR in PFS (reference treatment). Along with this scheme, the best PFS results were obtained by combination of daratumumab, lenalidomide, and dexamethasone (HR 1.2, 95% CrI 0.64‐2.4) and bortezomib with lenalidomide and dexamethasone (HR 1.6, 95% CrI 0.81‐3.0).

Conclusions

Schemes with the best PFS results were daratumumab treatments and combination of bortezomib, lenalidomide, and dexamethasone, although the latter scheme has been analyzed in heterogeneous populations.
Seascape genomics as a new tool to empower coral reef conservation strategies: An example on north‐western PacificAcropora digitifera
Authors: Selmoni Oliver , Rochat Estelle , Lecellier Gael , Berteaux‐Lecellier Veronique , Joost Stéphane
Published: March 2020

Coral reefs are suffering a major decline due to the environmental constraints imposed by climate change. Over the last 20 years, three major coral bleaching events occurred in concomitance with anomalous heatwaves, provoking a severe loss of coral cover worldwide. The conservation strategies for preserving reefs, as they are implemented now, cannot cope with global climatic shifts. Consequently, researchers are advocating for preservation networks to be set‐up to reinforce coral adaptive potential. However, the main obstacle to this implementation is that studies on coral adaption are usually hard to generalize at the scale of a reef system. Here, we study the relationships between genotype frequencies and environmental characteristics of the sea (seascape genomics), in combination with connectivity analysis, to investigate the adaptive potential of a flagship coral species of the Ryukyu Archipelago (Japan). By associating genotype frequencies with descriptors of historical environmental conditions, we discovered six genomic regions hosting polymorphisms that might promote resistance against heat stress. Remarkably, annotations of genes in these regions were consistent with molecular roles associated with heat responses. Furthermore, we combined information on genetic and spatial distances between reefs to predict connectivity at a regional scale. The combination of these results portrayed the adaptive potential of this population: we were able to identify reefs carrying potential heat stress adapted genotypes and to understand how they disperse to neighbouring reefs. This information was summarized by objective, quantifiable and mappable indices covering the whole region, which can be extremely useful for future prioritization of reefs in conservation planning. This framework is transferable to any coral species on any reef system and therefore represents a valuable tool for empowering preservation efforts dedicated to the protection of coral reefs in warming oceans.
Sources of epigenetic variation and their applications in natural populations
Authors: Angers Bernard , Perez Maëva , Menicucci Tatiana , Leung Christelle
Published: March 2020

Epigenetic processes manage gene expression and products in a real‐time manner, allowing a single genome to display different phenotypes. In this paper, we discussed the relevance of assessing the different sources of epigenetic variation in natural populations. For a given genotype, the epigenetic variation could be environmentally induced or occur randomly. Strategies developed by organisms to face environmental fluctuations such as phenotypic plasticity and diversified bet‐hedging rely, respectively, on these different sources. Random variation can also represent a proxy of developmental stability and can be used to assess how organisms deal with stressful environmental conditions. We then proposed the microbiome as an extension of the epigenotype of the host to assess the factors determining the establishment of the community of microorganisms. Finally, we discussed these perspectives in the applied context of conservation.
First report of equine parvovirus‐hepatitis‐associated Theiler’s disease in Europe
Authors: Vengust Modest , Jager Mason C. , Zalig Valentina , Cociancich Vasilij , Laverack Melissa , Renshaw Randall W. , Dubovi Edward , Tomlinson Joy E. , Van de Walle Gerlinde R. , Divers Thomas J.
Published: March 2020

Background

Equine parvovirus‐hepatitis (EqPV‐H) has been proposed as the aetiological cause of Theiler's disease, also known as serum hepatitis. EqPV‐H‐associated Theiler's disease has not been previously reported in Europe.

Objectives

To determine whether EqPV‐H infection was associated with a 2018‐2019 outbreak of Theiler's disease in four horses on a studfarm.

Study design

Descriptive case series.

Methods

The medical records of four horses from the same farm diagnosed with fatal Theiler's disease were examined retrospectively. Information collected included a clinical history, physical examination findings, tetanus antitoxin exposure, serum biochemistry and necropsy reports. Liver tissue from all four horses was tested for EqPV‐H using PCR and in situ hybridisation (ISH) assays.

Results

Three of the horses had a history of recent (7‐11 weeks) tetanus antitoxin administration. Liver tissue from all four horses tested positive for EqPV‐H with PCR. In situ hybridisation revealed a widespread distribution of viral nucleic acid in hepatocytes in one case, and a more sporadic distribution in the remaining three cases.

Main limitations

Case controls were not available from the farm in question given the retrospective nature of analysis.

Conclusions

This case series documents the first reported EqPV‐H‐associated Theiler's disease in Europe and the first use of ISH to visualise the viral nucleic acid in liver tissues of horses with Theiler's disease.
The prevalence of uveitis in a population of donkeys in the UK
Authors: Bradley Claire , Grundon Rachael , Sansom Philip G.
Published: March 2020

Background

Uveitis is reported to be a leading cause of blindness in horses. Little work has been undertaken to date to investigate whether donkeys are affected by a similar disease prevalence.

Objectives

To investigate the disease prevalence of uveitis in a population of donkeys in the UK.

Study design

Descriptive observational study.

Methods

An ophthalmic examination was performed on each donkey, in a darkened stable. Each donkey underwent slit lamp biomicroscopy, and direct and/or indirect ophthalmoscopy. Fluorescein staining, STT1 and IOPs were measured when deemed clinically necessary. Pharmacological pupillary dilation was achieved using 1% tropicamide.

Results

A total of 207 donkeys were examined: 139 males (67.1%) and 68 females (32.9%). Age range was 2‐37 years (median: 17 years, interquartile range: 9‐25 years). Three donkeys (1.5%) were blind in one eye, and one was monocular at the time of examination. Signs consistent with either previous or current uveitis were identified in eight eyes of six animals (2.9%). Clinical signs included are as follows: miosis (n = 1), corpora nigra atrophy (n = 6), anterior lens capsule pigment (n = 2), cataract (n = 8), posterior synechiae (n = 3), lens subluxation (n = 1), vitreal changes (n = 2), peripapillary scarring (n = 3) and phthisis bulbi (n = 1). Significant ocular pathology precluded fundic examination in three eyes. Three out of eight eyes (37.5%) were blinded by the pathology. The risk of uveitis was found to increase with age (OR 1.1, CI: 1.01‐1.25) on univariable analysis (P = .046.).

Main limitations

Fluorescein staining, tonometry and Schirmer tear test measurements were not performed on all donkeys.

Conclusions

The disease prevalence reported here is comparable to that reported for horses in the UK. Larger prospective studies are necessary to determine whether there is a similar trend in disease prevalence in the donkey population worldwide. In addition, further investigations should aim to establish whether uveitis in donkeys is similar to the ERU syndrome seen in horses.
Acute, subacute and chronic sequelae of horses accidentally exposed to monensin‐contaminated feed
Authors: Gy Clémentine , Leclere Mathilde , Bélanger Marie‐Claude , Allano Marion , Beauchamp Guy , Lavoie Jean‐Pierre
Published: March 2020

Background

Monensin is highly toxic to horses and inadvertent ingestion can result in cardiac injury and death.

Objectives

To describe sequelae of monensin ingestion and to determine clinical predictors of outcome.

Study design

Observational clinical study.

Methods

Physical examination, electrocardiogram and echocardiography were performed on 76 horses accidentally exposed to monensin‐contaminated feed. Four horses were examined within 14 days of exposure (acute period), 29 horses were examined between 15 and 45 days post‐exposure (subacute period) and 70 horses were examined 4‐10 months after exposure (chronic period). Follow‐up information was obtained for 56 horses by telephone interviews approximately 16 months after exposure.

Results

Cardiac abnormalities were detected in 4/4, 19/29 and 31/70 horses during the acute, subacute and chronic periods, respectively. Sixteen months post‐exposure, 34 of the 64 horses (53%) for which the outcome was known had returned to their previous use, 13 (20%) were reported to be exercise intolerant, three (5%) were retired and 14 (22%) were dead (two deaths, 12 euthanasia). Thinning of the myocardium observed at any point in time was associated with a negative outcome. Heterogeneity of the myocardium observed in the acute/subacute period was associated with a negative outcome while subjective contractile intraventricular dyssynchrony, cardiac chamber dilation, decreased fractional shortening and multiple premature ventricular complexes observed in the chronic period were associated with a negative outcome. Some horses with significant changes associated with a negative outcome in the chronic phase still returned to their previous work.

Main limitations

No control group and only 27 horses were examined more than once.

Conclusions

Clinical outcome of horses exposed to sublethal doses of monensin is highly variable. The presence of heterogeneity and thinning of the myocardium shortly after intoxication were associated with a negative outcome.
Murine dorsal hair type is genetically determined by polymorphisms in candidate genes that influence BMP and WNT signalling
Authors: Villani Rehan M. , Johnson Ayaka , Galbraith Jack A. , Baz Betoul , Handoko Herlina Y. , Walker Graeme J. , Khosrotehrani Kiarash
Published: March 2020

Mouse dorsal coat hair types, guard, awl, auchene and zigzag, develop in three consecutive waves. To date, it is unclear if these hair types are determined genetically through expression of specific factors or can change based on their mesenchymal environment. We undertook a novel approach to this question by studying individual hair type in 67 Collaborative Cross (CC) mouse lines and found significant variation in the proportion of each type between strains. Variation in the proportion of zigzag, awl and auchene, but not guard hair, was largely due to germline genetic variation. We utilised this variation to map a quantitative trait locus (QTL) on chromosome 12 that appears to influence a decision point switch controlling the propensity for either second (awl and auchene) or third wave (zigzag) hairs to develop. This locus contains two strong candidates, Sostdc1 and Twist1, each of which carry several ENCODE regulatory variants, specific to the causal allele, that can influence gene expression, are expressed in the developing hair follicle, and have been previously reported to be involved in regulating human and murine hair behaviour, but not hair subtype determination. Both of these genes are likely to play a part in hair type determination via regulation of BMP and/or WNT signalling.
Beyond antibodies: B cells in Hidradenitis Suppurativa: Bystanders, contributors or therapeutic targets?
Authors: Frew John W. , Grand David , Navrazhina Kristina , Krueger James G.
Published: March 2020

Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis in which B cells play a prominent but unclear role. Our understanding of the role of B cells in innate and adaptive immunity (including antibody production, antigen presentation and effector functions) is rapidly evolving; and these novel findings require integration into the pathophysiologic model of HS. B cells are transiently present in normal human skin and have functions in the maintenance of innate cutaneous immunity. Recruitment and trafficking of B cells in significant numbers to skin is mediated via B cell‐specific chemokines as well as shared signalling with T‐cells. The evidence suggests that the presence of antibody‐secreting B cells is not sufficient to induce clinical disease and T‐cell interaction is required to induce clinical disease. Such interactions can occur in secondary lymphoid organs adjacent to involved tissue or in tertiary lymphoid organs which develop in response to the HS inflammatory milieu. This milieu directly mediates the types of antibodies produced by B cells, given the role of cytokines in B‐cell class switching. Identified antibodies in HS (IgG, IgM, ASCA, ACPA) currently demonstrate no evidence of pathogenicity, but may be novel biomarkers for disease severity. B cells also have anti‐inflammatory properties through production of IL‐10 and IL‐35 which require experimental validation. Overall, B cells in HS are likely to be involved in amplification of a pre‐existing inflammatory response; but it remains unclear whether they may be directly pathogenic.
Prescription patterns of first‐ and second‐generation antipsychotic drugs in the French population
Authors: Kovess‐Masfety Viviane , Balusson Frédéric , Leray Emmanuelle , Husky Mathilde , Scailteux Lucie‐Marie
Published: March 2020

This study assessed in depth the use of first‐ and second‐generation antipsychotic (FGAP/SGAP) drugs in France. A 1/97th random sample of beneficiaries affiliated to the French Health Insurance system—Echantillon Généraliste des Bénéficiaires (EGB)—was used: (i) 621 662 persons in 2015 among which 11 319 had an antipsychotic (AP) prescription; (ii) a sample of first AP prescriptions concerning 5 935 patients in 2013 and 2014 (no AP in the last 6 months of 2012) for whom diagnosis was available in 40% of cases. In 2015, AP prevalence was 21.9/1 000. SGAP/FGAP ratio was 1.02. Long‐lasting prescriptions were rare: 1.79/1 000 for FGAP and 1.38/1 000 for SGAP. FGAP first prescriptions were higher than SGAP for each age class, except for <18 aged patients; 2.85% had both generations; 50.7% of the patients had another psychotropic. GPs prescribed more FGAPs than SGAPs, psychiatrists prescribed more SGAPs and hospital‐based practitioners prescribed both generations equally, and these patterns changed across age ranges: For the elderly, GPs are the more frequent prescribers. SGAP/FGAP ratio is different by diagnostic categories. In France, FGAPs are largely prescribed by GPs mainly for the elderly, but young and adult patients are concerned as well. Inappropriate antipsychotic consumption through off‐label use, which adds to the co‐prescription, especially in vulnerable population groups, mainly concerns FGAP prescriptions by GPs who do not have psychiatric training and limited contact with psychiatrists. Attention should then be brought to the regulatory advisory agencies in order to better inform and train the prescribers.
Bupivacaine inhibits angiogenesis through oxidative stress‐dependent inhibition of Akt/mTOR and activation of AMPK
Authors: Zhu Qiong , Zhu Guanhua , Xu Wei , Dan Jiapeng , Xia Rui , Liu Weiwei
Published: March 2020

Although substantial evidence shows the link of local anesthesia and decreased tumor recurrence, the role of amide‐linked local anesthetics, particularly bupivacaine, on angiogenesis (a hallmark of tumor progression and metastasis) has not been revealed. In this work, we demonstrate the anti‐angiogenic activity of bupivacaine and its underlying mechanism in endothelial cells. We show that bupivacaine inhibits early stage of capillary network formation via suppressing endothelial cell migration without affecting adhesion to matrix. Bupivacaine also inhibits endothelial cell growth and survival. Mechanism analysis indicates that bupivacaine inhibits mitochondrial respiration via decreasing mitochondrial respiratory activity of complex I and II but not IV or V, resulting in energy depletion, oxidative stress, inhibition of Akt/mTOR, and activation of AMPK pathway. The rescue of an antioxidant NAC on the effects of bupivacaine confirms that bupivacaine inhibits angiogenesis through oxidative stress‐dependent inhibition of Akt/mTOR and activation of AMPK. Our work clearly demonstrates the inhibitory effects of bupivacaine on angiogenesis via targeting mitochondria. Our findings are in line with the previous work providing the preclinical evidence on how local anesthetics could influence the outcome of cancer patients.
Annexin A13 predicts poor prognosis for lung adenocarcinoma patients and accelerates the proliferation and migration of lung adenocarcinoma cells by modulating epithelial–mesenchymal transition
Authors: Xue Guo‐Liang , Zhang Cong , Zheng Gui‐Li , Zhang Lian‐Jun , Bi Jing‐Wang
Published: March 2020

This study aimed to investigate the role of ANXA13 in lung adenocarcinoma (LUAD) growth, migration, and the underlying mechanisms. Firstly, in the TCGA dataset for LUAD, ANXA13 is found to be highly expressed in patients with LUAD and high expression of ANXA13 predicted poor outcomes in LUAD patients. Consistently, the data of qRT‐PCR showed that the expression of ANXA13 was higher in LUAD cell lines (Calu‐3, LTEP‐a‐2, and NCI‐H1395) than that in normal lung cell line BEAS2B. Then, we performed gain‐ and loss of function of ANXA13 in NCI‐H1395 and Calu‐3 cells, respectively. The results displayed that deficiency of ANXA13 suppresses cell proliferation, invasion, and migration in Calu‐3 cells and overexpression of ANXA13 augments cell proliferation, invasion, and migration in NCI‐H1395 cells. Finally, it was found that silencing of ANXA13 obviously raised the protein expression levels of E‐cadherin and reduced the protein levels of N‐cadherin, Vimentin, and Snail in Calu‐3 cells whereas overexpression of ANXA13 obviously receded the protein expression levels of E‐cadherin and enhanced the protein levels of N‐cadherin, Vimentin, and Snail in NCI‐H1395 cells. This study analyzed the biological effects of ANXA13 in LUAD cells, indicating that ANXA13 could regard as a therapeutic target for LUAD.
Host expression system modulates recombinant Hsp70 activity through post‐translational modifications
Authors: Rigo Mauricio M. , Borges Thiago J. , Lang Benjamin J. , Murshid Ayesha ,   Nitika , Wolfgeher Donald , Calderwood Stuart K. , Truman Andrew W. , Bonorino Cristina
Published: March 2020

The use of model organisms for recombinant protein production results in the addition of model‐specific post‐translational modifications (PTMs) that can affect the structure, charge, and function of the protein. The 70‐kDa heat shock proteins (Hsp70) were originally described as intracellular chaperones, with ATPase and foldase activity. More recently, new extracellular activities of Hsp70 proteins (e.g., as immunomodulators) have been identified. While some studies indicate an inflammatory potential for extracellular Hsp70 proteins, others suggest an immunosuppressive activity. We hypothesized that the production of recombinant Hsp70 in different expression systems would result in the addition of different PTMs, perhaps explaining at least some of these opposing immunological outcomes. We produced and purified Mycobacterium tuberculosis DnaK from two different systems, Escherichia coli and Pichia pastoris, and analyzed by mass spectrometry of the protein preparations, investigating the impact of PTMs in an in silico and in vitro perspective. The comparisons of DnaK structures in silico highlighted that electrostatic and topographical differences exist that are dependent upon the expression system. Production of DnaK in the eukaryotic system dramatically affected its ATPase activity and significantly altered its ability to downregulate MHC II and CD86 expression on murine dendritic cells (DCs). Phosphatase treatment of DnaK indicated that some of these differences related specifically to phosphorylation. Altogether, our data indicate that PTMs are an important characteristic of the expression system, with differences that impact interactions of Hsps with their ligands and subsequent functional activities.

Database

Mass spectrometry proteomic data are available in the PRIDE database under the accession number PXD011583.
Mitotic entry upon Topo II catalytic inhibition is controlled by Chk1 and Plk1
Authors: Arroyo Maria , Cañuelo Ana , Calahorra Jesús , Hastert Florian D. , Sánchez Antonio , Clarke Duncan J. , Marchal J. Alberto
Published: March 2020

Catalytic inhibition of topoisomerase II during G2 phase delays onset of mitosis due to the activation of the so‐called decatenation checkpoint. This checkpoint is less known compared with the extensively studied G2 DNA damage checkpoint and is partially compromised in many tumor cells. We recently identified MCPH1 as a key regulator that confers cells with the capacity to adapt to the decatenation checkpoint. In the present work, we have explored the contributions of checkpoint kinase 1 (Chk1) and polo‐like kinase 1 (Plk1), in order to better understand the molecular basis of decatenation checkpoint. Our results demonstrate that Chk1 function is required to sustain the G2 arrest induced by catalytic inhibition of Topo II. Interestingly, Chk1 loss of function restores adaptation in cells lacking MCPH1. Furthermore, we demonstrate that Plk1 function is required to bypass the decatenation checkpoint arrest in cells following Chk1 inhibition. Taken together, our data suggest that MCPH1 is critical to allow checkpoint adaptation by counteracting Chk1‐mediated inactivation of Plk1. Importantly, we also provide evidence that MCPH1 function is not required to allow recovery from this checkpoint, which lends support to the notion that checkpoint adaptation and recovery are different mechanisms distinguished in part by specific effectors.
The ECM path of senescence in aging: components and modifiers
Authors: Levi Naama , Papismadov Nurit , Solomonov Inna , Sagi Irit , Krizhanovsky Valery
Published: March 2020

The extracellular matrix (ECM) is a key noncellular component in all organs and tissues. It is composed of a large number of proteins including collagens, glycoproteins (GP), and ECM‐associated proteins, which show diversity of biochemical and biophysical functions. The ECM is dynamic both in normal physiology of tissues and under pathological conditions. One cellular phenomenon associated with changes in both ECM components expression and in ECM remodeling enzymes secretion is cellular senescence. It represents a stable state form of cell cycle arrest induced in proliferating cells by various forms of stress. Short‐term induction of senescence is essential for tumor suppression and tissue repair. However, long‐term presence of senescent cells in tissues may have a detrimental role in promoting tissue damage and aging. Up to date, there is insufficient knowledge about the interplay between the ECM and senescence cells. Since changes in the ECM occur in many physiological and pathological conditions in which senescent cells are present, a better understanding of ECM‐senescence interactions is necessary. Here, we will review the functions of the different ECM components and will discuss the current knowledge about their regulation in senescent cells and their influence on the senescence state.
NAG‐thiazoline is a potent inhibitor of the Vibrio campbellii GH20 β‐N‐Acetylglucosaminidase
Authors: Meekrathok Piyanat , Stubbs Keith A. , Aunkham Anuwat , Kaewmaneewat Anuphon , Kardkuntod Apinya , Bulmer David M. , van den Berg Bert , Suginta Wipa
Published: March 2020

Vibrio spp. play a vital role in the recycling of chitin in oceans, but several Vibrio strains are highly infectious to aquatic animals and humans. These bacteria require chitin for growth; thus, potent inhibitors of chitin‐degrading enzymes could serve as candidate drugs against Vibrio infections. This study examined NAG‐thiazoline (NGT)‐mediated inhibition of a recombinantly expressed GH20 β‐N‐acetylglucosaminidase, namely VhGlcNAcase from Vibrio campbellii (formerly V. harveyi) ATCC BAA‐1116. NGT strongly inhibited VhGlcNAcase with an IC50 of 11.9 ± 1.0 μm and Ki 62 ± 3 µm, respectively. NGT was also found to completely inhibit the growth of V. campbellii strain 650 with an minimal inhibitory concentration value of 0.5 µm. ITC data analysis showed direct binding of NGT to VhGlcNAcase with a Kd of 32 ± 1.2 μm. The observed ΔG°binding of −7.56 kcal·mol−1 is the result of a large negative enthalpy change and a small positive entropic compensation, suggesting that NGT binding is enthalpy‐driven. The structural complex shows that NGT fully occupies the substrate‐binding pocket of VhGlcNAcase and makes an exclusive hydrogen bond network, as well as hydrophobic interactions with the conserved residues around the −1 subsite. Our results strongly suggest that NGT could serve as an excellent scaffold for further development of antimicrobial agents against Vibrio infections.

Database

Structural data are available in PDB database under the accession number 6K35.
Moderate prenatal alcohol exposure impairs cognitive control, but not attention, on a rodent touchscreen continuous performance task
Authors: Olguin Sarah L. , Thompson Shannon M. , Young Jared W. , Brigman Jonathan L.
Published: March 2020

A common feature associated with fetal alcohol spectrum disorders is the inability to concentrate on a specific task while ignoring distractions. Human continuous performance tasks (CPT), measure vigilance and cognitive control simultaneously while these processes are traditionally measured separately in rodents. We recently established a touchscreen 5‐choice CPT (5C‐CPT) that measures vigilance and cognitive control simultaneously by incorporating both target and nontargets and showed it was sensitive to amphetamine‐induced improvement in humans and mice. Here, we examined the effects of moderate prenatal alcohol exposure (PAE) in male and female mice on performance of the 5‐choice serial reaction time task (5‐CSRTT), which contained only target trials, and the 5C‐CPT which incorporated both target and nontarget trials. In addition, we assessed gait and fine motor coordination in behavioral naïve PAE and control animals. We found that on the 5‐CSRTT mice were able to respond to target presentations with similar hit rates regardless of sex or treatment. However, on the 5C‐CPT PAE mice made significantly more false alarm responses vs controls. Compared with control animals, PAE mice had a significantly lower sensitivity index, a measure of ability to discriminate appropriate responses to stimuli types. During 5C‐CPT, female mice, regardless of treatment, also had increased mean latency to respond when correct and omitted more target trials. Gait assessment showed no significant differences in PAE and SAC mice on any measure. These findings suggest that moderate exposure to alcohol during development can have long lasting effects on cognitive control unaffected by gross motor alterations.
Determination of Trace Bismuth in Environmental Waters by ICP‐MS with Cobalt Ion‐Assisted Photochemical Vapour Generation
Authors: Yu Ying , Zhao Qian , Bao Haolin , Mou Qing , Shi Zeming , Chen Youliang , Gao Ying
Published: March 2020

With increasing use of bismuth in industry, a better understanding of its environmental behaviour is required, including an improved knowledge of its background concentration range in (non‐saline) freshwaters. However, the poor analytical sensitivity of previous methods may lead to inaccurate measurement results for Bi3+ in environmental samples. In this work, cobalt ion‐assisted photochemical vapour generation (PVG) was developed for the detection of trace Bi with inductively coupled plasma‐mass spectrometry (ICP‐MS) measurement. The volatile species of Bi was found to be (CH3)3Bi generated under UV irradiation in the presence of formic acid, acetic acid and Co2+. The major parameters potentially influencing the detection of Bi were investigated. Under optimised conditions, the limit of detection (3s, n = 11) of the proposed method was 0.3 ng l−1. The analytical sensitivity was enhanced about 70‐fold for Bi3+ compared with that using classic pneumatic nebulisation of ICP‐MS. Furthermore, the proposed method showed better analytical sensitivity and anti‐interference ability towards co‐existing ions compared with ferric ion‐assisted PVG systems. The accuracy of the proposed method was evaluated by analysis of environmental water samples and certified reference materials with satisfactory results.