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Simple Summary: Current ultrasound imaging methods for detecting breast cancer often face challenges with image quality, making it tough to accurately spot tumors. This paper introduces UCapsNet, a new model that combines two advanced techniques to enhance breast cancer detection in ultrasound images. By improving how tumors are segmented and classified, UCapsNet aims to deliver clearer and more accurate results compared to traditional methods. Our findings indicate that UCapsNet can greatly improve diagnostic precision, enabling earlier detection and better treatment options for patients. This research could significantly impact future studies and lead to improved breast cancer detection practices in the medical community. Background/Objectives: Breast cancer remains one of the biggest health challenges for women worldwide, and early detection can be truly lifesaving. Although ultrasound imaging is commonly used to detect tumors, the images are not always of sufficient quality, and, thus, traditional U-Net models often miss the finer details needed for accurate detection. This outcome can result in lower accuracy, making early and precise diagnosis more difficult. Methods: This study presents an enhanced U-Net model integrated with a Capsule Network (called UCapsNet) to overcome the limitations of conventional techniques. Our approach improves segmentation by leveraging higher filter counts and skip connections, while the capsule network enhances classification by preserving spatial hierarchies through dynamic routing. The proposed UCapsNet model operates in two stages: first, it segments tumor regions using an enhanced U-Net, followed by a classification of the segmented images with the capsule network. Results: We have tested our model against well-known pre-trained models, including VGG-19, DenseNet, MobileNet, ResNet-50, and Xception. By properly addressing the limitations found in previous studies and using a capsule network trained on the Breast Ultrasound Image (BUSI) dataset, our model resulted in top-achieving impressive precision, recall, and accuracy rates of 98.12%, 99.52%, and 99.22%, respectively. Conclusions: By combining the U-Net's powerful segmentation capabilities with the capsule network's high classification accuracy, UCapsNet boosts diagnostic precision and addresses key weaknesses in existing methods. The findings demonstrate that the proposed model is not only more effective in detecting tumors but also more reliable for practical applications in clinical settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung nodules detected by computed tomography (CT) often require invasive procedures for definitive diagnosis. With the increasing use of CT, incidental lung nodules have increased significantly. An adjunctive blood-based biomarker test that predicts lung cancer risk could reduce unnecessary interventions and focus diagnostic efforts on high-risk patients. This study introduces a blood-based biomarker test that predicts lung cancer risk in CT-detected nodules with a sensitivity of 78.4% (95% CI: 75.7–81.1) and a specificity of 93.1% (95% CI: 90.0–96.3). Background and Objectives: Lung nodules detected by chest computed tomography (CT) often require invasive biopsies for definitive diagnosis, leading to unnecessary procedures for benign lesions. A blood-based biomarker test that predicts lung cancer risk in CT-detected nodules could help stratify patients and direct invasive diagnostics toward high-risk individuals. Methods: In this multicenter, single-blinded clinical trial, we evaluated a test measuring plasma levels of p53, anti-p53 autoantibodies, CYFRA 21-1, and anti-CYFRA 21-1 autoantibodies in patients with CT-detected lung nodules. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, and subgroup analyses by gender, age, and smoking status were performed. A total of 1132 patients who had CT-detected lung nodules, including 885 lung cancer cases and 247 benign lesions, were enrolled from two academic hospitals in South Korea. Results: The test demonstrated a sensitivity of 78.4% (95% CI: 75.7–81.1) and specificity of 93.1% (95% CI: 90.0–96.3) in predicting lung cancer in CT-detected nodules. The PPV was 97.6%, and the NPV was 54.6%. Performance was consistent across gender (sensitivity 79.3% in men and 76.8% in women) and age groups, with a specificity of 93.4% in men and 92.7% in women. Stage I lung cancer was detected with a sensitivity of 80.6%. Conclusions: The Lung Cancer test based on 9G technology presented here offers a non-invasive method for stratifying lung cancer risk in patients with CT-detected nodules. Its integration into clinical practice could reduce unnecessary interventions and foster earlier detection. [ABSTRACT FROM AUTHOR]

Simple Summary: Prognosis, early detection, and relapse identification are jointly crucial factors for effective lung cancer treatment. Blood-based liquid biopsy, a non-invasive method, can provide solutions to the deadlocks in the management of this widespread cancer type by eliciting biomarkers. In this research, an integrated approach is developed, which combines the use of databases and experimental validation to find adequate biomarkers in non-small-cell lung cancer. The arising results, concerning miR-29a-3p in exosomes and lncRNA H19 in cfRNA, widen the horizons for identifying and exploiting promising biomarkers in non-small-cell lung cancer. Background and Objective: Lung cancer, the second most prevalent cancer globally, poses significant challenges in early detection and prognostic assessment. Despite advancements in targeted therapies and immunotherapy, the timely identification of relapse remains elusive. Blood-based liquid biopsy biomarkers, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating-free RNAs (cfRNAs), and extracellular vesicles (EVs)/exosomes, offer promise for non-invasive monitoring. Methods: We employ a comprehensive approach integrating miRNA/lncRNA/metabolomic datasets, following a mixed-methods content analysis, to identify candidate biomarkers in NSCLC. NSCLC-associated miRNA/gene/lncRNA associations were linked to in silico-derived molecular pathways. Results: For data validation, mass spectrometry-based untargeted metabolomics of plasma EVs highlighted miRNA/lncRNA/metabotypes, linking "glycerophospholipid metabolism" to lncRNA H19 and "alanine, aspartate and glutamate metabolism" to miR-29a-3p. Prognostic significance was established for miR-29a-3p, showing lower expression in NSCLC patients with disease progression compared to stable disease (p = 0.004). Kaplan–Meier survival analysis indicated that patients with miR-29a-3p under-expression had significantly shorter overall survival (OS) (p = 0.038). Despite the expression of lncRNA H19 in plasma EVs being undetected, its expression in plasma cfRNAs correlated significantly with disease progression (p = 0.035). Conclusions: Herein, we showcase the potential of plasma EV-derived miR-29a-3p as a prognostic biomarker and underscore the intricate interplay of miRNAs, lncRNAs, and metabolites in NSCLC biology. Our findings offer new insights and avenues for further exploration, contributing to the ongoing quest for effective biomarkers in early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the U.S. National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose computed tomography (LDCT) for early lung cancer detection, LDCT has emerged as a critical tool for identifying lung cancer in high-risk populations. This retrospective study evaluates trends in non-small cell lung cancer (NSCLC) staging at Kaohsiung Medical University Hospital (KMUH) from 2011 to 2020, with a particular focus on the effects of LDCT screening, which was introduced in 2013. We examined correlations between the number of LDCT screenings and NSCLC stage distribution, emphasizing early-stage (stages 0 and I) and late-stage (stage IV) diagnoses. Additionally, we assessed histopathological differences between adenocarcinoma and squamous cell carcinoma identified via LDCT and evaluated the impact of early diagnosis on five-year survival rates. Background: Low-dose computed tomography (LDCT) has been widely adopted for lung cancer screening due to its proven ability to reduce lung cancer mortality, especially among high-risk populations. Methods: This retrospective study aims to evaluate the impact of LDCT screening on non-small cell lung cancer (NSCLC) staging at Kaohsiung Medical University Hospital (KMUH) from 2011 to 2020, following the introduction of LDCT in 2013. The study examines the correlation between LDCT screening volume and changes in the distribution of NSCLC stages, particularly early-stage (stages 0 and I) and late-stage (stage IV) diagnoses. Additionally, it explores the differences in histopathological subtypes, focusing on adenocarcinoma and squamous cell carcinoma, and assesses the impact of early detection on five-year survival rates. Results: The results show a significant increase in early-stage NSCLC diagnoses, particularly in adenocarcinoma cases, where early-stage diagnoses rose from 10.4% in 2010 to 38.7% in 2019. However, the number of stage IV cases remained stable, indicating that LDCT may not substantially reduce late-stage diagnoses. Pearson's correlation analysis demonstrated a strong positive correlation between LDCT screening and early-stage NSCLC detection, particularly for adenocarcinoma (p < 0.001), though the early detection of squamous cell carcinoma and small cell carcinoma remained limited. Conclusions: The study concludes that LDCT screening plays a crucial role in improving early NSCLC detection and five-year survival rates. Future research should focus on optimizing screening strategies to capture more at-risk populations and enhance the detection of harder-to-diagnose subtypes like squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis B virus (HBV)—hepatitis delta virus (HDV) coinfection accounts for an estimated 8–10% of cases of hepatocellular carcinoma (HCC) worldwide. Recent meta-analyses suggest that HDV increases the risk of HCC associated with HBV, but its pathogenic role remains poorly elucidated. HCC related to HBV–HDV coinfection tends to be diagnosed by surveillance but in the background of severe liver dysfunction, which has therapeutic implications, with a high rate of liver transplantation, and high mortality in patients not eligible for liver transplantation. Hepatitis delta virus (HDV) infection requires the presence of hepatitis B virus (HBV), and chronic HBV–HDV coinfection is considered the most severe form of viral hepatitis. When compared with HBV mono-infection, HBV–HDV coinfection is associated with higher rates of liver cirrhosis and hepatocellular carcinoma (HCC). In this review, we aim to elucidate the complex relationship between HDV infection and the development of HCC. The exact mechanisms underlying the carcinogenic potential of HDV remain to be fully elucidated. Evidence suggests that HDV has both indirect and direct oncogenic effects. Indirect effects promote accelerated progression to liver cirrhosis, which results in a different tumor microenvironment. Direct oncogenic effects are suggested by a distinct molecular signature. The recent epidemiological data regarding HBV–HDV coinfection should make us reconsider the HCC screening strategy, with special focus in younger non-cirrhotic patients. Finally, treating HCC in patients with chronic HDV poses unique challenges due to the complex interplay between HBV and HDV and the severity of liver disease. An in-depth understanding of the epidemiology and pathophysiology of HDV infection and carcinogenesis is essential to improve disease management in this high-risk population. [ABSTRACT FROM AUTHOR]

Background: Lung cancer remains a significant health concern, and the effectiveness of early detection significantly enhances patient survival rates. Identifying lung tumors with high precision is a challenge due to the complex nature of tumor structures and the surrounding lung tissues. Methods: To address these hurdles, this paper presents an innovative three-step approach that leverages Generative Adversarial Networks (GAN), Long Short-Term Memory (LSTM), and VGG16 algorithms for the accurate reconstruction of three-dimensional (3D) lung tumor images. The first challenge we address is the accurate segmentation of lung tissues from CT images, a task complicated by the overwhelming presence of non-lung pixels, which can lead to classifier imbalance. Our solution employs a GAN model trained with a reinforcement learning (RL)-based algorithm to mitigate this imbalance and enhance segmentation accuracy. The second challenge involves precisely detecting tumors within the segmented lung regions. We introduce a second GAN model with a novel loss function that significantly improves tumor detection accuracy. Following successful segmentation and tumor detection, the VGG16 algorithm is utilized for feature extraction, preparing the data for the final 3D reconstruction. These features are then processed through an LSTM network and converted into a format suitable for the reconstructive GAN. This GAN, equipped with dilated convolution layers in its discriminator, captures extensive contextual information, enabling the accurate reconstruction of the tumor's 3D structure. Results: The effectiveness of our method is demonstrated through rigorous evaluation against established techniques using the LIDC-IDRI dataset and standard performance metrics, showcasing its superior performance and potential for enhancing early lung cancer detection. Conclusions:This study highlights the benefits of combining GANs, LSTM, and VGG16 into a unified framework. This approach significantly improves the accuracy of detecting and reconstructing lung tumors, promising to enhance diagnostic methods and patient results in lung cancer treatment. [ABSTRACT FROM AUTHOR]

Background: By using optimal insertion techniques with water infusion and dynamic position changes, pain during colonoscopy is greatly reduced and the procedures can usually be performed without sedation. We investigated whether the excellent results with water-aided colonoscopy reported by experts are reproducible in daily practice in a regional hospital. Methods: During the year 2023, 500 consecutive outpatients 50–75 years old presenting for colorectal cancer screening and surveillance could choose between unsedated or on-demand minimally sedated colonoscopy, moderate sedation with midazolam, or deep sedation with propofol. A total of 57% opted for unsedated colonoscopy, and of those patients, 250 consecutive patients were included. The primary outcome was the feasibility of the procedure. Cecal intubation rate (CIR), pain scores, use of midazolam, and willingness to repeat future procedures in the same way were registered periprocedural. Additional outcomes were cecal intubation time (CIT), detection rate of lesions, polyp resection rate, rate of adequate bowel preparation, and volume of water aspirated during insertion. Results: 250 consecutive sedation-free or on-demand minimally sedated water-based colonoscopies were analyzed. The CIR was 98%. A total of 96.5% completed without sedation and 5% of the procedures were perceived as moderately painful, but none had severe pain. The willingness to repeat was 97%. The mean CIT was 8.2 min. Conclusions: Using water-aided insertion techniques, comfortable sedation-free, or on-demand minimally sedated colonoscopy in daily practice in a regional hospital is feasible in the vast majority of patients presenting for colorectal cancer screening and surveillance, and the willingness to repeat is very high. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is the most common gynecological malignancy, with rising incidence and mortality rates. Key risk factors, including obesity, prolonged estrogen exposure, and metabolic disorders, underscore the urgent need for non-invasive, early diagnostic tools. This review focuses on the role of DNA methylation as a potential biomarker for early EC detection. Aberrant DNA methylation in the promoter regions of tumor suppressor genes can lead to gene silencing and cancer progression. We examine recent studies utilizing minimally invasive samples, such as urine, cervicovaginal, and cervical scrapes, to detect early-stage EC through DNA methylation patterns. Markers such as RASSF1A, HIST1H4F, GHSR, SST, and ZIC1 have demonstrated high diagnostic accuracy, with AUC values up to 0.95, effectively distinguishing EC from non-cancerous conditions. This review highlights the potential of DNA methylation-based testing as a non-invasive alternative to traditional diagnostic methods, offering earlier detection, better risk stratification, and more personalized treatment plans. These innovations hold the promise of transforming clinical practice by enabling more timely and effective management of endometrial cancer. [ABSTRACT FROM AUTHOR]

The specificity and sensitivity of a simple non-invasive multi-cancer screening method in detecting breast, lung, prostate, and colorectal cancer in breath samples were evaluated in a double-blind study. Breath samples of 1386 participants (59.7% males, median age 56.0 years) who underwent screening for cancer using gold-standard screening methods, or a biopsy for a suspected malignancy were collected. The samples were analyzed using a bio-hybrid platform comprising trained detection canines and artificial intelligence tools. According to cancer screening/biopsy results, 1048 (75.6%) were negative for cancer and 338 (24.4%) were positive. Among the 338 positive samples, 261 (77.2%) were positive for one of the four cancer types that the bio-hybrid platform was trained to detect, with an overall sensitivity and specificity of 93.9% (95% confidence interval [CI] 90.3-96.2%) and 94.3% (95% CI 92.7%-95.5%), respectively. The sensitivity of each cancer type was similar; breast: 95.0% (95% CI 87.8-98.0%), lung: 95.0% (95% CI 87.8-98.0%), colorectal: 90.0% (95% CI 74.4-96.5%), prostate: 93.0% (95% CI 84.6-97.0%). The sensitivity of 14 other malignant tumors that the bio-hybrid platform was not trained to detect, but identified, was 81.8% (95% CI 71.8%-88.8%). Early cancer (0–2) detection sensitivity was 94.8% (95% CI 91.0%-97.1%). This bio-hybrid multi-cancer screening platform demonstrated high sensitivity and specificity and enables early-stage cancer detection. [ABSTRACT FROM AUTHOR]

Background: Effective bowel cancer screening is freely available in Australia, however, there are inequities in utilisation amongst non-English speakers at home. This study estimates the health impacts and cost-effectiveness of recruitment interventions targeted at Arabic and Mandarin speaking populations in Victoria, Australia to increase bowel cancer screening participation. Methods: A Markov microsimulation model simulated the development of bowel cancer, considering National Bowel Cancer Screening Program participation rates. Culturally specific recruitment interventions e.g., community education and tailored paid media for 50–74-year-olds were compared to usual practice. A cost-utility analysis was conducted over a 50-year time horizon from a healthcare perspective, to estimate the cost per quality-adjusted life year (QALY) based on plausible effectiveness levels. Costs are in 2019 Australian dollars. Results: Intervention costs were $6.90 per person for the Arabic speaking group and $3.10 for Mandarin speakers. The estimated cost/QALY was $2,781 (95% uncertainty interval [UI]: $2,144─$3,277) when screening increased by 0.2% in the Arabic group, and an estimated 5–6 additional adenoma and cancer cases were detected. In the Mandarin group, the estimated cost/QALY was $1,024/QALY (95%UI: $749─$1,272) when screening increased by 1.1%, and an estimated 18–23 additional adenoma and cancer cases were detected. Conclusions: Culturally specific recruitment interventions to increase bowel cancer screening are inexpensive and likely to be cost-effective. Improvements in capturing language spoken at home by the National program would facilitate more precise estimates of the effectiveness and cost-effectiveness of these interventions. [ABSTRACT FROM AUTHOR]

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have increased cancer risk. Platinum retention in healthy tissue may contribute to carcinogenesis. We assessed total platinum concentrations in plasma, urine, and normal colonic mucosa samples in TCS treated with cisplatin. From the total TCS treated with ≥3 cycles cisplatin who participated in a colonoscopy-screening study in four Dutch hospitals (n = 154), plasma (n = 131) and urine (n = 115) samples were collected. During colonoscopy, 60 biopsies of normal colonic mucosa (two samples each per 30 randomly selected patients undergoing colonoscopy) were obtained. Samples were analyzed for total platinum concentrations using inductively coupled plasma mass spectrometry and compared with controls (plasma: 10, urine: 3, normal colonic mucosa: 9). The median age at colonoscopy was 50 years (interquartile range (IQR): 43–57) and the median time since treatment was 20 years (IQR:16–26). Median platinum concentrations in plasma (38 pg/mL; IQR: 24–61 pg/mL) and urine (376 pg/mL; IQR: 208–698 pg/mL) remained elevated in TCS up to 40 years post-treatment and were higher than in controls (all controls were below limits of detection [plasma: 25 pg/mL, urine: 6 pg/mL]). The median platinum concentration in normal colonic mucosa was 0.58 pg/mg (IQR: 0.33–1.59 pg/mg) in the transverse and 0.51 pg/mg (IQR:0.26–1.25 pg/mg) in the descending colon. Cisplatin treatment is associated with long-term retention of platinum in various patient sample types. This might increase cancer risk by causing somatic mutations, potentially explaining the elevated risk of second malignant neoplasms in TCS. The long-term effects of platinum retention should be monitored to understand carcinogenesis and to provide guidelines for early second cancer detection. Trial registration: ClinicalTrials.Gov:NCT04180033. [ABSTRACT FROM AUTHOR]

There is a growing interest in using fecal mRNA transcripts as biomarkers for non-invasive detection of colorectal cancer (CRC). The following study compares different RNA extraction and reverse transcription PCR (RT-PCR) methods for mRNA detection in stool and identifies a robust and sensitive protocol. A combination of the Stool total RNA purification kit (Norgen) and the Superscript III one-step RT-PCR kit (Invitrogen) provided high RNA purity and sensitive and consistent mRNA detection, making them well-suited candidates for large-scale studies. We tested the protocol by detecting the mRNA of several immune genes (CXCL1, IL8, IL1B, IL6, PTGS2, and SPP1) in 22 CRCs, 24 adenomatous polyps, and 22 control stool samples. All these inflammatory markers, except for CXCL1, showed a strong association with CRC. Cancer stool samples showed increased levels of IL1B, IL8, and PTGS2 transcripts compared to polyp and control groups. Thus, this work supports the potential use of fecal mRNA as biomarkers for CRC detection. [ABSTRACT FROM AUTHOR]

Computer-assisted diagnosis (CAD) plays a key role in cancer diagnosis or screening. Whereas, current CAD performs poorly on whole slide image (WSI) analysis, and thus fails to generalize well. This research aims to develop an automatic classification system to distinguish between different types of carcinomas. Obtaining rich deep features in multi-class classification while achieving high accuracy is still a challenging problem. The detection and classification of cancerous cells in WSI are quite challenging due to the misclassification of normal lumps and cancerous cells. This is due to cluttering, occlusion, and irregular cell distribution. Researchers in the past mostly obtained the hand-crafted features while neglecting the above-mentioned challenges which led to a reduction of the classification accuracy. To mitigate this problem we proposed an efficient dual attention-based network (CytoNet). The proposed network is composed of two main modules (i) Efficient-Net and (ii) Dual Attention Module (DAM). Efficient-Net is capable of obtaining higher accuracy and enhancing efficiency as compared to existing Convolutional Neural Networks (CNNs). It is also useful to obtain the most generic features as it has been trained on ImageNet. Whereas DAM is very robust in obtaining attention and targeted features while negating the background. In this way, the combination of an efficient and attention module is useful to obtain the robust, and intrinsic features to obtain comparable performance. Further, we evaluated the proposed network on two well-known datasets (i) Our generated thyroid dataset (ii) Mendeley Cervical dataset (Hussain in Data Brief, 2019) with enhanced performance compared to their counterparts. CytoNet demonstrated a 99% accuracy rate on the thyroid dataset in comparison to its counterpart. The precision, recall, and F1-score values achieved on the Mendeley Cervical dataset are 0.992, 0.985, and 0.977, respectively. The code implementation is available on GitHub. https://github.com/naveedilyas/CytoNet-An-Efficient-Dual-Attention-based-Automatic-Prediction-of-Cancer-Sub-types-in-Cytol. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is a genetic disease that affects people worldwide, and breast cancer is the most common cancer in women. Studies have been conducted on molecular parameters to predict tumor behavior and develop therapeutic strategies. Telomeres, which are at the end of chromosomes, have been studied for their relationship with breast cancer, but more research is needed to understand their role in the disease. Circulating‐free DNA (cfDNA) is DNA that is free in the bloodstream and is considered a promising target for early cancer detection, treatment response monitoring, and prognosis assessment. This study is aimed at comparing cfDNA telomere length of breast cancer patients and healthy individuals and analyzing the impact of neoadjuvant chemotherapy on telomere length in cfDNA. Materials and Methods: Blood samples were collected from 33 breast cancer patients undergoing neoadjuvant chemotherapy before and after treatment. The quantitative PCR method is used to measure the average telomere lengths. Results: This study found that the telomere length of cfDNA in breast cancer patients before and after treatment is significantly shorter than in the control group. Neoadjuvant chemotherapy is found to shorten the cfDNA telomere length, especially in the treatment‐responsive group. Conclusion: Our study suggests that telomere length in cfDNA may be a useful biomarker for predicting therapy response and possible reoccurrence of the disease in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer remains a significant global health concern, with some types of human papillomavirus (HPV) infection playing a pivotal role in its etiology. This research was conducted to explore the awareness and knowledge regarding Pap tests and HPV typing as screening tools for Cervical Cancer in Edo North, Nigeria. Methods: Data was collected with the use of a pretested structured questionnaire that includes open ended and close ended response format to assess knowledge. Data was analyzed using the IBM SPSS version 29. Results: This study utilized a descriptive cross-sectional study design with 113 participants aged 25–65 years. A significant knowledge gap regarding the purpose of Pap tests and HPV testing was observed, with only 32.7% of participants aware of their purpose. Only 20.4% of participants had undergone cervical screening, with inconsistencies in screening frequency. HPV vaccination rates were low, with only one vaccinated individual. Conclusion: This study reveals a concerning low level of awareness and knowledge among participants regarding Pap tests and HPV testing in cervical cancer screening. These findings emphasize the need for improved education and communication about cervical cancer screening methods to empower individuals to make informed decisions about their healthcare. [ABSTRACT FROM AUTHOR]

With the emergence of computer‐aided diagnostic (CAD) systems, the speed of histopathological image analysis and the accuracy of cancer detection have considerably improved. However, the appearance of histopathological slides can vary depending on the consistency of tissue thickness, stain concentrations, and equipment, thus affecting the judgment of CAD systems. This study proposes a palette‐based colour normalization method for histopathology images is proposed to solve the problem of colour differences between histopathology images. The method builds a graphical user interface based on an improved palette generation algorithm and colour transfer definitions, through which the user can complete the corresponding colour modification to achieve colour normalization. The evaluation of the metrics on histopathological images shows that our method is able to achieve higher image quality and better preservation of structural information of the source image compared with four other colour normalization algorithms. The peak signal‐to‐noise ratio values obtained by the proposed method on two publicly available datasets were 24.1914 and 21.3666, and the structural similarity index matrix values were 0.9871 and 0.9760. The proposed method provides new ideas for the development and design of CAD systems. [ABSTRACT FROM AUTHOR]

Objectives Patients and Methods Results Conclusion To evaluate the additional prostate cancer detection yield and clinical implications of performing contralateral systematic biopsies in men with unilateral suspicious magnetic resonance imaging (MRI) findings undergoing MRI‐guided transperineal (TP) biopsies in an outpatient clinic.A prospective study of 655 consecutive men with unilateral MRI suspicious findings undergoing office‐based MRI‐guided TP biopsies between May 2022 and December 2023. All men had pre‐biopsy MRI followed by MRI‐guided TP fusion biopsies with at least four targeted cores per lesion plus five contralateral systematic biopsies. The primary objective was the clinically significant prostate cancer (csPCa) detection rate of contralateral systematic biopsies in men with no or insignificant PCa on targeted biopsies. Secondary objectives included the impact of contralateral biopsies on PCa grade upgrading, additional insignificant PCa diagnoses, and the clinical implications of multifocal csPCa detected on both targeted and contralateral cores.Any and csPCa (Gleason Grade Group [GG] ≥2) was detected in 564/655 (85%) and 471/655 (71%) men with a median age of 66 years and PSA level of 7.6 ng/mL. Overall, seven of 655 (1%) men had csPCa detected by contralateral systematic biopsies missed on MRI‐targeted biopsy, all of whom had low‐volume Gleason GG 2 PCa eligible for active surveillance. Furthermore, 70/464 (15%) men with csPCa on MRI‐targeted biopsy had matching Gleason GG 2–5 PCa on contralateral biopsy, and another seven had higher Gleason GG. However, the additional information from contralateral biopsies did not seem to influence whole‐gland treatment allocation and nerve‐sparing during surgery.Contralateral systematic biopsies in men with unilateral MRI findings undergoing MRI‐guided TP targeted biopsies have limited value for csPCa detection and risk assessment for whole‐gland treatment but may be important for determining PCa multifocality considering focal therapy eligibility. [ABSTRACT FROM AUTHOR]

Simple graphical displays such as icon arrays and tree diagrams have been proposed for communicating health risks and supporting informed decisions. The UK’s National Health Service (NHS) uses tree diagrams to communicate the chances of different cervical cancer screening results, but their effectiveness has not been compared to icon arrays. We conducted a well-powered longitudinal experiment involving 3,100 UK women eligible for cervical screening (25–64 years) to examine the effectiveness of icon arrays to communicate possible cervical screening results, relative to the UK NHS’s tree diagram and to a numerical-only format. We also examined whether the presence (vs. absence) of explanatory text referring to different types of results (i.e. distinguishing between HPV positive results with vs. without abnormal cervical cells) moderated effects of presentation format. Presentation format did not affect verbatim or gist knowledge of probabilities at initial assessment (i.e. immediately after participants viewed the displays), but icon arrays were associated with better gist knowledge of absolute magnitudes than tree diagrams and numerical-only formats at 1-month follow-up. Participants exposed to icon arrays also perceived lower likelihood of adverse screening results and reported stronger screening intentions at initial assessment. For displays without explanatory text, icon arrays were also associated with more positive user evaluations and less negative affective reactions than tree diagrams at initial assessment. Overall, our findings suggest that icon arrays support enduring knowledge of approximate magnitudes of probabilities and are better suited than tree diagrams for communicating possible screening results. [ABSTRACT FROM AUTHOR]

Breast cancer is a prevalent and highly lethal cancer affecting women globally. While non-invasive techniques like ultrasound and mammogram are used for diagnosis, histological examination after biopsy is considered the gold standard. However, manual examination of tissues for abnormality is labor-intensive, expensive, and requires prior domain knowledge. Early detection, awareness, and access to specialized medical infrastructure in resource-constrained and remote areas are significant challenges but crucial for saving lives. In recent years, deep learning-based approaches have shown promising results in breast cancer detection, facilitated by advancements in GPU memory, computation power, and the availability of digital data. Motivated by these observations, we propose the Breast-NET deep convolutional neural network model for breast cancer detection and grading using histological images. Our model's performance is evaluated on the BreakHis dataset, and we demonstrate its generalization ability on the Invasive Ductal Carcinoma (IDC) grading and IDC datasets. Extensive experimental and statistical performance analysis, along with an ablation study, validates the efficiency of our proposed model. Furthermore, we demonstrate the effectiveness of transfer learning with seven pre-trained convolutional neural networks for breast cancer detection and grading. Experimental results show that our framework outperforms state-of-the-art approaches in terms of accuracy, space, and computational complexity for the BreakHis, IDC grading, and IDC datasets. [ABSTRACT FROM AUTHOR]

Segmentation of nuclei in histology images is key in analyzing and quantifying morphology changes of nuclei features and tissue structures. Conventional diagnosis, segmenting, and detection methods have relied heavily on the manual-visual inspection of histology images. These methods are only effective on clearly visible cancerous lesions on histology images thus limited in their performance due to the complexity of tissue structures in histology images. Hence, early detection of breast cancer is key for treatment and profits from Computer-Aided-Diagnostic (CAD) systems introduced to efficiently and automatically segment and detect nuclei cells in pathology. This paper proposes, an automatic watershed segmentation method of cancerous lesions in unsupervised human breast histology images. Firstly, this approach pre-processes data through various augmentation methods to increase the size of dataset images, then a stain normalization technique is applied to these augmented images to isolate nuclei features from tissue structures. Secondly, data enhancement techniques namely; erosion, dilation, and distance transform are used to highlight foreground and background pixels while removing unwanted regions from the highlighted nuclei objects on the image. Consequently, the connected components method groups these highlighted pixel components with similar intensity values and, assigns them to their relevant labeled component binary mask. Once all binary masked groups have been determined, a deep-learning recurrent neural network from the Keras architecture uses this information to automatically segment nuclei objects with cancerous lesions and their edges on the image via watershed filling. This segmentation method is evaluated on an unsupervised, augmented human breast cancer histology dataset of 11,151 images. This proposed method produced a significant evaluation result of 98 % F1-accuracy score. [ABSTRACT FROM AUTHOR]

Background: This study investigates breast cancer screening disparities among Mexican immigrant women in rural and urban U.S. communities, focusing on cultural beliefs, healthcare access, and geographical differences. Methods: A cross-sectional study of 350 Mexican immigrant women aged 40+ without prior cancer diagnosis was conducted in rural (<2000 population) and urban parts of the U.S. in 2015. Culturally tailored surveys during household visits, clinic appointments, and community meetings assessed cultural beliefs, mammography engagement, and family support. Comparative analyses t -tests and chi-square tests were conducted, with significance set at P <.05. Results: Rural women demonstrated higher adherence to spiritualismo (M = 4.31, SD = 1.13) compared to their urban counterparts (M = 3.91, SD = 1.36), marianismo (M = 3.33, SD = 0.45 vs M = 3.21, SD = 0.48), and machismo (M = 3.02, SD = 0.52 vs M = 2.80, SD = 0.61). The rural women also reported higher mammography rates (54.4% vs 45.6%), with 60.4% undergoing four or more mammograms. Despite barriers such as doctor non-recommendation (55.0% rural vs 45.0% urban) and embarrassment (67.9% rural vs 32.1% urban), rural women engaged more in family discussions about cancer screenings (61.7% vs 38.3%) and received more family assistance in finding health information (59.8% vs 40.2%). Conclusions: This study elucidates significant rural-urban disparities in cultural adherence and family support among Mexican immigrant women, underscoring the necessity for culturally tailored interventions to enhance breast cancer screening rates and health outcomes. [ABSTRACT FROM AUTHOR]

Purpose: County-level hospitals in China constitute a vital component of the healthcare system, delivering essential medical services, emergency care, and specialized treatments, particularly in oncology. This study aimed to comprehensively evaluate the current status of cancer diagnosis and treatment in county hospitals and assess their overall capacity. Methods: A nationwide cross-sectional survey by the China Anti-cancer Association (CACA) from February to May 2023 assessed cancer diagnosis and treatment in mainland China's county hospitals. Using a multi-center approach, a fifty-five-question questionnaire was administered to oncology professionals and management staffs, focusing on hospital facilities, oncology specialists, cancer cases, treatment capabilities, and healthcare collaboration. Questionnaire reliability and validity were established in a 2022 national survey. Participants, aged 18 or older, were recruited through purposive sampling, receiving self-administered questionnaires for confidentiality. SAS 9.4 software facilitated statistical analysis. Results: The study encompassed 76 county-level medical institutions, with 82.9% of them featuring established oncology departments providing comprehensive cancer care, including early screening, diagnosis, treatment, and long-term follow-up. Notably, a total of 56.6% of the institutions surveyed implemented programs for cancer screening and early diagnosis. A significant proportion of advanced cancer patients received treatment and follow-up at the county level. Persistent disparities in medical insurance policies at the county level were identified as a continuing challenge. Furthermore, 82.9% of hospitals had cultivated collaborative relationships with higher-level institutions to enhance patient care quality and treatment capacity. The study revealed a 56.6% shortage of remote collaboration platforms in these hospitals. The need for a patient-centered approach in county hospitals was underscored. Conclusion: While county-level hospitals face challenges, such as a shortage of specialized oncologists and advanced resources, they exhibit progress in standardizing cancer care to enhance diagnosis and treatment in rural areas. [ABSTRACT FROM AUTHOR]

The incidence of Early-Onset Colorectal Cancer (EOCRC) is increasing. However, the prognosis of EOCRC compared to Late-Onset Colorectal Cancer (LOCRC), and the ideal age for initial colorectal cancer (CRC) screening are not clear. In this study, we identified the pathological differences between the groups and determined the optimal screening age for CRC patients. We included 10,172 patients diagnosed with CRC from January 2011 to December 2021 in this study. Survival differences were compared by plotting Kaplan–Meier survival curves and conducting landmark analysis. Additionally, the diagnostic age of CRC patients was analyzed using age cumulative curves. Compared to LOCRC patients, EOCRC patients had a higher proportion of deficient mismatch repair (dMMR) and more advanced TNM staging (P < 0.05). The five-year survival of EOCRC patients was significantly better than that of LOCRC patients (P < 0.05). Laparoscopic surgery improved the long-term survival of EOCRC patients. Proficient mismatch repair (pMMR) favored the long-term survival of EOCRC patients. The survival rate of EOCRC patients at TNM stages I and II was higher than that of LOCRC patients at the same stages (P < 0.05). The age cumulative curve showed a substantial increase in the number of CRC patients at 40 years. The long-term prognosis of EOCRC patients is better than that of LOCRC patients, especially among those with pMMR, stages I–II, and who undergo laparoscopic surgery. For people with a high risk of cancer, such as a family history of cancer and poor lifestyle habits, the starting age for CRC screening should be 40 years. [ABSTRACT FROM AUTHOR]

Establishing an accurate prognosis for women diagnosed with breast cancer (BC) is extremely challenging. Axillary lymph node (ALN) evaluation is considered of major prognostic value. The one‐step nucleic acid amplification (OSNA) assay is currently used for assessing axillary sentinel lymph node (SLN) status in BC. Additionally, total tumor load (TTL) may help predict further metastatic axillary involvement beyond the SLN. The prognostic value of primary BC location remains controversial due to lack of consensus on the biological differences among tumors at various sites. Evidence suggests that tumors in the internal quadrants (INLs) have worse prognosis compared to those in the external quadrants. Furthermore, ALN involvement is believed to be mainly associated with external quadrant tumors, mainly due to the lymphatic drainage system of the breast. This pilot observational study, despite lacking a control group and having a relatively small sample size, is the first to evaluate the potential relationship between primary BC location and ALN metastasis using the OSNA assay. A sample of consecutive BC patients undergoing axillary staging with the OSNA assay were included. Tumors were categorized into three groups based on primary location: external quadrants and axillary tail (EXL), INLs, and nipple and areola location (NAL). Although not statistically significant, the INL group exhibited a higher mean TTL. Additionally, no significant differences were observed between groups concerning SLN detection techniques, SLN status, number of metastatic SLN, or mean TTL. These findings support the use of the innovative tracer superparamagnetic iron oxide regardless of tumor site. This study underscores the importance of understanding the relationship between BC location and ALN status, which may improve prognostic stratification and targeted therapies based on tumor site. If these observations are confirmed in larger, multicentric studies, the potential conclusions may shift the paradigm of INL tumor treatment, significantly impacting clinical practice and research. [ABSTRACT FROM AUTHOR]

Aim: The faecal immunochemical test (FIT) is now widely used in English primary care to triage people who exhibit signs or symptoms of colorectal cancer (CRC). National guidelines for FIT implementation were based on data that acknowledged limitations. This study examines FIT accuracy in primary care patients with low‐ and high‐risk symptoms of CRC. Methods: This study describes a retrospective cohort study in South Yorkshire, UK (n = 2029). Consecutive symptomatic adult patients in primary care undergoing a FIT between 01/04/2021 and 30/04/2021 were assessed. A threshold > 10 μg Hb/g was defined as a positive FIT result. Lower gastrointestinal tract (LGI) investigations were the reference standard. Follow‐up over 24 months was used to identify serious colorectal diseases (CRC, high‐risk polyps and inflammatory bowel disease [IBD]). Results: Five hundred and fifteen (25.4%) patients had a positive FIT. The CRC prevalence was 1.2% (24/2029). Nineteen (79.1%) of the 24 CRC cases had NG12 symptoms, with two (8.3%) having a negative FIT. For CRC detection, FIT showed 91.7% sensitivity (95% CI: 71.5%–98.5%), 75.4% specificity (95% CI: 73.4%–77.2%), 4.3% positive predictive value (PPV) (95% CI: 2.8%–6.5%) and 99.9% negative predictive value (NPV) (95% CI: 99.5%–99.97%). Combining CRC, high‐risk polyps and IBD increased PPV and specificity but decreased sensitivity and NPV. Conclusions: In primary care, FIT safely triages patients having at‐risk CRC risk symptoms. Negative FIT results indicate a low likelihood of CRC and supports safety‐netting interventions. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSSmall-molecule compounds exhibit distinct pharmacological properties and clinical effectiveness. Over the past decade, advances in covalent drug discovery have led to successful small-molecule drugs, such as EGFR, BTK, and KRAS (G12C) inhibitors, for cancer therapy. Researchers are paying more attention to refining drug screening methods aiming for high throughput, fast speed, high specificity, and accuracy. Therefore, the discovery and development of small-molecule drugs has been facilitated by significantly reducing screening time and financial resources, and increasing promising lead compounds compared with traditional methods. This review aims to introduce classical and emerging methods for screening small-molecule compounds in targeted cancer therapy. It includes classification, principles, advantages, disadvantages, and successful applications, serving as valuable references for subsequent researchers.Classical and emerging methods for screening small-molecule compounds.Target-based drug screening approaches widely used for drug development.Phenotype-based screening approaches for discovering candidate compounds.Chemoproteomics as an unbiased screening technology to identify compound targets.Computer-aided drug discovery to reduce the number of compounds screened experimentally.Classical and emerging methods for screening small-molecule compounds.Target-based drug screening approaches widely used for drug development.Phenotype-based screening approaches for discovering candidate compounds.Chemoproteomics as an unbiased screening technology to identify compound targets.Computer-aided drug discovery to reduce the number of compounds screened experimentally. [ABSTRACT FROM AUTHOR]

Background: Sulfur microbial diet (SMD) is a dietary pattern closely related to the intestinal load of sulfur-metabolizing microbes in humans. Diet and microbes may play an important role in the carcinogenesis of esophagus. However, epidemiological studies on SMD and esophageal cancer (EC) risk are scarce. Here, we evaluated this association based on a large American cohort. Methods: In the cohort of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a SMD score was calculated to evaluate participants' compliance of SMD pattern, with higher scores presenting greater adherence. Cox hazards regression model was used to explore the association between the SMD score and the incidence of EC, esophageal squamous cell carcinoma (ESCC), and esophageal adenocarcinoma (EA). Subgroup analyses were conducted to figure out potential modifiers interacting with SMD on EC. Sensitivity analyses were used to testify the robustness of our main result. Results: Among 101,752 participants, 154 EC cases, consisted of 41 ESCC cases and 97 EA cases, were identified with mean follow-up of 8.9 years. In the fully adjusted model, the highest versus the lowest quartiles of the SMD score were found to be associated with an increased risk of EC and ESCC (EC: HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HRQ4 vs. Q1: 1.41; P = 0.144 for trend). The main result remained through a series of sensitivity analyses. Subgroup analyses showed a stronger association between SMD and EC in participants with no regular consumption of aspirin (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 vs. Q1: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction). Conclusion: Adherence to the SMD pattern may be associated with increased risks of EC and ESCC, particularly for EC in individuals who do not regularly consume aspirin. [ABSTRACT FROM AUTHOR]

Background: The purpose of the Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) Program, a Cancer Moonshot℠ Initiative, is to support research to build the evidence base on multilevel interventions that increase rates of colorectal cancer screening, follow-up, and referral to care to address disparities in colorectal cancer screening. The National Cancer Institute funded eight Research Projects to implement multilevel interventions to improve colorectal cancer screening among communities who traditionally have been medically underserved. To analyze the impact of ACCSIS across Research Projects, the consortium developed a set of common data elements. The purpose of this paper is to describe the process of developing the common data elements to facilitate analysis of ACCSIS data as well as support and inform implementation science research studies. Methods: The ACCSIS Data, Design, and Analysis Work Group was tasked with designing common data elements through a review of existing data collection instruments, examination of data elements proposed by the ACCSIS Research Projects, and deliberations on the data required to compare across the Research Projects. ACCSIS Consortium members drafted, revised, and finalized a common data elements document consisting of variables to collect and surveys to administer to evaluate ACCSIS implementation activities and outcomes in a standardized manner across the Research Projects. Results: The ACCSIS Consortium decided to collect the following categories of common data elements: characteristics across multiple levels of the multicomponent interventions, implementation climate, and determinants; interventions and strategies; implementation outcome constructs and definitions; colorectal cancer screening episodes (screening, diagnostic testing follow-up, cancer detection, and cancer treatment); and cost measures. To assess implementation climate, the consortium prioritized constructs from five domains of the Consolidated Framework for Implementation Research. Conclusions: The ACCSIS common data elements offer a set of harmonization data for future implementation efforts. The consortium is conducting a systematic assessment using both quantitative and qualitative approaches to assess data quality and approaches to improve and sustain data collection. Lessons learned from these ongoing activities will offer additional insights to tailor the ACCSIS common data elements and support efforts to increase colorectal cancer screening for populations experiencing disparities. [ABSTRACT FROM AUTHOR]

Early detection and treatment of skin cancer are important for patient recovery and survival. Dermoscopy images can help clinicians for timely identification of cancer, but manual diagnosis is time-consuming, costly, and prone to human error. To conduct this, an innovative deep learning-based approach has been proposed for automatic melanoma detection. The proposed method involves preprocessing dermoscopy images to remove artifacts, enhance contrast, and cancel noise, followed by feeding them into an optimized Convolutional Neural Network (CNN). The CNN is trained using an innovative metaheuristic called the Improved Chameleon Swarm Algorithm (CSA) to optimize its performance. The approach has been validated using the SIIM-ISIC Melanoma dataset and the results have been confirmed through rigorous evaluation metrics. Simulation results demonstrate the efficacy of the proposed method in accurately diagnosing melanoma from dermoscopy images by highlighting its potential as a valuable tool for clinicians in early cancer detection. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is the second most prevalent malignancy among males and ranks as the fifth primary cause of mortality worldwide, underscoring its substantial impact on public health. Notably, there is a lack of research focused on PCa within the context of Saudi Arabia. Consequently, this study endeavours to elucidate the knowledge, attitudes, and screening practices related to PCa among males in Jazan, Saudi Arabia. Methodology: A cross‐sectional survey was carried out on males over 40 years old in the Jazan region of Saudi Arabia between December 2022 and March 2023. The survey used a web‐based questionnaire containing questions about sociodemographic characteristics, PCa knowledge, and attitudes toward screening practices. Descriptive and inferential statistical analysis evaluated the participants' knowledge and attitudes toward PCa screening. Results: Out of the 468 male participants aged over 40 years, approximately 44% demonstrated limited awareness about PCa. Intriguingly, 60.3% of participants showed a positive attitude toward PCa screening. Moreover, 35.7% reported consulting a urologist for screening purposes. Furthermore, 25.6% had undergone a prostate‐specific antigen (PSA) test, with the predominant rationale (25.8%) being medical advice. Multivariate analysis revealed that being married (adjusted odds ratio (AOR) = 4.5, p = 0.011) and having a family history of PCa (AOR = 4.6, p = 0.001) were significant predictors of heightened PCa awareness. Concurrently, a history of PCa (AOR = 6.8, p = 0.001) and holding a postgraduate qualification (AOR = 5.5, p = 0.024) emerged as significant determinants of proactive practices toward PCa. Conclusion: The results revealed a significant lack of knowledge regarding PCa and the screening practices associated with it among the study participants. These results emphasize the urgent need to provide men with comprehensive information about the benefits and limitations of PCa screening in order to enable them to make more informed decisions. [ABSTRACT FROM AUTHOR]

Clinical breast examination (CBE) screening for breast cancer in Vietnam was proved to be cost‐effective and acceptable to women. However, the outcomes of the implementation of such proposed programme are unknown. To inform the design and implementation planning of the proposed screening programme, this study investigated and analysed the contextual factors of implementing a CBE programme as part of primary care in Vietnam. Regarding methods, the Breast Health Global Initiative Framework and its seven contextual domains for breast cancer health care (including i. epidemiological, ii. policy/legal, iii. geographical/environmental, iv. service and organisational, v. financial, vi. social and economic, vii. cultural and psychosocial) guided the programme implementation analysis. Literature review, documentary analysis of polices, and key informant interviews (with representatives of health authorities at all four levels of Vietnam health system) were used to gather data for each domain. The results show that Vietnam's policy context pointed to the focus on cancer early detection through screening. According to key informants, district level was the most appropriate level for organising and delivering a CBE programme, and only doctors should perform a CBE. Knowledge about breast cancer and perceived susceptibility to receiving a breast cancer diagnosis was positively associated with CBE uptake. In conclusions, the current policy framework supports the implementation of a CBE screening programme in Vietnam. CBE should be performed by doctors, at the district level, and alongside health promotion. [ABSTRACT FROM AUTHOR]

TumorDiagX is a cutting‐edge framework that combines deep learning and computer vision to accurately identify and classify cancers. Our collection of colonoscopies 1518 images is meticulously pre‐processed, including greyscale conversion and local binary pattern (LBP) extraction, before being securely stored on the Google Cloud platform. In the second phase, we fully assess three different convolutional neural networks (CNNs): residual network with 50 layers (ResNet‐50), DenseNet‐201 and visual geometry group with 16 layers (VGG‐16). Stage three introduces four integrated CNNs (ResNet‐50+DenseNet‐201 (RD‐22), DenseNet‐201+VGG‐16 (DV‐22), ResNet‐50+VGG‐16 (RV‐22), and ResNet‐50+DenseNet‐201=VGG‐16 (RDV‐22)) to improve cancer detection by combining the capabilities of several networks. Comprehensive analysis and training on the datasets provide significant insights into CNN's performance. The fourth step involves an extensive comparison, integrating and comparing all three data sets using individual and integrated CNNs to determine the best effective models for cancer diagnosis. In this final step, image segmentation leverages an encoder–decoder network, namely a Universal Network (U‐Net) CNN, to aid in the visual detection of malignant cancer lesions. The results highlight the effectiveness of TumorDiagX, with the feature fusion CNN using DenseNet‐201 attaining training and testing accuracies of 97.27% and 97.35%. Notably, CNN (feature fusion) in combination with RDV‐22 performs better, with training and testing accuracy of 98.47% and 97.93%, respectively, and a dice coefficient of 0.92. The information is privately maintained in the cloud and acts as an essential asset for healthcare practitioners, allowing for specific cancer prediction and prompt detection. Our method, with its meticulous performance metrics and multifaceted approach, has the potential to advance early cancer identification and treatment. [ABSTRACT FROM AUTHOR]

Background: The challenges associated with ensuring widespread system changes to enable early diagnosis and prevention of oral cancer could benefit from interprofessional practice. A needs assessment study was conducted to inform the Interprofessional Education and Collaborative Practice (IPECP) course related to oral cancer. The primary objectives of this study were 1) to establish a tool assess the knowledge attitude and practice (KAP) related to prevention and early detection of oral cancer of health professional students, and 2) to assess the same KAP of pre-licensure dental students. Additional objectives were to consider the possibility that dental students would demonstrate good scores related to early detection and prevention of oral cancer thus indicating their readiness for interprofessional learning and collaborative practice. Methods: Two questionnaires were utilized for this study which included 1) Readiness for interprofessional learning was assessed using the pre- validated tool of Readiness for Interprofessional Learning Scale (RIPLS) 2) A questionnaire to assess the KAP related to early diagnosis and prevention of oral cancer which was developed, validated, and evaluated. Statistical analysis includes, descriptive statistics, Mann–Whitney U test, Ordered logistic regression and Probit analysis. p value was set at < 0.05. Results: A total of 130 dental students (74.6% female) were included in the study. Mean scores related to KAP were 15.96 ± 1.394, 4.70 + 1.146, 7.02 ± 1.019 respectively. The mean score of RIPLS was 73.15 ± 15.961. The probability of overall samples to have good RIPLS scores was around 0.68 to 0.76 (Male 0.68—0.82 & Female 0.68 -0.74). The percentage of students having good knowledge score was 93.8%, good attitude score was around 54.6% and good practice score was around 90%. Conclusion: Knowledge and practice related to prevention and early detection of oral cancer were scored highly. Attitude scores were lower in a relatively higher proportion of participants and needed to be addressed in the curriculum. RIPLS score indicates a positive attitude towards interprofessional learning. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer, albeit preventable, is the second-most deadly gynecological cancer in developing nations. Little is known about cervical cancer among Bangladeshi women. This study aims to estimate the prevalence of cervical cancer screening and demographic correlates to identify potential variabilities in screening rates among different demographic groups and regions. Methods: This study used secondary data from the WHO STEPS 2018 Survey. We used Bayesian regression to perform the bivariate analyses between the outcome and each explanatory factor, as it generates more acceptable results and improves parameter estimates. The top-ranked socio-demographic factors were identified using a two-step cluster analysis. This method determines the relevance of predictor variables and automatically establishes the number of clusters. Results: The prevalence of Bangladeshi women who had ever been screened for cervical cancer was 6.2%. In the adjusted model, women with the following socio-demographic factors had a higher likelihood of developing cervical cancer: being 18–29 years old (AOR = 3.3, 95% CI: 0.24, 15.27) or 45–59 years old (AOR = 2.8, 95% CI: 1.22, 6.0), currently married (AOR = 2.3, 95% CI: 1.36, 3.70), and employed (AOR = 2.4, 95% CI: 1.40, 4.06). Women in the Barisal division were found to have higher odds of being screened for cervical cancer (AOR = 21, 95% CI: 0.66, 121.97). Cluster analysis found residence status predisposes women to cervical cancer screening. Conclusion: There is a significant potential for substantial reductions in the burden of cervical cancer in Bangladesh by strengthening the application of cervical cancer screening. Future studies should examine how socioeconomic status, culture, and healthcare access affect cervical cancer screening trends for different divisions in Bangladesh. An independent national cancer registry is urgently needed to evaluate screening trends and outcomes. [ABSTRACT FROM AUTHOR]

Background: The efficacy of lung cancer screening (LCS) to reduce lung cancer specific mortality is heavily dependent on adherence to recommended screening guidelines, with real-world adherence rates reported to be drastically lower than rates described in clinical trials. There is a dearth in the literature on reminder processes and clinical workflows used to address adherence and robust data is needed to fully understand which clinical set-ups, processes, and context enhance and increase continued LCS participation. This paper describes a protocol for an environmental scan of adherence and reminder processes that are currently used in LCS programs across the United States. Methods: This study will triangulate data using a 3-step explanatory sequential mixed methods design to describe mechanisms of current adherence and reminder systems within academic and community LCS programs to pinpoint clinic or system barrier and facilitator combinations that contribute to increased adherence. In step 1, surveys from a nationally representative sample of LCS programs will yield quantitative data about program structure, volume, and tracking/reminder processes and messages. After completion of the survey, interested LCS program personnel will be invited to participate in an in-depth interview (step 2) to explore current processes and interventions used for adherence at the participant and program level. Finally, in step 3, triangulation of quantitative and qualitative data will be completed through qualitative comparative analysis to identify combinations of components that affect higher or lower adherence. Discussion: This research advances the state of the science by filling a gap in knowledge about LCS program characteristics and processes associated with better adherence which can inform the development and implementation of interventions that are scalable and sustainable across a wide variety of clinical practice settings. [ABSTRACT FROM AUTHOR]

Background and aims: Several non-invasive tests for detecting bladder cancer (BC) are commercially available and are based on detecting small panels of BC-associated mutations and/or methylation changes in urine DNA. However, it is not clear which type of biomarker is best, or if a combination of the two is needed. In this study we address this question by taking a 23-gene mutation panel (GALEAS™ Bladder, GB) and testing if adding a panel of methylation markers improves the sensitivity of BC detection. Methods: Twenty-three methylation markers were assessed in urine DNA by bisulphite conversion, multiplex PCR, and next generation sequencing in 118 randomly selected haematuria patients with pre-existing GB data (56 BCs and 62 non-BCs), split into training and test sets. We also analysed an additional 16 GB false-negative urine DNAs. Results: The methylation panel detected bladder cancer in haematuria patients with 69% sensitivity at 96% specificity (test set results, 95% CIs 52-87% and 80-99%, respectively). Corresponding sensitivity and specificity for GB were 92% and 89%. Methylation and mutation markers were highly concordant in urine, with all GB false-negative samples also negative for methylation markers. Conclusions and limitations: Our data show that, with a comprehensive mutation panel, any gains from adding methylation markers are, at best, marginal. It is likely that low tumour content is the commonest cause of false-negative urine test results. Our study does have a limited sample size and other methylation markers might behave differently to the those studied here. [ABSTRACT FROM AUTHOR]

The role of collagen and its receptor, discoidin domain receptor 1 (DDR1) in immune response of colorectal cancer (CRC) remains unclear. We identified DDR1 as a promising target of immunotherapy resistance using a pooled in vivo CRISPR/sgRNA screening in microsatellite stable (MSS) CRC mouse models. Our findings demonstrated that knockdown or inhibition of DDR1 could enhance infiltration of CD8+ T cells and sensitize MSS CRC to PD-1 blockade. Furthermore, DDR1 was found to facilitate kinase domain phosphorylation, upregulate EZH2, consequently elevating H3K27me3 levels at the CXCL10 promotor, which led to the suppression of CXCL10 transcription once bound to collagen in ECM. Lastly, DDR1 was found positively correlated with collagen I expression in MSS CRC specimens. These findings indicated that targeting DDR1 or its inhibitor 7rh might be potential strategy for overcoming immunotherapy resistance in MSS CRC. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of differences in Prostate-Specific Antigen (PSA) testing rates on prostate cancer (PCa) diagnosis and PCa-specific mortality among Māori men in a New Zealand (NZ) population. Patients and Methods: Māori men aged 40 years or older, without a history of PCa, with a PSA test between 2006 and 2018 were included. The cohort was divided into two groups; the “screened group” (ScG) consisting of men who had at least one PSA test every four years or less, and the “non-screened group” (non-SG). We measured the rate of cancer diagnoses and used competing risk analysis to assess survival. Results: The study cohort included 63,939 Māori men, with 37,048 (58%) in the ScG. PCa was more frequently diagnosed in the ScG (3.7% vs. 3.0%, P < 0.001). A higher proportion of high-grade cancers were found in the non-SG (32.7% vs. 25.6%, P = 0.001). The 10-year cancer-specific survival was significantly higher in the ScG (99.4% vs. 98.5%, P < 0.001). In a multivariable risk model, PSA testing frequency was an independent predictor of PCa mortality. (HR 2.43, [95% CI 1.97–3.01], P < 0.001). Conclusions: In a cohort of only Māori men, lower PSA testing rates were associated with a higher risk of PCa-related death. Therefore, regular PSA testing for Māori could improve cancer-specific survival among Māori men. Regular PSA testing should be considered a priority area for improving PCa survival in this population. [ABSTRACT FROM AUTHOR]

To examine the impact of the COVID-19 pandemic on cervical cancer screening rates of Hispanic individuals compared to non-Hispanic White (NHW) individuals in the United States, whether a responsive surge in catch-up screenings occurred as society adapted to pandemic changes, and to investigate the sociodemographic characteristics between the study populations. Using cross-sectional data from the All of Us Research Program, which incorporates electronic health record data and survey data from a demographically, geographically, and medically diverse participant group, we assessed the annual cervical cancer screening rates during 2019–2021 by race/ethnicity among eligible individuals ages 21–64. Among 116,052 unique individuals (78,829 NHW and 37,223 Hispanic), Hispanic individuals had lower annual cervical cancer screening rates than NHWI across the three years studied. They experienced a more significant decrease in screening from 2019 to 2020 (39.27 %) compared to NHWIs (21.15 %) and less of a rebound increase in the following year, 2021 (10.33 % vs 13.83 %). Hispanic individuals aged 50–64 experienced the sharpest decline in screening rates (−43.01 % from 2019 to 2020). Hispanic individuals also experienced greater adverse social conditions, including lack of insurance or employment, lower educational attainment, and lower household income. Hispanic individuals experienced a more significant decrease in cervical cancer screening rates with the onset of the COVID-19 pandemic compared with NHW individuals and did not experience a robust rebound in cervical cancer screening rates in 2021. As a result, the disparity in cervical cancer screening rates between NHW and Hispanic individuals considerably worsened with the COVID-19 pandemic. [Display omitted] • Cervical cancer screening disparities dramatically worsened with the COVID-19 pandemic. • Hispanic individuals experienced a greater decrease in screening in 2020 than non-Hispanic White individuals. • The screening rates of Hispanic individuals did not rebound as much as non-Hispanic individuals in 2021. • Hispanic individuals aged 50‐64 experienced the sharpest decline in screening rates. • A higher proportion of Hispanics were unemployed, uninsured, and had lower household incomes. [ABSTRACT FROM AUTHOR]

In 2012, updated ASCCP management guidelines for abnormal cervical cytology recommended observation rather than immediate referral to colposcopy for low-grade abnormalities in women ages 21–24. We evaluated the impact of these guidelines on changes in colposcopy procedure rates among young women. We analyzed administrative and claims data from the largest statewide family planning program between July 2011 and June 2015. Using a difference-in-differences approach, we estimated changes in colposcopy procedure rates among women ages 21–24 years before and after the 2012 ASCCP management guidelines, relative to a comparison group of women ages 25–44. Our analysis included 333,977 women from 216 primary care provider sites. After publication of the 2012 ASCCP management guidelines, colposcopy rates significantly declined from 6.70% (95% CI 6.21–7.19) to 3.94% (95% CI 3.60–4.29) among women ages 21–24 and from 4.35% (95% CI 4.03–4.67) to 3.53% (3.25–3.80) among women over 24 years. These declines correspond to a 1.93 percentage point reduction (95% CI 1.62–2.25; p < 0.001) in colposcopy rate among women 21–24 vs. over 24 years, or a two-fold relative reduction. Among women ages 21–24, colposcopy receipt was associated with speaking primarily English vs. non-English (OR 1.46, 95% CI 1.35–1.57), having a cervical cytology test within the past year vs. not (OR 1.55, 95% CI 1.44–1.66), and receiving care from a public vs. private provider (OR 1.31, 95% CI 1.06–1.62). Colposcopy procedure rates among young women significantly declined following publication of the 2012 management guidelines, which has implications for reducing potential harms of overtreatment. • Colposcopy rates declined among young women after the 2012 ASCCP guidelines for management of abnormal cervical cytology. • Colposcopy among young women was associated with English language, recent screening test, and care from a public provider. • Findings have implications for reducing potential overtreatment among young women. [ABSTRACT FROM AUTHOR]

The convergence of tumor epigenetics and molecularly imprinted polymers (MIPs) holds promise in early cancer diagnostics. To the best of knowledge, none of the studies has achieved DNA methylation detection yet using MIPs and the proposed research will pioneer the application of MIPs for detecting DNA methylation, introducing a novel approach to enhance early diagnostic precision. [ABSTRACT FROM AUTHOR]

The life of humans faces several disasters that sometimes may be deadly and cause severe effects on future endeavors. One major cause of lifestyle change is the several types of disease among which some are unrecognizable, and some are untreatable. Cancer is one of the chronic diseases that occur due to the uncontrollable cell division and in the category of cancer, breast cancer is the second disease with the lowest survival rate throughout the world. Prediction of breast cancer at its early stage enhances the survival rate. To maximize the survival rate and a healthy environment, researches on various techniques of breast cancer prediction have emerged. Though these researches have paved a better way for prediction, they also had some drawbacks that minimized the efficacy of the research outcomes. To overcome all these drawbacks, the proposed self-attention-based deep Convolutional Neural Network (Self-attention DCNN) is utilized and the classifier’s performance is enhanced with the Smack Echolocation Optimization (SELO). In addition, a better segmentation method called SELO-optimized ensemble masked Region-based CNN (SELO-mask RCNN) is introduced in the research that segments the region of interest to incorporate the fine-grained segmentation as well as the semantic understanding of the image. The performance of research is evaluated with F1-measure, Precision, and Recall that achieved 98.27%, 99.21%, and 98.99%, respectively. [ABSTRACT FROM AUTHOR]

Background: Research on breast cancer risk factors and mortality is gaining recognition and attention globally; there is need to add more information on its determinants among patients admitted in hospital. Some studies on risk factors and mortality of breast cancer in Nigeria hospitals conducted in the urban and suburban areas have been documented. Therefore, an addition of a study conducted in the setting of a rural health institution is necessary. This study assessed the risk factors and determinants of mortality among patients admitted for breast cancer in rural Southwestern Nigeria. Methods: A retrospective observational study was conducted on 260 patients who were admitted for breast cancer between January 2010 and December 2023 using a data form and a standardized information form. The data were analyzed using SPSS version 22.0. The risk factors and the determinants of mortality of patients with breast cancer were identified using multivariate regression model. Results: The breast cancer risk factors were old age, family history, tobacco smoking, combined oral contraceptives, and hormonal therapy use. The case fatality rate was 38.1%, and its determinants of mortality were patients who were older (adjusted odds ratio [AOR], 1.956; 95% confidence interval [CI]:1.341-4.333), obese (AOR, 2.635; 95% CI: 1.485-6.778), stage IV (AOR, 1.895; 95% CI: 1.146-8.9742), mastectomy (AOR, 2.512; 95% CI: 1.003-6.569), discontinued adjuvant chemotherapy (AOR, 1.785; 95% CI: 1.092-4.6311), and yet to commence adjuvant chemotherapy (AOR, 2.568; 95% CI: 1.367-5.002). Conclusion: The study revealed that patients with breast cancer were associated with high mortality. Sustained health education to promote early diagnosis, managed co-morbidities, and access to treatment may contribute to reduction in breast cancer mortality in rural Nigeria. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a major global health issue, with 604,000 diagnoses and 342,000 deaths in 2020. Despite the importance of early detection, only 5% of eligible women in Ethiopia are screened. Therefore, this study aimed to assess the determinants of cervical cancer screening uptake among reproductive-age women at selected public hospitals in southwest Ethiopia. Methods: A case-control study involving 392 women (98 cases and 294 controls) aged 15-49 was conducted across three hospitals. Cases were women aged 15 to 49 who had cervical cancer screening, while controls were reproductive-age women seeking antenatal care or family planning but not screened. Data were collected via face-to-face interviews with pretested questionnaires and analyzed using SPSS 25. Bivariate analysis identified candidate variables with P-values < 0.25, and a multivariable logistic regression model determined factors with P-values < 0.05 as significant for cervical cancer screening uptake. Results: Determinants of cervical cancer screening uptake included high knowledge of screening (AOR=6.23; 95%CI: 1.96, 19.79), a positive attitude toward screening (AOR=6.12; 95%CI: 2.40, 15.58), women aged 30-39 (AOR=3.94; 95%CI: 1.79, 8.63) and 40-49 (AOR=3.54; 95%CI: 1.52, 8.22), and those who reached health facilities within 60 minutes (AOR=2.32; 95%CI: 1.21, 4.45). Conclusion: The study pinpointed age, knowledge, attitude toward cervical cancer screening, and accessibility to health facilities within a 60-minute radius as pivotal factors impacting cervical cancer screening uptake among reproductive-age women. These findings highlight the importance of targeted education, promoting positive attitudes, and enhancing healthcare accessibility to improve screening uptake and reduce the burden of cervical cancer. [ABSTRACT FROM AUTHOR]

Background & objectives Cancer is a leading cause of death worldwide and constitutes a public health priority. Delays in diagnosis and treatment of cancer can adversely impact survival, recovery, and cost of treatment. The objective of this study was to estimate the proportion seeking timely care among those having early warning signals for oral, breast or cervical cancer and to explore the facilitators and barriers to early detection. Methods The study was conducted among 241 participants, including those having early signals for selected cancers and women who underwent opportunistic cervical cancer screening in the selected health facilities. Information regarding symptom appearance, presentation to any registered medical practitioner, confirmatory diagnosis, and treatment initiation were obtained from medical records. In-depth Interviews (IDIs) were conducted among six participants to explore facilitators and barriers to cancer detection. Results Among 7300 people screened using the Community Based Assessment Checklist (CBAC), 128 (1.7%) had warning signals for any one of the cancers. The percentage of people who sought medical care for oral, breast and cervical cancer symptoms were 80 per cent, 82 per cent and 57 per cent, respectively. Among those who underwent opportunistic cervical cancer screening in health centres (113), the screen positivity rate was 11 per cent, and adherence to referral for confirmation was 80 per cent. The median pre-diagnostic and diagnostic delays for the three cancers were 79 [Interquartile range (IQR): 44-126] and 27 (IQR: 13-73) days. One individual was diagnosed with oral cancer, and the treatment delay was 27 days. Facilitators identified for early seeking of care were encouragement by family and low-cost treatment at public facilities. Major barriers identified were neglect of symptoms by participants and their responsibilities towards family. Interpretation & conclusions Although very few people were identified to have early warning symptoms using CBAC, a substantial proportion of them sought medical care and underwent confirmatory diagnosis. Screen positivity rate and treatment-seeking behaviour were better among women undergoing opportunistic cervical cancer screening in the health centres. Measures need to be taken to improve health literacy among people to reduce diagnostic delay for cancers. [ABSTRACT FROM AUTHOR]

Despite significant advancements in early breast cancer detection, mastectomy remains a crucial treatment option for some patients. Immediate breast reconstruction post-mastectomy has emerged as an ideal procedure to minimize physical and psychosocial patient impacts, striving for improved cosmetic results. The "enhanced "Goldilocks mastectomy technique, characterized by nipple preservation or grafting and utilizing the fifth perforator anatomy, offers a sound approach to reconstruction in comorbid and large-breasted patients. This paper discusses the advantages, disadvantages, and real-world application of Goldilocks mastectomy in enhancing breast reconstruction outcomes and meeting patients' diverse needs. [ABSTRACT FROM AUTHOR]

Background: In Saudi Arabia (SA) no data are available on precancerous stomach lesions (PSLs) or the associated risk factors. We aimed to identify PSLs and investigate factors associated with PSLs and their progression. Methods: This 7-year prospective study screened for PSLs in asymptomatic Saudi patients aged 45–75 years in central SA (n = 35,640). Those who had high-sensitivity guaiac fecal occult blood tests (HSgFOBT+) and negative colonoscopy results (n = 1242) were subjected to upper GI endoscopy to identify PSLs and were followed up every 3 years or earlier, depending on the type of PSL. Factors associated with PSLs were investigated. Results: The 7-year participation rate was 86.9% (1080/1242). The 7-year prevalence of PSLs was 30.9% (334/1080). The incidence rate of PSLs was 134 new cases/100,000 population/year, total population at risk - 35,640 and 44.3 new cases/1,000 persons/year among the 1080 participants with HSgFOBT+ and negative colonoscopy results. Among the 334 participants with PSLs, 8 (2.4%) had neoplastic progression to GC during the surveillance period. Age, Helicobacter pylori infection, smoking status, a diet with preserved salty foods, low income, and a family history of GC were associated with PSLs. Conclusions: The incidence of GC is low in central SA, but screening for PSLs among participants with HSgFOBT+ and negative colonoscopy findings may contribute to the early detection and subsequent treatment of GC. HP eradication, not smoking, normal body weight, and adhering to a healthy diet seem to be potential factors associated with the development of PSLs. Further studies are needed to search if such interventions would decrease the incidence of PSLs and progression to early GC. [ABSTRACT FROM AUTHOR]

Objective: High-risk human papillomavirus (HR-HPV) infection is a leading cause of cervical cancer, of which human papillomavirus (HPV)-16 and HPV-18 account for about 70% of cases. Since HPV infection is common, it is important to focus on the HPV genotypes that pose the highest risk for effective cervical cancer screening. In this study, we evaluated the clinical usefulness of HPV-16/HPV-18 genotyping for cervical cancer screening. Methods: A total of 86,022 women aged 25 years or older was analyzed in this study. Sensitivity, specificity, positive predictive value, and negative predictive value of HPV genotyping and cytology were analyzed. In addition, we subdivided participants into two groups according to cytology results, negative for intraepithelial lesion of malignancy (NILM) and atypical squamous cells of undetermined significance (ASC-US), and analyzed absolute risk (AR) and relative risk (RR) of cervical intraepithelial neoplasia (CIN) 3 or worse according to HPV genotype. Results: The AR of CIN 3 or worse was 77.0 times higher in HR-HPV-positive compared to HR-HPV-negative. Compared to 12 other HR-HPV-positive, the AR of CIN 3 or worse was 4.2 times higher in HPV-16 and/or HPV-18 positive. This finding was more evident in women with NILM than in women with ASC-US. The RR of CIN 3 or worse was 7.0 in women with NILM and 4.5 in women with ASC-US. Conclusion: Regardless of the cytology results, the risk of CIN 3 or worse was higher in HPV-16/HPV-18 than in other HR-HPV. HPV-16/HPV-18 genotyping is recommended to screen women with a high risk of cervical cancer. [ABSTRACT FROM AUTHOR]

Adrenal cortical carcinoma (ACC) is an extremely rare malignancy, and advanced ACC carries a very poor prognosis. Early detection is critical since early-stage disease can be cured with surgical resection. ACC can be seen in Lynch syndrome; this case and review of the literature provide insight as to the potential biological origin of this malignancy. Clinicians should be aware of this association and the potential impact on cancer screening in these kindreds. We describe a novel kindred with hereditary adrenal cortical carcinoma and the Muir- Torre syndrome, a phenotypic variant of Lynch syndrome that includes sebaceous neoplasms and visceral malignancies. We report a 59-year-old Caucasian man with an MSH2 deletion who was diagnosed with metastatic adrenal cortical carcinoma. The patient's brother also had a history of adrenal cortical carcinoma. The patient's cancer initially responded to immunotherapy with pembrolizumab. Somatic genetic testing performed on a tumor biopsy did not identify the germline MSH2 deletion. A review of the literature identifies an association between germline MSH2 mutations and ACC, suggesting a potential biological basis for carcinogenesis. This case highlights the importance of ACC screening for patients with Lynch Syndrome and a family history of adrenal cortical carcinoma due to the high mortality from this malignancy. This case also highlights the importance of separate germline and somatic testing for patients with a concerning personal or family history of cancers. [ABSTRACT FROM AUTHOR]

• Whole exome sequencing of 210 breast cancer patients revealed 16 individuals with CHEK2 germline variants. • CHEK2 c.1343T> G (p.Ile448Ser) was found in 5 African American individuals (2.4 %), suggesting an increased risk associated with this variant. • Novel frameshift variants, CHEK2 c.1350delA (p.Val451Serfs*18) and c.1528delC (p.Gln510Argfs*3), were identified. • Functional studies support the reclassification of a variant of uncertain significance, CHEK2 p.Leu332His, to likely-pathogenic. • Repeating testing and expanding the scope of genes can identify more variants within hereditary cancer predisposition genes providing a more comprehensive cancer risk assessment. The cell cycle checkpoint kinase 2 (CHEK2) is a tumor suppressor gene coding for a protein kinase with a role in the cell cycle and DNA repair pathways. Variants within CHEK2 are associated with an increased risk of developing breast, colorectal, prostate and several other types of cancer. Comprehensive genetic risk assessment leads to early detection of hereditary cancer and provides an opportunity for better survival. Multigene panel screening can identify the presence of pathogenic variants in hereditary cancer predisposition genes (HCPG), including CHEK2. Multigene panels, however, also result in large quantities of genetic data some of which cannot be interpreted and are classified as variants of uncertain significance (VUS). A VUS provides no information for use in medical management and leads to ambiguity in genetic counseling. In the absence of variant segregation data, in vitro functional analyses can be used to clarify variant annotations, aiding in accurate clinical management of patient risk and treatment plans. In this study, we performed whole exome sequencing (WES) to investigate the prevalence of germline variants in 210 breast cancer (BC) patients and conspicuously among the many variants in HCPGs that we found, we identified 16 individuals with non-synonymous or frameshift CHEK2 variants, sometimes along with additional variants within other BC susceptibility genes. Using this data, we investigated the prevalence of these CHEK2 variants in African American (AA) and Caucasian (CA) populations identifying the presence of two novel frameshift variants, c.1350delA (p.Val451Serfs*18) and c.1528delC (p.Gln510Argfs*3) and a novel missense variant, c262C>T (p.Pro88Ser). Along with the current clinical classifications, we assembled available experimental data and computational predictions of function for these CHEK2 variants, as well as explored the role these variants may play in polygenic risk assessment. [ABSTRACT FROM AUTHOR]