Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 69
Filter
1.
Pract Lab Med ; 40: e00399, 2024 May.
Article in English | MEDLINE | ID: mdl-38812907

ABSTRACT

a Objectives: Dopamine is known to cause negative interference on enzymatic creatinine measurement. However, its effect on the Jaffe reaction, and its concentration required to interfere with enzymatic reactions, remain uncertain. This study was designed to study the interference of stable dopamine infusion on Jaffe and enzymatic creatinine assays, as well as the effect of dopamine infusion drip arm contamination on both creatinine assays. b Design and Methods: For the first part of the study, dopamine was spiked into pooled plasma samples at different concentrations to mimic the scenario of patients on dopamine infusion at an infusion rate between 2 and 20 µg/kg/min. For the second part, dopamine preparation of 2 g/L (same as the preparation used clinically) was mixed with pooled plasma samples at different proportions to mimic drip arm contamination. Creatinine concentrations were measured using Jaffe and enzymatic reactions. c Results: The first part showed that creatinine measurements were not interfered by dopamine infusion at an infusion rate between 2 and 20 µg/kg/min. The second part showed that dopamine could negatively interfere with enzymatic creatinine assays, even with minute drip arm contamination. The effect on the Jaffe reaction was less significant. d Discussion: Creatinine concentration could be reliably measured by Jaffe or enzymatic reactions if samples are from venous access sites other than the site of dopamine infusion. When dopamine interference on enzymatic creatinine assays is suspected, using the Jaffe reaction to cross-check may provide additional useful information.

3.
Genome Res ; 34(2): 189-200, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38408788

ABSTRACT

Recent studies have revealed an unexplored population of long cell-free DNA (cfDNA) molecules in human plasma using long-read sequencing technologies. However, the biological properties of long cfDNA molecules (>500 bp) remain largely unknown. To this end, we have investigated the origins of long cfDNA molecules from different genomic elements. Analysis of plasma cfDNA using long-read sequencing reveals an uneven distribution of long molecules from across the genome. Long cfDNA molecules show overrepresentation in euchromatic regions of the genome, in sharp contrast to short DNA molecules. We observe a stronger relationship between the abundance of long molecules and mRNA gene expression levels, compared with short molecules (Pearson's r = 0.71 vs. -0.14). Moreover, long and short molecules show distinct fragmentation patterns surrounding CpG sites. Leveraging the cleavage preferences surrounding CpG sites, the combined cleavage ratios of long and short molecules can differentiate patients with hepatocellular carcinoma (HCC) from non-HCC subjects (AUC = 0.87). We also investigated knockout mice in which selected nuclease genes had been inactivated in comparison with wild-type mice. The proportion of long molecules originating from transcription start sites are lower in Dffb-deficient mice but higher in Dnase1l3-deficient mice compared with that of wild-type mice. This work thus provides new insights into the biological properties and potential clinical applications of long cfDNA molecules.


Subject(s)
Carcinoma, Hepatocellular , Cell-Free Nucleic Acids , Liver Neoplasms , Humans , Animals , Mice , Cell-Free Nucleic Acids/genetics , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , DNA/genetics , Genomics , Mice, Knockout , Endodeoxyribonucleases/genetics
4.
Prenat Diagn ; 43(11): 1385-1393, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37655424

ABSTRACT

OBJECTIVE: Long cell-free DNA (cfDNA) can be found in the plasma of pregnant women and cancer patients. We investigated if droplet digital PCR (ddPCR) can analyze such molecules for diagnostic purposes using preeclampsia as a model. METHOD: Plasma samples from ten preeclamptic and sixteen normal pregnancies were analyzed. Two ddPCR assays targeting a single-copy gene, VCP, and one ddPCR assay targeting LINE-1 repetitive regions were used to measure the percentages of long cfDNA >533, 1001, and 170 bp, respectively. The LINE-1 assay was developed as guided by in silico PCR analyses to better differentiate preeclamptic and normal pregnancies. RESULTS: Preeclamptic patients had a significantly lower median percentage of long cfDNA than healthy pregnant controls, as determined by the LINE-1 170 bp assay (28.9% vs. 35.1%, p < 0.0001) and the VCP 533 bp assay (6.6% vs. 8.7%, p = 0.014). The LINE-1 assay provided a better differentiation than the VCP 533 bp assay (area under ROC curves, 0.94 vs. 0.79). CONCLUSION: ddPCR is a cost-effective approach for unlocking diagnostic information carried by long cfDNA in plasma and may have applications for the detection of preeclampsia. Further longitudinal studies with larger cohorts are required to assess the clinical utility of this test.

5.
School Ment Health ; 15(2): 583-599, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37622166

ABSTRACT

Racial/ethnic minoritized (REM) youth represent a high-risk group for suicide, yet there are striking disparities in their use of mental health services (MHS) even after risk is identified in schools. Prior research suggests that school-based risk assessments and hospitalization encounters can be negatively experienced by REM youth and families, thus deterring likelihood of seeking follow-up care. The Safe Alternatives for Teens and Youth-Acute (SAFETY-A) is a brief, strengths-based, cognitive-behavioral family intervention demonstrated to increase linkage to MHS when implemented in emergency departments. With its focus on strengths and family engagement, SAFETY-A may cultivate a positive therapeutic encounter suited to addressing disparities in MHS by enhancing trust and family collaboration, if appropriately adapted for schools. Thirty-seven school district leaders and frontline school MHS providers from districts serving primarily socioeconomically disadvantaged REM communities participated in key informant interviews and focus groups. First, interviews were conducted to understand usual care processes for responding to students with suicidal thoughts and behaviors, and perspectives on the strengths and disadvantages of current practices. An as-is process analysis was used to describe current practices spanning risk assessment, crisis intervention, and follow-up. Second, focus groups were conducted to solicit perceptions of the fit of SAFETY-A for these school contexts. Thematic analysis of the interviews and focus groups was used to identify multilevel facilitators and barriers to SAFETY-A implementation, and potential tailoring variables for implementation strategies across school districts.

6.
J Behav Health Serv Res ; 50(4): 468-485, 2023 10.
Article in English | MEDLINE | ID: mdl-37430134

ABSTRACT

Evidence-based practices (EBPs) are often adapted during community implementation to improve EBP fit for clients and the service context. Augmenting EBPs with additional dosing and content may improve fit. However, reducing EBP content can reduce EBP effectiveness. Using multilevel regression models, this study examined whether supportive program climate and program-furnished EBP-specific implementation strategies (e.g., materials, ongoing training, in-house experts) are associated with augmenting and reducing adaptations, and whether therapist emotional exhaustion moderated these associations. Data were collected from surveys completed by 439 therapists from 102 programs 9 years after a system-driven EBP implementation initiative. Supportive program climate was associated with more augmenting adaptations. Emotional exhaustion was a significant moderator. When organizations used more EBP-specific implementation strategies, more emotionally exhausted therapists reduced EBPs less and less emotionally exhausted therapists augmented EBPs more. Findings provide guidance on how organizations can support appropriate EBP adaptations in spite of therapist emotional exhaustion.


Subject(s)
Evidence-Based Practice , Mental Health , Humans , Child , Adolescent , Surveys and Questionnaires , Allied Health Personnel , Emotions
7.
Mol Diagn Ther ; 27(5): 563-571, 2023 09.
Article in English | MEDLINE | ID: mdl-37474843

ABSTRACT

Liquid biopsy using cell-free DNA (cfDNA) has gained global interest as a molecular diagnostic tool. However, the analysis of cfDNA in cancer patients and pregnant women has been focused on short DNA molecules (e.g., ≤ 600 bp). With the detection of long cfDNA in the plasma of pregnant women and cancer patients in two recent studies, a new avenue of long cfDNA-based liquid biopsy has been opened. In this review, we summarize our current knowledge in this nascent field of long cfDNA analysis, focusing on the fragmentomic and epigenetic features of long cfDNA. In particular, long-read sequencing enabled single-molecule methylation analysis and subsequent determination of the tissue-of-origin of long cfDNA, which has promising clinical potential in prenatal and cancer testing. We also examine some of the limitations that may hinder the immediate clinical applications of long cfDNA analysis and the current efforts involved in addressing them. With concerted efforts in this area, it is hoped that long cfDNA analysis will add to the expanding armamentarium of liquid biopsy.


Subject(s)
Cell-Free Nucleic Acids , Neoplasms , Humans , Female , Pregnancy , Liquid Biopsy , Neoplasms/diagnosis , Neoplasms/genetics , DNA/genetics , DNA Methylation
8.
Elife ; 122023 04 25.
Article in English | MEDLINE | ID: mdl-37096663

ABSTRACT

In value-based decision making, options are selected according to subjective values assigned by the individual to available goods and actions. Despite the importance of this faculty of the mind, the neural mechanisms of value assignments, and how choices are directed by them, remain obscure. To investigate this problem, we used a classic measure of utility maximization, the Generalized Axiom of Revealed Preference, to quantify internal consistency of food preferences in Caenorhabditis elegans, a nematode worm with a nervous system of only 302 neurons. Using a novel combination of microfluidics and electrophysiology, we found that C. elegans food choices fulfill the necessary and sufficient conditions for utility maximization, indicating that nematodes behave as if they maintain, and attempt to maximize, an underlying representation of subjective value. Food choices are well-fit by a utility function widely used to model human consumers. Moreover, as in many other animals, subjective values in C. elegans are learned, a process we find requires intact dopamine signaling. Differential responses of identified chemosensory neurons to foods with distinct growth potentials are amplified by prior consumption of these foods, suggesting that these neurons may be part of a value-assignment system. The demonstration of utility maximization in an organism with a very small nervous system sets a new lower bound on the computational requirements for utility maximization and offers the prospect of an essentially complete explanation of value-based decision making at single neuron resolution in this organism.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/physiology , Caenorhabditis elegans Proteins/metabolism , Food , Food Preferences , Signal Transduction
9.
Proc Natl Acad Sci U S A ; 120(17): e2220982120, 2023 04 25.
Article in English | MEDLINE | ID: mdl-37075072

ABSTRACT

Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.


Subject(s)
Cell-Free Nucleic Acids , Humans , Mice , Animals , Cell-Free Nucleic Acids/genetics , Deoxyribonucleases/genetics , Mice, Knockout , Endonucleases/genetics , DNA Fragmentation , Endodeoxyribonucleases/genetics
10.
Behav Ther ; 54(1): 101-118, 2023 01.
Article in English | MEDLINE | ID: mdl-36608968

ABSTRACT

Understanding patient responsiveness, a component of fidelity, is essential as it impacts treatment outcome and ongoing use of treatment elements. This study evaluated patient responsiveness-operationalized as receptivity to treatment modules and ratings of the usefulness and the utilization of treatment elements-to the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) in a sample of adults with serious mental illness (SMI) and sleep/circadian dysfunction. Adults with SMI and sleep/circadian dysfunction (N = 104) received TranS-C in a community mental health setting. Independent raters rated TranS-C sessions to assess receptivity. At posttreatment and 6-month follow-up, participants completed a usefulness scale, utilization scale, the PROMIS Sleep Disturbance (PROMIS-SD) and Sleep-Related Impairment (PROMIS-SRI) scales, DSM-5 Cross-Cutting Measure (DSM-5-CC), and Sheehan Disability Scale (SDS). Receptivity was rated as somewhat to fully understood, and predicted a reduction on the DSM-5-CC. On average, participants rated TranS-C as moderately useful and utilized treatment elements occasionally. Ratings of usefulness were associated with the PROMIS-SD, PROMIS-SRI, and DSM-5-CC at posttreatment, but not with the SDS. Ratings of utilization were not associated with outcome. The findings add to the literature on patient responsiveness, an implementation outcome, and provide data on the utility of TranS-C within a community mental health setting.


Subject(s)
Sleep Wake Disorders , Sleep , Humans , Adult , Sleep Wake Disorders/therapy , Sleep Wake Disorders/diagnosis , Treatment Outcome , Patients , Longitudinal Studies
11.
Ann Am Thorac Soc ; 20(5): 713-720, 2023 05.
Article in English | MEDLINE | ID: mdl-36508292

ABSTRACT

Rationale: Family members of critically ill patients with coronavirus disease (COVID-19) have described increased symptoms of posttraumatic stress disorder (PTSD). Little is known about how these symptoms may change over time. Objectives: We studied changes in PTSD symptoms in family members of critically ill patients with COVID-19 over 12 months. Methods: This prospective, multisite observational cohort study recruited participants at 12 hospitals in five states. Calls were made to participants at 3-4 months, 6 months, and 12 months after patient admission to the intensive care unit. Results: There were 955 eligible family members, of whom 330 (53.3% of those reached) consented to participate. Complete longitudinal data was acquired for 115 individuals (34.8% consented). PTSD symptoms were measured by the IES-6 (Impact of Events Scale-6), with a score of at least 10 identifying significant symptoms. At 3 months, the mean IES-6 score was 11.9 ± 6.1, with 63.6% having significant symptoms, decreasing to 32.9% at 1 year (mean IES-6 score, 7.6 ± 5.0). Three clusters of symptom evolution emerged over time: persistent symptoms (34.8%, n = 40), recovered symptoms (33.0%, n = 38), and nondevelopment of symptoms (32.2%, n = 37). Although participants identifying as Hispanic demonstrated initially higher adjusted IES-6 scores (2.57 points higher [95% confidence interval (CI), 1.1-4.1; P < 0.001]), they also demonstrated a more dramatic improvement in adjusted scores over time (4.7 greater decrease at 12 months [95% CI, 3.2-6.3; P < 0.001]). Conclusions: One year later, some family members of patients with COVID-19 continue to experience significant symptoms of PTSD. Further studies are needed to better understand how various differences contribute to increased risk for these symptoms.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/etiology , Prospective Studies , Critical Illness , COVID-19/complications , Family
12.
Clin Chem ; 69(2): 168-179, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36322427

ABSTRACT

BACKGROUND: Recent studies using single molecule, real-time (SMRT) sequencing revealed a substantial population of analyzable long cell-free DNA (cfDNA) in plasma. Potential clinical utilities of such long cfDNA in pregnancy and cancer have been demonstrated. However, the performance of different long-read sequencing platforms for the analysis of long cfDNA remains unknown. METHODS: Size biases of SMRT sequencing by Pacific Biosciences (PacBio) and nanopore sequencing by Oxford Nanopore Technologies (ONT) were evaluated using artificial mixtures of sonicated human and mouse DNA of different sizes. cfDNA from plasma samples of pregnant women at different trimesters, hepatitis B carriers, and patients with hepatocellular carcinoma were sequenced with the 2 platforms. RESULTS: Both platforms showed biases to sequence longer (1500 bp vs 200 bp) DNA fragments, with PacBio showing a stronger bias (5-fold overrepresentation of long fragments vs 2-fold in ONT). Percentages of cfDNA fragments 500 bp were around 6-fold higher in PacBio compared with ONT. End motif profiles of cfDNA from PacBio and ONT were similar, yet exhibited platform-dependent patterns. Tissue-of-origin analysis based on single-molecule methylation patterns showed comparable performance on both platforms. CONCLUSIONS: SMRT sequencing generated data with higher percentages of long cfDNA compared with nanopore sequencing. Yet, a higher number of long cfDNA fragments eligible for the tissue-of-origin analysis could be obtained from nanopore sequencing due to its much higher throughput. When analyzing the size and end motif of cfDNA, one should be aware of the analytical characteristics and possible biases of the sequencing platforms being used.


Subject(s)
Cell-Free Nucleic Acids , Liver Neoplasms , Nanopore Sequencing , Humans , Female , Pregnancy , Animals , Mice , Cell-Free Nucleic Acids/genetics , High-Throughput Nucleotide Sequencing , Sequence Analysis, DNA , DNA/genetics
13.
Clin Chem ; 69(2): 189-201, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36576350

ABSTRACT

BACKGROUND: Nuclear-derived cell-free DNA (cfDNA) molecules in blood plasma are nonrandomly fragmented, bearing a wealth of information related to tissues of origin. DNASE1L3 (deoxyribonuclease 1 like 3) is an important player in shaping the fragmentation of nuclear-derived cfDNA molecules, preferentially generating molecules with 5 CC dinucleotide termini (i.e., 5 CC-end motif). However, the fragment end properties of microbial cfDNA and its clinical implication remain to be explored. METHODS: We performed end motif analysis on microbial cfDNA fragments in plasma samples from patients with sepsis. A sequence context-based normalization method was used to minimize the potential biases for end motif analysis. RESULTS: The end motif profiles of microbial cfDNA appeared to resemble that of nuclear cfDNA (Spearman correlation coefficient: 0.82, P value 0.001). The CC-end motif was the most preferred end motif in microbial cfDNA, suggesting that DNASE1L3 might also play a role in the fragmentation of microbe-derived cfDNA in plasma. Of note, differential end motifs were present between microbial cfDNA originating from infection-causing pathogens (enriched at the CC-end) and contaminating microbial DNA potentially derived from reagents or the environment (nearly random). The use of fragment end signatures allowed differentiation between confirmed pathogens and contaminating microbes, with an area under the receiver operating characteristic curve of 0.99. The performance appeared to be superior to conventional analysis based on microbial cfDNA abundance alone. CONCLUSIONS: The use of fragmentomic features could facilitate the differentiation of underlying contaminating microbes from true pathogens in sepsis. This work demonstrates the potential usefulness of microbial cfDNA fragmentomics in metagenomics analysis.


Subject(s)
Cell-Free Nucleic Acids , Sepsis , Humans , DNA/genetics , Sepsis/diagnosis , DNA Fragmentation
14.
Clin Case Rep ; 10(12): e6629, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36483860

ABSTRACT

Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is often misdiagnosed as other forms of diabetes. A 42-year-old pregnant lady with pre-existing diabetes was treated with insulin during first trimester. Fetal growth restriction was noted since mid-second trimester. Genetic testing suggested the diagnosis of GCK-MODY.

16.
Proc Natl Acad Sci U S A ; 119(44): e2209852119, 2022 11.
Article in English | MEDLINE | ID: mdl-36288287

ABSTRACT

Cell-free DNA (cfDNA) fragmentation patterns contain important molecular information linked to tissues of origin. We explored the possibility of using fragmentation patterns to predict cytosine-phosphate-guanine (CpG) methylation of cfDNA, obviating the use of bisulfite treatment and associated risks of DNA degradation. This study investigated the cfDNA cleavage profile surrounding a CpG (i.e., within an 11-nucleotide [nt] window) to analyze cfDNA methylation. The cfDNA cleavage proportion across positions within the window appeared nonrandom and exhibited correlation with methylation status. The mean cleavage proportion was ∼twofold higher at the cytosine of methylated CpGs than unmethylated ones in healthy controls. In contrast, the mean cleavage proportion rapidly decreased at the 1-nt position immediately preceding methylated CpGs. Such differential cleavages resulted in a characteristic change in relative presentations of CGN and NCG motifs at 5' ends, where N represented any nucleotide. CGN/NCG motif ratios were correlated with methylation levels at tissue-specific methylated CpGs (e.g., placenta or liver) (Pearson's absolute r > 0.86). cfDNA cleavage profiles were thus informative for cfDNA methylation and tissue-of-origin analyses. Using CG-containing end motifs, we achieved an area under a receiver operating characteristic curve (AUC) of 0.98 in differentiating patients with and without hepatocellular carcinoma and enhanced the positive predictive value of nasopharyngeal carcinoma screening (from 19.6 to 26.8%). Furthermore, we elucidated the feasibility of using cfDNA cleavage patterns to deduce CpG methylation at single CpG resolution using a deep learning algorithm and achieved an AUC of 0.93. FRAGmentomics-based Methylation Analysis (FRAGMA) presents many possibilities for noninvasive prenatal, cancer, and organ transplantation assessment.


Subject(s)
Cell-Free Nucleic Acids , Liver Neoplasms , Pregnancy , Female , Humans , Cell-Free Nucleic Acids/genetics , Biomarkers, Tumor/genetics , DNA Methylation , Liver Neoplasms/genetics , Epigenesis, Genetic , DNA/genetics , Cytosine , Guanine , Nucleotides , Phosphates
17.
Article in English | MEDLINE | ID: mdl-36315616

ABSTRACT

OBJECTIVES: Racial/ethnic discrimination has been linked to behavioral and emotional problems in youth from marginalized groups. However, the psychological experience associated with discrimination may differ between immigrant and nonimmigrant youth. Race-based discrimination may impact an adolescent's view of their own group (private regard) and/or their sense of how others view their group (public regard). Owing to differences in racialization, immigrant adolescents may be affected differently by experiences of discrimination than their U.S.-born peers. The present study examined whether nativity moderated the paths from racial/ethnic discrimination to private and public regard to mental health problems among Vietnamese American youth. METHOD: Surveys were completed by 718 Vietnamese American 10th and 11th graders (Mage = 15.54 years, 61.4% female, 38.6% male). In this sample, 21.2% were first-generation (i.e., born outside of the United States) and 78.8% were second-generation (i.e., born in the United States with at least one parent born outside of the United States). RESULTS: Multigroup path analysis tested the direct and indirect effects of racial/ethnic discrimination on behavioral and emotional problems via private and public regard and whether associations differed for first- versus second-generation youth. Racial/ethnic discrimination was associated with lower public regard, but not private regard, for both first- and second-generation Vietnamese American youth. Public regard was negatively associated with behavioral and emotional problems only among second-generation youth. No indirect effects were significant. CONCLUSIONS: Findings suggest differences in racialized experiences, as well as opportunities to support second-generation Vietnamese American and other marginalized youth from immigrant families from the mental health impacts of discrimination. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

19.
Clin Chem ; 68(9): 1151-1163, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35587130

ABSTRACT

BACKGROUND: Analysis of circulating tumor DNA has become increasingly important as a tool for cancer care. However, the focus of previous studies has been on short fragments of DNA. Also, bisulfite sequencing, a conventional approach for methylation analysis, causes DNA degradation, which is not ideal for the assessment of long DNA properties and methylation patterns. This study attempted to overcome such obstacles by single-molecule sequencing. METHODS: Single-molecule real-time (SMRT) sequencing was used to sequence plasma DNA. We performed fragment size and direct methylation analysis for each molecule. A methylation score concerning single-molecule methylation patterns was used for cancer detection. RESULTS: A substantial proportion of plasma DNA was longer than 1 kb with a median of 16% in hepatocellular carcinoma (HCC) patients, hepatitis B virus carriers, and healthy individuals. The longest plasma DNA molecule in the HCC patients was 39.8 kb. Tumoral cell-free DNA (cfDNA) was generally shorter than nontumoral cfDNA. The longest tumoral cfDNA was 13.6 kb. Tumoral cfDNA had lower methylation levels compared with nontumoral cfDNA (median: 59.3% vs 76.9%). We developed and analyzed a metric reflecting single-molecule methylation patterns associated with cancer, named the HCC methylation score. HCC patients displayed significantly higher HCC methylation scores than those without HCC. Interestingly, compared to using short cfDNA (area under the receiver operating characteristic [ROC] curve, AUC: 0.75), the use of long cfDNA molecules greatly enhanced the discriminatory power (AUC: 0.91). CONCLUSIONS: A previously unidentified long cfDNA population was revealed in cancer patients. The presence and direct methylation analysis of these molecules open new possibilities for cancer liquid biopsy.


Subject(s)
Carcinoma, Hepatocellular , Cell-Free Nucleic Acids , Liver Neoplasms , Biomarkers, Tumor , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Cell-Free Nucleic Acids/genetics , DNA , DNA Methylation , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics
20.
JAMA Intern Med ; 182(6): 624-633, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35467698

ABSTRACT

Importance: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined. Objective: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission. Design, Setting, and Participants: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states. Exposure: Having a family member in the ICU with COVID-19. Main Outcomes and Measures: Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). Results: A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients' child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P < .001) than male participants, whereas Hispanic participants scored a mean of 2.7 points higher compared with non-Hispanic participants (95% CI, 1.0-4.3; P = .002). Those with graduate school experience had an adjusted mean score of 3.3 points lower (95% CI, 1.5-5.1; P < .001) compared with those with up to a high school degree or equivalent. Qualitative analyses found no substantive differences in the emotional or communication-related experiences between those with high vs low PTSD scores, but those with higher scores exhibited more distrust of practitioners. Conclusions and Relevance: In this cohort study, symptoms of PTSD among family members of ICU patients with COVID-19 were high. Hispanic ethnicity and female gender were associated with higher symptoms. Those with higher scores reported more distrust of practitioners.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , COVID-19/epidemiology , Child , Cohort Studies , Family/psychology , Female , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Prospective Studies , Stress Disorders, Post-Traumatic/psychology
SELECTION OF CITATIONS
SEARCH DETAIL
...