PTMNavigator: interactive visualization of differentially regulated post-translational modifications in cellular signaling pathways.

Post-translational modifications (PTMs) play pivotal roles in regulating cellular signaling, fine-tuning protein function, and orchestrating complex biological processes. Despite their importance, the lack of comprehensive tools for studying PTMs from a pathway-centric perspective has limited our ability to understand how PTMs modulate cellular pathways on a molecular level. Here, we present PTMNavigator, a tool integrated into the ProteomicsDB platform that offers an interactive interface for researchers to overlay experimental PTM data with pathway diagrams.

Right ventricular strain impairment due to hypoxia in patients with COPD: a post hoc analysis of two randomised controlled trials.

Background: Hypoxic pulmonary vasoconstriction leads to an increase in pulmonary artery pressure (PAP) and potentially right heart failure in healthy individuals and patients with respiratory diseases. Previous studies in patients with chronic obstructive pulmonary disease (COPD) exposed to hypobaric hypoxia have shown an increase in PAP, while traditional echocardiographic parameters revealed only minimal changes at high altitude. Speckle-tracking-derived analysis is potentially more sensitive to assess right ventricular (RV) function and we used this method to investigate the impact on RV function of patients with COPD ascending to high altitude and compared the results with the traditional echocardiographic parameters.

The acute effect of high-dose supplemental oxygen on haemodynamics assessed by echocardiography in patients with pulmonary vascular disease living in Quito at 2850 m: a randomized, single-blind, placebo-controlled crossover trial.

Aims: More than 220 Mio people live at altitudes above 2000 m, many of whom have pre-existing chronic diseases, including pulmonary vascular diseases (PVDs) such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). We investigated the acute effects of high-dose supplemental oxygen on pulmonary haemodynamics assessed by echocardiography in patients with PVD permanently living at 2850 m.

Methods And Results: In a randomized, single-blind, placebo-controlled crossover trial, patients with PVD diagnosed with PAH or CTEPH were allocated to receive 10 L/min supplemental oxygen (FiO ≈ 95%) and placebo air administered via a facial mask with reservoir near their living altitude in Quito at 2850 m (FiO0.

Effects of acetazolamide on sleep disordered breathing in pulmonary vascular disease: a randomised controlled trial.

Background: Patients with pulmonary vascular disease (PVD) often suffer from nocturnal hypoxaemia, but also from sleep apnoea. Short-term use of acetazolamide increases ventilation due to metabolic acidosis and also reduces loop gain. We investigated whether prolonged use of acetazolamide improves sleep disordered breathing in PVD.

Heart rate variability in pulmonary vascular disease at altitude: a randomised trial.

Background: Hypoxia is a trigger for sympathetic activation and autonomic cardiovascular dysfunction. Pulmonary vascular disease (PVD) is associated with hypoxaemia, which increases with altitude. The aim was to investigate how exposure of patients with PVD to hypobaric hypoxia at altitude affects autonomic cardiovascular regulation.

Feasibility and usefulness of postoperative mobilization goals in the enhanced recovery after surgery (ERAS) clinical pathway for elective colorectal surgery.

Purpose: Despite mobilization is highly recommended in the ERAS colorectal guideline, studies suggest that more than half of patients don't reach the daily goal of 360 min out of bed. However, data used to quantify mobilization are predominantly based on self-assessments, for which the accuracy is uncertain. This study aims to accurately measure postoperative mobilization in ERAS-patients by validated motion data from body sensors.

Cardiac sarcoidosis in patients with recurrent ventricular arrhythmias refractory to endocardial ablation.

Introduction: The clinical presentation of cardiac sarcoidosis is diverse. Detection of granuloma in histopathological evaluation proves the diagnosis, but endomyocardial biopsy (EMB) is associated with a high sampling error. However, prompt immunosuppressive therapy may significantly affect patient's prognosis.

Impact of steroid hormone levels on estradiol-mediated regulation of cytochrome P450 2B6 compared to 1B1 in breast cancer cells.

Pharmacogenetic variants of the steroid hormone-metabolizing enzyme cytochrome P450 2B6 (CYP2B6) were reported to be associated with breast cancer (BC) risk and prognosis. CYP2B6 expression is inducible by estradiol (E2) but induction was demonstrated only under steroid hormone-deprived medium conditions. Physiological conditions, however, even under endocrinological BC treatment, do not correspond to complete steroid hormone depletion.

Metabolic activation of WHO-congeners PCB28, 52, and 101 by human CYP2A6: evidence from in vitro and in vivo experiments.

Despite extensive research on the metabolism of polychlorinated biphenyls (PCBs), knowledge gaps persist regarding their isoform-specific biotransformation pathways. This study aimed to elucidate the role of different cytochrome P450 enzymes in PCB metabolism, focusing on WHO-congeners 2,4,4'-trichlorobiphenyl (PCB28), 2,2',5,5'-tetrachlorobiphenyl (PCB52), and 2,2',4,5,5'-pentachlorobiphenyl (PCB101). Utilizing engineered HEK293 cell lines, we investigated the in vitro metabolism of these PCBs by CYP1A2, CYP2C8, CYP2C9, CYP3A4, CYP2A6, and CYP2E1, revealing robust production of hydroxylated metabolites.

A screening for cerebral deoxygenation during VT ablations in patients with structural heart disease.

Background: Patients undergoing ventricular tachycardia (VT) ablation often present with structural heart disease (SHD) and reduced ejection fraction. Inducing VT by programmed electrical stimulation (PES) puts these patients at risk for hemodynamic instability and cerebral hypoperfusion.

Objective: The present study screens for cerebral oxygen desaturation phases (ODPs) in patients undergoing VT ablation.

Submaximal, Low-Dose Eccentric vs Traditional Cycling Exercise: Reduced Oxygen Uptake and Pulmonary Artery Pressure Assessed by Echocardiography in Healthy Middle-aged Adults. A Randomized Controlled, Crossover Trial.

Objective: To investigate the ventilatory and circulatory differences between eccentric (ECC) and concentric (CON) cycling exercise at submaximal, low-dose intensity from onset to end-exercise in healthy middle-aged participants.

Design: Randomized controlled crossover trial.

Setting: The participants underwent 1 ECC and 1 CON test according to stepwise incremental exercise protocols at identical, submaximal intensities.

Prognosis and treatment strategies for atrial fibrillation in heart failure with mildly reduced ejection fraction.

Aims: The study investigates the prognosis of atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Data concerning the prognostic impact of AF in patients with HFmrEF is scarce.

Methods And Results: Consecutive patients with HFmrEF [i.

Motivational Interviewing improves postoperative nutrition goals within the Enhanced Recovery after Surgery (ERAS®) pathway in elective bowel surgery - A randomized clinical pilot trial.

Background & Aims: Exploration whether Motivational Interviewing (MI) could be learned and implemented with ease within a surgical in-hospital setting and whether participation in the intervention led to significantly higher compliance with ERAS®-recommended protein intake goals. The individual healing process of many patients is delayed because they fail to cover their calorie requirement, which could be counteracted by a patient-centered conversational intervention that is new in perioperative practice.

Methods: This patient-blinded pilot-RCT included 60 patients (≥18 years) following the certified ERAS® bowel protocol for colorectal surgery between March and August 2022.

Characteristics Associated with Ventricular Tachyarrhythmias and Their Prognostic Impact in Heart Failure with Mildly Reduced Ejection Fraction.

: The occurrence of ventricular tachyarrhythmias represents an established risk factor of mortality in heart failure (HF). However, data concerning their prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF) is limited. Therefore, the present study aims to investigate patient characteristics associated with ventricular tachyarrhythmias and their prognostic impact in patients with HFmrEF.

Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics.

Proteomics is making important contributions to drug discovery, from target deconvolution to mechanism of action (MoA) elucidation and the identification of biomarkers of drug response. Here we introduce decryptE, a proteome-wide approach that measures the full dose-response characteristics of drug-induced protein expression changes that informs cellular drug MoA. Assaying 144 clinical drugs and research compounds against 8,000 proteins resulted in more than 1 million dose-response curves that can be interactively explored online in ProteomicsDB and a custom-built Shiny App.

Influence of motivational interviewing on postoperative mobilization in the enhanced recovery after surgery (ERAS®) pathway in elective colorectal surgery - a randomized patient-blinded pilot study.

Purpose: Early mobilization is an essential component of the Enhanced Recovery after Surgery (ERAS®)-pathway. However, a large percentage of patients fail to achieve the ERAS® recommended goal (360 min out of bed from post-operative day 1/POD1). Motivational Interviewing (MI) is an evidence-based type of patient-centered consultation to promote intrinsic motivation.

SARS-CoV-2 Transmission during High-Altitude Field Studies.

Grimm, Mirjam, Lucie Ziegler, Annina Seglias, Maamed Mademilov, Kamila Magdieva, Gulzada Mirzalieva, Aijan Taalaibekova, Simone Suter, Simon R. Schneider, Fiona Zoller, Vera Bissig, Lukas Reinhard, Meret Bauer, Julian Müller, Tanja L. Ulrich, Arcangelo F.

Simultaneous analysis of cannabinoids and terpenes in Cannabis sativa inflorescence using full comprehensive two-dimensional liquid chromatography coupled to smart active modulation.

Nowadays, the higher peak capacity achievable by comprehensive two-dimensional liquid chromatography (LC×LC) for the analysis of vegetal samples is well-recognized. In addition, numerous compounds may be present in very different amounts. Cannabinoids and terpenes represent the main components of Cannabis sativa inflorescence samples, whose quantities are relevant for many application purposes.

Uncoupling of Cytochrome P450 2B6 and stimulation of reactive oxygen species production in pharmacogenomic alleles affected by interethnic variability.

Cytochrome P450 mediated substrate metabolism is generally characterized by the formation of reactive intermediates. In vitro and in vivo reaction uncoupling, results in the accumulation and dissociation of reactive intermediates, leading to increased ROS formation. The susceptibility towards uncoupling and altered metabolic activity is partly modulated by pharmacogenomic alleles resulting in amino acid substitutions.

The effect of high altitude (2500 m) on incremental cycling exercise in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a randomised controlled crossover trial.

Background: Our objective was to investigate the effect of a day-long exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: In a randomised controlled crossover trial, stable patients with PAH or distal CTEPH without resting hypoxaemia at low altitude performed two incremental exercise tests to exhaustion: one after 3-5 h at high altitude (2500 m) and one at low altitude (470 m).

Results: In 27 patients with PAH/CTEPH (44% females, mean±sd age 62±14 years), maximal work rate was 110±64 W at 2500 m and 123±64 W at 470 m (-11%, 95% CI -16- -11%; p<0.

Effects of 5-Week Oral Acetazolamide on Incremental Cycling Exercise in Pulmonary Arterial and Chronic Thromboembolic Pulmonary Hypertension: A Randomized Placebo-Controlled, Double-Blinded, Crossover Trial.

Introduction: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance.

Methods: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout.

Results: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol.

Illuminating phenotypic drug responses of sarcoma cells to kinase inhibitors by phosphoproteomics.

Kinase inhibitors (KIs) are important cancer drugs but often feature polypharmacology that is molecularly not understood. This disconnect is particularly apparent in cancer entities such as sarcomas for which the oncogenic drivers are often not clear. To investigate more systematically how the cellular proteotypes of sarcoma cells shape their response to molecularly targeted drugs, we profiled the proteomes and phosphoproteomes of 17 sarcoma cell lines and screened the same against 150 cancer drugs.