bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Retinal Melanopsin on Lens-induced Myopia in Guinea Pigs
Authors: Zheng Wei , Chen Yao , Zhou Xuezhi , Zhang Xueyong , Chen Yuanyuan , Guan Xinyu , Mao Junfeng 
Published: July 2020

SIGNIFICANCE
Investigation of the mechanism and the role of melanopsin in lens-induced myopia is necessary to find out potential targets in the prevention of myopia development.

PURPOSE
We aimed to study the effect and mechanism of retinal melanopsin on lens-induced myopia in guinea pigs, as well as the interactions between melanopsin and other myopic regulation neurotransmitters such as dopamine and melatonin, and to explore the possible role of melanopsin in the prevention of myopia development.

METHODS
Twenty-day-old tricolor guinea pigs were randomly divided into four groups: control group, defocus group, defocus + AA92593 group, and defocus + dimethyl sulfoxide (DMSO) group. The defocus eyes wore −6.00 D lens. In the defocus + AA92593 group, the vitreous cavities were injected with melanopsin antagonist AA92593. In the defocus + DMSO group, the vitreous cavities were injected with 5% DMSO as the administration control. The expression of retinal melanopsin protein was measured with immunofluorescence staining and Western blot. The content of dopamine and melatonin in the retina was determined by the high-performance liquid chromatography electrochemical method.

RESULTS
Compared with the defocus group, intravitreal injection of AA92593 resulted in increased axial length of the defocus eyes (defocus, 8.05 ± 0.09 mm; defocus + AA92593, 8.15 ± 0.11 mm; P = .008), lower refractive degree (defocus, −1.98 ± 0.82 D; defocus + AA92593, −2.59 ± 0.97 D; P = .05), decreased relative expression of retinal melanopsin protein (defocus, 0.67 ± 0.11; defocus + AA92593, 0.20 ± 0.06; P < .0001), and increased melatonin content in the defocus eyes (defocus, 0.38 ± 0.09 ng/mg; defocus + AA92593, 0.55 ± 0.13 ng/mg; P = .01), but it had no obvious effect on dopamine content (defocus, 0.64 ± 0.18 ng/mg; defocus + AA9259, 0.61 ± 0.17 ng/mg; P > .99). The melatonin content of retina in the defocus + AA92593 group was correlated with refractive error (Pearson correlation coefficient = −0.68, P = .006) and eye axis length (Pearson correlation coefficient = 0.74, P = .02).

CONCLUSIONS
Retinal melanopsin has inhibitory effect on lens-induced myopia development in guinea pigs, and such effect may be related to retinal melatonin.
Validation of a More Reliable Method of Eye Drop Self-Administration
Authors: Freddo Thomas F. , Ho Derek Y. , Steenbakkers Michelle , Furtado Nadine 
Published: July 2020

SIGNIFICANCE
We propose an alternative method for eye drop self-administration. Similar IOP reductions were found with this method compared with clinician instillation. The alternative method of self-administration potentially benefits patients who have trouble successfully instilling drops.

PURPOSE
The purpose of this study was to validate the efficacy of an alternative method of drop instillation.

METHODS
This study is a randomized controlled crossover clinical trial. Thirty participants were recruited. A drop of 0.5% timolol maleate was instilled into subject's eye on two separate visits. On one visit, eye drop instillation was by a trained clinician, and on the other, self-instillation using an alternative method was used. The order was randomly chosen. Intraocular pressure was measured before drop instillation and 2 hours after drop instillation. The investigator was masked during measurement, and an observer recorded the IOP measurements.

RESULTS
Mean ± SD IOP measurement before 0.5% timolol maleate instillation measured 13.89 ± 2.29 mmHg. An average reduction 3.75 ± 2.36 mmHg was found with clinician administration, and an average reduction of 3.32 ± 2.31 mmHg was recorded with the new method. No significance was found in IOP reduction between two groups P < .45. Percent reduction was 25.17 ± 16.21% and 24.38 ± 16.31% in clinician instillation and alternative instillation method group, respectively. No significant difference was found. This percentage reduction was similar to previously reported studies. No reported cases of eye infection or irritation were found in any case, within a 3-month follow-up period.

CONCLUSIONS
We have proposed a more reliable method for instillation that provides a larger area for instillation and lessen the risk of contamination and patient's fear for eye drops. Similar efficacy was found compared with that of having a clinician directly administer the drop. This alternative method could potentially benefit patients who require topical eye drop therapy and result in increased compliance.
Topical Review: Optic Disc Pits and Associated Maculopathy
Authors: Anglo Miriam 
Published: July 2020

SIGNIFICANCEAlthough the treatment of optic disc pit maculopathy is controversial, this review concludes that the most successful current intervention is pars plana vitrectomy with peeling of the internal limiting membrane and induction of posterior vitreous detachment.Initially described in 1882, an optic disc pit is a rare defect of the optic nerve. This anomaly can result in sight-threatening retinopathy in the form of macular detachment and/or schisis. Outlined in this review of the literature are the incidence, clinical presentation, ancillary testing, pathogenesis, and management of optic disc pits and optic disc pit maculopathy.
The Effect of a Photochromic Contact Lens on Visual Function Indoors: A Randomized, Controlled Trial
Authors: Renzi-Hammond Lisa M. , Buch John R. , Hacker Lauren , Cannon Jessica , Hammond Billy R. 
Published: July 2020

SIGNIFICANCE
Photochromic soft contact lenses contain light-sensitive additives that allow them to darken when exposed to ultraviolet or violet light. One question, however, is whether the lenses influence vision indoors (minimally activated). In this study, we found that the minimally activated lenses improved many aspects of visual function under bright light.

PURPOSE
Photochromic contact lenses were designed to darken when exposed to outdoor sunlight. The filtering that results improves visual function under bright light conditions. Not all bright light exposures occur outdoors. In this study, we tested whether a photochromic contact lens improved visual function under conditions where the lens was minimally activated (i.e., no more than it normally would be in an indoor environment).

METHODS
A subject-masked contralateral design was used comparing a photochromic contact lens randomized to one eye against a nonphotochromic contact in the other eye of the same subject. Sixty subjects (mean = 34.90 ± 11.24 years) were tested. The primary endpoints consisted of four visual function outcomes: photostress recovery, glare disability, glare discomfort, and chromatic contrast. Photostress recovery was quantified by measuring the time needed to recover visual acquisition of a grating target after 5 seconds of an intense xenon white flash exposure; glare disability was evaluated as the energy in a surrounding xenon white annulus necessary to veil a central grating target; and glare discomfort was assessed using bioimaging of the squint response. Chromatic contrast was measured as thresholds for a green-yellow (580 nm) grating target superposed on a blue (460 nm) background.

RESULTS
The minimally activated photochromic contact demonstrated improved visual performance compared with the nonphotochromic control across all visual functions tested (P < .01).

CONCLUSIONS
Even under conditions of exiguous activation (e.g., as would be expected indoors or while driving at night), a photochromic contact will improve many of the more deleterious aspects of bright light.
Validation of the International Reading Speed Texts in a Canadian Sample
Authors: Morrice Elliott , Hughes Julian , Stark Zoey , Wittich Walter , Johnson Aaron 
Published: July 2020

SIGNIFICANCE
The International Reading Speed Texts (IReST) is a valid measure of reading speed in a Canadian sample. However, if clinicians desire to assess reading comprehension using the IReST, this will significantly reduce reading speeds of individuals with normal vision or reduced visual acuity and therefore should use the values presented here.

PURPOSE
The purposes of this study are (1) to validate the IReST in an English-speaking Canadian sample and (2) to examine how reading comprehension questions and reduced visual acuity affect reading speed on the IReST.

METHODS
For study 1, Canadian English speakers (n = 25) read all 10 IReST following the procedures used in the original IReST validation. For study 2, Canadian English speakers (n = 50) read all 10 IReST, half with normal/corrected-to-normal vision and half with reduced visual acuity, and were asked reading comprehension questions.

RESULTS
No significant differences were found between Canadian sample and the published IReST values (in all cases, P > .05; mean difference [M
diff] = −5.30 to +11.43; Cohen d = −0.15 to +0.27; Bayes factors = 0.41, 0.09). Assessing reading comprehension with multiple-choice questions on the IReST significantly reduced reading speeds in the normal vision condition (M
diff = 25.3; 95% confidence interval, −16.7 to −34.1) and in the simulated impairment condition (M
diff = 59.3; 95% confidence interval, −47.7 to −71).

CONCLUSIONS
The IReST is a valid measure that can be used to assess reading speed in a Canadian English-speaking sample. If researchers/clinicians wish to assess both reading speed and comprehension, using multiple-choice reading comprehension questions, then the values provided by the IReST will likely underestimate an individual's true reading speed in individuals with normal/corrected-to-normal vision or reduced visual acuity.
Gordonia mangrovi sp. nov., a novel actinobacterium isolated from mangrove soil in Hainan
Authors: Xie Yuhui , Zhou Shuangqing , Xu Yun , Wu Wenqiang , Xia Wei , Zhang Rongping , Huang Dongyi , Huang Xiaolong 
Published: July 2020

A novel actinobacterium, designated strain HNM0687T, was isolated from mangrove soil samples collected from Hainan Province, PR China and its polyphasic taxonomy was studied. Based on the results of 16S rRNA gene sequence analysis, strain HNM0687T was closely related to

Gordonia bronchialis

NBRC 16047T (98.7 %),

Gordonia rhizosphera

NBRC 16068T (98.2 %),

Gordonia oryzae

RS15-1ST (97.9 %),

Gordonia polyisoprenivorans

NBRC 16320T (97.7 %) and

Gordonia sediminis

AMA 120T (97.7 %). Genome-based comparisons revealed a clear distinction in average nucleotide identity values between strain HNM0687T and its closely related strains (74.4–78.3 %). Strain HNM0687T contained meso-diaminopimelic acid, arabinose and galactose in whole-cell hydrolysates. Mycolic acid was present. The menaquinones of strain HNM0687T were MK-9(H2) and MK-7(H2). The phospholipids of the isolate were composed of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major fatty acids were C16 : 0, C16 : 1
ω7c/C16 : 1
ω6c, C18 : 010-methyl (TBSA), C18 : 0 and C18 : 1
ω9c. Based on its genotypic, chemotaxonomic and phenotypic characteristics, it is concluded that strain HNM0687T represents a novel species of the genus

Gordonia

for which the name Gordonia mangrovi sp. nov. is proposed. The type strain is HNM0687T (=CCTCC AA 2019074 T=KCTC 49383 T).
Solving the trade-off by differences in handling of intracellular K+: why substrate translocation by the dopamine transporter but not by the serotonin transporter is voltage-dependent
Authors: Bhat Shreyas , Niello Marco , Schicker Klaus , Pifl Christian , Sitte Harald H. , Freissmuth Michael , Sandtner Walter 
Published: July 2020

AbstractThe dopamine transporter (DAT) retrieves dopamine into presynaptic terminals after synaptic release. The concentrative power of DAT is thought to be fueled by the transmembrane Na+gradient, but it is conceivable that DAT can also rely on other energy sources, e.g. membrane voltage and/or the K+gradient. Here, we recorded uptake of dopamine or the fluorescent substrate APP+((4-(4-dimethylamino)phenyl-1-methylpyridinium) in DAT-expressing cells under voltage control. We show that DAT differs substantially from the closely related serotonin transporter (SERT): substrate uptake by DAT was voltage-dependent, intracellular K+binding to DAT was electrogenic but transient in nature thus precluding antiport of K+by DAT. There is a trade-off between maintaining constant uptake and harvesting membrane potential for concentrative power. Based on our observations, we conclude that subtle differences in the kinetics of co-substrate ion binding allow closely related transporters to select between voltage-independent uptake and high concentrative power.
Mendelian randomisation analyses of eosinophils and other blood cell types in relation to lung function and disease
Authors: Guyatt Anna L , John Catherine , Williams Alexander T , Shrine Nick , Reeve Nicola ,   SpiroMeta consortium, Hall Ian P , Wain Louise V , Sheehan Nuala A , Dudbridge Frank , Tobin Martin D 
Published: July 2020

AbstractBackgroundEosinophils are granulocytes associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled by interleukin-5: anti-interleukin-5 agents reduce asthma and COPD exacerbation frequency, and response correlates with baseline eosinophil counts. However, causal relationships between eosinophils and other respiratory phenotypes are less studied.MethodsWe investigated causality between eosinophils and: lung function, acute exacerbations of COPD (AECOPD), asthma-COPD overlap (ACO), moderate-to-severe asthma, and respiratory infections. We performed Mendelian randomization (MR) using 151 genetic variants from genome-wide association studies of blood eosinophil counts in UK Biobank/INTERVAL, and respiratory data from UK Biobank, using MR methods relying on different assumptions for validity. Multivariable MR using eight blood cell type exposures was performed for outcomes showing evidence of causation by eosinophils.FindingsThere was evidence that higher eosinophils reduce FEV1/FVC and FEV1 (weighted median estimator, SD change FEV1/FVC per SD eosinophils: −0.054 [95%CI −0.078,−0.029]. There was also evidence that eosinophils cause ACO (weighted median OR 1.44 [95%CI 1.19,1.74]), and asthma (weighted median OR 1.50 [95%CI 1.23,1.83]). Multivariable MR for FEV1/FVC, FEV1, ACO and asthma suggested that eosinophils were the cell type with the most important effect. Causal estimates of individual variants were heterogeneous, which may arise from pleiotropy.InterpretationWe found evidence that eosinophils reduce lung function, and increase ACO and asthma risk, on average over the set of genetic variants studied. Eosinophils appear to be causal determinants of fixed airflow obstruction among individuals with features of both asthma and COPD.FundingWellcome, BHF, MRC, BBSRC CASE studentship with GSK, GSK/BLF.
Accurate classification of secondary progression in multiple sclerosis
Authors: Ramanujam Ryan , Zhu Feng , Fink Katharina , Danylaitė Karrenbauer Virginija , Lorscheider Johannes , Benkert Pascal , Kingwell Elaine , Tremlett Helen , Hillert Jan , Manouchehrinia Ali ,   The BeAMS Study group
Published: July 2020

AbstractTransition from a relapsing-remitting to the secondary progressive phenotype is an important milestone in the clinical evolution of multiple sclerosis. In the absence of reliable imaging or biological markers of phenotype transition, assignment of current phenotype status relies on retrospective evaluation of the medical history of an individual. Here, we sought to determine if demographic and clinical information from multiple sclerosis patients can be used to accurately assign current disease phenotypes: either relapsing-remitting or secondary progressive status. Data from the most recent clinical visit of 14,387 multiple sclerosis patients were extracted from the Swedish Multiple Sclerosis Registry. Decision trees based on sex, symptom onset age, Expanded Disability Scale Status score, and age & disease duration at the most recent clinic visit, were examined to build a classifier to determine disease phenotype. Validation was conducted using an independent cohort of multiple sclerosis patients from British Columbia, Canada, and a previously published classifier to assign phenotype was also tested. Clinical records of 100 randomly selected patients were used to manually categorize phenotype by three independent neurologists. A decision tree (the classifier) containing only most recently available disability score and age obtained 89.3% (95% confidence intervals (CI): 88.8% to 89.8%) classification accuracy, defined as concordance with the latest reported status in the registry. Replication in an independent cohort from British Columbia resulted in 82.0% (95%CI: 81.0% to 83.1%) accuracy. A previously published classification algorithm with slight modifications achieved 77.8% (95%CI: 77.1% to 78.4%) accuracy when assigning disease phenotype. With complete patient history data, three neurologists obtained 84.7% accuracy on average compared with 85 for the classifier using the same data. The model is easily interpretable and could allow research studies and randomized clinical trials to estimate the probability of patients having already reached the secondary progressive stage when they have not yet been retrospectively assigned this status, and to standardize definitions of disease phenotype across different cohorts. Clinically, this model could assist neurologists by providing additional information about the probability of having secondary progressive disease. This could also benefit patients who may be introduced to new therapies targeting progressive multiple sclerosis.
Estimating the causal effect of genetic liability to prevalent disease on hospital costs using Mendelian Randomization
Authors: Dixon Padraig , Harrison Sean , Hollingworth William , Davies Neil M , Smith George Davey 
Published: July 2020

ABSTRACTBACKGROUNDAccurate measurement of the effects of disease status on healthcare cost is important in the pragmatic evaluation of interventions but is complicated by endogeneity biases due to omitted variables and reverse causality. Mendelian Randomization, the use of random perturbations in germline genetic variation as instrumental variables, can avoid these limitations. We report a novel Mendelian Randomization analysis of the causal effect of liability to disease on healthcare costs.METHODSWe used Mendelian Randomization to model the causal impact on inpatient hospital costs of liability to six highly prevalent diseases: asthma, eczema, migraine, coronary heart disease, type 2 diabetes, and major depressive disorder. We identified genetic variants from replicated genome-wide associations studies and estimated their association with inpatient hospital costs using data from UK Biobank, a large prospective cohort study of individuals linked to records of hospital care. We assessed potential violations of the instrumental variable assumptions, particularly the exclusion restriction (i.e. variants affecting costs through alternative paths). We also conducted new genome wide association studies of hospital costs within the UK Biobank cohort as a further “split sample”sensitivity analysis.RESULTSWe analyzed data on 307,032 individuals. Genetic variants explained only a small portion of the variance in each disease phenotype. Liability to coronary heart disease had substantial impacts (mean per person per year increase in costs from allele score Mendelian Randomization models: £712 (95% confidence interval: £238 to £1,186)) on inpatient hospital costs in causal analysis, but other results were imprecise. There was concordance of findings across varieties of sensitivity analyses, including stratification by sex, and those obtained from the split sample analysis.CONCLUSIONA novel Mendelian Randomization analysis of the causal effect of liability to disease on healthcare cost demonstrates that this type of analysis is feasible and informative in this context. There was concordance across data sources and across methods bearing different assumptions. Selection into the relatively healthy UK Biobank cohort and the modest proportion of variance in disease status accounted for by the allele scores reduced the precision of our estimates. We therefore could not exclude the possibility of substantial costs due to these diseases.JEL Classification NumbersH51, I10, I11, I18,
Transcription Factor EB regulates phosphatidylinositol-3-phosphate levels on endomembranes and alters lysosome positioning in the bladder cancer model
Authors: Mathur Pallavi , Santos Camilla De Barros , Lachuer Hugo , Latgé Bruno , Radvanyi François , Goud Bruno , Schauer Kristine 
Published: July 2020

AbstractLysosomes orchestrate degradation and recycling of exogenous and endogenous material, thus controlling cellular homeostasis. Little is known how this organelle changes during malignant transformation. We investigate the intracellular landscape of lysosomes in a cellular model of bladder cancer. Employing standardized cell culture on micropatterns we identify a phenotype of peripheral lysosome positioning prevailing in bladder cancer but not normal urothelium. We show that lysosome positioning is controlled by transcription factor EB (TFEB) and that lysosomal dispersion results from TFEB activation downstream of lysosomal Ca2+release. Remarkably, we find that TFEB regulates phosphatidylinositol-3-phosphate (PtdIns3P) levels on endomembranes which recruit FYVE-domain containing proteins, such as the motor adaptor protrudin, for anterograde movement of lysosomes. Altogether, we uncover lysosome positioning as result of PtdIns3P activation downstream of TFEB as a potential biomarker for bladder cancer. Moreover, we reveal a novel role of TFEB in regulating cellular PtdIns levels, conceptually clarifying the dual role of TFEB as regulator of endosomal maturation and autophagy, two distinct processes controlled by PtdIns3P.Statement of significanceHere we provide the first atlas for the landscape of the lysosomal compartment in bladder cancer and reveal the mechanistic role of TFEB in regulating endosomal PtdIns3P levels and subsequent lysosomal dispersion. We unveiled lysosomal positioning as a potential biomarker for malignant bladder cancer which might arise as an actionable target for cancer therapy.