bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart transplantation in the early phase of the COVID‐19 pandemic: A single‐center case series
Authors: Hsu Jeffrey J. , Al‐Saffar Farah , Ardehali Reza , Baas Arnold S. , Carlson Margrit , Cruz Daniel , Deng Mario , Fan Ashley , Fraschilla Stephanie , Gaynor Pryce , Kamath Megan , Kubak Bernard M. , Schaenman Joanna , Stimpson Emily , Vucicevic Darko , Ardehali Abbas , Nsair Ali
Published: July 2020

The infectious disease coronavirus disease 2019 (COVID‐19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID‐19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re‐evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID‐19 screening scrutiny and recipient waiting list management in anticipation of COVID‐19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end‐stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.
Donor‐recipient age interaction and the impact on clinical results after heart transplantation
Authors: Lechiancole Andrea , Vendramin Igor , Sponga Sandro , Guzzi Giorgio , Ferrara Veronica , Nalli Chiara , Di Nora Concetta , Bortolotti Uberto , Livi Ugolino
Published: July 2020

To evaluate the impact of donor‐recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990‐December 2018, mean follow‐up 111 ± 80 months) were stratified into 4 groups (young‐R/young‐D, young‐R/old‐D, old‐R/young‐D, old‐R/old‐D) according to the recipient (young‐R < 60, old‐R ≥ 60 years) and the donor (young‐D < 50, old‐D ≥ 50 years) age. No difference was found among 30‐day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young‐R/young‐D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2‐3.4), 2.1(1.4‐3.8) and 2.5(1.6‐4.1) for groups old‐R/young‐D, young‐R/old‐D, old‐R/old‐D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old‐R/young‐D group [adjusted HR 0.4(0.2‐0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.
Targeting the NLRP3 inflammasome to reduce warm ischemic injury in donation after circulatory death heart
Authors: Quader Mohammed , Mezzaroma Eleonora , Kenning Kristine , Toldo Stefano
Published: July 2020

While the donation after circulatory death (DCD) heart transplantation is an emerging clinical practice, the primary source of donor hearts for transplantation remains donation after brain death (DBD) donors. DCD process induces formation of NOD‐like receptor family pyrin domain containing‐3 (NLRP3) inflammasome, a key mediator of inflammation‐driven damage to heart. Inhibition of NLRP3 inflammasome formation could be protective to DCD hearts. Five groups (n = 8 each) of mice were studied—control beating heart donor (CBD) wild‐type (WT), DCD WT, CBD NLRP3 knockout (KO), DCD NLRP3 KO, and DCD WT NLRP3 inhibitor group. Hearts were procured and reanimated on a Langendorff system to assess physiologic parameters and then for molecular assays. NLRP3 inhibitor (50 µmol/L) was administered to the DCD‐NLRP3 inhibitor group at reanimation. Tissue NLRP3 levels were 80% higher in the DCD WT group compared with the CBD‐WT group. Caspase‐1 activity was significantly elevated in DCD WT but not in KO or NLRP3 inhibitor groups. The developed pressures and ±dP/dt were significantly impaired in the DCD WT group compared with the CBD‐WT group, P < .05, but were well preserved in DCD‐NLRP3 inhibitor group. The DCD process activates the NLRP3 inflammasome, contributing to myocardial damage and dysfunction. NLRP3 inflammasome inhibition limits myocardial injury and preserves DCD heart function.
Basal cell carcinoma with perineural invasion: A prospective study examining subtype, tumor surface diameter, invasion depth, and anatomic site in 3005 consecutive cases
Authors: Pyne John H. , Myint Esther , Hou Ruihang , Clark Simon P. , Wong Cheri , Gorji Madhieh
Published: July 2020

Background

Basal cell carcinoma (BCC) may present with or without perineural invasion (PNI). We reviewed BCC for PNI by subtype, microscopic tumor surface diameter, invasion depth, and anatomic site.

Method

Consecutive excisions were prospectively collected in an Australian center 2016‐2018.

Results

Total cases were 3005 including 40 with PNI: 28 in males, 12 in females. Superficial and nodular subtypes had no PNI. As the percentage tumor mass of infiltrative BCC increased beyond 90% the presence of PNI substantially escalated (OR7.0). Comparing PNI absent or present the respective maximum mean tumor microscopic surface diameters ranged from (95%CI [9.6‐10.0] P < .001) to 11.2 mm (95%CI [9.4‐13.0] P = .59). Respective maximum mean invasion depths were from 1.0 mm (95%CI [0.98‐1.05] P < .001) to 2.3 mm (95%CI [1.8‐2.7] P < .001). Respective maximum mean invasion depths were from 1.0 mm (95%CI [0.98‐1.05] P < .001) to 2.3 mm (95%CI [1.8‐2.7] P < .001) to 2.3 mm (95%CI[1.8‐2.7] P < .001). Males recorded most PNI on the scalp, followed by cheek and chin. Patients with more than two BCC cases had a greater proportional PNI risk (OR3.7). Mean PNI nerve diameters were 0.06 mm2 (males) and 0.03 mm2 (females).

Conclusion

Increases in percentage infiltrative subtype within the tumor mass, microscopic tumor diameter, tumor invasion depth, and BCC cases per patient all recorded more PNI. Minimum invasion depths with PNI were 1.0 mm on males (nose) and 1.0 mm females (forehead).
Relevance of rosette patterns in variants of papillary thyroid carcinoma
Authors: Dell'Aquila Marco , Musarra Teresa , Fiorentino Vincenzo , Brunelli Chiara , De Marco Costanza , Raffaelli Marco , Traini Emanuela , Pio Lombardi Celestino , Fadda Guido , Larocca Luigi Maria , Pantanowitz Liron , Rossi Esther Diana
Published: July 2020

Introduction

The detection of rosette‐like clusters (RLC) of follicular cells in thyroid carcinoma has been reported mostly in the columnar cell variant of papillary thyroid carcinoma (PTC). Despite the fact that diagnosing variants of PTC is no longer encouraged by The Bethesda System for Reporting Thyroid Cytopathology, the identification of cytomorphological features such as RLC linked with these tumours might help reduce possible misinterpretation in thyroid fine needle aspiration (FNA) cytology. We accordingly investigated the potential correlation of architectural patterns including RLC with PTC variants.

Methods

We analysed 225 thyroid FNA cytology cases diagnosed as suspicious for malignancy (SFM) and positive for malignancy (M) over a 1‐year time where all samples had corresponding histology. We also included 150 benign lesions from the same period. The presence of RLC vs similar appearing solid clusters, papillary structures and microfollicles were evaluated. We also performed immunocytochemistry and molecular testing for BRAFV600E.

Results

We included 100 (44.4%) SFM favouring PTC and 125 (55.6%) M cases with cyto‐histological correlation. On histology, all SFM and M cases showed malignancy including 140 (62.2%) classic PTC and 85 (37.8%) PTC variants. The cytomorphological patterns in all FNA samples included solid (74%), papillary (89%), microfollicular (70%), and pseudo‐RLC morphology (25.7%). We identified only pseudo‐RLC in 33 FNA specimens from PTC variant cases that included tall cell variant (42.4%), hobnail variant (21.2%) and miscellaneous variants (36.3%) of PTC. No definitive RLC were detected in our series. Immunocytochemistry and BRAFV600E were not specifically linked with an RLC pattern.

Conclusions

These findings demonstrate that in our dataset the architectural pattern of RLC was not recognised within PTC variants. However, we did identify a pseudo‐RLC pattern that was observed in association with tall cell variant and hobnail variant cases of PTC.
The link between per capita alcohol consumption and alcohol‐related harm in educational groups
Authors: Norström Thor , Landberg Jonas
Published: July 2020

Introduction and Aims

Research based on individual‐level data suggests that the same amount of alcohol yields more harm in low‐socioeconomic status (SES) groups than in high‐SES groups. Little is known whether the effect of changes in population‐level alcohol consumption on harm rates differs by SES‐groups. The aim of this study was to elucidate this issue by estimating the association between per capita alcohol consumption and SES‐specific rates of alcohol‐related mortality.

Design and Methods

Per capita alcohol consumption was proxied by Systembolaget's alcohol sales (litres 100% alcohol per capita 15+). Quarterly data on mortality and alcohol consumption spanned the period 1991Q1‐2017Q4. We used two outcomes: (i) alcohol‐specific mortality (deaths with an explicit alcohol diagnosis); and (ii) violent deaths. SES was measured by education. We used three educational groups: (i) low (<10 years); (ii): intermediate (10–12 years); and (iii) high (13+ years). We applied error correction modelling to estimate the association between alcohol and alcohol‐specific mortality, and seasonal autoregressive integrated moving average‐modelling to estimate the association between alcohol and violent deaths.

Results

The estimated associations between per capita consumption and the two outcomes were positive and statistically significant in the two groups with low and intermediate education, but not in the high education group. There was a significant gradient in the level of association between alcohol consumption and alcohol‐related harm by educational group; the association was stronger the lower the educational group.

Discussion and Conclusions

Our findings suggest that the association between per capita consumption and alcohol‐related harm was stronger the lower the educational group.
The value of proactive goal setting and choice in 3‐ to 7‐year‐olds' use of working memory gating strategies in a naturalistic task
Authors: Freier Livia , Gupta Pankaj , Badre David , Amso Dima
Published: July 2020

Rule‐guided behavior depends on the ability to strategically update and act on content held in working memory. Proactive and reactive control strategies were contrasted across two experiments using an adapted input/output gating paradigm (Neuron, 81, 2014 and 930). Behavioral accuracies of 3‐, 5‐, and 7‐year‐olds were higher when a contextual cue appeared at the beginning of the task (input gating) rather than at the end (output gating). This finding supports prior work in older children, suggesting that children are better when input gating but rely on the more effortful output gating strategy for goal‐oriented action selection (Cognition, 155, 2016 and 8). A manipulation was added to investigate whether children's use of working memory strategies becomes more flexible when task goals are specified internally rather than externally provided by the experimenter. A shift toward more proactive control was observed when children chose the task goal among two alternatives. Scan path analyses of saccadic eye movement indicated that giving children agency and choice over the task goal resulted in less use of a reactive strategy than when the goal was determined by the experimenter.
Continuous developmental change explains discontinuities in word learning
Authors: Fourtassi Abdellah , Regan Sophie , Frank Michael C.
Published: July 2020

Cognitive development is often characterized in terms of discontinuities, but these discontinuities can sometimes be apparent rather than actual and can arise from continuous developmental change. To explore this idea, we use as a case study the finding by Stager and Werker (1997) that children's early ability to distinguish similar sounds does not automatically translate into word learning skills. Early explanations proposed that children may not be able to encode subtle phonetic contrasts when learning novel word meanings, thus suggesting a discontinuous/stage‐like pattern of development. However, later work has revealed (e.g., through using more precise testing methods) that children do encode such contrasts, thus favoring a continuous pattern of development. Here, we propose a probabilistic model that represents word knowledge in a graded fashion and characterizes developmental change as improvement in the precision of this graded knowledge. Our model explained previous findings in the literature and provided a new prediction – the referents' visual similarity modulates word learning accuracy. The models' predictions were corroborated by human data collected from both preschool children and adults. The broader impact of this work is to show that computational models, such as ours, can help us explore the extent to which episodes of cognitive development that are typically thought of as discontinuities may emerge from simpler, continuous mechanisms.
Lessons from the Ebola epidemics and their applications for COVID‐19 pandemic response in sub‐Saharan Africa
Authors: Afolabi Muhammed O. , Folayan Morenike Oluwatoyin , Munung Nchangwi Syntia , Yakubu Aminu , Ndow Gibril , Jegede Ayodele , Ambe Jennyfer , Kombe Francis
Published: July 2020

COVID‐19, caused by a novel coronavirus named SARS‐CoV‐2, was identified in December 2019, in Wuhan, China. It was first confirmed in sub‐Saharan Africa in Nigeria on 27 February 2020 and has since spread quickly to all sub‐Saharan African countries, causing more than 111,309 confirmed cases and 2,498 deaths as of 03 June 2020. The lessons learned during the recent Ebola virus disease (EVD) outbreaks in some sub‐Saharan African countries were expected to shape and influence the region’s responses to COVID‐19 pandemic. However, some of the challenges associated with the management of the EVD outbreaks persist and create obstacles for the effective management of the COVID‐19 pandemic. This article describes the commonalities between the EVD epidemics and COVID‐19 pandemic, with a view to draw on lessons learned to effectively tackle the ongoing pandemic. Key successes, failures and lessons learned from previous EVD outbreaks are discussed. Recommendations on how these lessons can be translated to strengthen the COVID‐19 response in sub‐Saharan Africa are provided.
Recognizing chronic pain in cerebral palsy
Authors: Ferland Catherine E
Published: July 2020

This commentary is on the original article by McKinnon et al. on pages 1293–1300 of this issue.
Determinants of clinical outcomes in patients with mixed mitral valve disease
Authors: Cho In‐Jeong , Lee Sang‐Eun , Jeong Hyeonju , Chang Hyuk‐Jae
Published: July 2020

Background

Although significant stenosis and regurgitation can be observed on a single heart valve, studies on the outcome predictors for mixed valve disease are limited. The purpose of the current study was to investigate the fate and determinants of clinical outcomes in patients with mixed single mitral valve disease who have concomitant mitral stenosis (MS) and mitral regurgitation (MR).

Methods

We retrospectively reviewed 82 consecutive patients with rheumatic heart disease who had both significant MS (MVA ≤ 1.5 cm2) and at least moderate MR, excluding patients with significant aortic valve stenosis or regurgitation. The primary endpoint was a composite of all‐cause mortality during follow‐up, mitral valve replacement, heart failure admission, and stroke.

Results

There were 37 events (45.1%), 5 all‐cause deaths (6.0%), and 32 mitral valve replacements (39.0%). In a multivariable Cox regression analysis, a transmitral mean pressure gradient (TMPG) over 6 mm Hg was the only independent echocardiographic predictor for events (hazard ratio 3.69, 95% confidential interval 1.31–10.44, P = .014), after adjusting for sex, age, symptoms, and the severity of MS and MR. The estimated 6‐year event‐free survival rate was significantly lower in patients with TMPG ≥ 6 mm Hg than in those with TMPG < 6 mm Hg (76.3% vs 22.9%, log‐rank P < .001).

Conclusion

Transmitral mean pressure gradient, which reflects the hemodynamic burden of the mitral valve lesion, appears to be the most important echocardiographic predictor of clinical outcomes in patients with mixed mitral valve disease.
A case of nonvalvular endocarditis with biventricular apical infected thrombi
Authors: Vani Anish , Ahluwalia Monica , Donnino Robert , Jung Albert , Vaynblat Mikhail , Latson Larry , Saric Muhamed
Published: July 2020

We report what appears to be the first case of biopsy‐proven nonvalvular endocarditis with biventricular apical infected thrombi. A 47‐year‐old man presented with hypoxic respiratory failure from a multilobar pneumonia due to methicillin‐resistant Staphylococcus aureus (MRSA). Transthoracic echocardiography and cardiac magnetic resonance imaging revealed biventricular apical masses suggestive of nonvalvular endocarditis with infected thrombi. Given concern for ongoing septic embolization to the lungs and brain despite appropriate antimicrobial therapy, the masses were surgically resected. Culture and histopathology confirmed MRSA‐positive infected thrombi. In this case report, we highlight the differential diagnosis of apical masses and the role of multimodality imaging.
Usefulness of echocardiography to detect cardiac involvement in COVID‐19 patients
Authors: Cameli Matteo , Pastore Maria Concetta , Soliman Aboumarie Hatem , Mandoli Giulia Elena , D'Ascenzi Flavio , Cameli Paolo , Bigio Elisa , Franchi Federico , Mondillo Sergio , Valente Serafina
Published: July 2020

Coronavirus disease 2019 (COVID‐19) outbreak is a current global healthcare burden, leading to the life‐threatening severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, evidence showed that, even if the prevalence of COVID‐19 damage consists in pulmonary lesions and symptoms, it could also affect other organs, such as heart, liver, and spleen. Particularly, some infected patients refer to the emergency department for cardiovascular symptoms, and around 10% of COVID‐19 victims had finally developed heart injury. Therefore, the use of echocardiography, according to the safety local protocols and ensuring the use of personal protective equipment, could be useful firstly to discriminate between primary cardiac disease or COVID‐19–related myocardial damage, and then for assessing and monitoring COVID‐19 cardiovascular complications: acute myocarditis and arrhythmias, acute heart failure, sepsis‐induced myocardial impairment, and right ventricular failure derived from treatment with high‐pressure mechanical ventilation. The present review aims to enlighten the applications of transthoracic echocardiography for the diagnostic and therapeutic management of myocardial damage in COVID‐19 patients.
Cardiovascular risk estimation with 5 different algorithms before and after 5 years of bDMARD treatment in rheumatoid arthritis
Authors: Cacciapaglia Fabio , Fornaro Marco , Venerito Vincenzo , Perniola Simone , Urso Livio , Iannone Florenzo
Published: July 2020

Background

Assessing cardiovascular (CV) risk represents a challenge for clinicians because more variables can impact CV risk. The aim of this study was to evaluate the change of CV risk after 5 years of biological treatment in rheumatoid arthritis (RA) patients and impact of prolonged low disease activity on 5 different CV risk algorithms.

Materials and methods

We estimated the CV risk, at baseline and at 5‐year follow‐up (FU), with the Systematic COronary Risk Evaluation(SCORE) charts, the algorithm ‘Progetto Cuore’, the QRISK3‐2018 score, the Reynold Risk Score(RRS) and the Expanded Risk Score in RA(ERS‐RA). Clinical disease activity index(CDAI) was used to define RA activity. Wilcoxon signed‐rank test was used to compare CV risk scores.

Results

In 110 patients with a 5‐year FU on biological disease‐modifying anti‐rheumatic drug treatment, we observed an increase in the 10‐year CV risk estimated by SCORE charts [from mean (SD) 0.9% (1.4) to 1.1% (1.5), P < .001], ‘Progetto Cuore’ [from mean (SD) 5.5% (7.2) to 6.2% (6.8), P < .001], QRISK3‐2018 [from mean (SD) 9.3% (10.1) to 11.9% (10.8), P < .001) and RRS [from mean (SD) 5.6% (6.4) to 6.2% (7.5), P < .05], mainly due to age raise. ERS‐RA highlighted a significant decrease of estimated CV risk in patients with persistent CDAI ≤ 10[from mean (SD) 9.6% (11.2) to 7.3% (6.4), P < .05], despite age increase and its impact on the CV risk score.

Conclusions

Algorithms commonly used to estimate 10‐year CV risk in RA perform differently. Scores that include specific inflammatory RA‐related variables seem to decrease with amelioration of disease activity. Further investigations are warranted to explore the predictive value of their changing over time.
Disclosing conflict of interest does not mitigate healthcare bias and harm: It is time to sever industry ties
Authors: James Jack E.
Published: July 2020

Disclosing conflict of interest is widely believed to mitigate bias and harm from industry entanglement in healthcare research, education and practice.

However, evidence is lacking of disclosure‐related mitigation.

Radical and extensive severing of industry ties to health care is necessary to curtail industry‐related bias and harm.
The impact of COVID‐19 on dental education in North America—Where do we go next?
Authors: Wu David T. , Wu Kevin Y. , Nguyen Thomas T. , Tran Simon D.
Published: July 2020

During the COVID‐19 pandemic, the dental education community faced unprecedented challenges. In this commentary, we share the perspectives of faculty clinicians, residents and students in academic dental institutions in the United States and Canada. We discuss COVID‐19’s impact on various aspects of academic dentistry including patient care, education, research and raise key concerns regarding the future of dental education post‐pandemic.
Temporal associations between sleep slow oscillations, spindles and ripples
Authors: Oyanedel Carlos N. , Durán Ernesto , Niethard Niels , Inostroza Marion , Born Jan
Published: July 2020

The systems consolidation of memory during slow‐wave sleep (SWS) is thought to rely on a dialogue between hippocampus and neocortex that is regulated by an interaction between neocortical slow oscillations (SOs), thalamic spindles and hippocampal ripples. Here, we examined the occurrence rates of and the temporal relationships between these oscillatory events in rats, to identify the possible direction of interaction between these events under natural conditions. To facilitate comparisons with findings in humans, we combined frontal and parietal surface EEG with local field potential (LFP) recordings in medial prefrontal cortex (mPFC) and dorsal hippocampus (dHC). Consistent with a top‐down driving influence, EEG SO upstates were associated with an increase in spindles and hippocampal ripples. This increase was missing in SO upstates identified in mPFC recordings. Ripples in dHC recordings always followed the onset of spindles consistent with spindles timing ripple occurrence. Comparing ripple activity during co‐occurring SO‐spindle events with that during isolated SOs or spindles, suggested that ripple dynamics during SO‐spindle events are mainly determined by the spindle, with only the SO downstate providing a global inhibitory signal to both thalamus and hippocampus. As to bottom‐up influences, we found an increase in hippocampal ripples ~200 ms before the SO downstate, but no similar increase of spindles preceding SO downstates. Overall, the temporal pattern is consistent with a loop‐like scenario where, top‐down, SOs can trigger thalamic spindles which, in turn, regulate the occurrence of hippocampal ripples. Ripples, bottom‐up, and independent from thalamic spindles, can contribute to the emergence of neocortical SOs.
First record of Ceroplastes japonicus (Gray) (Hemiptera: Coccidae) in Greece and a combined approach of morphological identification and DNA barcoding
Authors: Papadopoulou S. , Kaydan M. , Manganaris A. , Loukovitis D. , Chrysochoidis C.
Published: July 2020

High levels of infestation of a wax soft scale insect (Hemiptera: Coccidae) have been observed on Laurus nobilis L. (Lauraceae) and Diospyros kaki Thunb. (Ebanaceae) in Greece in recent years. Specimens of Ceroplastes were collected from regions of Thessaloniki, Naousa and Kavala (northern Greece) and Attica (southern Greece) in 2012–2017. The specimens were identified based on DNA barcoding and female morphological characteristics as Ceroplastes japonicus Green (Hemiptera: Coccidae).
Ritual Forms and Ritual Stuff: Implications of Lawson and McCauley's Ritual Form Hypothesis for Material Culture
Authors: Hornbeck Ryan G. , Barrett Justin L.
Published: July 2020

Lawson and McCauley's ritual form hypothesis (RFH) appeals to natural cognition to capture several commonly observed features of religious rituals in one explanatory theory: (1) their repetition in the life of a participant tends to be distributed in bipolar fashion (typically only once in a lifetime or repeatedly, on the order of annually, monthly, weekly, or even daily); (2) their effects may or may not be reversed through other rituals; (3) their range in centrality to a religious tradition (from peripheral to essential); and (4) their range from dull, tedious affairs to evocative, emotional, life‐changing events high in sensory pageantry. In this article, we summarize RFH and then turn to its potential application to material culture. If RFH can partially explain which sorts of religious rituals will be religiously frequent, central, and high in sensory pageantry, then it may also probabilistically predict the sorts of materials used in these rituals.
A century of intermittent eco‐evolutionary feedbacks resulted in novel trait combinations in invasive Great Lakes alewives (Alosa pseudoharengus)
Authors: Smith Shelby E. , Palkovacs Eric P. , Weidel Brian C. , Bunnell David B. , Jones Andrew W. , Bloom Devin D.
Published: July 2020

Species introductions provide opportunities to quantify rates and patterns of evolutionary change in response to novel environments. Alewives (Alosa pseudoharengus) are native to the East Coast of North America where they ascend coastal rivers to spawn in lakes and then return to the ocean. Some populations have become landlocked within the last 350 years and diverged phenotypically from their ancestral marine population. More recently, alewives were introduced to the Laurentian Great Lakes (~150 years ago), but these populations have not been compared to East Coast anadromous and landlocked populations. We quantified 95 years of evolution in foraging traits and overall body shape of Great Lakes alewives and compared patterns of phenotypic evolution of Great Lakes alewives to East Coast anadromous and landlocked populations. Our results suggest that gill raker spacing in Great Lakes alewives has evolved in a dynamic pattern that is consistent with responses to strong but intermittent eco‐evolutionary feedbacks with zooplankton size. Following their initial colonization of Lakes Ontario and Michigan, dense alewife populations likely depleted large‐bodied zooplankton, which drove a decrease in alewife gill raker spacing. However, the introduction of large, non‐native zooplankton to the Great Lakes in later decades resulted in an increase in gill raker spacing, and present‐day Great Lakes alewives have gill raker spacing patterns that are similar to the ancestral East Coast anadromous population. Conversely, contemporary Great Lakes alewife populations possess a gape width consistent with East Coast landlocked populations. Body shape showed remarkable parallel evolution with East Coast landlocked populations, likely due to a shared response to the loss of long‐distance movement or migrations. Our results suggest the colonization of a new environment and cessation of migration can result in rapid parallel evolution in some traits, but contingency also plays a role, and a dynamic ecosystem can also yield novel trait combinations.
Evolutionary legacy of a forest plantation tree species (Pinus armandii): Implications for widespread afforestation
Authors: Jia Yun , Milne Richard I. , Zhu Juan , Gao Lian‐Ming , Zhu Guang‐Fu , Zhao Gui‐Fang , Liu Jie , Li Zhong‐Hu
Published: July 2020

Many natural systems are subject to profound and persistent anthropogenic influence. Human‐induced gene movement through afforestation and the selective transportation of genotypes might enhance the potential for intraspecific hybridization, which could lead to outbreeding depression. However, the evolutionary legacy of afforestation on the spatial genetic structure of forest tree species has barely been investigated. To do this properly, the effects of anthropogenic and natural processes must be examined simultaneously. A multidisciplinary approach, integrating phylogeography, population genetics, species distribution modeling, and niche divergence would permit evaluation of potential anthropogenic impacts, such as mass planting near‐native material. Here, these approaches were applied to Pinus armandii, a Chinese endemic coniferous tree species, that has been mass planted across its native range. Population genetic analyses showed that natural populations of P. armandii comprised three lineages that diverged around the late Miocene, during a period of massive uplifts of the Hengduan Mountains, and intensification of Asian Summer Monsoon. Only limited gene flow was detected between lineages, indicating that each largely maintained is genetic integrity. Moreover, most or all planted populations were found to have been sourced within the same region, minimizing disruption of large‐scale spatial genetic structure within P. armandii. This might be because each of the three lineages had a distinct climatic niche, according to ecological niche modeling and niche divergence tests. The current study provides empirical genetic and ecological evidence for the site‐species matching principle in forestry and will be useful to manage restoration efforts by identifying suitable areas and climates for introducing and planting new forests. Our results also highlight the urgent need to evaluate the genetic impacts of large‐scale afforestation in other native tree species.
The clinical features and short‐term treatment outcomes of scirrhous cord: A retrospective study of 32 cases
Authors: Duggan M. , Mair T. , Durham A. , Pengelly T. , Sherlock C.
Published: July 2020

Scirrhous cord (SC) is an uncommon complication of castration, characterised by chronic infection of the spermatic cord remnant. It is reported that surgical excision of the infected tissue is the most effective means of treatment, but there are few published studies assessing the outcomes of horses treated for SC. The aims of this retrospective study were to describe the clinical features and short‐term outcomes in horses treated for SC at two equine hospitals in the UK. The clinical records of horses diagnosed with SC over a 10‐year period were reviewed. A diagnosis of SC was made if the gelding presented with typical clinical signs with confirmation at surgery. Thirty‐two cases of SC were identified at the two equine hospitals. The mean age at presentation was 6 years (range 2–14 years, n = 22), and the median time from castration to presentation was 29.5 days (range 20–2500 days). Mean age at castration was 4.3 years (range 6 months to 10 years, n = 10). Clinical signs included scrotal swelling, discharging wounds, hindlimb lameness and pyrexia. Five horses demonstrated hyperfibrinogenaemia (n = 8). Microbial culture isolated various bacterial species. All 32 cases were treated with surgical excision of the infected tissue and discharged from the hospitals between 1 and 10 days post‐operatively. A limitation of this study is that it was a retrospective study with no long‐term follow‐up available. It was concluded that the results of this study confirm that SC can present at variable time points following castration, even many years later, and that a variety of bacterial species may be involved. Surgical excision of infected tissue is a successful treatment with a good short‐term prognosis for survival.
Whole‐genome sequencing identifies missense mutation in GRM6 as the likely cause of congenital stationary night blindness in a Tennessee Walking Horse
Authors: Hack Yael L. , Crabtree Elizabeth E. , Avila Felipe , Sutton Roger B. , Grahn Robert , Oh Annie , Gilger Brian , Bellone Rebecca R.
Published: July 2020

Background

The only known genetic cause of congenital stationary night blindness (CSNB) in horses is a 1378 bp insertion in TRPM1. However, an affected Tennessee Walking Horse was found to have no copies of this variant.

Objectives

To identify the genetic cause for CSNB in an affected Tennessee Walking Horse.

Study design

Case report detailing a whole‐genome sequencing (WGS) approach to identify a causal variant.

Methods

A complete ophthalmic exam, including an electroretinogram (ERG), was performed on suspected CSNB‐affected horse. WGS data were generated from the case and compared with data from seven other breeds (n = 29). One hundred candidate genes were evaluated for coding variants homozygous in the case and absent in all other horses. Protein modelling was used to assess the functional effects of the identified variant. A random cohort of 90 unrelated Tennessee Walking Horses and 273 horses from additional breeds were screened to estimate allele frequency of the GRM6 variant.

Results

ERG results were consistent with CSNB. WGS analysis identified a missense mutation in metabotropic glutamate receptor 6 (GRM6) (c.533C>T p.Thr178Met). This single nucleotide polymorphism (SNP) is predicted to be deleterious and protein modelling supports impaired binding of the neurotransmitter glutamate. This variant was not detected in 273 horses from three additional breeds. The estimated allele frequency in Tennessee Walking Horses is 10%.

Main limitations

Limited phenotype information for controls and no additional cases with which to replicate this finding.

Conclusions

We identified a likely causal recessive missense variant in GRM6. Based on protein modelling, this variant alters GRM6 binding, and thus signalling from the retinal rod cell to the ON‐bipolar cell, impairing vision in low light conditions. Given the 10% population allele frequency, it is likely that additional affected horses exist in this breed and further work is needed to identify and examine these animals.
A radiomics platform for computing imaging features from µCT images of Thoroughbred racehorse proximal sesamoid bones: Benchmark performance and evaluation
Authors: Basran Parminder S. , Gao Jonathan , Palmer Scott , Reesink Heidi L.
Published: July 2020

Background

Proximal sesamoid bone (PSB) fractures are the most common fatal musculoskeletal injury in North American racehorses. Computed tomography has the potential to detect morphological changes in bone structure but can be challenging to analyse reliably and quantitatively.

Objectives

To develop a radiomics platform that allows the comparison of features from micro‐CTs (µCT) of PSBs in horses that sustained catastrophic fractures with horses that did not. To compare features calculated with a radiomics approach with features calculated from a previously published study that used quantitative µCT in the same specimens.

Study design

Retrospective study of cadaver specimens of µCT images of PSBs using prospectively applied radiomics.

Methods

Radiomics features were computed on standardised CT datasets to benchmark the software. Features from µCT images of PSBs from eight horses that sustained PSB fracture and eight controls were computed using the contralateral, intact forelimb from horses sustaining PSB fracture (cases, n = 19) and all available forelimbs for controls (n = 30). Two‐hundred and fifteen radiomic features were calculated, and similar or comparable features were compared with those reported in a previous study that used the same specimens.

Results

Morphologic features computed with the radiomics approach, such as volume, minor axis dimensions and anisotropy were highly correlated with previously published data. A high number of imperceptible radiomic features, such as entropy, coarseness and histogram features were also found to be significantly different (P < .01). The extent of the differences in image features for the cases and controls PSBs depends on radiomic calculation settings.

Main limitations

Only datasets obtained from cadaver specimens were included in the study.

Conclusions

A radiomics approach for analysing µCT images of PSBs was able to identify and reproduce differences in image features in cases and controls. Furthermore, radiomics revealed many more imperceptible image features between cases and control PSBs.
Molecular approaches to equine sarcoids
Authors: Semik‐Gurgul Ewelina
Published: July 2020

Sarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto‐oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA differential expression and DNA methylation status. This review focuses on selected groups of genes that contribute to the molecular mechanisms of sarcoid formation. These genes have the potential to complement current clinical examinations of equine sarcoid disease in diagnosis, prognosis, therapeutic response and screening.
Vitamin D receptor(s): In the nucleus but also at membranes?
Authors: Zmijewski Michal A. , Carlberg Carsten
Published: July 2020

The genomic actions of the vitamin D are mediated via its biologically most potent metabolite 1α,25‐dihydroxyvitamin D3 (1,25(OH)2D3) and the transcription factor vitamin D receptor (VDR). Activation of VDR by 1,25(OH)2D3 leads to change in the expression of more 1000 genes in various human tissues. Based on (epi)genome, transcriptome and crystal structure data the molecular details of this nuclear vitamin D signalling pathway are well understood. Vitamin D is known for its role on calcium homeostasis and bone formation, but it also modulates energy metabolism, innate and adaptive immunity as well as cellular growth, differentiation and apoptosis. The observation of rapid, non‐genomic effects of 1,25(OH)2D3 at cellular membranes and in the cytosol initiated the question, whether there are alternative vitamin D‐binding proteins in these cellular compartments. So far, the best candidate is the enzyme PDIA3 (protein disulphide isomerase family A member 3), which is found at various subcellular locations. Furthermore, also VDR seems to play a role in membrane‐based responses to vitamin D. In this viewpoint, we will dispute whether these rapid, non‐genomic pathways are a meaningful addition to the genome‐wide effects of vitamin D.
Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis
Authors: Luengas‐Martinez Andrea , Hardman‐Smart Jonathan , Paus Ralf , Young Helen S.
Published: July 2020

Vascular endothelial growth factor‐A (VEGF‐A), the main angiogenic mediator, plays a critical role in the pathogenesis of several inflammatory immune‐mediated diseases, including psoriasis. Even though anti‐angiogenic therapies, such as VEGF inhibitors, are licensed for the treatment of various cancers and eye disease, VEGF‐targeting interventions are not part of current psoriasis therapy. In this viewpoint essay, we argue that the existing preclinical research evidence on the role of VEGF‐A in the pathogenesis of psoriasis as well as clinical observations in patients who have experienced psoriasis remission during oncological anti‐VEGF‐A therapy strongly suggests to systematically explore angiogenesis targeting also in the management of psoriasis. We also point out that some psoriasis therapies decrease circulating levels of VEGF‐A and normalise the psoriasis‐associated vascular pathology in the papillary dermis of plaques of psoriasis and that a subset of patients with constitutionally high levels of VEGF‐A may benefit most from the anti‐angiogenic therapy we advocate here. Given that novel, well‐targeted personalised medicine therapies for the development of psoriasis need to be developed, we explore the hypothesis that VEGF‐A and signalling through its receptors constitute a promising target for therapeutic intervention in the future management of psoriasis.
Sympathetic activation: a potential link between comorbidities and COVID‐19
Authors: Porzionato Andrea , Emmi Aron , Barbon Silvia , Boscolo‐Berto Rafael , Stecco Carla , Stocco Elena , Macchi Veronica , De Caro Raffaele
Published: July 2020

In coronavirus disease 2019 (COVID‐19), higher morbidity and mortality are associated with age, male gender, and comorbidities, such as chronic lung diseases, cardiovascular pathologies, hypertension, kidney diseases, diabetes mellitus, and obesity. All of the above conditions are characterized by increased sympathetic discharge, which may exert significant detrimental effects on COVID‐19 patients, through actions on the lungs, heart, blood vessels, kidneys, metabolism, and/or immune system. Furthermore, COVID‐19 may also increase sympathetic discharge, through changes in blood gases (chronic intermittent hypoxia, hyperpnea), angiotensin‐converting enzyme (ACE)1/ACE2 imbalance, immune/inflammatory factors, or emotional distress. Nevertheless, the potential role of the sympathetic nervous system has not yet been considered in the pathophysiology of COVID‐19. In our opinion, sympathetic overactivation could represent a so‐far undervalued mechanism for a vicious circle between COVID‐19 and comorbidities.
Targeting hepatocyte carbohydrate transport to mimic fasting and calorie restriction
Authors: Kading Jacqueline , Finck Brian N. , DeBosch Brian J.
Published: July 2020

The pervasion of three daily meals and snacks is a relatively new introduction to our shared experience and is coincident with an epidemic rise in obesity and cardiometabolic disorders of overnutrition. The past two decades have yielded convincing evidence regarding the adaptive, protective effects of calorie restriction (CR) and intermittent fasting (IF) against cardiometabolic, neurodegenerative, proteostatic, and inflammatory diseases. Yet, durable adherence to intensive lifestyle changes is rarely attainable. New evidence now demonstrates that restricting carbohydrate entry into the hepatocyte by itself mimics several key signaling responses and physiological outcomes of IF and CR. This discovery raises the intriguing proposition that targeting hepatocyte carbohydrate transport to mimic fasting and caloric restriction can abate cardiometabolic and perhaps other fasting‐treatable diseases. Here, we review the metabolic and signaling fates of a hepatocyte carbohydrate, identify evidence to target the key mediators within these pathways, and provide rationale and data to highlight carbohydrate transport as a broad, proximal intervention to block the deleterious sequelae of hepatic glucose and fructose metabolism.
Climatic breadth of calling behaviour in two widespread Neotropical frogs: Insights from humidity extremes
Authors: Bonnefond Anaïs , Courtois Elodie A. , Sueur Jérôme , Sugai Larissa Sayuri M. , Llusia Diego
Published: July 2020

Climate change is severely altering precipitation regimes at local and global scales, yet the capacity of species to cope with these changes has been insufficiently examined. Amphibians are globally endangered and particularly sensitive to moisture conditions. For mating, most amphibian species rely on calling behaviour, which is a key weather‐dependent trait. Using passive acoustics, we monitored the calling behaviour of two widespread Neotropical frogs in 12 populations located at the humidity extremes but thermal mean of the species distribution. Based on 2,554 hr of recordings over a breeding season, we found that both the aquatic speciesPseudis paradoxaand the arboreal speciesBoana ranicepsexhibited calling behaviour at a wide range of relative humidity. Calling humidity was significantly lower in conspecific populations subjected to drier conditions, while calling temperature did not differ between populations or species. Overall, no variation in climatic breadth was observed between large and small choruses, and calling behaviour was scarcely detected during the driest, hottest and coldest potential periods of breeding. Our results showed that calling humidity of the studied species varies according to the precipitation regime, suggesting that widespread Neotropical anurans may have the capacity to exhibit sexual displays in different climatic environments. Regardless of the underlying mechanism (plasticity or local adaptation), which should be determined by common garden experiments, a wide and population‐specific climatic breadth of calling behaviour may assist species to deal with changing humidity conditions. To our knowledge, this is the first study to explore the response capacity of anurans to perform calling behaviour under contrasting precipitation regimes.
Spruce beetle outbreak was not driven by drought stress: Evidence from a tree‐ring iso‐demographic approach indicates temperatures were more important
Authors: Pettit Jessika M. , Voelker Steve L. , DeRose R. Justin , Burton Julia I.
Published: July 2020

Climate change has amplified eruptive bark beetle outbreaks over recent decades, including spruce beetle (Dendroctonus rufipennis). However, for projecting future bark beetle dynamics there is a critical lack of evidence to differentiate how outbreaks have been promoted by direct effects of warmer temperatures on beetle life cycles versus indirect effects of drought on host susceptibility. To diagnose whether drought‐induced host‐weakening was important to beetle attack success we used an iso‐demographic approach in Engelmann spruce (Picea engelmannii) forests that experienced widespread mortality caused by spruce beetle outbreaks in the 1990s, during a prolonged drought across the central and southern Rocky Mountain region. We determined tree death date demography during this outbreak to differentiate early‐ and late‐dying trees in stands distributed across a landscape within this larger regional mortality event. To directly test for a role of drought stress during outbreak initiation we determined whether early‐dying trees had greater sensitivity of tree‐ring carbon isotope discrimination (∆13C) to drought compared to late‐dying trees. Rather, evidence indicated the abundance and size of host trees may have modified ∆13C responses to drought. ∆13C sensitivity to drought did not differ among early‐ versus late‐dying trees, which runs contrary to previously proposed links between spruce beetle outbreaks and drought. Overall, our results provide strong support for the view that irruptive spruce beetle outbreaks across North America have primarily been driven by warming‐amplified beetle life cycles whereas drought‐weakened host defenses appear to have been a distant secondary driver of these major disturbance events.