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Primary care screening for sexually transmitted infections in the United States from 2019 to 2021
Get PDFBACKGROUND: Early identification and treatment of sexually transmitted infections (STIs) is critical to improve patient outcomes. Barriers to healthcare seeking are potentially exacerbated by COVID-19. This study examined trends in STI testing and positivity from 2019 to 2021 in primary care in the United States. METHODS: This is a retrospective study using the PRIME Registry, a national primary care EHR registry, from January 1, 2019-December 31, 2021. We calculated age-standardized monthly and annual testing rates for chlamydia, gonorrhea, syphilis, and human immunodeficiency virus stratified by gender and race/ethnicity. We also generated quarterly and annual rates for test positivity. Chi-square tests and 95% confidence intervals were used for comparison. 753 practices and 4,410,609 patients were included, with 180,558 having STI tests. RESULTS: We observed a substantial decline in testing rates for STIs from March-April 2020 (31% for chlamydia, 30% for gonorrhea, 23% for syphilis, 24% for HIV), followed by a rapid increase in May-June 2020 (64% for chlamydia, 65% for gonorrhea, 32% for syphilis, 48% for HIV). Testing rates per 100,000 decreased from 2019 to 2021 for chlamydia (3,592 vs 2,355 vs 2,181) while increased for gonorrhea in 2020 (2,129 vs 2,207 vs 2,057). STI testing rates from 2019 to 2021 for females and non-Hispanic Black or African American patients were higher than other groups. An increase in test positivity from 2019 to 2021 was observed for gonorrhea (0.4% vs 0.4% vs 0.5%) but no significant change for chlamydia (1.5% vs 1.6% vs 1.5%). CONCLUSION: Testing rates for STIs substantially dropped during stay-at-home orders early in the pandemic and recovered after these were relaxed. Gender and race/ethnicity STI testing differences may reflect primary care's prioritization of higher risk populations. This study emphasizes the role of primary care EHR data in monitoring and an opportunity for closer collaboration with public health agencies
Highly multiplexed molecular inversion probe panel in Plasmodium falciparum targeting common SNPs approximates whole-genome sequencing assessments for selection and relatedness
Get PDFThe use of next-generation sequencing technologies (NGS) to study parasite populations and their response and evolution to interventions is important to support malaria control and elimination efforts. While whole-genome sequencing (WGS) is optimal in terms of assessing the entire genome, it is costly for numerous samples. Targeted approaches selectively enriching for the sequence of interest are more affordable and have higher throughput but sometimes lack adequate information content for key analyses. We have developed a highly multiplexed molecular inversion probe (MIP) panel (IBC2FULL) targeting 4,264 single-nucleotide polymorphisms (SNPs) with ≥5% minor allele frequency (MAF) in Sub-Saharan African regions from publicly available Plasmodium falciparum WGS (n = 3,693). We optimized the panel alone and in combination with antimalarial drug resistance MIPs in laboratory P. falciparum strains at different parasitemias and validated it by sequencing field isolates from the Democratic Republic of Congo, Ethiopia, Ghana, Mali, Rwanda, Tanzania, and Uganda and evaluating the population structure, identity-by-descent (IBD), signals of selection, and complexity of infection (COI). The new panel IBC2FULL consisted of 2,128 MIPs (containing 4,264 common SNPs) spaced by 5.1–18.4 kb across the entire genome. While these microhaplotypes were developed based on variations from Sub-Saharan African WGS data, 59.3% (2,529) of SNPs were also common in Southeast Asia. The MIPs were balanced to produce more a uniform and higher depth of coverage at low parasitemia (100 parasites/μL) along with MIPs targeting antimalarial drug resistance genes. Comparing targeted regions extracted from public WGS, we observed that IBC2FULL provided a higher resolution of the local population structure in Sub-Saharan Africa than current PCR-based targeted sequencing panels. For sequencing field samples (n = 140), IBC2FULL approximated WGS measures of relatedness, population structure, and COI. Interestingly, genome-wide analysis of extended haplotype homozygosity detected the same major peaks of selection as WGS. We also chose a subset of 305 high-performing MIPs to create a core panel (IBC2CORE) that produced high-quality data for basic population genomic analysis and accurate estimation of COI. IBC2FULL and IBC2CORE panels have been designed to provide an improved platform for malaria genomic epidemiology and biology that can approximate WGS for many applications and is deployable for malaria molecular surveillance in resource-limited settings
The Rab18/Ras/ERK/FosB/MMP3 Signaling Pathway Mediates Cell Migration Regulation by 2′3′-cGAMP
Get PDFThe unique secondary messenger 2′3′-cGAMP, produced by cGAS in response to cytosolic dsDNA, plays a critical role in activating innate immunity by binding to and activating STING via cell-intrinsic, autocrine, or paracrine mechanisms. Recently, we identified Rab18 as a novel, STING-independent binder of 2′3′-cGAMP. Binding of 2′3′-cGAMP to Rab18 promotes Rab18 activation and induces cell migration. However, the downstream mechanisms by which 2′3′-cGAMP-induced Rab18 activation regulates cell migration remain largely unclear. Herein, using phospho-profiling analysis, we identify MAPK signaling as a key downstream effector of the 2′3′-cGAMP/Rab18 axis that promotes the expression of FosB2 and drives cell migration. Furthermore, we identify MMP3 as a major transcriptional target of FosB2, through which the 2′3′-cGAMP/Rab18/MAPK/FosB2 signaling pathway positively regulates cell migration. Together, our findings provide new mechanistic insights into how 2′3′-cGAMP signaling controls cell migration and suggest the potential of MAPK inhibitors to block 2′3′-cGAMP-induced migratory responses
Understanding Adolescents’ Family Communication During COVID-19: An Ecological Momentary Design Study
Get PDFThe COVID-19 pandemic presented many new challenges for families to navigate. The present study took place between May and September 2020 and included a racially diverse sample of adolescents (34% White/European, 30% Latine, 24% Black/African American, 9% multiracial/other race; N = 213, Mage = 15 years, 53% girls). Participants reported their affective responses to COVID-19 in a baseline survey and completed 14 days of ecological momentary assessments (3× daily) of the frequency, mode, and quality of communication with their parents and siblings, and their positive and negative affect. Adolescents with more COVID-19 negative affect reported more frequent digital communication with their siblings and reported the quality of their communication with parents and siblings as more negative. During hours when adolescents reported the quality of their communication with parents as more positive, they also reported higher positive affect and lower negative affect. During hours when adolescents reported the quality of their communication with siblings as more positive, they reported higher positive affect in the same hour. Relatedly, during hours with less negative communication with parents and siblings, adolescents reported more positive affect in the same hour. These associations were not contingent on if communication was digital or in-person. Results highlight the importance of the quality of family communication for understanding adolescents' emotions during the pandemic.
Computational Insights into the Polypharmacological Landscape of BCR-ABL Inhibitors: Emphasis on Imatinib and Nilotinib
Get PDFBackground: BCR-ABL inhibitors such as imatinib and nilotinib exhibit multi-kinase activity that extends beyond oncology, offering significant potential for drug repurposing. Objectives: This study aims to systematically evaluate and prioritize the repurposing potential of BCR-ABL inhibitors, particularly imatinib and nilotinib. Methods: An integrated pharmacoinformatics framework was applied to analyze seven BCR-ABL inhibitors. Structural clustering, cheminformatics analysis, and transcriptomic profiling using the Connectivity Map were employed to evaluate structural relationships, target profiles, and gene expression signatures associated with non-oncology indications. Results: Structurally, imatinib and nilotinib clustered closely, while HY-11007 exhibited distinct features. Nilotinib’s high selectivity correlated with strong transcriptional effects in neurodegeneration-related pathways (e.g., HSP90 and LYN), whereas imatinib’s broader kinase profile (PDGFR and c-KIT) was linked to fibrosis and metabolic regulation. Connectivity Map analysis identified more than 30 non-cancer indications, including known off-target uses (e.g., imatinib for pulmonary hypertension) and novel hypotheses (e.g., nilotinib for Alzheimer’s via HSPA5 modulation). A substantial portion of these predictions aligned with the existing literature, underscoring the translational relevance of the approach. Conclusions: These findings highlight the importance of integrating structure–activity relationships and transcriptomic signatures to guide rational repurposing. We propose prioritizing nilotinib for CNS disorders and imatinib for systemic fibrotic diseases, supporting their advancement into preclinical and clinical evaluation. More broadly, this framework offers a versatile platform for uncovering hidden therapeutic potential across other drug classes with complex polypharmacology
A Genome-Wide Association Study of Anti-Müllerian Hormone (AMH) Levels in Samoan Women
Get PDFBackground/Objectives:The anti-Müllerian hormone (AMH) is a key biomarker of the ovarian reserve, correlating with ovarian follicle count, fertility outcomes, and menopause timing. Understanding its genetic determinants has broad implications for female reproductive health. However, prior genome-wide association studies (GWASs) have focused exclusively on women of European ancestry, limiting insights into diverse populations. Methods: We conducted a GWAS to identify genetic loci associated with circulating AMH levels in a sample of 1185 Samoan women from two independently recruited samples. Using a Cox mixed-effects model we accounted for AMH levels below detectable limits and meta-analysed the summary statistics using a fixed-effect model. To prioritize variants and genes, we used FUMA and performed colocalization and transcriptome-wide association analysis (TWAS). We also assessed whether any previously reported loci were replicated in our GWAS. Results: We identified eleven genome-wide suggestive loci, with the strongest signal at ARID3A (19-946163-G-C; p = 2.32 × 10⁻⁷) and replicated rs10093345 near EIF4EBP1. The gene-based testing revealed ARID3A and R3HDM4 as significant genes. Integrating GWAS results with expression quantitative trait loci via TWAS, we detected seven transcriptome-wide significant genes. The lead variant in ARID3A is in high linkage disequilibrium (r² = 0.79) with the known age-at-menopause variant 19-950694-G-A. Nearby KISS1R is a biologically plausible candidate gene that encodes the kisspeptin receptor, a regulator of ovarian follicle development linked to AMH levels. Conclusions: This study expands our understandings of AMH genetics by focusing on Samoan women. While these findings may be particularly relevant to Pacific Islanders, they hold broader implications for reproductive phenotypes such as the ovarian reserve, menopause timing, and polycystic ovary syndrome
LncRNAOmics: A Comprehensive Review of Long Non-Coding RNAs in Plants
Get PDFThe large portion of the eukaryotic genomes was considered non-functional and called the “dark matter” of the genome, now appearing as regulatory hubs coding for RNAs without the potential for making proteins, known as non-coding RNA. Long non-coding RNA (lncRNA) is defined as functional RNA molecules having lengths larger than 200 nucleotides without the potential for coding for proteins. Thousands of lncRNAs are identified in different plants and animals. LncRNAs are characterized by a low abundance, fewer exons than mRNA, tissue-specific expression, and low sequence conservation compared to protein-coding genes (PCGs). LncRNAs, like PCGs, are regulated by promoters and enhancers with characteristic chromatin signatures, DNA methylation, multiple exons, introns, and alternate splicing. LncRNAs interact with DNA, mRNA, microRNA, and proteins, including chromatin/histone modifiers, transcription factors/repressors, epigenetic regulators, spliceosomal, and RNA-binding proteins. Recent observations indicate that lncRNAs code for small peptides, also called micropeptides (<100 amino acids), and are involved in the development and growth of plants, suggesting the bi-functional activities of lncRNAs. LncRNAs have emerged as the major regulators of diverse functions, principally by altering the transcription of target genes. LncRNAs are involved in plant growth, development, immune responses, and various physiological processes. Abiotic, biotic, nutrient, and other environmental stresses alter the expressions of numerous lncRNAs. Understanding the mechanisms of actions of lncRNAs opens up the possibility of improving agronomic traits by manipulating lncRNAs. However, further studies are required in order to find the interactions among the deregulated lncRNAs and validate the findings from high-throughput studies to harness their potential in crop improvement
Drug overdose mortality in North Carolina among healthcare patients and publicly and privately insured people: 2006-2022
Get PDFBackground: The drug overdose epidemic claimed approximately 108,000 lives in the U.S. in 2022 alone and costs the country around $1 trillion annually. We compared overdose death rates among three separate cohorts defined as a healthcare patient population, a privately insured cohort and a cohort of Medicaid enrollees in North Carolina (NC) from 2006-2022.Methods: Records from a large, integrated, healthcare delivery system, Medicaid and privately insured NC individuals, were linked to death certificate data . Overdose deaths from all drugs, opioids, and multiple drugs (polydrug overdose) were identified using International Classification of Disease Version 10 (ICD-10) codes for primary and contributing causes of death. Polydrug overdoses were defined as those where the ICD-10 codes included more than one drug. Indirect standardization with the NC general population as the reference group was used to report age, sex, and calendar year adjusted mortality rates and standardized mortality ratios (SMRs) between 2006-2022.Results: Between 2014-2022, for individuals aged 12 to 64, the overall drug, opioid, and polydrug overdose mortality rates in the NC general population were 28.8 , 25.0, and 18.0 per 100,000 person-years (PY), respectively. The corresponding mortality rates among healthcare patients were 105.5, 86.6, and 63.1 per 100,000 PY, respectively - with SMRs of 3.7, 3.5, and 3.5 compared to the general population. Among Medicaid enrollees, the adjusted mortality rates for any drug, opioid, and polydrug overdoses were 85.3, 63.5, and 46.2 per 100,000 PY, respectively. Corresponding SMRs were 3.0, 2.5, and 2.6. Among those with private health insurance, the adjusted mortality rates were lower compared to the general population—16.1, 12.3, and 8.6 per 100,000 PY respectively—with SMRs of 0.6, 0.5, and 0.5.Conclusions: Individuals receiving care within the health system experienced the highest overdose mortality rates, followed by those with Medicaid insurance, with both substantially exceeding the rates observed among privately insured individuals. These findings highlight significant socioeconomic health inequities that could benefit from targeting overdose prevention interventions among resource-limited populations.
Zero-sum or Coalition? A Dyadic Approach for Testing Discrimination’s Impact on Perceptions of Ethnoracial Outgroups
Get PDFIntergroup relations research suggests that individuals perceive racial politics through a zero-sum framework, whereas scholarship on mobilization and social movements has shown the importance of cross-racial solidarity in effecting political change through coalition-building. We apply these two theoretical perspectives to the question of discrimination, asking whether perceptions or experiences with discrimination against one’s own racial group lead to diminished (zero-sum) or heightened (coalition) beliefs that other racial groups also face discrimination. To do so, we use a dyadic approach, examining all possible relationships between four major ethnoracial groups in the United States. Analyzing nationally representative data from the 2020 American National Election Studies (ANES), we find evidence for the zero-sum framework for one of the dyads (White ⇔ Black) and evidence for the coalition framework within four of the dyads (Black ⇔ Hispanic, Hispanic ⇔ Asian, White ⇒ Asian, White ⇒ Hispanic). We also find that personal experiences with discrimination matter only for Whites’ outgroup perceptions, whereas group experiences with discrimination are related to outgroup perceptions for ethnoracial minorities. Results demonstrate the power of the dyadic approach by revealing the asymmetry in these dynamics, highlighting the differing role of personal versus group discrimination for various ethnoracial groups, and illustrating the unique nature of anti-Black sentiment among Whites. These results have important implications for scholarship on race and ethnicity as well as political sociology. Our findings are also critical for informing efforts to mobilize and educate the broader public about issues of discrimination and racial injustice
Different-sex American couples’ stress, uncertainty, and fertility desires during the COVID-19 pandemic
Get PDFThe Narratives of the Future (NofF) framework has drawn attention to the role of subjective well-being and uncertainty as key determinants of individual fertility intentions. We apply the NofF framework to the Traits–Desires–Intentions–Behavior (TDIB) model, arguing that perceptions of current and future well-being are aspects of traits and thus that desires—not intentions—would be most strongly related to perceptions. Further, although most research on subjective well-being and uncertainty has focused on economic aspects, a life course perspective suggests that other domains, such as health or relationship concerns, are also relevant. Finally, few studies consider the dyadic nature of fertility decision-making. We address these gaps by using the U.S.-based National Couples’ Health and Time Study (NCHAT), collected during the COVID-19 pandemic, to investigate how subjective concerns across economic, health, and relational domains relate to American couples’ agreement on wanting a(another) child and how men’s and women’s own fertility desires are related to their own stress and their partner’s relative stress across different domains. We find that couples’ higher levels of stress—across domains—is related to greater couple-level uncertainty and disagreement about fertility desires. Women’s own fertility desires are associated with their partner’s relative stress across domains, with less evidence that men’s fertility desires are related to their partner’s relative stress. Our findings point to the importance of considering stress and uncertainty across multiple domains, at least during the COVID-19 pandemic, as important for the formation of fertility desires as well as the need to incorporate both partners’ experiences as key factors in fertility decision-making