Tumor Screening Research Articles

Appraisal of folate functionalized bosutinib cubosomes against hepatic cancer cells: In-vitro, In-silico, and in-vivo pharmacokinetic study

Targeted therapies enhance the efficacy of tumour screening and management while lowering side effects. Multiple tumours, including liver cancer, exhibit elevated levels of folate receptor expression. This research attempted to develop surface-functionalised bosutinib cubosomes against hepatocellular carcinoma. The novelty of this work is the anti-hepatic action of bosutinib (BST) and folic acid-modified bosutinib cubosomes (BSTMF) established through proto-oncogene tyrosine-protein kinase (SrC)/ focal adhesion kinase(FAK), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and cell cytotoxicity. Later, the in-vivo pharmacokinetics of BSTMF were determined for the first time. The strong affinity of folic acid (FA) for folate receptors allows BSTMF to enter cells via FA receptor-mediated endocytosis. The particle size of the prepared BSTMF was 188.5 ± 2.25 nm, and its zeta potential was −20.19 ± 2.01 mV, an encapsulation efficiency of 90.31 ± 3.15 %, and a drug release rate of 76.70 ± 2.10 % for 48 h. The surface architecture of BSTMF was identified using transmission electron microscopy (TEM) and Atomic force microscopy (AFM). Cell-line studies demonstrated that BSTMF substantially lowered the viability of Hep G2 cells compared to BST and bosutinib-loaded cubosomes (BSTF). BSTMF demonstrated an elevated BST concentration in tumour tissue than in other organs and also displayed superior pharmacokinetics, implying that they hold potential against hepatic cancers. This is the first study to show that BSTMF may be effective against liver cancer by targeting folate receptors and triggering SrC/FAK-dependent apoptotic pathways. Multiple parameters demonstrated that BSTMF enhanced anticancer targeting, therapeutic efficacy, and safety in NDEA-induced hepatocellular carcinoma.

Abstract IA004: Universal tumor screening for Lynch syndrome versus germline multi-gene panel testing for all endometrial cancer patients

Abstract Introduction: Implementation of universal tumor screening for Lynch syndrome has been adopted more slowly for endometrial cancer patients than colorectal cancer patients yet the data is very similar. Recent guidelines have suggested doing both universal tumor screening and considering multi-gene panel testing for all colorectal cancer patients and so the data in endometrial cancer patients was reviewed to determine if the same recommendation could be made for endometrial cancer. Methods: Review of the literature found 4 large studies of universal tumor screening for Lynch syndrome among and 6 large studies of universal multi-gene panel testing among large cohorts of endometrial cancer patients. Results were reviewed and a meta-analysis performed. Results: Four large studies have looked at universal tumor screening among all endometrial cancer patients. They found that 23-26.7% of endometrial cancers are MSI-high or dMMR. The majority of these dMMR endometrial cancers are caused by MLH1 promoter hypermethylation which is present in 14-20.2% of all EC cases (60.3-75.8% of dMMR cases). Lynch syndrome was ultimately diagnosed in 2.5-3.3% of all endometrial cancer patients. The mutation distribution among Lynch syndrome patient diagnosed through universal tumor screening was 53.1% MSH6, 24.5% MSH2, 12.2% MLH1, and 10.2% PMS2. IHC was better at identifying Lynch syndrome cases than MSI among endometrial cancers (mainly due to MSH6 tumors not always being MSI-high). Multi-gene panel testing (MGPT) for all endometrial cancer patients has been reported in 6 studies of endometrial cancer patients (3 high risk and 3 unselected). MGPT studies found that 10 – 14% of unselected and 9 - 15% of selected endometrial cancer patients have a pathogenic variant in a cancer susceptibility gene. Patients diagnosed under age 50 were not significantly more likely to test positive. In the three selected cohorts, the prevalence of Lynch syndrome was 8.1% (575/7095). In the three unselected cohorts, the prevalence of Lynch syndrome was 2.7% (73/2742). Conclusions: Tumor screening with MSI or MMR IHC for all endometrial cancers will only identify Lynch syndrome (as intended). It will miss patiesporadicny other hereditary cancer syndrome and some patients with Lynch syndrome who have a sporadic endometrial cancer. However, it is now necessary for treatment purposes (Immune Checkpoint Blockade therapy). Universal germline MGPT testing for all endometrial cancers will identify some Lynch syndrome cases who have normal tumor screening and will identify many non-Lynch syndrome cases that would be completely missed by tumor screening. Citation Format: Heather Hampel. Universal tumor screening for Lynch syndrome versus germline multi-gene panel testing for all endometrial cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA004.

Raman spectroscopy combined with multivariate statistical algorithms for the simultaneous screening of cervical and breast cancers.

Breast and cervical cancers are becoming the leading causes of death among women worldwide, but current diagnostic methods have many drawbacks, such as being time-consuming and high cost. Raman spectroscopy, as a rapid, reliable, and non-destructive spectroscopic detection technique, has achieved many breakthrough results in the screening and prognosis of various cancer tumors. Therefore, in this study, Raman spectroscopy technology was used to diagnose breast cancer and cervical cancer. A total of 225 spectra were recorded from 87 patients with cervical cancer, 60 patients with breast cancer, and 78 healthy individuals. The obvious difference in Raman spectrum between the three groups was mainly shown at 809cm-1 (tyrosine), 958cm-1 (carotenoid), 1004cm-1 (phenylalanine), 1154cm-1 (β-carotene), 1267cm-1 (Amide III), 1445cm-1 (phospholipids), 1515cm-1 (β-carotene), and 1585cm-1 (C = C olefinic stretch). We used one-way analysis of variance for these peaks and demonstrated that they were significantly different. Then, we combined the detected Raman spectra with multivariate statistical calculations using the principal component analysis-linear discrimination algorithm (PCA-LDA) to discriminate between the three groups of collected serum samples. The diagnostic results showed that the model's accuracy, precision, recall, and F1 score of the model were 92.90%, 92.62%, 92.10%, and 92.36%, respectively. These results suggest that Raman spectroscopy can achieve ultra-sensitive detection of serum, and the developed diagnostic models have great potential for the prognosis and simultaneous screening of cervical and breast cancers.

Factor VIII as a Novel Biomarker for Diagnosis, Prognosis, and Therapy Prediction in Human Cancer and Other Disorders.

Coagulation factor VIII (FVIII) is an essential cofactor in the coagulation cascade, encoded by the F8 gene on the long arm of chromosome X (Xq28). FVIII is normally circulated in complex with Von Willebrand factor (VWF) and has relevant emerging extracoagulative functions. Dysregulation of FVIII is associated with tumor progression, and could be used as a novel biomarker for tumor screening and monitoring. In breast cancer, bladder cancer, colorectal carcinoma, esophageal carcinoma, hepatocellular carcinoma and lung cancer, F8 is regarded as an oncogene. In coronary heart disease, hemophilia A and liver disease, F8 dysregulation has been recognized as a potential biomarker for disease diagnosis and prognosis. However, the basis of these differential expression levels remains to be understood. In this review, which is a mixture of literature review and bioinformatics analysis we described the biological functions and characteristics of FVIII, and also its expression level in non-malignant disorders and various cancers.

LC-MS/MS-assisted label-free SERS blood analysis by self-position plasmonic platform for tumor screening

Label-free surface-enhanced Raman spectroscopy (SERS) blood analysis become an emerging technique in biomedical diagnosis. However, the poor signal homogeneity, the unsatisfied spectral features, and the low throughput of spectral analysis hinder its further clinical application. Herein, we illustrated a self-position SERS platform driven by the hydrophilic-hydrophobic features and combined with machine learning algorithm for precise lung cancer identification from benign group. To solve the problem that biomolecular information in SERS spectra partly lost caused by the formation of “protein crown”, the SERS signals from serum components with different molecular weights were analyzed through the serum filtration process with a Nanosep tool, which results were confirmed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods. Following that, robust machine learning classifiers were employed to explore the potential diagnostic information contained in the blood spectral data, achieving the exciting detection accuracy of 96.3% for identifying samples of the lung cancer from the of benign ones. This blood-SERS technology provides a promising way to overcome the clinical challenges in the identification of lung malignant and benign groups, and the functional SERS platform proposed in this work would further advance the application of blood-SERS technology in clinical cancer detection.

Use of N-acetylcysteine plus simethicone to improve mucosal visibility in upper digestive endoscopy via systematic alphanumeric-coded endoscopy: a randomized, double-blind controlled trial.

The use of antifoaming and mucolytic agents prior to upper gastrointestinal (GI) endoscopy and a thorough systematic review are essential to optimize lesion detection. This study evaluated the effect of simethicone and N-acetylcysteine on the adequate mucosal visibility (AMV) of the upper GI tract by an innovative systematic method. This randomized, double-blind controlled trial included consecutive patients who underwent diagnostic upper GI endoscopy for screening for early neoplasms between August 2019 and December 2019. The upper GI tract was systematically assessed by systematic alphanumeric-coded endoscopy. Patients were divided into 4 groups: 1) water; 2) only simethicone; 3) N-acetylcysteine + simethicone; and 4) only N-acetylcysteine. The following parameters were assessed in each group: age, sex, body mass index, level of adequate mucosal visibility, and side-effects. A total of 4564 images from upper GI areas were obtained for evaluation. The mean AMV in the 4 groups was 93.98±7.36%. The N-acetylcysteine + simethicone group had a higher cleaning percentage compared with the other groups (P=0.001). There was no significant difference among the remaining groups, but several areas had better cleaning when a mucolytic or antifoam alone was used. No side-effects were found in any group. The combination of N-acetylcysteine plus simethicone optimizes the visibility of the mucosa of the upper GI tract, which could potentially increase diagnostic yield.

Clinically amyopathic dermatomyositis associated with cutaneous ulcerations: a case-based review

Introduction and importance: Dermatomyositis (DM) is an autoimmune myopathy primarily affecting both muscles and skin. When muscle weakness is not clinically apparent, but characteristic skin lesions are present, the condition is referred to as clinically amyopathic dermatomyositis (CADM). Case presentation: The authors present the case of a 52-year-old female with a typical DM rash, interstitial pneumonia, and multiple skin ulcers. The skin biopsy was consistent with DM, and there were no signs of muscle involvement. Myositis-related and myositis-specific autoantibodies were also negative. Significant improvement was not observed until the patient received successive monthly pulses of methylprednisolone and the introduction of methotrexate. This treatment regimen allowed for the complete tapering of prednisone and resulted in sustained disease control. Clinical discussion: In addition to the case presentation, a narrative literature review was conducted using the MEDLINE database, and an evidence-based treatment flowchart is proposed. CADM is a subtype of DM, related to higher incidences of interstitial lung disease, skin vasculopathy and malignancy. When ulcers or interstitial pneumonia are present, treatment should be early and aggressive. Active screening for neoplasms is recommended, particularly within the first 5 years. Conclusion: The authors presented a case of seronegative CADM featuring skin vasculopathy, successfully treated with consecutive methylprednisolone pulses. Our literature review emphasized the importance of focused CADM management trials, highlighting the need for further research.

Prediction of Response to Chemoradiotherapy by Dynamic Changes of Circulating Exosome Levels in Patients with Esophageal Squamous Cell Carcinoma.

The exosomes-based liquid biopsy represents a prospective biomarker for tumor screening, prognosis prediction, and tumor regression. This study aimed to isolate circulating exosomes (CEs) from plasma of the esophageal squamous cell carcinoma (ESCC) patients who received chemoradiotherapy through exosome detection method via the ultrafast-isolation system (EXODUS) and investigated the association between the dynamic changes of CE levels and therapeuticeffect. We isolated and quantitatively analyzed CEs from plasma of locally advanced ESCC patients received chemoradiotherapy at 2 time points: baseline (pre-chemoradiotherapy) and 2 months after the chemoradiotherapy (post-chemoradiotherapy). We isolated exosomes from plasma by EXODUS platform and confirmed them through nanoparticle tracking analysis (NTA), transmission electron microscope (TEM), and Western blot. The associations of CE level with clinicopathological characteristics, tumor regression, and progression-free survival (PFS) were analyzed. The average diameter of CEs was 107.4±14.3 nm at baseline and 101.7±17.1 nm at post-chemoradiotherapy. The mean exosome concentration significantly decreased after chemoradiotherapy (7.3×1011 particles/mL vs 5.4×1011 particles/mL, P < 0.001). The patients with stage III-IVA and tumor length ≥5cm had obviously higher baseline CE levels. Dynamic changes in CE levels were successfully applied for evaluation of chemoradiotherapy response and PFS. Furthermore, through multivariate Cox regression analysis, it was revealed that dynamic changes of CE levels were an independent predictor of PFS in locally advanced ESCC patients who received chemoradiotherapy. Here, we demonstrated EXODUS platform isolated and enriched CEs from plasma of ESCC patients with high-purity and high-yield. The EXODUS platform can facilitate liquid biopsy based on exosomes translation to the clinic. Baseline CE levels can reflect ESCC tumor burden. The dynamic changes of CE levels during chemoradiotherapy allow the prediction of treatment effect and PFS of ESCC patients, requiring further investigations in larger patient cohorts.

Development and validation of a simple, fast and sensitive liquid chromatography-tandem mass spectrometry method to establish reference intervals for 24-h urinary free normetanephrine, metanephrine and methoxytyramine

ObjectiveTo develop and validate a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect urinary free metanephrines and methoxytyramine, establishing reference intervals. MethodsUrine samples were diluted with isotope internal standard solution, then analyzed directly using tandem mass spectrometry with multiple reaction monitoring measurement and electrospray ionization source in positive ion mode. Analytical parameters including linearity, lower limit of quantitation, imprecision and accuracy of the method were evaluated. The reference intervals for urinary catecholamine metabolites were established by analyzing 24-h urine samples collected from 81 apparently healthy volunteers. ResultsThe analytical times for MN, NMN, and 3-MT were at 2.79, 2.80, and 2.74 min, respectively. The method displayed excellent linearity (r > 0.99) in the range of 1-1000 ng/mL, with lower limits of quantification (LLOQ) at 0.50 ng/mL for MN and NMN, and 0.25 ng/mL for 3-MT. The method's intra-day and inter-day imprecisions were less than 8 %. The method recovery ranged from 96.8% to 105.8 % for MN, 89.7%–106.4 % for NMN, and 93.5%–106.2 % for 3-MT. No carry-over was observed during the analysis of all analytes. The LC-MS/MS method was used to establish reference intervals in 24-h urine samples from 81 apparently healthy volunteers. There was no association of sex with urinary free metabolites. ConclusionThis study established a novel, fast and sensitive LC-MS/MS method for determining urinary free catecholamine metabolites, which could facilitate screening and diagnosis for catecholamine-related tumors more conveniently and quickly.

The Advances and Applications of Characterization Technique for Exosomes: From Dynamic Light Scattering to Super-Resolution Imaging Technology

Exosomes distributed by extracellular vesicles carry various information highly consistent with cells, becoming a new type of biomarker for tumor screening. However, although conventional characterization technologies can quantify size and morphology for exosomes, they are limited in related fields such as function tracing, protein quantification at unit point, and microstructural information. In this paper, firstly, different exosome characterization methods are systematically reviewed, such as dynamic light scattering, nanoparticle tracking analysis, flow cytometry, electron microscope, and emerging super-resolution imaging technologies. Then, advances in applications are described one by one. Last but not least, we compare the features of different technologies for exosomes and propose that super-resolution imaging technology can not only take into account the advantages of conventional characterization techniques but also provide accurate, real-time, and super-resolution quantitative analysis for exosomes. It provides a fine guide for exosome-related biomedical research, as well as application in liquid biopsy and analysis techniques.

Specific characteristics and challenges associated with breast cancer diagnostics in women after breast augmentation and reconstructive surgeries with implants

Background. The number of plastic surgeries is constantly growing worldwide. Breast augmentation remains the most common surgical procedure in women, which demonstrated a 0.5 % increase over the past 4 years. As the number of women with breast implants increases, specialists and patients themselves face difficulties related to screening, diagnosis, and treatment of tumors, including breast cancer.Aim. To analyze specific characteristics of breast examination in patients after breast augmentation who were examined and treated in the mammological clinic of Russian Research Center of Radiology, Ministry of Health of the Russian Federation.Materials and methods. This study included 273 patients aged between 21 and 63 years (mean age 49.0 ± 7.6 years) after breast augmentation and after reconstructive surgery for breast cancer and symmetrizing surgery on the contralateral side. All women underwent clinical examination plus breast ultrasound (for patients under 40 years of age) or mammography followed by ultrasound (patients over 40 years of age). Patients who were found to have BI-RADS 3–4 tumors underwent ultrasound-guided or stereotactic breast biopsy. In case of suspicious intraductal formations according to breast nipple smears the patients were referred to breast ductography. Patients with suspected implant rupture or capsular contracture, as well as patients requiring the assessment of the disease stage underwent contrast-enhanced magnetic resonance imaging.Results. After comprehensive examination, 12 patients (5.4 %) were diagnosed with breast cancer; 38 patients (13.9 %), with implant rupture; 3 patients (1 %), with intraductal formations.Conclusion. Breast augmentation is not a contraindication to mammography in women aged over 40 years with glandular tissue. Additional examination methods include breast ultrasound, contrast-enhanced mammography, and breast magnetic resonance imaging. In case of no glandular tissue, contrast-enhanced breast magnetic resonance imaging and breast ultrasound are the methods of choice. It is important to develop new standards of screening and diagnosis of breast diseases in women after aesthetic surgery, since breast cancer incidence is likely to increase among women after breast augmentation over the next decades, considering the fact that breast cancer is the most common malignancy in women and its incidence is constantly growing.

Clinical value of oral contrast-enhanced ultrasonography in diagnosis of gastric tumors.

The incidence of gastric cancer remains high, and it is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide. Oral contrast-enhanced ultrasonography is a simple, non-invasive, and painless method for the diagnosis of gastric tumors. To explore the diagnostic value of oral contrast-enhanced ultrasonography for the detection of gastric tumors. The screening results based on oral contrast-enhanced ultrasonography and electronic gastroscopy were compared with those of the postoperative pathological examination. Among 42 patients with gastric tumors enrolled in the study, the diagnostic accordance rate was 95.2% for oral contrast-enhanced ultrasonography (n = 40) and 90.5% for electronic gastroscopy (n = 38) compared with postoperative pathological examination. The Kappa value of consistency test with pathological findings was 0.812 for oral contrast-enhanced ultrasonography and 0.718 for electronic gastroscopy, and there was no significant difference between them (P = 0.397). For the TNM staging of gastric tumors, the accuracy rate of oral contrast-enhanced ultrasonography was 81.9% for the overall T staging and 50%, 77.8%, 100%, and 100% for T1, T2, T3, and T4 staging, respectively. The sensitivity and specificity were both 100% for stages T3 and T4. The diagnostic accuracy rate of oral contrast-enhanced ultrasonography was 93.8%, 80%, 100%, and 100% for stages N0, N1-N3, M0, and M1, respectively. The accordance rate of qualitative diagnosis by oral contrast-enhanced ultrasonography is comparable to that of gastroscopy, and it could be used as the preferred method for the early screening of gastric tumors.

O-14 A rare case of hypercalcaemia in pregnancy

Abstract Introduction Hypercalcaemia is infrequent during pregnancy, but it is associated with foetal and maternal morbidity and mortality. Although primary hyperparathyroidism (pHPT) accounts for the majority of the cases, other aetiologies such as genetic causes in a young population should be considered. Clinical Case A 27-year-old female was diagnosed with pHPT during her 16th week of gestation after she presented with vomiting and was found to have raised adjusted calcium of 3.22 mmol/L, low phosphate of 0.6 mmol/L and Parathyroid Hormone of 10.6 pmol/L. The patient's hypercalcaemia dated back 2 years, she had a history of three previous miscarriages, and was not on any hypercalcaemia-inducing medications. Unbeknownst to her, her father was also being evaluated for hypercalcaemia. Her thyroid-stimulating hormone was fully suppressed with raised free thyroid hormones and negative TSH receptor antibodies; this was improved with Carbimazole therapy. Plasma and urine Metanephrines were normal, and neck ultrasound did not reveal any parathyroid lesions. She underwent parathyroidectomy three weeks later after a period of intravenous hydration. A 2 cm left superior parathyroid adenoma was excised, and the plasma calcium level promptly normalised. Genetic testing for familial hyperparathyroidism revealed an autosomal dominant heterozygous CDC73 variant, which is associated with Hyperparathyroidism-Jaw Tumour syndrome. The Clinical Genetics team is arranging genetic testing for her first-degree relatives. She delivered a live baby at 38 + 6 weeks of gestation via emergency caesarean section, performed for foetal hypoxia on cardiotocography, and genetic testing of the newborn child using umbilical cord blood was performed at the time of delivery. She will undergo regular screening for uterine, renal and jaw tumours (every 5 years), and is planned for 6-monthly calcium and parathyroid hormone tests. Conclusion Primary hyperparathyroidism is best treated with parathyroidectomy before pregnancy as the maternal and foetal complications increase according to the hypercalcaemia severity. During pregnancy, mild cases could be treated conservatively while parathyroidectomy is reserved for severe cases and is performed in the second trimester. Germline CDC73 analysis is recommended in young pHPT patients, and in this case revealed a pathological variant associated with Hyperparathyroidism-Jaw Tumour syndrome, familial isolated pHPT and parathyroid carcinoma.

Imaging of Pheochromocytomas and Paragangliomas.

Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.

Molecular and Clinicopathologic Characterization of Mismatch Repair-Deficient Endometrial Carcinoma Not Related to MLH1 Promoter Hypermethylation

Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed through the identification of germline MMR pathogenic variants (PV). In cases where these are not detected, emerging evidence highlights the significance of double-somatic MMR gene alterations as a sporadic cause of MMRd, alongside POLE/POLD1 exonuclease domain (EDM) PV leading to secondary MMR PV. Our understanding of the incidence of different MMRd EC origins not related to MLH1-PHM, their associations with clinicopathologic characteristics, and the prognostic implications remains limited.In a combined analysis of the PORTEC-1, -2, and -3 trials (n = 1254), 84 MMRd EC not related to MLH1-PHM were identified that successfully underwent paired tumor–normal tissue next-generation sequencing of the MMR and POLE/POLD1 genes. Among these, 37% were LS associated (LS-MMRd EC), 38% were due to double-somatic hits (DS-MMRd EC), and 25% remained unexplained. LS-MMRd EC exhibited higher rates of MSH6 (52% vs 19%) or PMS2 loss (29% vs 3%) than DS-MMRd EC, and exclusively showed MMR-deficient gland foci. DS-MMRd EC had higher rates of combined MSH2/MSH6 loss (47% vs 16%), loss of >2 MMR proteins (16% vs 3%), and somatic POLE-EDM PV (25% vs 3%) than LS-MMRd EC. Clinicopathologic characteristics, including age at tumor onset and prognosis, did not differ among the various groups.Our study validates the use of paired tumor–normal next-generation sequencing to identify definitive sporadic causes in MMRd EC unrelated to MLH1-PHM. MMR immunohistochemistry and POLE-EDM mutation status can aid in the differentiation between LS-MMRd EC and DS-MMRd EC. These findings emphasize the need for integrating tumor sequencing into LS diagnostics, along with clear interpretation guidelines, to improve clinical management. Although not impacting prognosis, confirmation of DS-MMRd EC may release patients and relatives from burdensome LS surveillance.

The actual issues of improvement of organization of screening of skin neoplasms in out-patient conditions

The skin malignant neoplasms constitute one of significant problems of public health. The increasing of morbidity and mortality of melanoma and other types of skin cancers is registered. The early detection of disease assures mortality decreasing and increases survival of patients. The purpose of the study is to develop optimal model of organizational and preventive measures of early diagnostic of malignant skin tumors. The comprehensive study was carried out, which included assessment of survey of patients using questionnaire "Melanoma Diagnosis Day". Also it included identification of level of awareness of physicians about screening, medical records of patients during COVID-19 pandemic, risk groups identification and effectiveness of selecting patient for screening. The total number of observations is 21 581. The selective and continuous observation method was applied and parametric and non-parametric methods as well. The study determined that during COVID-19 pandemic in 2020, there was significant reliable uncompensated decrease in the number of patients with diagnosis of ICD D23, L82, C44 and decrease in the number of detected diseases. The melanoma, basalioma and other skin malignant neoplasms are reliably more common in patients of medium-high risk group, aged 60 years and older and in persons sunburned at the age of 18 years. The assignation of separate specialist to diagnose skin neoplasms allows statistically reliably increase rate of morphological confirmation of malignant neoplasms as compared to common reception by dermatologist. The sociological survey of physicians revealed statistically reliable difference in knowledge between dermatovenereologists, oncologists and physicians of other specialties concerning screening issues. The results of the study permitted to develop complex of organizational measures to improve screening. The model of organizational and preventive measures for early diagnostic of skin malignant tumors in outpatient conditions was proposed.

Multimodal Feature Fusion Using Optimal Transfer Learning Approach for Lung Cancer Detection and Classification on CT Images

Lung cancer detection is the process of detecting the presence of lung tumor or abnormalities in the lungs. Early diagnosis is crucial for increasing the chances of patient survival and successful treatment. When compared to X-rays, Computed Tomography (CT) images are more sensitive and are increasingly being used for the diagnosis and screening of lung tumors. They provide complete cross-sectional images of the lungs and it will even detect small lesions. AI and Machine learning (ML) approaches are most commonly employed to analyse medical images (e.g. CT scans) and detect lung cancer. This algorithm can help radiologists identify patterns indicative or subtle abnormalities of cancer. Medical diagnosis, particularly in complex diseases such as lung cancer, frequently involves ambiguity. The diagnostic system can alleviate ambiguity via cross-verifying findings from various sources by fusing multimodal features. Multimodal feature fusion using deep learning (DL) algorithm is an advanced technology that leverages the abilities of deep neural networks to combine data from three different modalities or sources for better robustness in several applications, namely natural language processing, image, and data analysis, etc. This study introduces a Multimodal Feature Fusion using an Optimal Transfer Learning Method for Lung Cancer Detection and Classification (MFFOTL-LCDC) methodology on CT images. The chief objective of the MFFOTL-LCDC methodology is to exploit the feature fusion process for the identification and classification of lung tumor. To attain this, the MFFOTL-LCDC model undergoes a multimodal feature fusion approach to derive feature vectors using 3 DL approaches such as SqueezeNet, CapsNet, and Inception v3 models. Besides, the MFFOTL-LCDC technique applies the remora optimization algorithm (ROA) for the hyperparameter choice of 3 DL models. For lung cancer recognition, the MFFOTL-LCDC algorithm exploits the deep extreme learning machine (DELM) algorithm. A series of simulations were conducted to ensure the greater lung cancer recognition outcomes of the MFFOTL-LCDC methodology. The extensive outcomes determine the improved results of the MFFOTL-LCDC technique over recent DL approaches.

Correlation Between CT Density, Incidence, Mortality, and Mortality-to-Incidence Ratio in Central Nervous System Cancers: An Exploratory Analysis of Global Data.

Cancers of the central nervous system (CNS) pose a significant burden, despite their relatively low incidence compared to other types of cancers. The mortality-to-incidence ratio (MIR) is a crucial indicator of long-term survival and healthcare system performance. Computed tomography (CT) plays a crucial role in the screening, diagnosis, and monitoring of brain tumors, enabling early intervention and treatment. This study aimed to explore the relationship between CT density, CNS cancer incidence, mortality, and MIR to investigate regional variations in CT utilization and their impact on CNS cancer mortality rates. Changes in MIR, referred to as δMIR, were calculated based on data from 2012 and 2018. CT density data for the year 2013 were retrieved from the Global Health Observatory data repository. The association between variables was analyzed using Spearman's rank correlation coefficient. Analysis of data from 107 countries revealed a positive association between CT density and both CNS cancer incidence and mortality. However, a trend was observed between CT density and MIR. These findings suggest that in countries with greater accessibility to CT imaging, CNS cancer cases may be detected earlier and lower mortality rates can be achieved. Our research contributes to the understanding of the impact of CT imaging on the management and outcomes of CNS cancers. It informs healthcare strategies and resource allocation to improve patient care.

APTAnet: an atom-level peptide-TCR interaction affinity prediction model.

The prediction of affinity between TCRs and peptides is crucial for the further development of TIL (Tumor-Infiltrating Lymphocytes) immunotherapy. Inspired by the broader research of drug-protein interaction (DPI), we propose an atom-level peptide-TCR interaction (PTI) affinity prediction model APTAnet using natural language processing methods. APTAnet model achieved an average ROC-AUC and PR-AUC of 0.893 and 0.877, respectively, in ten-fold cross-validation on 25,675 pairs of PTI data. Furthermore, experimental results on an independent test set from the McPAS database showed that APTAnet outperformed the current mainstream models. Finally, through the validation on 11 cases of real tumor patient data, we found that the APTAnet model can effectively identify tumor peptides and screen tumor-specific TCRs.

Colorimetric aptasensor based on temporally controllable light-stimulated oxidase-mimicking fluorescein for the sensitive detection of exosomes in mild conditions.

Analysis of exosomes provides important information for rapid and non-invasive screening of tumors. However, sensitive and convenient detection of exosomes remains technically challenging to date. Herein, a colorimetric aptasensor based on the light-stimulated oxidase-mimicking activity of FITC was constructed for detecting ovarian cancer (OC) exosomes. The aptasensor contained an EpCAM aptamer to capture OC exosomes. Cholesterol and fluorescein (FITC) were used to modify either end of the DNA (DNA anchor). The DNA anchor could combine with exosomes through a hydrophobic reaction between cholesterol and the lipid membrane. FITC oxidized 3,3',5,5'-tetramethylbenzidine (TMB) under a 365 nm LED light source in a temporally controllable manner under mild conditions, causing the solution to change from colorless to blue, and the corresponding UV-vis absorbance increased. Based on this principle, the exosomes were qualitatively analyzed by observing the color change with the naked eye. In parallel, the exosome concentration was also detected using UV-vis spectrophotometry. The linear range was from 2 × 105 to 100 × 105 particles per mL with a limit of detection of 1.77 × 105 particles per mL. The developed aptasensor also exhibited favorable selectivity and could discriminate the exosomes from OC cells and normal cells. Besides, the receiver operating characteristic (ROC) curve demonstrates that it is possible to distinguish between patients with OC and healthy donors (HDs) using exosomes as the biomarker. Our technology may expand the applications of DNA-based detection method-enabled OC diagnostic tools.