Primary Site Research Articles

Understanding the Impacts of Presystemic Metabolism on the Human Oral Bioavailability of Chemicals.

Animal-free new approach methods promote chemical assessments based on the comparison between in vitro bioactivity and human internal concentrations, which necessitates a dependable knowledge of human oral bioavailability, i.e., the fraction of an orally ingested chemical that escapes from presystemic ("first-pass") metabolic processes and eventually enters systemic circulation. Using a physiologically based toxicokinetic model, we show how human oral bioavailability is impacted by presystemic metabolism within the gut lumen, gut wall, and liver and how this impact differs among chemicals with various permeability and stability properties. Our results highlight the gut lumen as a primary site of presystemic metabolism of certain chemicals, such as di-2-ethylhexyl phthalate (DEHP), for which the gut lumen may even exceed the liver in importance of presystemic metabolism due to these metabolic processes occurring in sequence. For chemicals with low transmembrane permeability and low stability, metabolism within the gut lumen is the most remarkable of the three presystemic metabolic processes. Notably, for chemicals that undergo substantial metabolism within the gut lumen, where the metabolites have high permeability, there is a notable discrepancy between the "theoretical bioavailability" (bioavailability of the unchanged parent compound) and the "apparent bioavailability" in measurement practices (bioavailability inferred from measured metabolites). Our work highlights the importance of considering presystemic metabolism, notably within the gut lumen, in human exposure and toxicokinetic modeling.

Metastasis to the External Auditory Canal: A Systematic Review.

To systematically review the literature and understand the behavior, diagnosis, management, and mortality of metastasis to the external auditory canal (EAC). PubMed/Medline, EMBASE, Web of Science. Studies from 1948 to June 2023 describing metastasis to the EAC were included. Non-English literature was excluded. Data extraction: Study design, age, sex, pathology, primary site, staging, additional sites of metastasis, time to EAC metastasis from diagnosis, time from diagnosis of EAC metastasis to death, symptoms, exam and imaging findings, and management. Data were synthesized qualitatively with means calculated. Thirty-two studies met the criteria, totaling 37 patients with EAC metastasis. Mean age was 58 years; 73% were male. The most common pathologies were adenocarcinoma (37.8%), acute myelogenous leukemia (8.1%), and renal cell carcinoma (8.1%). Sites of primary malignancy were hematologic (10.8%), breast (8.1%), esophagus (8.1%), renal (8.1%), and prostate (8.1%). Within the temporal bone, 73% had isolated EAC metastasis. Median time to EAC metastasis from the diagnosis of primary malignancy was 18 months. Metastasis to the EAC was the first presentation of malignancy in 21.6% of patients. Median time to death was 4.5 months. Symptoms included hearing loss (59.5%), otalgia (27.0%), otorrhagia (24.3%), facial paralysis (21.6%), otorrhea (16.2%), and aural fullness (13.5%). On imaging, bony erosion was present in 50% of cases. Treatment was primarily palliative with excision and radiation. EAC metastasis has a distinct presentation from other temporal bone subsites. Early biopsy to establish a diagnosis and intervene is critical.

Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease

The mechanisms underlying lipid metabolic disorders in Parkinson's diseases (PD) remain unclear. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify PD-related modular genes and differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from Molecular Signatures Database. Candidate genes were assessed with overlapping modular genes, DEGs, and LMRGs for the purpose of building protein–protein interaction (PPI) networks. Then, biomarkers were generated by machine learning and Backpropagation Neural Network development according to candidate genes. Biomarker-based enrichment and network modulation analyses were executed to investigate related signaling pathways. Following dimensionality reduction clustering and annotation, scRNA-seq was submitted to cellular interactions and trajectory analysis to analyze regulatory mechanisms of critical cells. Finally, qRT-PCR was conducted to confirm the expression of biomarkers in PD patients. Four biomarkers (MSMO1, ELOVL6, AACS, and CERS2) were obtained and highly predictive after analysis mentioned above. Then, OPC, Oli, and Neu cells were the primary expression sites for biomarkers according to scRNA-seq studies. Finally, we confirmed mRNA of MSMO1, ELOVL6 and AACS were downregulated in PD patients comparing with control, while CERS2 was upregulated. In conclusion, MSMO1, ELOVL6, AACS, and CERS2 related to LMRGs could be new biomarkers for diagnosing and treating PD.

Establishment of nomogram to predict overall survival and cancer-specific survival of local tumor resection in patients with colorectal cancer liver metastasis with unresectable metastases: a large population-based analysis

Background and PurposeThe tumour-node metastasis (TNM) classification is a common model for evaluating the prognostic value of tumour patients. However, few models have been used to predict the survival outcomes of patients with colorectal cancer liver metastasis (CRLM) with unresectable metastases who received the primary local surgery. Thus, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to establish novel nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of these patients.MethodsExtracted primary data on CRLM patients by local surgery from SEER database. All prognostic factors of OS and CSS were determined by Cox regression analysis. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were used to further evaluate the accuracy and discrimination of these nomograms. Decision curve analysis (DCA) was executed to evaluate the nomograms for the clinical net benefit. Risk stratification analysis (RSA) was used to evaluate the reliability of them in clinical.Results3622 eligible patients were screened and assigned to training cohort (1812) or validation cohort (1810). The age, chemotherapy, tumour grade, primary tumour site, tumour size, lymph node positive rate (LNR), marital status, and carcinoembryonic antigen (CEA) were independent prognostic factors of OS. Additionally, the age, chemotherapy, tumour grade, primary tumour site, tumour size, LNR, and CEA were independent prognostic factors of CSS. The results of C-indexes and ROC curves indicated that the established nomograms exhibited better discrimination power than TNM classification. The calibration curves demonstrated excellent agreement between the predicted and actual survival rates for 1-, 3-, and 5 year OS and CSS. Meanwhile, the validation cohort demonstrated similar results. Background the clinic context, the DCA showed that these nomograms have higher net benefits, and the RSA showed that patients were further divided into low risk, medium risk, and high risk groups according to the predicted scores from nomograms. And, the Kaplan–Meier curve and log-rank test showed that the survival differences among the three groups are statistically significant.ConclusionsThe prognostic nomograms showed very high accuracy, identifiability, and clinical practicality in predicting the OS and CSS of CRLM patients with unresectable metastases treated by local surgery at 1-, 3-, and 5 years, which might improve individualized predictions of survival risks and help clinicians formulate treatment plans.

Network meta-analysis of adjuvant chemotherapy in biliary tract cancers: Setting the scene for new randomized evidence.

The best adjuvant chemotherapy for resected biliary tract cancer (BTC) is under debate, with capecitabine supported by weak evidence. Aim of this network meta-analysis is to estimate the efficacy of different phase II/III regimens, comparing monotherapies (gemcitabine or fluoropyrimidines) head-to-head, against observation and combination regimens. A comprehensive literature search was conducted on PubMed and EMBASE for phase II/III randomized clinical trials (RCTs) available as of December 2023, reporting hazard ratios (HRs) of overall survival (OS) and event-free survival (EFS). A frequentist framework employing a random-effects model was applied; treatment rankings were outlined according to P-score, based on direct and indirect evidence. Exploratory subgroup analyses for OS were also performed (primary site, resected margin status and nodal involvement). Six RCTs (1979 total patients) were identified. Fluoropyrimidine monotherapy showed significantly better OS (HR .84 [.72-.97]) and EFS (HR .79 [.69-.91]) than observation, as any monotherapy did (HR .84 [.74-.96]; HR .79 [.70-.89]). In the head-to-head comparison for OS, only S1 confirmed to be superior to observation alone (HR .69 [.49-.98]) while fluoropyrimidines achieved the best P score (.81), similarly to any monotherapy (0.92). Combinations failed to prove superior to monotherapies with respect both to OS and EFS. Subgroup analyses were inconclusive due to results' inconsistency and limited sample size. Our work confirmed that adjuvant chemotherapy grants OS and EFS benefit for resected BTC patients. Fluoropyrimidines appeared the most effective option, confirming capecitabine as the preferred choice for the Western population.

NQO1 Triggers Neutrophil Recruitment and NET formation to Drive Lung Metastasis of Invasive Breast Cancer.

Metastasis to the lungs is a leading cause of death for breast cancer patients. Therefore, effective therapies are urgently needed to prevent and treat breast cancer lung metastasis In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in breast cancer patients.

Intramedullary Metastases to Conus Medullaris: A Review of the Literature with a Case Illustration.

Introduction: Intramedullary metastases to the conus medullaris spinalis (IMCM) pose a rare problem in neurosurgical oncology and are usually encountered as a complicated clinical scenario in the setting of advanced systemic malignancy with poor overall survival. Despite the progress in interdisciplinary oncological care, their management remains complicated. Research Question: We performed a PRISMA-guided literature search to achieve a pooled analysis of all previously reported IMCM cases that contained detailed clinical data on this problem to investigate the currently employed management options and respective outcomes. We obtained a clinical vignette and performed a comprehensive narrative review of IMCM management. Materials and Methods: The PubMed/MEDLINE/Google Scholar, Cochrane and Embase databases were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All relevant publications retrieved were subjected to full-text analysis in detail and pertinent information was extracted. Results: The most common systemic primary tumor site as the origin of IMCM was the lung, followed by the breast. Overall, the pooled median survival was 6 months (range 0.5-36 months). Patients who received both surgery and radiation therapy had the longest overall survival (OS) (mean 9.9 months) and those who received no oncological treatment (neither surgery nor adjuvant therapy) had the shortest OS (mean 3.6 months). In cases where surgical resection was performed as part of the treatment plan for metastases, those with partial tumor resection had a more favorable neurological outcome than patients who underwent aggressive gross total resection. Conclusions: Based on the results of our analysis, we find that diligent microsurgical resection (subtotal or total) followed by radiation therapy appears as an effective and suitable treatment in select patients with IMCM. When surgery is not feasible as part of the treatment algorithm, radiation therapy alone (conventional or radiosurgery) also appears to be a suitable treatment option that confers a benefit to the patient.

Race, Gender, Sexuality, and the Pursuit of Modernity: British Biopower and Female Sexuality in Domestic and Colonial Practice

This paper explores how female sexuality became a primary site for the exercise of British biopolitical regulation as illustrated both in colonial Hong Kong and Singapore, and in domestic practice within the metropole. The application of biopolitical regulation on the subject of female sexuality was based on a discursive production making indissociable the success of the imperial project and the survival of the imperial race and the control of the female body. This discursive production mobilized intersections of race, class, gender, and sexuality through the Victorian cult of domesticity, resulting in a racialization of female sexuality with implications transcending the permeable frontier between the metropole and the colonies. Making “the prostitute” the exemplar of deviant, dangerous, and immoral sexuality had discursive repercussions for female sexuality more broadly; explained in contrast to “the prostitute,” the construction of sexual deviance had implications for understandings of sexual conformity and acceptability both in Victorian society and abroad.

Synchronous or selective removal of nitrate and Cr(VI) by montmorillonite supported sulfidized nanoscale zerovalent iron: Role of Fe(II) and S0

The reduction process of Cr(VI) and NO3−-N by sulfidized nanoscale zerovalent iron (S-nZVI) under coexistence conditions has yet to be investigated. This study innovatively confirmed that NO3−-N and Cr(VI) could be reduced synchronously or selectively by synthesizing diverse montmorillonite-supported S-nZVI (S-nZVI@MMT) to meet different remediation requirements. Concretely speaking, S-nZVI@MMT at low S/Fe could synchronously reduce NO3−-N and Cr(VI) to NH4+-N and Cr(III). S-nZVI@MMT at high S/Fe selectively removed Cr(VI). The vital roles of Fe(II) and S0 in S-nZVI@MMT were clearly revealed. Fe(II) mainly involved in the generation of Fe3O4 during the reaction at low S/Fe, while participating in the transformation of amorphous phases of Fe3O4, FeS, and FeS2 at high S/Fe. The Fe0 and converted Fe3O4 were the primary reactive sites for the synchronous removal of NO3−-N and Cr(VI) while the surface-bound Fe(II) and converted amorphous phases of Fe3O4 and FeSx determined the selective removal of Cr(VI). Meanwhile, the high contents of S0 in S-nZVI@MMT at high S/Fe mediated the generation of FeSx during the reaction and blocked the adsorption and reduction of NO3−-N which was critical for the selective removal of Cr(VI). The variations in the reactive species of S-nZVI@MMT at different S/Fe led to discrepant Cr(VI) reaction pathways. The findings provided new insights and strategies for the practical applicability of S-nZVI. SynopsisStudy provides a new insight into the synchronous/selective removal of Cr(VI) and NO3−-N by S-nZVI to meet the remediation requirements for different application scenarios.

Capturing low-concentration benzene: Design and mechanism of high-performance Cu1-Ox,Ny-C single-atom adsorbents

Common adsorbents, such as active carbons, zeolites, and metal–organic frameworks (MOFs), struggle to capture low concentrations of benzene. Single-atom adsorbents (SAAs), boasting exceptional atomic utilization efficiency and precisely tailored electronic structures, offer a promising solution. This study first designed Cu1-Ox,Ny-C SAAs and explored their enhanced benzene adsorption through density functional theory (DFT). Particularly, a crucial link between the SA coordination configuration and its affinity for benzene was established. Next, Cu1-Ox,Ny-C was synthesized from the MOF MIL-101(Cr) and extensively characterized using high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) and X-ray absorption fine structure (XAFS) spectroscopy, etc. to determine the coordination configuration of Cu single atoms. Finally, a thorough evaluation of the Cu1-Ox,Ny-C’ capacity and stability was conducted. Theoretical analysis revealed that Cu single atoms within the Ox,Ny-C matrix act as the primary adsorption sites for benzene. Notably, O and N atoms work synergistically: oxygen atoms promote adsorption, while nitrogen atoms mainly stabilize single-atom sites. Cu1-Ox,Ny-C was successfully synthesized, and characterization revealed that Cu1-O2,N2(trans)-C and Cu1-O3,N1-C were the dominant coordination configurations. Remarkably, despite a fourfold decrease in specific surface area compared to MIL-101(Cr), Cu1-Ox,Ny-C exhibited a threefold increase in chemisorption capacity for low-concentration benzene. Moreover, it exhibits excellent resistance to H2O and can be effectively reused. This study demonstrates a valuable strategy for designing and creating highly efficient SAAs for capturing low concentrations of benzene.

Heterogeneity or change in cell of origin in diffuse large B-cell lymphomas determined using hans algorithm

This study aimed to analyze the heterogeneity or change in cell of origin (COO) in diffuse large B-cell lymphoma (DLBCLs) using the Hans algorithm including 156 patients with multiple DLBCL specimens. COO was detected via immunohistochemical staining for CD10, BCL6, and MUM1. The COO of the main tumor at initial diagnosis was germinal center B-cell (GCB) and non-GCB type in 50 (32%) and 106 (68%) patients, respectively. It did not change in 126 patients (81%). However, it changed in 30 patients (19%), from GCB to non-GCB in 12 patients and vice versa in 18 patients. The COO was heterogeneous or changed in 14% of simultaneous samples at other sites during the initial diagnosis, in 7% of primary refractory sites, and in 20% of samples obtained in the relapse phase other than the primary site. Changes in CD10, BCL6, and MUM1 expression were observed in 15%, 23%, and 24% samples, respectively. A low incidence of change in COO was observed in DLBCL with CD10+/BCL6+/MUM1- (4%), CD10-/BCL6-/MUM1+ (3%), and CD10-/BCL6-/MUM1- (0%) patterns, whereas DLBCL with other patterns showed COO changes at rates of 20–37%. In conclusion, COO was heterogeneous or changed in 19% of DLBCL cases. The COO should be re-examined in other biopsy samples to determine the optimal treatment.

A Comprehensive Review of In vitro Testing and Emerging Strategies Employed in Anticancer Drug Discovery Therapy

Cancer is a broad category of diseases characterized through the unchecked proliferation and dissemination of atypical cells. It is among the primary causes of morbidity and mortality globally. The multistage genesis of cancer, which begins with genetic abnormalities that cause normal cells to become malignant, is what gives cancer its complexity. There are several steps involved in the genesis of cancer, including six key cancer distinguishing features known to influence malignant change has been identified. Anticancer drug development is a laborious process that includes numerous in vitro, in vivo, and clinical trials. In vitro assays provide a foundation for cancer medication development techniques. Numerous in vitro procedures and tests have been developed to analyze every defining aspect of cancer; the choice of a specific in vitro technique or assay is largely based on the research question(s) under investigation. Currently, oncology researchers are attempting to create cancer nanomedicines that are both safe and effective. While nanoparticles have opened up new therapeutic and diagnostic avenues, stem cell treatment has demonstrated potential usefulness in renewing and repairing defective or damaged tissues by tackling primary and metastatic cancer sites. With minimal harm to healthy cells, targeted therapy has the potential to stop the development and propagation of specific cancer cells. In place of open surgery, ablation therapy has become a popular minimally invasive method for destroying or freezing tumors. Naturally occurring antioxidants have demonstrated the ability to find free radicals and counteract their harmful effects, potentially treating or preventing cancer. A number of novel technologies have previously received authorization, and some are presently the subject of clinical trials. This review article's objective is to provide an extensive overview of the state of our knowledge on cancer, covering its causes, kinds, diagnosis, therapy, in vitro assays to screen cancer and most recent scientific developments.

Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC): Cancer Survivors' Perspective Through In-Depth Interviews.

CRS/HIPEC patients face unique quality of life (QoL) challenges due to advanced disease (peritoneal carcinomatosis), the extent of procedure, and risk for long-term complications. Standard QoL questionnaires are generic, focusing on tumor type and standard treatments, and likely do not capture this select population's full experience, suggesting the need for tailored instruments. We aimed to characterize the QoL challenges faced by CRS/HIPEC cancer survivors and determine whether these were captured by astandard QoL questionnaire. An anonymous, semi-structured individual interview was conducted with CRS/HIPEC patients addressing their experience at diagnosis, challenges related to CRS/HIPEC, and access to CRS/HIPEC information. Verbatim transcripts were interpreted using thematic analysis. Code and theme identification was inductive. Questions addressing common themes that were not encompassed by astandard QoL questionnaire were developed. We interviewed eight patients. Median age was 55 (range 30-71) years and 75% (n = 6) were women. Primary tumor sites included appendix (n = 4), ovarian (n = 3), and peritoneal mesothelioma (n = 1). Median time from CRS/HIPEC was 40.1 (range 3.1-216.3) months. Overall, 133 codes were identified and categorized into 9 themes. The most recurring were physical symptoms after CRS/HIPEC (specifically gastrointestinal symptoms), adjusting to survivorship, mental health, expectations from CRS/HIPEC, and access to care. A total of 22 questions that did not overlap with a standardized QoL questionnaire were developed. There is an unmet need to understand the unique QoL challenges CRS/HIPEC patients encounter. Patient-centered QoL questionnaires based on CRS/HIPEC patient experiences can capture these unique challenges and help guide future studies and care.

Demographic, health and socioeconomic characteristics related to lung cancer diagnosis: a population analysis in New South Wales, Australia

BackgroundLung cancer is a major cause of health loss internationally, and in Australia. Most of that loss is inequitably concentrated among vulnerable or disadvantaged people and amenable to prevention and earlier detection. In response, best practice lung cancer care considers peoples’ background, circumstances and care needs. Comprehensive, person level descriptions of demographic, health and discrete socio-economic disadvantage related factors are therefore required to inform best practice. We examine population wide correlations of demographic, health and socioeconomic characteristics with lung cancer diagnosis for use in cancer control programs, including screening.MethodsA study of 5,504,777 (89.9%) adults living in New South Wales and participating in Australia’s Census in August 2016 with subsequent follow-up to the end of 2018. The Australian Bureau of Statistics’ (ABS) person-level integrated data asset linked census records with the NSW population cancer registry which includes primary site. Our study compared census participants who did not experience cancer in the follow-up period with those diagnosed with lung cancer, (n = 6160 and ICD10 C33-34). Outcomes are expressed as the adjusted relative odds (aOR) of incident lung cancer among adults in the community and measured using multi-variable logistic regression models. Validated ABS methods informed categorisation of social and economic variables.ResultsMultivariable comparison of those with lung cancer and those without a first cancer diagnosis (3276 lung cancers among 2,484,145 males; 2884 lung cancers among 2,944,148 females) showed associations with increasing age, varying ancestry, living alone (aOR = 1.30 95% CI 1.19–1.42 males; 1.24 95% CI 1.14–1.35 females), number of health conditions medicated, less than Year 12 education (aOR = 1.40 95% CI 1.30–1.51 males; 1.37 95% CI 1.27–1.48 females) and housing authority rental (aOR = 1.69 95% CI 1.48–1.94 males; 1.85 95% CI 1.63–2.11 females). Additional associations occurred among males with low income, disabilities before age 70, those unemployed and labouring occupations. As numbers of characteristics increased, so did the likelihood of lung cancer.ConclusionWe provided a population wide description of characteristics relevant to lung cancer diagnosis. Deeper knowledge of these characteristics inform continuing development of lung cancer programs in prevention (e.g. tobacco control) and detection (e.g. lung cancer screening), then help prioritise targeted delivery of those programs.

Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: focus on mitochondrial dysfunction.

As a vital component of blood vessels, endothelial cells play a key role in maintaining overall physiological function by residing between circulating blood and semi-solid tissue. Various stress stimuli can induce endothelial injury, leading to the onset of corresponding diseases in the body. In recent years, the importance of mitochondria in vascular endothelial injury has become increasingly apparent. Mitochondria, as the primary site of cellular aerobic respiration and the organelle for "energy information transfer," can detect endothelial cell damage by integrating and receiving various external stress signals. The generation of reactive oxygen species (ROS) and mitochondrial dysfunction often determine the evolution of endothelial cell injury towards necrosis or apoptosis. Therefore, mitochondria are closely associated with endothelial cell function, helping to determine the progression of clinical diseases. This article comprehensively reviews the interconnection and pathogenesis of mitochondrial-induced vascular endothelial cell injury in cardiovascular diseases, renal diseases, pulmonary-related diseases, cerebrovascular diseases, and microvascular diseases associated with diabetes. Corresponding therapeutic approaches are also provided. Additionally, strategies for using clinical drugs to treat vascular endothelial injury-based diseases are discussed, aiming to offer new insights and treatment options for the clinical diagnosis of related vascular injuries.

A prognostic framework for predicting lung signet ring cell carcinoma via a machine learning based cox proportional hazard model

PurposeSignet ring cell carcinoma (SRCC) is a rare type of lung cancer. The conventional survival nomogram used to predict lung cancer performs poorly for SRCC. Therefore, a novel nomogram specifically for studying SRCC is highly required.MethodsBaseline characteristics of lung signet ring cell carcinoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression and random forest analysis were performed on the training group data, respectively. Subsequently, we compared results from these two types of analyses. A nomogram model was developed to predict 1-year, 3-year, and 5-year overall survival (OS) for patients, and receiver operating characteristic (ROC) curves and calibration curves were used to assess the prediction accuracy. Decision curve analysis (DCA) was used to assess the clinical applicability of the proposed model. For treatment modalities, Kaplan-Meier curves were adopted to analyze condition-specific effects.ResultsWe obtained 731 patients diagnosed with lung signet ring cell carcinoma (LSRCC) in the SEER database and randomized the patients into a training group (551) and a validation group (220) with a ratio of 7:3. Eight factors including age, primary site, T, N, and M.Stage, surgery, chemotherapy, and radiation were included in the nomogram analysis. Results suggested that treatment methods (like surgery, chemotherapy, and radiation) and T-Stage factors had significant prognostic effects. The results of ROC curves, calibration curves, and DCA in the training and validation groups demonstrated that the nomogram we constructed could precisely predict survival and prognosis in LSRCC patients. Through deep verification, we found the constructed model had a high C-index, indicating that the model had a strong predictive power. Further, we found that all surgical interventions had good effects on OS and cancer-specific survival (CSS). The survival curves showed a relatively favorable prognosis for T0 patients overall, regardless of the treatment modality.ConclusionsOur nomogram is demonstrated to be clinically beneficial for the prognosis of LSRCC patients. The surgical intervention was successful regardless of the tumor stage, and the Cox proportional hazard (CPH) model had better performance than the machine learning model in terms of effectiveness.

Second primary malignancy for early-stage head and neck squamous cell carcinoma by SEER17 registries.

Investigating treatment modalities' association with second primary malignancy risk in early-stage head and neck squamous cell carcinoma (HNSCC). Data of 5-year survivors of early-stage (stages I-II, seventh TNM staging manual) HNSCC from 2000 to 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio and excess absolute risk were used to assess second primary malignancy (SPM) development externally. Relative risk was estimated to compare SPM risk within groups. Fine-Gray's model estimated cumulative incidence of second primary malignancy. Overall, 8957 5-year survivors with early-stage HNSCC were enrolled. Patients receiving definitive radiotherapy had poorer survival than surgery patients. Surgery correlated with lower risk of second primary malignancy (RR = 0.89, 95% CI 0.80-0.99), especially for oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39-0.82). Differences in the risk of second primary malignancy among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect risk of second primary malignancy within each subgroup. Surgery led to better survival and lower risk of second primary malignancy compared to definitive radiotherapy in 5-year survivors. Incidence and sites of second primary malignancy varied by primary sites, emphasizing targeted long-term surveillance's importance.

Solder scavenging from hole-and-cap food cans in the Western Australian goldfields: Identifying site modification processes

Site modification via large and dense can dumps dating from the gold rushes of the 1880s and later in the Western Australian goldfields may profoundly affect the archaeological interpretation of these sites. A can dump has been examined in the abandoned campground of Muslim cameleers that dated from the 1892 gold rush to after the First World War. Here, can dumps comprising hundreds of cans, stacked up and in mutual contact and without other artefacts such as bottles, were not all the unmodified remains of meals and camps of transient people. This work presents a geochemical technique applied to soil samples around these dumps, showing high levels of tin and lead contamination, inconsistent with the underlying geology and similar to the composition of the solder used to seal the cans. This is consistent with the written reminiscences of a family supplementing its income by scavenging solder from hole-and-cap food cans over the period 1894–1909. This process of site modification by solder scavenging must be considered before food-can distribution patterns can be interpreted in terms of primary site occupation.

Glucagon Clearance is Decreased in Chronic Kidney Disease, but Preserved in Liver Cirrhosis.

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n =16), individuals with Child-Pugh A-C cirrhosis (n = 16) and matched control individuals (n = 16), before, during and after a 60-minute glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) both compared to individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and to control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] minutes) compared to individuals with cirrhosis (5.7 [5.2;6.3] minutes, P = 0.002) and control individuals (5.7 [5.2;6.3] minutes, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, chronic kidney disease, but not liver cirrhosis leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.

Comparing the Microbiome of the Adenoids in Children with Secretory Otitis Media and Children without Middle Ear Effusion.

The adenoids, primary sites of microbial colonization in the upper airways, can influence the development of various conditions, including otitis media with effusion (OME). Alterations in the adenoid microbiota have been implicated in the pathogenesis of such conditions. This study aims to utilize 16S rRNA genetic sequencing to identify and compare the bacterial communities on the adenoid surfaces of children with OME and children with healthy middle ears. Additionally, we seek to assess the differences in bacterial diversity between these two groups. We collected adenoid surface swabs from forty children, divided into two groups: twenty samples from children with healthy middle ears and twenty samples from children with OME. The V3-V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Alpha and beta diversity indices were calculated, and statistical analyses were performed to identify significant differences in bacterial composition. Alpha diversity analysis, using Pielou's index, revealed significantly greater evenness in the bacterial communities on the adenoid surfaces of the healthy ear group compared with the OME group. Beta diversity analysis indicated greater variability in the microbial composition of the OME group. The most common bacterial genera in both groups were Haemophilus, Fusobacterium, Streptococcus, Moraxella, and Peptostreptococcus. The healthy ear group was primarily dominated by Haemophilus and Streptococcus, whereas the OME group showed higher abundance of Fusobacterium and Peptostreptococcus. Additionally, the OME group exhibited statistically significant higher levels of Alloprevotella, Peptostreptococcus, Porphyromonas, Johnsonella, Parvimonas, and Bordetella compared with the healthy ear group. Our study identified significant differences in the bacterial composition and diversity on the adenoid surfaces of children with healthy middle ears and those with OME. The OME group exhibited greater microbial variability and higher abundances of specific bacterial genera. These findings suggest that the adenoid surface microbiota may play a role in the pathogenesis of OME. Further research with larger sample sizes and control groups is needed to validate these results and explore potential clinical applications.