Search

Recent studies in social endocrinology have explored the effects of social relationships on female reproductive steroid hormones-estradiol and progesterone-investigating whether they are suppressed in partnered and parous women. Results have been mixed for these hormones although evidence is more consistent that partnered women and women with young children have lower levels of testosterone. These studies were sequential to earlier research on men, based on Wingfield's Challenge Hypothesis, which showed that men in committed relationships, or with young children, have lower levels of testosterone than unpartnered men or men with older or no children. The study described here explored associations between estradiol and progesterone with partnership and parity among women from two different ethnicities: South Asian and white British. We hypothesized that both steroid hormones would be lower among partnered and/or parous women with children ≤3 years old, regardless of ethnicity. In this study we analyzed data from 320 Bangladeshi and British women of European origin aged 18 to 50 who participated in two previous studies of reproductive ecology and health. Levels of estradiol and progesterone were assayed using saliva and/or serum samples and the body mass index calculated from anthropometric data. Questionnaires provided other covariates. Multiple linear regressions were used to analyze the data. The hypotheses were not supported. We argue here that, unlike links between testosterone and male social relationships, theoretical foundations for such relationships with female reproductive steroid hormones are lacking, especially given the primary role of these steroids in regulating female reproductive function. Further longitudinal studies are needed to explore the bases of independent relationships between social factors and female reproductive steroid hormones., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: While many aspects of female ovarian function respond to environmental stressors, estradiol (E2) appears less sensitive to stressors than progesterone, except under extreme ecological conditions. However, earlier studies relied on saliva samples, considered less sensitive than blood. Here, we investigated E2 variation among 177 Bangladeshi and UK white women, aged 35-59, using single serum samples. Bangladeshi women either grew up in Sylhet, Bangladesh (exposed to poor sanitation, limited health care, and higher pathogen loads but not poor energy availability), or in the UK., Methods: We collected samples on days 4-6 of the menstrual cycle in menstruating women and on any day for post-menopausal women. Participants included: (i) Bangladeshi sedentees (n = 36), (ii) Bangladeshis who migrated to the UK as adults (n = 52), (iii) Bangladeshis who migrated as children (n = 40), and (iv) UK white women matched for neighborhood residence to the migrants (n = 49). Serum was obtained by venipuncture and analyzed using electrochemiluminescence. We collected anthropometrics and supplementary sociodemographic and reproductive data through questionnaires. We analyzed the data using multivariate regression., Results: E2 levels did not differ between migrant groups after controlling for age, BMI, physical activity, psychosocial stress, parity, and time since last birth (parous women). Paralleling results from salivary E2, serum E2 did not differ among women who experienced varying developmental conditions., Conclusion: Our results reinforce the hypothesis that E2 levels are stable under challenging environmental conditions. Interpopulation variation may only arise under chronic conditions of extreme nutritional scarcity, energy expenditure, and/or high disease burdens., (© 2021 Wiley Periodicals LLC.)

Background: High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (cHPV-DNA) has demonstrated high sensitivity and specificity in patients with locally advanced cervix cancers. We hypothesised that cHPV-DNA is detectable in early invasive cervical cancers but not in pre-invasive lesions (CIN)., Methods: Blood samples were collected from patients with CIN ( n = 52) and FIGO stage 1A-1B CC ( n = 12) prior to treatment and at follow-up. DNA extraction from plasma, followed by NGS, was used for the detection of cHPV-DNA., Results: None of the patients with pre-invasive lesions were positive for CHPV-DNA. In invasive tumours, plasma from one patient (10%) reached the threshold of positivity for cHPV-DNA in plasma., Conclusion: Low detection of cHPV-DNA in early CC may be explained by small tumour size, poorer access to lymphatics and circulation, and therefore little shedding of cHPV-DNA in plasma at detectable levels. The detection rate of cHPV-DNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies lacks adequate sensitivity for clinical utility.

Objectives: This study examined the association of minority religious identification (Hindu or Muslim) with self-reported stress and psychological symptoms among sedentee and immigrant Bangladeshi women., Methods: Women, aged 35-59 (n = 531) were drawn from Sylhet, Bangladesh and London, England. Muslim immigrants in London and Hindu sedentees in Sylhet represented minority religious identities. Muslim sedentees in Sylhet and Londoners of European descent represented majority religious identities. In bivariate analyses, minority religious identity was examined in relation to self-reported measures of stress, nervous tension, and depressed mood. Logistic regression was applied to examine the relationship between these variables while adjusting for marital status, parity, daily walking, and perceived financial comfort., Results: In bivariate analyses, religious minorities reported more stress than religious majorities in all group comparisons (p < .05), and minority Muslims reported more nervous tension and depressed mood than majority Muslims (p < .05). In logistic regression models, minority Muslims had greater odds of high stress than majority Muslims (OR 2.00, 95% CI 1.18-3.39). Minority Muslims had greater odds of stress (OR 3.05, 95% CI 1.51-6.17) and nervous tension (OR 3.37, 95% CI 1.66-6.87) than majority Londoners. Financial comfort reduced odds of stress and symptoms in all models., Conclusions: Socioeconomic situation, immigration history, and minority ethnicity appear to influence the relationship between religious identity and psychosomatic symptoms in Bangladeshi women. Attention to personal and socioeconomic context is important for research examining the association between religion and mental health., (© 2024 Wiley Periodicals LLC.)

Despite prevention strategies, cervical cancer remains a significant public health issue. Human papillomavirus plays a critical role in its development, and early detection is vital to improve patient outcomes. The incidence of cervical cancer is projected to rise, necessitating better diagnostic tools. Traditional screening methods like the cytological examination and human papillomavirus testing have limitations in sensitivity and reproducibility. Liquid-based cytology offers some improvements, but the need for more reliable and sensitive techniques persists, particularly for detecting precancerous lesions. Liquid biopsy is a non-invasive method that analyzes cancer-derived products in biofluids like blood, offering potential for real-time monitoring of tumor progression, metastasis, and treatment response. It can be based on detection of circulating tumor cells (CTCs), circulating free DNA (cfDNA), and microRNAs (miRNAs). This review particularly underlines the potential of microRNAs, which are transported by extracellular vesicles. Overall, this article underscores the importance of continued research into non-invasive diagnostic methods like liquid biopsy to enhance cervical cancer screening and treatment monitoring. [ABSTRACT FROM AUTHOR]

Lynch syndrome, one of the most common genetic syndromes predisposing to cancer, is associated with a series of malignant conditions, among which the most frequent is colorectal cancer, but gynecologic cancers (especially endometrial) are also quite common. Despite the significant progress made in understanding this condition over time, there are still aspects in managing this condition that have not demonstrated clear benefits. This article aims to summarize the recommendations of international societies and present the latest developments in managing Lynch syndrome, focusing on gynecologic cancer screening and possible prevention strategies. Advances in genetic testing procedures and discoveries related to the association between oncological pathology frequency and the affected pathogenic variant type will probably lead to personalized medicine focused on the individual patient in the coming years. Although various screening methods for gynecological cancers in patients with Lynch syndrome have been used over time, they have not shown significant survival benefits. This highlights the need for studying and implementing new screening and diagnostic methods, which have been under investigation in recent years and are mentioned in this article. [ABSTRACT FROM AUTHOR]

Background: In current scenario breast cancer measured as one of the dangerous health issues. An effective therapeutic class of drug known as aromatase inhibitors (AIs) is dominant against estrogen receptorpositive breast cancer. However, there is an urgent need to create target-specific AIs with better anti-breast cancer profiles due to the increased toxicity and adverse effects related to currently existing anti-breast cancer drugs., Objectives: In the present study, we have designed of 100 novel tiazole analogues as aromatase inhibitors their pharmacophoric features were explored., Method: Molecular docking was applied to a series of 4-substituted-1, 2, 3-triazoles containing letrozole for their aromatase inhibitory effects. The aromatase inhibitory activity of the compound in a series varies in the range of (IC 50 = 0.008-31.26 μM). A hydrogen atom positioned at R1 of the triazole ring in compound (01) was responsible for the most potent compound (IC 50 = 0.008 μM) in the series of 28 compounds as compared to letrozole. The self-organizing molecular field study was used to assess the molecular characteristics and biological activities of the compounds. The four models were developed using PLS and MLR methods. The PLS method was good for statistical analysis. The letrozole scaffold-based 100 compounds were designed by selecting an effective pharmacophore responsible for aromatase inhibitory activity. The designed compound was placed on the previous model as a test set, and its IC 50 values were calculated., Result: Hydrogen bonds were established between the potent molecule (01) and the essential residues Met 374 and Arg 115, which were responsible for the aromatase-inhibiting action. Cross-validated q2 (0.6349) & noncross- validated r2 (0.7163) were discovered in the statistical findings as having reliable predictive power. Among 100 designed compounds, seven compounds showed good aromatase inhibitory activities., Conclusion: The additional final SOMFA model created for the interactions between the aromatase and the triazole inhibitors may be helpful for future modification and enhancement of the inhibitors of this crucial enzyme., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To evaluate the performance of stool methylated syndecan2 (mSDC2), methylated septin9 (mSEPT9), fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in detecting colorectal neoplasia and adenomas. Methods: Blood-borne CEA, CA125, and CA199 levels were measured by electrochemiluminescence. The SDC2 methylation was detected by Methylation Detection Kit for Human SDC2 Gene (Real time PCR), and the SEPT9 methylation was detected by the Septin9 Gene Methylation Detection Kit based on PCR fluorescent probe assay. The colonoscopy combined with tissue biopsy pathology was used as a validation criterion for colorectal neoplasia. Results: In detecting colorectal neoplasia, the AUCs of mSDC2, FOBT and mSEPT9 were 0.935 (95% CI: 0.915-0.956, P<0.001), 0.824 (95% CI: 0.617-1.000, P<0.001) and 0.671 (95% CI: 0.511-0.831, P<0.001), respectively. The sensitivity of mSDC2, FOBT and mSEPT9 were 100.0%, 66.7% and 40.0%, respectively. But the AUC of CEA, CA125 and CA199 were not statistically significant for colorectal neoplasia (all P>0.05). The combined application of mSEPT9 and mSDC2 showed the best predictive performance (AUC: 0.956, 95% CI: 0.887~1.000). For adenomas, the AUC of FOBT was extremely low (AUC: 0.524, 95% CI: 0.502-0.545, P=0.004). The CEA, CA125, CA199, mSEPT9 and mSDC2 were not statistically significant in detecting adenomas (all P>0.05). Conclusions: For individual tests, FOBT and mSDC2 are relatively better indicators for detecting colorectal neoplasia compared to mSEPT9, CEA, CA125 and CA199. The combined form of mSEPT9 and mSDC2 to detect colorectal neoplasia has good predictive performance. However, none of these indicators demonstrated significant predictive power for detecting adenomas in our study. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer. Patients and methods: The clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients. Results: About 377 (87.27%) of the 432 patients had AR expression. No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470–21.569), PR (OR = 7.690, 95%CI: 3.974–16.129, Her-2 (OR = 10.489, 95%CI: 2.779–23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031–0.377 were significant independent risk factors affecting AR expression. Conclusions: AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer. [ABSTRACT FROM AUTHOR]

Background: The grim (<10% 5-year) survival rates for pancreatic ductal adenocarcinoma (PDAC) are attributed to its complex intrinsic biology and most often late-stage detection. The overlap of symptoms with benign gastrointestinal conditions in early stage further complicates timely detection. The suboptimal diagnostic performance of carbohydrate antigen (CA) 19–9 and elevation in benign hyperbilirubinaemia undermine its reliability, leaving a notable absence of accurate diagnostic biomarkers. Using a selected patient cohort with benign pancreatic and biliary tract conditions we aimed to develop a data analysis protocol leading to a biomarker signature capable of distinguishing patients with non-specific yet concerning clinical presentations, from those with PDAC. Methods: 539 patient serum samples collected under the Accelerated Diagnosis of neuro Endocrine and Pancreatic TumourS (ADEPTS) study (benign disease controls and PDACs) and the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, healthy controls) were screened using the Olink Oncology II panel, supplemented with five in-house markers. 16 specialized base-learner classifiers were stacked to select and enhance biomarker performances and robustness in blinded samples. Each base-learner was constructed through cross-validation and recursive feature elimination in a discovery set comprising approximately two thirds of the ADEPTS and UKCTOCS samples and contrasted specific diagnosis with PDAC. Results: The signature which was developed using diagnosis-specific ensemble learning demonstrated predictive capabilities outperforming CA19-9, the only biomarker currently accepted by the FDA and the National Comprehensive Cancer Network guidelines for pancreatic cancer, and other individual biomarkers and combinations in both discovery and held-out validation sets. An AUC of 0.98 (95% CI 0.98–0.99) and sensitivity of 0.99 (95% CI 0.98–1) at 90% specificity was achieved with the ensemble method, which was significantly larger than the AUC of 0.79 (95% CI 0.66–0.91) and sensitivity 0.67 (95% CI 0.50–0.83), also at 90% specificity, for CA19-9, in the discovery set (p = 0.0016 and p = 0.00050, respectively). During ensemble signature validation in the held-out set, an AUC of 0.95 (95% CI 0.91–0.99), sensitivity 0.86 (95% CI 0.68–1), was attained compared to an AUC of 0.80 (95% CI 0.66–0.93), sensitivity 0.65 (95% CI 0.48–0.56) at 90% specificity for CA19-9 alone (p = 0.0082 and p = 0.024, respectively). When validated only on the benign disease controls and PDACs collected from ADEPTS, the diagnostic-specific signature achieved an AUC of 0.96 (95% CI 0.92–0.99), sensitivity 0.82 (95% CI 0.64–0.95) at 90% specificity, which was still significantly higher than the performance for CA19-9 taken as a single predictor, AUC of 0.79 (95% CI 0.64–0.93) and sensitivity of 0.18 (95% CI 0.03–0.69) (p = 0.013 and p = 0.0055, respectively). Conclusion: Our ensemble modelling technique outperformed CA19-9, individual biomarkers and indices developed with prevailing algorithms in distinguishing patients with non-specific but concerning symptoms from those with PDAC, with implications for improving its early detection in individuals at risk. Author summary: Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates among cancers, primarily due to its complex biology and late-stage diagnosis. Early symptoms often mimic benign gastrointestinal conditions, complicating timely detection. The standard biomarker, carbohydrate antigen (CA) 19–9, is not reliable due to its suboptimal performance and elevation in benign conditions, highlighting the need for better diagnostic tools. In our study, we aimed to develop a biomarker signature to distinguish between benign pancreatic/biliary conditions and PDAC using serum samples from the Accelerated Diagnosis of neuro Endocrine and Pancreatic Tumours and UK Collaborative Trial of Ovarian Cancer Screening studies. We screened 539 patient serum samples with state-of-the-art biomarker panels and developed a robust predictive signature by applying specialized machine learning methods. This new signature significantly outperformed CA19-9 and other panels reported in the literature. Our findings suggest that this new biomarker signature can improve early detection of PDAC in patients with ambiguous clinical symptoms, potentially leading to better outcomes for those at risk. [ABSTRACT FROM AUTHOR]

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMECs) at 2.5% w/v, and it was found that MH reduced the proliferation of MCF-7 cells but not that of HMECs. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, the effects of MH induced the activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose-dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro, which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions. [ABSTRACT FROM AUTHOR]

Aim: The prognosis of high-risk, locally advanced cervical cancer (LACC) remains poor following concurrent chemoradiotherapy (CCRT). We investigated whether the effect of CCRT can be enhanced by programmed cell death protein 1 (PD-1) inhibitor. Methods: A retrospective cohort study was conducted to compare the efficacy and safety of CCRT group (n = 82) and PD-1 inhibitor plus CCRT group (n = 70). Results: Compared with the CCRT group, the PD-1 inhibitor plus CCRT group had significantly higher objective response rate, median progression-free survival, leukopenia and fatigue. The addition of PD-1 inhibitor to CCRT showed a favorable trend in overall survival without statistical significance. Conclusion: PD-1 inhibitor plus CCRT presented a significant survival benefit and a manageable safety profile in high-risk LACC. Article highlights The prognosis of high-risk locally advanced cervical cancer (LACC) (FIGO 2014 stage IB2–IIB with positive para-aortic lymph nodes and stage IIIA–IVA) remains poor after concurrent chemoradiotherapy (CCRT). Programmed death ligand-1 (PD-1) inhibitors have shown efficacy in patients with cervical cancer, and whether the effect of CCRT can be enhanced by PD-1 inhibitor is a hot topic in high-risk LACC research. This retrospective cohort study was conducted to compare the efficacy and safety of CCRT alone (n = 82 patients) and PD-1 inhibitor plus CCRT (n = 70 patients). Compared with the CCRT-alone group, the PD-1 inhibitor plus CCRT group had a significantly higher objective response rate and median progression-free survival (PFS) but also higher incidence of leukopenia and fatigue. The addition of PD-1 inhibitor to CCRT showed a favorable trend in overall survival (OS) without statistical significance. Compared with the PD-L1-negative subgroup, PFS (p = 0.002) and OS (p = 0.032) in the PD-L1-positive subgroup were significantly improved. Multivariate analysis showed that total radiotherapy duration >56 days (hazard ratio [HR]: 4.799), FIGO 2009 stage IVA (HR: 6.464), and combined PD-1 inhibitor (HR: 0.324) were independent determinants of disease progression. PD-1 inhibitor plus CCRT presented a significant survival benefit and a manageable safety profile in high-risk LACC. It can be considered as a new alternative treatment for this patient population. The effects of different timing of PD-1 inhibitor combination with radiotherapy and different duration of PD-1 inhibitor maintenance therapy on survival outcomes need to be further explored in future studies. This is an exploratory study that adds to the literature on high-risk LACC and PD-1 inhibitor, prospective studies are needed to determine the value of PD-1 inhibitor plus CCRT for high-risk LACC. [ABSTRACT FROM AUTHOR]

Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age‐related disease. Ninety‐eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24–86 years). We used nonlinear and penalized regression to model CA and time to all‐cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type‐2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all‐cause mortality. Seven‐fold cross‐validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8–9 years). Metabolomic age models, adjusted for CA, were associated with C‐reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29–0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is one of the deadliest gynecological cancers worldwide. Human papillomavirus is the main etiological agent responsible for the initiation and development of most CC cases. The standard method utilized for CC screening in the global population is the cytological Pap smear test. Despite its effective validity in detecting precancerous lesions and its response to layer stages of this disease, greater screening and diagnostic reliability are needed, as well as an improvement in specificity and sensitivity. In this context, the use of liquid biopsies, like blood, for the isolation of circulating tumor DNA (ctDNA) in CC screening, diagnosis, prognosis, and surveillance could fill the gaps that still exist. In the present review, we aim to study the literature in order to collect knowledge on blood-based liquid biopsy based on descriptions of its precious molecular content and its utilization as a potential tool for CC patients' management. We will mainly focus on the important role of the novel ctDNA and the unique possibilities to additionally use HPV-ctDNA in CC at various stages of clinical application. [ABSTRACT FROM AUTHOR]

Purpose: Carcinoembryonic antigen (CEA) is an important prognostic factor for rectal cancer. This study aims to introduce a novel cutoff point for CEA within the normal range to improve prognosis prediction and enhance patient stratification in rectal cancer patients., Methods: A total of 316 patients with stages I to III rectal cancer who underwent surgical tumor resection were enrolled. The Cox proportional hazards regression model was used to evaluate the impact of preoperative CEA level and other co-variates on overall survival (OS). The Youden Index method was used for CEA optimal cutoff estimation., Results: The mean follow-up period was 46.47 months. In risk-adjusted Cox proportional analysis, higher preoperative CEA levels (HR 1.17, CI 1.131.21; P < 0.001), and T-stage were associated with poor OS. The mean preoperative CEA level was significantly higher in patients with positive lymphovascular invasion (LVI) and perineural invasion (PNI) (CI: 1.06-2.45 and 0.75-2.33, respectively, P < 0.001, t test). Pathologic complete response (pCR) occurred in 71 (22.4%) cases. Patients with pCR had lower levels of preoperative CEA than non-pCR group (P = 0.002, CEA pCR -CEA nonpCR  =  - 1.3; t test). Using Youden Index, the estimated optimal CEA cutoff value for predicting OS was 2.8 ng/mL (sensitivity 90%; specificity 78.5%). Lower preoperative CEA levels predict higher pCR rates, aiding patient stratification and planning., Conclusion: Preoperative CEA may play a role in the prediction of pCR in rectal cancer. Considering the CEA level of 2.8 ng/ml, as a newly defined cutoff point, patients with a worse prognosis can be identified prior to operation. PNI, along with LVI as independent predictors, may be contemplated as prognostic indicators to improve treatment strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

One of the greatest challenges in modern gynecological oncology is ovarian cancer. Despite the numerous studies currently being conducted, it is still sometimes detected at late clinical stages, where the prognosis is unfavorable. One significant contributing factor is the absence of sensitive and specific parameters that could aid in early diagnosis. An ideal screening test, in view of the low incidence of ovarian cancer, should have a sensitivity of greater than 75% and a specificity of at least 99.6%. To enhance sensitivity and specificity, diagnostic panels are being created by combining individual markers. The drive to develop better screening tests for ovarian cancer focuses on modern diagnostic methods based on molecular testing, which in turn aims to find increasingly effective biomarkers. Currently, researchers' efforts are focused on the search for a complementary parameter to those most commonly used that would satisfactorily enhance the sensitivity and specificity of assays. Several biomarkers, including microRNA molecules, autoantibodies, cDNA, adipocytokines, and galectins, are currently being investigated by researchers. This article reviews recent studies comparing the sensitivity and specificity of selected parameters used alone and in combination to increase detection of ovarian cancer at an early stage. [ABSTRACT FROM AUTHOR]

Background: N6-methyladenosine (m6A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6A levels in CRC. Methods: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6A levels and the expression of m6A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model. Results: PB RNA m6A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased. Conclusions: PB RNA m6A levels are a potential diagnostic biomarker for patients with CRC. [ABSTRACT FROM AUTHOR]

Purpose: The preoperative diagnosis of endometriosis associated ovarian cancer (EAOC) remains challenging for lack of effective diagnostic biomarker. We aimed to study clinical characteristics and develop a nomogram for diagnosing EAOC before surgery. Methods: A total of 87 patients with EAOC and 348 patients with ovarian endometrioma (OEM) were enrolled in our study. Least absolute shrinkage and selection operator (LASSO) regression and Logistic regression were utilized to select variables and construct the prediction model. The performance of the model was assessed using receiver operating characteristic (ROC) analyses and calibration plots, while decision curve analyses (DCAs) were conducted to assess clinical value. Bootstrap resampling was used to evaluated the stability of the model in the derivation set. Results: The EAOC patients were older compared to the OEM patients (46.41 ± 9.62 vs. 36.49 ± 8.09 year, P < 0.001) and proportion of postmenopausal women was higher in EAOC group than in the OEM group (34.5 vs. 1.5%, P < 0.001). Our prediction model, which included age at diagnosis, tumor size, cancer antigen (CA) 19–9 and risk of ovarian malignancy algorithm (ROMA), demonstrated an area under the curve (AUC) of 0.858 (95% confidence interval (CI): 0.795–0.920) in the derivation set (N = 304) and an AUC of 0.870 (95% CI: 0.779–0.961) in the validation set (N = 131). The model fitted both the derivation (Hosmer–Lemeshow test (HL) chi-square = 12.600, P = 0.247) and the validation (HL chi-square = 8.210, P = 0.608) sets well. Conclusion: Compared to patients with OEM, those with EAOC exhibited distinct clinical characteristics. Our four-variable prediction model demonstrated excellent performance in both the derivation and validation sets, suggesting its potential to assist with preoperative diagnosis of EAOC. [ABSTRACT FROM AUTHOR]

BACKGROUND The establishment of maternal–fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal–fetal interface and their associations with pathological processes. OBJECTIVE AND RATIONALE This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal–fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal–fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed. SEARCH METHODS A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal–fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included. OUTCOMES The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal–fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal–fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal–fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groundwork for further exploration of glycans in reproductive biology under both physiological and pathological conditions. WIDER IMPLICATIONS A deep understanding of the functions of glycan structures would provide insights into the molecular mechanisms underlying their involvement in the physiological and pathological regulation of early pregnancy. Glycans may also potentially serve as novel early predictive markers and therapeutic targets for repeated implantation failure, pregnancy loss, and other pregnancy complications. [ABSTRACT FROM AUTHOR]

High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. This paper reviews the classic and novel risk factors for HGSOC and methods of diagnosis and prediction, including serum biomarkers, the liquid biopsy of circulating tumor cells or circulating tumor DNA, epigenetic markers, exosomes, and genomic and proteomic biomarkers. The novel future complex approach to ovarian cancer diagnosis should be devised based on these findings, and the general outcome of such an approach is proposed and discussed in the paper. [ABSTRACT FROM AUTHOR]

Background/Aim: Circulating tumor DNA (ctDNA), which is shed from cancer cells into the bloodstream, offers a potential minimally invasive approach for cancer diagnosis and monitoring. This research aimed to assess the preoperative ctDNA levels in ovarian tumors patients' plasma and establish correlations with clinicopathological parameters and patient prognosis. Patients and Methods: Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/ml and variant allele frequency. Results: Somatic mutations were found in 24 tumor samples, 17 of which were from ovarian cancer patients. The most frequently mutated gene was TP53. Preoperative plasma ctDNA levels were detected in 14 of the 24 patients. With higher stage, plasma ctDNA mutant concentration increased (p for trend <0.001). The overall survival of cancer patients with more than 10 ctDNA mutant copies/ml in plasma was significantly worse (p=0.008). Conclusion: Pre-operative ctDNA measurement in ovarian cancer patients' plasma holds promise as a predictive biomarker for tumor staging and prognosis. [ABSTRACT FROM AUTHOR]

Background: Methylated stool DNA (sDNA) is a reliable noninvasive biomarker for early colorectal cancer (CRC) diagnosis. However, there are barely any diagnostic panels that can achieve both a sensitivity and specificity exceeding 90% simultaneously., Objective: We aimed to identify a novel methylated sDNA panel and model for the early diagnosis of CRC., Methods: We conducted methyl-CpG binding domain isolated genome sequencing (MiGS) on CpG island methylation phenotype (CIMP)-positive (n = 3) and CIMP-negative CRC tissues (n = 3) and their corresponding normal adjacent tissues. Subsequently, by utilizing both the aforementioned data and public datasets, we identified a set of promising methylated sDNA markers for CRC. Next, we validated 5 of these genes using pyrosequencing in CRC patients (n = 31). Then, we developed a combined diagnostic model (CDM) for CRC based on the methylation status of PRDM12, FOXE1, and SDC2 by a Training cohort (n = 231). Finally, the performance of CDM was evaluated in an independent multicenter Validation cohort (n = 800)., Results: A total of 1062 participants were included in this study. The area under the curve (AUC) of the CDM was 0.979 (95% CI: 0.960-0.997), and the optimal sensitivity and specificity were 97.35% and 99.05%, respectively, in the training cohort (n = 231). In the independent validation cohort (n = 800), the AUC was 0.950 (95% CI: 0.927-0.973), along with the optimal sensitivity of 92.75% and specificity of 97.21%. When CRC and advanced adenoma (AAD) were used as diagnostic targets, the model AUC was 0.945 (95% CI: 0.922-0.969), with an optimal sensitivity of 91.89% and a specificity of 95.21%. The model sensitivity for nonadvanced adenoma patients was 68.66%., Conclusion: The sDNA diagnostic model CDM, developed from both CIMP-P and CIMP-N, exhibited exceptional performance in CRC and could serve as a potential alternative strategy for CRC screening., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Human papillomavirus (HPV) has emerged as a significant contributor to cancer incidence globally, particularly in the context of oropharyngeal squamous cell carcinoma (OPSCC) and cancer of unknown primary (HNCUP). This study aimed to develop and validate droplet digital PCR (ddPCR) assays for the detection of circulating tumor HPV DNA (ctHPV-DNA) in plasma, focusing on high-risk HPV genotypes associated with these cancers., Methods: ddPCR assays for HPV16, 18, 33, 35, 56, and 59 were developed and tested using gBlocks, HPV cell-free DNA, fragmented tumor HPV+ DNA, and plasma samples from patients with HPV+ OPSCC (n = 110) and HNCUP (n = 9)., Results: Assays demonstrated robust technical sensitivity across all tested HPV genotypes. Clinical application of the assays on a cohort of patients with HPV+ OPSCC and HNCUP revealed high sensitivity (91.6%) and wide variability in ctHPV-DNA levels. Analyses revealed correlations between ctHPV-DNA levels and TNM stage and tumor viral load. The association between ctHPV-DNA and tumor viral load persisted even after adjusting for TNM stage. At posttreatment, 72.5% of samples had reached undetectable ctHPV-DNA levels. Having detectable ctHPV-DNA posttreatment was associated with a higher ctHPV-DNA level at diagnosis and higher viral load at diagnosis., Conclusion: The findings underscore the potential of ctHPV-DNA as a biomarker for monitoring HPV+ cancers and offer insights into tumor dynamics. Implementation of these assays in clinical practice could enhance no-invasive treatment monitoring and recurrence detection in HPV-associated cancers., Clinical Trials: NCT05904327., (© 2024. The Author(s).)

To construct a nomogram for overall survival (OS) in colorectal cancer. Using Cox univariate and multivariate analysis, significant variables were plotted into a nomogram. The predictive accuracy and discriminative ability of the nomogram was determined using the concordance index (C-index), receiver operator characteristic curve and calibration curve. CA125 and tumor node metastasis (TNM) were identified as independent predictors for OS in colorectal cancer patients. Area under the curve (AUC) for 1, 3, and 5 years was 0.89, 0.723, and 0.71 respectively in primary cohort, and C-index was 0.702 (95% CI, 0.610 to 0.794) in validation cohort, which indicated a middle degree of accuracy. High-quality calibration plots were seen in the OS nomogram models. Age, CA125, and TNM were identified as poor predictors of colorectal cancer. This nomogram is a valuable predictive tool for the prognosis of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the diagnostic performance of carcinogenic antigen (CA) 125, (HE)-4 (Human epididymis protein 4), and ultrasound (International Ovarian Tumor Analysis [IOTA]) Simple Rules individually and to derive a composite score in the differentiating ovarian cancer from benign ovarian mass. Subjects and Methods: Consecutive patients (n = 100) with pelvic mass admitted during February 2018-August 2019 were included prospectively. Patients with either known case of epithelial ovarian cancer (EOC) or metastatic EOC were excluded. The primary outcome was to assess the sensitivity and specificity of CA-125, HE-4, and IOTA Simple Rules in predicting benign from malignant mass independently, while secondary outcome was derivation of a new model incorporating these variables using multivariate logistic regression analysis to predict benign from malignant lesions. Receiver operator curve (ROC) was drawn to redefine the best-performing cutoff values and difference between area under the ROC (AUROC) were compared by DeLong's method. Results: Out of 100 cases of adnexal mass selected, the sensitivity and specificity of CA-125 were 73.8% and 77.6%, HE-4 were 90.5% and 87.9%, and IOTA Simple Rules were 92.9% and 81.0%. CA-125, HE-4, and IOTA Simple Rules were independently associated with the likelihood of malignancy/borderline (P < 0.001). The area under the curve for the "composite score" (AUC = 0.93) was the highest and was significantly better than that of CA-125 (AUC = 0.786) (P = 0.004 using DeLong's test) and comparable with HE-4 (AUROC = 0.90; P = 0.128 using DeLong's Test). Conclusion: The sensitivity and specificity of HE-4 and IOTA Simple Rules for predicting malignant ovarian tumor was better than those of CA-125. The diagnostic performance of "composite score" was comparable to those of either HE-4 or IOTA Simple Rules and significantly better than CA-125. [ABSTRACT FROM AUTHOR]

AGR2 is a secreted protein widely existing in breast. In precancerous lesions, primary tumors and metastatic tumors, the expression of AGR2 is increased, which has aroused our interest. This review introduces the gene and protein structure of AGR2. Its endoplasmic reticulum retention sequence, protein disulfide isomerase active site and multiple protein binding sequences endow AGR2 with diverse functions inside and outside breast cancer cells. This review also enumerates the role of AGR2 in the progress and prognosis of breast cancer, and emphasizes that AGR2 can be a promising biomarker and a target for immunotherapy of breast cancer, providing new ideas for early diagnosis and treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Background Our study aimed to establish ’real-world’ performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). Methods Our study recruited 875 female BRCA1/2- heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. Results Our study identified 8 OCs during 1277women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9–100), 75% (34.9–96.8) and 99.9% (99.9–100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER costsaving of -£102,496/QALY. Conclusion OC surveillance for women deferring RRSO in a ’real-world’ setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery. [ABSTRACT FROM AUTHOR]

Germline pathogenic variants (GPVs) in the cancer predisposition genes BRCA1, BRCA2, MLH1, MSH2, MSH6, BRIP1, PALB2, RAD51D and RAD51C are identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV in BRCA1, BRCA2, MLH1, MSH2 and MSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV in BRIP1, PALB2, RAD51D and RAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition of RAD51C and RAD51D as OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management of BRIP1, PALB2, RAD51D and RAD51C carriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for earlystage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers, but they have never before been quantified in OC. We investigated the diagnostic utility of GD2 and GD3 for diagnosis of all subtypes and stages of OC. Methods: This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299) and in two cohorts of serum samples by quantitative ELISA. A discovery cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent model cohort (n=200) was used to train and cross-validate a diagnostic model. Results: GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A diagnostic model that included serum levels of GD2+GD3+age was superior to the standard of care (CA125, p<0.001) in diagnosing OC and early-stage (I/II) OC. Conclusion: GD2 and GD3 expression was associated with high rates of selectivity and specificity for OC. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early stage. Further research exploring the utility of GD2 and GD3 for diagnosis of OC is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Early cancer detection is a challenge in treating cancer patients. Remarkably, carcinomas of the breast, lung, liver, pancreas, ovary, and colon contribute to more than 50% of total incidences and mortality annually, which could be reduced by early detection. As mucins are highly upregulated during the early progression of these cancers, several studies have explored mucins as potential biomarkers. Due to their membrane-bound and secretory nature, mucins have been detected in tumor biopsies and liquid biopsies of cancer patients, including blood and urine samples. We compiled here previous studies advocating for the use of mucins as potential biomarkers for the early detection of cancer and discuss the opportunities and challenges related to the use of mucin biomarkers in combination with other biomarkers and detection modalities. Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis. As mucin deregulation is one of the earliest events in most epithelial malignancies following oncogenic transformation, these high-molecular-weight glycoproteins are considered potential candidates for biomarker development. The diagnostic potential of mucins is mainly attributed to their deregulated expression, altered glycosylation, splicing, and ability to induce autoantibodies. Secretory and shed mucins are commonly detected in patients' sera, body fluids, and tumor biopsies. For instance, CA125, also called MUC16, is one of the biomarkers implemented for the diagnosis of ovarian cancer and is currently being investigated for other malignancies. Similarly, MUC5AC, a secretory mucin, is a potential biomarker for pancreatic cancer. Moreover, anti-mucin autoantibodies and mucin-packaged exosomes have opened new avenues of biomarker development for early cancer diagnosis. In this review, we discuss the diagnostic potential of mucins in epithelial cancers and provide evidence and a rationale for developing a mucin-based biomarker panel for early cancer detection. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein–Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages. [ABSTRACT FROM AUTHOR]

Vitamin D plays a pivotal role in calcium metabolism and bone mineralization. Sufficient vitamin D levels are important for the health and functionality of the musculoskeletal system. Hypovitaminosis D is a phenomenon affecting orthopedic patients worldwide. This study researched whether most orthopedic patients in two different cities of different countries had hypovitaminosis D, whether there was a correlation between sunshine hours and vitamin D serum levels, and whether hours of sunshine alone were enough to achieve vitamin D sufficiency among orthopedic patients regardless of their activities. The vitamin D serum levels of 500 orthopedic patients in Regensburg and 500 in Patras were assessed, in addition to their medical histories. The mean sunshine hours throughout the year were also calculated. Both the German and Greek groups showed hypovitaminosis D. Older patients were more affected. Although there were more hours of sunshine in Greece, Greek orthopedic patients also showed hypovitaminosis D. Hypovitaminosis D affects orthopedic patients independent of their latitude. Supplementation of vitamin D may be considered among orthopedic patients to achieve sufficient levels in serum. Sufficient vitamin D levels may be helpful for the treatment of orthopedic patients, reduce the negative effects of operations or postoperational settings. [ABSTRACT FROM AUTHOR]

This study aims to reveal the effect of integration of work achievement where selfefficacy, work Interest, emotional intelligence and motivation as Moderating variables. This type of research is associative quantitative. The population of this study as many as 151 employees. Sampling using simple random sampling technique as many as 109 respondents. Data analysis using path analysis. The results showed that the variables of work interest and emotional intelligence have a positive and significant effect on job performance through motivation as an intervening variable. [ABSTRACT FROM AUTHOR]

Simple Summary: High-grade serous ovarian cancer (HGSOC) remains a lethal malignancy. There is an urgent need to establish whether a mass is benign or malignant prior to surgery. The HGSOC microenvironment harbours a mixture of immunosuppressive and inflammatory immune parameters that correlate independently with disease progression; however, their relationship is not well understood. We hypothesised that the inclusion of such diverse biomarkers would improve the prediction of ovarian malignancy. We quantified 29 soluble factors in blood, as well as the proportions of circulating T cell subsets using 16 phenotypic markers by multiparameter flow cytometry, in patients with suspected ovarian cancer or volunteers undergoing ovarian cancer risk reduction surgery. Out of all the soluble and cellular subsets tested, a combination of tumour necrosis factor receptor type 2 (TNFR2)-expressing regulatory T cells (Tregs) and interleukin 6 (IL-6) showed superior predictive ability over the biomarkers currently used to discriminate between benign and malignant tumors. We propose combining soluble and cellular circulating biomarkers as a useful approach to improve cancer diagnoses. We hypothesised that the inclusion of immunosuppressive and inflammatory biomarkers in HGSOC patients would improve the sensitivity and specificity of the preoperative marker prediction of malignancy in patients with ovarian masses. We tested a panel of 29 soluble immune factors by multiplex bead immunoassay and 16 phenotypic T cell markers by flow cytometry in pre-treatment blood samples from 66 patients undergoing surgery for suspected ovarian cancer or ovarian cancer risk reduction. The potential diagnostic utility of all parameters was explored using Volcano plots, principal component analysis (PCA) and receiver operator characteristic (ROC) analysis. We also assessed the effect of culturing PBMCs from 20 healthy donors in the presence of malignant ascites fluid. The combination of TNFR2+ Tregs and IL-6 in the pre-treatment blood of patients with advanced HGSOC effectively discriminated patients with benign or malignant ovarian masses. In vitro culturing of the PBMCs of healthy donors in malignant ascites promoted an increase in TNFR2-expressing Tregs, which were decreased following blockade with IL-6 or STAT3 activity. Pre-treatment serum IL-6 and peripheral blood TNFR2+ Tregs may be potential clinical biomarkers that can discriminate patients with malignant compared to benign ovarian cancer masses, and the relationship between IL-6 and TNFR2+ Treg is likely to be mediated via the STAT3 signalling pathway. [ABSTRACT FROM AUTHOR]

Owing to the high incidence and mortality rates of colorectal cancer (CRC), novel biomarkers for CRC diagnosis are critically needed. Therefore, this study is aimed at exploring the clinical utility of serum C-X-C motif chemokine 8 (CXCL-8) for CRC diagnosis and progression compared to the routinely used biomarkers, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). This study included 227 patients with CRC, 110 patients with colorectal adenoma (CA), and 123 healthy participants, who were recruited from the Fujian Medical University Union Hospital from July 1, 2019 to October 31, 2020. Serum concentrations of CXCL-8, CEA, and CA19-9 were detected using enzyme-linked immunosorbent assay and chemiluminescent microparticle immunoassay. Clinicopathological features of patients with CRC were collected and analyzed. The diagnostic efficacy of CXCL-8, CEA, and CA19-9 for CRC was evaluated using receiver operating characteristic (ROC) curves. We found that the serum concentrations of CXCL-8, CEA, and CA19-9 were significantly higher in patients with CRC than those in patients with CA and healthy controls. The diagnostic sensitivity of CXCL-8 alone was higher than those of CEA and CA19-9 both and when combined; thus, CXCL-8 may be better at discriminating patients with CRC from healthy controls and patients with CA. Moreover, combining CXCL-8 with CEA or CA19-9 improved their respective diagnostic performances in distinguishing patients with CRC from CA patients and healthy participants. Notably, we also found that serum concentrations of CXCL-8 were positively correlated with metastases and tumor size. Therefore, our study suggests that serum CXCL-8 may serve as an improved biomarker for CRC diagnosis compared to the traditional tumor markers CEA and CA19-9. Moreover, our findings indicate the potential efficacy of serum CXCL-8 levels as a CRC prognostic biomarker. [ABSTRACT FROM AUTHOR]

Estradiol is known as one of the most potent estrogenic endocrine-disrupting chemicals (EDCs) that may cause various health implications on human growth, metabolism regulation, the reproduction system, and possibly cancers. The detection of these EDCs in our surroundings, such as in foods and beverages, is important to prevent such harmful effects on humans. Aptamers are a promising class of bio-receptors for estradiol detection due to their chemical stability and high affinity. With the development of aptamer technology, electrochemical aptasensing became an important tool for estradiol detection. This review provides detailed information on various technological interventions in electrochemical estradiol detection in solutions and categorized the aptasensing mechanisms, aptamer immobilization strategies, and electrode materials. Moreover, we also discussed the role of estradiol in human physiology and signaling mechanisms. The level of estradiol in circulation is associated with normal and diseased conditions. The aptamer-based electrochemical sensing techniques are powerful and sensitive for estradiol detection. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. We evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We found that, to prevent misidentification, it is necessary to understand the underlying disease that can increase tumor marker levels or benign tumors, which are difficult to distinguish from malignant tumors in imaging tests and several rare histopathologies with low risk of ovarian malignancy algorithm values. The malignant prediction of tumor markers and imaging was different in many patients with ovarian tumors, and this study will help to reduce the misidentification of tumors. Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. Therefore, we evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We enrolled 1047 patients with ovarian tumors. The predictive values and concordance rates between the preoperative risk of ovarian malignancy algorithm (ROMA) and imaging, including CT and MRI, were evaluated. Diagnoses of 561 CT (77.9%) and 322 MRI group (69.2%) participants were consistent with the ROMA. Among them, 96.4% of the CT (541/561) and 92.5% of the MRI (298/322) group predicted an accurate diagnosis. In contrast, 67.3% (101/150) of CT and 75.2% (100/133) of MRI cases accurately predicted the diagnosis in cases with discrepancies between ROMA and CT or MRI; a total of 32% (48/150) of the CT and 25.5% (34/133) of the MRI group showed an accurate ROMA diagnosis in cases with discrepancies between ROMA and imaging. In the event of a discrepancy between ROMA and imaging when ovarian tumor malignancy prediction, the question is which method should take precedence. This study demonstrates that MRI has the greatest diagnostic accuracy, followed by CT and ROMA. It is also important to understand underlying diseases and benign conditions and rare histopathologies of malignant tumors. [ABSTRACT FROM AUTHOR]

Background: N 6 -methyladenosine (m 6 A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m 6 A levels in CRC., Methods: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m 6 A levels and the expression of m 6 A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model., Results: PB RNA m 6 A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m 6 A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m 6 A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m 6 A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m 6 A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased., Conclusions: PB RNA m 6 A levels are a potential diagnostic biomarker for patients with CRC., (© 2024. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the potentiality of chemokines, including MCP-1, CCL15, CCL20, and CXCL14, as biomarkers for differential diagnosis between benign tumors and ovarian cancer (OC). Methods: A cross-sectional study was conducted in women aged >18 years who had adnexal masses treated with elective surgery at the HRH Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, between 2020 and 2021. The preoperative MCP-1, CCL15, CCL20, and CXCL14 serum levels were measured using a sandwich enzyme-linked immunosorbent assay. Preoperative diagnosis was defined according to the risk of malignancy index. The histological diagnosis and cancer subtype were confirmed using pathological specimens. Results: Ninety-eight participants were preoperatively diagnosed with malignant tumors. The pathological diagnosis confirmed OC in 33 patients and disclosed 27 misdiagnosed cases, of which endometriotic cyst was the most common (44.44%). CCL20 and CA125 serum levels were significantly higher in the patients with cancer than in those with benign. In addition, CCL20 level could differentiate between benign and early-stage malignancy. Furthermore, only CCL20 levels could distinguish endometriotic cysts from OC, whereas CA125 levels could not. Concordant with the serum protein level, the increased mRNA level of CCL20 was observed in ovarian cancers comparing with that in benign tissues. We found that CCL20 levels could differentiate between benign tumors and OC with 60.61% sensitivity and 75.44% specificity at the optimal cutoff value of 38.79 pg/ml. Finally, the logistic regression model integrating CCL20, CA125, and menopause status promoted diagnostic accuracy by increasing the specificity to 91.23%. Conclusions: Our study revealed the potential usefulness of CCL20 level as a biomarker for diagnosing early-stage OC with endometriosis differentiation. We recommend further studies to confirm the accuracy of CCL20 levels with the current diagnosis in a large patient sample. [ABSTRACT FROM AUTHOR]

Clinical bioinformatics is a newly emerging field that applies bioinformatics techniques for facilitating the identification of diseases, discovery of biomarkers, and therapy decision. Mathematical modelling is part of bioinformatics analysis pipelines and a fundamental step to extract clinical insights from genomes, transcriptomes and proteomes of patients. Often, the chosen modelling techniques relies on either statistical, machine learning or deterministic approaches. Research that combines bioinformatics with modelling techniques have been generating innovative biomedical technology, algorithms and models with biotech applications, attracting private investment to develop new business; however, startups that emerge from these technologies have been facing difficulties to implement clinical bioinformatics pipelines, protect their technology and generate profit. In this commentary, we discuss the main concepts that startups should know for enabling a successful application of predictive modelling in clinical bioinformatics. Here we will focus on key modelling concepts, provide some successful examples and briefly discuss the modelling framework choice. We also highlight some aspects to be taken into account for a successful implementation of cost-effective bioinformatics from a business perspective. [ABSTRACT FROM AUTHOR]