Detailed bladder cancer immunoprofiling reveals new clues for immunotherapeutic strategies.

Objectives: Bladder cancer (BlCa) is the tenth most frequent malignancy worldwide and the costliest to treat and monitor. Muscle-invasive BlCa (MIBC) has a dismal prognosis, entailing the need for alternative therapies for the standard radical cystectomy. Checkpoint blockade immunotherapy has been approved for high-grade non-muscle-invasive BlCa (HG NMIBC) and metastatic disease, but its effectiveness in localised MIBC remains under scrutiny.

Atmospheric features and risk of ST-elevation myocardial infarction in Porto (Portugal): A temperate Mediterranean (Csb) city.

Introduction And Objectives: Some atmospheric features have been linked to the triggering of myocardial infarction. Because data from the Temperate-Mediterranean is scarce, we sought to study whether meteorological parameters influence the incidence of ST-elevation myocardial infarction (STEMI) as confirmed by primary percutaneous intervention in a city with temperate weather (Porto, Portugal).

Methods: Retrospective analysis of a series of STEMI-patients from January 2010 to December 2017.

Cell Architecture-Dependent Constraints: Critical Safeguards to Carcinogenesis.

Animal cells display great diversity in their shape. These morphological characteristics result from crosstalk between the plasma membrane and the force-generating capacities of the cytoskeleton macromolecules. Changes in cell shape are not merely byproducts of cell fate determinants, they also actively drive cell fate decisions, including proliferation and differentiation.

MiRNA biomarkers in cancers of the male reproductive system: Are we approaching clinical application?

Background: Specific cancer types face specific clinical management challenges. Owing to their stability, robustness and fast, easy and cost-effective detection, microRNAs (miRNAs) are attractive candidate biomarkers to the clinic.

Objectives: Based on a comprehensive review of the relevant literature in the field, we explore the potential of miRNAs as biomarkers to answer relevant clinical dilemmas inherent to cancers of the male reproductive tract (prostate [PCa], testis [TGCTs] and penis [PeCa]) and identify some of the challenges/limitations hampering their widely application.

DigiMir Test: Establishing a Novel Pipeline for MiR-371a Quantification Using Droplet Digital PCR in Liquid Biopsies From Testicular Germ Cell Tumor Patients.

Testicular germ cell tumors (TGCTs) are the most common cancers in young-adult male patients aged between 15 and 39 years. Hsa-miR-371a-3p is currently the most reliable biomarker for diagnosis and monitoring of these patients non-invasively in liquid biopsies, and it is destined to be introduced in the clinic due to improved performance compared to the classical serum tumor markers available. Current studies have focused on real-time quantitative PCR (RT-qPCR) protocols for its determination; still, some challenges remain, since these protocols often require preamplification steps (costly and time-consuming), and report relative levels normalized to a housekeeping microRNA, not always performed the same way.

DNA Methylation Biomarkers for Prediction of Response to Platinum-Based Chemotherapy: Where Do We Stand?

Platinum-based chemotherapy is routinely used for the treatment of several cancers. Despite all the advances made in cancer research regarding this therapy and its mechanisms of action, tumor resistance remains a major concern, limiting its effectiveness. DNA methylation-based biomarkers may assist in the selection of patients that may benefit (or not) from this type of treatment and provide new targets to circumvent platinum chemoresistance, namely, through demethylating agents.

High diversity of pathogenic Escherichia coli clones carrying mcr-1 among gulls underlines the need for strategies at the environment-livestock-human interface.

The expansion of mcr-carrying bacteria is a well-recognized public health problem. Measures to contain mcr spread have mainly been focused on the food-animal production sector. Nevertheless, the spread of MCR producers at the environmental interface particularly driven by the increasing population of gulls in coastal cities has been less explored.

Epigenetically-regulated miR-30a/c-5p directly target TWF1 and hamper ccRCC cell aggressiveness.

Clear cell renal cell carcinoma (ccRCC) is highly prone to metastasize and displays an extremely low 5-year survival rate. Not only miRNAs (miRs) are key gene expression regulators but can also be epigenetically modified. Abnormal miR expression has been linked with epithelial-mesenchymal transition (EMT)-driven ccRCC progression.

From Therapy Resistance to Targeted Therapies in Prostate Cancer.

Prostate cancer (PCa) is the second most common malignancy among men worldwide. Although early-stage disease is curable, advanced stage PCa is mostly incurable and eventually becomes resistant to standard therapeutic options. Different genetic and epigenetic alterations are associated with the development of therapy resistant PCa, with specific players being particularly involved in this process.

Papillary renal cell carcinoma: current and controversial issues.

Purpose Of The Review: Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15-20% of all RCC. Classification of pRCC is changing because novel tumour entities have been discovered in the last years. In this review, we summarise recent studies relevant for the understanding of the molecular complexity and the broader differential diagnosis of pRCC.

WHO 2022 landscape of papillary and chromophobe renal cell carcinoma.

The 5th edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems contains relevant revisions and introduces a group of molecularly defined renal tumour subtypes. Herein we present the World Health Organization (WHO) 2022 perspectives on papillary and chromophobe renal cell carcinoma with emphasis on their evolving classification, differential diagnosis, and emerging entities. The WHO 2022 classification eliminated the type 1/2 papillary renal cell carcinoma (pRCC) subcategorization, given the recognition of frequent mixed tumour phenotypes and the existence of entities with a different molecular background within the type 2 pRCC category.

One sample fits all: a microfluidic-assisted methodology for label-free isolation of CTCs with downstream methylation analysis of cfDNA in lung cancer.

Lung cancer (LC) is a major cause of mortality. Late diagnosis, associated with limitations in tissue biopsies for adequate tumor characterization contribute to limited survival of lung cancer patients. Liquid biopsies have been introduced to improve tumor characetrization through the analysis of biomarkers, including circulating tumour cells (CTCs) and cell-free DNA (cfDNA).

G9a inhibition by CM-272: Developing a novel anti-tumoral strategy for castration-resistant prostate cancer using 2D and 3D in vitro models.

Castration-resistant prostate cancer (CRPC) is an incurable form of prostate cancer (PCa), with DNMT1 and G9a being reported as overexpressed, rendering them highly attractive targets for precision medicine. CM-272 is a dual inhibitor of both methyltransferases' activity. Herein, we assessed the response of different PCa cell lines to CM-272, in both 2D and 3D models, and explored the molecular mechanisms underlying CM-272 inhibitory effects.

Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study.

To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients.

Morphological spectrum and molecular features of somatic malignant transformation in germ cell tumours.

Aims: Somatic malignant transformation (SMT) arising in germ cell tumours (GCTs) is an infrequent, but clinically relevant event. There is only limited knowledge on the morphological spectrum of SMT, and the therapeutic management of these patients is poorly defined. In this work we revisit two consecutive case series (n = 756) of GCTs.

Eosinophilic solid and cystic renal cell carcinoma and renal cell carcinomas with TFEB alterations: a comparative study.

Aims: Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a recently described renal tumour entity with frequent cytokeratin (CK)20 positivity, commonly harbouring TSC mutations. In contrast, frequency of CK20 expression and presence of TSC mutations are unclear in TFEB-amplified RCC and TFEB-translocated RCC, which frequently express Melan A. Herein, we provide a comparative analysis of six ESC RCC with four TFEB-amplified/translocated RCC.

Anti-NMDAr Encephalitis and COVID-19 in a Patient With Systemic pANCA-Vasculitis and Recurrent Varicella Zoster Infection.

Introduction: There is a complex interplay between systemic autoimmunity, immunosuppression, and infections. Any or all of these can result in neurologic manifestations, requiring diligence on the part of neurologists.

Case Report: We herein report a case of a patient on immunosuppressive treatment for a vasculitis that resulted in zoster meningoencephalitis.

Feasibility of an online training and support program for dementia carers: results from a mixed-methods pilot randomized controlled trial.

Background: iSupport is an online program developed by the World Health Organization to provide education, skills training, and social support to informal carers of persons with dementia. This pilot study examines the feasibility of the protocol for a main effectiveness trial of iSupport-Portugal and explores how the intervention and control arms compare over time on well-being outcomes.

Methods: A mixed-methods experimental parallel between-group design with two arms is followed.

Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm.

TGCTs represent a model of curable disease afflicting especially young men. Defining tumor biological characteristics is crucial to increase current knowledge and tailor the best clinical management. Ki67, a potential prognostic marker, still exhibits heterogenous associations with patient outcomes, thus bringing the need of corroboration with larger cohorts in clinical practice.

LiKidMiRs: A ddPCR-Based Panel of 4 Circulating miRNAs for Detection of Renal Cell Carcinoma.

Background: Decreased renal cell cancer-related mortality is an important societal goal, embodied by efforts to develop effective biomarkers enabling early detection and increasing the likelihood of curative treatment. Herein, we sought to develop a new biomarker for early and minimally invasive detection of renal cell carcinoma (RCC) based on a microRNA panel assessed by ddPCR.

Methods: Plasma samples from patients with RCC ( = 124) or oncocytomas ( = 15), and 64 healthy donors, were selected.

Digital Pathology Implementation in Private Practice: Specific Challenges and Opportunities.

Digital pathology (DP) is being deployed in many pathology laboratories, but most reported experiences refer to public health facilities. In this paper, we report our experience in DP transition at a high-volume private laboratory, addressing the main challenges in DP implementation in a private practice setting and how to overcome these issues. We started our implementation in 2020 and we are currently scanning 100% of our histology cases.

The modulatory role of internet-supported mindfulness-based cognitive therapy on extracellular vesicles and psychological distress in people who have had cancer: a protocol for a two-armed randomized controlled study.

Background: Mindfulness-based interventions (MBIs) have been used in oncology contexts as a promising tool with numerous benefits for various health-related and psychosocial outcomes. Despite the increasing popularity of MBIs, few randomized controlled trials (RCTs) have examined their effects upon biological parameters. Specifically, no previous study has examined the effects of MBIs on extracellular vesicles (EVs), which are potentially important markers of health, disease, and stress.

Integration of Automatic Text Mining and Genomic and Proteomic Analysis to Unravel Prostate Cancer Biomarkers.

Prostate cancer (PCa) is the most prevalent noncutaneous cancer among men. The limited accuracy and/or invasive nature of the current diagnostic tools have driven the demand for new and noninvasive biomarkers. Urine as a noninvasive sample that contains prostatic secretions is a promising source of PCa markers.