The effect of PSMA PET/CT on clinical decision-making of radical prostatectomy and pelvic lymph node dissection.

Objective: To evaluate the effect of prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) on clinical decision-making of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) after its utilization in daily clinical practice at an European high-volume cancer center.

Materials And Methods: Patients who had unfavorable intermediate- and high-risk prostate cancer between 2017 and 2021 were included retrospectively and divided into two groups; those who staged using PSMA PET/CT (group 1) and those who staged using conventional modalities (group 2). Clinical decision-making of RP over nonsurgical treatments and f PLND were primary endpoints and evaluated using regression models.

Comparative Strength Study of Indirect Permanent Restorations: 3D-Printed, Milled, and Conventional Dental Composites.

: Limited research has been performed to assess the strength of resin-bonded 3D-printed restorations. Based on that, this study investigates the impact of different manufacturing methods on the fracture load of indirect composite restorations (ICRs) following an aging process. : Three manufacturing techniques-conventional (CRC), milled (MRC), and printed (PRC)-were evaluated using 60 specimens, each with a diameter of 10 mm and a thickness of 1.

Osimertinib Plasma Trough Concentration in Relation to Brain Metastases Development in Patients With Advanced -Mutated NSCLC.

Introduction: Brain metastases (BM) are common in patients with advanced -mutated (m+) NSCLC. Despite good BM-related outcomes of osimertinib, several patients still experience intracranial progression. A possible explanation is pharmacologic failure due to low plasma trough levels (C) and consequently limited intracranial osimertinib exposure.

Exploring the impact of patient-specific clinical features on osimertinib effectiveness in a real-world cohort of patients with EGFR mutated non-small cell lung cancer.

Osimertinib is prescribed to patients with metastatic non-small cell lung cancer (NSCLC) and a sensitizing EGFR mutation. Limited data exists on the impact of patient characteristics or osimertinib exposure on effectiveness outcomes. This was a Dutch, multicenter cohort study.

Patient-reported outcome measures compared to clinician reported outcomes regarding incontinence and erectile dysfunction in localized prostate carcinoma after robot assisted radical prostatectomy: Impact on management.

Purpose/ Background: Patient-reported outcome measures (PROMs) are widely used after robot assisted radical prostatectomy (RARP) in order to evaluate the impact/burden of the treatment. The most bothersome side effects of RARP are urine incontinence (UI) and erectile dysfunction (ED). During the follow up consultations, clinicians report these side effects in interviewing patients.

Influence of germline variations in drug transporters ABCB1 and ABCG2 on intracerebral osimertinib efficacy in patients with non-small cell lung cancer.

Background: Central nervous system (CNS) metastases are present in approximately 40% of patients with metastatic epidermal growth factor receptor-mutated (m+) non-small cell lung cancer (NSCLC). The EGFR-tyrosine kinase inhibitor osimertinib is a substrate of transporters ABCB1 and ABCG2 and metabolized by CYP3A4. We investigated relationships between single nucleotide polymorphisms (SNPs) 3435C>T, 421C>A and 34G>A, and and CNS treatment efficacy of osimertinib in m+ NSCLC patients.

Cardiac Toxicity of Alectinib in Patients With ALK+ Lung Cancer: Outcomes of Cardio-Oncology Follow-Up.

Background: Anaplastic lymphoma kinase (ALK) translocations in metastatic non-small cell lung cancer (3% to 7%) predict for response to ALK-inhibitors (eg, alectinib, first line), resulting in a 5-year survival rate of ∼60% and median progression-free survival of 34.8 months. Although the overall toxicity rate of alectinib is acceptable, unexplained adverse events, including edema and bradycardia, may indicate potential cardiac toxicity.

Outcomes from integrating anti-cervical cancer teachings into the curriculum of high schools in a South-Eastern Nigerian State.

Background: Quests for the global elimination of cervical cancer and its related SDG goals by 2030 are achievable if realistic approaches for improving outcomes in LMICs are entrenched. Targeting teenage high schoolers in these countries, which largely lack universally-affordable anti-cervical cancer measures, can be a game-changer. This paper evaluates a 2019 Harvard-endorsed measure that integrated relevant teachings into the curricula of some Nigerian high schools, in what was a global-first.

Influence of esomeprazole on the bioavailability of afatinib: A pharmacokinetic cross-over study in patients with non-small cell lung cancer.

Afatinib is an oral small-molecule kinase inhibitor (SMKI) approved for treatment of metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) driver mutation. Although oral administration is convenient, most SMKIs experience pH-dependent solubility. A drug-drug interaction between afatinib and proton-pump inhibitors (PPIs) has, however, never been studied in humans.

Improving the tolerability of osimertinib by identifying its toxic limit.

Background: Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand.

The influence of green tea extract on nintedanib's bioavailability in patients with pulmonary fibrosis.

Nintedanib is an oral small-molecule kinase inhibitor and first-line treatment for idiopathic pulmonary fibrosis. Nintedanib is a substrate of the drug efflux transporter ABCB1. Green tea flavonoids --especially epigallocatechin gallate (EGCG)-- are potent ABCB1 modulators.

Thermo-electrochemical redox flow cycle for continuous conversion of low-grade waste heat to power.

Here we assess the route to convert low grade waste heat (< 100 °C) into electricity by leveraging the temperature dependency of redox potentials, similar to the Seebeck effect in semiconductor physics. We use fluid-based redox-active species, which can be easily heated and cooled using heat exchangers. By using a first principles approach, we designed a redox flow battery system with Fe(CN)/Fe(CN) and I/I chemistry.

Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.

Objectives: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic.

Maturation of hiPSC-derived cardiomyocytes promotes adult alternative splicing of SCN5A and reveals changes in sodium current associated with cardiac arrhythmia.

Aims: Human-induced pluripotent stem cell-cardiomyocytes (hiPSC-CMs) are widely used to study arrhythmia-associated mutations in ion channels. Among these, the cardiac sodium channel SCN5A undergoes foetal-to-adult isoform switching around birth. Conventional hiPSC-CM cultures, which are phenotypically foetal, have thus far been unable to capture mutations in adult gene isoforms.

Clozapine and COVID-19 Vaccination: Effects on blood levels and leukocytes. An observational cohort study.

Objective: To investigate the safety of COVID-19 vaccination in patients on clozapine as regards plasma clozapine concentration and haematological parameters.

Methods: We conducted a multicentre observational cohort study from 22 February 2021 to 2 September 2021. Primary outcomes were clinically relevant increase in clozapine blood levels (>100 μg/L increase compared to baseline) and clozapine alert levels (>1000 μg/L).

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy.

Recruitment of lymphocytes into tumors is critical for anti-tumor immunity and efficacious immunotherapy. We show in murine models that tumor-associated high endothelial venules (TA-HEVs) are major sites of lymphocyte entry into tumors at baseline and upon treatment with anti-PD-1/anti-CTLA-4 immune checkpoint blockade (ICB). TA-HEV endothelial cells (TA-HECs) derive from post-capillary venules, co-express MECA-79 HEV sialomucins and E/P-selectins, and are associated with homing and infiltration into tumors of various T cell subsets.

Targeting the Microtubule EB1-CLASP2 Complex Modulates Na1.5 at Intercalated Discs.

[Figure: see text].

A new model for regulation of sphingosine kinase 1 translocation to the plasma membrane in breast cancer cells.

The translocation of sphingosine kinase 1 (SK1) to the plasma membrane (PM) is crucial in promoting oncogenesis. We have previously proposed that SK1 exists as both a monomer and dimer in equilibrium, although it is unclear whether these species translocate to the PM via the same or different mechanisms. We therefore investigated the structural determinants involved to better understand how translocation might potentially be targeted for therapeutic intervention.

Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer.

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the preferred treatment for patients with -mutated non-small cell lung cancer (NSCLC), not all patients benefit. We therefore explored the impact of the presence of mutations found in cell-free DNA (cfDNA) and TKI plasma concentrations during treatment on progression-free survival (PFS). In the prospective START-TKI study blood samples from 41 patients with -mutated NSCLC treated with EGFR-TKIs were available.

Reverse Electrodialysis: Co- and Counterflow Optimization of Multistage Configurations for Maximum Energy Efficiency.

Reverse electrodialysis (RED) is one of the techniques able to harvest energy from the salinity gradient between different salt solutions. There is a tradeoff between efficiency and generated power in a RED stack. This paper focuses on efficiency.

Influence of Cow's Milk and Esomeprazole on the Absorption of Erlotinib: A Randomized, Crossover Pharmacokinetic Study in Lung Cancer Patients.

Introduction: Erlotinib's gastrointestinal solubility and absorption are decreased by proton pump inhibitors (PPIs). Since erlotinib is a lipophilic drug, we hypothesized that concomitant intake with the fatty beverage milk may be a feasible way to increase erlotinib uptake. We performed a two-period, randomized, crossover study to investigate the influence of cow's milk with 3.

Effects of environmental temperature on saliva flow rate and secretion of protein, amylase and mucin 5B.

Objective: The aim of this study is to evaluate the short term effects of environmental temperature on saliva flow rate and composition.

Methods: In a cross-over study design 20 subjects (18-25 years old, 14 women, 6 men) were exposed in randomized order at different days to three temperatures (4 °C, 21 °C and 37 °C). Five minutes after a subject was exposed to the test temperature, collection of resting saliva was started for 5 min at the same temperature.

Allogenicity Boosts Extracellular Vesicle-Induced Antigen-Specific Immunity and Mediates Tumor Protection and Long-Term Memory In Vivo.

Extracellular vesicles (EV) are candidates for cancer immunotherapy because of their capacity to stimulate tumor-specific activity in vivo. However, clinical trials using peptide-loaded autologous EVs have so far only showed moderate T cell responses, suggesting a need for optimization of EV-induced immunity in humans. We previously demonstrated that induction of Ag-specific CD8 T cells and antitumor responses to whole Ag were independent of MHC class I on EVs and hypothesized that multiple injections of allogeneic EVs could potentiate Ag-specific responses.

Quantification of the tyrosine kinase inhibitor erlotinib in human scalp hair by liquid chromatography-tandem mass spectrometry: Pitfalls for clinical application.

An LC-MS/MS method was developed and validated to quantify the tyrosine kinase inhibitor erlotinib in human scalp hair, as alternative matrix to monitor long-term erlotinib exposure. Hair samples from 10 lung cancer patients were measured and correlated with plasma concentrations. Hair segments of 1 ± 0.