Surgical Castration as an Alternative to Improve Systemic Treatment for Advanced Prostate Cancer: A Window of Opportunity for Developing Countries.

Purpose: The Brazilian Public Health System (BPHS) serves approximately 71,730 patients with prostate cancer (PC) every year for which androgen deprivation therapy (ADT) is the primary treatment for patients with advanced hormone-sensitive prostate cancer (aHSPC). Androgen receptor pathway inhibitors (ARPIs) are not accessible through the BPHS. Using the BPHS as a model, this study assesses the long-term economic effect of surgical versus medical castration in aHSPC treatment to strategize cost reduction and the incorporation of ARPI in developing countries.

Reconstructing the sequence specificities of RNA-binding proteins across eukaryotes.

RNA-binding proteins (RBPs) are key regulators of gene expression. Here, we introduce EuPRI (Eukaryotic Protein-RNA Interactions) - a freely available resource of RNA motifs for 34,736 RBPs from 690 eukaryotes. EuPRI includes binding data for 504 RBPs, including newly collected RNAcompete data for 174 RBPs, along with thousands of reconstructed motifs.

Quick and effective approximation of in silico saturation mutagenesis experiments with first-order taylor expansion.

To understand the decision process of genomic sequence-to-function models, explainable AI algorithms determine the importance of each nucleotide in a given input sequence to the model's predictions and enable discovery of regulatory motifs for gene regulation. The most commonly applied method is saturation mutagenesis (ISM) because its per-nucleotide importance scores can be intuitively understood as the computational counterpart to saturation mutagenesis experiments. While ISM is highly interpretable, it is computationally challenging to perform for many sequences, and becomes prohibitive as the length of the input sequences and size of the model grows.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

Purpose: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil.

Efficacy of immune checkpoint inhibitors combinations as first-line systemic treatment in patients with advanced urothelial carcinoma: A systematic review and network meta-analysis.

Background: Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results.

Methods: Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR).

Benchmarking of deep neural networks for predicting personal gene expression from DNA sequence highlights shortcomings.

Deep learning methods have recently become the state of the art in a variety of regulatory genomic tasks, including the prediction of gene expression from genomic DNA. As such, these methods promise to serve as important tools in interpreting the full spectrum of genetic variation observed in personal genomes. Previous evaluation strategies have assessed their predictions of gene expression across genomic regions; however, systematic benchmarking is lacking to assess their predictions across individuals, which would directly evaluate their utility as personal DNA interpreters.

Dose-Volume Predictors of Radiation Pneumonitis After Thoracic Hypofractionated Radiation Therapy.

Purpose: Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis.

Methods And Materials: All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020.

Impact on splicing in of random 50-base sequences inserted into an intron.

Intron splicing is a key regulatory step in gene expression in eukaryotes. Three sequence elements required for splicing-5' and 3' splice sites and a branchpoint-are especially well-characterized in , but our understanding of additional intron features that impact splicing in this organism is incomplete, due largely to its small number of introns. To overcome this limitation, we constructed a library in of random 50-nt (N50) elements individually inserted into the intron of a reporter gene and quantified canonical splicing and the use of cryptic splice sites by sequencing analysis.

A multimodality approach to a rare case of ruptured sinus of Valsalva aneurysm with tricuspid valve involvement: a case report.

Background: Ruptured sinus of Valsalva aneurysm is a rare disease entity that is potentially life-threatening if left untreated. While imaging is the mainstay of diagnosis, resultant tricuspid valve involvement may mask typical findings providing a diagnostic challenge. Disruption of the tricuspid valve during ruptured sinus of Valsalva aneurysm with consequent tricuspid regurgitation is rare and infrequently described in the literature.

Erratum: Single-center developing country analysis of radium-223 therapy in prostate cancer-preliminary results.

[This corrects the article on p. 352 in vol. 11, PMID: 34754606.

Benefit of inhalation aromatherapy as a complementary treatment for stress and anxiety in a clinical setting - A systematic review.

Objective: The purpose of this systematic review is to ascertain the impact of inhalation aromatherapy on stress and anxiety in clinical settings.

Methods: A search strategy was developed using various databases. Randomised Controlled Trials (RCTs) as well as single and double-blind pilot clinical studies (non-RCT) using inhalation aromatherapy with an essential oil blend or a single essential oil were examined.

Benchmarking of deep neural networks for predicting personal gene expression from DNA sequence highlights shortcomings.

Deep learning methods have recently become the state-of-the-art in a variety of regulatory genomic tasks including the prediction of gene expression from genomic DNA. As such, these methods promise to serve as important tools in interpreting the full spectrum of genetic variation observed in personal genomes. Previous evaluation strategies have assessed their predictions of gene expression across genomic regions, however, systematic benchmarking is lacking to assess their predictions across individuals, which would directly evaluates their utility as personal DNA interpreters.

30th Annual GPA Medicinal Chemistry Conference.

The Group for the Promotion of Pharmaceutical Chemistry in Academia (GPA) held their 30th annual conference in August 2022 in Trinity College Dublin, Ireland. There were 9 keynote presentations, 10 early career researcher presentations and 41 poster presentations.

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages.

"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine.

The preventable productivity burden of sleep apnea in Australia: a lifetime modelling study.

Obstructive sleep apnea (OSA) is a common disorder. OSA is associated with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM) and depression, among other comorbidities. We aim to determine the productivity burden of OSA in Australia using productivity-adjusted life-years (PALYs).

"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

Introduction: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC.

The Traditional Chinese Medicine Houttuynia cordata Thunb decoction alters intestinal barrier function via an EGFR dependent MAPK (ERK1/2) signalling pathway.

Background: A traditionally prepared aqueous extract (= decoction) of Houttuynia cordata Thunb (Yu xing cao) (HC) is widely used in Traditional Chinese Medicine (TCM) to treat inflammatory disease. Previous chemical and biological studies on HC have mainly focused on organic extracts rather than the aqueous decoction, which is the traditional formulation.

Purpose: The study aimed to investigate whether the chemical composition of HC aqueous decoction (HCD) varies with geographical sourcing, to investigate the mechanism of action of HCD, and to determine if chemical variation impacts on HCDs anti-inflammatory activity.

Cholesterol treatment in patients with acute coronary syndromes: does stating a target improve management?

Aim: Previous research in New Zealand has demonstrated high rates of statin prescription in patients with acute coronary syndromes (ACS), but how widely a treat to target approach is adopted is unclear.

Methods: We retrospectively examined cholesterol management in 100 consecutive patients admitted with confirmed ACS. The primary end point was reaching low-density lipoprotein-cholesterol (LDL-C) target of <1.

A Systematic Review and Meta-Analysis of the Role of Immune Checkpoint Inhibitors (ICI) as Adjuvant Treatment for Localized High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC).

Nivolumab, a PD-1 ICI has been recently approved for the adjuvant treatment of high-risk MIUC patients. However, conflicting data from another randomized controlled trial (RCT) with atezolizumab makes the benefit of this treatment uncertain. We performed a systematic review and study-level meta-analysis to evaluate the benefit in terms of disease-free survival (DFS) with ICI adjuvant treatment for patients with high-risk MIUC.

Hypofractionated standard radiotherapy for locally advanced limited-stage small cell lung cancer.

Background: Hypofractionated radiotherapy in locally advanced limited-stage small cell lung cancer is preferred in many Western countries but not used regularly in the United States. We examined practice patterns and overall survival with definitive hypofractionated radiotherapy and chemotherapy standard radiotherapy in this setting.

Methods: We included patients in the National Cancer Database with unresected primary stage II-III small cell lung cancer in 2008-2016 who underwent chemotherapy within six months of either hypofractionated radiotherapy (40-45 Gy/15 fractions) or standard radiotherapy (45 Gy/30 fractions or 60-70 Gy/30-35 fractions) in this retrospective cohort study.

Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients.

Cancer therapies with anthracyclines have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of B-cell lymphoma and to examine whether doxorubicin (DOX)-treated ACT-iPSC cardiomyocytes (CM) can recapitulate the clinical features exhibited by patients, and thus help uncover a DOX-dependent pathomechanism. ACT-iPSC CM generated from individuals with CD20 B-cell lymphoma who had received high doses of DOX and suffered cardiac dysfunction were studied and compared to control-iPSC CM from cancer survivors without cardiac symptoms.

Establishing an ad hoc COVID-19 mortality surveillance during the first epidemic wave in Belgium, 1 March to 21 June 2020.

BackgroundCOVID-19-related mortality in Belgium has drawn attention for two reasons: its high level, and a good completeness in reporting of deaths. An ad hoc surveillance was established to register COVID-19 death numbers in hospitals, long-term care facilities (LTCF) and the community. Belgium adopted broad inclusion criteria for the COVID-19 death notifications, also including possible cases, resulting in a robust correlation between COVID-19 and all-cause mortality.