Protein codes promote selective subcellular compartmentalization.

Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must efficiently assemble. Here, we demonstrate that proteins with shared functions share amino acid sequence codes that guide them to compartment destinations. A protein language model, ProtGPS, was developed that predicts with high performance the compartment localization of human proteins excluded from the training set.

Distinct chemical environments in biomolecular condensates.

Diverse mechanisms have been described for selective enrichment of biomolecules in membrane-bound organelles, but less is known about mechanisms by which molecules are selectively incorporated into biomolecular assemblies such as condensates that lack surrounding membranes. The chemical environments within condensates may differ from those outside these bodies, and if these differed among various types of condensate, then the different solvation environments would provide a mechanism for selective distribution among these intracellular bodies. Here we use small molecule probes to show that different condensates have distinct chemical solvating properties and that selective partitioning of probes in condensates can be predicted with deep learning approaches.

Leveraging Cell Painting Images to Expand the Applicability Domain and Actively Improve Deep Learning Quantitative Structure-Activity Relationship Models.

The search for chemical hit material is a lengthy and increasingly expensive drug discovery process. To improve it, ligand-based quantitative structure-activity relationship models have been broadly applied to optimize primary and secondary compound properties. Although these models can be deployed as early as the stage of molecule design, they have a limited applicability domain─if the structures of interest differ substantially from the chemical space on which the model was trained, a reliable prediction will not be possible.

Single dose tocilizumab for COVID-19 associated cytokine storm syndrome: Less is more.

Aims: We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm syndrome (CSS).

Methods: MP pre-treated patients with COVID-19-associated CSS, defined as at least two elevations of C-reactive protein (CRP) >100 mg/L, ferritin >900 μg/L or D-dimers >1500 μg/L, received intravenous TCZ (8 mg/kg, max. 800 mg) upon clinical deterioration.

The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review.

Background And Aims: NAFLD is a leading cause of liver-related morbidity and mortality. We assessed the global and regional prevalence, incidence, and mortality of NAFLD using an in-depth meta-analytic approach.

Approach And Results: PubMed and Ovid MEDLINE were searched for NAFLD population-based studies from 1990 to 2019 survey year (last published 2022) per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Sarcopenia, healthy living, and mortality in patients with chronic liver diseases.

Chronic liver diseases (CLDs) are associated with increased morbidity and mortality. Sarcopenia is an important complication of CLD that can be impacted by several modifiable risk factors. Our aim was to assess the associations between healthy living, sarcopenia, and long-term outcomes among patients with CLD.

Intraoperative hypotension and delirium among older adults undergoing transcatheter aortic valve replacement.

Background: Postoperative delirium (POD) is a frequently observed complication after transcatheter aortic valve replacement (TAVR). The effects of intraoperative hypotension (IOH) on POD occurrence are currently unclear.

Methods: A retrospective observational cohort study of patients who underwent TAVR was conducted.

Hemocytometric characteristics of COVID-19 patients with and without cytokine storm syndrome on the sysmex XN-10 hematology analyzer.

Objectives: COVID-19 is an ongoing global pandemic. There is an urgent need for identification and understanding of clinical and laboratory parameters related to progression towards a severe and fatal form of this illness, often preceded by a so-called cytokine-storm syndrome (CSS). Therefore, we explored the hemocytometric characteristics of COVID-19 patients in relation to the deteriorating clinical condition CSS, using the Sysmex XN-10 hematology analyzer.

Unusually Rapid Development of Pulmonary Hypertension and Right Ventricular Failure after COVID-19 Pneumonia.

Unlabelled: COVID-19 is a novel viral disease caused by SARS-CoV-2. The mid- and long-term outcomes have not yet been determined. COVID-19 infection is increasingly being associated with systemic and multi-organ involvement, encompassing cytokine release syndrome and thromboembolic, vascular and cardiac events.

The Use of Three-Dimensional Photography and Printing in the Fabrication of a Nasal Prosthesis.

Objective: Facial prosthetic rehabilitation using additive manufacturing technology relies on data acquisition from computed tomography or magnetic resonance imaging. Three-dimensional (3D) photography has become widespread in craniofacial and plastic surgery due to its ability to provide more comprehensive topographical data than radiographic techniques. Despite the rising popularity of 3D photography in preoperative planning, reports on the use of this technology for facial prosthetic rehabilitation are lacking.

Tocilizumab in Severe COVID-19 Pneumonia and Concomitant Cytokine Release Syndrome.

Unlabelled: Younger patients with COVID-19 may experience an exaggerated immune response to SARS-CoV-2 infection and develop cytokine release syndrome (CRS), which may be life threatening. There is no proven antiviral therapy for COVID-19 so far, but profound immunosuppression has recently been suggested as a treatment for COVID-19-associated CRS. We present a case of life-threatening CRS caused by COVID-19 infection with a favourable response to immunosuppressive therapy with tocilizumab (TCZ).

Impact of baseline cigarette smoking status on clinical outcome after transcatheter aortic valve replacement.

Objectives: To explore the prevalence of smoking, and its association with clinical and mortality outcome among patients undergoing transcatheter aortic valve replacement (TAVR).

Background: Less data exist regarding the effect of baseline smoking status on clinical and mortality outcome among patients undergoing TAVR.

Methods: Consecutive patients who underwent TAVR at two high volume Dutch centers were included.

Postoperative Delirium in Individuals Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the incidence of in-hospital postoperative delirium (IHPOD) after transcatheter aortic valve replacement (TAVR).

Design: Systematic review and meta-analysis.

Setting: Elective procedures PARTICIPANTS: Individuals undergoing TAVR.

A comparison of the embryonic stem cell test and whole embryo culture assay combined with the BeWo placental passage model for predicting the embryotoxicity of azoles.

In the present study, we show the value of combining toxico-dynamic and -kinetic in vitro approaches for embryotoxicity testing of azoles. Both the whole embryo culture (WEC) and the embryonic stem cells test (EST) predicted the in vivo potency ranking of twelve tested azoles with moderate accuracy. Combining these results with relative placental transfer rates (Papp values) as determined in the BeWo cell culture model, increased the predictability of both WEC and EST, with R values increasing from 0.

Short-Term and Long-Term Outcomes of a Vocational Rehabilitation Program for Patients with Acquired Brain Injury in The Netherlands.

Purpose To describe short-term and long-term work status after a vocational rehabilitation (VR) program in patients with acquired brain injury (ABI) in the Netherlands. Methods Patients with ABI who participated in a VR program between 2007 and 2010 were included in this study. The 4-month VR program included a multidisciplinary assessment, three meetings with all stakeholders and reintegration with coaching on the job.

Evaluation of Cognitive Function Following Transcatheter Aortic Valve Replacement.

Background: Transcatheter aortic valve replacement (TAVR) is associated with procedural-related neurological events and acute cognitive decline. However, data on the effect of TAVR on mid-term cognitive outcome are scarce. Therefore, we aimed to assess the impact of TAVR on mid-term cognitive outcome using different neurocognitive test batteries.

The Effects of 5-year Etanercept Therapy on Cardiovascular Risk Factors in Patients with Psoriatic Arthritis.

Objective: To investigate the effects of etanercept (ETN) on lipid metabolism and other known cardiovascular disease (CVD) risk factors in patients with psoriatic arthritis (PsA).

Methods: In an observational cohort of 118 consecutive patients with PsA, CVD risk factors were assessed over 5 years. Mixed-model analyses were performed to investigate the effects of ETN therapy on CVD risk factors over time.

Effect of body mass index on clinical outcome and all-cause mortality in patients undergoing transcatheter aortic valve implantation.

Objectives: To assess the effect of body mass index (BMI) on outcome among patients with severe aortic stenosis (AS) admitted for transcatheter aortic valve implantation (TAVI).

Background: Being overweight or obese is associated with improved outcome following certain medical treatments, suggesting the existence of a BMI paradox. However, the relationship between BMI and mortality after TAVI remains controversial.

Diastolic left ventricular dysfunction in ankylosing spondylitis--a systematic review and meta-analysis.

Objectives: Ankylosing spondylitis (AS) is associated with increased mortality largely due to cardiovascular disease. Diastolic left ventricular (LV) dysfunction serves as a precursor to chronic heart failure and may cause morbidity and mortality. A systematic literature search was conducted to determine the prevalence of diastolic LV dysfunction in patients with AS.

Personalised treatment using serum drug levels of adalimumab in patients with rheumatoid arthritis: an evaluation of costs and effects.

Objective: To evaluate the cost-effectiveness of personalised treatment for rheumatoid arthritis (RA) using clinical response and serum adalimumab levels.

Methods: A personalised treatment algorithm defined, based on clinical (European League Against Rheumatism) response and drug levels at 6 months, whether adalimumab treatment should be continued in a specific dose or discontinued and/or switched to a next biological. Outcomes were simulated using a patient level Markov model, with 3 months cycles, based on a cohort of 272 adalimumab-treated patients with RA for 3 years and data of patients from the Utrecht Rheumatoid Arthritis Cohort.

[The happy doctor].

Objective: Descriptive, questionnaire-based. To study what makes doctors and medical students happy: Descriptive, questionnaire-based.

Design: Descriptive, questionnaire-based.

[Behçet and his triad].

Hulusi Behçet (1889-1948) was an internationally oriented Turkish dermatologist. He was closely involved in establishing the Istanbul Faculty of Medicine, where he later became a professor. In addition, Behçet was a scientist and an editor of the German professional journal, Dermatologische Wochenschrift.