bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of modelling assumptions and empirical evidence: Does parasite transmission increase nonlinearly with host density?
Authors: Hopkins Skylar R. , Fleming‐Davies Arietta E. , Belden Lisa K. , Wojdak Jeremy M.
Published: January 2020

Host–parasite dynamics are impacted by the relationship between host density and parasite transmission, and thus, all epidemiological models contain a central transmission–density function. Recent theoretical work demonstrates that this central parasite transmission function might be best represented by a nonlinear continuum from one linear extreme to another: density‐dependent transmission at low host densities to density‐independent transmission at high host densities. But how often are nonlinear transmission functions used, and when are they better at describing transmission in real host–parasite systems?

To quantify existing modelling practices, we systematically reviewed seven representative ecology journals, finding 262 studies containing host–parasite models that contained linear and/or nonlinear transmission functions. We also reviewed the literature to find 28 experimental and observational studies that compared multiple transmission functions in real host–parasite systems, and tallied which functions were best supported in those systems. Finally, we created a flexible model simulation tool to explore and quantify the bias in model parameter estimates that is created when using an inaccurate transmission function.

We found that most experimental and observational studies reported that nonlinear transmission–density functions outperformed simple linear transmission–density functions, supporting recent theoretical work. In contrast, most studies containing host–parasite models assumed that host density was constant and/or used a single, linear transmission function to explain how transmission rates changed with density. Using the wrong linear function and/or using a linear function when the underlying transmission–density relationship is even slightly nonlinear can substantially bias model parameter estimates, as demonstrated by our simulations over a broad parameter space.

Some modelling studies may be using linear functions in host–parasite systems where nonlinear functions are more appropriate. If true, these models would yield substantially biased parameter estimates. To avoid such biases that compromise ecological understanding and prediction, we recommend that future studies compare multiple transmission functions, including nonlinear options, whenever possible.
Multivariate classification of earthquake survivors with post‐traumatic stress disorder based on large‐scale brain networks
Authors: Zhu H. , Yuan M. , Qiu C. , Ren Z. , Li Y. , Wang J. , Huang X. , Lui S. , Gong Q. , Zhang W. , Zhang Y.
Published: January 2020

Objective

The identification of post‐traumatic stress disorder (PTSD) among natural disaster survivors is remarkably challenging, and there are no reliable objective signatures that can be used to assist clinical diagnosis and optimize treatment. The current study aimed to establish a neurobiological signature of PTSD from the connectivity of large‐scale brain networks and clarify the brain network mechanisms of PTSD.

Methods

We examined fifty‐seven unmedicated survivors with chronic PTSD and 59 matched trauma‐exposed healthy controls (TEHCs) using resting‐state functional magnetic resonance imaging (rs‐fMRI). We extracted the node‐to‐network connectivity and obtained a feature vector with a dimensionality of 864 (108 nodes × 8 networks) to represent each subject’s functional connectivity (FC) profile. Multivariate pattern analysis with a relevance vector machine was then used to distinguish PTSD patients from TEHCs.

Results

We achieved a promising diagnostic accuracy of 89.2% in distinguishing PTSD patients from TEHCs. The most heavily weighted connections for PTSD classification were among the default mode network (DMN), visual network (VIS), somatomotor network, limbic network, and dorsal attention network (DAN). The strength of the anticorrelation of FC between the ventral medial prefrontal cortex (vMPFC) in DMN and the VIS and DAN was associated with the severity of PTSD.

Conclusions

This study achieved relatively high accuracy in classifying PTSD patients vs. TEHCs at the individual level. This performance demonstrates that rs‐fMRI‐derived multivariate classification based on large‐scale brain networks can provide potential signatures both to facilitate clinical diagnosis and to clarify the underlying brain network mechanisms of PTSD caused by natural disasters.
Laparoscopic hyperthermic intraperitoneal chemotherapy for appendiceal tumors
Authors: Sommariva Antonio , Tonello Marco , De Simoni Ottavia , Barina Andrea , Riccardo Rossi Carlo , Pilati Pierluigi
Published: January 2020

Introduction

The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal and appendix cancer at risk of peritoneal seeding is an appealing strategy to prevent peritoneal metastases. Here, we present the technical details and postoperative outcomes of laparoscopic HIPEC performed with prophylactic intent in three patients with low‐grade appendiceal neoplasm (LAMN) considered at risk of peritoneal recurrence.

Materials and Surgical Technique

Three patients with LAMN previously treated outside our department were selected for second‐look laparoscopic exploration and HIPEC. The study received institutional review board approval. A Hasson trocar was inserted around the umbilicus. Four additional 10‐mm trocars were inserted—one each in the left and right upper and lower quadrants. After full abdominal exploration, laparoscopic cytoreductive surgery was performed. Perfusion catheters were inserted through the four lateral trocars in the abdominal quadrants. HIPEC was performed with mitomycin 12 mg/m2 and cisplatin 90 mg/m2 for 60 minutes at a target temperature of 41.0°C. The postoperative course was uneventful, except for an episode of fluid leak due to dural tear (treated with supine bed rest for 48 hours and resulting in no adverse sequelae). The median length of hospital stay was 11 days. After a median follow‐up of 36 months, all patients were asymptomatic with no evidence of recurrence.

Discussion

Laparoscopic HIPEC for LAMN at risk of peritoneal recurrence appeared to be feasible, safe, and associated with a favorable postoperative outcome. More studies with larger samples of patients and with a standardized design are needed to better analyze the oncological value of this approach.
The role of recalling previous errors in middle‐school children's learning
Authors: Loehr Abbey M. , Fazio Lisa K. , Rittle‐Johnson Bethany
Published: January 2020

Background

Committing errors is a common part of the learning process, and adults are more likely to correct errors that they can recall. However, preadolescent children's recall of previous errors (i.e., memory for errors) may be limited.

Aims

We examined children's ability to recall their past errors and tested whether recalling an error aids error correction.

Samples

We worked with 102 (Study 1) and 173 (Study 2) middle‐school children in the United States.

Methods

In Study 1, children studied and were tested on their memory for math definitions. After reviewing the correct answers, children recalled their initial test answers and then took a final test. Reminders of past errors were provided for some children in Study 2. In two other conditions, children either recalled their past errors or studied the correct answers only.

Results

Children's recall of their past errors was poor, and errors that were recalled were no more likely to be corrected than errors that were not recalled. Across children, there was a positive association between memory for errors and error correction even after controlling for covariates. Being reminded of past errors and recalling past errors reduced error correction relative to studying the correct answers only.

Conclusions

Preadolescents' memory for errors is very limited, their ability to recall past errors predicts error correction overall, and recalling an error or being reminded of an error does not facilitate error correction.
The prevalence and significance of monoclonal gammopathy of undetermined significance in acute medical admissions
Authors: Atkin Catherine , Reddy‐Kolanu Vinay , Drayson Mark T. , Sapey Elizabeth , Richter Alex G.
Published: January 2020

Monoclonal gammopathy of undetermined significance (MGUS) affects 3·2% of adults aged >50 years. MGUS carries a life‐long risk of progression to multiple myeloma and causes complications including infection and renal impairment; common causes of hospital admission. This study aimed to assess MGUS prevalence in emergency medical hospital admissions. Patients were recruited from unselected emergency medical admissions in a hospital in the United Kingdom. Serum protein electrophoresis was performed, with immunofixation of abnormal results. Reason for admission and routine test results were recorded. After education about MGUS and myeloma, patients chose whether they wished to be informed of new diagnoses. A total of 660 patients were tested and 35 had a paraprotein suggestive of MGUS. The overall rate of MGUS was 5·3%. MGUS prevalence in those aged >50 years was 6·94%, higher than the previously published rate of 3·2% (P < 0·0005). There were higher rates in those with chronic kidney disease (13·75% vs. 4·14%, P = 0·002), heart failure (14% vs. 4·59%, P = 0·012), anaemia (8·96% vs. 3·41%, P = 0·003) or leucocytosis (9·33% vs. 3·04%, P = 0·002). In all, 96% of patients wished to be informed of their screening results. The prevalence of MGUS in emergency hospital admissions is higher than expected based on previous population‐based rates. This may suggest a selected population for screening.
Occupational mobility and the returns to training
Authors: Kambourov Gueorgui , Manovskii Iourii , Plesca Miana
Published: January 2020

The literature on the returns to training has pointed out that, immediately following a training episode, wages of participants in employer‐sponsored training increase substantially while wages of participants in government‐sponsored training hardly change. We argue that there is a potential selection issue—most of the government‐sponsored trainees are occupation switchers while most participants in employer‐sponsored training are occupation stayers. An occupational switch involves a substantial destruction of human capital, and once we account for the associated decline in wages, we find a large positive impact of both employer‐ and government‐sponsored training on workers’ human capital.
Epithelial V‐like antigen 1 promotes hepatocellular carcinoma growth and metastasis via the ERBB‐PI3K‐AKT pathway
Authors: Ni QianZhi , Chen Zhenhua , Zheng Qianwen , Xie Dong , Li Jing‐Jing , Cheng Shuqun , Ma Xingyuan
Published: January 2020

The role of epithelial V‐like antigen 1 (EVA1) has been well studied in thymic development and homostasis; however, its putative relationship with cancer remains largely unknown. Therefore, here we investigated the role of EVA1 in hepatocellular carcinoma. Interestingly, EVA1 expression was significantly increased in hepatocellular carcinoma (HCC) and was also associated with a poor prognosis and recurrence in HCC patients. Overexpression of EVA1 promoted cell growth, invasion and migration in vitro. Consistently, knockdown of EVA1 expression inhibited proliferation and migration in vitro, while repressing metastasis of HCC cells in vivo. RNA‐seq analysis indicated that EVA1 is able to upregulate the expression of genes in the ERBB3‐PI3K pathway. Accordingly, an increased level of AKT phosphorylation was detected in HCC cells after EVA1 overexpression. LY294002, a PI3K inhibitor, inhibited AKT phosphorylation and rescued the tumor‐promoting effect of EVA1 overexpression. Altogether, the present study has revealed the oncogenic role of EVA1 during HCC progression and metastasis through the ERBB‐PI3K‐AKT signaling pathway, reiterating the potential use of EVA1 as a therapeutic target and/or prognostic marker for HCC.
Report of the first patient with a homozygous OTUD7A variant responsible for epileptic encephalopathy and related proteasome dysfunction
Authors: Garret Philippine , Ebstein Frédéric , Delplancq Geoffroy , Dozieres‐Puyravel Blandine , Boughalem Aïcha , Auvin Stéphane , Duffourd Yannis , Klafack Sandro , Zieba Barbara A. , Mahmoudi Sana , Singh Karun K. , Duplomb Laurence , Thauvin‐Robinet Christel , Costa Jean‐Marc , Krüger Elke , Trost Detlef , Verloes Alain , Faivre Laurence , Vitobello Antonio
Published: January 2020

Heterozygous microdeletions of chromosome 15q13.3 (MIM: 612001) show incomplete penetrance and are associated with a highly variable phenotype that may include intellectual disability, epilepsy, facial dysmorphism and digit anomalies. Rare patients carrying homozygous deletions show more severe phenotypes including epileptic encephalopathy, hypotonia and poor growth. For years, CHRNA7 (MIM: 118511), was considered the candidate gene that could account for this syndrome. However, recent studies in mouse models have shown that OTUD7A/CEZANNE2 (MIM: 612024), which encodes for an ovarian tumor (OTU) deubiquitinase, should be considered the critical gene responsible for brain dysfunction. In this study, a patient presenting with severe global developmental delay, language impairment and epileptic encephalopathy was referred to our genetics center. Trio exome sequencing (tES) analysis identified a homozygous OTUD7A missense variant (NM_130901.2:c.697C>T), predicted to alter an ultraconserved amino acid, p.(Leu233Phe), lying within the OTU catalytic domain. Its subsequent segregation analysis revealed that the parents, presenting with learning disability, and brother were heterozygous carriers. Biochemical assays demonstrated that proteasome complex formation and function were significantly reduced in patient‐derived fibroblasts and in OTUD7A knockout HAP1 cell line. We provide evidence that biallelic pathogenic OTUD7A variation is linked to early‐onset epileptic encephalopathy and proteasome dysfunction.
Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion
Authors: Spratt John R. , Mattison Lars M. , Kerns Natalie K. , Huddleston Stephen J. , Meyer Linette , Iles Tinen L. , Loor Gabriel , Iaizzo Paul A.
Published: January 2020

Many lung donor offers are refused despite increasing demand. Portable normothermic ex vivo lung perfusion (EVLP) could increase donor yield by monitoring and reconditioning extended criteria donor (ECD) lungs. We report its use in human lungs declined for clinical transplantation. Ten sets of such lungs were procured from brain‐dead donors and underwent 24 hours of normothermic EVLP using a perfusate based on donor whole blood. Hemodynamic and ventilatory data and P:F ratios were measured. Advanced donor age and borderline oxygenation (donor mean P:F 228 ± 73) were the most commonly cited reasons for refusal for transplantation. There was no significant worsening of pulmonary hemodynamics or compliance or significant P:F decline during preservation in the overall cohort. Mean P:F ratio in the overall cohort was 315 ± 88 mm Hg after 24 hours EVLP. At EVLP termination 5/10 lung blocks met standard EVLP thresholds for acceptability for transplant. Eventual EVLP performance was poorly predicted by donor P:F ratio but well predicted by data gathered early in EVLP. Portable normothermic EVLP is useful for transportation, monitoring, and reconditioning of ECD lungs. Early EVLP measurements are more effective than preprocurement donor P:F in predicting eventual allograft performance. We advocate an aggressive strategy of evaluation of ECD lungs using blood‐based EVLP.
Marine epibenthic functional diversity on Flemish Cap (north‐west Atlantic)—Identifying trait responses to the environment and mapping ecosystem functions
Authors: Murillo Francisco Javier , Weigel Benjamin , Bouchard Marmen Marieve , Kenchington Ellen
Published: January 2020

Aim

To characterize the functional diversity and selected ecological functions of marine epibenthic invertebrate communities at the ecosystem scale and to evaluate the relative contributions of environmental filtering, including bottom‐contact fishing, and competitive interactions to benthic community assembly.

Location

Flemish Cap, an ecosystem production unit and fishing bank in the high seas of the north‐west Atlantic Ocean.

Methods

Through the use of Hierarchical Modelling of Species Communities (HMSC), we have explored seven community response traits to the environment applied to 105 epibenthic species and evaluated the influence of such traits on the community assembly processes. Assumed bioturbation, nutrient cycling and habitat provision functions, linked to individual or a combination of biological traits, were mapped using random forest modelling.

Results

Functional richness within benthic communities reached an asymptote for trawl sets with roughly more than 30 species. Assemblages on top of the Flemish Cap (<500 m depth) were characterized by higher biomass of small‐ and medium‐sized species with short life spans, whereas large species with longer life spans and broadcast spawners were dominant in the deeper assemblages (500–1,500 m depth). The amount of variation explained by the species’ responses to the covariates mediated by the traits was relatively high (25%) indicating their relevance to community assembly. Community‐weighted mean trait values changed with depth and physical oceanographic variables, indicating that environmental filtering was occurring. Interspecific interactions, as inferred from the random effect at the sample level, accounted for 16.3% of the variance in the model, while fishing effort explained only 5.2% of the variance but conferred strong negative impacts for most species.

Main conclusions

Our results suggest that while bottom‐contact fishing impacts have an effect on functional diversity, changes to the physical oceanography of the system are likely to have more profound impacts. The maps of benthic functioning can aid assessments of ecosystem impacts of fishing.
Pollution control can help mitigate future climate change impact on European grayling in the UK
Authors: Huml J. Vanessa , Harris W. Edwin , Taylor Martin I. , Sen Robin , Prudhomme Christel , Ellis Jonathan S.
Published: January 2020

Aim

We compare the performance of habitat suitability models using climate data only or climate data together with water chemistry, land cover and predation pressure data to model the distribution of European grayling (Thymallus thymallus). From these models, we (a) investigate the relationship between habitat suitability and genetic diversity; (b) project the distribution of grayling under future climate change; and (c) model the effects of habitat mitigation on future distributions.

Location

United Kingdom.

Methods

Maxent species distribution modelling was implemented using a Simple model (only climate parameters) or a Full model (climate, water chemistry, land use and predation pressure parameters). Areas of high and low habitat suitability were designated. Associations between habitat suitability and genetic diversity for both neutral and adaptive markers were examined. Distribution under minimal and maximal future climate change scenarios was modelled for 2050, incorporating projections of future flow scenarios obtained from the Centre for Ecology and Hydrology. To examine potential mitigation effects within habitats, models were run with manipulation of orthophosphate, nitrite and copper concentrations.

Results

We mapped suitable habitat for grayling in the present and the future. The Full model achieved substantially higher discriminative power than the Simple model. For low suitability habitat, higher levels of inbreeding were observed for adaptive, but not neutral, loci. Future projections predict a significant contraction of highly suitable areas. Under habitat mitigation, modelling suggests that recovery of suitable habitat of up to 10% is possible.

Main conclusions

Extending the climate‐only model improves estimates of habitat suitability. Significantly higher inbreeding coefficients were found at immune genes, but not neutral markers in low suitability habitat, indicating a possible impact of environmental stress on evolutionary potential. The potential for habitat mitigation to alleviate distributional changes under future climate change is demonstrated, and specific recommendations are made for habitat recovery on a regional basis.
Diagnostic algorithm of magnifying endoscopy with crystal violet staining for non‐ampullary duodenal epithelial tumors
Authors: Toya Yosuke , Endo Masaki , Oizumi Tomofumi , Akasaka Risaburo , Yanai Shunichi , Kawasaki Keisuke , Nakamura Shotaro , Eizuka Makoto , Fujita Yasuko , Uesugi Noriyuki , Ishida Kazuyuki , Sugai Tamotsu , Matsumoto Takayuki
Published: January 2020

Objectives

Little is known about the usefulness of magnifying endoscopy with crystal violet staining (ME‐CV) for the diagnosis of duodenal tumors. We assessed the ability of ME‐CV to distinguish Vienna classification (VCL) category 4/5 (C4/5) from category 3 (C3) non‐ampullary duodenal epithelial tumors (NADETs).

Methods

A total of 76 NADETs were studied. We retrospectively analyzed the diagnostic values of the white light endoscopy (WLE) scoring system and the ME‐CV algorithm with receiver operating characteristic (ROC) curves, and three endoscopists calculated the sensitivity, specificity, accuracy, and the area under the curve (AUC) of each. The diagnostic values were tested among NADETs overall and among subgroups of tumors with gastric, gastrointestinal or intestinal mucin phenotypes. Inter‐observer agreement of the diagnostic results was also calculated.

Results

According to the VCL, 54 lesions (71.1%) were regarded as C3 and 22 lesions (28.9%) as C4/5. The sensitivity, specificity, accuracy and AUC of ME‐CV were higher than those of the WLE scoring system (63.6 vs 54.5, 85.2 vs 75.9, 78.9 vs 69.7, 0.744 vs 0.652, respectively). Inter‐observer agreements of the WLE scoring system and ME‐CV were both moderate (kappa 0.45 and 0.41). ME‐CV had higher sensitivity, specificity, accuracy and AUC than those of the WLE scoring system among the gastric and intestinal phenotypes of NADETs.

Conclusions

ME‐CV is appropriate for the diagnosis of C4/5 and C3 NADETs.
Associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes: analysis at the municipality level in North Rhine‐Westphalia, Germany
Authors: Castillo‐Reinado K. , Maier W. , Holle R. , Stahl‐Pehe A. , Baechle C. , Kuss O. , Hermann J. , Holl R. W. , Rosenbauer J.
Published: January 2020

Aim

To analyse the associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes in the German federal state of North Rhine‐Westphalia.

Methods

Data of incident type 1 diabetes cases in children and adolescents aged <20 years between 2007 and 2014 were extracted from a population‐based diabetes register. Population data, indicators of area deprivation and urban/rural traits at the municipality level (396 entities) were obtained from official statistics. Area deprivation was assessed in five groups based on quintiles of an index of multiple deprivation and its seven deprivation domains. Poisson regression accounting for spatial dependence was applied to investigate associations of area deprivation and urban/rural traits with type 1 diabetes incidence.

Results

Between 2007 and 2014, 6143 incident cases were reported (99% completeness); the crude incidence was 22.3 cases per 100 000 person‐years. The incidence decreased with increasing employment and environmental deprivation (relative risk of the most vs. the least deprived municipalities: 0.905 [95% CI: 0.813, 1.007] and 0.839 [0.752, 0.937], respectively) but was not associated with the composite deprivation index. The incidence was higher in more peripheral, rural, smaller and less densely populated municipalities, and the strongest association was estimated for the location trait (relative risk of peripheral/very peripheral compared with very central location: 1.231 [1.044, 1.452]).

Conclusions

The results suggest that the type 1 diabetes risk is higher in more remote, more rural, less densely populated and less deprived areas. Urban/rural traits were stronger predictors of type 1 diabetes risk than area deprivation indicators.
Is Neuregulin‐4 a predictive marker of microvascular complications in type 2 diabetes mellitus?
Authors: Kocak Mehmet Zahid , Aktas Gulali , Atak Burcin M. , Duman Tuba T. , Yis Ozgur Mehmet , Erkus Edip , Savli Haluk
Published: January 2020

Background and Aims

Neuregulin‐4 (Nrg‐4) is a new adipokine released from brown adipose tissue. It plays pivotal role in regulating systemic energy balance, glucose and lipid metabolism and in reducing chronic inflammation. We aimed to investigate the relation between diabetic microvascular complications (DMC) and serum (Nrg‐4) levels in patients with type 2 diabetes mellitus.

Methods

Patients with type 2 diabetes mellitus were divided into DMC and diabetic patients without microvascular complications (non‐DMC). Nrg‐4 levels of the patients were compared.

Results

Fifty and 29 patients enrolled to the DMC and non‐DMC groups, respectively. Nrg‐4 was 1.23 (0.02‐5.1) ng/mL and 2.5 (0.21‐6.01) ng/mL in DMC and in non‐DMC groups, respectively (P < .001). In patients with DMC, FPG was 189.5 (89‐446) mg/ dL, whereas it was 128 (95‐278) mg/dL in non‐DMC diabetic patients (P < .001). HbA1c was also significantly higher in the DMC group than in the non‐DMC group (P < .001). Negative correlation was found between Nrg‐4 and FPG (r = −0.231, P = .03), HBA1c (r = −0.312, P = .003) and microalbuminuria (r = −0.277, P = .009). Logistic regression analysis showed a 1‐unit decrease in Nrg‐4 to increase the presence of DMC by 1.9 times. The best cut‐off value of Nrg‐4 was 1.56 ng/mL with 82.1% sensitivity and 64% specificity, in predicting DMC.

Conclusion

In patients with diabetes, Nrg‐4 levels may be a good predictor of early detection of one or more DMC, as microvascular dysfunction in an organ system is considered to be an initial onset of subclinical systemic damage.
Scaling‐up biodiversity‐ecosystem functioning research
Authors: Gonzalez Andrew , Germain Rachel M. , Srivastava Diane S. , Filotas Elise , Dee Laura E. , Gravel Dominique , Thompson Patrick L. , Isbell Forest , Wang Shaopeng , Kéfi Sonia , Montoya Jose , Zelnik Yuval R. , Loreau Michel
Published: January 2020

A rich body of knowledge links biodiversity to ecosystem functioning (BEF), but it is primarily focused on small scales. We review the current theory and identify six expectations for scale dependence in the BEF relationship: (1) a nonlinear change in the slope of the BEF relationship with spatial scale; (2) a scale‐dependent relationship between ecosystem stability and spatial extent; (3) coexistence within and among sites will result in a positive BEF relationship at larger scales; (4) temporal autocorrelation in environmental variability affects species turnover and thus the change in BEF slope with scale; (5) connectivity in metacommunities generates nonlinear BEF and stability relationships by affecting population  synchrony at local and regional scales; (6) spatial scaling in food web structure and diversity will generate scale dependence in ecosystem functioning. We suggest directions for synthesis that combine approaches in metaecosystem and metacommunity ecology and integrate cross‐scale feedbacks. Tests of this theory may combine remote sensing with a generation of networked experiments that assess effects at multiple scales. We also show how anthropogenic land cover change may alter the scaling of the BEF relationship. New research on the role of scale in BEF will guide policy linking the goals of managing biodiversity and ecosystems.
Prevalence of visual snow syndrome in the UK
Authors: Kondziella D. , Olsen M. H. , Dreier J. P.
Published: January 2020

Background and purpose

Visual snow syndrome is a recently described condition of unknown prevalence. We investigated the prevalence in a representative population sample from the UK and tested the hypothesis that visual snow syndrome is associated with young age, headache, tinnitus and mood impairment.

Methods

Using a crowdsourcing platform, we recruited a representative sample of 1015 adult laypeople from the UK, matched for age, gender and ethnicity according to national census data. Participants were unprimed, i.e. were inquired about the ‘frequency of certain medical conditions’ but not ‘visual snow syndrome’.

Results

A total of 38 of 1015 participants reported symptoms compatible with visual snow [3.7%; 95% confidence interval (CI), 2.7–5.2] and 22/1015 met criteria for visual snow syndrome (2.2%; 95% CI, 1.4–3.3). The female‐to–male ratio for visual snow syndrome was 1.6:1. Subjects with visual snow syndrome were older (50.6 ± 14 years) than the population mean (44.8 ± 15 years), although this was not statistically different (P = 0.06). Of 22 participants with visual snow syndrome, 16 had mood symptoms (72.7%; P = 0.01), 12 had headache (54.5%; P = 0.06), including five with visual migraine aura (22.7%; P = 0.15) and 13 had tinnitus (59.1%; P < 0.001). No participant had diabetes or a cleft lip (control questions). Following a multivariable regression analysis to adjust for age and gender, only the association between visual snow syndrome and tinnitus remained significant (odds ratio, 3.93; 95% CI, 1.63–9.9; P = 0.003).

Conclusions

The UK prevalence of visual snow syndrome is around 2%. We confirmed an association with tinnitus, but unprimed laypeople with visual snow syndrome are on average older than those seeking medical attention.
Serious infections in patients with myasthenia gravis: population‐based cohort study
Authors: Kassardjian C. D. , Widdifield J. , Paterson J. M. , Kopp A. , Nagamuthu C. , Barnett C. , Tu K. , Breiner A.
Published: January 2020

Background and purpose

To characterize the frequency and risk of serious infections in patients with myasthenia gravis (MG) relative to age/sex/area‐matched comparators.

Methods

This was a population‐based cohort study in Ontario, Canada of patients with newly‐diagnosed MG and 1:4 age/sex/area‐matched general population comparators accrued from 1 April 2002 to 31 December 2015. The main outcome was a serious infection, defined by a primary diagnosis code on a hospitalization or emergency department record. We computed crude overall and sex‐specific rates of infection among patients with MG and comparators, and the frequency of specific types of infection. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox regression.

Results

Among 3823 patients with MG, 1275 (33.4%) experienced a serious infection compared with 2973/15 292 (19.4%) of comparators over a mean follow‐up of over 5 years. Crude infection rates among patients with MG were twice those in comparators (72.5 vs. 35.0 per 1000 person‐years, respectively). The most common infection types were respiratory infections, particularly bacterial pneumonia. After adjustment for potential confounders, MG was associated with a 39% increased infection risk (adjusted hazard ratio, 1.39; 95% confidence intervals, 1.28–1.51).

Conclusions

Patients with MG are at a significantly higher absolute and relative risk of serious infections compared with age/sex/area‐matched comparators. This needs to be considered when selecting MG treatments and when planning vaccination/prophylaxis. Determining whether this risk is due to the use of immunosuppressive medications (vs. MG itself) is an important area for future research.
Should posterior cerebral artery occlusions be recanalized? Insights from the Trevo Registry
Authors: Clarençon F. , Baronnet F. , Shotar E. , Degos V. , Rolla‐Bigliani C. , Bartolini B. , Veznedaroglu E. , Budzik R. , English J. , Baxter B. , Liebeskind D. S. , Krajina A. , Gupta R. , Miralbes S. , Lüttich A. , Nogueira R. G. , Samson Y. , Alamowitch S. , Sourour N.‐A.
Published: January 2020

Background and purpose

The purpose of this study was to evaluate the safety and effectiveness of mechanical thrombectomy (MT) in patients with acute ischaemic stroke related to isolated and primary posterior cerebral artery (PCA) occlusions amongst the patients enrolled in the multicentre post‐market Trevo Registry.

Method

Amongst the 2008 patients enrolled in the Trevo Registry with acute ischaemic stroke due to large vessel occlusion treated by MT, 22 patients (1.1%) [10 females (45.5%), mean age 66.2 ± 14.3 years (range 28–91)] had a PCA occlusion [17 P1 (77.3%) and five P2 occlusions (22.7%)]. Recanalization after the first Trevo (Stryker, Fremont, CA, USA) pass and at the end of the procedure was rated using the modified Thrombolysis in Cerebral Infarction (mTICI) score. Procedure‐related complications (i.e. groin puncture complication, perforation, symptomatic haemorrhage, embolus in a new territory) were also recorded. The modified Rankin Scale at 90 days was assessed.

Results

Median National Institutes of Health Stroke Scale at admission was 14 (interquartile range 8–16). Stroke aetiology was cardio‐embolic in 68.2% of cases. Half of the patients (11/22) received intravenous tissue plasminogen activator. 54.5% of the patients were treated under general anaesthesia. Reperfusion (i.e. mTICI 2b or 3) after first pass was obtained in 65% of cases. Final mTICI 2b–3 reperfusion was obtained in all cases. Only one (4.5%) procedure‐related complication was recorded (puncture site) that resolved after surgery. At 90‐day follow‐up, modified Rankin Scale 0–2 was obtained in 59% of the patients and 9.1% died within the first 3 months after MT.

Conclusion

Mechanical thrombectomy for PCA occlusions seems to be safe (<5% procedure‐related complications) and effective. Larger repository datasets are needed.
The school social environment and oral health‐related quality of life in children: a multilevel analysis
Authors: Pauli Laís A. , Correa Marcos B. , Demarco Flávio F. , Goettems Marília L.
Published: January 2020

This study aimed to explore the association between schoolchildren's oral health‐related quality of life (OHRQoL) and the school‐related social environment (contextual factors). A cross‐sectional study was performed with 1,211 children, aged 8–12 yr, from 20 private and public schools. Sociodemographic information was collected from a questionnaire given to parents, and children were interviewed using the Child Perceptions Questionnaire (CPQ) and examined for oral health conditions. Contextual variables were obtained from school coordinators regarding the social environment. Data analysis was performed through multilevel Poisson regression. A high negative impact on OHRQoL was found for participants who were girls, older, had very severe malocclusion, had dental trauma and caries, and had mothers with less schooling. A negative impact on OHRQoL was also found for children who attended schools in which police security was required (rate ratios [RR] = 1.11; 95% CI: 1.01–1.22) and in which violence among students occurred in the last year (RR = 1.17; 95% CI: 1.02–1.35). The need for police security was associated with a negative impact on the emotional well‐being domain, and violence among students was associated with negative impact on the oral symptoms, functional limitations, and social well‐being domains. Children in healthier environments have better OHRQoL.
Amikacin induces rapid dose‐dependent apoptotic cell death in equine chondrocytes and synovial cells in vitro
Authors: Pezzanite Lynn , Chow Lyndah , Soontararak Sirikul , Phillips Jennifer , Goodrich Laurie , Dow Steven
Published: January 2020

Background

Equine veterinarians frequently inject aminoglycoside antibiotics intra‐articularly, either to treat septic arthritis or for prophylaxis with other medications when injecting joints for osteoarthritis. Although aminoglycosides have been demonstrated to be toxic to equine mesenchymal stem cells (MSC), their effects on resident joint cells have not been previously investigated. Moreover, safe and effective intra‐articular doses have not been defined.

Objectives

To determine effects of concentration, duration of exposure, pH and the presence of synovial fluid on the cytotoxic effects of amikacin on equine chondrocytes, synoviocytes and bone marrow– and adipose‐derived MSC.

Study design

In vitro experimental study.

Methods

Four cell types were harvested from three donor horses and plated in triplicate wells for 48 hours prior to the addition of amikacin. The effects of amikacin on cell viability were assessed for different exposure times, concentrations and with pH buffered or unbuffered in media, as well as in the presence of synovial fluid. Cell metabolism/viability was assessed by colorimetric MTT assay. Cell proliferation was assessed by live cell imaging. Cell viability was assessed using trypan blue and dimeric cyanine nucleic acid stain (yoyo‐1). To determine the mechanism of cell death, apoptosis was evaluated using Annexin V and 7AAD staining with flow cytometric quantification. Induction of apoptotic cell death pathways was assessed using caspase‐3 expression.

Results

Amikacin is cytotoxic to equine joint cells and MSC in a rapid, dose‐dependent, pH‐independent manner, which occurs primarily by apoptosis. Amikacin cytotoxicity was not mitigated by the addition of synovial fluid in vitro.

Main limitations

Further studies are necessary to determine whether these in vitro results predict joint injury in live animal models.

Conclusions

Amikacin at clinically applied doses induces rapid, pronounced cell death of equine joint cells. These findings suggest that amikacin doses currently used intra‐articularly should be reconsidered pending in vivo joint titration studies.
Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA‐1 phototherapy
Authors: Cuellar‐Barboza Adrian , Cardenas‐de la Garza Jesus Alberto , Cruz‐Gómez Luis Gerardo , Barboza‐Quintana Oralia , Flores‐Gutiérrez Juan Pablo , Gómez‐Flores Minerva , Welsh Oliverio , Ocampo‐Candiani Jorge , Herz‐Ruelas Maira E.
Published: January 2020

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic‐pituitary‐adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin‐releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α‐melanocyte‐stimulating hormone (α‐MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA‐1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA‐1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA‐1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α‐MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P = .037) in the post‐treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P = .032) in the post‐treatment samples compared with the initial value. CRH was significantly higher in intensity (P = .013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P = .626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA‐1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.
Nucleotide‐induced folding of cell division protein FtsZ from Staphylococcus aureus
Authors: Huecas Sonia , Canosa‐Valls Alejandro J. , Araújo‐Bazán Lidia , Ruiz Federico M. , Laurents Douglas V. , Fernández‐Tornero Carlos , Andreu José M.
Published: January 2020

The essential bacterial division protein FtsZ uses GTP binding and hydrolysis to assemble into dynamic filaments that treadmill around the Z‐ring, guiding septal wall synthesis and cell division. FtsZ is a structural homolog of tubulin and a target for discovering new antibiotics. Here, using FtsZ from the pathogen S. aureus (SaFtsZ), we reveal that, prior to assembly, FtsZ monomers require nucleotide binding for folding; this is possibly relevant to other mesophilic FtsZs. Apo‐SaFtsZ is essentially unfolded, as assessed by nuclear magnetic resonance and circular dichroism. Binding of GTP (≥ 1 mm) dramatically shifts the equilibrium toward the active folded protein. Supportingly, SaFtsZ refolded with GDP crystallizes in a native structure. Apo‐SaFtsZ also folds with 3.4 m glycerol, enabling high‐affinity GTP binding (KD 20 nm determined by isothermal titration calorimetry) similar to thermophilic stable FtsZ. Other stabilizing agents that enhance nucleotide binding include ethylene glycol, trimethylamine N‐oxide, and several bacterial osmolytes. High salt stabilizes SaFtsZ without bound nucleotide in an inactive twisted conformation. We identified a cavity behind the SaFtsZ‐GDP nucleotide‐binding pocket that harbors different small compounds, which is available for extended nucleotide‐replacing inhibitors. Furthermore, we devised a competition assay to detect any inhibitors that overlap the nucleotide site of SaFtsZ, or Escherichia coli FtsZ, employing osmolyte‐stabilized apo‐FtsZs and the specific fluorescence anisotropy change in mant‐GTP upon dissociation from the protein. This robust assay provides a basis to screening for high‐affinity GTP‐replacing ligands, which combined with structural studies and phenotypic profiling should facilitate development of a next generation of FtsZ‐targeting antibacterial inhibitors.
Transition modelling of surface flaws to through cracks
Authors: Satin Morris , Johnson W. Steven , Neu Richard W. , Annigeri Balkrishna , Ziegler Brett , Kersey Raymond Keith
Published: January 2020

Cracks starting at surfaces will grow under fatigue loading conditions both along the surface and in the thickness directions of the component geometry. In those cases where the crack grows through the thickness, the fatigue crack may transition to a corresponding through crack geometry. While the fatigue crack growth behaviour of both the surface flaws and complete through cracks are well understood, the method for modelling the process by which they transition from one to the other is not. This paper seeks to bring greater clarity and understanding to the transition process by implementing a transition method and developing the associated codes and equations to do so based on careful consideration of boundary conditions, experimental data, and finite element simulations.
Polygenic score for neuroticism is related to sleep difficulties
Authors: Stephan Yannick , Sutin Angelina R. , Luchetti Martina , Terracciano Antonio
Published: January 2020

Neuroticism, a broad trait measure of the tendency to experience negative emotions and vulnerability to stress, is consistently related to poor sleep quality. Less is known about potential pleiotropy in the genetic risk for high neuroticism and poor sleep. Therefore, the present study examined whether polygenic score (PGS) for neuroticism is related to sleep quality in two large samples of adults. In addition, depressive symptoms, anxiety and phenotypical neuroticism were tested as mediators in both samples. Participants were 8316 individuals aged from 50 to 101 years (mean age = 68.29, SD = 9.83) from the Health and Retirement Study, and 4973 individuals aged from 63 to 67 years (mean age = 64.30, SD = 0.68) from the Wisconsin Longitudinal Study. Participants from both samples were genotyped and answered questions on sleep quality. A higher PGS for neuroticism was related to lower sleep quality concurrently and over time in both samples. Anxiety, depressive symptoms and neuroticism mediated these relationships in the two samples. Although effect sizes were small, the present study provides replicable evidence that individuals with a higher genetic predisposition to experience negative emotions and distress are at risk of sleep difficulties.
Species richness in North Atlantic fish: Process concealed by pattern
Authors: Gislason Henrik , Collie Jeremy , MacKenzie Brian R. , Nielsen Anders , Borges Maria de Fatima , Bottari Teresa , Chaves Corina , Dolgov Andrey V. , Dulčić Jakov , Duplisea Daniel , Fock Heino O. , Gascuel Didier , Gil de Sola Luís , Hiddink Jan Geert , ter Hofstede Remment , Isajlović Igor , Jonasson Jónas Páll , Jørgensen Ole , Kristinsson Kristján , Marteinsdottir Gudrun , Masski Hicham , Matić‐Skoko Sanja , Payne Mark R. , Peharda Melita , Reinert Jakup , Sólmundsson Jón , Silva Cristina , Stefansdottir Lilja , Velasco Francisco , Vrgoč Nedo
Published: January 2020

Aim

Previous analyses of marine fish species richness based on presence‐absence data have shown changes with latitude and average species size, but little is known about the underlying processes. To elucidate these processes we use metabolic, neutral and descriptive statistical models to analyse how richness responds to maximum species length, fish abundance, temperature, primary production, depth, latitude and longitude, while accounting for differences in species catchability, sampling effort and mesh size.

Data

Results from 53,382 bottom trawl hauls representing 50 fish assemblages.

Location

The northern Atlantic from Nova Scotia to Guinea.

Time period

1977–2013.

Methods

A descriptive generalized additive model was used to identify functional relationships between species richness and potential drivers, after which nonlinear estimation techniques were used to parameterize: (a) a ‘best’ fitting model of species richness built on the functional relationships, (b) an environmental model based on latitude, longitude and depth, and mechanistic models based on (c) metabolic and (d) neutral theory.

Results

In the ‘best’ model the number of species observed is a lognormal function of maximum species length. It increases significantly with temperature, primary production, sampling effort, and abundance, and declines with depth and, for small species, with the mesh size in the trawl. The ‘best’ model explains close to 90% of the deviance and the neutral, metabolic and environmental models 89%. In all four models, maximum species length and either temperature or latitude account for more than half of the deviance explained.

Main conclusions

The two mechanistic models explain the patterns in demersal fish species richness in the northern Atlantic almost equally well. A better understanding of the underlying drivers is likely to require development of dynamic mechanistic models of richness and size evolution, fit not only to extant distributions, but also to historical environmental conditions and to past speciation and extinction rates.