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Lancet (London, England) Oct 2023Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating...
BACKGROUND
Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening.
METHODS
In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without signs or symptoms of cancer consented to MCED testing. We collected blood, analysed cfDNA, and returned results to participants' doctors. If a methylation signature indicative of cancer was detected, predicted cancer signal origin(s) informed diagnostic assessment. The primary outcome was time to, and extent of, diagnostic testing required to confirm the presence or absence of cancer. This trial is registered at ClinicalTrials.gov, NCT04241796, and is completed.
FINDINGS
Between Dec 12, 2019, and Dec 4, 2020, we recruited 6662 participants. 4204 (63·5%) of 6621 participants with analysable results were women, 2417 (36·5%) were men, and 6071 (91·7%) were White. A cancer signal was detected in 92 (1·4%) of 6621 participants with analysable results. 35 (38%) participants were diagnosed with cancer (true positives) and 57 (62%) had no cancer diagnosis (false positives). Excluding two participants whose diagnostic assessments began before MCED test results were reported, median time to diagnostic resolution was 79 days (IQR 37-219): 57 days (33-143) in true-positive and 162 days (44-248) in false-positive participants. Most participants had both laboratory tests (26 [79%] of 33 with true-positive results and 50 [88%] of 57 with false-positive results) and imaging (30 [91%] of 33 with true-positive results and 53 [93%] of 57 with false-positive results). Fewer procedures were done in participants with false-positive results (17 [30%] of 57) than true-positive results (27 [82%] of 33) and few had surgery (one with a false-positive result and three with a true-positive result).
INTERPRETATION
This study supports the feasibility of MCED screening for cancer and underscores the need for further research investigating the test's clinical utility.
FUNDING
GRAIL.
Topics: Male; Humans; Female; Prospective Studies; Early Detection of Cancer; Hematologic Tests; Neoplasms; Cell-Free Nucleic Acids
PubMed: 37805216
DOI: 10.1016/S0140-6736(23)01700-2 -
American Journal of Epidemiology Apr 2024The World Health Organization specifies that sexual health requires the potential for pleasurable and safe sexual experiences. Yet epidemiologic research into sexual...
The World Health Organization specifies that sexual health requires the potential for pleasurable and safe sexual experiences. Yet epidemiologic research into sexual pleasure and other positive sexual outcomes has been scant. In this commentary, we aim to support the development and adoption of sex-positive epidemiology, which we define as epidemiology that incorporates the study of pleasure and other positive features alongside sexually transmitted infections and other familiar negative outcomes. We first call epidemiologists' attention to the potential role that stigma plays in the suppression of sex-positive research. We further describe existing measures of sex-positive constructs that may be useful in epidemiologic research. Finally, the study of sex-positive constructs is vulnerable to biases that are well-known to epidemiologists, especially selection bias, information bias, and confounding. We outline how these biases influence existing research and identify opportunities for future research. Epidemiologists have the potential to contribute a great deal to the study of sexuality by bringing their considerable methodological expertise to long-standing challenges in the field. We hope to encourage epidemiologists to broaden their sexual health research to encompass positive outcomes and pleasure.
PubMed: 38634632
DOI: 10.1093/aje/kwae054 -
International Journal of Clinical... Aug 2023HPV plays a vital role in the development of cervical cancers and oropharyngeal cancers, but it is controversial whether HPV is involved in oral cancer development and... (Review)
Review
HPV plays a vital role in the development of cervical cancers and oropharyngeal cancers, but it is controversial whether HPV is involved in oral cancer development and to what extent. In this review, the clinical characteristics, diagnosis, treatment, and prognosis of HPV-positive oral cancers are summarized, and the mechanisms of HPV-related oral cancer development are discussed. HPV DNA positivity rates are 20-30% in oral squamous cell carcinoma (OSCC), and HPV16 is the most common high-risk HPV. E6/E7 mRNA positivity rates are 2-6% in OSCC. Detection of both high-risk HPV DNA and E6/E7 mRNA is recommended to determine the presence of active HPV, in agreement with high-risk HPV infection in OSCC. Surgical treatment is the first-line therapy for HPV-positive and -negative oral cancer, but there is no unified view about the prognosis of HPV-positive OSCC patients. HPV16 may play a vital role in malignant transformation in oral epithelial dysplasia, and a model of synergistic carcinogenic impact of HPV and tobacco smoking is predicted. Additionally, it is hypothesized that there are different HPV-associated oral cancers, such as integrated HPV DNA-positive OSCC with stable E6/E7 expression and episomal HPV DNA-positive OSCC. In summary, the role of HPV in oral carcinogenesis seems to be limited because of the low E6/E7 positivity in OSCCs; however, episomal HPV DNA may play a vital role in the malignant transformation of HPV-positive oral premalignant lesions. Further investigation is required to promote new insights into the role of episomal HPV DNA in oral carcinogenesis.
Topics: Female; Humans; Mouth Neoplasms; Human Papillomavirus Viruses; Papillomavirus E7 Proteins; Papillomavirus Infections; Carcinoma, Squamous Cell; DNA, Viral; Uterine Cervical Neoplasms; Human papillomavirus 16; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Carcinogenesis; RNA, Messenger; Oncogene Proteins, Viral; Papillomaviridae
PubMed: 36929094
DOI: 10.1007/s10147-023-02327-9 -
Journal of Personality and Social... Dec 2023Authenticity is often described using terms like "real," "genuine," and "true" suggesting that unbiased and objective self-perception is a core component of the...
Authenticity is often described using terms like "real," "genuine," and "true" suggesting that unbiased and objective self-perception is a core component of the construct. However, people tend to view themselves in an overly positive way. Therefore, we propose that experiencing a positive self-versus an unbiased self-will increase authenticity. We find support for this in seven studies ( = 1,795) with two operationalizations of self-rated authenticity: attributed and state authenticity. We find that authenticity emerges from positive self-beliefs (Study 1), positive personality assessments (Study 2), and positive self-expressions (Study 3a and b). Further, we find that these effects are not driven only by positivity, but positive selves (Study 4), and mediated by the identity centrality (Study 5). Finally, Study 6 finds that this positivity bias does not extend to other-rated authenticity: People who present an overly positive self seem less authentic to others relative to a mixed or negative self-presentation. Taken together, these findings suggest that being "unreal" through positive self-illusions can, paradoxically, make one feel more real. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Humans; Self Concept; Emotions; Research Design; Personality Assessment
PubMed: 37856411
DOI: 10.1037/pspa0000359 -
Clinical and Translational... Sep 2023Helicobacter pylori colonizes the human stomach. Infection causes chronic gastritis and increases the risk of gastroduodenal ulcer and gastric cancer. Its chronic...
INTRODUCTION
Helicobacter pylori colonizes the human stomach. Infection causes chronic gastritis and increases the risk of gastroduodenal ulcer and gastric cancer. Its chronic colonization in the stomach triggers aberrant epithelial and inflammatory signals that are also associated with systemic alterations.
METHODS
Using a PheWAS analysis in more than 8,000 participants in the community-based UK Biobank, we explored the association of H. pylori positivity with gastric and extragastric disease and mortality in a European country.
RESULTS
Along with well-established gastric diseases, we dominantly found overrepresented cardiovascular, respiratory, and metabolic disorders. Using multivariate analysis, the overall mortality of H. pylori -positive participants was not altered, while the respiratory and Coronovirus 2019-associated mortality increased. Lipidomic analysis for H. pylori -positive participants revealed a dyslipidemic profile with reduced high-density lipoprotein cholesterol and omega-3 fatty acids, which may represent a causative link between infection, systemic inflammation, and disease.
DISCUSSION
Our study of H. pylori positivity demonstrates that it plays an organ- and disease entity-specific role in the development of human disease and highlights the importance of further research into the systemic effects of H. pylori infection.
Topics: Humans; Helicobacter pylori; Gastritis; Gastritis, Atrophic; Peptic Ulcer; Stomach Neoplasms; Helicobacter Infections
PubMed: 37367296
DOI: 10.14309/ctg.0000000000000610 -
Frontiers in Immunology 2023Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically...
BACKGROUND
Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically to cerebellar degeneration-related protein 2 (CDR2), predominantly affecting women with gynecologic or breast adenocarcinoma. Single-modality CDR2 testing may produce false-positive results. We assessed the performance characteristics of the more recently purported major PCA-1/Yo antigen, CDR2-like (CDR2L), side by side with CDR2, in a line blot format.
METHODS
CDR2 and CDR2L were tested in six specimen groups (serum and cerebrospinal fluid (CSF)). Group 1, PCA-1/Yo mouse brain indirect immunofluorescence assay (IFA) positives; Group 2, PCA-1/Yo IFA mimics; Group 3, suspected CDR2 line blot false positives; Group 4, consecutive patient samples tested for neural antibodies over 1 year; Group 5, healthy subject serums; and Group 6, polyclonal (non-specific) immunoglobulin G (IgG)-positive serums.
RESULTS
Group 1: Of 64 samples tested, all but two were CDR2 positive (both CSF samples) and all were CDR2L positive. In individual patients, CDR2L values were always higher than CDR2. The two "CDR2L-only" positives were CSF samples with low titer PCA-1/Yo by IFA with serum negativity but with typical clinical phenotype. Group 2: All 51 PCA-1/Yo mimics were CDR2/CDR2L negative. Group 3: Nine samples [six of 1289 (0.47%) serums and three of 700 CSF samples (0.43%) were PCA-1/Yo IFA negative/CDR2 positive; two of the six available (serums from the same patient) were also CDR2L positive; the other four CDR2L negative had low CDR2 values (17-22). Group 4: Twenty-two patients had unexpected CDR2 or CDR2L positivity; none had tissue IFA positivity. Eleven of the 2,132 serum (0.5%) and three of the 677 CSF (0.4%) samples were CDR2 positive; median value was 19 (range, 11-48). Seven of the 2,132 serum (0.3%) and three of the 677 CSF (0.4%) samples were CDR2L positive; median value was 18 (range, 11-96). Group 5: All 151 healthy serum samples were negative. Group 6: One of the 46 polyclonal serum samples was CDR2L positive. Optimum overall performance was accomplished by requiring both CDR2 and CDR2L positivity in serum (sensitivity, 100%; and specificity, 99.9%) and positivity for CDR2L in CSF (sensitivity, 100%; and specificity, 99.6%).
CONCLUSION
CDR2L provides additional PCA-1/anti-Yo sensitivity in CSF, and dual positivity with CDR2 provides additional specificity assurance in serum. Combining antigen-specific and tissue-based assays optimizes PCA-1/anti-Yo testing.
Topics: Animals; Mice; Humans; Female; Autoantibodies; Autoimmunity; Paraneoplastic Cerebellar Degeneration; Nerve Tissue Proteins; Cytoplasm; Neurodegenerative Diseases
PubMed: 37841252
DOI: 10.3389/fimmu.2023.1265797 -
Perspectives on Psychological Science :... Sep 2023Humans now understand the world as multilevel in nature. For example, societies emerge from individuals, and general experiences of life consist of specific aspects and...
Humans now understand the world as multilevel in nature. For example, societies emerge from individuals, and general experiences of life consist of specific aspects and momentary episodes. A critical feature of multilevel phenomena is between-level incongruences. Applied to human positivity, this means that positive higher-level units are not simply composed of positive lower-level units and that what is good for lower-level units may not be good for higher-level units (and vice versa). For example, killjoys may improve societal well-being, personal achievement may require giving up on certain goals, and a happy life may not arise from simply happy moments. In this article, I provide examples (organized by the positive outcome of well-being and performance and by the social, structural, and temporal forms of multilevel phenomena) to show that such between-level incongruences are ubiquitous. Next, I analyze a few mechanisms that may govern the diverse instantiations of between-level incongruences in positivity. Finally, I discuss implications of this perspective, such as why positivity claims should always qualify their level of analysis; how psychological science may benefit from a multilevel, dynamical, and computational perspective; and how to improve human positivity in light of between-level incongruences.
PubMed: 37669013
DOI: 10.1177/17456916231190824 -
Critical Reviews in Oncology/hematology Sep 2023Our study aims to evaluate programmed cell death ligand-1 (PD-L1) expression and its prognostic significance in cervical cancer (CC), endometrial cancer (EC) and ovarian... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Our study aims to evaluate programmed cell death ligand-1 (PD-L1) expression and its prognostic significance in cervical cancer (CC), endometrial cancer (EC) and ovarian cancer (OC).
METHODS
Several electronic databases were searched. Fixed effects models or random effects models were employed to calculate the pooled prevalence of PD-L1 positivity and pooled hazard ratios (HRs) as appropriate. Heterogeneity and publication bias were also assessed.
RESULTS
The pooled prevalence of PD-L1 positivity was 58.1%, 33.8% and 37.5% for CC, EC and OC patients, respectively. There were significant differences in the pooled estimates after stratification by PD-L1-positive assessment criteria and antibody clones. PD-L1 positivity was associated with worse OS in CC and EC patients and poorer progression-free survival (PFS) in CC patients.
CONCLUSIONS
The prevalence of PD-L1-positive expression was considerably high in CC and modestly high in EC and OC patients. PD-L1 expression has the potential to be a prognostic biomarker for predicting the clinical outcomes of patients with CC and EC but not OC.
Topics: Female; Humans; Prognosis; B7-H1 Antigen; Prevalence; Ovarian Neoplasms; Proportional Hazards Models; Uterine Cervical Neoplasms; Endometrial Neoplasms
PubMed: 37536446
DOI: 10.1016/j.critrevonc.2023.104084 -
Annals of Neurology Jul 2024The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) testing.
OBJECTIVE
The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) testing.
METHODS
We retrospectively identified patients for CSF MOG-IgG testing from January 1, 1996, to May 1, 2023, at Mayo Clinic and other medical centers that sent CSF MOG-IgG for testing including: controls, 282; serum MOG-IgG positive MOG antibody-associated disease (MOGAD), 74; serum MOG-IgG negative high-risk phenotypes, 73; serum false positive MOG-IgG with alternative diagnoses, 18. A live cell-based assay assessed CSF MOG-IgG positivity (IgG-binding-index [IBI], ≥2.5) using multiple anti-human secondary antibodies and end-titers were calculated if sufficient sample volume. Correlation of CSF MOG-IgG IBI and titer was assessed.
RESULTS
The pan-IgG Fc-specific secondary was optimal, yielding CSF MOG-IgG sensitivity of 90% and specificity of 98% (Youden's index 0.88). CSF MOG-IgG was positive in: 4/282 (1.4%) controls; 66/74 (89%) serum MOG-IgG positive MOGAD patients; and 9/73 (12%) serum MOG-IgG negative patients with high-risk phenotypes. Serum negative but CSF positive MOG-IgG accounted for 9/83 (11%) MOGAD patients, and all fulfilled 2023 MOGAD diagnostic criteria. Subgroup analysis of serum MOG-IgG low-positives revealed CSF MOG-IgG positivity more in MOGAD (13/16[81%]) than other diseases with false positive serum MOG-IgG (3/15[20%]) (p = 0.01). CSF MOG-IgG IBI and CSF MOG-IgG titer (both available in 29 samples) were correlated (Spearman's r = 0.64, p < 0.001).
INTERPRETATION
CSF MOG-IgG testing has diagnostic utility in patients with a suspicious phenotype but negative serum MOG-IgG, and those with low positive serum MOG-IgG results and diagnostic uncertainty. These findings support a role for CSF MOG-IgG testing in the appropriate clinical setting. ANN NEUROL 2024;96:34-45.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Retrospective Studies; Female; Male; Autoantibodies; Adult; Middle Aged; Immunoglobulin G; Sensitivity and Specificity; Aged; Adolescent; Young Adult; Child
PubMed: 38591875
DOI: 10.1002/ana.26931