TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TH2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.

Orthogonal IMiD-Degron Pairs Induce Selective Protein Degradation in Cells.

Immunomodulatory imide drugs (IMiDs) including thalidomide, lenalidomide, and pomalidomide, can be used to induce degradation of a protein of interest that is fused to a short zinc finger (ZF) degron motif. These IMiDs, however, also induce degradation of endogenous neosubstrates, including IKZF1 and IKZF3. To improve degradation selectivity, we took a bump-and-hole approach to design and screen bumped IMiD analogs against 8380 ZF mutants. This yielded a bumped IMiD analog that induces efficient degradation of a mutant ZF degron, while not affecting other cellular proteins, including IKZF1 and IKZF3. In proof-of-concept studies, this system was applied to induce efficient degradation of TRIM28, a disease-relevant protein with no known small molecule binders. We anticipate that this system will make a valuable addition to the current arsenal of degron systems for use in target validation.

HPV and Cervical Cancer Awareness and Screening Practices among Migrant Women: A Narrative Review.

This narrative review explores the barriers and facilitators that migrant women face globally. The review explored a range of studies conducted in various countries, including the United States of America (USA), the United Kingdom (UK), Canada, Australia, and the United Arab Emirates (UAE). It also specialises in the experiences of migrant women living in Sydney, Australia, and women living in Ras Al Khaimah (RAK), UAE. Cervical cancer ranks as the fourth most prevalent form of cancer among women worldwide. It is the fourteenth most common cancer among women in Australia and the fourth most common cancer in the UAE. Despite the availability of vaccinations and cervical screening initiatives in many countries, including the USA, the UK, Canada, Australia, and the UAE, migrant women living in these countries continue to experience considerable health gaps when accessing cervical cancer screening services. Addressing these disparities is crucial to ensuring everyone has equal healthcare access. An electronic search was conducted using three databases to identify articles published between 2011 and 2021. Qualitative, quantitative, and mixed-methods research studies were included in the search. The identified factors were classified into categories of barriers and facilitators of cervical screening uptake, which were then sub-categorized. This narrative review examines the awareness of cervical cancer and screening behaviours, attitudes, barriers, and facilitators associated with cervical cancer screening. According to the study, several factors pose significant obstacles for migrant women worldwide, particularly those living in the USA, the UK, Canada, and Sydney, Australia, and Emirati and non-Emirati women (migrant women) residing in RAK when it comes to undergoing cervical cancer screening. These barriers include inadequate knowledge and emotional, cultural, religious, psychological, and organisational factors. On the other hand, social support, awareness campaigns, and the availability of screening services were found to promote the uptake of cervical cancer screening. The findings from this review suggest that healthcare providers should adopt culturally sensitive approaches to enhance awareness and encourage participation in screening programs among migrant women. Based on the findings of this narrative review, it is strongly suggested that healthcare providers and policymakers prioritise developing culturally sensitive screening initiatives for migrant women. It is essential to address the psychological and emotional barriers that prevent migrant women from accessing screening services. This can be accomplished by offering education and awareness campaigns in their native languages and implementing a community-based approach to encourage social support and increase awareness of cervical cancer and screening services. Furthermore, healthcare providers and organisations should provide educational tools that address common misconceptions based on cultural and religious factors that prevent women from accessing screening services.

Structure and dynamics determine G protein coupling specificity at a class A GPCR.

G protein coupled receptors (GPCRs) exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of GPCR-G protein complexes, little is known about the mechanism of G protein coupling specificity. The ß2-adrenergic receptor is an example of GPCR with high selectivity for Gαs, the stimulatory G protein for adenylyl cyclase, and much weaker for the Gαi family of G proteins inhibiting adenylyl cyclase. By developing a new Gαi-biased agonist (LM189), we provide structural and biophysical evidence supporting that distinct conformations at ICL2 and TM6 are required for coupling of the different G protein subtypes Gαs and Gαi. These results deepen our understanding of G protein specificity and bias and can accelerate the design of ligands that select for preferred signaling pathways.

Pla2g5 contributes to viral-like-induced lung inflammation through macrophage proliferation and LA/Ffar1 lung cell recruitment.

Macrophages expressing group V phospholipase A2 (Pla2g5) release the free fatty acid (FFA) linoleic acid (LA), potentiating lung type 2 inflammation. Although Pla2g5 and LA increase in viral infections, their role remains obscure. We generated Pla2g5flox/flox mice, deleted Pla2g5 by using the Cx3cr1cre transgene, and activated bone marrow-derived macrophages (BM-Macs) with poly:IC, a synthetic double-stranded RNA that triggers a viral-like immune response, known Pla2g5-dependent stimuli (IL-4, LPS + IFNγ, IL-33 + IL-4 + GM-CSF) and poly:IC + LA followed by lipidomic and transcriptomic analysis. Poly:IC-activated Pla2g5flox/flox;Cx3cr1cre/+ BM-Macs had downregulation of major bioactive lipids and critical enzymes producing those bioactive lipids. In addition, AKT phosphorylation was lower in poly:IC-stimulated Pla2g5flox/flox;Cx3cr1cre/+ BM-Macs, which was not restored by adding LA to poly:IC-stimulated BM-Macs. Consistently, Pla2g5flox/flox;Cx3cr1cre/+ mice had diminished poly:IC-induced lung inflammation, including inflammatory macrophage proliferation, while challenging Pla2g5flox/flox;Cx3cr1cre/+ mice with poly:IC + LA partially restored lung inflammation and inflammatory macrophage proliferation. Finally, mice lacking FFA receptor-1 (Ffar1)-null mice had reduced poly:IC-induced lung cell recruitment and tissue macrophage proliferation, not corrected by LA. Thus, Pla2g5 contributes to poly:IC-induced lung inflammation by regulating inflammatory macrophage proliferation and LA/Ffar1-mediated lung cell recruitment and tissue macrophage proliferation.

Computer-extracted global radiomic features can predict the radiologists' first impression about the abnormality of a screening mammogram.

OBJECTIVE: Radiologists can detect the gist of abnormal based on their rapid initial impression on a mammogram (ie, global gist signal [GGS]). This study explores (1) whether global radiomic (ie, computer-extracted) features can predict the GGS; and if so, (ii) what features are the most important drivers of the signals. METHODS: The GGS of cases in two extreme conditions was considered: when observers detect a very strong gist (high-gist) and when the gist of abnormal was not/poorly perceived (low-gist). Gist signals/scores from 13 observers reading 4191 craniocaudal mammograms were collected. As gist is a noisy signal, the gist scores from all observers were averaged and assigned to each image. The high-gist and low-gist categories contained all images in the fourth and first quartiles, respectively. One hundred thirty handcrafted global radiomic features (GRFs) per mammogram were extracted and utilized to construct eight separate machine learning random forest classifiers (All, Normal, Cancer, Prior-1, Prior-2, Missed, Prior-Visible, and Prior-Invisible) for characterizing high-gist from low-gist images. The models were trained and validated using the 10-fold cross-validation approach. The models' performances were evaluated by the area under receiver operating characteristic curve (AUC). Important features for each model were identified through a scree test. RESULTS: The Prior-Visible model achieved the highest AUC of 0.84 followed by the Prior-Invisible (0.83), Normal (0.82), Prior-1 (0.81), All (0.79), Prior-2 (0.77), Missed (0.75), and Cancer model (0.69). Cluster shade, standard deviation, skewness, kurtosis, and range were identified to be the most important features. CONCLUSIONS: Our findings suggest that GRFs can accurately classify high- from low-gist images. ADVANCES IN KNOWLEDGE: Global mammographic radiomic features can accurately predict high- from low-gist images with five features identified to be valuable in describing high-gist images. These are critical in providing better understanding of the mammographic image characteristics that drive the strength of the GGSs which could be exploited to advance breast cancer (BC) screening and risk prediction, enabling early detection and treatment of BC thereby further reducing BC-related deaths.

Nurse practitioners' use of diagnostic imaging: A scoping review.

AIM: To explore the nature and extent of peer-reviewed literature related to the use of diagnostic imaging by nurse practitioners (NPs) to inform future practice and research. BACKGROUND: Nurse practitioners undertake advanced assessment, diagnosis, and management of patients, including requesting and interpretation of diagnostic imaging. It is unclear what evidence exists related to the quality use of radiological investigations by NPs in recent years. DESIGN: A scoping review based on the steps suggested by the Joanna Briggs Institute. METHODS: A structured review of the databases Medline, CINAHL and Embase was undertaken using the keywords and MESH terms 'nurse practitioner', 'medical imaging', 'diagnostic imaging', 'scan' and 'radiography'. Only English language articles were included, and no date limit was applied. Database review was completed on 30 May 2021. RESULTS: Eight themes were identified-country and clinical context, requesting diagnostic imaging, performing diagnostic imaging, image-guided interventions, interpreting diagnostic imaging, training education and knowledge, impact on resource usage and comparison with medical practitioners. There were more studies across a greater breadth of clinical specialties and imaging modalities in the United States than in other countries. Nurse practitioner practice is frequently benchmarked against that of medical colleagues. There is a paucity of studies focusing on educational preparation and the lack of relevant university curricula for NPs around diagnostic imaging. CONCLUSION: There are significant gaps in the evidence outside of the United States across several of the identified themes. Further studies are needed to explore NP access to and use of diagnostic imaging and to understand the barriers and facilitators to this. RELEVANCE TO CLINICAL PRACTICE: Studies from four countries were included in this review. The evidence suggests that, where studied, nurse practitioners (NPs) can safely and appropriately request and interpret plain x-rays in the emergency and minor injuries setting. Further research is needed to evaluate the educational needs of NPs in relation to diagnostic imaging and their use of advanced imaging techniques, particularly outside of the United States. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

PPARγ agonist treatment reduces fibroadipose tissue in secondary lymphedema by exhausting fibroadipogenic PDGFRα+ mesenchymal cells.

Secondary lymphedema occurs in up to 20% of patients after lymphadenectomy performed for the surgical management of tumors involving the breast, prostate, uterus, and skin. Patients develop progressive edema of the affected extremity due to retention of protein-rich lymphatic fluid. Despite compression therapy, patients progress to chronic lymphedema in which noncompressible fibrosis and adipose tissue are deposited within the extremity. The presence of fibrosis led to our hypothesis that rosiglitazone, a PPARγ agonist that inhibits fibrosis, would reduce fibrosis in a mouse model of secondary lymphedema after hind limb lymphadenectomy. In vivo, rosiglitazone reduced fibrosis in the hind limb after lymphadenectomy. Our findings verified that rosiglitazone reestablished the adipogenic features of TGF-ß1-treated mesenchymal cells in vitro. Despite this, rosiglitazone led to a reduction in adipose tissue deposition. Single-cell RNA-Seq data obtained from human tissues and flow cytometric and histological evaluation of mouse tissues demonstrated increased presence of PDGFRα+ cells in lymphedema; human tissue analysis verified these cells have the capacity for adipogenic and fibrogenic differentiation. Upon treatment with rosiglitazone, we noted a reduction in the overall quantity of PDGFRα+ cells and LipidTOX+ cells. Our findings provide a framework for treating secondary lymphedema as a condition of fibrosis and adipose tissue deposition, both of which, paradoxically, can be prevented with a pro-adipogenic agent.

Propagation-based phase-contrast imaging of the breast: image quality and the effect of X-ray energy and radiation dose.

OBJECTIVES: Propagation-based phase-contrast computed tomography (PB-CT) is a new imaging technique that exploits refractive and absorption properties of X-rays to enhance soft tissue contrast and improve image quality. This study compares image quality of PB-CT and absorption-based CT (AB-CT) for breast imaging while exploring X-ray energy and radiation dose. METHODS: Thirty-nine mastectomy samples were scanned at energy levels of 28-34keV using a flat panel detector at radiation dose levels of 4mGy and 2mGy. Image quality was assessed using signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), spatial resolution (res) and visibility (vis). Statistical analysis was performed to compare PB-CT images against their corresponding AB-CT images scanned at 32keV and 4mGy. RESULTS: The PB-CT images at 4mGy, across nearly all energy levels, demonstrated superior image quality than AB-CT images at the same dose. At some energy levels, the 2mGy PB-CT images also showed better image quality in terms of CNR/Res and vis compared to the 4mGy AB-CT images. At both investigated doses, SNR and SNR/res were found to have a statistically significant difference across all energy levels. The difference in vis was statistically significant at some energy levels. CONCLUSION: This study demonstrates superior image quality of PB-CT over AB-CT, with X-ray energy playing a crucial role in determining image quality parameters. ADVANCES IN KNOWLEDGE: Our findings reveal that standard dose PB-CT outperforms standard dose AB-CT across all image quality metrics. Additionally, we demonstrate that low dose PB-CT can produce superior images compared to standard dose AB-CT in terms of CNR/Res and vis.

RRIMS: Radiation Risk In Mammography Screening - model evaluation.

OBJECTIVE: The Radiation Risk In Mammography Screening (RRIMS) model was introduced as a novel tool to help females accurately calculate their lifetime mean glandular dose (MGD) and estimate their population-level risk of radiation-induced breast cancer incidence and mortality. METHODS: The model's accuracy was evaluated by comparing the received MGD of 317 women who had undergone a total of 733 visits across one to four rounds of screening. This was achieved by comparing the RRIMS predicted dose values with the same examination dose calculated manually by hand. Qualitative and quantitative statistical analyses were performed to assess the percentage difference (% diff) or agreement between the two values. RESULTS: Qualitative statistical analysis using the Bland-Altman plots demonstrated a statistically significant bias for the % diff between the manually calculated and RRIMS predicted dose values, where the mean (bias) was -2.02% with an upper and lower limit of agreement of 40.24% and -44.27%, respectively. Quantitative statistical analysis revealed an intraclass correlation coefficient (ICC, 3,1) of 0.64 (p-value < 0.001) and a Kendall's W of 0.83 (p-value < 0.001). CONCLUSION: The results indicate a statistically significant and reasonably good level of agreement between the manually calculated vs RRIMS predicted dose values. This work was focused on one of the major mammography equipment manufacturers that is Hologic, however there is potential for a multivendor applicability study of this model with future iterations. This will further improve upon this innovative dose and risk prediction tool that can empower healthcare professionals when making informed decisions and enhance patient care. ADVANCES IN KNOWLEDGE: This paper assesses the precision of the dose and risk model that our team has previously established. The results bring us one step closer to providing females and clinicians with a useful tool that can help explain and contextualise the benefits and risks associated with screening mammography.

COVID-19 vaccine uptake before and after a vaccine mandate at a major academic hospital: Trends by race/ethnicity and level of patient contact.

OBJECTIVES: To assess vaccine coverage rates before and after implementation of a COVID-19 vaccine mandate among Health care Personnel (HCP) and demographic characteristics associated with vaccine uptake Design, Setting, and Participants: Cohort study conducted among 10,889 hospital employees followed from Dec 16, 2020 - October 31, 2021, at a large academic hospital in Philadelphia. MAIN OUTCOME AND MEASURES: Time to COVID-19 vaccination and vaccine series completion rates before and after implementation of a COVID-19 vaccine mandate based on age, gender, race/ethnicity, and level of patient contact/occupational group. RESULTS: The vaccination series completion rate was 86.0% prior to mandate announcement, and increased to 98.7% after mandate implementation. Rates before mandate announcement were highest among Asians (96.2%), Whites (94.0%), males (89.7%), employees ≥ 65 years of age (95.2%), and employees with direct patient care (physicians, 99.0%, and nurses, 93.3%). Hospital educational initiatives (including Town Halls and discussions with Black and Hispanic employees with the lowest vaccination rates) appeared to improve uptake. The largest increase in series completion after mandate announcement occurred among Blacks, those of other/multiracial backgrounds, and Hispanics (35.6%, 22.4%, and 10.8%, respectively) as well as those with some or no direct patient contact (24.5% and 18.3%, respectively). Medical or religious exemptions were approved for 64 (<0.6%) employees and 38 (<0.4%) left their positions (8 voluntary, 30 involuntary) specifically due to the COVID-19 vaccine mandate. No clinically meaningful differences by age, gender, or race/ethnicity for those who were vaccinated under the mandate versus those who left their positions were noted. CONCLUSIONS AND RELEVANCE: These results suggest that while mandates may be challenging to institutions and enforcement unpopular, they play an important role in reducing hesitancy and securing high vaccination rates among HCP, a group at high risk of COVID-19 given their employment and who can be a source of disease transmission to patients.

Using Radiomics-Based Machine Learning to Create Targeted Test Sets to Improve Specific Mammography Reader Cohort Performance: A Feasibility Study.

Mammography interpretation is challenging with high error rates. This study aims to reduce the errors in mammography reading by mapping diagnostic errors against global mammographic characteristics using a radiomics-based machine learning approach. A total of 36 radiologists from cohort A (n = 20) and cohort B (n = 16) read 60 high-density mammographic cases. Radiomic features were extracted from three regions of interest (ROIs), and random forest models were trained to predict diagnostic errors for each cohort. Performance was evaluated using sensitivity, specificity, accuracy, and AUC. The impact of ROI placement and normalization on prediction was investigated. Our approach successfully predicted both the false positive and false negative errors of both cohorts but did not consistently predict location errors. The errors produced by radiologists from cohort B were less predictable compared to those in cohort A. The performance of the models did not show significant improvement after feature normalization, despite the mammograms being produced by different vendors. Our novel radiomics-based machine learning pipeline focusing on global radiomic features could predict false positive and false negative errors. The proposed method can be used to develop group-tailored mammographic educational strategies to help improve future mammography reader performance.

Reducing ' probably benign ' assessments in normal mammograms: The role of radiologist experience.

Rationale and objectives: to investigate the relationship between radiologists' experience in reporting mammograms, their caseloads, and the classification of category '3' or 'Probably Benign' on normal mammograms. Materials and Methods: A total of 92 board-certified radiologists participated. Self-reported parameters related to experience, including age, years since qualifying as a radiologist, years of experience reading mammograms, number of mammograms read per year, and hours spent reading mammograms per week, were documented. To assess the radiologists' accuracy, "Probably Benign fractions" was calculated by dividing the number of "Probably Benign findings" given by each radiologist in the normal cases by the total number of normal cases Probably Benign fractions were correlated with various factors, such as the radiologists' experience. Results: The results of the statistical analysis revealed a significant negative correlation between radiologist experience and 'Probably Benign' fractions for normal images. Specifically, for normal cases, the number of mammograms read per year (r = -0.29, P = 0.006) and the number of mammograms read over the radiologist's lifetime (r = -0.21, P = 0.049) were both negatively correlated with 'Probably Benign' fractions. Conclusion: The results indicate that a relationship exists between increased reading volumes and reduced assessments of 'Probably Benign' in normal mammograms. The implications of these findings extend to the effectiveness of screening programs and the recall rates.

Global Radiomic Features from Mammography for Predicting Difficult-To-Interpret Normal Cases.

This work aimed to investigate whether global radiomic features (GRFs) from mammograms can predict difficult-to-interpret normal cases (NCs). Assessments from 537 readers interpreting 239 normal mammograms were used to categorise cases as 120 difficult-to-interpret and 119 easy-to-interpret based on cases having the highest and lowest difficulty scores, respectively. Using lattice- and squared-based approaches, 34 handcrafted GRFs per image were extracted and normalised. Three classifiers were constructed: (i) CC and (ii) MLO using the GRFs from corresponding craniocaudal and mediolateral oblique images only, based on the random forest technique for distinguishing difficult- from easy-to-interpret NCs, and (iii) CC + MLO using the median predictive scores from both CC and MLO models. Useful GRFs for the CC and MLO models were recognised using a scree test. The CC and MLO models were trained and validated using the leave-one-out-cross-validation. The models' performances were assessed by the AUC and compared using the DeLong test. A Kruskal-Wallis test was used to examine if the 34 GRFs differed between difficult- and easy-to-interpret NCs and if difficulty level based on the traditional breast density (BD) categories differed among 115 low-BD and 124 high-BD NCs. The CC + MLO model achieved higher performance (0.71 AUC) than the individual CC and MLO model alone (0.66 each), but statistically non-significant difference was found (all p > 0.05). Six GRFs were identified to be valuable in describing difficult-to-interpret NCs. Twenty features, when compared between difficult- and easy-to-interpret NCs, differed significantly (p < 0.05). No statistically significant difference was observed in difficulty between low- and high-BD NCs (p = 0.709). GRF mammographic analysis can predict difficult-to-interpret NCs.

Incidence, mortality, survival, and disease burden of breast cancer in China compared to other developed countries.

Breast cancer was the most diagnosed malignant neoplasm and the second leading cause of cancer mortality among Chinese females in 2020. Increased risk factors and widespread adoption of westernized lifestyles have resulted in an upward trend in the occurrence of breast cancer. Up to date knowledge on the incidence, mortality, survival, and burden of breast cancer is essential for optimized cancer prevention and control. To better understand the status of breast cancer in China, this narrative literature review collected data from multiple sources, including studies obtained from the PubMed database and text references, national annual cancer report, government cancer database, Global Cancer Statistics 2020, and Global Burden of Disease study (2019). This review provides an overview of the incidence, mortality, and survival rates of breast cancer, as well as a summary of disability-adjusted life years associated with breast cancer in China from 1990 to 2019, with comparisons to Japan, South Korea, Australia and the United States.

Reliability of radiologists' first impression when interpreting a screening mammogram.

Previous studies showed that radiologists can detect the gist of an abnormality in a mammogram based on a half-second image presentation through global processing of screening mammograms. This study investigated the intra- and inter-observer reliability of the radiologists' initial impressions about the abnormality (or "gist signal"). It also examined if a subset of radiologists produced more reliable and accurate gist signals. Thirty-nine radiologists provided their initial impressions on two separate occasions, viewing each mammogram for half a second each time. The intra-class correlation (ICC) values showed poor to moderate intra-reader reliability. Only 13 radiologists had an ICC of 0.6 or above, which is considered the minimum standard for reliability, and only three radiologists had an ICC exceeding 0.7. The median value for the weighted Cohen's Kappa was 0.478 (interquartile range = 0.419-0.555). The Mann-Whitney U-test showed that the "Gist Experts", defined as those who outperformed others, had significantly higher ICC values (p = 0.002) and weighted Cohen's Kappa scores (p = 0.026). However, even for these experts, the intra-radiologist agreements were not strong, as an ICC of at least 0.75 indicates good reliability and the signal from none of the readers reached this level of reliability as determined by ICC values. The inter-reader reliability of the gist signal was poor, with an ICC score of 0.31 (CI = 0.26-0.37). The Fleiss Kappa score of 0.106 (CI = 0.105-0.106), indicating only slight inter-reader agreement, confirms the findings from the ICC analysis. The intra- and inter-reader reliability analysis showed that the radiologists' initial impressions are not reliable signals. In particular, the absence of an abnormal gist does not reliably signal a normal case, so radiologists should keep searching. This highlights the importance of "discovery scanning," or coarse screening to detect potential targets before ending the visual search.

Associations of Breast Arterial Calcifications with Cardiovascular Disease.

Cardiovascular diseases (CVD), including coronary artery disease (CAD), continue to be the leading cause of global mortality among women. While traditional CVD/CAD prevention tools play a significant role in reducing morbidity and mortality among both men and women, current tools for preventing CVD/CAD rely on traditional risk factor-based algorithms that often underestimate CVD/CAD risk in women compared with men. In recent years, some studies have suggested that breast arterial calcifications (BAC), which are benign calcifications seen in mammograms, may be linked to CVD/CAD. Considering that millions of women older than 40 years undergo annual screening mammography for breast cancer as a regular activity, innovative risk prediction factors for CVD/CAD involving mammographic data could offer a gender-specific and convenient solution. Such factors that may be independent of, or complementary to, current risk models without extra cost or radiation exposure are worthy of detailed investigation. This review aims to discuss relevant studies examining the association between BAC and CVD/CAD and highlights some of the issues related to previous studies' design such as sample size, population types, method of assessing BAC and CVD/CAD, definition of cardiovascular events, and other confounding factors. The work may also offer insights for future CVD risk prediction research directions using routine mammograms and radiomic features other than BAC such as breast density and macrocalcifications.

Variations of image interpretations of radiologists from different populations in mammography and tomosynthesis with different levels of breast density.

Purpose: This study aims to investigate the diagnostic performances of Australian and Shanghai-based Chinese radiologists in reading full-field digital mammogram (FFDM) and digital breast tomosynthesis (DBT) with different levels of breast density. Approach: Eighty-two Australian radiologists interpreted a 60-case FFDM set, and 29 radiologists also reported a 35-case DBT set. Sixty Shanghai radiologists read the same FFDM set, and 32 radiologists read the DBT set. The diagnostic performances of Australian and Shanghai radiologists were assessed using truth data (cancer cases were biopsy proven) and compared overall in specificity, case sensitivity, lesion sensitivity, receiver operating characteristics (ROC) area under the curve, and jack-knife free-response receiver operating characteristics (JAFROC) figure of merit, and they were stratified by case characteristics using the Mann-Whitney U test. The Spearman rank test was used to explore the association between radiologists' performances and their work experience in mammogram interpretation. Results: There were significantly higher performances of Australian radiologists compared with Shanghai radiologists in low breast density for case sensitivity, lesion sensitivity, ROC, and JAFROC in the FFDM set ( P < 0.0001 ); in high breast density, Shanghai radiologists' performances in lesion sensitivity and JAFROC were also lower than Australian radiologists ( P < 0.0001 ). In the DBT test set, Australian radiologists performed better than Shanghai radiologists in cancer detection in both low and high breast density. The work experience of Australian radiologists was positively linked to their diagnostic performances, whereas this association was not statistically significant in Shanghai radiologists. Conclusion: There were significant variations in reading performances between Australian and Shanghai radiologists in FFDM and DBT across different levels of breast density, lesion types, and lesion sizes. An effective training initiative tailored to suit local readers is essential to enhancing the diagnostic accuracy of Shanghai radiologists.

Radiologists' performance in reading digital breast tomosynthesis with and without synthesized views for cancer detection.

OBJECTIVE: The study aims to evaluate the diagnostic efficacy of radiologists and radiology trainees in digital breast tomosynthesis (DBT) alone vs DBT plus synthesized view (SV) for an understanding of the adequacy of DBT images to identify cancer lesions. METHODS: Fifty-five observers (30 radiologists and 25 radiology trainees) participated in reading a set of 35 cases (15 cancer) with 28 readers reading DBT and 27 readers reading DBT plus SV. Two groups of readers had similar experience in interpreting mammograms. The performances of participants in each reading mode were compared with the ground truth and calculated in term of specificity, sensitivity, and ROC AUC. The cancer detection rate in various levels of breast density, lesion types and lesion sizes between 'DBT' and 'DBT + SV' were also analyzed. The difference in diagnostic accuracy of readers between two reading modes was assessed using Man-Whitney U test. p < 0.05 indicated a significant result. RESULTS: There was no significant difference in specificity (0.67-vs-0.65; p = 0.69), sensitivity (0.77-vs-0.71; p = 0.09), ROC AUC (0.77-vs-0.73; p = 0.19) of radiologists reading DBT plus SV compared with radiologists reading DBT. Similar result was found in radiology trainees with no significant difference in specificity (0.70-vs-0.63; p = 0.29), sensitivity (0.44-vs-0.55; p = 0.19), ROC AUC (0.59-vs-0.62; p = 0.60) between two reading modes. Radiologists and trainees obtained similar results in two reading modes for cancer detection rate with different levels of breast density, cancer types and sizes of lesions (p > 0.05). CONCLUSION: Findings show that the diagnostic performances of radiologists and radiology trainees in DBT alone and DBT plus SV were equivalent in identifying cancer and normal cases. ADVANCES IN KNOWLEDGE: DBT alone had equivalent diagnostic accuracy as DBT plus SV which could imply the consideration of using DBT as a sole modality without SV.

Periapical Radiography versus Cone Beam Computed Tomography in Endodontic Disease Detection: A Free-response, Factorial Study.

AIM: To assess and compare reader performance in interpreting digital periapical (PA) radiography and cone beam computed tomography (CBCT) in endodontic disease detection, using a free-response, factorial model. MATERIALS AND METHODS: A reader performance study of 2 image test sets was undertaken using a factorial, free-response design, accounting for the independent variables: case type, case severity, reader type, and imaging modality. Twenty-two readers interpreted 60 PA and 60 CBCT images divided into 5 categories: diseased-subtle, diseased-moderate, diseased-obvious, nondiseased-subtle, and nondiseased-obvious. Lesion localization fraction, specificity, false positive (FP) marks, and the weighted alternative free-response receiver operating characteristic figure of merit were calculated. RESULTS: CBCT had greater specificity than PA in the obvious nondiseased cases (P = .01) and no significant difference in the subtle nondiseased category. Weighted alternative free-response receiver operating characteristic values were higher for PA than CBCT in the subtle diseased (P = .02) and moderate diseased (P = .01) groups with no significant difference between in the obvious diseased groups. CBCT had higher mean FPs than PA (P < .05) in subtle diseased cases. Mean lesion localization fraction in the moderate diseased group was higher in PA than CBCT (P = .003). No relationships were found between clinical experience and all diagnostic performance measures, except for in the obvious diseased CBCT group, where increasing experience was associated mean FP marks (P = .04). CONCLUSIONS: Reader performance in the detection of endodontic disease is better with PA radiography than CBCT. Clinical experience does not impact upon the accuracy of interpretation of both PA radiography and CBCT.