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Archaea are vital components of the human microbiome, yet their study within the gastrointestinal tract (GIT) is limited by the scarcity of cultured representatives. Our study presents a method for the targeted enrichment and isolation of methanogenic archaea from human fecal samples. The procedure combines methane breath testing, in silico metabolic modeling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyzes include the co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits. Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which are absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from individual donors revealed features potentially associated with gastrointestinal diseases. Our work broadens available archaeal representatives for GIT studies, and offers insights into Candidatus Methanobrevibacter intestini genomes' adaptability in critical microbiome contexts., (© 2024. The Author(s).)

Objective: Patients with TNM T1a cervical cancer have excellent prognosis; however, the risk for recurrence remains an issue of concern and management guidelines are based on limited data. Here we performed subgroup analysis of the Surveillance in Cervical Cancer (SCCAN) consortium with the objective of defining the prognosis of T1a cervical cancer patients., Methods: SCCAN was an international, multicentric, retrospective cohort study of patients with cervical cancer undergoing surgical treatment in tertiary centers. Inclusion criteria included: histologically confirmed cervical cancer treated between 2007 and 2016; TNM T1a; primary surgical management; and at least 1-year of follow-up data availability. Exclusion criteria included treatment with primary chemo-radiation, and missing treatment-related or clinical data., Results: Out of 975 patients included, 554 (57 %) were T1a1 and 421 (43 %) T1a2. The majority had squamous-cell carcinoma (78 %). 79 patients (8.1 %) had lymphovascular space invasion (LVSI). 455 patients (47 %) underwent radical hysterectomy/ parametrectomy. Laparoscopic and open surgery was performed in 401 (41 %) and in 361 (37 %) patients, respectively. Adjuvant treatment was administered to 56 patients (5.7 %). Assessment of lymph nodes (LN) was performed in 524 patients (54 %), with LN involvement found in 15 (2.9 %). There were 40 (4.1 %) recurrences, occurring at a median of 26 months (4-106), out of which 33 (82.5 %) occurred in pelvis. Among T1a1 cases, there were 10 recurrences (2.0 %) if LVSI was negative, and 3 recurrences (6.7 %) if LVSI was positive. Among T1a2 cases, there were 23 recurrences (6.7 %) if LVSI was negative, and 4 recurrences (5.1 %) if LVSI was positive. There were 3 recurrences in the LN+ group (recurrence rate 20 %)., Conclusions: The risk of recurrence in T1a cervical cancer was 4.1 % corresponding to the rates seen in patients with FIGO 1B cancer in recently published prospective trials. LN involvement represents a risk factor for disease recurrence. Our results indicate that stage T1a cervical cancer, apart from T1a1 LVSI negative disease, should follow the same principles in the management as that of FIGO stage 1B cancer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest for this research publication., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers., Methods: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data., Results: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations., Conclusion: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aim: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer., Methods: International, multicenter, retrospective study., Inclusion Criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy ('SLN' group) or pelvic lymphadenectomy alone ('non-SLN' group)., Results: 1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5-98.5 versus 92.0 %,95 %CI:90.0-94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8-99.9 versus 96.8 %,95 %CI:95.4-98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266-0.959, p = 0.037 and HR:2.703,95 %CI:1.389-5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039)., Conclusion: Adding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Abu-Rustum received research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC., Methods: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor., Results: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations ( p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS., Conclusions: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

I. INTRODUCTION 793 II. AN OVERVIEW OF TV A v. HILL, ROMERO-BARCELO, AND OAKLAND CANNABIS 796 III. SYNTHESIZING TV A v. HILL, ROMERO-BARCELO, AND OAKLAND CANNABIS 799 IV. THE POTENTIAL [...]

High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Modern humanity has changed the biosphere at a global scale, threatening its own sustainability. It is claimed that through technology humans maximize the extraction of energy from the natural system towards their own benefit, with rates of appropriation that surpass the time-scales for systemic adaptation. This time-decoupled coevolutionary dynamic is at the core of human societal unsustainability. Here, we developed in silico experiments of an open energy-based flowing network toy model of natural systems and study the effects that greedy evolutionary strategies, resembling human societal demands, have upon the performance and scarcity tolerance of the system. We aim to determine the flexibility that those biased evolutionary dynamics have for matching or surpassing natural evolution outcomes. We studied four different indexes of system's growth and development (total system throughflow (TST), average mutual information, ascendency and entropy difference) and compare their scarcity tolerance and performance outcomes with respect to four different greedy scenarios. The results showed that greedy strategies rarely surpassed the tolerance and performance achieved by natural systemic evolution. The nature of the greedy scenarios developed were closely related to increases in TST and therefore, we emphasized this comparison. Here, the maximum percentage of greedy networks capable of surpassing natural dynamics was around one-third (approx. 35%). However, results suggest the existence of a space parameter where local increases of energy flow can outperform the outcomes of natural systemic evolution, but no evident network property seems to characterize those greedy networks. A mild inverse relationship was found between the number of links that greedy nodes have towards the output and their capacity to outpass the control evolution. As many of the human societal effect upon biospheric processes have dissipative byproducts, knowing that such dynamics might diminish the systems tolerance and performance suggest care in their (ab)use. This article is part of the theme issue 'Evolution and sustainability: gathering the strands for an Anthropocene synthesis'. [ABSTRACT FROM AUTHOR]

Objective: A comprehensive overview of surgical treatment of recurrent gynecological malignancies. Recurrent breast malignancies are not included in this review., Methodology: A review providing overview of surgical treatment options for recurrent malignancies of adnexa of the uterus (ovary, fallopian tube), uterine corpus, uterine cervix, and carcinoma of the vagina and vulva., Conclusion: Optimal surgical treatment for patients with recurrent cancer is based on multidisciplinary approach with stratification according to individual prognostic markers. These include patient's performance status, outcome of primary surgery, current extent of recurrence, and histopathological, molecular, and biochemical characteristics. Decision about choice of treatment should be individually discussed and evaluated by the multidisciplinary oncogynecological commission board.

This article presents a comprehensive review of factors that increase the risk of malignancy in ultrasound findings of an endometrial polyp. We collected original studies, reviews, and meta-analyses that dealt with the topic of endometrial polyps and the risk of developing endometrial cancer. Each presumed risk factor was analysed individually. According to searched studies, abnormal uterine bleeding, old age, and body mass index are valid risk factors for developing endometrial cancer in endometrial polyps. Lynch syndrome patients are also in a high-risk group for endometrial cancer. On the other hand, the number of polyps, their size, diabetes mellitus, hypertension, and positive family history are factors with inconclusive results. There are either not enough data or different results among several studies.

The Guidelines for Clinical Practice for carriers of pathogenic variants in clinically relevant cancer predisposition genes define the steps of primary and secondary prevention that should be provided to these individuals at high risk of developing hereditary cancer in the Czech Republic. The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society (SLG ČLS JEP) in cooperation with the representatives of oncology and oncogynecology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.

Introduction: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial., Methods: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer., Results: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e., , Auc: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive., Conclusion: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease., Objective: Evaluation of novel long non-coding RNAs biomarkers for breast cancer., Methods: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics., Results: The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality., Conclusions: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.

The article focuses on issues surrounding same-sex fathers affecting the perception of heterosexual caretaking fathers and heterosexual non-caretaking mothers in the U.S. Topics discussed include the masculinities theory applied to fathers and the feminine work of caregiving, the U.S Supreme Court case Weinberger v. Wiesenfeld based on law giving additional benefits to widows, but not widowers, and the case Nevada Department of Human Resources v. Hibbs.