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American Journal of Human Genetics Dec 2022Recommendations from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) for interpreting sequence variants...
Recommendations from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) for interpreting sequence variants specify the use of computational predictors as "supporting" level of evidence for pathogenicity or benignity using criteria PP3 and BP4, respectively. However, score intervals defined by tool developers, and ACMG/AMP recommendations that require the consensus of multiple predictors, lack quantitative support. Previously, we described a probabilistic framework that quantified the strengths of evidence (supporting, moderate, strong, very strong) within ACMG/AMP recommendations. We have extended this framework to computational predictors and introduce a new standard that converts a tool's scores to PP3 and BP4 evidence strengths. Our approach is based on estimating the local positive predictive value and can calibrate any computational tool or other continuous-scale evidence on any variant type. We estimate thresholds (score intervals) corresponding to each strength of evidence for pathogenicity and benignity for thirteen missense variant interpretation tools, using carefully assembled independent data sets. Most tools achieved supporting evidence level for both pathogenic and benign classification using newly established thresholds. Multiple tools reached score thresholds justifying moderate and several reached strong evidence levels. One tool reached very strong evidence level for benign classification on some variants. Based on these findings, we provide recommendations for evidence-based revisions of the PP3 and BP4 ACMG/AMP criteria using individual tools and future assessment of computational methods for clinical interpretation.
Topics: Humans; Calibration; Consensus; Educational Status; Virulence
PubMed: 36413997
DOI: 10.1016/j.ajhg.2022.10.013 -
Therapeutische Umschau. Revue... Apr 2023
Topics: Humans; Male; Prostatic Hyperplasia
PubMed: 36975034
DOI: 10.1024/0040-5930/a001421 -
RoFo : Fortschritte Auf Dem Gebiete Der... Jun 2023The Liver Imaging Reporting and Data System (LI-RADS v2018) standardizes the interpretation and reporting of MDCT and MRI examinations in patients at risk for... (Review)
Review
PURPOSE
The Liver Imaging Reporting and Data System (LI-RADS v2018) standardizes the interpretation and reporting of MDCT and MRI examinations in patients at risk for hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
For focal liver lesions (called "observations") it assigns categories (LR-1 to 5, LR-M, LR-TIV, LR-TR), which reflect the probability of benignity or malignancy (HCC or other non-HCC malignancies) of the respective observation. The categories assigned are based on major and ancillary image features, which have been developed by the American College of Radiology (ACR), revised several times (now v2018), and validated in many studies. The value of ancillary features to modify LI-RADS categories assigned to observations based on major features is shown.
RESULTS
This review summarizes the relevant CT and MRI features and presents a step-by-step approach for readers not familiar with LI-RADS on how to use the system. Relevant imaging features and the value of different modalities (contrast-enhanced CT, MRI with extracellular gadolinium chelates or liver-specific contrast agents) is explained.
CONCLUSION
The widespread adoption of LI-RADS for CT/MRI reporting in high-risk patients would help to reduce inter-reader variability. It could improve communication between radiologists, oncologists, hepatologists, pathologists, and liver surgeons, and lead to better patient management.
KEY POINTS
· LI-RADS has been developed and revised to address the need for improved diagnosis and standardized categorization of findings in chronic liver disease.. · CT/MRI LI-RADS consists of major criteria and ancillary features to classify observations.. · LI-RADS terminology helps to clarify the communication of liver observations between radiologists and referring physicians..
CITATION FORMAT
· Schima W, Kopf H, Eisenhuber E. LI-RADS made Easy. Fortschr Röntgenstr 2023; 195: 486 - 494.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Magnetic Resonance Imaging; Contrast Media; Sensitivity and Specificity
PubMed: 36724803
DOI: 10.1055/a-1990-5924 -
JAMA Network Open Jan 2020Approximately one-quarter of adnexal masses detected at ultrasonography are indeterminate for benignity or malignancy, posing a substantial clinical dilemma. (Comparative Study)
Comparative Study
IMPORTANCE
Approximately one-quarter of adnexal masses detected at ultrasonography are indeterminate for benignity or malignancy, posing a substantial clinical dilemma.
OBJECTIVE
To validate the accuracy of a 5-point Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) score for risk stratification of adnexal masses.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter cohort study was conducted between March 1, 2013, and March 31, 2016. Among patients undergoing expectant management, 2-year follow-up data were completed by March 31, 2018. A routine pelvic MRI was performed among consecutive patients referred to characterize a sonographically indeterminate adnexal mass according to routine diagnostic practice at 15 referral centers. The MRI score was prospectively applied by 2 onsite readers and by 1 reader masked to clinical and ultrasonographic data. Data analysis was conducted between April and November 2018.
MAIN OUTCOMES AND MEASURES
The primary end point was the joint analysis of true-negative and false-negative rates according to the MRI score compared with the reference standard (ie, histology or 2-year follow-up).
RESULTS
A total of 1340 women (mean [range] age, 49 [18-96] years) were enrolled. Of 1194 evaluable women, 1130 (94.6%) had a pelvic mass on MRI with a reference standard (surgery, 768 [67.9%]; 2-year follow-up, 362 [32.1%]). A total of 203 patients (18.0%) had at least 1 malignant adnexal or nonadnexal pelvic mass. No invasive cancer was assigned a score of 2. Positive likelihood ratios were 0.01 for score 2, 0.27 for score 3, 4.42 for score 4, and 38.81 for score 5. Area under the receiver operating characteristic curve was 0.961 (95% CI, 0.948-0.971) among experienced readers, with a sensitivity of 0.93 (95% CI, 0.89-0.96; 189 of 203 patients) and a specificity of 0.91 (95% CI, 0.89-0.93; 848 of 927 patients). There was good interrater agreement among both experienced and junior readers (κ = 0.784; 95% CI, 0.743-0824). Of 580 of 1130 women (51.3%) with a mass on MRI and no specific gynecological symptoms, 362 (62.4%) underwent surgery. Of them, 244 (67.4%) had benign lesions and a score of 3 or less. The MRI score correctly reclassified the mass origin as nonadnexal with a sensitivity of 0.99 (95% CI, 0.98-0.99; 1360 of 1372 patients) and a specificity of 0.78 (95% CI, 0.71-0.85; 102 of 130 patients).
CONCLUSIONS AND RELEVANCE
In this study, the O-RADS MRI score was accurate when stratifying the risk of malignancy in adnexal masses.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; False Negative Reactions; False Positive Reactions; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Ovarian Diseases; Risk Assessment; Sensitivity and Specificity; Ultrasonography; Young Adult
PubMed: 31977064
DOI: 10.1001/jamanetworkopen.2019.19896 -
ACS Omega Dec 2022Envisage a world where discarded electrical/electronic devices and single-use consumables can dematerialize and lapse into the environment after the end-of-useful life... (Review)
Review
Envisage a world where discarded electrical/electronic devices and single-use consumables can dematerialize and lapse into the environment after the end-of-useful life without constituting health and environmental burdens. As available resources are consumed and human activities build up wastes, there is an urgency for the consolidation of efforts and strategies in meeting current materials needs while assuaging the concomitant negative impacts of conventional materials exploration, usage, and disposal. Hence, the emerging field of transient technology (Green Technology), rooted in eco-design and closing the material loop toward a friendlier and sustainable materials system, holds enormous possibilities for assuaging current challenges in materials usage and disposability. The core requirements for transient materials are anchored on meeting multicomponent functionality, low-cost production, simplicity in disposability, flexibility in materials fabrication and design, biodegradability, biocompatibility, and environmental benignity. In this regard, biorenewables such as cellulose-based materials have demonstrated capacity as promising platforms to fabricate scalable, renewable, greener, and efficient materials and devices such as membranes, sensors, display units (for example, OLEDs), and so on. This work critically reviews the recent progress of nanocellulosic materials in transient technologies toward mitigating current environmental challenges resulting from traditional material exploration, usage, and disposal. While spotlighting important fundamental properties and functions in the material selection toward practicability and identifying current difficulties, we propose crucial research directions in advancing transient technology and cellulose-based materials in closing the loop for conventional materials and sustainability.
PubMed: 36591168
DOI: 10.1021/acsomega.2c05848 -
Life (Basel, Switzerland) Nov 2022Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative... (Review)
Review
Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative estimation of benignancy and malignancy, histological type, and malignancy grade and can be performed on an outpatient basis. In recent years, cell blocks prepared with core needle biopsy (CNB) and liquid-based cytology (LBC) have increased the reliability of immunostaining and molecular biological testing, leading to improved diagnostic accuracy. In 2018, the Milan System for Reporting Salivary Gland Cytology was introduced, but it does not include malignancy grade or histological type, so we proposed the Osaka Medical College classification as a more clinically based cell classification that includes both types of information, and we have reported on its usefulness. This review gives an overview of the history and use of FNA and describes CNB and LBC and the two classification systems.
PubMed: 36431032
DOI: 10.3390/life12111897 -
Cell Death & Disease Jun 2023Cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in many types of cancer, including hepatocellular carcinoma (HCC). Epigenetic...
Cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in many types of cancer, including hepatocellular carcinoma (HCC). Epigenetic reprogramming of CSCs has emerged as a promising strategy for inducing the transition from malignancy to benignity. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is required for DNA methylation inheritance. Here, we investigated the role and mechanism of UHRF1 in regulating CSC properties and evaluated the impact of UHRF1 targeting on HCC. Hepatocyte-specific Uhrf1 knockout (Uhrf1) strongly suppressed tumor initiation and CSC self-renewal in both diethylnitrosamine (DEN)/CCl-induced and Myc-transgenic HCC mouse models. Ablation of UHRF1 in human HCC cell lines yielded consistent phenotypes. Integrated RNA-seq and whole genome bisulfite sequencing revealed widespread hypomethylation induced by UHRF1 silencing epigenetically reprogrammed cancer cells toward differentiation and tumor suppression. Mechanistically, UHRF1 deficiency upregulated CEBPA and subsequently inhibited GLI1 and Hedgehog signaling. Administration of hinokitiol, a potential UHRF1 inhibitor, significantly reduced tumor growth and CSC phenotypes in mice with Myc-driven HCC. Of pathophysiological significance, the expression levels of UHRF1, GLI1, and key axis proteins consistently increased in the livers of mice and patients with HCC. These findings highlight the regulatory mechanism of UHRF1 in liver CSCs and have important implications for the development of therapeutic strategies for HCC.
Topics: Humans; Hedgehog Proteins; Carcinoma, Hepatocellular; Zinc Finger Protein GLI1; Liver Neoplasms; Carcinogenesis; Cell Transformation, Neoplastic; Neoplastic Stem Cells; CCAAT-Enhancer-Binding Proteins; Ubiquitin-Protein Ligases
PubMed: 37380646
DOI: 10.1038/s41419-023-05895-w -
Advanced Science (Weinheim,... Jan 2022Lithium-sulfur batteries (LSBs) hold great promise as one of the next-generation power supplies for portable electronics and electric vehicles due to their ultrahigh... (Review)
Review
Lithium-sulfur batteries (LSBs) hold great promise as one of the next-generation power supplies for portable electronics and electric vehicles due to their ultrahigh energy density, cost effectiveness, and environmental benignity. However, their practical application has been impeded owing to the electronic insulation of sulfur and its intermediates, serious shuttle effect, large volume variation, and uncontrollable formation of lithium dendrites. Over the past decades, many pioneering strategies have been developed to address these issues via improving electrodes, electrolytes, separators and binders. Remarkably, polymers can be readily applied to all these aspects due to their structural designability, functional versatility, superior chemical stability and processability. Moreover, their lightweight and rich resource characteristics enable the production of LSBs with high-volume energy density at low cost. Surprisingly, there have been few reviews on development of polymers in LSBs. Herein, breakthroughs and future perspectives of emerging polymers in LSBs are scrutinized. Significant attention is centered on recent implementation of polymers in each component of LSBs with an emphasis on intrinsic mechanisms underlying their specific functions. The review offers a comprehensive overview of state-of-the-art polymers for LSBs, provides in-depth insights into addressing key challenges, and affords important resources for researchers working on electrochemical energy systems.
PubMed: 34741443
DOI: 10.1002/advs.202103798 -
Quantitative Imaging in Medicine and... Jan 2022Pulmonary part-solid nodules (PSNs) reportedly have a high possibility of malignancy, while benign PSNs are common. This study aimed to reveal the differences between...
BACKGROUND
Pulmonary part-solid nodules (PSNs) reportedly have a high possibility of malignancy, while benign PSNs are common. This study aimed to reveal the differences between benign and malignant PSNs by comparing their thin-section computed tomography (CT) features.
METHODS
Patients with PSNs confirmed by postoperative pathological examination or follow-up (at the same period) were retrospectively enrolled from March 2016 to January 2020. The clinical data of patients and CT features of benign and malignant PSNs were reviewed and compared. Binary logistic regression analysis was performed to reveal the predictors of malignant PSNs.
RESULTS
A total of 119 PSNs in 117 patients [age (mean ± standard deviation), 56±11 years; 70 women] were evaluated. Of the 119 PSNs, 44 (37.0%) were benign, and 75 (63.0%) were malignant (12 adenocarcinomas , 22 minimally invasive adenocarcinomas, and 41 invasive adenocarcinomas). There were significant differences in the patients' age and smoking history between benign and malignant PSNs. In terms of CT characteristics, malignant and benign lesions significantly differed in the following CT features: whole nodule, internal solid component, and peripheral ground-glass opacity. The binary logistic regression analysis revealed that well-defined border [odds ratio (OR), 4.574; 95% confidence interval (CI), 1.186-17.643; P=0.027] and lobulation (OR, 61.739; 95% CI, 5.230-728.860; P=0.001) of the nodule, as well as irregular shape (OR, 9.502; 95% CI, 1.788-50.482; P=0.008) and scattered distribution (OR, 13.238; 95% CI, 1.359-128.924; P=0.026) of the internal solid components were significant independent predictors distinguishing malignant PSNs. However, the lesion shape, density, and margin were similar between malignant and benign lesions.
CONCLUSIONS
Well-defined and lobulated PSNs with irregular and scattered solid components are highly likely to be malignant.
PubMed: 34993112
DOI: 10.21037/qims-21-145