Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and somatic traits.

Co-occurring psychiatric, medical, and substance use disorders (SUDs) are common, but the complex pathways leading to such comorbidities are poorly understood. A greater understanding of genetic influences on this phenomenon could inform precision medicine efforts. We used the Yale-Penn dataset, a cross-sectional sample enriched for individuals with SUDs, to examine pleiotropic effects of genetic liability for psychiatric and somatic traits. Participants completed an in-depth interview that provides information on demographics, environment, medical illnesses, and psychiatric and SUDs. Polygenic scores (PGS) for psychiatric disorders and somatic traits were calculated in European-ancestry (EUR; n = 5691) participants and, when discovery datasets were available, for African-ancestry (AFR; n = 4918) participants. Phenome-wide association studies (PheWAS) were then conducted. In AFR participants, the only PGS with significant associations was bipolar disorder (BD), all of which were with substance use phenotypes. In EUR participants, PGS for major depressive disorder (MDD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), body mass index (BMI), coronary artery disease (CAD), and type 2 diabetes (T2D) all showed significant associations, the majority of which were with phenotypes in the substance use categories. For instance, PGSMDD was associated with over 200 phenotypes, 15 of which were depression-related (e.g., depression criterion count), 55 of which were other psychiatric phenotypes, and 126 of which were substance use phenotypes; and PGSBMI was associated with 138 phenotypes, 105 of which were substance related. Genetic liability for psychiatric and somatic traits is associated with numerous phenotypes across multiple categories, indicative of the broad genetic liability of these traits.

Endocrinology During Pregnancy.

Disequilibrium of hormonal intercommunication between the maternal brain and the developing fetal-placental unit increases morbidity and mortality risk for the mother-baby dyad. As a novel yet temporary endocrine organ, the placenta serves as a physical and immunologic barrier that facilitates exchange of nutrients and elimination of fetal waste. Steroid and peptide-based hormones secreted by the placenta and other neuroendocrine organs induce adaptations in maternal physiology accommodating fetal growth and development and enabling lactation postpartum. Human placental growth hormone, a peptide hormone continuously secreted at increasing concentrations throughout pregnancy, is a primary determinant of maternal insulin resistance and gestational diabetes.

Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence.

Adverse childhood events (ACEs) contribute to the development of mood and anxiety disorders and substance dependence. However, the extent to which these effects are direct or indirect and whether genetic risk moderates them is unclear. We examined associations among ACEs, mood/anxiety disorders and substance dependence in 12,668 individuals (44.9% female, 42.5% African American/Black, 42.1% European American/white). Using latent variables for each phenotype, we modelled direct and indirect associations of ACEs with substance dependence, mediated by mood/anxiety disorders (the forward or 'self-medication' model) and of ACEs with mood/anxiety disorders, mediated by substance dependence (the reverse or 'substance-induced' model). In a subsample, we tested polygenic scores for the substance dependence and mood/anxiety disorder factors as moderators in the mediation models. Although there were significant indirect paths in both directions, mediation by mood/anxiety disorders (the forward model) was greater than that by substance dependence (the reverse model). Greater genetic risk for substance use disorders was associated with a weaker direct association between ACEs and substance dependence in both ancestry groups (reflecting gene × environment interactions) and a weaker indirect association in European-ancestry individuals (reflecting moderated mediation). We found greater evidence that substance dependence reflects self-medication of mood/anxiety disorders than that mood/anxiety disorders are substance induced. Among individuals at higher genetic risk for substance dependence, ACEs were less associated with that outcome. Following exposure to ACEs, multiple pathways appear to underlie the associations between mood/anxiety disorders and substance dependence. Specification of these pathways could inform individually targeted prevention and treatment approaches.

Exploratory Analysis of Concordance Between Clinician-Collected and Self-Sampled Human Papillomavirus Tests in a Small Cohort of Average- and High-Risk Patients.

Objectives: Cervical cancer screening rates have stagnated, but self-sampling modalities have the potential to increase uptake. This study compares the test characteristics of self-sampled high-risk human papillomavirus (hrHPV) tests with clinician-collected hrHPV tests in average-risk (i.e., undergoing routine screening) and high-risk patients (i.e., receiving follow-up after abnormal screening results). Methods: In this cross-sectional study, a relatively small cohort of average-risk (n = 35) and high-risk (n = 12) participants completed both clinician-collected and self-sampled hrHPV testing, along with a brief phone survey. We assessed hrHPV positivity, concordance, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity across both methods (for types 16, 18, or other hrHPV). We also explored the relationship between test concordance and sociodemographic/behavioral factors. Results: Among average-risk participants, hrHPV positivity was 6% for both test methods (i.e., hrHPV-positive cases: n = 2), resulting in reported concordance, PPV, NPV, sensitivity, and specificity of 100%. Among high-risk participants, hrHPV positivity was 100% for clinician-collected tests but only 67% for self-sampled tests, showing varied concordance and sensitivity. Concordance was not associated with sociodemographic or behavioral factors. Conclusions: Self-sampled hrHPV testing demonstrated high accuracy for average-risk patients in this exploratory study. However, its performance was less consistent in high-risk patients who had already received an abnormal screening result, which could be attributed to spontaneous viral clearance over time. The limited number of participants, particularly HPV-positive cases, suggests caution in interpreting these results. Further research with larger cohorts is necessary to validate these findings and to explore the integration of self-sampled hrHPV testing into routine clinical care, particularly for patients with a history of cervical abnormalities. Clinical Trial Registration: NCT04591977, NCT04585243.

Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and medical traits.

Co-occurring psychiatric, medical, and substance use disorders (SUDs) are common, but the complex pathways leading to such comorbidities are poorly understood. A greater understanding of genetic influences on this phenomenon could inform precision medicine efforts. We used the Yale-Penn dataset, a cross-sectional sample enriched for individuals with SUDs, to examine pleiotropic effects of genetic liability for psychiatric and medical traits. Participants completed an in-depth interview that provides information on demographics, environment, medical illnesses, and psychiatric and SUDs. Polygenic scores (PGS) for psychiatric disorders and medical traits were calculated in European-ancestry (EUR; n=5,691) participants and, when discovery datasets were available, for African-ancestry (AFR; n=4,918) participants. Phenome-wide association studies (PheWAS) were then conducted. In AFR participants, the only PGS with significant associations was bipolar disorder (BD), all of which were with substance use phenotypes. In EUR participants, PGS for major depressive disorder (MDD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), body mass index (BMI), coronary artery disease (CAD), and type 2 diabetes (T2D) all showed significant associations, the majority of which were with phenotypes in the substance use categories. For instance, PGS MDD was associated with over 200 phenotypes, 15 of which were depression-related (e.g., depression criterion count), 55 of which were other psychiatric phenotypes, and 126 of which were substance use phenotypes; and PGS BMI was associated with 138 phenotypes, 105 of which were substance related. Genetic liability for psychiatric and medical traits is associated with numerous phenotypes across multiple categories, indicative of the broad genetic liability of these traits.

Adverse Childhood Events, Mood and Anxiety Disorders, and Substance Dependence: Gene X Environment Effects and Moderated Mediation.

Background: Adverse childhood events (ACEs) contribute to the development of mood and anxiety disorders and substance dependence. However, the extent to which these effects are direct or indirect and whether genetic risk moderates them is unclear. Methods: We examined associations among ACEs, mood/anxiety disorders, and substance dependence in 12,668 individuals (44.9% female, 42.5% African American/Black, 42.1% European American/White). We generated latent variables for each phenotype and modeled direct and indirect effects of ACEs on substance dependence, mediated by mood/anxiety disorders (forward or "self-medication" model) and of ACEs on mood/anxiety disorders, mediated by substance dependence (reverse or "substance-induced" model). In a sub-sample, we also generated polygenic scores for substance dependence and mood/anxiety disorder factors, which we tested as moderators in the mediation models. Results: Although there were significant indirect effects in both directions, mediation by mood/anxiety disorders (forward model) was greater than by substance dependence (reverse model). Greater genetic risk for substance dependence was associated with a weaker direct effect of ACEs on substance dependence in both the African- and European-ancestry groups (i.e., gene-environment interaction) and a weaker indirect effect in European-ancestry individuals (i.e., moderated mediation). Conclusion: We found greater evidence that substance dependence results from self-medication of mood/anxiety disorders than that mood/anxiety disorders are substance induced. Among individuals at higher genetic risk for substance dependence who are more likely to develop a dependence diagnosis, ACEs exert less of an effect in promoting that outcome. Following exposure to ACEs, multiple pathways lead to mood/anxiety disorders and substance dependence. Specification of these pathways could inform individually targeted prevention and treatment approaches.

Adverse Childhood Events, Mood and Anxiety Disorders, and Substance Dependence: Gene x Environment Effects and Moderated Mediation.

Background: Adverse childhood events (ACEs) contribute to the development of mood and anxiety disorders and substance dependence. However, the extent to which these effects are direct or indirect and whether genetic risk moderates them is unclear. Methods: We examined associations among ACEs, mood/anxiety disorders, and substance dependence in 12,668 individuals (44.9% female, 42.5% African American/Black, 42.1% European American/White). We generated latent variables for each phenotype and modeled direct and indirect effects of ACEs on substance dependence, mediated by mood/anxiety disorders (forward or "self-medication" model) and of ACEs on mood/anxiety disorders, mediated by substance dependence (reverse or "substance-induced" model). In a sub-sample, we also generated polygenic scores for substance dependence and mood/anxiety disorder factors, which we tested as moderators in the mediation models. Results: Although there were significant indirect effects in both directions, mediation by mood/anxiety disorders (forward model) was greater than by substance dependence (reverse model). Greater genetic risk for substance dependence was associated with a weaker direct effect of ACEs on substance dependence in both the African- and European-ancestry groups (i.e., gene-environment interaction) and a weaker indirect effect in European-ancestry individuals (i.e., moderated mediation). Conclusion: We found greater evidence that substance dependence results from self-medication of mood/anxiety disorders than that mood/anxiety disorders are substance induced. Among individuals at higher genetic risk for substance dependence who are more likely to develop a dependence diagnosis, ACEs exert less of an effect in promoting that outcome. Following exposure to ACEs, multiple pathways lead to mood/anxiety disorders and substance dependence. Specification of these pathways could inform individually targeted prevention and treatment approaches.

Assessing the Feasibility of a Faith-Based Colorectal Cancer Education and Screening Intervention for Latino Men in Pennsylvania.

Introduction: Limited health knowledge, literacy, engagement in preventive health services, participation in health promotion behaviors, and cultural factors place Latino men at high risk for colorectal cancer (CRC). This pilot study aimed to determine the feasibility and acceptability of a faith-based cancer education intervention focusing on Latino men between 45 and 74 years old. Methods: This pilot study used a single group pre- and post-intervention research design to compare changes in knowledge, perceived benefit of screening, perceived susceptibility and severity of CRC, and the completion of CRC screening after the intervention. Results: In this study, Latino men were willing to participate in a CRC educational intervention supported by a faith-based institution. The participants had limited knowledge about CRC, yet most recognized that screening is beneficial and that getting CRC is serious. Sixty percent of the participants completed the fecal immunochemical screening test, which showed that the intervention impacted the screening uptake among this group. Conclusion: The findings of this study support the further development of faith-based interventions focusing on Latino men.

Prenatal Care: An Evidence-Based Approach.

Well-coordinated prenatal care that follows an evidence-based, informed process results in fewer hospital admissions, improved education, greater satisfaction, and lower pregnancy-associated morbidity and mortality. Care initiated at 10 weeks or earlier improves outcomes. Identification and treatment of periodontal disease decreases preterm delivery risk. A prepregnancy body mass index greater than 25 kg per m2 is associated with gestational diabetes mellitus, hypertension, miscarriage, and stillbirth. Advanced maternal and paternal age (35 years or older) is associated with gestational diabetes, hypertension, miscarriage, intrauterine growth restriction, aneuploidy, birth defects, and stillbirth. Rho(D) immune globulin decreases alloimmunization risk in a patient who is RhD-negative carrying a fetus who is RhD-positive. Treatment of iron deficiency anemia decreases the risk of preterm delivery, intrauterine growth restriction, and perinatal depression. Ancestry-based genetic risk stratification using family history can inform genetic screening. Folic acid supplementation (400 to 800 mcg daily) decreases the risk of neural tube defects. All pregnant patients should be screened for asymptomatic bacteriuria, sexually transmitted infections, and immunity against rubella and varicella and should receive tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), influenza, and COVID-19 vaccines. Testing for group B Streptococcus should be performed between 36 and 37 weeks, and intrapartum antibiotic prophylaxis should be initiated to decrease the risk of neonatal infection. Because of the impact of social determinants of health on outcomes, universal screening for depression, anxiety, intimate partner violence, substance use, and food insecurity is recommended early in pregnancy. Screening for gestational diabetes between 24 and 28 weeks is recommended for all patients. People at risk of preeclampsia, including those diagnosed with COVID-19 in pregnancy, should be offered 81 mg of aspirin daily starting at 12 weeks. Chronic hypertension should be treated to a blood pressure of less than 140/90 mm Hg.

Derivation of a Unique, Algorithm-Based Approach to Cancer Patient Navigator Workload Management.

PURPOSE: Cancer patient navigators (CPNs) can decrease the time from diagnosis to treatment, but workloads vary widely, which may lead to burnout and less optimal navigation. Current practice for patient distribution among CPNs at our institution approximates random distribution. A literature search did not uncover previous reports of an automated algorithm to distribute patients to CPNs. We sought to develop an automated algorithm to fairly distribute new patients among CPNs specializing in the same cancer type(s) and assess its performance through simulation on a retrospective data set. METHODS: Using a 3-year data set, a proxy for CPN work was identified and multiple models were developed to predict the upcoming week's workload for each patient. An XGBoost-based predictor was retained on the basis of its superior performance. A distribution model was developed to fairly distribute new patients among CPNs within a specialty on the basis of predicted work needed. The predicted work included the week's predicted workload from a CPN's existing patients plus that of newly distributed patients to the CPN. Resulting workload unfairness was compared between predictor-informed and random distribution. RESULTS: Predictor-informed distribution significantly outperformed random distribution for equalizing weekly workloads across CPNs within a specialty. CONCLUSION: This derivation work demonstrates the feasibility of an automated model to distribute new patients more fairly than random assignment (with unfairness assessed using a workload proxy). Improved workload management may help reduce CPN burnout and improve navigation assistance for patients with cancer.

Evaluation of the Spanish-Language Cancer Educational Webinar Series "Vamos a educarnos contra el cáncer" with the RE-AIM Framework.

The COVID-19 pandemic disrupted healthcare for patients with chronic diseases, including cancer. Barriers to healthcare increased, especially for racial and ethnic minorities. While many institutions developed webinars to educate community members, few webinars used a community-based participatory approach, employed a theory-based engagement design, and were evaluated. This manuscript reports the outcomes of "Vamos a educarnos contra el cáncer," a 2021 webinar series. Monthly educational webinars were conducted in Spanish on cancer-related topics. The presentations were delivered by Spanish-speaking content experts from different organizations. Webinars were conducted using the video conferencing platform Zoom. Polls were launched during the webinar to collect data and evaluate each webinar. The RE-AIM model of reach, effectiveness, adoption, implementation, and maintenance was used to evaluate the series. The SAS Analytics Software was used for analysis and data management. Two hundred ninety-seven people participated with over 3000 views of the webinar recordings (Reach); 90% rated the sessions as good or excellent (Effectiveness); 86% agreed to adopt or improve a cancer-related behavior, and 90% reported willingness to adopt or improve a cancer-related action for someone else (Adoption); 92% reported feeling engaged (Implementation). The series has produced a resource library, manual of operations, and agreement of the Hispanic/Latino Cancer Community Advisory Board (CAB) to continue the webinar series in the future (Maintenance). Overall, these results highlight the impact of this webinar series and provide a standard approach to planning, delivering, and evaluating webinars as a strategy for cancer prevention and control in a culturally appropriate manner.

Screening for Social Determinants of Health: Active and Passive Information Retrieval Methods.

Screening for social determinants of health (SDOH) is recommended, but numerous barriers exist to implementing SDOH screening in clinical spaces. In this study, the authors identified how both active and passive information retrieval methods may be used in clinical spaces to screen for SDOH and meet patient needs. The authors conducted a retrospective sequential cohort analysis comparing the active identification of SDOH through a patient-led digital manual screening process completed in primary care offices from September 2019 to January 2020 and passive identification of SDOH through natural language processing (NLP) from September 2016 to August 2018, among 1735 patients at a large midwestern tertiary referral hospital system and its associated outlying primary care and outpatient facilities. The percent of patients identified by both the passive and active identification methods as experiencing SDOH varied from 0.3% to 4.7%. The active identification method identified social integration, domestic safety, financial resources, food insecurity, transportation, housing, and stress in proportions ranging from 5% to 36%. The passive method contributed to the identification of financial resource issues and stress, identifying 9.6% and 3% of patients to be experiencing these issues, respectively. SDOH documentation varied by provider type. The combination of passive and active SDOH screening methods can provide a more comprehensive picture by leveraging historic patient interactions, while also eliciting current patient needs. Using passive, NLP-based methods to screen for SDOH will also help providers overcome barriers that have historically prevented screening.

Improving cervical cancer screening rates: a scoping review of resources and interventions.

INTRODUCTION: Cervical cancer mortality can be prevented through early detection with screening methods such as Pap and high-risk human papillomavirus (hrHPV) tests; however, only 81% of women aged 21-65 are up-to-date on screening. Many interventions to increase cervical cancer screening have been implemented, but there is limited understanding about which intervention components are most successful. METHODS: We conducted a scoping review of existing literature and available resources for cervical cancer screening interventions to identify gaps in the research. We used t tests and correlations to identify associations among intervention components and effect sizes. RESULTS: Out of nine studies, the mean overall effect size for interventions was 11.3% increase in Pap testing for cervical cancer screening (range = - 4-24%). Interventions that included community health workers or one-on-one interaction had the biggest effect size (p < 0.05). No associations with effect size were noted for literacy level, number of intervention components, or targeting by race/ethnicity. CONCLUSIONS: Future interventions may include educational sessions with community health workers or one-on-one patient interaction to improve cervical cancer screening. Further research is needed to establish effect sizes for large-scale interventions and hrHPV screening interventions.

Closing the Gap: A Comparison of Engagement Interventions to Achieve Equitable Breast Cancer Screening in Rural Illinois.

Mammography screening rates are typically lower in those with less economic advantage (EA). This study, conducted at an integrated health care system covering a mixed rurality population, assessed the ability of interventions (text messages linking to a Web microsite, digital health care workers, and a community health fair) to affect mammography screening rates and disparity in those rates among different EA populations. Payor type served as a proxy for greater (commercially insured) versus lower (Medicaid insured) EA. 4,342 subjects were included across the preintervention ("Pre") and postintervention ("Post") periods. Interventions were prospectively applied to all Medicaid subjects and randomly selected commercial subjects. Applying interventions only to lower EA subjects reversed the screening rate disparity (2.6% Pre vs. -3.7% Post, odds ratio [OR] 2.4 P < 0.01). When intervention arms ("Least," "More," "Most") were equally applied, screening rates in both EA groups significantly increased in the More arm (Medicaid OR = 2.04 P = 0.04, Commercial OR = 3.08 P < 0.01) and Most arm (Medicaid OR 2.57 P < 0.01, Commercial OR 2.33 P < 0.01), but not in the Least (text-only) arm (Medicaid OR 1.83 P = 0.11, Commercial OR 1.72 P = 0.09), although this text-only arm was inadequately powered to detect a difference. In summary, targeting interventions to those with lower EA reversed screening rate disparities, text messaging combined with other interventions improved screening rates in both groups, and future research is needed to determine whether interventions can simultaneously improve screening rates for all without worsening the disparity.

Parathyroid Disorders.

Parathyroid disorders are most often identified incidentally by abnormalities in serum calcium levels when screening for renal or bone disease or other conditions. Parathyroid hormone, which is released by the parathyroid glands primarily in response to low calcium levels, stimulates osteoclastic bone resorption and serum calcium elevation, reduces renal calcium clearance, and stimulates intestinal calcium absorption through synthesis of 1,25-dihydroxyvitamin D. Primary hyperparathyroidism, in which calcium levels are elevated without appropriate suppression of parathyroid hormone levels, is the most common cause of hypercalcemia and is often managed surgically. Indications for parathyroidectomy in primary hyperparathyroidism include presence of symptoms, age 50 years or younger, serum calcium level more than 1 mg per dL above the upper limit of normal, osteoporosis, creatinine clearance less than 60 mL per minute per 1.73 m2, nephrolithiasis, nephrocalcinosis, and hypercalciuria. Secondary hyperparathyroidism is caused by alterations in calcium, phosphate, and vitamin D regulation that result in elevated parathyroid hormone levels. It most commonly occurs with chronic kidney disease and vitamin D deficiency, and less commonly with gastrointestinal conditions that impair calcium absorption. Secondary hyperparathyroidism can be managed with calcium and vitamin D replacement and reduction of high phosphate levels. There is limited evidence for the use of calcimimetics and vitamin D analogues for persistently elevated parathyroid hormone levels. Hypoparathyroidism, which is most commonly caused by iatrogenic surgical destruction of the parathyroid glands, is less common and results in hypocalcemia. Multiple endocrine neoplasia types 1 and 2A are rare familial syndromes that can result in primary hyperparathyroidism and warrant genetic testing of family members, whereas parathyroid cancer is a rare finding in patients with hyperparathyroidism.

Covid-19 vaccine acceptance and associated factors among pregnant women in Pennsylvania 2020.

Data on factors associated with vaccine acceptance among pregnant women are critical to the rapid scale up of interventions to improve vaccine uptake. When COVID-19 vaccines were still in the testing phases of research, we surveyed pregnant women accessing prenatal care at an academic medical institution in Central Pennsylvania, United States to examine factors associated with vaccine acceptance. Willingness to receive a COVID-19 vaccine once a vaccine became available was asked as part of an ongoing study on the COVID-19 pandemic and pregnancy (n = 196). Overall, 65% of women reported they would be willing or somewhat willing to receive the COVID-19 vaccine. Women who had received an influenza vaccine within the past year were more likely to be willing to receive the COVID-19 vaccine than women who had never received an influenza vaccine or those who received it over one year ago (aOR 4.82; 95% CI 2.17, 10.72). Similarly, women who were employed full-time were more willing to receive the COVID-19 vaccine than women who were not employed full time (aOR 2.22; 95% CI 1.02, 4.81), and women who reported feeling overloaded were more willing to receive the COVID-19 vaccine than women who did not feel overloaded (aOR 2.18; 95% CI 1.02, 4.68). Our findings support the need to increase vaccination education among pregnant women before vaccines are rolled out, especially those who have not received an influenza vaccine within the past year. Improved understanding of willingness to vaccinate among pregnant women will improve future pandemic responses and current vaccination efforts.

Disparities in Cancer Screening: The Role of County-Level Metropolitan Status and Racial Residential Segregation.

Mortality from cervical and colorectal cancers can be reduced through routine screening, which can often be accessed through primary care. However, uptake of screening in the US remains suboptimal, with disparities observed across geographic characteristics, such as metropolitan status or level of racial residential segregation. Little is known about the interaction of metropolitan status and segregation in their relationship with cancer screening. We conducted a quantitative survey of 474 women aged 45-65 in central Pennsylvania. The survey collected county-level characteristics and participant-level demographics, beliefs, cancer screening barriers, and cervical and colorectal cancer screening. We used bivariate and multivariable logistic regression to analyze relationships between metropolitan status and segregation with screening. For cervical cancer screening, 82.8% of participants were up-to-date, which did not differ by county type in the final analysis. Higher healthcare trust, higher cancer fatalism, and reporting cost as a barrier were associated with cervical cancer screening. For colorectal cancer screening, 55.4% of participants were up-to-date, which differed by county type. In metropolitan counties, segregation was not associated with colorectal cancer screening, but in non-metropolitan counties, segregation was associated with greater colorectal cancer screening. The relationship between metropolitan status and being up-to-date with colorectal, but not cervical, cancer screening varied by segregation. Other important beliefs and barriers to screening varied by county type. This research can guide future cancer screening interventions in primary care settings in underserved communities.

Detection of SARS-CoV-2 Virus Amplification Using a Crumpled Graphene Field-Effect Transistor Biosensor.

The rapid and unexpected spread of SARS-CoV-2 worldwide has caused unprecedented disruption to daily life and has brought forward critical challenges for public health. The disease was the largest cause of death in the United States in early 2021. Likewise, the COVID-19 pandemic has highlighted the need for rapid and accurate diagnoses at scales larger than ever before. To improve the availability of current gold standard diagnostic testing methods, the development of point-of-care devices that can maintain gold standard sensitivity while reducing the cost and providing portability is much needed. In this work, we combine the amplification capabilities of reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) techniques with high-sensitivity end-point detection of crumpled graphene field-effect transistors (cgFETs) to develop a portable detection cell. This electrical detection method takes advantage of the ability of graphene to adsorb single-stranded DNA due to noncovalent π-π bonds but not double-stranded DNA. These devices have demonstrated the ability to detect the presence of the SARS-CoV-2 virus in a range from 10 to 104 copies/µL in 20 viral transport medium (VTM) clinical samples. As a result, we achieved 100% PPV, NPV, sensitivity, and specificity with 10 positive and 10 negative VTM clinical samples. Further, the cgFET devices can differentiate between positive and negative VTM clinical samples in 35 min based on the Dirac point shift. Likewise, the improved sensing capabilities of the crumpled gFET were compared with those of the traditional flat gFET devices.

Management of Cervical Dysplasia Using Office Loop Electrosurgical Excision Procedure.

Declining cervical cancer rates in the United States highlights the value of prevention and early detection of premalignant cervical disease afforded by the human papillomavirus vaccine and Pap smear. The availability of in-office loop electrosurgical excision procedure affords clinicians with a cost-effective and preferred tool for the excision of high-grade lesions of the cervix with minimal risk for severe adverse outcomes. The most recent American Society for Colposcopy and Cervical Pathology guidelines recommend a risk-based approach for the detection, treatment, and surveillance of cervical disease and specifically focus on the risk of developing cervical intraepithelial neoplasia 3 or worse histology.