Modified scoring system for the quantitative assessment of histological regression in peritoneal carcinomatosis after pressurized intraperitoneal aerosol chemotherapy: A pilot study.

Peritoneal carcinomatosis is one of the leading causes of death in patients with gastrointestinal cancer. Newer locoregional treatment concepts include pressurized intraperitoneal aerosol chemotherapy (PIPAC), the regional application of pressurized chemotherapeutic agents to the abdominal cavity, which is usually performed every 4 to 8 weeks. One of the main challenges of PIPAC therapy remains the objective assessment of treatment response. The present study describes a new scoring system to histologically assess the regression of peritoneal cancer following PIPAC therapy, quantitative assessment of histological regression in peritoneal carcinomatosis (QARP). Peritoneal biopsies from 27 patients with peritoneal metastases undergoing PIPAC were obtained and processed in a standardized fashion. Biopsies were scored according to the QARP grading system. The five-tiered system was graded as follows, Grade 0, no residual tumor cells with regressive changes present; grade 1, 1-25% viable tumor cells per tumor focus with regressive changes present; grade 2, 26-50% viable tumor cells per tumor focus with regressive changes present; grade 3, 51-75% viable tumor cells per tumor focus with few regressive changes; grade 4, >75% viable tumor cells per tumor focus with minimal or no regressive changes. Based on the new grading system, the study cohort was divided into QARP responders and QARP non-responders following PIPAC treatment. Higher QARP scores were significantly correlated with higher PCI scores (r=0.32; P=0.007). However, no difference in overall survival was detected between QARP responders and QARP non-responders. Further studies are required to ascertain the reproducibility and prognostic significance of QARP.

NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.

PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs. RESULTS: NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup (P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers. CONCLUSION: NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.

Critical evaluation of artificial intelligence as a digital twin of pathologists for prostate cancer pathology.

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

Impact of (nano ZnO/multi-wall CNTs) prepared by arc discharge method on the removal efficiency of stable iodine 127I and radioactive iodine 131I from water.

Radioactive iodine isotopes especially 131I are used for diagnosis and treatment of different types of cancer diseases. Due to the leak of radioactive iodine into the patient's urine in turn, the wastewater would be contaminated, so it is worth preparing a novel adsorption green material to remove the radioactive iodine from wastewater efficiently. The removal of 127I and 131I contaminants from aqueous solution is a problem of interest. Therefore, this work presents a new study for removing the stable iodine 127I- and radioactive iodine 131I from aqueous solutions by using the novel nano adsorbent (Nano ZnO/MWCNTs) which is synthesized by the arc discharge method. It is an economic method for treating contaminated water from undesired dissolved iodine isotopes. The optimal conditions for maximum removal are (5 mg/100 ml) as optimum dose with shacking (200 rpm) for contact time of (60 min), at (25 °C) in an acidic medium of (pH = 5). After the adsorption process, the solution is filtrated and the residual iodide (127I-) is measured at a maximum UV wavelength absorbance of 225 nm. The maximum adsorption capacity is (15.25 mg/g); therefore the prepared nano adsorbent (Nano ZnO/MWCNTs) is suitable for treating polluted water from low iodide concentrations. The adsorption mechanism of 127I- on to the surface of (Nano ZnO/MWCNTs) is multilayer physical adsorption according to Freundlich isotherm model and obeys the Pseudo-first order kinetic model. According to Temkin isotherm model the adsorption is exothermic. The removal efficiency of Nano ZnO/MWCNTs for stable iodine (127I-) from aqueous solutions has reached 97.23%, 89.75%, and 64.78% in case of initial concentrations; 0.1843 ppm, 0.5014 ppm and 1.0331 ppm, respectively. For the prepared radio iodine (131I-) solution of radioactivity (20 µCi), the dose of nano adsorbent was (10 mg/100 ml) and the contact time was (60 min) at (pH = 5) with shacking (200 rpm) at (25 °C). The filtration process was done by using a syringe filter of a pore size (450 nm) after 2 days to equilibrate. The removal efficiency reached (34.16%) after the first cycle of treatment and the percentage of residual radio iodine was (65.86%). The removal efficiency reached (94.76%) after five cycles of treatment and the percentage of residual radio iodine was (5.24%). This last percentage was less than (42.15%) which produces due to the natural decay during 10 days.

Novel composite based on silicone rubber and a nano mixture of SnO2, Bi2O3, and CdO for gamma radiation protection.

Recently, there has been a surge of interest in the application of radiation-shielding materials. One promising research avenue involves using free-lead metal oxides/polymer composites, which have been studied for their radiation shielding and characterization properties. This study reinforced the dimethylpolysiloxane (silicone rubber) composites with micro- and nano-sized particles of tin oxide, cadmium oxide, and bismuth oxide as additive materials. The composites were tested with 20 and 50 weight fractions, and their attenuation coefficients were measured using a NaI(TI) detector at gamma-ray energies ranging from 59.54 to 1408.01 keV. Also, the thermal and mechanical properties of the composites were observed and compared with those of free silicone rubber. The results showed that the 50% nano metal oxide/SR composites exhibited better thermal stability and attenuation properties than the other composites, also possessing unique attributes such as lightweight composition and exceptional flexibility. Consequently, this composite material holds immense potential for safeguarding vital organs, including the eyes and gonads, during radiological diagnosis or treatment procedures. Its exceptional ability to absorb a significant portion of incident rays makes it an invaluable asset in the field of radiation protection.

Heavy Metals Assessment and Health Risk to Consumers of Two Commercial Fish Species from Polyculture Fishponds in El-Sharkia and Kafr El-Sheikh, Egypt: Physiological and Biochemical Study.

Metal pollution is a major environmental concern worldwide, especially in Egypt. The aquaculture industry uses widespread artificial feeds to stimulate fish production, leading to metal accumulation in the aquatic environment. Heavy metal concentrations (HMCs) in sediments, water, and tissues were studied to study the effect of pollution levels on heamatological, and biochemical, immunological aspects of farmed fish as well as on human health. Results declared that the HMC levels in the water and sediment were significantly different between El-Sharkia and Kafr El-Sheikh fishponds (T-test, p < 0.05). This was supported by the metal pollution index in the water and sediment, indicating that El-Sharkia fishponds (ES fishponds) were more contaminated than Kafr El-Sheikh fishponds (KES fishponds). Also, HMCs in fish tissues were significantly increased in fish cultivated in ES fishponds than in KES fishponds. Haematological, immunological, and biochemical alterations of Bolti (Oreochromis niloticus) and Topara (Chelon ramada) fish were significantly different within the different fish species as well as the different fishponds. From the human health perspective, the THQ-HMC and HI-HMC associated with the consumption of muscle suggest a safe non-carcinogenic risk to human health. In contrast, cadmium poses a cancer risk to children who consume the muscular tissue of Bolti fish from ES fishponds, which should be regarded as a warning sign based on data indices and a human health perspective. In order to minimise HMC pollution in the aquaculture sector, it is advisable to take possible assessments and carry out continuous monitoring considering international WHO/FAO assessments.

Immunohistochemical expression of TROP­2 (TACSTD2) on the urothelial carcinoma of the urinary bladder and other types of cancer.

In metastatic or locally advanced urothelial carcinoma (UC), therapeutic options have been limited to chemotherapy and immune checkpoint inhibitors. Novel targets and drugs such as antibody drug conjugates have been developed, and enfortumab vedotin targeting nectin-4 and sacituzumab govitecan (SG) targeting trophoblast cell surface antigen 2 (TROP-2), the protein product of the TACSTD2 gene, have been approved. The expression of TROP-2 was investigated within UC and other types of carcinomas, and within the tissue of different healthy organs to understand treatment responses and toxicities. The expression of TROP-2 in the tissues of 42 patients with UC, 13 patients with other types of cancer and in the normal tissues of 11 patients was retrospectively analyzed. Immunohistochemical staining of the TROP-2 protein was performed on a BenchMark ULTRA IHC/ISH System (Roche Tissue Diagnostics; Roche Diagnostics, Ltd.) according to accredited staining protocols in a routine immunohistochemistry accredited and certified facility of the laboratory of immunohistochemistry at the Institute of Pathology (Gerhard-Domagk Institute)- University Hospital Muenster (UKM)-Muenster-Germany]. Different expression levels of TROP-2 were observed, and the highest expression rate of TROP-2 was observed in UC, independent of the tumor stage. However, normal urothelial cells had similar expression levels. Except for ductal carcinoma in situ, the expression of TROP-2 was reduced in other types of cancer and in the healthy tissues from other organs, including pancreas, gall bladder, colon and prostate. Given the treatment response based on the expression level of TROP-2, SG would be effective in almost all cases of UC. However, it would also have an effect on the normal urothelium.

Artificial Intelligence Reveals Distinct Prognostic Subgroups of Muscle-Invasive Bladder Cancer on Histology Images.

Muscle-invasive bladder cancer (MIBC) is a highly heterogeneous and costly disease with significant morbidity and mortality. Understanding tumor histopathology leads to tailored therapies and improved outcomes. In this study, we employed a weakly supervised learning and neural architecture search to develop a data-driven scoring system. This system aimed to capture prognostic histopathological patterns observed in H&E-stained whole-slide images. We constructed and externally validated our scoring system using multi-institutional datasets with 653 whole-slide images. Additionally, we explored the association between our scoring system, seven histopathological features, and 126 molecular signatures. Through our analysis, we identified two distinct risk groups with varying prognoses, reflecting inherent differences in histopathological and molecular subtypes. The adjusted hazard ratio for overall mortality was 1.46 (95% CI 1.05-2.02; z: 2.23; p = 0.03), thus identifying two prognostic subgroups in high-grade MIBC. Furthermore, we observed an association between our novel digital biomarker and the squamous phenotype, subtypes of miRNA, mRNA, long non-coding RNA, DNA hypomethylation, and several gene mutations, including FGFR3 in MIBC. Our findings underscore the risk of confounding bias when reducing the complex biological and clinical behavior of tumors to a single mutation. Histopathological changes can only be fully captured through comprehensive multi-omics profiles. The introduction of our scoring system has the potential to enhance daily clinical decision making for MIBC. It facilitates shared decision making by offering comprehensive and precise risk stratification, treatment planning, and cost-effective preselection for expensive molecular characterization.

Heavy Metal Levels and Cancer Risk Assessments of the Commercial Denis, Sparus aurata Collected from Bardawil Lake and Private Fish Farm Waters as a Cultured Source, Egypt.

Heavy metal pollution of natural and cultivated habitats may be caused by agricultural, industrial, and human activities. Fish living in these habitats easily accumulate metals in their organs; for food safety and human health, the heavy metals in fish flesh are of major concern due to the harmful nature of these pollutants even in low quantities. In this study, metals (Iron, Fe; Lead, Pb; Cadmium, Cd; Nickel, Ni; Copper, Cu and Zinc, Zn) in the muscle, liver, intestine, and gill of gilthead seabream (Sparus aurata, Denis is local name) were monitored to determine the contamination levels and to investigate the protective impact of cooking methods on the reduction or mitigation of metal levels. Although the Denis samples exhibited relatively low Pb and Cd levels, most fish samples had elevated levels of Fe and Zn. The examined metals accumulated at the highest level in the liver and gills compared to the other organs. Results showed that cooking methods had a considerable effect on concentrations of metals. However, the levels of metal in S. aurata from various sources were reduced significantly (P < 0.05) by frying, microwave, and grilling cooking, which was ordered in the following sequence as microwave cooking < grilling < frying. The consumption of Denis fish from different sources (wild and cultured) has no negative effects on health, according to a study of health hazards based on indices of carcinogenic and non-carcinogenic. The metal results indicated that different fish sources (wild and cultured) could be acceptable for human consumption. Data hypothesized a positive impact of awareness among the native community.

Impact of micro/nano cadmium oxide on shielding properties of cement-ball clay matrix.

This study investigates the gamma radiation shielding properties of cement-ball clay matrix composites doped with micro- and nano-sized cadmium oxide (CdO) particles. The linear attenuation coefficient (LAC) was determined using a sodium iodide (NaI) detector and five radioactive point sources with energies ranging from 59.5 to 1408 keV. The LAC values obtained were compared to the XCOM database and found to be in good agreement. The composites' half-value layer (HVL), tenth value layer (TVL), mean free path (MFP), effective atomic number (Zeff), equivalent atomic number (Zeq), and absorption buildup factor (EABF) were determined. The results showed that the addition of CdO particles improved the radiation-shielding behavior of the composites and increasing the weight fraction of CdO particles increased the shielding effectiveness. The results also illustrated that when nano-sized CdO particles were compared to their micro-sized counterparts, there was a significant enhancement in radiation shielding effectiveness. For instance, a composite material composed of 50% cement, 41.7% ball clay, and 3.8% nano CdO at an energy level of 0.0595 MeV exhibited a remarkable 12.2% increase in attenuation, surpassing the performance of the micro-sized sample with an equivalent concentration. Similarly, another composite consisting of 50% cement, 33.3% ball clay, and 16.7% nano CdO demonstrated a significant 15.4% increase in attenuation at the same energy level, when compared to the micro-sized sample. The study demonstrates the potential of CdO-doped cement-ball clay matrix composites for gamma radiation shielding applications.

Novel slag/natural rubber composite as flexible material for protecting workers against radiation hazards.

This work is an attempt to employ the electric arc furnace (EAF) slag as a by-product material to develop an alternative and environmentally friendly material for gamma-radiation protection applications such as in medical and industrial areas. For this purpose, different concentrations of micro-sized EAF slag (0, 20, 40, 60, 80, 100, 500, and 800 phr) were incorporated as fillers in the natural rubber (NR) matrix to produce the shielding composites. In addition, nano-sized EAF slag particles were prepared by using a high-energy ball milling technique to investigate the effect of particle size on the gamma-radiation shielding properties. The synthesized micro and nano EAF/NR composites were tested as protective materials against gamma-radiation by employing NaI(Tl) scintillation detector and standard radioactive point sources (152Eu, 137Cs, 133Ba, and 60Co). Different shielding parameters such as linear and mass attenuation coefficient, half value layer (HVL), tenth value layer, mean free path, effective atomic number (Zeff), and effective electron density (Neff) were determined to assess the radiation shielding capability of the EAF/NR composites. Furthermore, equivalent atomic number (Zeq) and the exposure buildup factor values for photon energy in the range from 0.015 to 15 MeV were also computed by Geometric Progression method. The experimental results of micro EAF/NR composites showed that at 121.78 keV, EAF0 composite (without EAF slag content) had the lowest µ value of 0.1695 cm-1, while the EAF800 composite (which was loaded with 800 phr of micro EAF slag) had the highest µ value of 0.2939 cm-1 at the same energy, which in turn decreases the HVL from 4.09 to 2.36 cm, respectively. Therefore, increasing the filler weight fractions of EAF slag in the NR matrix, increases the shielding properties of the composites. Moreover, the NR composite reinforced with 800 phr of nano EAF slag has better gamma-radiation shielding efficiency compared to that filled with 800 phr of micro EAF slag. The success of this work was to prepare a flexible, lightweight, low-cost, and lead-free material with better shielding capability.

Prevalence of High-Risk HPV Subtypes and Efficacy of the HPV Vaccine in Preventing Cervical Epithelial Lesions: Survey and Insights from a German Study.

BACKGROUND: Historically, cervical cytology has been the standard method for detecting dysplastic cervical changes. However, extensive research has established that human papillomavirus (HPV) infection is a primary cause of these changes, necessitating a shift in screening and preventive strategies towards the molecular detection of high-risk HPV subtypes. To combat HPV infection, prophylactic vaccines have been developed, including the nonavalent, quadrivalent, and bivalent vaccines. An essential criterion for an effective HPV vaccine is to provide comprehensive coverage against the most prevalent high-risk HPV types associated with cervical cancer, ensuring optimal efficacy in preventing cervical lesions. Long-term protection against these types is crucial for effective prevention strategies; Material and Methods: A cohort of 210,510 women's samples was included in the analysis conducted within one year of implementing a screening program in Germany. The screening program involved the molecular detection of high-risk HPV subtypes, targeting specific age groups. The cohort comprised 63,710 women below 35 years of age and 146,800 women aged 35 years and above. The selection of high-risk HPV subtypes followed the guidelines provided by Becton-Dickinson. This study focused exclusively on cases with a documented history of vaccination, which were categorized into two main groups: Group I consisted of vaccinated individuals under 35 years old (12,765 cases), while Group II comprised vaccinated individuals aged 35 years and above (296 cases); Results: The HPV types HPV56/59/66 were found to be widely distributed across all age groups, with certain age groups exhibiting a higher incidence compared to HPV16 and HPV18. Similarly, HPV35/39/69, along with HPV31 and HPV45, were also observed to have a broad distribution among women. The incidence of high-grade squamous intraepithelial lesions (HSIL), including both CIN2 and CIN3, varied between 0.076% and 0.5% across all age groups, regardless of the individuals' vaccination status; Aim of the study: Our study provides valuable insights into the distribution, incidence, and prevalence of various high-risk HPV subtypes, including HPV56/59/66, HPV33/58, HPV35/39/68, and HPV45, in relation to precancerous cervical lesions. These subtypes are not adequately covered by the currently available HPV vaccines. Addressing the discrepancies between the prevalent HPV subtypes and existing vaccines is crucial in developing an ideal HPV vaccine that offers comprehensive protection. Tailoring screening programs and vaccination strategies to the local distribution of HPV subtypes is essential for effective prevention. By raising awareness and implementing targeted preventive measures, including vaccination, we can significantly reduce the incidence of precancerous and cancerous cervical lesions.

A New Environmentally Friendly Mortar from Cement, Waste Marble and Nano Iron Slag as Radiation Shielding.

Improving mortar shielding properties to preserve environmental and human safety in radiation facilities is essential. Conventional cement mortars, composed of cement, water, and lime aggregate, are crucial for radiation shielding. Using recycled aggregates to produce new mortar and concrete compositions has attracted the attention of several researchers. In the current study, waste marble and iron slag as aggregates are used to create novel cement mortar compositions to study the aggregate's impact on the radiation attenuation capability of the mortar. Three mortar groups, including a control mortar (CM-Ctrl), were prepared based on cement and waste marble. The other two groups (CM-MIS, CM-NIS), contained 25% iron slag at different particle sizes as a replacement for a waste marble. The study aims to compare iron slag in their micro and nano sizes to discuss the effect of particle size on the mortar radiation capability. For this purpose, the NaI scintillation detector and radioactive point sources (241Am, 133Ba, 137Cs, 60Co, and 152Eu) were utilized to measure several shielding parameters, such as the linear attenuation coefficient (LAC), mass attenuation coefficient (MAC), half-value layer (HVL), tenth-value layer (TVL), and mean free path (MFP), for the produced mortars at different photon energies. Furthermore, the transmission electron microscope (TEM) is used to measure the particle size of the aggregates. In addition, a scanning electron microscope (SEM) is utilized to acquire the cross-section morphologies of the prepared mortars. According to our findings, mortars prepared with nano-iron slag and waste marble offered superior shielding capabilities than mortars containing natural sand or fine crushed stone. The nano iron slag mortar can be utilized in place of typical sand mortar for applications as rendering or plastering materials for building medical diagnostic and CT scanner rooms, due to its improved shielding abilities.

Enhancing the Gamma-Radiation-Shielding Properties of Gypsum-Lime-Waste Marble Mortars by Incorporating Micro- and Nano-PbO Particles.

In the current study, the gamma-radiation-shielding characteristics of novel gypsum-lime-waste marble-based mortars reinforced with micro-PbO and nano-PbO powders were investigated. In total, seven mortar groups, including a control mortar (named GLM), were prepared. The other groups contained10, 20, and 30 wt.% of both micro-PbO and nano-PbO as a waste marble replacement. This study aimed to explore the effect of particle size and concentrations of PbO powders on the γ-ray-shielding capability of GLM mortars. For this purpose, an HPGe detector and five standard radioactive point sources (241Am, 133Ba, 137Cs, 60Co, and 152Eu) were employed to measure different shielding parameters, including the linear attenuation coefficient (µ), mass attenuation coefficient (µm), mean free path (MFP), half-value layer (HVL), and tenth-value layer (TVL), for the prepared samples in the energy range between 59.53 keV to 1408.01 keV. On the basis of µm values, other significant shielding parameters such as effective atomic number (Zeff), effective electron density (Neff), equivalent atomic number (Zeq), and exposure buildup factor (EBF) were also computed to explore the potential usage of the proposed mortars as radiation protective materials. The results reported that the smallest HVL, TVL, and MPF, as well as the largest attenuation values, were obtained for mortars reinforced by nano-PbO compared to those containing micro-PbO. It can be concluded from the results that the mortar samples containing nano-PbO had a remarkably improved gamma-radiation-shielding ability. Thus, these mortars can be used for radiation shielding on walls in nuclear facilities to reduce the transmitted radiation dose.

Nano tin oxide/dimethyl polysiloxane reinforced composite as a flexible radiation protecting material.

Reinforced polymer composites are a recent type of advanced shielding material that has been studied experimentally and theoretically. This work described the protection properties of silicon rubber filled with nano and micro tin oxide (II). These shielding materials are evaluated by parameters such as mass attenuation coefficient, linear attenuation coefficient, mean free path, effective atomic number, and buildup factor. The morphology and mechanical properties of silicon rubber, which is reinforced with tin oxide (II) particles in terms of weight fraction and size, have been studied. The results explain that the mass attenuation coefficient increases as tin oxide (II) concentration increases at a particular photon energy. It was found that the shielding properties of nano tin oxide (II) composites are more effective than micro tin oxide (II) composites against gamma rays. The effective atomic number values increase by increasing tin oxide (II) and so on equivalent atomic number. On the other hand, increasing tin oxide (II) weight fraction led to an increase in buildup factor maximum, which proved that tin oxide (II) concentration has significant effectiveness in radiation protection.

Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance.

PURPOSE: The antibody-drug conjugate enfortumab vedotin (EV) releases a cytotoxic agent into tumor cells via binding to the membrane receptor NECTIN-4. EV was recently approved for patients with metastatic urothelial carcinoma (mUC) without prior assessment of the tumor receptor status as ubiquitous NECTIN-4 expression is assumed. Our objective was to determine the prevalence of membranous NECTIN-4 protein expression in primary tumors (PRIM) and patient-matched distant metastases (MET). EXPERIMENTAL DESIGN: Membranous NECTIN-4 protein expression was measured (H-score) by IHC in PRIM and corresponding MET (N = 137) and in a multicenter EV-treated cohort (N = 47). Progression-free survival (PFS) after initiation of EV treatment was assessed for the NECTIN-4-negative/weak (H-score 0-99) versus moderate/strong (H-score 100-300) subgroup. The specificity of the NECTIN-4 IHC staining protocol was validated by establishing CRISPR-Cas9-induced polyclonal NECTIN-4 knockouts. RESULTS: In our cohort, membranous NECTIN-4 expression significantly decreased during metastatic spread (Wilcoxon matched pairs P < 0.001; median H-score = 40; interquartile range, 0-140), with 39.4% of MET lacking membranous NECTIN-4 expression. In our multicenter EV cohort, absence or weak membranous NECTIN-4 expression (34.0% of the cohort) was associated with a significantly shortened PFS on EV (log-rank P < 0.001). CONCLUSIONS: Membranous NECTIN-4 expression is frequently decreased or absent in mUC tissue. Of note, the clinical benefit of EV strongly depends on membranous NECTIN-4 expression. Thus, our results are of highest clinical relevance and argue for a critical reconsideration of the current practice and suggest that the NECTIN-4 receptor status should be determined (ideally in a metastatic/progressive lesion) before initiation of EV. See related commentary by Aggen et al., p. 1377.

Distribution and incidence of atypical glandular lesions in cervical cytology focusing on the association with high-risk human papillomavirus subtypes.

Adenocarcinoma in situ (AIS) is considered a precursor of adenocarcinoma. Cervical adenocarcinoma has been associated with human papillomavirus (HPV), while other subtypes of AIS and endocervical adenocarcinoma have no precursor lesions and are not associated with HPV. Cervical cytology and HPV genotyping are important in the detection of these different subtypes. Notably, endometrial lesions and infiltration with secondary adenocarcinoma may lead to misdiagnosis of endocervical lesions. The aim of the present study was to avoid misdiagnosis of squamous cell changes and endometrial lesions as endocervical lesions in cervical screening. A total of 210,510 female cytological samples were analyzed between the beginning of January 2020 and the beginning of January 2021. The samples were processed for conventional cytological techniques, and for molecular detection and subtyping of high-risk HPV (HPV-HR) according to the advice and measurements of BD Biosciences (117,765 samples) and the PapilloCheck® HPV test (5,579 samples). The present study was carried out in Germany using the Munich classification III. II-g (Bethesda classification: atypical glandular cells not otherwise specified) was detected in 0.12% of cases under the age of 35 years. Another peak was noticed within the 41-60-years age group (0.11%). In the 41-50-years age group, a peak for II-e (Bethesda classification: Endometrial cells) (1.5%) was identified. An association was revealed between HPV16, HPV18 and HPV45 with cervical intraepithelial neoplasia III, AIS, endocervical adenocarcinoma and squamous cell carcinoma, in addition to other HPV-HR subtypes, such as HPV33/58, as well as 52, 56/59/66 in the different age groups. In patients aged <35 years, 0.03% of cases were vaccinated cases against HPV. In the 35-40-years age group, there was only one vaccinated case (0.0045%); in the 41-50-years age group, there were 11 vaccinated cases (0.031%); and in the 51-60-years age group, there was one vaccinated case (0.002%). No patients aged >60 years were vaccinated against HPV in the analyzed cohort. In conclusion, most cases of HPV-associated glandular dysplastic changes and neoplasia occurred in sexually active women aged between 35 and 60 years. In addition, endocervical adenocarcinoma may occur at any age with or without an HPV infection.

Bioaccumulation, Biosedimentation, and Health Hazards of Elements in Crayfish, Procambarus clarkii from El-Rahawi Drain and El-Qanatir in the River Nile, Egypt.

Elements accumulation in crayfish is proportional to the increase in bioavailability (direct contact) with the surrounding water, sediment, and feeding. Five heavy metals (Cu, Cr, Mn, Ni, and Ag) and lithium (Li) were analyzed in the sediment, water, and crayfish tissues. Elements (heavy metals and lithium) concentrations in sediment, water, and crayfish tissues showed significant differences between the two sampling stations (El-Qanatir and El-Rahawi drain). However, the levels of elements in crayfish tissues were arranged in declining order as hepatopancreas > gills > exoskeleton > muscles for Cu and Cr; hepatopancreas > exoskeleton > gills > muscles for Ni and Ag; and exoskeleton > gills > hepatopancreas > muscles for Li and Mn. The human health hazard evaluation of heavy metals and lithium exposure via edible tissue consumption was assessed for both children and adult consumers. The target hazard quotient THQ values of crayfish edible tissues (less than 1) will not impose any health implications for consumers who ingest edible tissues in sufficient quantities. Furthermore, the hazard index (HI) values reported for children and adult consumers were lower than one, indicating non-carcinogenic and carcinogenic hazards, suggesting that crayfish edible tissues are safe for human ingestion. This evidence also found that Procambarus clarkii could be a good bio-indicator organism for monitoring potentially metals in aquatic systems.

Effect of Kaolin Clay and ZnO-Nanoparticles on the Radiation Shielding Properties of Epoxy Resin Composites.

The use of radiation is mandatory in modern life, but the harms of radiation cannot be avoided. To minimize the effect of radiation, protection is required for the safety of the environment and human life. Hence, inventing a better shield than a conventional shielding material is the priority of researchers. Due to this reason, this current research deals with an innovative shielding material named EKZ samples having a composition of (epoxy resin (90-40) wt %-kaolin clay (10-25) wt %-ZnO-nano particles (0-35) wt %). The numerous compositional variations of (epoxy resin, kaolin clay, and ZnO-nano particles on the prepared EKZ samples varied the density of the samples from 1.24 to 1.95 g/cm3. The radiation shielding parameter of linear attenuation coefficient (LAC), half value layer (HVL), tenth value layer (TVL), and radiation protection efficiency (RPE) were measured to evaluate the radiation diffusion efficiency of newly made EKZ samples. These radiation shielding parameters were measured with the help of the HPGe detector utilizing the three-point sources (Am-241, Cs-137, and Co-60). The obtained results exposed that the value of linear attenuation coefficient (LAC) and radiation protection efficiency (RPE) was maximum, yet the value of half value layer (HVL), and tenth value layer (TVL), were minimum due to the greater amount of kaolin clay and ZnO-nanoparticles, whereas the amount of epoxy resin was lesser. In addition, it has been clear that as-prepared EKZ samples are suitable for low-dose shielding applications as well as EKZ-35 showed a better shielding ability.

HPV-genotyping versus conventional cervical cytology as a screening method to detect dysplastic cervical epithelial changes.

The world health organization (WHO) called for coordinated global action in 2018 to eliminate cervical cancer, ensuring that every woman is screened and treated for precancerous lesions (World Health Organization. Cervical cancer: an NCD we can overcome. Geneva, 2018. http://www.who.int/director-general/speeches/detail/cervical-cancer-an-ncd-we-can-overcome.tegy ). Cytology-based screening has been for decades the conventional method of screening. Ancillary techniques have been added like immunocytochemistry with P16/Ki67 and L1-Capsid, but these methods require maintenance of complex infrastructure and highly trained personnel as well as relatively short screening intervals. HPV-based screening method to detect high-risk groups is a faster and automated method, which does not need morphologically highly qualified personal with high social costs. In the study, we have focused on the distribution of cervical lesions in the age groups with concordance of detection HPV high-risk subtypes (HPV-HR) and on the safety of the screening method. In the Institute for Pathology and Cytology-Schuettorf-Leer-Germany 146.800 samples of women from the age of and above 35 years were analyzed between the beginnings of 2020 until the beginning of 2021. 63.710 cases under 35 years old were analyzed. The samples were processed for both conventional cytological techniques and for molecular detection and subtyping of HPV-HR according to the advice and measurements of BD-manufacture. In this study, we have studied the histopathological results (Table 2) after colposcopy according to the age subgroups. The histopathological results were subdivided into no dysplasia, cervical intraepithelial neoplasia I (CIN I), cervical intraepithelial neoplasia II (CIN II), cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (Sq.c.c), adenocarcinoma in situ (AIS), endometrial carcinoma, endocervical adenocarcinoma and cases without biopsy during the colposcopy (COB). We have used the muenchener classification III (Table 3) as a subgrading system for the cytological specimens. The frequency of detecting HPV56/59/66 is higher as detecting HPV-16 and HPV18 in age groups under 35 years old, 41-50 years old and 51-60 years old. HPV16 is detected higher in age groups 35-40 years old and above 60 years. The incidence of high squamous intraepithelial lesions (CIN II and III) is 0.92% in age group 35-40 years, 0.54% in age under 35 years, 0.59% in age group 41-50 years old, 0.35% in age group 51-60 years old and 0.15% in age group above 60 years old. There is no significance (p value = 0.4060). Low grade cervical lesions (CIN I) were 0.13% (< 35 Ys), 0.35% (35-40 Ys), 0.36% (41-50 Ys), 0.25% (51-60 Ys) and 0.098% (> 60Y s), which was statistically significant (p value = 0.04,0.60). Without dysplasia 0.19% (< 35 Ys), 0.5% (35-40 Ys), 0.56% (41-50 Ys), 0.51 (51-60 Ys) and 0.26% (> 60 Ys). There is no significance between occurrence of cervical dysplasia and without dysplasia despite of detection of HPV-HR subtypes (p value = 0.1754). The only use of HPV-subtyping is not a secure method and a protective way for women. There are worldwide many HPV-positive cases, which have been psychologically impaired with higher costs, although they have no cervical epithelial changes during the HPV-infection. There are many HPV-negative cases, in some studies up to 13% of cases, which develop cervical cancer. We have the opinion and are convinced that the screening should be both morphologically via cytological examination and may be with adding immunocytochemistry to detect the really dysplastic cervical lesions. HPV-subtyping may be added every three years to detect the concomitant subtype.