Hitting the refractive target in corneal endothelial transplantation triple procedures: A systematic review

In phakic patients Descemet stripping automated endothelial keratoplasty (DSAEK) or Descemet membrane endothelial keratoplasty (DMEK) are frequently combined with phacoemulsification and intraocular lens (IOL) implantation (triple procedure). This surgery might cause a refractive shift difficult to predict. Early DMEK and DSAEK results have shown a tendency toward a hyperopic shift. Myopic postoperative refraction is typically intended to correct this postoperative refractive defect and to bring all eyes as close to emmetropia as possible. We sought to understand the mechanism underlying the hyperopization and to identify predictive factors for poorer refractive outcomes, the most suitable target refraction and IOL calculation methods in patients undergoing combined cataract extraction and lamellar endothelial corneal transplantation (DSAEK or DMEK) for endothelial dysfunctions. Of the 407 articles analyzed, only 18 were included in the analysis. A myopic target between -0.50 D and -0.75 was the most common (up to -1.50 for DSAEK triple procedures), even though no optimum target was found. Hyperopic surprises appeared more frequently in corneas that were flatter in the center than in the periphery (oblate posterior profile). Among the numerous IOL calculation formulas, there was no apparent preference

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Development of a New Wearable 3D Sensor Node and Innovative Open Classification System for Dairy Cows' Behavior

Simple Summary In order to keep dairy cows under satisfactory health and welfare conditions, it is very important to monitor the animals in their living environment. With the support of technology, and, in particular, with the installation of sensors on neck-collars, cow behavior can be adequately monitored, and different behavioral patterns can be classified. In this study, an open and customizable device has been developed to classify the behaviors of dairy cows. The device communicates with a mobile application via Bluetooth to acquire raw data from behavioral observations and via an ad hoc radio channel to send the data from the device to the gateway. After observing 32 cows on 3 farms for a total of 108 h, several machine learning algorithms were trained to classify their behaviors. The decision tree algorithm was found to be the best compromise between complexity and accuracy to classify standing, lying, eating, and ruminating. The open nature of the system enables the addition of other functions (e.g., localization) and the integration with other information sources, e.g., climatic sensors, to provide a more complete picture of cow health and welfare in the barn. Monitoring dairy cattle behavior can improve the detection of health and welfare issues for early interventions. Often commercial sensors do not provide researchers with sufficient raw and open data; therefore, the aim of this study was to develop an open and customizable system to classify cattle behaviors. A 3D accelerometer device and host-board (i.e., sensor node) were embedded in a case and fixed on a dairy cow collar. It was developed to work in two modes: (1) acquisition mode, where a mobile application supported the raw data collection during observations; and (2) operating mode, where data was processed and sent to a gateway and on the cloud. Accelerations were sampled at 25 Hz and behaviors were classified in 10-min windows. Several algorithms were trained with the 108 h of behavioral data acquired from 32 cows on 3 farms, and after evaluating their computational/memory complexity and accuracy, the Decision Tree algorithm was selected. This model detected standing, lying, eating, and ruminating with an average accuracy of 85.12%. The open nature of this system enables for the addition of other functions (e.g., real-time localization of cows) and the integration with other information sources, e.g., microenvironment and air quality sensors, thereby enhancing data processing potential

Reproducibility and Reliability of Spectralis II OCT Angiography Vascular Measurements

Purpose: to investigate the reproducibility and reliability of OCT-A vascular measurements using Heidelberg Spectralis II OCT-A. Methods: a prospective study involving a single eye of patients aged 18 or older with no ocular disease. In order to investigate the reliability of the first and second OCT-A scans, the coefficient of variation of the foveal avascular zone (FAZ) and the vessel density (VD) in the superficial (SCP), intermediate (ICP) and deep capillary plexus (DCP) were calculated. Results: A total of 75 eyes were included in the study. The mean FAZ in the first and second scan was 0.36 × 0.13 mm2 and 0.37 × 0.12 mm2, respectively, in the SCP, 0.23 × 0.10 mm2 and 0.23 × 0.09 mm2 in the ICP, and 0.42 × 0.11 mm2 and 0.43 × 0.12 mm2 in the DCP. The overall VD was 36.05 × 9.01 and 35.33 × 9.92 at the first and second scan, respectively, in the SCP, 21.87 × 5.00 and 21.32 × 5.56 in the ICP, and 23.84 × 6.53 and 23.20 × 6.83 in the DCP. No statistically significant differences in FAZ measurements and VD in all sectors of each capillary plexus were observed between the first and second scan (p > 0.05). Conclusion: our study demonstrated the good reproducibility and reliability of OCT-A vascular measurements in the analysis of the FAZ and the quantification of VD in each capillary plexus of the retina

GNE-related thrombocytopenia: evidence for a mutational hotspot in the ADP/substrate domain of the GNE bifunctional enzyme

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KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C

Natural killer (NK) cells play pivotal roles in immune responses against infection with viruses, such as hepatitis C virus (HCV), and killer cell immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells. The aim of this study was to investigate the possibility that KIR genes and their human leukocyte antigen (HLA) ligands influence progression to cirrhosis in patients infected with genotype 1 of HCV. A total of 145 Brazilian patients with confirmed chronic hepatitis C grouped from F0 to F4 according to fibrosis progression to cirrhosis were evaluated. Genotyping of KIR and HLA genes was performed by polymerase chain reaction with sequence-specific oligonucleotide probes. The HLA-C2 KIR ligand was more frequent in patients than in healthy controls (74.5% vs 64.3%, p = 0.04, odds ratio (OR) = 1.6, 95% confidence interval (Cl) = 1.03-2.52). Moreover, the HLA-C1C2 genotype was more frequent in patients with advanced fibrosis or cirrhosis (F3-F4 group) than in patients in the F0-F2 group (61.6% vs 44.7%, p = 0.06) and in the F4 group compared with the F0-F3 group (65.7% vs 46.7%, p = 0.05, OR = 2.19, 95% CI = 1.01-4.73). NK and KIR ligands may contribute to the development of liver damage in patients chronically infected by HCV. (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

GNE-related thrombocytopenia:evidence for a mutational hotspot in the ADP/substrate domain of the GNE bifunctional enzyme.

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Integrative Analysis of the Ethanol Tolerance of Saccharomyces cerevisiae.

Ethanol (EtOH) alters many cellular processes in yeast. An integrated view of different EtOH-tolerant phenotypes and their long noncoding RNAs (lncRNAs) is not yet available. Here, large-scale data integration showed the core EtOH-responsive pathways, lncRNAs, and triggers of higher (HT) and lower (LT) EtOH-tolerant phenotypes. LncRNAs act in a strain-specific manner in the EtOH stress response. Network and omics analyses revealed that cells prepare for stress relief by favoring activation of life-essential systems. Therefore, longevity, peroxisomal, energy, lipid, and RNA/protein metabolisms are the core processes that drive EtOH tolerance. By integrating omics, network analysis, and several other experiments, we showed how the HT and LT phenotypes may arise: (1) the divergence occurs after cell signaling reaches the longevity and peroxisomal pathways, with CTA1 and ROS playing key roles; (2) signals reaching essential ribosomal and RNA pathways via SUI2 enhance the divergence; (3) specific lipid metabolism pathways also act on phenotype-specific profiles; (4) HTs take greater advantage of degradation and membraneless structures to cope with EtOH stress; and (5) our EtOH stress-buffering model suggests that diauxic shift drives EtOH buffering through an energy burst, mainly in HTs. Finally, critical genes, pathways, and the first models including lncRNAs to describe nuances of EtOH tolerance are reported here