Trends in Healthcare Service Disruptions and Associations with COVID-19 Outcomes among Patients with SMI vs. Non-SMI during COVID-19.

Objective: The study aims to quantify differential changes in outpatient mental health service utilization among 3,724,348 individuals, contrasting those with Severe Mental Illness (SMI) to those without, in the context of the COVID-19 pandemic. Design & Setting: A retrospective cohort study was conducted, utilizing data from Healthix, the second-largest health information exchange in the U.S. Participants: The study population included 3,134,959 Non-SMI patients (84.2%), 355,397 SMI patients (9.5%), and 149,345 Recurrent SMI Patients (4.0%). Exposures: The primary exposure was the COVID-19 pandemic, with a focus on its impact on outpatient mental health services. Main Outcomes and Measures: The primary outcome was the rate of utilization of outpatient mental health services. Secondary outcomes included COVID-19 infection rates and vaccination rates among the study cohorts. Results: Among the non-SMI patients, there was a 30% decline in emergency visits from 650,000 pre-COVID to 455,000 post-COVID (OR=0.70, p < 0.001), and outpatient visits decreased by 50% from 1.2 million to 600,000 (OR=0.50, p = 0.002). In contrast, the SMI group witnessed a 20% reduction in outpatient visits from 120,000 to 96,000 (OR=0.80, p = 0.015) and a 40% decrease in inpatient visits from 50,000 to 30,000 (OR=0.60, p = 0.008). Recurrent SMI patients exhibited a 25% decline in emergency visits from 32,000 to 24,000 (OR=0.75, p = 0.03) and a 35% drop in outpatient visits from 40,000 to 26,000 (OR=0.65, p = 0.009).The pandemic influenced the type of disorders diagnosed. Non-SMI patients experienced a 23% rise in anxiety-related disorders (n=80,000, OR=1.23, p = 0.01) and an 18% increase in stress-related disorders (n=70,000, OR=1.18, p = 0.04). SMI patients had a 15% surge in severe anxiety disorders (n=9,000, OR=1.15, p = 0.02) and a 12% uptick in substance-related disorders (n=7,200, OR=1.12, p = 0.05). Recurrent SMI patients showed a 20% increase in anxiety and adjustment disorders (n=6,400, OR=1.20, p = 0.03).SMI patients were more adversely affected by COVID-19, with a higher infection rate of 7.8% (n=45,972) compared to 4.2% (n=131,669) in non-SMI patients (OR=1.88, p < 0.001). Hospitalization rates also followed this trend, with 5.2% (n=30,648) of SMI patients being hospitalized compared to 3.7% (n=115,995) among non-SMI patients (OR=1.41, p = 0.007). Moreover, SMI patients had lower vaccination rates of 45.6% (n=268,888) versus 58.9% (n=1,844,261) among non-SMI patients (OR=0.77, p = 0.019). Conclusions: In conclusion, our findings reveal significant disparities in healthcare service utilization between individuals with Serious Mental Illness (SMI) and those without. Notably, the SMI cohort experienced greater disruptions in service continuity, with a more pronounced decline in both outpatient and inpatient visits. Furthermore, the types of disorders diagnosed among this group also saw a shift, emphasizing the need for specialized care and attention during times of crisis. The higher rates of COVID-19 infection and hospitalization among SMI patients compared to non-SMI patients underscore the urgency of targeted public health interventions for this vulnerable group. The lower vaccination rates in the SMI cohort highlight another layer of healthcare disparity that needs to be urgently addressed. These findings suggest that the pandemic has amplified pre-existing inequalities in healthcare access and outcomes for individuals with SMI, calling for immediate, evidence-based interventions to mitigate these effects and ensure equitable healthcare service provision.

Reference genes selection for expression studies in Maconellicoccus hirsutus (Green) (Pseudococcidae: Hemiptera) under specific experimental conditions.

BACKGROUND: Maconellicoccus hirsutus is a destructive pest which causes severe losses of agricultural and horticultural crops. For the management of M. hirsutus, many insecticides have been used and it has been exposed to insufficient dosage or uneven spray coverage which resulted in the development of insecticide resistance. Xenobiotic metabolism can be better understood with the help of gene expression studies by unveiling the underlying molecular mechanisms. The qRT-PCR is the simplest method to analyse gene expression, however, it highly relies on suitable reference genes concerning the different experimental conditions. METHODS AND RESULTS: We evaluated the stability of five reference genes in two sets of experimental conditions viz. developmental stages (nymphs and adults) and agrochemical stress (GA3 and Buprofezin sprayed) against M. hirsutus, using different softwares-NormFinder, geNorm, BestKeeper, and RefFinder. The study revealed that ATP51a and GAPDH can be used as reference genes for gene expression studies when exposed to Gibberellic acid. Additionally, the study revealed that the ideal pair of reference genes for data validation in M. hirsutus treated with Buprofezin was GAPDH and ß-tubulin. The ideal reference gene combination for various developmental stages was found to be 28S and Actin. CONCLUSION: According to the study, GAPDH can be utilized as a reliable reference gene in the agrochemical (GA3 and Buprofezin) exposure set. The genes can be utilized as a suitable reference for qRT-PCR gene expression studies of xenobiotic metabolism to understand the underlying molecular mechanism, which will help further to design suitable management strategies.

Characterizing variability of electronic health record-driven phenotype definitions.

OBJECTIVE: The aim of this study was to analyze a publicly available sample of rule-based phenotype definitions to characterize and evaluate the variability of logical constructs used. MATERIALS AND METHODS: A sample of 33 preexisting phenotype definitions used in research that are represented using Fast Healthcare Interoperability Resources and Clinical Quality Language (CQL) was analyzed using automated analysis of the computable representation of the CQL libraries. RESULTS: Most of the phenotype definitions include narrative descriptions and flowcharts, while few provide pseudocode or executable artifacts. Most use 4 or fewer medical terminologies. The number of codes used ranges from 5 to 6865, and value sets from 1 to 19. We found that the most common expressions used were literal, data, and logical expressions. Aggregate and arithmetic expressions are the least common. Expression depth ranges from 4 to 27. DISCUSSION: Despite the range of conditions, we found that all of the phenotype definitions consisted of logical criteria, representing both clinical and operational logic, and tabular data, consisting of codes from standard terminologies and keywords for natural language processing. The total number and variety of expressions are low, which may be to simplify implementation, or authors may limit complexity due to data availability constraints. CONCLUSIONS: The phenotype definitions analyzed show significant variation in specific logical, arithmetic, and other operators but are all composed of the same high-level components, namely tabular data and logical expressions. A standard representation for phenotype definitions should support these formats and be modular to support localization and shared logic.

Comparative Transcriptome Analysis to Reveal Differentially Expressed Cytochrome P450 in Response to Imidacloprid in the Aphid Lion, Chrysoperla zastrowi sillemi (Esben-Petersen).

The aphid lion, Chrysoperla zastrowi sillemi (Neuroptera: Chrysopidae) is a highly effective beneficial predator of many agricultural pests and has developed resistance to several insecticides. Understanding the molecular mechanism of insecticide resistance in the predators is crucial for its effective application in IPM programs. Therefore, transcriptomes of imidacloprid-resistant and susceptible strains have been assessed using RNA-seq. Cytochrome P450 is one of the important gene families involved in xenobiotic metabolism. Hence, our study focused on the CYP gene family where mining, nomenclature, and phylogenetic analysis revealed a total of 95 unique CYP genes with considerable expansion in CYP3 and CYP4 clans. Further, differential gene expression (DGE) analysis revealed ten CYP genes from CYP3 and CYP4 clans to be differentially expressed, out of which nine genes (CYP4419A1, CYP4XK1, CYP4416A10, CYP4416A-fragment8, CYP6YL1, CYP6YH6, CYP9GK-fragment16, CYP9GN2, CYP9GK6) were downregulated and one (CYP9GK3) was upregulated in the resistant strain as compared to the susceptible strain. Expression validation by quantitative real-time PCR (qRT-PCR) is consistent with the DGE results. The expansion and differential expression of CYP genes may be an indicator of the capacity of the predator to detoxify a particular group of insecticides.

Deciphering the Molecular Mechanisms of Insecticide Resistance From the Transcriptome Data of Field Evolved Spinosad Resistant and Susceptible Populations of Plutella xylostella (Lepidoptera: Plutellidae).

Diamondback moth, Plutella xylostella is a serious pest of cruciferous vegetables and causes substantial economic loss all over the world. This study was undertaken to decipher the molecular mechanisms involved in the field evolved insecticide resistance in P. xylostella upon exposure to spinosad. To do so, spinosad-resistant and susceptible larval populations were subjected to transcriptome analysis using Illumina paired-end sequencing. De novo assembly was generated from raw reads of both the samples which resulted in the identification of 41,205 unigenes. Functional annotation and digital gene expression analysis were carried out to determine the differentially expressed genes. 1,348 unigenes were found to have a significant differential expression in the resistant population. Several genes involved in insecticide resistance like CYP P450, GSTs, small heat shock protein, and UDP glycosyltransferase were found to be up-regulated while genes related to mitochondrial energy metabolism and cuticular processes were down-regulated. Further, gene mining and phylogenetic analysis of two important gene families namely, CYP and GSTs were performed and the results revealed that these genes could play a major role in the development of field evolved spinosad resistance in P. xylostella by gene duplication and differential gene expression.

Insights of Lr28 mediated wheat leaf rust resistance: Transcriptomic approach.

Leaf rust is a fungal disease that causes severe yield losses in wheat. Resistant varieties with major and quantitative resistance genes are the most effective method to control the disease. However, the main problem is inadequate information for understanding resistance mechanism and its usefulness. This paper presents Lr28 mediated genome-wide response of known and unknown genes during wheat-Puccinia triticina interaction. In this study, we prepared Serial Analysis of Gene Expression (SAGE) libraries using seedling wheat mRNA for infected and mock conditions. The libraries were sequenced on Sequencing by Oligonucleotide Ligation and Detection (SOLiD) system generating 37-48 million reads. After mapping and gene expression analysis of ~6-12 million trimmed reads/library, we revealed five major categories comprised of Lr28 controlled transcripts in resistant (+Lr28) isoline (39), transcripts specific to susceptible (-Lr28) isoline (785), transcripts specific to hypersensitive-response (HR) (375), transcripts specific for basal-defense (153) and transcripts for establishment of pathogen (1616). We estimated the impact of specific genes and pathways through mapping on plant resistant gene database (PRGdb), reactive oxygen species (ROS) and phytohormone database. Functional annotation results revealed, receptor binding, homeostatic processes and cytoskeletal components as the major discriminating factors between susceptibility and resistance. We validated 28 key genes using qRT-PCR and found positive results. These findings were projected on hypothetical interaction model to demonstrate interaction mechanism. The study might have significant impact on future rust-resistance breeding through knowledge based smart genetic selection of quantitative resistance genes besides major effect R-gene.

De Novo Assembled Wheat Transcriptomes Delineate Differentially Expressed Host Genes in Response to Leaf Rust Infection.

Pathogens like Puccinia triticina, the causal organism for leaf rust, extensively damages wheat production. The interaction at molecular level between wheat and the pathogen is complex and less explored. The pathogen induced response was characterized using mock- or pathogen inoculated near-isogenic wheat lines (with or without seedling leaf rust resistance gene Lr28). Four Serial Analysis of Gene Expression libraries were prepared from mock- and pathogen inoculated plants and were subjected to Sequencing by Oligonucleotide Ligation and Detection, which generated a total of 165,767,777 reads, each 35 bases long. The reads were processed and multiple k-mers were attempted for de novo transcript assembly; 22 k-mers showed the best results. Altogether 21,345 contigs were generated and functionally characterized by gene ontology annotation, mining for transcription factors and resistance genes. Expression analysis among the four libraries showed extensive alterations in the transcriptome in response to pathogen infection, reflecting reorganizations in major biological processes and metabolic pathways. Role of auxin in determining pathogenesis in susceptible and resistant lines were imperative. The qPCR expression study of four LRR-RLK (Leucine-rich repeat receptor-like protein kinases) genes showed higher expression at 24 hrs after inoculation with pathogen. In summary, the conceptual model of induced resistance in wheat contributes insights on defense responses and imparts knowledge of Puccinia triticina-induced defense transcripts in wheat plants.

Electronic medical records and genomics (eMERGE) network exploration in cataract: several new potential susceptibility loci.

PURPOSE: Cataract is the leading cause of blindness in the world, and in the United States accounts for approximately 60% of Medicare costs related to vision. The purpose of this study was to identify genetic markers for age-related cataract through a genome-wide association study (GWAS). METHODS: In the electronic medical records and genomics (eMERGE) network, we ran an electronic phenotyping algorithm on individuals in each of five sites with electronic medical records linked to DNA biobanks. We performed a GWAS using 530,101 SNPs from the Illumina 660W-Quad in a total of 7,397 individuals (5,503 cases and 1,894 controls). We also performed an age-at-diagnosis case-only analysis. RESULTS: We identified several statistically significant associations with age-related cataract (45 SNPs) as well as age at diagnosis (44 SNPs). The 45 SNPs associated with cataract at p<1×10(-5) are in several interesting genes, including ALDOB, MAP3K1, and MEF2C. All have potential biologic relationships with cataracts. CONCLUSIONS: This is the first genome-wide association study of age-related cataract, and several regions of interest have been identified. The eMERGE network has pioneered the exploration of genomic associations in biobanks linked to electronic health records, and this study is another example of the utility of such resources. Explorations of age-related cataract including validation and replication of the association results identified herein are needed in future studies.