The dynamic risk factors of cardiovascular disease among people living with HIV: a real-world data study.

BACKGROUND: This study aims to investigate the incidence and dynamic risk factors for cardiovascular diseases (CVD) among people living with HIV (PLWH). METHODS: In this population-based statewide cohort study, we utilized integrated electronic health records data to identify adult (age ≥ 18) who were diagnosed with HIV between 2006 and 2019 and were CVD event-free at the HIV diagnosis in South Carolina. The associations of HIV-related factors and traditional risk factors with the CVD incidence were investigated during the overall study period, and by different follow-up periods (i.e., 0-5yrs, 6-10yrs 11-15yrs) using multivariable logistic regression models. RESULTS: Among 9,082 eligible participants, the incidence of CVD was 18.64 cases per 1000 person-years. Overall, conventional risk factors, such as tobacco use, hypertension, obesity, chronic kidney disease (CKD), were persistently associated with the outcome across all three groups. While HIV-related factors, such as recent CD4 count (e.g., > 350 vs. <200 cells/mm3: adjusted odds ratio [aOR] range: 0.18-0.25), and percent of years in retention (e.g., 31-75% vs. 0-30%: aOR range: 0.24-0.57) were associated with lower odds of CVD incidence regardless of different follow up periods. The impact of the percent of days with viral suppression gradually diminished as the follow-up period increased. CONCLUSIONS: Maintaining an optimal viral suppression might prevent CVD incidence in the short term, whereas restoring immune recovery may be beneficial for reducing CVD risk regardless of the duration of HIV diagnosis. Our findings suggest the necessity of conducting more targeted interventions during different periods of HIV infection.

Comparison of different genetic testing modalities applied in paediatric patients with steroid-resistant nephrotic syndrome.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) are monogenic in some cases, however, there are still no clear guidelines on genetic testing in the clinical practice of SRNS in children. METHODS: Three hundred thirty-two children were diagnosed with SRNS, and all children underwent genetic testing, including gene panels and/or whole-exome/genome sequencing (WES/WGS), during treatment. We analysed the relationship between clinical manifestation and genotype, and compared different genetic testing methods' detection rates and prices. RESULTS: In this study, 30.12% (100/332) of children diagnosed with SRNS had monogenic causes of the disease. With 33.7% (122/332) of children achieving complete remission, 88.5% (108/122) received steroids combined with tacrolimus (TAC). In detectability, WES increased by 8.69% (4/46) on gene panel testing, while WGS increased by 4.27% (5/117) on WES, and WES was approximately 1/7 of the price of WGS for every further 1% increase in pathogenicity. CONCLUSIONS: We verified that steroids combined with TAC were the most effective option in paediatric SRNS. In detection efficiency, we found that WGS was the highest, followed by WES. The panel was the lowest, but the most cost-effective method when considering the economic-benefit ratio, and thus it should be recommended first in SRNS.

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort.

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97-9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Quantitative assessment of retinochoroidal microvasculature in patients with carotid artery stenosis using OCT angiography.

PURPOSE: To investigate the alterations in retinochoroidal parameters measured by optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with carotid artery stenosis (CAS) and assess their associations with digital subtraction angiography (DSA) data. METHOD: This study enrolled patients diagnosed with CAS and age-matched healthy controls. Both groups underwent OCT and OCTA examinations. DSA and assessment of carotid artery stenosis were performed only in the CAS group. The study evaluated various retinochoroidal parameters from OCT and OCTA, including linear vessel density (LVD), foveal avascular zone (FAZ), choroidal thickness (ChT), and retinal nerve fiber layer (RNFL) thickness. DSA-derived measures included cervical segment (C1) diameter, cavernous segment (C4) diameter, stenosis percentage, ophthalmic artery (OA) filling time, C1-OA filling time, and residual stenosis. RESULTS: A total of 42 eyes from 30 CAS patients and 60 eyes from 30 healthy controls were included. Patients with CAS displayed significantly decreased LVD compared to controls (p < 0.001). Additionally, the CAS group had thinner choroid and RNFL (p = 0.047 and p < 0.001, respectively). Macular LVD negatively correlated with both stenosis percentage and C1-OA filling time (p = 0.010 and p = 0.014, respectively). In patients who underwent carotid artery stenting, preoperative ChT significantly correlated with residual stenosis (Pearson r = -0.480, p = 0.020). CONCLUSION: OCT and OCTA provide a quantitative assessment of retinochoroidal microstructural changes associated with CAS, suggesting potential for noninvasive evaluation of the disease. This might contribute to the prevention of irreversible ocular complications and early detection of CAS. Furthermore, ChT may not only aid in diagnosing CAS more reliably but also offer prognostic information.

Novel Binder with Cross-Linking Reconfiguration Functionality for Silicon Anodes of Lithium-Ion Batteries.

Silicon is expected to be used as a high theoretical capacity anode material in lithium-ion batteries with high energy densities. However, the huge volume change incurred when silicon de-embeds lithium ions, leading to destruction of the electrode structure and a rapid reduction in battery capacity. Although binders play a key role in maintaining the stability of the electrode structure, commonly used binders cannot withstand the large volume expansion of the silicon. To alleviate this problem, we propose a PGC cross-linking reconfiguration binder based on poly(acrylic acid) (PAA), gelatin (GN), and ß-cyclodextrin (ß-CD). Within PGC, PAA supports the main chain and provides a large number of carboxyl groups (-COOH), GN provides rich carboxyl and amide groups that can form a cross-linking network with PAA, and ß-CD offers rich hydroxyl groups and a cone-shaped hollow ring structure that can alleviate stress accumulation in the polymer chain by forming a new dynamic cross-linking coordination conformation during stretching. In the half cell, the silicon negative prepared by the PGC binder exhibited a high specific capacity and capacity maintenance ratio, and the specific capacity of the silicon negative electrode prepared by the PGC binder is still 1809 mAh g-1 and the capacity maintenance ratio is 73.76% following 200 cycles at 2 A g-1 current density, indicating that PGC sufficiently maintains the silicon negative structure during the battery cycle. The PGC binder has a simple preparation method and good capacity retention ability, making it a potential reference for the further development of silicon negative electrodes.

Sexual orientation and gender identity measures and viral suppression for people living with HIV: a protocol for a population-based cohort study.

INTRODUCTION: The measure of sexual orientation and gender identity (SOGI) data in electronic health records (EHR) has been critical for addressing health disparities and inequalities, especially for HIV care. Given that gender and sexual minorities (eg, transgender, men who have sex with men and intersex) are key groups in people living with HIV (PLWH), SOGI data can facilitate a more accurate understanding about the HIV outcomes (eg, viral suppression) among this key group and then lead to tailored therapeutic services. The two-step SOGI collection method as an emerging gender measurement can be used to measure SOGI status in medical settings. Using the statewide cohort of PLWH in South Carolina (SC), this project aims to: (1) integrate statewide PLWH cohort data with their birth certificate data to evaluate SOGI measurements from multiple EHR sources; and (2) examine differences in viral suppression based on SOGI measurements. METHODS AND ANALYSIS: Our EHR database includes several HIV data sources with patients' gender information, such as SC Department of Health and Environmental Control Centre (DHEC), Health Sciences South Carolina (HSSC) and Prisma as well as birth certificate data to retrieve the sex at birth. The SC Enhanced HIV/AIDS Reporting System (e-HARS) from DHEC will provide longitudinal viral load information to define a variety of viral suppression status. Datasources like the SC office of Revenue and Fiscal Affairs (RFA) will extract longitudinal EHR clinical data of all PLWH in SC from multiple health systems; obtain data from other state agencies and link the patient-level data with county-level data from multiple publicly available data sources. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board at the University of South Carolina (Pro00129906) as a Non-Human Subject study. The study's findings will be published in peer-reviewed journals and disseminated at national and international conferences and through social media.

Examining Incidence of Diabetes in People Living with HIV: Tracking the Shift in Traditional and HIV-related Risk Factors.

BACKGROUND AND OBJECTIVE: The risk factors of diabetes mellitus (DM) in people with HIV (PWH) may be dynamic in a life course manner. This study aimed to describe incidence of DM and investigate the trajectory of changes in risk factor associated with DM incidence over around 15 years among a statewide cohort of PWH in South Carolina (SC). DESIGN: This is a population-based cohort study. METHODS: Data were retrieved from the integrated statewide electronic health records between 2006 and 2020 in SC. Separate subgroup analysis was conducted according to the patients' different follow up duration (i.e., 5, 10, and 15 years) to observe the evolving risk factors of DM development, using multivariable logistic regressions. RESULTS: The DM incidence among a total of 9115 PWH was 8.9 per 1000 person-years. In the overall model, being >60 years old, hypertension, and obesity were positively associated with DM while alcohol consumption, years of HIV diagnosis and high percentage days of viral suppression were negatively associated with the outcome. In the subgroup analyses, similar risk factors were observed. The odds of DM increased in a graded fashion with age. Hypertension was positively associated with DM in all groups and retention to care was negatively associated with the outcome in groups 1 and 3. CONCLUSION: This large-scale population-based study has revealed a relatively lower incidence of DM among PWH than some other US States. The evolving risk factors over time underline the need for maintaining retention to care to prevent the occurrence of DM.

Transcriptomic changes and prediction of time since deposition of blood stains.

In forensics, it is important to determine the time since deposition (TSD) of bloodstains, one of the most common types of biological evidence in criminal cases. However, no effective TSD inference methods have been established despite extensive attempts in forensic science. Our study investigated the changes in the blood transcriptome over time, and we found that degradation could be divided into four stages (days 0-2, 4-14, 21-56, and 84-168) at 4 °C. A random forest prediction model based on these transcriptional changes was trained on experimental samples and tested in separate test samples. This model was able to successfully predict TSD (area under the curve [AUC] = 0.995, precision = 1, and recall = 1). Thus, this proof-of-concept pilot study has practical significance for assessing physical evidence. Meanwhile, 11 upregulated and 13 downregulated transcripts were identified as potential time-marker transcripts, laying a foundation for further development of TSD analysis methods in forensic science and crime scene investigation.

Reorganization of intrinsic functional connectivity in early-stage Parkinson's disease patients with probable REM sleep behavior disorder.

REM sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.

Suicide Ideation and Attempt Among People With HIV: A Statewide Population-level Cohort Analysis Between 2005 and 2020.

BACKGROUND: Risk factors for suicidality among people with HIV (PWH) may evolve over their disease course, particularly as they develop comorbidities such as mental health disorders over time. SETTING: This study compared the leading risk factors of suicide ideation/attempt among PWH in South Carolina across different combination antiretroviral therapy (cART) eras. METHODS: A statewide cohort of PWH who were diagnosed between 2005 and 2016, with a follow-up record until 2020, was involved in the study. A Cox proportional hazards model was used to examine the association of suicide ideation/attempt and predictors, including demographics, HIV-related characteristics, and mental health conditions. RESULTS: Among 8567 PWH, the incidence of suicide ideation/attempt increased from 537.7 per 100,000 person-years [95% confidence interval (CI): 460.2 to 615.1] in the early cART cohort (2005-2008) to 782.5 (95% CI: 697.6 to 867.4) in the late cART cohort (2009-2016). Leading risk factors of suicide ideation/attempt changed across the cART cohort. In the early cART cohort, PWH with suicide ideation/attempt were more likely to be White and diagnosed with bipolar disorder ( P' s < 0.05). In the late cART cohort, suicide ideation/attempt was positively associated with transmission through injection drug use, anxiety, posttraumatic stress disorder, schizophrenia, and personality disorder ( P' s < 0.05). CONCLUSIONS: Mental health conditions have emerged as more prominent risk factors for suicide ideation/attempt in the late cART cohort. Enhanced access to psychiatric care could facilitate the early identification of mental health conditions, enabling timely counseling or psychosocial interventions that may mitigate mental health issues and, consequently, reduce the likelihood of suicide ideation/attempts among PWH.

COVID-19 breakthrough infections among people living with and without HIV: A statewide cohort analysis.

OBJECTIVES: This study aims to characterize and compare COVID-19 breakthrough infections between people living with and without HIV across different phases of the pandemic. METHODS: Using statewide HIV cohort data, the study population included adult residents in South Carolina (SC) (>18 years old) who were fully vaccinated between January 02, 2021 and April 14, 2022 when Alpha, Delta, and Omicron variants were circulating in SC. We used the Cox proportional hazard model to investigate the association between HIV infection and breakthrough infection, adjusting for relevant covariates. RESULTS: Among 2,144,415 vaccinated individuals, 8,335 were people living with HIV (PLWH) and 2,136,080 were people without HIV (PWoH). After propensity score matching, HIV infection was not significantly associated with breakthrough infection rate. However, when comparing breakthrough infections among individuals without any booster dose, PLWH had a higher risk of breakthrough infections (adjusted Hazard Ration: 1.19; 95% confidence interval: 1.03-1.39). Compared to PWoH, PLWH with high levels of clusters of differentiation 4 (CD4) count or viral suppression were not associated with breakthrough infections. CONCLUSIONS: Our findings do not support a broad conclusion that COVID-19 vaccine effectiveness is lower among PLWH, while we did find that PLWH had a higher risk of breakthrough infection compared to PWoH if they did not receive a booster dose.

Residential Segregation and County-Level COVID-19 Booster Coverage in the Deep South: Surveillance Report and Ecological Study.

BACKGROUND: COVID-19 had a greater impact in the Deep South compared with other regions in the United States. While vaccination remains a top priority for all eligible individuals, data regarding the progress of booster coverage in the Deep South and how the coverage varies by county and age are sparse. Despite existing evidence of racial and ethnic disparities in COVID-19 vaccinations at the individual level, there is an urgent need for evidence at the population level. Such information could highlight vulnerable communities and guide future health care policy-making and resource allocation. OBJECTIVE: We aimed to evaluate county-level COVID-19 booster coverage by age group in the Deep South and explore its association with residential segregation. METHODS: An ecological study was conducted at the population level by integrating COVID-19 vaccine surveillance data, residential segregation index, and county-level factors across the 418 counties of 5 Deep South states from December 15, 2021, to October 19, 2022. We analyzed the cumulative percentages of county-level COVID-19 booster uptake by age group (eg, 12 to 17 years, 18 to 64 years, and at least 65 years) by the end of the study period. The longitudinal relationships were examined between residential segregation, the interaction of time and residential segregation, and COVID-19 booster coverage using the Poisson model. RESULTS: As of October 19, 2022, among the 418 counties, the median of booster uptake was 40% (IQR 37.8%-43%). Compared with older adults (ie, at least 65 years; median 63.1%, IQR 59.5%-66.5%), youth (ie, 12 to 17 years; median 14.1%, IQR 11.3%-17.4%) and adults (ie, 18 to 64 years; median 33.4%, IQR 30.5%-36.5%) had lower percentages of booster uptake. There was geospatial heterogeneity in the county-level COVID-19 booster coverage. We found that higher segregated counties had lower percentages of booster coverage. Such relationships attenuated as time increased. The findings were consistent across the age groups. CONCLUSIONS: The progress of county-level COVID-19 booster coverage in the Deep South was slow and varied by age group. Residential segregation precluded the county-level COVID-19 booster coverage across age groups. Future efforts regarding vaccination strategies should focus on youth and adults. Health care facilities and resources are needed in racial and ethnic minority communities.

Patterns and predictors of racial/ethnic disparities in HIV care continuum in the Southern USA: protocol for a population-based cohort study.

INTRODUCTION: Health disparities exist at every step of the HIV care continuum (HCC) among racial/ethnic minority population. Such racial/ethnic disparities may have significantly delayed the progress in HCC in the Southern US states that are strongly represented among geographic focus areas in the 2019 federal initiative titled 'Ending the HIV Epidemic: A Plan for America'. However, limited efforts have been made to quantify the long-term spatiotemporal variations of HCC disparities and their contributing factors over time, particularly in the context of COVID-19 pandemic. This project aims to identify the spatiotemporal patterns of racial disparities of each HCC outcome and then determine the contribution of contextual features for temporal change of disparities in HCC. METHODS AND ANALYSIS: This cohort study will use statewide HIV cohort data in South Carolina, including all people living with HIV (PLWH) who were diagnosed with HIV in 2005-2020. The healthcare encounter data will be extracted from longitudinal EHR from six state agencies and then linked to aggregated county-level community and social structural-level data (eg, structural racism, COVID-19 pandemic) from multiple publicly available data sources. The South Carolina Revenue of Fiscal and Affairs will serve as the honest broker to link the patient-level and county-level information. We will first quantify the HCC-related disparities by creating a county-level racial/ethnic disparity index (RDI) for each key HCC outcomes (eg, HIV testing, timely diagnosis), examine the temporal patterns of each RDI over time and then using geographical weighted lasso model examine which contextual factors have significant impacts on the change of county-level RDI from 2005 to 2020. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board at the University of South Carolina (Pro00121718) as a Non-Human Subject study. The study's findings will be published in peer-reviewed journals and disseminated at national and international conferences and through social media.

COVID-19 Testing Among People with HIV: A Population Level Analysis Based on Statewide Data in South Carolina.

People with HIV (PWH) are at an elevated risk of developing severe COVID-19 outcomes because of compromised immunity and more comorbidities. However, existing literature suggests a lower rate of COVID-testing among PWH. This study aimed to explore the temporal trend of county-level COVID-19 testing rate and multi-level predictors of COVID-19 ever-testing among PWH in South Carolina (SC). Leveraging linked statewide HIV and COVID-19 datasets, we defined the study population as all adult (18 + years) PWH who were alive on March 2020 and living in SC. PWH with a COVID-19 testing record between March 2020 and October 2021 were defined as COVID-19 ever-testers. Logistic regression and generalized mixed models were used to investigate the association of PWH's demographic profile, HIV clinical characteristics (e.g., CD4 count, viral load), comorbidities, and social factors with COVID-19 testing among PWH. Among 15,660 adult PWH, 8,005 (51.12%) had ever tested for COVID-19 during the study period (March 2020-October 2021). PWH with older age, being male, and Hispanics were less likely to take COVID-19 testing, while men who have sex with men or injection drug users were more likely to take COVID-19 testing. PWH with higher recent viral load (10,000-100,000 copies/ml vs. <200 copies/ml: adjusted odds ratio [AOR]: 0.64, 95%CI: 0.55-0.75) and lower CD4 counts (> 350 cells/mm3 vs. <200 cells/mm3: AOR: 1.25, 95%CI: 1.09-1.45) had lower odds for COVID-19 testing. Additionally, PWH with lower comorbidity burden and those living in rural areas were less likely to be tested for COVID-19. Differences in COVID-19 test-seeking behaviors were observed among PWH in the current study, which could help provide empirical evidence to inform the prioritization of further disease monitoring and targeted intervention. More efforts on building effective surveillance and screening systems are needed to allow early case detection and curbing disease transmission among older, male, Hispanic, and immune-suppressed PWH, especially in rural areas.

Generation and characterization of PDGFRα-GFP knock-in mice for visualization of PDGFRα+ fibroblasts in vivo.

The platelet-derived growth factor (PDGF) and its receptor, PDGFRα, are critical for tissue development and injury repair. To track PDGFRα-expressing cells in vivo, we generated a knock-in mouse line that expresses green fluorescent protein (GFP) under the control of the PDGFRα promoter. This genetic tool enabled us to detect PDGFRα expression in various organs during both neonatal and adult stages. Additionally, we confirmed the correlation between endogenous PDGFRα and transgenic PDGFRα expression using mouse injury models, showing the potential of this genetic reporter for studying PDGFRα-mediated signaling pathways and developing therapeutic strategies. Overall, the PDGFRα-GFP knock-in mouse line serves as a valuable tool for investigating the biology of PDGFRα and its role in normal development and disease.

Understanding social risk factors of county-level disparities in COVID-19 tests per confirmed case in South Carolina using statewide electronic health records data.

BACKGROUND: COVID-19 testing is essential for pandemic control, and insufficient testing in areas with high disease burdens could magnify the risk of poor health outcomes. However, few area-based studies on COVID-19 testing disparities have considered the disease burden (e.g., confirmed cases). The current study aims to investigate socioeconomic drivers of geospatial disparities in COVID-19 testing relative to disease burden across 46 counties in South Carolina (SC) in the early (from April 1, 2020, to June 30, 2020) and later (from July 1, 2020, to September 30, 2021) phases of the pandemic. METHODS: Using SC statewide COVID-19 testing data, the COVID-19 testing coverage was measured by monthly COVID-19 tests per confirmed case (hereafter CTPC) in each county. We used modified Lorenz curves to describe the unequal geographic distribution of CTPC and generalized linear mixed-effects regression models to assess the association of county-level social risk factors with CTPC in two phases of the pandemic in SC. RESULTS: As of September 30, 2021, a total of 641,201 out of 2,941,227 tests were positive in SC. The Lorenz curve showed that county-level disparities in CTPC were less apparent in the later phase of the pandemic. Counties with a larger percentage of Black had lower CTPC during the early phase (ß = -0.94, 95%CI: -1.80, -0.08), while such associations reversed in the later phase (ß = 0.28, 95%CI: 0.01, 0.55). The association of some other social risk factors diminished as the pandemic evolved, such as food insecurity (ß: -1.19 and -0.42; p-value is < 0.05 for both). CONCLUSIONS: County-level disparities in CTPC and their predictors are dynamic across the pandemic. These results highlight the systematic inequalities in COVID-19 testing resources and accessibility, especially in the early stage of the pandemic. Counties with greater social vulnerability and those with fewer health care resources should be paid extra attention in the early and later phases, respectively. The current study provided empirical evidence for public health agencies to conduct more targeted community-based testing campaigns to enhance access to testing in future public health crises.

The association between the maternal pre-pregnancy platelet count and fecundability in mainland China: a population-based cohort study.

BACKGROUND: Currently, awareness about platelet count (PC) and its consequences for perinatal outcome have increased, but there is little reliable evidence on fecundability. METHODS: Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 5,524,886 couples met the inclusion criteria were included in this cohort study. Cox regression models were adopted to estimate fecundability ratios (FRs) and their 95% confidence intervals for pre-pregnancy PC quintiles. Restricted cubic splines were used to flexibly model and visualize the relationship of PC with FRs. Microsoft SQL server and R software were used for data management and analysis. RESULTS: The median of pre-pregnancy PC among women was 221.00×109/L. The first (<177.00 ×109/L) and second quintile (177.00-207.99 ×109/L) of PC showed slightly increased fecundability (Q1: adjusted FR 1.05, 95% CI 1.04-1.06; Q2: adjusted FR 1.04, 95% CI 1.03-1.05), while higher quintals (Q4: 236.00-271.99 ×109/L; Q5: ≥272.00 ×109/L) were related to reduction of fecundability, when compared with the third quintile of PC (208.00-235.99 ×109/L) (Q4: adjusted FR 0.96, 95% CI 0.95-0.97; Q5: adjusted FR 0.88, 95% CI 0.87-0.89). In the first quintiles (<177.00×109/L), only 20.93% women had PC below 129.94×109/L. An inverse-U shape association was consistently observed among women such that the lower PC of normal range (<118.03×109/L) and higher PC (>223.06×109/L) were associated with the risk of reduced female fecundability (P for non-linearity < 0.01). CONCLUSION: PC is associated with female fecundability. Further classification of PC levels may deepen our understanding of the early warnings and significance of female fecundability.

CBCT-to-CT Synthesis for Cervical Cancer Adaptive Radiotherapy via U-Net-Based Model Hierarchically Trained with Hybrid Dataset.

PURPOSE: To develop a deep learning framework based on a hybrid dataset to enhance the quality of CBCT images and obtain accurate HU values. MATERIALS AND METHODS: A total of 228 cervical cancer patients treated in different LINACs were enrolled. We developed an encoder-decoder architecture with residual learning and skip connections. The model was hierarchically trained and validated on 5279 paired CBCT/planning CT images and tested on 1302 paired images. The mean absolute error (MAE), peak signal to noise ratio (PSNR), and structural similarity index (SSIM) were utilized to access the quality of the synthetic CT images generated by our model. RESULTS: The MAE between synthetic CT images generated by our model and planning CT was 10.93 HU, compared to 50.02 HU for the CBCT images. The PSNR increased from 27.79 dB to 33.91 dB, and the SSIM increased from 0.76 to 0.90. Compared with synthetic CT images generated by the convolution neural networks with residual blocks, our model had superior performance both in qualitative and quantitative aspects. CONCLUSIONS: Our model could synthesize CT images with enhanced image quality and accurate HU values. The synthetic CT images preserved the edges of tissues well, which is important for downstream tasks in adaptive radiotherapy.