bluuebunny/crossref_metadata_2025 huggingface dataset:
Local jasmonic acid cues drive systemic acquired resistance signal generation
Authors: Sales Jennifer , Pabst Elisabeth , Wenig Marion , Breitenbach Heiko H. , Perez Gerardo , Knappe Claudia , Hammerl Richard , Liu Jinghui , Rozhon Wilfried , Poppenberger Brigitte , Grill Erwin , Dawid Corinna , Vlot A. Corina
Published: January 2021

The phytohormones salicylic acid (SA) and jasmonic acid (JA) promote two, mutually antagonistic immune pathways respectively protecting plants from biotrophic pathogens and necrotrophic pathogens or insects. This trade-off largely precludes the exploitation of SA and JA immune components for crop protection, raising the interest in immune signalling components that disrupt SA-JA antagonism. A local pathogen infection primes SA-dependent immunity in systemic tissues. This so-called systemic acquired resistance (SAR) ensures a long-lasting, broad-spectrum disease resistance that is not subject to SA-JA antagonism. Here, we show that two sequence-related LEGUME LECTIN-LIKE PROTEINs (LLPs) promote SAR through spatially separated functions with JA promoting local SAR signal generation through LLP3. In concert with LLP1, which is important for systemic recognition and propagation of SAR signals, LLP3 promotes both SA-dependent SAR and JA-mediated immunity. Thus, exploitation of LLP-associated signalling cues might allow application of plant innate immune signals to promote (crop) plant health.
GABA facilitates spike propagation through branch points of sensory axons in the spinal cord
Authors: Hari Krishnapriya , Lucas-Osma Ana M. , Metz Krista , Lin Shihao , Pardell Noah , Roszko David A. , Black Sophie , Minarik Anna , Singla Rahul , Stephens Marilee J. , Pearce Robert A. , Fouad Karim , Jones Kelvin E. , Gorassini Monica A. , Fenrich Keith K. , Li Yaqing , Bennett David J.
Published: January 2021

Movement and posture depend on sensory feedback that is regulated by specialized GABAergic neurons (GAD2+) that form axo-axonic contacts onto myelinated proprioceptive sensory axons and are thought to be inhibitory. However, we report here that activating GAD2+neurons, directly with optogenetics or indirectly by cutaneous stimulation, facilitates sensory feedback to motoneurons in awake rodents and humans. GABAAreceptors and GAD2+innervation at or near nodes of Ranvier of sensory axons cause this facilitation, preventing spike propagation failure at the many axon branch points, which is otherwise common without GABA. In contrast, GABAAreceptors are generally lacking from axon terminals (unlike GABAB) and do not presynaptically inhibit transmitter release onto motoneurons. GABAergic innervation near nodes and branch points allows individual branches to function autonomously, with GAD2+neurons regulating which branches conduct, adding a computational layer to the neuronal networks generating movement and likely generalizing to other CNS axons.
Lipid fingerprints are similar between SLC6 transporters in the neuronal membrane
Authors: Wilson Katie A. , Wang Lily , Lin Yie Chang , O’Mara Megan L.
Published: January 2021

We use molecular dynamics simulations to characterise the local lipid annulus, or “fingerprint”, of three SLC6 transporters (dDAT, hSERT, and GlyT2) embedded into a complex neuronal membrane. New membrane analysis tools were created to improve leaflet detection and leaflet-dependent properties. Overall, lipid fingerprints are comprised of similar lipids when grouped by headgroup or tail saturation. The enrichment and depletion of specific lipids, including sites of cholesterol contacts, varies between transporters. The subtle differences in lipid fingerprints results in varying membrane biophysical properties near the transporter. Through comparisons to previous literature, we highlight that the lipid-fingerprint in complex membranes is highly dependent on membrane composition. Furthermore, through embedding these transporters in a simplified model membrane, we show that the simplified membrane is not able to capture the biophysical properties of the complex membrane. Our results further characterise how the presence and identity of membrane proteins affects the complex interplay of lipid-protein interactions, including the local lipid environment and membrane biophysical properties.

HIGHLIGHTS

Lipid fingerprints are comprised of similar lipid classes

Sites of specific lipid contacts, including CHOL, varies between transporters

Changes in lipid annulus result in variable local membrane biophysical properties

Membrane composition, including that of complex membranes, affects lipid annulus

GRAPHICAL ABSTRACT
Competitive cocrystallization and its application in the separation of flavonoids
Authors: Xia Yanming , Wei Yuanfeng , Chen Hui , Qian Shuai , Zhang Jianjun , Gao Yuan
Published: January 2021

Recently, cocrystallization has been widely employed to tailor physicochemical properties of drugs in the pharmaceutical field. In this study, cocrystallization was applied to separate natural compounds with similar structures. Three flavonoids [baicalein (BAI), quercetin (QUE) and myricetin (MYR)] were used as model compounds. The coformer caffeine (CAF) could form cocrystals with all three flavonoids, namely BAI–CAF (cocrystal 1), QUE–CAF (cocrystal 2) and MYR–CAF (cocrystal 3). After adding CAF to methanol solution containing MYR and QUE (or QUE and BAI), cocrystal 3 (or cocrystal 2) preferentially formed rather than cocrystal 2 (or cocrystal 1), indicating that flavonoid separation could be achieved by competitive cocrystallization. After co-mixing the slurry of two flavonoids with CAF followed by centrifugation, the resolution ratio that could be achieved was 70–80% with purity >90%. Among the three cocrystals, cocrystal 3 showed the lowest formation constant with a negative Gibbs free energy of nucleation and the highest energy gap. Hirshfeld surface analysis and density of states analysis found that cocrystal 3 had the highest strong interaction contribution and the closest electronic density, respectively, followed by cocrystal 2 and cocrystal 1, suggesting CAF could competitively form a cocrystal with MYR much more easily than QUE and BAI. Cocrystallization is a promising approach for green and effective separation of natural products with similar chemical structures.
Employment and output effects of federal regulations on small business
Authors: Chambers Dustin , Guo Jang‐Ting
Published: January 2021

This paper examines the disparate impact of US federal regulations on small businesses. Using a two‐sector dynamic general equilibrium model, we obtained two implications of higher regulation on small firms that have yet to be empirically tested in the published literature. First, as regulations increase, small firms’ share of employment shrinks. Second, as regulations rise, small firms’ share of total output falls. Using a panel of industry‐specific US regulatory restrictions, we found that a 10% increase in federal regulations was associated with an approximate 0.8% reduction in small firms’ share of industry employment and a nearly 1.5% decline in small firms’ share of industry output.
Implied Equity Duration: A Measure of Pandemic Shutdown Risk
Authors: DECHOW PATRICIA M. , ERHARD RYAN D. , SLOAN RICHARD G. , SOLIMAN AND MARK T.
Published: January 2021

Implied equity duration was originally developed to analyze the sensitivity of equity prices to discount rate changes. We demonstrate that implied equity duration is also useful for analyzing the sensitivity of equity prices to pandemic shutdowns. Pandemic shutdowns primarily impact short‐term cash flows, thus they have a greater impact on low‐duration equities. We show that implied equity duration has a strong positive relation to U.S. equity returns and analyst forecast revisions during the onset of the 2020 COVID‐19 shutdown. Our analysis also demonstrates that the underperformance of “value” stocks during this period is a rational response to their lower durations.
Tumor‐educated leukocytes mRNA as a diagnostic biomarker for non‐small cell lung cancer
Authors: Niu Limin , Guo Wei , Song Xingguo , Song Xianrang , Xie Li
Published: January 2021

Background

This study aimed to investigate the diagnostic and prognostic role of tumor‐educated leukocytes (TELs) mRNA in Chinese patients with non‐small cell lung cancer (NSCLC).

Methods

The TELs collected underwent total RNA isolation. RNA‐sequencing (RNA‐seq) technology was used to analyze the transcriptome of the TELs. The mRNA expression levels of differential genes were analyzed by RT‐qPCR. Statistical analyses were performed using Prism and SPSS by Mann–Whitney nonparametric test, Kruskal‐Wallis test and one‐way ANOVA.

Results

We used RNA‐seq technology to screen 95 differential genes (DEGs) from seven NSCLC and four controls, wherein 15 genes were upregulated, and 80 were downregulated. Of these, four genes were selected for further analysis, wherein one was upregulated (GPX1) and three were downregulated (BCL9L, MAP3K7CL, PCSK7). RT‐qPCR was performed in 431 samples (237 NSCLC, 194 healthy donors). The four‐gene panel showed significant differences (p < 0.001) in the expression levels between NSCLC and healthy samples. ROC curves of the panel revealed an AUC of 0.803, with a sensitivity of 73.8% and specificity of 75.3%. GPX1, BCL9L and PCSK7 genes distinguished early‐stage NSCLC patients from healthy group (p < 0.05). When the three genes were combined to diagnose early‐stage NSCLC, the diagnostic efficacy was 0.772, sensitivity was 73.7%, and specificity was 72.2%. In addition, the downregulated gene BCL9L was associated with chemotherapeutic effect.

Conclusions

The present study provided a systematic description of gene expression profiling in the TELs. It is worth noting that these four genes may be potential candidate genes for NSCLC diagnostic biomarkers and provide a basis for further biological and functional studies.
What is the role of pre‐operative blood parameters in forecasting varicocelectomy success?
Authors: Erdogan Omer , Ok Fesih , Carkci Serkan
Published: January 2021

Background

We aimed to examine the effects of pre‐operative blood values on varicocelectomy success.

Materials and methods

A total of 130 patients who underwent varicocelectomy in our clinic were retrospectively analyzed. Operation success was defined as the return of all semen parameters (concentration, progressive motility, and morphology) to normal values 6 months after surgery. The patients were separated as two groups as benefiting from the treatment (Group A) and not (Group B).

Results

The best cut‐off value for the neutrophil/lymphocyte ratio (NLR), which can predict varicocelectomy success, was assigned to be 2.27, with AUC of 0.859 (%95 CI 0.795–0.922). The highest sensitivity and specificity were 0.857 and 0.731 (p < 0.001). The best cut‐off value for the mean platelet volüme (MPV) value, which can predict varicocelectomy success, was assigned to be 9.45, with AUC of 0.729 (%95 CI 0.639–0.819). The highest sensitivity and specificity were 0.655 and 0.635 (p < 0.001). Binary logistic regression analysis showed NLR ratio (odds ratio (OR): 11.2, p < 0.001) and MPV (OR: 2.65, p = 0.002) parameters as independent predictive factors in predicting varicocelectomy success.

Discussion and conclusion

Our study showed that low NLR ratio (≤2.27) and high MPV (≥9.45) ratio levels may be a useful pre‐operative predictive tool in identifying men who benefit most from varicocelectomy in infertile patients with varicocoele.
Using Textbook Outcomes to benchmark practice in pancreatic surgery
Authors: Nicholas Ella , van Roessel Stijn , de Burlet Kirsten , Hore Todd , Besselink Marc G. , Connor Saxon
Published: January 2021

Background

Textbook Outcome (TO) is a novel composite measure of clinical outcomes that can be used to measure the quality of surgical outcomes. TOs for pancreatic surgery were published by the Dutch Pancreatic Cancer Group (DPCG) in 2020. The aim of this study was to explore how a medium volume hepatopancreaticobiliary unit could use TO to benchmark local outcomes following pancreatic surgery.

Methods

Retrospective analysis of prospectively collected data from patients who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) for all indications between March 2005 and February 2020 at Christchurch Hospital (CH). Analysis of TO items as defined by the DPCG was performed and compared to nationwide Dutch outcomes (2014–2017), including cumulative analysis using CuSum.

Results

In total, 273 patients were included (median age 63 years; 51% female) of which 182 (67%) underwent PD and 91 (33%) underwent DP (median annual volume 12 PDs/6 DPs). Overall, 58% of patients undergoing PD and 74% of patients undergoing DP achieved TO, compared with 58% and 67%, P = 0.944 and P = 0.231, respectively, for the Netherlands (median annual volume 33 PDs/8 DPs per hospital).

Conclusions

TO offers a useful quality measure to benchmark local outcomes following pancreatic surgery against an external nationwide analysis. The results show that as a medium volume centre performance was comparable to previously published Dutch results, which included high volume centres. Applying CuSum methodology to the TO metric allows a continuous measure of performance. This offers the potential to provide feedback for quality improvement strategies.
The effect of national public health interventions for COVID‐19 on emergency general surgery in Northland, New Zealand
Authors: McGuinness Matthew J. , Harmston Christopher
Published: January 2021

Background

The New Zealand government instituted escalating public health interventions to prevent the spread of COVID‐19. There was concern this would affect health seeking behaviour leading to delayed presentation and worse outcomes. The aim of this study was to examine the effects of these interventions on rate and severity of acute general surgical admissions in Northland, New Zealand.

Methods

A retrospective comparative cohort study was performed. Two cohorts were identified: 28 February to 8 June 2020 and same period in 2019. Data for surgical admissions and operations and emergency department (ED) presentation were obtained from the hospital data warehouse. Three index diagnoses were assessed for severity.

Results

There were 650 acute general surgical admissions in 2019 and 627 in 2020 (P 0.353). Operations were performed in 226 and 224 patients respectively (P 0.829). ED presentations decreased from 11 398 to 8743 (P < 0.001). No difference in severity of acute appendicitis (P 0.970), acute diverticulitis (P 0.333) or acute pancreatitis (P 0.803) was detected. Median length‐of‐stay, 30‐day mortality and admission diagnosis were comparable.

Conclusion

Despite a significant reduction in ED presentations, interventions for COVID‐19 did not result in a difference in the rate or severity of acute general surgical admissions.
Blood plasma metabolomics of children and adolescents with sickle cell anaemia treated with hydroxycarbamide: a new tool for uncovering biochemical alterations
Authors: Ribeiro Paulo R. , Teixeira Rozana dos S. , Souza Alzenir R. , Pereira Tayla C. S. , Boffo Elisangela F. , Carosio Maria G. A. , Ferreira Antonio G. , Oliveira Regina V. , Rodrigues Luiz E. A. , Silva Jacqueline de J. , de Souza Amancio J. , Ladeia Ana Marice T.
Published: January 2021

Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long‐term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non‐SCA individuals. Fifty‐three metabolites were identified by ultra‐high performance liquid chromatography coupled to high‐resolution mass spectrometry (UHPLC‐HRMS) and 1H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least‐squares discriminant analysis (PLS‐DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients’ metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands’ cycle and increased synthesis of sphingosine 1‐phosphate. Putative novel biomarkers are suggested.
Efficacy and safety of glucagon‐like peptide‐1/glucagon receptor co‐agonist JNJ‐64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose‐ranging study
Authors: Alba Maria , Yee Jaqueline , Frustaci Mary Ellen , Samtani Mahesh N. , Fleck Penny
Published: January 2021

Individuals with obesity have a heightened risk of developing serious comorbidities, and pharmacological treatments for people with obesity are limited. This phase 2 study assessed the safety and efficacy of JNJ‐64565111, a dual agonist of glucagon‐like peptide‐1 and glucagon receptors, in individuals with class II/III obesity without type 2 diabetes. In this randomized, double‐blind, placebo‐controlled and open‐label active‐controlled, parallel‐group, multicentre study, participants aged 18 to 70 years with a body mass index of 35 to 50 kg/m2 and stable weight were randomly assigned in a 1:1:2:2:2 ratio to blinded treatment with placebo; JNJ‐64565111 (5.0, 7.4 or 10.0 mg, each with no dose escalation), or open‐label liraglutide 3.0 mg. The primary efficacy endpoint was percent change from baseline in body weight at week 26. Four‐hundred seventy four participants were randomized and 343 (72.4%) completed treatment. At week 26, placebo‐subtracted body weight changes (adjusted for multiplicity) were −6.8%, −8.1% and −10.0% for the JNJ‐64565111 5.0 mg, 7.4 mg and 10.0 mg groups, respectively, and −5.8% for the liraglutide group. Incidence of treatment‐emergent adverse events, especially nausea and vomiting, was higher in each JNJ‐64565111 treatment group compared to placebo and liraglutide. JNJ‐64565111 significantly reduced body weight in a dose‐dependent manner vs placebo but was associated with greater incidence of treatment‐emergent adverse events.
Efficacy and safety of glucagon‐like peptide‐1/glucagon receptor co‐agonist JNJ‐64565111 in individuals with type 2 diabetes mellitus and obesity: A randomized dose‐ranging study
Authors: Di Prospero Nicholas A. , Yee Jaqueline , Frustaci Mary E. , Samtani Mahesh N. , Alba Maria , Fleck Penny
Published: January 2021

Weight loss has been shown to improve metabolic parameters and cardiovascular risk in people with type 2 diabetes mellitus (T2DM). This phase 2 study evaluated the safety and efficacy of JNJ‐64565111, a dual agonist of GLP‐1 and glucagon receptors, in individuals with T2DM and class II/III obesity. In this randomized, double‐blind study, participants with T2DM (HbA1c 6.5%‐9.5%), body mass index of 35 to 50 kg/m2 and stable weight were randomly assigned (1:1:1:1) to placebo or JNJ‐64565111 (5.0 mg, 7.4 mg or 10.0 mg). The primary endpoint was percent change from baseline in body weight at week 12. Of 195 dosed participants, 144 (73.8%) completed treatment. At week 12, placebo‐subtracted body weight changes were −4.6%, −5.9% and −7.2% with JNJ‐64565111 5.0 mg, 7.4 mg and 10.0 mg, respectively. All JNJ‐64565111 doses were associated with no change in HbA1c and slight numerical elevation of fasting insulin. Numerical increases in fasting plasma glucose were observed with JNJ‐64565111 5.0 mg and 7.4 mg. Incidence of treatment‐emergent adverse events, especially nausea and vomiting, was higher with JNJ‐64565111 vs placebo. Overall, JNJ‐64565111 significantly reduced body weight in a dose‐dependent manner vs placebo but was associated with greater incidence of treatment‐emergent adverse events, no HbA1c reductions, and increased fasting plasma glucose and fasting insulin.
Impact of a history of metastases or synchronous metastases on survival in patients with locally recurrent rectal cancer
Authors: Voogt E. L. K. , van Zoggel D. M. G. I. , Kusters M. , Nieuwenhuijzen G. A. P. , Cnossen J. S. , Creemers G. J. , van Lijnschoten G. , Nederend J. , Roef M. J. , Burger J. W. A. , Rutten H. J. T.
Published: January 2021

Aim

Patients with locally recurrent rectal cancer (LRRC) frequently present with either synchronous metastases or a history of metastases. This study was conducted to evaluate whether LRRC patients without metastases have a different oncological outcome compared to patients with a history of metastases treated with curative intent or patients with potentially curable synchronous metastases.

Method

All consecutive LRRC patients who underwent intentionally curative surgery between 2005 and 2017 in a large tertiary hospital were retrospectively reviewed and categorized as having no metastases, a history of (curatively treated) metastases or synchronous metastases. Patients with unresectable distant metastases were excluded from the analysis.

Results

Of the 349 patients who were analysed, 261 (75%) had no metastases, 42 (12%) had a history of metastases and 46 (13%) had synchronous metastases. The 3‐year metastasis‐free survival was 52%, 33% and 13% in patients without metastases, with a history of metastases, and with synchronous metastases, respectively (P < 0.001) A history of metastases did not influence overall survival (OS), but there was a trend towards a worse OS in patients with synchronous metastases compared with patients without synchronous metastases (hazard ratio 1.43; 95% CI 0.98–2.11).

Conclusion

LRRC patients with a history of curatively treated metastases have an OS comparable to that in patients without metastases and should therefore be treated with curative intent. However, LRRC patients with synchronous metastases have a poor metastasis‐free survival and worse OS; in these patients, an individualized treatment approach to observe the behaviour of the disease is recommended.
Season‐long characterization of high‐cannabinoid hemp (Cannabis sativa L.) reveals variation in cannabinoid accumulation, flowering time, and disease resistance
Authors: Stack George M. , Toth Jacob A. , Carlson Craig H. , Cala Ali R. , Marrero‐González Mariana I. , Wilk Rebecca L. , Gentner Deanna R. , Crawford Jamie L. , Philippe Glenn , Rose Jocelyn K. C. , Viands Donald R. , Smart Christine D. , Smart Lawrence B.
Published: January 2021

Given the dramatic rise in high‐cannabinoid hemp (Cannabis sativa L.) production in the last decade, there is an increasingly urgent need to characterize available germplasm and develop knowledge to accelerate the breeding of uniform and stable cultivars. Despite persistent cultivation of hemp cultivars for grain and or fiber around the world, the diversity and genetic underpinning of key traits for breeding and cultivation are poorly understood. For 30 high‐cannabidiol hemp cultivars replicated on two field sites, we sought to evaluate yield, agronomic performance, and disease resistance while also conducting a detailed study of cannabinoid accumulation over the course of floral maturation. We observed significant variation in both within and among cultivars. During the growing season, the plants clustered into five groups by growth rate and varied in flowering time from photoperiod insensitive to photoperiod sensitive with very short critical photoperiods. Based on the observed ratio of total potential cannabidiol (CBD) to total potential tetrahydrocannabinol (THC), there was segregation for cannabinoid chemotype in some seeded cultivar populations. Analysis of cannabichromene (CBC) production revealed that some cultivars had a discretely lower CBD:CBC ratio than the others. There was a continuous range of powdery mildew severity by cultivar, with one that had little to no observed powdery mildew suggesting it might have genetic resistance. Biomass production at harvest was strongly influenced by location and cultivar, and there was variation by cultivar in the relative cannabinoid production in shoot tip samples compared with whole plant samples. While our results provide preliminary guidance regarding relative performance of current cultivars, our analyses indicate a need for additional hemp breeding to provide stable, uniform, and legally compliant cultivars with improved disease resistance and flowering times optimized for the latitudes of different growing locations.
Nanoscale Chemical Imaging by Photo‐Induced Force Microscopy: Technical Aspects and Application to the Geosciences
Authors: Otter Laura M. , Förster Michael W. , Belousova Elena , O’Reilly Padraic , Nowak Derek , Park Sung , Clark Simon , Foley Stephen F. , Jacob Dorrit E.
Published: January 2021

Photo‐induced force microscopy (PiFM) is a new‐frontier technique that combines the advantages of atomic force microscopy with infrared spectroscopy and allows for the simultaneous acquisition of 3D topographic data with molecular chemical information at high spatial (~ 5 nm) and spectral (~ 1 cm−1) resolution at the nanoscale. This non‐destructive technique is time efficient as it requires only conventional mirror‐polishing and has fast mapping rates on the order of a few minutes that allow the study of dynamic processes via time series. Here, we review the method’s historical development, working principle, data acquisition, and evaluation, and provide a comparison with traditional geochemical methods. We review PiFM studies in the areas of materials science, chemistry and biology. In addition, we provide the first applications for geochemical samples including the visualization of faint growth zonation in zircons, the identification of fluid speciation in high‐pressure experimental samples, and of nanoscale organic phases in biominerals. We demonstrate that PiFM analysis is a time‐ and cost‐efficient technique combining high‐resolution surface imaging with molecular chemical information at the nanoscale and, thus, complements and expands traditional geochemical methods.
Does plumage colour signal fitness in the tawny owl Strix aluco?
Authors: Solonen Tapio
Published: January 2021

Plumage colour has been hypothesized to signal fitness in its component parts survival and reproduction. In the tawny owl Strix aluco, grey individuals have been considered to be more viable and productive than brown ones in cold environmental conditions. The recent increase in the frequency of the brown morph in Finland has been explained by the climate warming. However, in recent decades there have been no trends in the general mildness of winters. Therefore, trends in the abundance of owls due to climate warming per se were unexpected. In a population near the southern coast of Finland, the abundance of grey (not brown) individuals increased significantly during the period 1986–2018, suggesting that natural selection has recently favoured the grey colour morph. During snowy and cold winters grey owls seemed to survive better than brown ones, suggesting that plumage colour signals adaptations to winter weather. The proportion of brown individuals in each year was best explained by the joint effect of snow cover and winter temperature. Extreme peaks in snow fall and cold winters seemed to affect substantially and rather similarly the abundance of both colour morphs. Between population differences in the occurrence of colour morphs were probably due to local and temporal differences in the snow cover. The number of fledglings was significantly related to the colour morph and weather conditions of the preceding winter in males but not in females. This suggests that coloration of males signals fitness in reproduction.
Video‐enhanced or textual rubrics: Does the Viewbrics' formative assessment methodology support the mastery of complex (21st century) skills?
Authors: Ackermans Kevin , Rusman Ellen , Nadolski Rob , Specht Marcus , Brand‐Gruwel Saskia
Published: January 2021

Learners in the process of developing complex skills need a rich mental model of what such skills entail. Textual analytics rubrics (TR) are a widely used instrument to support formative assessment of complex skills, supporting feedback, reflection, and thus mental model development of complex skills. However, the textual nature of a rubric limits the possibility to deliver contextual and dynamic (time‐and behaviour‐oriented) information. In the Viewbrics online tool, we developed a version supporting the delivery of contextual and dynamic information by adding video‐modelling examples with embedded self‐explanation prompts to textual analytics rubrics. We called this combination as video‐enhanced rubrics (VERs). Our current study investigates whether the Viewbrics online tool supports complex skills development and whether either textual‐ or video‐enhanced rubrics best support complex skills' mastery. The study was a three‐group (VERS n = 49, TR n = 54, control n = 50) within‐subjects design. Learners' performance of complex skills was measured through expert, peer, and self‐assessment using the Viewbrics online tool. A multilevel regression analysis shows learners in the TR and VERS conditions consistently outperforming the control condition to varying degrees across skills. However, no differences have been found between the two experimental conditions. Positive results across different complex skills indicate the Viewbrics online tool can be used to support the development of a wide range of complex skills in secondary education.
Ultralow temperature cryoablation: Safety and efficacy of preclinical atrial and ventricular lesions
Authors: Bourier Felix , Takigawa Masateru , Lam Anna , Vlachos Konstantinos , Ramirez F. Daniel , Martin Claire A. , Frontera Antonio , Kitamura Takeshi , Duchateau Josselin , Pambrun Thomas , Derval Nicolas , Denis Arnaud , Cox Jerry , Cabrita David , Babkin Alexander , Constantin Marion , Jais Pierre , Sacher Frédéric , Dubois Rémi , Bernus Oliver , Haissaguerre Michel , Hocini Mélèze
Published: January 2021

Background

Ultralow temperature cyroablation (ULTC) is designed to create focal, linear, and circumferential lesions. The aim of this study was to assess the safety, efficacy, and durability of atrial and ventricular ULTC lesions in preclinical large animal models.

Methods and Results

The ULTC system uses nitrogen near its liquid‐vapor critical point to cool 11‐cm ablation catheters. The catheter can be shaped to specific anatomies using pre‐shaped stylets. ULTC was used in 11 swine and four sheep to create atrial (pulmonary vein isolation and linear ablation) and ventricular lesions. Acute and 90‐day success were evaluated by intracardiac mapping and histologic examination. Cryoadherence was observed during all ULTC applications, ensuring catheter stability at target locations. Local electrograms were completely eliminated immediately after the first single‐shot ULTC application in 49 of 53 (92.5%) atrial and in 31 of 32 (96.9%) ventricular applications. Lesion depth as measured on histology preparations was 1.96 ± 0.8 mm in atrial and 5.61 ± 2.2 mm in ventricular lesions. In all animals, voltage maps and histology demonstrated transmural and durable lesions without gaps, surrounded by intact collagen fibers without injury to surrounding tissues. Transient coronary spasm could be provoked with endocardial ULTC in the left ventricle in close proximity to a coronary artery.

Conclusions

ULTC created effective and efficient atrial and ventricular lesions in vivo without procedural complications in two large animal models. ULTC lesions were transmural, contiguous, and durable over 3 months.
Politicization of Aiding Others: The Impact of Migration on European Public Opinion of Development Aid
Authors: Kiratli Osman Sabri
Published: January 2021

This article provides a longitudinal analysis on the driving forces behind Europeans' positions toward development aid and identifies changes in the dynamics following the migrant flows in 2015. Specifically, it assesses the extent to which policy‐makers' decisions to utilize development policy as a strategic tool to manage migration resonates at the public level. Using multilevel regression models on cross‐sectional survey data acquired from Eurobarometer surveys covering five waves between 2013 and 2018, supplemented by a series of macro‐level covariates both at the country and regional level, I show that voters in countries and regions with higher numbers of migrants are more supportive of foreign aid. The models also verify that support for foreign aid in polities that are the destination for migrants is substantially stronger in surveys conducted after 2015 than before and among voters who are interested in politics.
Efficacy of once‐daily glucagon‐like peptide‐1 receptor agonist lixisenatide as an add‐on treatment to basal insulin in Asian and white adults with type 2 diabetes mellitus: An individual‐level pooled analysis of phase III studies
Authors: Liu Fuqiang , Liu Yuan , Liu Minzhi , Wu Guangyu , Zhang Minlu , Zhang Xia , Cui Nan , Yin Huiqiu , Chen Li
Published: January 2021

Aims/Introduction

The prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin.

Materials and Methods

An individual‐level pooled analysis of two multi‐national phase III studies, GetGoal‐L and GetGoal‐L‐C, was carried out to assess the efficacy of lixisenatide versus placebo as an add‐on treatment to BI ± metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2‐h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control.

Results

Pooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference −0.49, 95% confidence interval −0.68 to − 0.30 and white patients least squares mean difference −0.45, 95% confidence interval −0.63 to − 0.26; P = 0.6287). Similarly, no significant difference was found in 2‐h PPG reduction between both groups (least squares mean difference for Asian vs white patients: −3.37 vs −3.93; P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of −0.56% after adjustment of baseline HbA1c level in Asian patients, and −0.41% in white patients.

Conclusions

Adding lixisenatide to BI significantly reduced HbA1c and 2‐h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations.
Autologous serum skin test reactions in chronic spontaneous urticaria differ from heterologous cell reactions
Authors: Baumann K. , Marcelino J. , Skov P.S. , Santos M.C.P. , Wyroslak I. , Scheffel J. , Altrichter S. , Woetmann A. , Costa C. , Maurer M.
Published: January 2021

Background

Autoimmune chronic spontaneous urticaria (CSU) is due to mast cell (MC)‐activating autoantibodies, which are screened for by the autologous serum skin test (ASST) and basophil tests (BTs). Many CSU patients are positive in only one of these tests. How often this occurs and why is currently unknown.

Objectives

To characterize the prevalence of mismatched ASST and BTs in CSU patients, and to investigate possible reasons for these mismatches.

Methods

We determined the rates of ASST+/BT− and ASST−/BT+ mismatches in published CSU studies. We assessed sera from 48 CSU patients by ASST, two BTs (basophil histamine release assay, BHRA; basophil activation test, BAT), a MC histamine release assay (MCHRA) and by ex vivo skin microdialysis (SMD).

Results

The ASST/BT mismatch rate in published CSU studies was 31% (ASST+/BT−: 22%, ASST−/BT+: 9%). In our patients, the ASST/BHRA and ASST/BAT mismatch rate was 35.4% (ASST+/BHRA−: 18.8% and ASST−/BHRA+: 16.7%) and 31.3% (ASST+/BAT−: 6.3% and ASST−/BAT+: 25.0%), respectively, and the two BTs were significantly correlated (P = 0.0002). The use of heterologous MCs, in vitro and in situ, instead of basophils produced similar results (MCHRA mismatch: 47.9%, ASST+/MCHRA−: 18.8%, ASST−/MCHRA+: 29.2%; SMD mismatch: 40.0%, ASST+/SMD−: 10.0% and ASST−/SMD+: 30.0%), and the MCHRA was highly correlated with SMD results (P = 0.0002).

Conclusions

The ASST and BTs show divergent results in a third of CSU patients. Mismatches cannot be explained by the choice of basophil assay, the type of heterologous cells exposed to CSU serum in vitro (basophils vs. mast cells), nor the experimental setting of heterologous skin mast cells (in vitro vs. in situ). Thus, serum‐induced whealing, in CSU patients, seems to involve autologous skin signals modulating MC degranulation.
Host‐specific preference of some Flavobacteriumpsychrophilum multilocus sequence typing genotypes determines their ability to cause bacterial coldwater disease in coho salmon (Oncorhynchuskisutch)
Authors: Knupp Christopher , Kiupel Matti , Brenden Travis O. , Loch Thomas P.
Published: January 2021

Flavobacterium psychrophilum causes bacterial coldwater disease (BCWD) in salmonids, resulting in significant losses worldwide. Several serotyping and genetic studies of F. psychrophilum have suggested some geno‐/serotypes may be either host‐specific or generalistic in nature; however, this association has not been adequately explored in vivo using more natural exposure routes. Herein, F. psychrophilum isolate US19‐COS, originally recovered from coho salmon (Oncorhynchus kisutch) and belonging to multilocus sequence typing clonal complex (CC) CC‐ST9, and isolate US53‐RBT, recovered from rainbow trout (Oncorhynchus mykiss) and belonging to CC‐ST10, were serotyped via PCR, evaluated for proteolytic activity and utilized to determine their median lethal dose in immersion‐challenged coho salmon fingerlings. US19‐COS belonged to serotype 0, hydrolysed casein and gelatin but not elastin, led to fulminant multiorgan infections and elicited severe gross and microscopic pathology. In contrast, US53‐RBT, belonging to serotype 2, hydrolysed all three substrates, but did not lead to detectable infections, disease signs or mortality in any exposed coho salmon despite proving virulent to rainbow trout in previous experiments. This study provides in vivo evidence for potential host specificity of some F. psychrophilum genotypes that can also be serologically distinct, a matter of importance towards better understanding F. psychrophilum disease ecology and epidemiology.
MRI Lesion State Modulates the Relationship Between Serum Neurofilament Light and Age in Multiple Sclerosis
Authors: Rosso Mattia , Healy Brian C. , Saxena Shrishti , Paul Anu , Bjornevik Kjetil , Kuhle Jens , Benkert Pascal , Leppert David , Guttmann Charles , Bakshi Rohit , Weiner Howard L. , Chitnis Tanuja
Published: January 2021

BACKGROUND AND PURPOSE

Serum neurofilament light (sNfL) has been studied as a biomarker of disease activity in multiple sclerosis (MS). Several factors, including age, can influence its dynamics, and several studies have shown that sNfL increases with age in controls. Our objective was to explore the relationship of sNfL and age at different MS disease stages, including remission and after a gadolinium‐enhancing (Gad+) lesion.

METHODS

We included 94 patients with MS with annual sNfL measurements performed with a single‐molecule array assay. We used multivariable linear mixed‐effects models with random intercept to test the association between age and sNfL during remission and after a Gad+ lesion (ie, within 90 days after the Gad+ lesion). The model was adjusted for medication use and sex.

RESULTS

We report a positive association between sNfL level and age during remission (adjusted estimate = 1.18% yearly increase, 95% CI = .34‐2.03%, P = .008). In contrast, a negative interaction between age and Gad+ lesion status was observed (adjusted estimate = −1.73%, 95% CI = −2.85 to −.58%, P = .004).

CONCLUSION

We propose that younger patients experience a greater elevation in sNfL than older patients in response to Gad+ lesions. Our study provides potential insights into the effects of aging on neuroinflammation in MS.
Differentiating Dementia with Lewy Bodies and Alzheimer's Disease by Deep Learning to Structural MRI
Authors: Nemoto Kiyotaka , Sakaguchi Hiromasa , Kasai Wataru , Hotta Masatoshi , Kamei Ryotaro , Noguchi Tomoyuki , Minamimoto Ryogo , Arai Tetsuaki , Asada Takashi
Published: January 2021

Background and Purpose

Dementia with Lewy bodies (DLB) is the second most prevalent cause of degenerative dementia next to Alzheimer's disease (AD). Though current DLB diagnostic criteria employ several indicative biomarkers, relative preservation of the medial temporal lobe as revealed by structural MRI suffers from low sensitivity and specificity, making them unreliable as sole supporting biomarkers. In this study, we investigated how a deep learning approach would be able to differentiate DLB from AD with structural MRI data.

Methods

Two‐hundred and eight patients (101 DLB, 69 AD, and 38 controls) participated in this retrospective study. Gray matter images were extracted using voxel‐based morphometry (VBM). In order to compare the conventional statistical analysis with deep‐learning feature extraction, we built a classification model for DLB and AD with a residual neural network (ResNet) type of convolutional neural network architecture, which is one of the deep learning models. The anatomically standardized gray matter images extracted in the same way as for the VBM process were used as inputs, and the classification performance achieved by our model was evaluated.

Results

Conventional statistical analysis detected no significant atrophy other than fine differences on the middle temporal pole and hippocampal regions. The feature extracted by the deep learning method differentiated DLB from AD with 79.15％ accuracy compared to the 68.41% of the conventional method.

Conclusions

Our results confirmed that the deep learning method with gray matter images can detect fine differences between DLB and AD that may be underestimated by the conventional method.
Prevalence of temporomandibular disorders in musicians: A systematic review and meta‐analysis
Authors: Campos Larissa Gabriely Nogueira , Pedrosa Bianca Higino , Cavalcanti Renata Veiga Andersen , Stechman‐Neto José , Gadotti Inae Caroline , de Araujo Cristiano Miranda , Taveira Karinna Veríssimo Meira
Published: January 2021

Objective

To determine the prevalence of temporomandibular disorders (TMD) in musicians.

Materials and methods

Electronic database searches and a manual search were performed. Qualitative and quantitative analysis including risk of bias was performed for studies that met the inclusion criteria. A meta‐analysis of proportions with a random effects model was performed, and heterogeneity was explored according to the moderating variable through subgroup analysis and metaregression. The certainty of the evidence was assessed using the GRADE tool.

Results

A total of 13 articles were included for the meta‐analysis. Pooled prevalence estimate was 52.8% (CI 95%; 33.4%‐71.7%) for wind instruments, 53.9% (CI 95%; 42.4%‐65.2%) for string instruments and 53.9% (CI 95%; 23.5%‐82.7%) for string and wind instruments. The average time of use of the musical instrument explained 82.38%, the heterogeneity between the sizes of the effects observed in the analysis (R2 = 82.38%; P < .0001). For prevalence of TMD, the GRADE criteria were considered very low.

Conclusion

The overall combined prevalence of TMD in musicians was approximately 53.9%, and musicians who use their instruments daily and for a long period of time may have a higher prevalence of TMD.

Clinical significance

Due to the high prevalence of TMD in musicians, health professionals must be careful not to underestimate signs and symptoms and correctly diagnose these cases.
Accuracy of 3D Printed Implant Casts Versus Stone Casts: A Comparative Study in the Anterior Maxilla
Authors: Banjar Ayman , Chen Yo‐wei , Kostagianni Aikaterini , Finkelman Matthew , Papathanasiou Aikaterini , Chochlidakis Konstantinos , Papaspyridakos Panos
Published: January 2021

Purpose

To conduct an in vitro comparison of the amount of three‐dimensional (3D) deviation of 3D printed casts generated from digital implant impressions with an intraoral scanner (IOS) to stone casts made of conventional impressions.

Material and Methods

A maxillary master cast with partially edentulous anterior area was fabricated with two internal connection implants (Regular CrossFit, Straumann). Stone casts (n = 10) that served as a control were fabricated with the splinted open‐tray impression technique. Twenty digital impressions were made using a white light IOS (TRIOS, 3shape) and the Standard Tesselation Language (STL) files obtained were saved. Based on the STL files, a digital light processing (DLP) and a stereolithographic (SLA) 3D printer (Varseo S and Form 2) were used to print casts (n = 10 from each 3D printer). The master cast and all casts generated from each group were digitized using the same IOS. The STL files obtained were superimposed on the master cast STL file (reference) to evaluate the amount of 3D deviation with inspection software using the root mean square value (RMS). The independent‐samples Kruskal‐Wallis test and Dunn's test with Bonferroni correction (for post hoc comparisons) were used for statistical analyses.

Results

The Varseo S group had the lowest median RMS value [77.5 µm (IQR = 91.4‐135.4)], followed closely by the Conventional group [77.7 µm (IQR = 61.5‐93.4)]. The Form 2 had the highest mean value [98.8 µm (IQR = 57.6‐87.9)]. The independent‐samples Kruskal‐Wallis test revealed a significant difference between the groups (p = 0.018). Post hoc testing revealed a significant difference between Varseo S and Form 2 (p = 0.009).

Conclusion

The casts generated from the Varseo S 3D printer had better 3D accuracy than did those from the Form 2 3D printer. Both the Varseo S group and the conventional stone casts groups had similar 3D accuracy.