bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of MYOC risk variants for glaucoma in different populations
Authors: Liuska Perttu J. , Harju Mika , Kivelä Tero T. , Turunen Joni A. 
Published: January 2021

AbstractPurposeTo assess the clinical relevance of myocilin (MYOC) gene variants as risk factors for glaucoma in literature and to estimate their prevalence in different populations.MethodsWe reviewed the literature for published MYOC variants in glaucoma patients and estimated their prevalence in general population using gnomAD and BRAVO databases. We used several bioinformatics tools and the criteria of the American College of Medical Genetics and Genomics (ACMG) to assess the pathogenicity of the variants. We evaluated the carrier frequency of the variants in gnomAD, including its subpopulations.ResultsWe found 13 missense and 5 loss‐of‐function (LOF) reported variants in MYOC that were both probable pathogenic or risk variants and listed in gnomAD. Six likely pathogenic missense variants were p.(Cys25Arg), p.(Gln48His), p.(Gly326Ser), p.(Thr353Ile), p.(Thr377Met) and p.(Gly399Val). They were most prevalent in East and South Asia (frequency, 0.92% and 0.81%, respectively). The most common missense variants were p.(Thr353Ile) (0.91% in East Asia) and p.(Gln48His) (0.79% in South Asia). Five LOF variants were p.(Arg46Ter), p.(Arg91Ter), p.(Arg272Ter), p.(Gln368Ter) and p.(Tyr453MetfsTer11). We considered these glaucoma risk variants. They were most prevalent in the East Asian and the Finnish population (0.93% and 0.33%, respectively).ConclusionPathogenic MYOC variants appear to be population‐associated. Our results highlight allelic heterogeneity of MYOC variants in open‐angle glaucoma. Many of the probable pathogenic variants are over‐represented in some of the populations causing doubt of their status as monogenic disease‐causing variants.
Recommendations for ophthalmologic practice during the easing of COVID‐19 control measures
Authors: Gegúndez‐Fernández José A. , Llovet‐Osuna Fernando , Fernández‐Vigo José I. , Mendicute del Barrio Javier , Pablo‐Júlvez Luis , Muñoz‐Negrete Francisco J. , Zarranz‐Ventura Javier , Durán de la Colina Juan , de Rojas Silva Victoria , Jiménez‐Alfaro Iñigo , Calonge‐Cano Margarita , Galindo‐Ferreiro Alicia , Castillo‐Gómez Alfredo , Mantolán‐Sarmiento Cristina , Duch‐Samper Antonio , Álvarez de Toledo‐Elizalde Juan , Duch‐Mestres Francesc , Elies‐Amat Daniel , Ortega‐Usobiaga Julio , Saornil‐Alvarez María Antonia , Villarrubia Cuadrado Alberto , Garay Aramburu Gonzaga , Fonollosa Carduch Alejandro , Cordero Coma José Miguel , García Delpech Salvador , Cárceles Cárceles Juan Antonio , Benítez del Castillo Sánchez José Manuel , Gómez de Liaño Sánchez Pilar , Harto Castaño Miguel , Arias Puente Alfonso , García‐Layana Alfredo ,   Spanish Ophthalmology Societies
Published: January 2021

AbstractIn the context of the COVID‐19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID‐19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS‐CoV‐2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow‐up of the ophthalmic diseases. With this update (5th) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID‐19 pandemic.
Assessment of macular microvasculature features before and after vitrectomy in the idiopathic macular epiretinal membrane using a grading system: An optical coherence tomography angiography study
Authors: Mao Jianbo , Xu Zhaokai , Lao Jimeng , Chen Yiqi , Xu Xiaoqiong , Wu Sulan , Zheng Zicheng , Liu Bowen , Shen Lijun 
Published: January 2021

AbstractPurposeTo evaluate pre‐ and postoperative microvasculature features in eyes with different idiopathic macular epiretinal membrane (iERM) classifications using optical coherence tomography angiography (OCTA).MethodsIn this retrospective study, 100 eyes with iERM were enrolled; 62 eyes underwent pars plana vitrectomy (PPV). All iERM eyes were evaluated and graded using optical coherence tomography (OCT). According to the thickness of the fovea relative to the surrounding macula from OCT radial line scans, we classified iERM into three grades. Optical coherence tomography angiography (OCTA) was used to measure the foveal avascular zone (FAZ)‐related parameters and the superficial and deep capillary plexus layers using 3 × 3 mm scans. Measurements were taken at baseline and 3 months postoperatively. Best corrected visual acuity (BCVA), vessel density (VD), FAZ area, FAZ perimeter (PERIM), acircularity index (AI), and foveal vessel density (FD) were evaluated.ResultsIdiopathic macular epiretinal membrane (iERM) eyes with a higher grade had a lower FAZ area and perimeter (p < 0.0001), higher foveal vessel density (FVD) both in the superficial capillary plexus (SCP) (p < 0.0001) and in the deep capillary plexus (DCP) (p < 0.05), and a lower parafoveal vessel density (PRVD) in the DCP (p < 0.0001). The macular vessel density ratio (MVR = FVD/PRVD) increased with an increase in grade both in the SCP and in the DCP (p < 0.0001). For grade 1 iERM eyes, only PRVD in the DCP significantly changed before versus after the operation (p < 0.05). For grade 2 iERM eyes, the FAZ area and perimeter became larger after the operation (p < 0.05). The MVR of grade 2 iERM eyes decreased postoperatively both in the SCP (p < 0.05) and in the DCP (p < 0.001). For grade 1 and grade 2 iERM eyes, preoperative LogMAR BCVA was negatively correlated with the FAZ area (p < 0.01) and perimeter (p < 0.01), and was positively correlated with the MVR in the SCP (p < 0.05). Postoperative LogMAR BCVA was positively correlated with the FVD in the DCP (p < 0.05).ConclusionsIdiopathic macular epiretinal membrane (iERM) eyes of different grades have significant differences in microvasculature features. According to OCTA, eyes with higher grades have more serious microvascular changes. Grading plays a part in predicting postoperative microvascular characteristics, and grade 1 iERM eyes have a better visual outcome compared with grade 2 iERM eyes.
A neurological presentation caused by brain metastases in a dog with interventricular septal hemangiosarcoma
Authors: Bunn TA , Robveille C , Irwin PJ , Langner KFA 
Published: January 2021

BackgroundBrain metastases are well known for disseminated hemangiosarcoma involving the right atrium/auricle.Case reportAn 8‐year‐old male Australian Shepherd Dog presented with a 3‐day history of circling to the left. A neurological examination revealed obtunded mentation, right hemi‐inattention, bilateral strabismus towards the left side and absent physiological nystagmus. In addition, the dog had muffled heart sounds on auscultation and exercise‐induced weakness. Laboratory findings included hypercoagulability and marked elevation in the C‐reactive protein concentration. Electrocardiography detected a sinus rhythm with right bundle‐branch block and ventricular bigeminy. Echocardiography revealed an extensive interventricular septal mass. Due to the grave prognosis, the owners elected for euthanasia, and a complete necropsy was performed. The main pathological findings were an interventricular septal and left ventricular hemangiosarcoma, with metastases in the brain, lungs, spleen and adrenal glands. No evidence of tumour infiltration was found in the right atrium.ConclusionTo the authors' knowledge, this is the first report of neurological signs due to confirmed brain metastases in a dog with interventricular septal hemangiosarcoma. Although the right atrium is the main location for cardiac hemangiosarcoma, the interventricular septum should be evaluated in all cases.
A survey of ewe mortality on the Central Tablelands of New South Wales in 2010, a year of above‐average rainfall
Authors: Watt B , Eppleston J , Dhand NK 
Published: January 2021

BackgroundSheep producers reported elevated ewe mortality following a wetter‐than‐average season on the tablelands of New South Wales in 2010. We conducted a survey of local producers to determine the extent and cause of ewe losses, as well as associated risk factors.MethodsA questionnaire was designed and posted to sheep producers running at least 1000 sheep. Data from questionnaires were analysed using linear mixed models to identify risk factors associated with ewe mortality. Data on the likely causes of deaths, particularly those associated with foot abscess, were analysed by ordinal generalised linear mixed models to determine the most prevalent causes of ewe death.ResultsThe mean annual ewe mortality was 5.4% (range 0.1%–28.6%). Higher mortality was associated with older ewes and lambing in paddocks with longer pastures. The two most important causes of ewe death reported by farmers were ‘died during lambing’ and ‘foot abscess’. Mortality due to foot abscess was more commonly reported in adult ewes than maiden ewes (odds ratio and 95% confidence interval: 5.61; 3.52, 8.94), when lambing on pasture longer than 5 cm than ≤5 cm (2.96; 1.54, 5.70) and when lambing in spring than in autumn (4.87; 1.36, 17.41).ConclusionsThe level of ewe mortality observed was at the upper end of that reported previously in Australia. Risk factor analysis suggested that, in wet years, losses due to foot abscess could be reduced by lambing older heavier ewes in autumn on pasture swards less than 5 cm high.
Neural changes in youth at high risk for bipolar disorder undergoing family‐focused therapy or psychoeducation
Authors: Garrett Amy S. , Chang Kiki D. , Singh Manpreet K. , Armstrong Casey C. , Walshaw Patricia D. , Miklowitz David J. 
Published: January 2021

AbstractBackgroundPatients with mood disorders may benefit from psychosocial interventions through changes in brain networks underlying emotion processing. In this study, we used functional magnetic resonance imaging (fMRI) to investigate treatment‐related changes in emotion processing networks in youth at familial high risk for bipolar disorder (BD).MethodsYouth, ages 9–17, were randomly assigned to family‐focused therapy for high‐risk youth (FFT‐HR) or an active comparison treatment, Enhanced Care (EC). Before and after these 4‐month treatments, participants underwent fMRI while viewing happy, fearful, and calm facial expressions. Twenty youth in FFT‐HR and 20 in EC were included in analyses of pre‐ to post‐treatment changes in activation across the whole brain. Significant clusters were assessed for correlation with mood symptom improvement.ResultsIn the dorsolateral prefrontal cortex (DLPFC), activation increased from pre‐ to post‐treatment in the FFT‐HR group and decreased in the EC group. Insula activation decreased in the FFT‐HR group and did not change in the EC group. Across both treatments, decreasing activation in the hippocampus and amygdala was correlated with pre‐ to post‐treatment improvement in hypomania, while increasing activation in the DLPFC was correlated with pre‐ to post‐treatment improvement in depression.DiscussionPsychosocial treatment addresses abnormalities in emotion regulation networks in youth at high risk for BD. Increased prefrontal cortex activation suggests enhanced emotion regulation from pre‐ to post‐treatment with FFT‐HR. Improvements in family interactions may facilitate the development of prefrontal resources that provide protection against future mood episodes.
Post‐selection inference for changepoint detection algorithms with application to copy number variation data
Authors: Hyun Sangwon , Lin Kevin Z. , G'Sell Max , Tibshirani Ryan J. 
Published: January 2021

AbstractChangepoint detection methods are used in many areas of science and engineering, for example, in the analysis of copy number variation data to detect abnormalities in copy numbers along the genome. Despite the broad array of available tools, methodology for quantifying our uncertainty in the strength (or the presence) of given changepoints post‐selection are lacking. Post‐selection inference offers a framework to fill this gap, but the most straightforward application of these methods results in low‐powered hypothesis tests and leaves open several important questions about practical usability. In this work, we carefully tailor post‐selection inference methods toward changepoint detection, focusing on copy number variation data. To accomplish this, we study commonly used changepoint algorithms: binary segmentation, as well as two of its most popular variants, wild and circular, and the fused lasso. We implement some of the latest developments in post‐selection inference theory, mainly auxiliary randomization. This improves the power, which requires implementations of Markov chain Monte Carlo algorithms (importance sampling and hit‐and‐run sampling) to carry out our tests. We also provide recommendations for improving practical useability, detailed simulations, and example analyses on array comparative genomic hybridization as well as sequencing data.
Small‐sample inference for cluster‐based outcome‐dependent sampling schemes in resource‐limited settings: Investigating low birthweight in Rwanda
Authors: Sauer Sara , Hedt‐Gauthier Bethany , Rivera‐Rodriguez Claudia , Haneuse Sebastien 
Published: January 2021

AbstractThe neonatal mortality rate in Rwanda remains above the United Nations Sustainable Development Goal 3 target of 12 deaths per 1000 live births. As part of a larger effort to reduce preventable neonatal deaths in the country, we conducted a study to examine risk factors for low birthweight. The data were collected via a cost‐efficient cluster‐based outcome‐dependent sampling (ODS) scheme wherein clusters of individuals (health centers) were selected on the basis of, in part, the outcome rate of the individuals. For a given data set collected via a cluster‐based ODS scheme, estimation for a marginal model may proceed via inverse‐probability‐weighted generalized estimating equations, where the cluster‐specific weights are the inverse probability of the health center's inclusion in the sample. In this paper, we provide a detailed treatment of the asymptotic properties of this estimator, together with an explicit expression for the asymptotic variance and a corresponding estimator. Furthermore, motivated by the study we conducted in Rwanda, we propose a number of small‐sample bias corrections to both the point estimates and the standard error estimates. Through simulation, we show that applying these corrections when the number of clusters is small generally reduces the bias in the point estimates, and results in closer to nominal coverage. The proposed methods are applied to data from 18 health centers and 1 district hospital in Rwanda.
Ilexgenin A restrains CRTC2 in the cytoplasm to prevent SREBP1 maturation via AMP kinase activation in the liver
Authors: Lu Yawen , Ma Jingjie , Li Ping , Liu Baolin , Wen Xiaodong , Yang Jie 
Published: January 2021

Background and PurposeIlexgenin A is a triterpenoid from ShanLv Cha with beneficial effects on metabolic homeostasis. We investigated whether ilexgenin A could inhibit hepatic de novo fatty acid synthesis via the interfering with SREBP1 maturation.Experimental ApproachThe effects of Ilexgenin A on CRTC2 translocation and SREBP1 maturation were investigated in the liver of fasted mice and hepatocytes exposed to saturated fatty acids. The effect of Iilexgenin A on hepatic lipid accumulation was also observed in high‐fat diet fed mice.Key ResultsSec23A and Sec31A are two subunits of COPII complex and their interaction is essential for the processing of SREBP1 maturation. Ilexgenin A activates AMPK by reducing cellular energy and preventing cytoplasmic CRTC2 to compete with Sec23A for binding to Sec31A under nutrient‐rich conditions. Consequently, ilexgenin A impaired COPII‐dependent SREBP1 maturation via disrupting Sec31A–Sec23A interaction, leading to the inhibition of de novo fatty acid synthesis in the liver. In contrast, mTORC1 phosphorylated Ser136 of CRTC2, facilitating the formation of Sec31A–Sec23A interaction to promote SREBP1 maturation, whereas this action was reversed by ilexgenin A in an AMPK‐dependent manner. Ilexgenin A protected CRTC2 function and restrained hepatic lipogenic response in high fat diet‐fed mice, providing in vivo evidence to support the beneficial effects of ilexgenin A on lipid metabolism.Conclusions and ImplicationsIlexgenin A activated AMPK and restrained CRTC2 to the cytoplasm to prevent SREBP1 maturation via impairing COPII function in the liver. This suggests that CRTC2 might be a potential target for pharmacological intervention to prevent hepatic lipid deposition.LINKED ARTICLESThis article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc
Hyperoxia‐induced miR‐342‐5p down‐regulation exacerbates neonatal bronchopulmonary dysplasia via the Raf1 regulator Spred3
Authors: Wen Xin , Zhang Hui , Xiang Bo , Zhang Weiyu , Gong Fang , Li Shiling , Chen Hongyan , Luo Xuan , Deng Juan , You Yaoyao , Hu Zhangxue , Jiang Changke 
Published: January 2021

Background and PurposeBronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA‐based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation.Experimental ApproachTwo murine models of hyperoxic lung injury (with or without miR‐342‐5p or Sprouty‐related, EVH1 domain‐containing protein 3 [Spred3] modulation) were employed: a hyperoxia‐induced acute lung injury model (100% O2 on postnatal days 1–7) and the BPD model (100% O2 on postnatal days 1–4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR‐342‐5p analysis.Key ResultsHyperoxia decreased miR‐342‐5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR‐342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD‐associated pulmonary arterial hypertension (PAH). T2AEC‐specific miR‐342 transgenic overexpression, as well as miR‐342‐5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR‐342‐5p targets the 3′UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR‐342‐5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR‐342‐5p levels relative to healthy control pellets.Conclusion and ImplicationsThese findings suggest that miR‐342‐5p mimic therapy may show promise in the treatment or prevention of BPD.
Can variation in seed removal patterns of Neotropical pioneer tree species be explained by local ant community composition?
Authors: Ruzi Selina A. , Zalamea Paul‐Camilo , Roche Daniel P. , Achury Rafael , Dalling James W. , Suarez Andrew V. 
Published: January 2021

AbstractMany plants depend on animals for seed dispersal, and ants commonly fill this role. We examined whether heterogeneity in ant community composition among sites, between above‐ and belowground foraging guilds, or between seasons predicts observed variation in seed removal rates for 12 nonmyrmecochorous Neotropical pioneer tree species on Barro Colorado Island, Panama. We also investigated whether ants associated with removing seeds differed in specific morphological characters from the larger ant community. We observed ant–seed interactions at caches to determine which ants removed seeds of 12 tree species. We also sampled ant community composition by placing 315 pitfall traps and 160 subterranean traps across the five sites where seed removal rates were quantified. Aboveground ant community composition varied by site but not season. Among‐site variation in ant composition did not predict seed removal patterns at these same sites. Belowground ant communities differed from aboveground ant communities but were not structured by either site or seed cache type. Finally, ants that removed seeds did not differ morphologically from the broader ant community. Overall, our results suggest ant communities vary over relatively small spatial scales but exhibit a high degree of functional redundancy in terms of seed removal services provided for Neotropical pioneer tree species.Abstract in Spanish is available with online material.
Trends in survival of leukemia among children, adolescents, and young adults: A population‐based study in Osaka, Japan
Authors: Nakata Kayo , Okawa Sumiyo , Fuji Shigeo , Sato Akira , Morishima Toshitaka , Tada Yuma , Inoue Masami , Hara Junichi , Kawa Keisei , Miyashiro Isao ,   the Osaka Cancer Association for Children, Adolescents, Young Adults
Published: January 2021

AbstractThis study focused on children as well as adolescents and young adults (AYAs) and aimed to examine trends in survival of leukemia over time using population‐based cancer registry data from Osaka, Japan. The study subjects comprised 2254 children (0‐14 years) and 2,905 AYAs (15‐39 years) who were diagnosed with leukemia during 1975‐2011. Leukemia was divided into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and other leukemias. We analyzed 5‐year overall survival probability (5y‐OS), using the Kaplan‐Meier method and expressed time trends using the joinpoint regression model. For recently diagnosed (2006‐2011) patients, a Cox proportional hazards model was applied to determine predictors of 5y‐OS, using age group, gender, and treatment hospital as covariates. Over the 37‐year period, 5y‐OS greatly improved among both children and AYAs, for each leukemia type. Among AYAs, 5y‐OS of ALL improved, especially after 2000 (65% in 2006‐2011), when the pediatric regimen was introduced but was still lower than that among children (87% in 2006‐2011, P < .001). Survival improvement was most remarkable in CML, and its 5y‐OS was over 90% among both children and AYAs after the introduction of molecularly targeted therapy with tyrosine kinase inhibitors. Among patients with recently diagnosed AML, the risk of death was significantly higher for patients treated at nondesignated hospitals than those treated at designated cancer care hospitals. The changes in survival improvement coincided with the introduction of treatment regimens or molecularly targeted therapies. Patient centralization might be one option which would improve survival.