Pathological Samples Research Articles

Abstract 4139187: Electrophysiological and Mechanical Characterization of Human Ventricular Myocardium from Patients with Primary or Secondary Cardiac Hypertrophy

Left-ventricular hypertrophy (LVH) is an adaptive condition to hemodynamic stress often involving the left ventricle (LV). This pathological condition is associated with clinical complications such as ventricular arrhythmias and diastolic dysfunction, the molecular and cellular mechanisms of which have been poorly investigated in the human heart. We collected myocardial samples from the upper interventricular septum of 132 patients with hypertrophic cardiomyopathy (HCM), 42 patients with aortic stenosis and severe LVH (AoS-LVH) and 12 non-failing non-hypertrophic patients with valve disease (NF-NH), who underwent myectomy operations at our cardiac surgery center. Samples were used to isolate single viable cardiomyocytes from the left ventricle to perform patch-clamp electrophysiological studies and intracellular calcium measurements with fluorescent dyes. Intact trabeculae were also dissected to perform isometric force measurements of electrically-stimulated twitches. Single-cell patch-clamp studies revealed a marked prolongation of action potential duration (APD) in HCM (N=82, mean APD at 90% repolarization=763±252ms at 0.5Hz) and AoS-LVH (N=22, APD90%=579±147ms) samples with respect to NF-NH (N=12, APD90%=447±88ms). In both HCM and AoS-LVH cardiomyocytes, APD prolongation was associated with increased late-Na + current with respect to NF-NH, while L-type Ca 2+ current was enlarged only in HCM samples. Ca 2+ -fluorescence studies revealed markedly slower Ca-transient (CaT) kinetics in myocardial samples from HCM (N=38, mean CaT 50% decay time at 0.5 Hz = 658±179ms) and AoS-LVH patients (N=9, CaT50%= 568±187ms), when compared with NF-NH samples (N=8, CaT50%=283±59ms), paralleled by elevated diastolic [Ca 2+ ]. Twitch force measurements in intact trabeculae revealed prolonged isometric contractions in HCM (N=78, overall twitch duration at 0.5Hz= 730±147ms) and in AoS-LVH patient-samples (N=24, TwD=669±116ms), as compared with NF-NH (N=7, TwD=511±73ms). Force-frequency relationship was flat in pathological samples, while NF-NH trabeculae showed a clear increase in twitch amplitude while increasing pacing rate to 2Hz. Our results suggest that the main features of functional cardiomyocyte remodeling (that is, changes in the expression and/or function of ion-channel and EC-coupling proteins) are qualitatively similar in primary vs. secondary LVH, albeit abnormalities are quantitatively more extensive in HCM samples.

QLTI-01. ASSESSING THE EFFECTIVENESS OF SUPPORT FROM ST. JUDE CHILDREN’S RESEARCH HOSPITAL TO VIETNAMESE TEAM IN TREATMENT FOR CHILDREN WITH BRAIN TUMORS

Abstract BACKGROUND Treatment for children with brain tumors requires multidisciplinary team (MDT) which is lacking in Vietnam which negatively impacts outcome. This study aims to describe the implementation and promotion of MDT approach in Vietnam with the support of St. Jude Children’s Research Hospital. METHODS We conducted a prospective descriptive study of St. Jude Children’s Research Hospital’s activities with the Vietnamese team between August 2023 and March 2024 and its impact on education, patient care and disseminating of MDC approach in Vietnam. RESULTS Onsite and online training were provided for the Vietnamese team during this time. The onsite training included exchange visits for both teams and St. Jude support for Vietnamese colleagues to attend regional and international neuro-oncology conferences. Online case discussions have been held every month from January 2024 and there are 40-60 participants each meeting from 5 main oncology centers in Vietnam. There are 3- 4 complex case discussions each meeting. A zalo group (a social media platform) for Vietnamese doctors (92 doctors) with multidisciplinary team members was established. After discussion, references and summaries of each case were distributed to the zalo group. For emergency cases, email consults are requested directly for timely input. In addition, key educational textbooks covering different disciplines of neuro-oncology (pathology, radiology and medical) were provided to different Vietnamese teams. All participants (92 doctors) found the online discussion (100.0%) benefical to further their knowledge in different fields (chemotherapy, radiation, pathology and surgery) and the outcome of consultations which guided teams to manage difficult cases. For some cases, pathology samples with local reports are sent to St. Jude to review the diagnosis and classification. CONCLUSIONS Training plays an important role in bringing knowledge and building team-based experience for Vietnamese clinicians in the treatment for children with brain tumor.

BIOM-01. CDKN2A HOMOZYGOUS DELETION HAS STRONGER PROGNOSTIC POWER THANIDH MUTATION IN CNS WHO GRADE 4 GLIOMAS

Abstract We conducted retrospective analysis of glioma cohorts in our institute. Medical records were reviewed for 142 glioblastoma patients for 15 years, and pathological slides were examined again for the updated diagnosis according to 2021 WHO classification of CNS tumors. The IDH mutation and CDKN2A deletion were examined by NGS analysis using ONCOaccuPanel®. Traditional prognostic factors were also examined. Mean follow-up duration was 27.5 months (ranged from 4.1 to 43.5 months) and mean overall survival (OS) was 19.4 months (95% CI 16.3 – 20.9 months). After the exclusion of 4 patients with poor status of pathologic samples, total 109 glioblastoma which were diagnosed by previous WHO criteria were changed into 26 (23.9%) astrocytoma, IDH-mutant, CNS WHO grade 4 and 83 (76.1%) glioblastoma, IDH-wildtype, CNS WHO grade 4. Among them, 61 patients (56.0%) had CDKN2A deletion. Group A was classified for 59 patients with IDH-wildtype and present CDKN2A deletion, group B was classified for 16 patients with IDH-mutant and present CDKN2A deletion, group C was classified for 48 patients with IDH-wildtype and absent CDKN2A deletion, and group D was classified for 13 patients with IDH-mutant and absent CDKN2A deletion. Group A had a mean OS of 15.70 months (95% CI 13.86 – 17.54 months), group B had a mean OS of 19.37 months (95% CI 13.43 – 25.30 months), group C had a mean OS of 22.63 months (95% CI 20.10 – 25.17 months), and group D had a mean OS of 33.38 months (95% CI 29.35 – 37.40 months). Multivariate analysis showed IDH mutation (mutant vs. wildtype; HR 6.358), and CDKN2A deletion (absence vs. presence; HR 13.452). The presenting study suggest that CDKN2A deletion should play a powerful prognostic role in CNS WHO grade 4 gliomas as well as low grade glioma. Even if CNS WHO grade 4 gliomas had mutant IDH, they can have poor clinical outcome due to CDKN2A deletion.

Comparison of histopathological diagnoses of ENT diseases in the COVID-19 pandemic with other periods

Abstract OBJECTIVE. It is aimed to reveal the frequency of histopathological diagnosis in ENT diseases during the COVID-19 period and whether it is different from diagnoses in other periods. MATERIAL AND METHODS. The files of 1442 patients diagnosed with pathological material in the ENT clinic between 2017 and 2022 were retrospectively scanned. Two groups were created: the 1st group of patients between 2017-2019 (non-COVID-19 period) (Group 1) and the 2nd group of patients between 2020-2022 (COVID-19 period) (Group 2). RESULTS. Pathological samples were sent from 1163 patients in Group 1 and from 279 patients in Group 2. Of 1442 patients, 815 were male and 627 were female, and the mean age was 25 (3-94 years). There was a statistically significant difference between the groups in terms of age (p=0.001). There was no significant difference in terms of gender (p=0.756). The most common histopathological diagnoses in both periods were chronic tonsillitis lymphoid hyperplasia (bilateral tonsillectomy + adenoidectomy) (19.5%), chronic inflammation lymphoid hyperplasia (adenoidectomy) (19.3%) and nasal polyp (19.2%). The incidence of malignant tumors was found to be 1.4% in Group 1 and 2.8% in Group 2. The incidence of benign tumors was found to be 7.6% in Group 1 and 12.8% in Group 2. In terms of frequency, the ratio of malignant and benign tumors was higher in Group 2. CONCLUSION. The number of patients with histopathological diagnoses decreased due to the decrease in hospitalizations during the COVID-19 period. Delayed diagnosis in malignant pathologies significantly worsens the prognosis. All these results show that new cancer diagnostic strategies are needed for epidemic diseases such as COVID-19.

Three-Dimensional Reconstruction of the Right Ventricle from a Radial Basis Morphing of the Inner Surface

In the realm of cardiac health research, accurate fluid dynamics simulations are vital for comprehending the heart function and diagnosing conditions. Central to these simulations is the precision of ventricular wall meshes used to model heart geometry. However, segmenting the wetted surface, particularly in the right ventricle (RV) with its significantly thinner parietal thickness compared to the left ventricle, presents challenges. This study focuses on qualitatively evaluating an automated reconstruction model for the RV’s outer wall using Radial Basis function (RBF) morphing. Two procedural criteria were compared, a random selection of control points and a curvature-based approach, which differ in terms of the identification of the control points of the RBF function. From these considerations, it emerges that a controlled use of the RBF function on the basis of the curvatures guarantees the greater controllability of the shape evolutions of the parietal structure of the RV, but it is more sensitive to any anomalies in the distribution of the vertices, as can be seen from the number of outliers, and its controllability is a function of the percentage of points chosen, exerting a greater impact on the required computational capacity. The definition of a strategic criterion for the selection of control points could represent a crucial aspect in the definition of an automatic reconstruction procedure of anatomical elements, which guarantees a morphological variability in line with the need to expand the pathological sample to be used for statistical formulations in the clinical field.

HAS THE INITIATION OF A FORMAL PATHWAY FOR TUMOUR TISSUE COLLECTION IN NEURO ONCOLOGY PATIENTS LED TO AN INCREASE IN PATIENT’S HAVING WHOLE GENOME SEQUENCING (WGS), AND HOW WILL THIS IMPACT ONCOLOGY MANAGEMENT IN THE FUTURE?

Abstract AIMS To change the standard of care for collection of glial tumour tissue at a London teaching hospital. This would enable WGS on the tumour tissue, and give patients access to further clinical trials. METHOD The previous standard of care was for brain tumour pathology samples to be stored in paraffin. This was not suitable for WGS or for many clinical trials; the tumour samples needed to be sent to the lab as fresh tissue. The introduction of a genomics clinical nurse specialist meant that relationships were built between the surgical team, pathology teams and ward teams. There was a teaching by one of the neurosurgical team to the theatre staff. Genomics CNS led training for the nursing team. Adults started having WGS in May 2023 but many patient’s still had tissue incorrectly stored and could not have the sequencing performed. There was an introduction of a formal pathway in theatre created by one of the neurosurgeons in Dec 2023. RESULTS From May 2023 - November 2023, 58% adult glioma patients had WGS. Since December 2023 - current (March 2023) and the introduction of the formal pathways, 71% had WGS. CONCLUSION A formal pathway has now changed the standard of care for collecting tissue. There is still not 100% compliance, and this remains multifactorial. However the introduction of a formal pathway has now increased the percentage of eligible patients receiving WGS. This positive outcome has now led to discussions about freezing the fresh glioma tissue to allow glioma patient’s wider access to clinical trials which they would previously not have had access to.

Heterotopic High-Grade Salivary duct Carcinoma Likely Arising within Cervical Lymph Nodes

Abstract Introduction/Objective Salivary duct carcinoma arising in heterotopic salivary gland tissue is an extremely rare occurrence, with less than five cases reported in the literature. We present a unique case of heterotopic high-grade salivary duct carcinoma likely arising within cervical lymph nodes. Methods/Case Report A 56-year-old male presented with enlarged cervical lymph nodes for few months. Physical examination was unremarkable. Computerized tomography (CT) scan of head and neck showed two enlarged level 1B lymph nodes, measuring 1.0 and 1.4 cm, with unremarkable salivary glands. Patient had left cervical level II lymph node biopsy that showed metastatic poorly differentiated carcinoma. Immunohistochemically, the tumor cells were positive for GATA3, cytokeratin 903, androgen receptor, p16 (variable nonspecific), and were negative for TTF-1, p40, p63, ER, PR and NKX3.1, favoring salivary gland ductal carcinoma. Positron emission tomography (PET) CT scan showed a hypermetabolic left submandibular gland and level 2A lymph nodes. Subsequently, the patient underwent left modified radical neck dissection. Sectioning of the submandibular gland revealed no discrete lesions. Multiple, firm to rubbery lymph nodes ranging from 0.4 cm to 2.3 cm, with tan-pink cut surfaces were identified. Microscopic examination showed normal submandibular salivary gland parenchyma. However, eight out of nineteen lymph nodes were positive for metastatic high-grade salivary duct carcinoma comprising tumor cells forming nests and cords with ample eosinophilic cytoplasm, pleomorphic round to oval nuclei and numerous mitotic figures. Several benign and malignant lymph nodes in levels I, II and IV showed heterotopic salivary gland tissue. Immunohistochemical stains for androgen receptor and p40 were positive and negative respectively, supported the final diagnosis of high-grade salivary duct carcinoma. Results (if a Case Study enter NA) NA Conclusion Given the absence of carcinoma in the completely sampled submandibular gland, the origin of the intra- nodal tumor deposits was most likely to be heterotopic salivary gland tissue. This case emphasizes the importance of meticulous pathological sampling required for definitive diagnosis.

Assessing the Feasibility of a Cancer Biomarker Testing Navigator in the Laboratory

Abstract Introduction/Objective Cancer biomarker testing is a crucial component of precision oncology, as it can guide medical treatment decisions with targeted therapies and immune checkpoint inhibitors. However, complex, fragmented, and inefficient operational processes involved in biomarker testing lead to delays, errors, and variability in testing. One potential solution is to introduce a novel role in the pathology laboratory: the cancer biomarker testing navigator (BTN). Methods/Case Report The American Society for Clinical Pathology (ASCP) conducted a mixed-methods project to assess the current state of biomarker testing operations and explore how a BTN may improve biomarker testing processes. ASCP conducted an online survey, focus groups, and worked with two hospital-based cancer centers on a feasibility pilot. Results (if a Case Study enter NA) Survey and focus group insights reveal several operational challenges around the biomarker testing process. 47 completed the survey and 16 participated in the focus groups. Participants report that biomarker test orders may be incorrect or incomplete. 37% of survey respondents experience delays preparing tissue samples for send-out cancer biomarker testing. 42% of survey respondents are unable to track the processing status of send-out tests. Excessive time is required to coordinate and facilitate send-out tests, especially when multiple reference laboratories are used since each has its own portal, requisition form, specimen requirements, etc. 87% agree they would benefit significantly from having a dedicated person to coordinate and manage cancer biomarker tests. The cancer centers that piloted this role found that they could catch and correct defects such as incorrect test ordered, incorrect specimen types marked on the test order, outdated requisition used, etc. The BTN also found instances where the test report was incomplete or had not been uploaded into the EHR. The BTN role could be justified by evaluating metrics such as task efficiency, workplace satisfaction in the lab, and levels of service satisfaction from oncologists. Patient care can be improved by reducing delays in testing and by reviewing other metrics of quality care delivery. Conclusion The BTN role in the laboratory is a novel solution for ensuring the proper collection and triage of pathology samples for biomarker testing. This role could serve as a liaison between the laboratory and ordering clinicians, provide collection and testing guidance, and help with benchmarking and quality measurement initiatives.

The prognostic and immune significance of Rab11A in pan-cancer and its function and mechanism underlying estrogen receptor targeting in breast cancer.

Rab11A is an important molecule for recycling endosomes and is closely related to the proliferation, invasion, and metastasis of tumors. This study investigated the prognostic and immune significance of Rab11A and validated its potential function and mechanism in breast cancer (BRCA). RNA sequencing data for 33 tumors were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases. Correlation analysis was used to evaluate the relationship between Rab11A expression and immune characteristics. Potential pathways were identified using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis. Immunohistochemical analysis, colony formation assay, bromodeoxyuridine incorporation assay, immunofluorescence, and Western blot were used to explore potential function and mechanism. Analysis of the TCGA database showed significant upregulation of Rab11A expression in a variety of cancers. Rab11A was up-regulated in 82.4% of BRCA. High Rab11A expression is associated with poor survival in cancer patients and is a predictor of poor prognosis. CIBERSORT analysis showed that Rab11A was negatively associated with almost all immune cycle activity scores pan-cancer. The results of the TCGA-BRCA cohort were further confirmed by using pathological samples from clinical BRCA patients. The results showed that Rab11A expression was correlated with estrogen receptor (ER) and progesterone receptor expression in BRCA (p<0.05). Knockdown and overexpression of Rab11A affected the proliferation of BRCA cells. Further mechanistic studies revealed that down-regulation of ER alpha (ERα) and up-regulation of ER beta (ERβ) mediated Rab11A-induced inhibition of BRCA cell proliferation. Rab11A expression in pan-cancer is associated with poor prognosis and immune profile. In particular, in BRCA, Rab11A expression regulates cell proliferation by targeting ERα and ERβ. High Rab11A expression is tightly associated with immune characteristics, tumor microenvironment, and genetic mutations. These results provide a reference for exploring the role of Rab11A in pan-cancer and provide a new perspective for revealing potential therapeutic targets in BRCA.

High-Resolution Terahertz Spectroscopy for MedicalDiagnostics.

The metabolomics-based approach to diagnostics and therapy monitoring is a fast-emerging trend in modern medicine. Terahertz nonstationary spectroscopy based on the induction and disintegration of freely decaying polarization in the gas mixture during the interaction of radiation with molecules at resonance frequencies is a high-sensitivity method for studying multicomponent gas mixtures, which is promising for identifying metabolites in the thermal decomposition products of biological samples. The paper presents the results of the application of high-resolution terahertz spectroscopy to the study of biological samples taken from patients with certain diseases (pathologically changed tissues of ear-nose-throat organs and similar pathologic tissues formed in other life support systems) to search for characteristic sets of metabolites characterizing the pathology. The world's first measurements of the spectra of pathologic samples of cysts, formed in different life support systems, were carried out, which made it possible to identify similar substances in tissues having the same pathology.

Graph neural networks in multi-stained pathological imaging: extended comparative analysis of Radiomic features.

This study investigates the application of Radiomic features within graph neural networks (GNNs) for the classification of multiple-epitope-ligand cartography (MELC) pathology samples. It aims to enhance the diagnosis of often misdiagnosed skin diseases such as eczema, lymphoma, and melanoma. The novel contribution lies in integrating Radiomic features with GNNs and comparing their efficacy against traditional multi-stain profiles. We utilized GNNs to process multiple pathological slides as cell-level graphs, comparing their performance with XGBoost and Random Forest classifiers. The analysis included two feature types: multi-stain profiles and Radiomic features. Dimensionality reduction techniques such as UMAP and t-SNE were applied to optimize the feature space, and graph connectivity was based on spatial and feature closeness. Integrating Radiomic features into spatially connected graphs significantly improved classification accuracy over traditional models. The application of UMAP further enhanced the performance of GNNs, particularly in classifying diseases with similar pathological features. The GNN model outperformed baseline methods, demonstrating its robustness in handling complex histopathological data. Radiomic features processed through GNNs show significant promise for multi-disease classification, improving diagnostic accuracy. This study's findings suggest that integrating advanced imaging analysis with graph-based modeling can lead to better diagnostic tools. Future research should expand these methods to a wider range of diseases to validate their generalizability and effectiveness.

CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas.

Background: We primarily investigated the prognostic role of CDKN2A homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. Materials: We conducted a retrospective analysis of the glioma cohorts at our institute. We reviewed medical records spanning a 15-year period and examined pathological slides for an updated diagnosis according to the 2021 WHO classification of CNS tumors. We examined the IDH1/2 mutation and CDKN2A deletion using NGS analysis with ONCOaccuPanel®. Further, we examined traditional prognostic factors, including age, WHO performance status, extent of resection, and MGMT promoter methylation status. Results: The mean follow-up duration was 27.5 months (range: 4.1-43.5 months) and mean overall survival (OS) was 20.7 months (SD, ±1.759). After the exclusion of six patients with a poor status of pathologic samples, a total of 136 glioblastoma cases diagnosed by previous WHO classification criteria were newly classified into 29 (21.3%) astrocytoma, IDH-mutant, and CNS WHO grade 4 cases, and 107 (78.7%) glioblastoma, IDH-wildtype, and CNS WHO grade 4 cases. Among them, 61 (56.0%) had CDKN2A deletions. The high-risk group with CDKN2A deletion regardless of IDH1/2 mutation had a mean OS of 16.65 months (SD, ±1.554), the intermediate-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 21.85 months (SD, ±2.082), and the low-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 33.38 months (SD, ±2.946). Multifactor analysis showed that age (≥50 years vs. <50 years; HR 4.645), WHO performance (0, 1 vs. 2; HR 5.002), extent of resection (gross total resection vs. others; HR 5.528), MGMT promoter methylation, (methylated vs. unmethylated; HR 5.078), IDH1/2 mutation (mutant vs. wildtype; HR 6.352), and CDKN2A deletion (absence vs. presence; HR 13.454) were associated with OS independently. Conclusions: The present study suggests that CDKN2A deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant IDH1/2, they may have poor clinical outcomes because of CDKN2A deletion.

Correlation of FAPI PET Uptake with Immunohistochemistry in Explanted Lungs from Patients with Advanced Interstitial Lung Disease.

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of 68Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis-associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUVmax and SUVmean showed a positive correlation with the immunohistochemical FAP expression score (SUVmax: r = 0.57, P = 0.001; SUVmean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

An approach to determine pathological breast tissue samples with free‐space measurement method at 24 GHz

AbstractPathology is an important branch of science in the diagnosis and treatment of several diseases. In cancer diseases, serious investigations have been made about the course of the diseases. A report that is essential for both the patient and the doctor is prepared by the pathologists as a result of a detailed cellular examination. These reports contain information about the disease. Access duration to these reports, which affects the form and duration of the treatment, is extremely important today. It is possible to shorten this period with systems using antenna technologies. The pathological breast tissue samples have been examined by using horn antenna structures with high gain in this study. Dual identical horn antennas have been placed opposite each other as receivers and transmitters in the measurement setup at 24 GHz. Measurements of normal and cancerous breast tissues have been made, and the normalization process has been applied to the measured scattering parameters. The different values between normal and cancerous breast tissues have been shown with this process. The normalized values are compared with other analyzed values. According to the results obtained, the percentage of normalized values for transmission is much more effective and meaningful than other results.

Development and Application of Reversible and Irreversible Covalent Probes for Human and Mouse Cathepsin-K Activity Detection, Revealing Nuclear Activity.

Cathepsin-K (CTSK) is an osteoclast-secreted cysteine protease that efficiently cleaves extracellular matrices and promotes bone homeostasis and remodeling, making it an excellent therapeutic target. Detection of CTSK activity in complex biological samples using tailored tools such as activity-based probes (ABPs) will aid tremendously in drug development. Here, potent and selective CTSK probes are designed and created, comparing irreversible and reversible covalent ABPs with improved recognition components and electrophiles. The newly developed CTSK ABPs precisely detect active CTSK in mouse and human cells and tissues, from diseased and healthy states such as inflamed tooth implants, osteoclasts, and lung samples, indicating changes in CTSK's activity in the pathological samples. These probes are used to study how acidic pH stimulates mature CTSK activation, specifically, its transition from pro-form to mature form. Furthermore, this study reveals for the first time, why intact cells and cell lysate exhibit diverse CTSK activity while having equal levels of mature CTSK enzyme. Interestingly, these tools enabled the discovery of active CTSK in human osteoclast nuclei and in the nucleoli. Altogether, these novel probes are excellent research tools and can be applied in vivo to examine CTSK activity and inhibition in diverse diseases without immunogenicity hazards.

Histological study to the thyrotoxicity between men and women of AL- Ramadi city

Thyrotoxicosis is the clinical manifestation of excess thyroid hormone action at the tissue level due to inappropriate high circulating thyroid hormone concentrations. Hyperthyroidism, a subset of thyrotoxicosis, refers specifically to excess thyroid hormone synthesis and secretion by the thyroid gland. This study aims to show the difference between men and women affected with thyrotoxicity in different ages and the histological changes with hormonal evaluation. This study was done using 50 patients with hyperthyroidism (25 women and 25 men). Patients have been taken from Arrazzi private hospital and Al- Ramadi hospital. Hormonal testes (TSH, T3, T4) was collected and recorded. Information of patents like name, age and gender was recorded. The pathological samples of thyroidectomy were collected after operation and saved in 10% formalin for Histopathological studies. A significant (p&lt; 0.05) increases in thyroid hormone (T3 and T 4) in women was observed as compared to men. Slides showed a diffuse area of hemorrhage and diffuse inter follicular lympho-neutrophilic infiltration was seen in the tissue. The results of the study reflected that the incidence of thyrotoxicity was more effective in women than men.

External validation of the PRECE nomogram model in a Central America cohort

Introduction: This is an external validation study of the PRECE prostate cancer nomogram in a Central American population. Methods: We present 102 consecutive cases of robotic radical prostatectomy, performed with preservation of the anterior fascia and we use the PRECE nomogram as a guide to preserve the prostatic neurovascular pedicles. We compared the predicted extra-capsular extension from the PRECE nomogram to the final prostatectomy pathology. Results: Analysis of post-prostatectomy pathological samples revealed that 61% patients had pT2; 27% had a pT3a and 12% had a pT3b, respectively The ROC curve for the PRECE nomogram at one (1) mm showed a model AUC of 0.91 (95% CI), which implies a high agreement with the PRECE nomogram in the prediction of extraprostatic disease. Conclusion: This is the first report of external validation of the PRECE nomogram in a Central American population. PRECE demonstrated high discrimination for the prediction of extraprostatic disease in an independent Latin American cohort. More external validation studies, from different geographic settings, are expected to confirm the reliability and reproducibility of PRECE in other clinical settings.

The role of trimethylation on histone H3 lysine 27 (H3K27me3) in temozolomide resistance of glioma

Temozolomide (TMZ) is the first-line chemotherapeutic agent for malignant glioma, but its resistance limited the benefits of the treated patients. In this study, the role and significance of trimethylation of histone H3 lysine 27 (H3K27me3) in TMZ resistance were investigated. Data from twenty advanced glioma patients were collected, and their pathological samples were analyzed for H3K27me3 levels. TMZ sensitivity was compared between glioma cells U87 and TMZ-resistant cells U87TR, with H3K27me3 levels determined in both cells. The effects of H3K27me3 demethylases inhibitor GSK-J4, combined with TMZ, were assessed on the proliferation and migration of U87TR cells. The results indicated that a high level of H3K27me3 predicts longer disease free survival (DFS) and overall survival (OS) in glioma patients receiving TMZ treatment. The H3K27me3 level was lower in U87TR cells compared to U87 cells. GSK-J4 increased the H3K27me3 level in U87TR cells and decreased their resistance to TMZ. In summary, this study identified a novel marker of TMZ resistance in glioma and provided a new strategy to address this challenge. These findings are significant for improving the clinical treatment of glioma in the future.

Spectral analysis comparison of pushbroom and snapshot hyperspectral cameras for in vivo brain tissues and chromophore identification.

Hyperspectral imaging sensors have rapidly advanced, aiding in tumor diagnostics for in vivo brain tumors. Linescan cameras effectively distinguish between pathological and healthy tissue, whereas snapshot cameras offer a potential alternative to reduce acquisition time. Our research compares linescan and snapshot hyperspectral cameras for in vivo brain tissues and chromophore identification. We compared a linescan pushbroom camera and a snapshot camera using images from 10 patients with various pathologies. Objective comparisons were made using unnormalized and normalized data for healthy and pathological tissues. We utilized the interquartile range (IQR) for the spectral angle mapping (SAM), the goodness-of-fit coefficient (GFC), and the root mean square error (RMSE) within the 659.95 to 951.42nm range. In addition, we assessed the ability of both cameras to capture tissue chromophores by analyzing absorbance from reflectance information. The SAM metric indicates reduced dispersion and high similarity between cameras for pathological samples, with a 9.68% IQR for normalized data compared with 2.38% for unnormalized data. This pattern is consistent across GFC and RMSE metrics, regardless of tissue type. Moreover, both cameras could identify absorption peaks of certain chromophores. For instance, using the absorbance measurements of the linescan camera, we obtained SAM values below 0.235 for four peaks, regardless of the tissue and type of data under inspection. These peaks are one for cytochrome b in its oxidized form at , two for at and , and one for water at . The spectral signatures of the cameras show more similarity with unnormalized data, likely due to snapshot sensor noise, resulting in noisier signatures post-normalization. Comparisons in this study suggest that snapshot cameras might be viable alternatives to linescan cameras for real-time brain tissue identification.

An adapted savings algorithm for planning heterogeneous logistics with uncrewed aerial vehicles

This paper proposes a new extension to the Sustainable Specimen Collection Problem (SSCP), where medical specimens are transported by vans, bikes, and uncrewed aerial vehicles (UAVs, or drones) from local medical practices/offices to a central hospital laboratory for analysis, employing a two-echelon collection approach. Time restrictions from existing operations and literature are also introduced, with the study being formulated as a weighted multi-objective problem seeking to minimise (i) operating costs; (ii) transit times; and (iii) energy/environmental impacts. A new adaptation of the Clarke and Wright Savings Algorithm is subsequently presented to create collection rounds that leverage each mode’s strengths. Subsequently, routes are compiled into workable fixed shifts using a modified bin-packing algorithm in each iteration.The approach of this study is based on a case study of the UK’s National Health Service (NHS), involving the collection of pathology samples using traditional vans operating within fixed time slots. Using case study data from the Solent region (England), a novel test instance generation methodology was also developed, whereby realistic site positioning and origin-destination travel data are captured to enable effective algorithm experimentation. The findings from applying the proposed algorithm to a set of test instances based on this methodology are subsequently discussed, where it was found that the adapted savings and bin-packing approach produced effective solutions quickly, with 90% of all large instances (200 sites) being solved within 15 min. Further algorithm developments and the application of the devised problem/methodologies are also discussed.