Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Charge transport in phthalocyanine thin-film transistors coupled with Fabry-Perot cavities

Strong light-matter coupling can form hybrid states at new energy levels that share properties of both light and matter. This principle offers new routes to control material functions without modifying the chemical structure of molecules. In this work, we coupled ambipolar semiconducting thin films to a Fabry-Perot cavity and investigated effects on charge transport. By constructing thin-film transistors inside optical cavities, we could simultaneously study coupling features and charge transport in the same samples. The cavity resonance was detuned by controlling the thickness of the top spacer layer in the cavity. We found no significant influence on charge transport for our systems, which may be related to insufficiently strong coupling. Possible additional origins and future directions are also discussed

Strong Plasmon–Exciton Coupling with Directional Absorption Features in Optically Thin Hybrid Nanohole Metasurfaces

Plasmons and excitons can interact to form new hybridized light–matter states, with a multitude of potential applications including optical logic circuits and single-photon switches. Here, we report the first observation of strong coupling based on optically thin plasmonic nanohole films. The absorptive plasmon resonances of these nanohole films lead to suppressed transmission and Fano-shaped extinction peaks. We prepared silver nanohole films by colloidal lithography, which enables large-scale fabrication of nanoholes distributed in a short-range order. When coated with J-aggregate molecules, both extinction and absorption spectra show clear formation of two separated polariton resonances, with vacuum Rabi splitting on the order of 300 meV determined from anticrossing experiments. In accordance with strong coupling theory, the splitting magnitude increases linearly with the square root of molecular concentration. The extinction peak positions are blue-shifted from the absorption polariton positions, as explained by additional Fano interference between the hybridized states and the metal film. This highlights that absorption measurements are important not only to prove strong coupling but also to correctly determine hybridized polariton positions and splitting magnitudes in hybrid plasmonic nanohole systems. The polariton absorption peaks also show strong dependence on illumination direction, as found related to inherent directionality of the plasmonic nanohole metasurface and differences in light interaction with nonhybridized molecules. Importantly, optical simulations could successfully reproduce the experimental results and all coupling features. Furthermore, simulated spatial distribution of the absorption provides additional evidence of strong coupling in the hybrid nanohole system. The work paves the way toward strong coupling applications based on optically thin nanohole systems, as further promoted by the scalable fabrication.Funding agencies: Wenner-Gren Foundations; Swedish Research Council; Swedish Foundation for Strategic Research; AForsk Foundation; Royal Swedish Academy of Sciences; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping Univer</p

Strengthening urban primary healthcare service delivery using electronic health technologies: A qualitative study in urban Nepal

Background Nepal is a South Asian country with a high burden of non-communicable diseases. Electronic health technologies are a promising strategy to mitigate the rising burden of non-communicable diseases by strengthening primary healthcare center service delivery. However, electronic health implementation in Nepal is limited. Furthermore, electronic health use at the primary healthcare center level is chronically understudied. This qualitative study seeks to understand the perceived awareness, benefits, and determinants of electronic health uptake in Nepal, focusing on primary healthcare center-level non-communicable disease management. Methods We conducted in-depth interviews with 27 participants including policymakers, health experts, facility administrators, providers, and non-communicable diseases patients in 2019. We selected six urban primary healthcare center facilities via cluster convenience sampling for recruiting facility administrators, providers, and patients, and used convenience sampling to recruit policymakers and experts. We conducted thematic data analysis inductively and deductively using the electronic health readiness assessment framework to understand perceived barriers and facilitators of electronic health implementation. Results While there was general awareness and acceptance of electronic health, multiple barriers impede readiness for implementation. These include policy making gaps, language barriers, low user technical literacy, concerns of overreliance on technology, and inadequate training for administrators and providers. Stakeholder suggestions include creating electronic health interfaces that meet the needs of end users (providers and patients), providing training to enable end users to effectively use electronic health technologies, and strong policy support at the national level. Conclusion We identify several determinants for effectively promoting the use of electronic health for non-communicable diseases service delivery at the primary healthcare center level in Nepal