Association of type II Waardenburg syndrome with hypermetropic amblyopia

We present a case of hypermetropic amblyopia in type II Waardenburg syndrome (WS) to highlight the association. WS is an “oculo-dermato-auditif” dysplasia described in 1947 by Waardenburg and by Klein in 1950. It is distributed worldwide, with no predilection for race or gender. The prevalence is estimated to be 1:42 000 live births in the general population. WS is a genetic disease with autosomal dominant transmission with incomplete penetrance and variable expressivity. Complex network of interaction between six genes have been identified to date. They are PAX3 gene, primarily responsible for type I and III WS; MITF, SOX10, and SNAI2 genes in type II WS; EDN3 and EDNRB genes in type IV WS

Case report: Outer lamellar macular hole and outer retinal detachment within myopic foveoschisis post-cataract surgery

BackgroundThis study aimed to report a case of outer lamellar macular hole and outer retinal detachment within myopic foveoschisis (MF) post-cataract surgery.Case presentationAn elderly female patient with bilateral high myopia and pre-existing myopic foveoschisis underwent uncomplicated sequential cataract surgeries 2 weeks apart. She was able to achieve a satisfactory visual outcome for her left eye with stable myopic foveoschisis and visual acuity of 6/7.5, near vision N6. However, her right eye vision remained poor postoperatively, with a visual acuity of 6/60. Macular optical coherence tomography (OCT) revealed a new right eye outer lamellar macular hole (OLMH) and outer retinal detachment (ORD) within pre-existing myopic foveoschisis. Her vision remained poor after 3 weeks of conservative management, and she was offered vitreoretinal surgical intervention with pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. However, she refused surgical intervention, and her right vision remained stable at 6/60 over 3 months of follow-up.ConclusionOuter lamellar macular hole and outer retinal detachment within myopic foveoschisis can occur soon after cataract surgery, which may be related to the progression of associated vitreomacular traction, and have a poor visual outcome if left untreated. Patients with high myopia should be informed of these complications as part of pre-operative counseling

Genome-Wide Association Study of Lung Adenocarcinoma in East Asia and Comparison With a European Population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Plasma-implanted Ti-doped hematite photoanodes with enhanced photoelectrochemical water oxidation performance

Hematite (α-Fe2O3) is recognized as a promising photoelectrode material for photoelectrochemical (PEC) water splitting, as a result of its abundance, non-toxicity, suitable bandgap, and photochemical stability. Nevertheless, the undesirable physical and photophysical behaviors, such as poor conductivity, short diffusion length, and rapid charge-carrier recombination, seriously restrict PEC water splitting efficiency of hematite semiconductors. Herein, we fabricate nanoporous titanium (Ti)-doped α-Fe2O3 thin films by a facile hydrothermal reaction, subsequently utilizing energetic plasma ion implantation with a post-annealing process to significantly enhance the photoelectrochemical water oxidation performance of hematite. On the basis of materials characterization and electrochemical analysis, the optimized Ti-doped Fe2O3, i.e., Ti-4-Fe2O3, exhibits improved photocurrents of 0.55 and 1.07 mA cm−2 at 1.23 and 1.5 V versus RHE respectively under illumination of 100 mW/cm2 with AM 1.5 G spectrum, showing approximately 1.6-fold increases compared to pristine Fe2O3. We attribute this increase to improved charge carrier transport induced by Ti doping that reduces the recombination of light-driven charge carriers. The work utilizing plasma-assisted doping technique provides new insights into the surface engineering of photo-responsive semiconductors for the development of emerging hydrogen technologie

Chemically derived graphene-metal oxide hybrids as electrodes for electrochemical energy storage: pre-graphenization or post-graphenization?

The introduction of a secondary phase is an efficient and effective way to improve the electrochemical performance of graphene towards energy storage applications. Two fundamental strategies including pre-graphenization and post-graphenization were widely employed for graphene-based hybrids. However, there is still an open question of which way is better. In this contribution, we investigated the differences in the structure and electrochemical properties of pre- and post-graphenized graphene-SnO2 hybrids. The pre-graphenization is realized by synthesis of thermally reduced graphene and subsequent impregnation of SnO2, while the post-graphenization is realized by introducing a Sn-containing phase onto GO sheets followed by chemical reduction. The pre-graphenization process provides a large amount of pores for ion diffusion, which is of benefit for loading of SnO2, fast ion diffusion for supercapacitors, and higher capacity for Li-ion batteries, but poor stability, while the post-graphenization process offers compact graphene and good interaction between the SnO2 and graphene, which provides stable structure for long term stability for supercapacitor and Li-ion battery use

Retinal changes and cardiac biomarker assessment in relation to chronic kidney disease: a single centre study

Background The prevalence of chronic kidney disease (CKD) is rising in Malaysia. Early detection is necessary to prevent disease progression, especially in terms of cardiovascular (CV) risk, the main cause of death in end-stage renal disease (ESRD). Retinal changes have proven to be a good predictor of CKD whereas cardiac biomarkers are useful in cardiovascular risk stratification. We aimed to demonstrate the correlation between retinal changes and cardiac biomarkers with CKD. Methods This single-centre cross-sectional study was conducted among patients with CKD stages 3, 4, and 5 (not on dialysis) from the Nephrology Clinic, Universiti Kebangsaan Malaysia Medical Centre. A total of 84 patients were recruited with an even distribution across all three stages. They underwent fundus photography where images were analysed for vessel calibre (central retinal venular equivalent (CRVE), central retinal arterial equivalent (CRAE), and tortuosity indices. Optical coherence tomography was used to measure macular volume. Blood samples were sent for laboratory measurement of high-sensitivity C-reactive protein (hs-CRP) and asymmetric dimethylarginine (ADMA). These parameters were analysed in relation to CKD. Results The mean age was 58.8 ± 11.7 years, with 52.4% male and 47.6% female patients. Among them, 64.3% were diabetics. Retinal vessel tortuosity (r = -0.220, p-value = 0.044) had a negative correlation with the estimated glomerular filtration rate (eGFR). CRVE showed a positive correlation with proteinuria (r = 0.342, p = 0.001) but negative correlation with eGFR (r = -0.236, p = 0.031). Hs-CRP positively correlated with proteinuria (r = 0.313, p = 0.04) and negatively correlated with eGFR (r = -0.370, p = 0.001). Diabetic patients had a higher CRVE compared to non-diabetic patients (p = 0.02). History of ischaemic heart disease was associated with a smaller macula volume (p = 0.038). Male gender (r2 = 0.066, p = 0.031) and HbA1c had a positive influence (r2 = 0.066, p = 0.047) on retinal vessel tortuosity. There was a positive influence of age (r2 = 0.183, p = 0.012) and hs-CRP (r2 = 0.183, p = 0.045) on CRVE. As for macula volume, it negatively correlated with diabetes (r2 = 0.015, p = 0.040) and positively correlated with smoking (r2 = 0.015, p = 0.012). Conclusion Our study showed that eGFR value affects retinal vessel tortuosity, CRVE and hs-CRP. These parameters bear potential to be used as non-invasive tools in assessing CKD. However, only macula volume may be associated with CVD risk among the CKD population