bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foveal thickness, foveal microvasculature, and refractive error in children with asymmetric involvement of retinopathy of prematurity
Authors: Celik Gokhan , Gunay Murat , Vural Asli , Kizilay Osman 
Published: May 2020

Objective To evaluate foveal thickness, foveal microvasculature, and refractive error in children with asymmetric involvement of retinopathy of prematurity who had laser treatment in one eye and spontaneously regressed retinopathy of prematurity in the fellow eye. Methods Totally, 17 children (34 eyes) with a history of asymmetric course of acute Zone II retinopathy of prematurity were assessed. Data on best-corrected visual acuity, refractive status, axial length, anterior chamber depth, and optical coherence tomography angiography findings were analyzed between treated and non-treated fellow eyes. Results Treated eyes were more myopic than non-treated eyes (mean, –0.09 ± 1.86 diopters vs mean, 0.07 ± 0.98 diopters, p = 0.026). Compared to non-treated eyes, treated eyes had shallower anterior chamber depth (mean, 3.27 ± 0.24 mm vs mean, 3.55 ± 0.19 mm, p = 0.02). No significant difference was observed regarding optical coherence tomography angiography parameters between two eyes of the children. The mean central foveal thickness was found to be higher in treated eyes than in non-treated eyes (297.46 ± 22.03 vs 275.55 ± 18.45, p = 0.009). Higher number of laser spots were associated with decreased parafoveal superficial capillary plexus vessel density ( r = –0.56, p = 0.02) and increased central foveal thickness ( r = 0.62, p = 0.008). Conclusion Our results revealed no difference in optical coherence tomography angiography parameters between laser-treated and non-treated eyes in children with asymmetric involvement of Zone II retinopathy of prematurity except for a higher central foveal thickness in laser-treated eyes. Treated eyes were more myopic than the non-treated eyes. Number of laser applications during treatment had an impact on parafoveal superficial capillary plexus vessel density.
The Canadian Dermatology Association’s Top Five Choosing Wisely Canada Recommendations
Authors: Zhou Linghong Linda , Nurmohamed Sabrina , Au Sheila , Beecker Jennifer , Green Peter , Robertson Lynne , Mydlarski Regine 
Published: May 2020

Introduction In this article, we present the Canadian Dermatology Association’s (CDA) Choosing Wisely Canada (CWC) list of top “Five Things Physicians and Patients Should Question in Dermatology” and the evidence in support of each recommendation. Methods Using a nominal technique, the CDA Working Group and Task Force generated an initial list based on literature review and expert consultation. After several rounds of list refinement via a modified Delphi process, a final list of recommendations was generated. These were approved by the CDA Board of Directors, presented at the CDA 93rd Annual Conference in 2018, and published by CWC in 2019. Results The top five recommendations are as follows: (1) Don’t routinely prescribe antibiotics for bilateral lower leg redness and swelling; (2) Don’t routinely prescribe topical combination corticosteroid/antifungal products; (3) Don’t routinely use topical antibiotics on a surgical wound; (4) Don’t prescribe systemic antifungals without mycological confirmation of dermatophyte infection; and (5) Don’t use oral antibiotics for acne vulgaris for more than 3 months without assessing efficacy. Discussion This list of recommendations aims to encourage both physicians and patients to reevaluate ineffective, yet common, practices in treating dermatologic conditions. These recommendations represent actionable changes in practice, and therefore have considerable potential to enhance value-based care in dermatology. Conclusions This list was developed to identify tangible changes in practice within dermatology that may reduce inefficiencies, prevent potential patient harm, and improve care. Future advocacy work may include updates, feedback obtainment, and patient care handouts, to continue to promote value-based healthcare and best practices.
Implementing early intensive behavioral intervention in community settings
Authors: Plavnick Joshua B , Bak M Y Savana , Avendaño Sarah M , Dueñas Ana D , Brodhead Matthew T , Sipila Emma S 
Published: May 2020

Although research shows early intensive behavioral intervention is efficacious when delivered in university or private intervention centers, little is known about effectiveness or feasibility of disseminating early intensive behavioral intervention to larger communities. The Michigan State University Early Learning Institute was developed to address gaps in distribution of early intensive behavioral intervention to community settings, with an emphasis of serving children and families on Medicaid. This short report describes the Early Learning Institute’s approach and preliminary utilization data among Medicaid families. Results suggest the model has potential for dissemination within community settings and promote utilization among Medicaid children. Lay abstract Although research shows early intensive behavioral intervention can be very beneficial for children with autism spectrum disorder when delivered in university or private intervention centers, little is known about the best way to provide early intensive behavioral intervention within the broader community. The Michigan State University Early Learning Institute was developed to address challenges with providing early intensive behavioral intervention in community settings, with an emphasis on serving children and families on Medicaid. This short report describes the approach taken by the Early Learning Institute and reports data regarding enrollment and utilization among Medicaid families. Results suggest the model has potential to be used within community settings and that children on Medicaid are likely to consistently attend their treatment sessions.
Hypogastric Artery Stenting for Chronic Intermittent Spinal Cord Ischemia After Thoracic Endovascular Aortic Repair
Authors: Gronert Catharina , Tsilimparis Nikolaos , Panuccio Giuseppe , Eleshra Ahmed , Rohlffs Fiona , Kölbel Tilo 
Published: May 2020

Purpose: To report a case of chronic intermittent spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) and its successful treatment using hypogastric artery stenting. Case Report: A 79-year-old patient presented in May 2013 with a thoracic aortic aneurysm (TAA) and a contained rupture. He urgently underwent TEVAR that covered 274 mm of descending thoracic aorta without immediate postoperative signs of acute SCI. At 3-month follow-up, he reported repeating incidents of sudden lower extremity weakness leading to a fall with a humerus fracture. A neurological consultation revealed the tentative diagnosis of intermittent SCI caused by TEVAR and initially recommended a conservative approach. During the following year there was no clinical improvement of the symptoms. Computed tomography angiography showed a high-grade stenosis of the right hypogastric artery, which was stented in November 2014 to improve the collateral network of spinal cord perfusion. Following treatment, the patient had no further neurological symptoms; at 32 months after the reintervention, the imaging follow-up documented a patent stent and continued exclusion of the TAA. Conclusion: Intermittent neurological symptoms after TEVAR should be suspected as chronic intermittent SCI. The improvement of collateral networks of the spinal cord by revascularization of the hypogastric artery is a viable treatment option.
Construction of irf4a Transgenic Zebrafish Using Tol2 System and Its Potential Application
Authors: Gou Yawei , Sun Wei , Liu Lingling , Zhang Mingming , Du Jianan , Wang Ruonan , Xu Xuesong 
Published: May 2020

Purpose:Interferon regulatory factor 4 (IRF4) is identified as a transcriptional factor and plays an important role in the immune response in mammals; however, there are few reports about the function of zebrafish IRF4.Methods:We first amplified the coding sequence of irf4a from the testis of zebrafish. Besides, the fragments of irf4a, P2A, EGFP, and Tol2 vector were added for homologous recombination. By sequencing, we can get the Tol2-ef1α-irf4a-EGFP recombinant plasmid and it was microinjected into zebrafish embryos. Fluorescence observation was proceeded at days 3 post fertilization; F0 generations expressing green fluorescence in multiple tissues throughout the body were screened as the founder and raised them to sexual maturity. After mating with WT zebrafish to generate F1 offspring, polymerase chain reaction was used to identify whether irf4a was integrated into the zebrafish genome.Conclusion:We obtained the systematic overexpressed irf4a transgenic zebrafish with green fluorescence labeled in spine, eyes, heart, brain, and other tissues. The transgenic zebrafish will be used as a tool for the role of IRF4a in the immune response to the inflammation preconditioning in the future study.
Admitting Low-Risk Patients With Intracerebral Hemorrhage to a Neurological Step-Down Unit Is Safe, Results in Shorter Length of Stay, and Reduces Intensive Care Utilization: A Retrospective Controlled Cohort Study
Authors: Laws Lindsay , Lee Flavia , Kumar Abhay , Dhar Rajat 
Published: May 2020

Background and Purpose: Patients suffering intracerebral hemorrhage (ICH) are at risk for early neurologic deterioration and are often admitted to intensive care units (ICU) for observation. There is limited data on the safety of admitting low-risk patients with ICH to a non-ICU setting. We hypothesized that admitting such patients to a neurologic step-down unit (SDU) is safe and less resource-intensive. Methods: We performed a retrospective analysis of patients with primary ICH admitted to our SDU. We compared this cohort to a control group of ICH patients admitted to a neurologic-ICU (NICU) at a partner institution. We analyzed patients with supratentorial ICH ≤15 cc, Glasgow Coma Scale ≥ 13, National Institutes of Health Stroke Scale ≤ 10, and no to minimal intraventricular hemorrhage. Primary end points were (re-)admission to an NICU and rates of hematoma expansion (HE). We also compared total NICU days and hospital length of stay (LOS). Results: Eighty patients with ICH were admitted to the SDU. Only 2 required transfer to the NICU for complications related to ICH, including 1 for HE. Seventy-four SDU patients met inclusion criteria and were compared to 58 patients admitted to an NICU. There was no difference in rates of NICU (re-)admission (7 vs 2, P = .17) or rates of HE (3 vs 5, P = .28). Median NICU days were 0 versus 1 ( P < .001). Step-down unit admission was associated with shorter LOS (3 vs 4 days, P = .05). Conclusions: Select patients with ICH can be safely admitted to an SDU. This may reduce LOS and ICU utilization. We also propose criteria for admitting patients with ICH to an SDU.
Alisol B 23-acetate attenuates CKD progression by regulating the renin–angiotensin system and gut–kidney axis
Authors: Chen Hua , Wang Min-Chang , Chen Yuan-Yuan , Chen Lin , Wang Yan-Ni , Vaziri Nosratola D. , Miao Hua , Zhao Ying-Yong 
Published: May 2020

Background: Increasing evidence suggests a link between the gut microbiome and various diseases including hypertension and chronic kidney disease (CKD). However, studies examining the efficacy of controlling blood pressure and inhibiting the renin–angiotensin system (RAS) in preventing CKD progression are limited. Methods: In the present study, we used 5/6 nephrectomised (NX) and unilateral ureteral obstructed (UUO) rat models and cultured renal tubular epithelial cells and fibroblasts to test whether alisol B 23-acetate (ABA) can attenuate renal fibrogenesis by regulating blood pressure and inhibiting RAS. Results: ABA treatment re-established dysbiosis of the gut microbiome, lowered blood pressure, reduced serum creatinine and proteinuria, suppressed expression of RAS constituents and inhibited the epithelial-to-mesenchymal transition in NX rats. Similarly, ABA treatment inhibited expression of collagen I, fibronectin, vimentin, α-smooth muscle actin and fibroblast-specific protein 1 at both mRNA and protein levels in UUO rats. ABA was also effective in suppressing activation of the transforming growth factor-β (TGF-β)/Smad3 and preserving Smad7 expression in both NX and UUO rats. In vitro experiments demonstrated that ABA treatment inhibited the Wnt/β-catenin and mitochondrial-associated caspase pathways. Conclusion: These data suggest that ABA attenuated renal fibrosis through a mechanism associated with re-establishing dysbiosis of the gut microbiome and regulating blood pressure, and Smad7-mediated inhibition of Smad3 phosphorylation. Thus, we demonstrate ABA as a promising candidate for treatment of CKD by improving the gut microbiome and regulating blood pressure.
Mirtazapine for treatment of visual snow syndrome: A case series with insights into pathophysiology and therapy
Authors: Eren Ozan , Schankin Christoph J 
Published: May 2020

Background: Patients with visual snow syndrome (VSS) describe tiny flickering dots in the entire visual field resembling the noise of a poorly adjusted channel of analogue television with additional symptoms. Little is known about the pathophysiology and therapeutic options for this debilitating condition. Objectives: We present a case series of three patients with VSS taking mirtazapine, one of the most often prescribed antidepressants, and discuss the utility of antidepressants by reviewing our current understanding of pathophysiology and therapy. Results: Mirtazapine has no effect on VSS, neither positive nor negative. This is in line with the reports from the literature suggested only some beneficial effects from lamotrigine. Conclusions: Since the pathophysiology of VSS is not fully understood, we still rely on the reports of individual cases or patient series. This includes not only the positive, but also the negative results to avoid unnecessary treatment trials. Looking into the literature, antidepressants do not seem to be a solution for the visual symptoms. So far, best data exists for the anticonvulsant lamotrigine.
Comparison of Diagnostic Accuracy in Vascular Neurology Between Neurology Residents and a Neurology Differential Diagnosis App: A Multi-Center Cross-Sectional Observational Study
Authors: Vinny Pulikottil Wilson , Padma Madakasira Vasantha , Sylaja P. N. , Kesav Praveen , Lal Vivek , Narasimhan Lakshmi , Dwivedi S. N. , Nair Pradeep P. , Iype Thomas , Gupta Anu , Patil Anuja , Vishnu Venugopalan Y. 
Published: May 2020

Background: Diagnostic errors in neurological diagnosis are a source of preventable harm. Software tools like Differential Diagnosis (DDx) apps in neurology that hold the potential to mitigate this harm are conspicuously lacking. Materials and Methods: A multicenter cross-sectional observational study was designed to compare the diagnostic accuracy of a Neurology DDx App (Neurology Dx) with neurology residents by using vascular neurology clinical vignettes. The study was conducted at 7 leading neurology institutes in India. Study participants comprised of 100 neurology residents from the participating institutes. Measurements: Detecting diagnostic accuracy of residents and App measured as a proportion of correctly identified high likely gold standard DDx was prespecified as the main outcome. Proportions of correctly identified first high likely, first 3 high likely, first 5 high likely, and combined moderate plus high likely gold standard differentials by residents and App were secondary outcomes. Results: 1,000 vignettes were attempted by residents. Frequency of gold standard, high likely differentials correctly identified by residents was 27% compared to 72% by App (absolute difference 45%, 95% CI 35.7-52.8). When high and moderate likely differentials were combined, residents scored 17% compared to 57% by App (absolute difference 40%, 95% CI 33.8-50.0). Residents correctly identified first high likely gold standard differential as their first high likely differential in 34% compared to 18% by App (absolute difference 16%, 95% CI 1.2-25.4). Conclusion: App with predefined knowledge base can complement clinical reasoning of neurology residents. Portability and functionality of such Apps may further strengthen this symbiosis between humans and algorithms (CTRI/2017/06/008838).
Search for multiple myeloma risk factors using Mendelian randomization
Authors: Went Molly , Cornish Alex J. , Law Philip J. , Kinnersley Ben , van Duin Mark , Weinhold Niels , Försti Asta , Hansson Markus , Sonneveld Pieter , Goldschmidt Hartmut , Morgan Gareth J. , Hemminki Kari , Nilsson Björn , Kaiser Martin , Houlston Richard S. 
Published: May 2020

AbstractThe etiology of multiple myeloma (MM) is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited in a Mendelian randomization (MR) phenome-wide association study (PheWAS) to search for factors influencing MM risk. We performed an MR-PheWAS analyzing 249 phenotypes, proxied by 10 225 genetic variants, and summary genetic data from a GWAS of 7717 MM cases and 29 304 controls. Odds ratios (ORs) per 1 standard deviation increase in each phenotype were estimated under an inverse variance weighted random effects model. A Bonferroni-corrected threshold of P = 2 × 10−4 was considered significant, whereas P &lt; .05 was considered suggestive of an association. Although no significant associations with MM risk were observed among the 249 phenotypes, 28 phenotypes showed evidence suggestive of association, including increased levels of serum vitamin B6 and blood carnitine (P = 1.1 × 10−3) with greater MM risk and ω-3 fatty acids (P = 5.4 × 10−4) with reduced MM risk. A suggestive association between increased telomere length and reduced MM risk was also noted; however, this association was primarily driven by the previously identified risk variant rs10936599 at 3q26 (TERC). Although not statistically significant, increased body mass index was associated with increased risk (OR, 1.10; 95% confidence interval, 0.99-1.22), supporting findings from a previous meta-analysis of prospective observational studies. Our study did not provide evidence supporting any modifiable factors examined as having a major influence on MM risk; however, it provides insight into factors for which the evidence has previously been mixed.
Prolonged lenalidomide maintenance therapy improves the depth of response in multiple myeloma
Authors: Alonso Rafael , Cedena María-Teresa , Wong Sandy , Shah Nina , Ríos-Tamayo Rafael , Moraleda José M. , López-Jiménez Javier , García Cristina , Bahri Natasha , Valeri Antonio , Sánchez Ricardo , Collado-Yurrita Luis , Martin Thomas , Wolf Jeffrey , Lahuerta Juan-José , Martínez-López Joaquín 
Published: May 2020

Abstract
Lenalidomide is an immunomodulatory drug approved for maintenance treatment in newly diagnosed multiple myeloma, and it has been shown to improve progression-free survival (PFS) and, in several studies, overall survival. Nevertheless, the impact of prolonged treatment with lenalidomide on the kinetics of minimal residual disease (MRD) and its prognostic impact have not been studied in depth. To obtain better knowledge in this regard, we retrospectively analyzed 139 patients who received lenalidomide maintenance in real-world clinical practice and whose MRD levels were observed during the treatment period by multiparametric flow cytometry or next-generation sequencing with a sensitivity of at least 10−4. Lenalidomide maintenance correlated with an increased depth of the disease response, with 38.1% of patients achieving maximal response during maintenance. Moreover, 34.3% of patients who were MRD positive after induction treatment achieved MRD-negative status during maintenance and ultimately had improved PFS. Sequential MRD assessments identified patients with progressively decreasing MRD levels who also had better PFS outcomes, compared with patients not showing a decreasing pattern of MRD. These results support the role of maintenance therapy, not only to sustain, but also to increase the depth of disease response with a PFS benefit. In addition, MRD monitoring during maintenance identifies patients with better prognosis and may help in their clinical management.
Competitive tight-binding inhibition of VKORC1 underlies warfarin dosage variation and antidotal efficacy
Authors: Li Shuang , Liu Shixuan , Liu Xiaoran Roger , Zhang Mengru Mira , Li Weikai 
Published: May 2020

AbstractDose control of warfarin is a major complication in anticoagulation therapy and overdose is reversed by the vitamin K antidote. Improving the dosage management and antidotal efficacy requires mechanistic understanding. Here we find that effects of the major predictor of warfarin dosage, SNP −1639 G&gt;A, follow a general correlation that warfarin 50% inhibitory concentration decreases with cellular level of vitamin K epoxide reductase (VKORC1), suggesting stoichiometric inhibition. Characterization of the inhibition kinetics required the use of microsomal VKORC1 with a native reductant, glutathione, that enables effective warfarin inhibition in vitro. The kinetics data can be fitted with the Morrison equation, giving a nanomolar inhibition constant and demonstrating that warfarin is a tight-binding inhibitor. However, warfarin is released from purified VKORC1-warfarin complex with increasing amount of vitamin K, indicating competitive inhibition. The competition occurs also in cells, resulting in rescued VKORC1 activity that augments the antidotal effects of vitamin K. Taken together, warfarin is a competitive inhibitor that binds VKORC1 tightly and inhibits at a stoichiometric (1:1) concentration, whereas exceeding the VKORC1 level results in warfarin overdose. Thus, warfarin dosage control should use VKORC1 level as a major indicator, and improved antidotes may be designed based on their competition with warfarin.
Impacts of local population history and ecology on the evolution of a globally dispersed pathogen
Authors: Castillo Andreina I. , Chacón-Díaz Carlos , Rodríguez-Murillo Neysa , Coletta-Filho Helvecio D. , Almeida Rodrigo P. P. 
Published: May 2020

AbstractBackgroundPathogens with a global distribution face diverse biotic and abiotic conditions across populations. Moreover, the ecological and evolutionary history of each population is unique.Xylella fastidiosais a xylem-dwelling bacterium infecting multiple plant hosts, often with detrimental effects. As a group,X. fastidiosais divided into distinct subspecies with allopatric historical distributions and patterns of multiple introductions from numerous source populations. The capacity ofX. fastidiosato successfully colonize and cause disease in naïve plant hosts varies among subspecies, and potentially, among populations. Within Central America (i.e. Costa Rica) twoX. fastidiosasubspecies coexist: the native subsp.fastidiosaand the introduced subsp.pauca. Using whole genome sequences, the patterns of gene gain/loss, genomic introgression, and genetic diversity were characterized within Costa Rica and contrasted to otherX. fastidiosapopulations.ResultsWithin Costa Rica, accessory and core genome analyses showed a highly malleable genome with numerous intra- and inter-subspecific gain/loss events. Likewise, variable levels of inter-subspecific introgression were found within and between both coexisting subspecies; nonetheless, the direction of donor/recipient subspecies to the recombinant segments varied. Some strains appeared to recombine more frequently than others; however, no group of genes or gene functions were overrepresented within recombinant segments. Finally, the patterns of genetic diversity of subsp.fastidiosain Costa Rica were consistent with those of other native populations (i.e. subsp.paucain Brazil).ConclusionsOverall, this study shows the importance of characterizing local evolutionary and ecological history in the context of world-wide pathogen distribution.