Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

Bodies as communication systems. The relevance of Michel Serres's philosophy of science for health care.

This article demonstrates the value of French philosophy of science for medical practice through an exposition of Michel Serres's philosophy of the body. It explores how Serres's examination of the similarity between scientific models and works of art can provide insight into different conceptions of the human body. What makes Serres's method of unique is that it does not see art and literature as subordinate to the natural sciences: they are both involved in mapping the communication lines of the body.

Sensitive liquid biopsy monitoring correlates with outcome in the prospective international GPOH-DCOG high-risk neuroblastoma RT-qPCR validation study.

Background: Liquid biopsies offer less burdensome sensitive disease monitoring. Bone marrow (BM) metastases, common in various cancers including neuroblastoma, is associated with poor outcomes. In pediatric high-risk neuroblastoma most patients initially respond to treatment, but in the majority the disease recurs with only 40% long-term survivors, stressing the need for more sensitive detection of disseminated disease during therapy.

Outbreak of cholera in the Southwest region of Cameroon, 2021-22: an epidemiological investigation.

Background: In October 2021, a large outbreak of cholera was declared in Cameroon, disproportionately affecting the Southwest region, one of 10 administrative regions in the country. In this region, the cases were concentrated in three major cities where a humanitarian crisis had concomitantly led to an influx of internally displaced persons. Meanwhile, across the border, Nigeria was facing an unprecedented cholera outbreak.

Use of extracorporeal blood purification therapies in sepsis: the current paradigm, available evidence, and future perspectives.

Background: Sepsis is the result of a dysregulated immune response to infection and is associated with acute organ dysfunction. The syndrome's complexity is contingent upon the underlying pathology and individual patient characteristics, including their immune response. The involvement of multiple organs and physiological functions adds complexity, with "organ cross-talk" emerging as a pivotal pathophysiological and clinical aspect.

Romantic Relationships Matter More to Men than to Women.

Women are often viewed as more romantic than men, and romantic relationships are assumed to be more central to the lives of women than to those of men. Despite the prevalence of these beliefs, some recent research paints a different picture. Using principles and insights based on the interdisciplinary literature on mixed-gender relationships, we advance a set of four propositions relevant to differences between men and women and their romantic relationships.

Lower risk of revision in fixed-bearing compared to mobile-bearing total ankle arthroplasties: A register based evaluation of 1246 patients in the Netherlands.

Background: Total ankle arthroplasty (TAA) has been developed as treatment for disabling tibiotalar osteoarthritis. TAAs are divided into mobile- and fixed-bearings. The aim was to determine the incidence and trends of fixed- and mobile bearings over time and investigate the association of bearing type and risk of revision after primary TAA in the Netherlands.

Ferret Gastroenterology.

Ferrets (Mustela putorius furo) commonly present with gastrointestinal disease, which can be of noninfectious and infectious origin. Clinical signs are often nonspecific, and can include lethargy, anorexia, vomiting, diarrhea, and melena. Obtaining a detailed history, followed by a thorough physical examination and systematic diagnostic approach are the key to obtaining a correct diagnosis.

Absence of Functional Autoantibodies Targeting Angiotensin II Type 1 Receptor (ATR) and Endothelin-1 Type A Receptor (ETR) in Circulation and Purified IgG from Patients with Systemic Sclerosis.

Objective: Systemic sclerosis (SSc) is a rare but severe autoimmune disease characterized by immune dysregulation, fibrosis, and vasculopathy. While previous studies have highlighted the presence of functional autoantibodies targeting the angiotensin II type 1 receptor (ATR) and endothelin-1 type A receptor (ETR), leading to autoantibody-mediated receptor stimulation and subsequent activation of endothelial cells (ECs), a comprehensive understanding of the direct interaction between these autoantibodies and their receptors is currently lacking. Moreover, existing data confirming the presence of these autoantibodies in SSc often rely on similar methodologies and assays.

Does a Restrictive Diagnostic Work-up for Thyroid Nodules Lead to a Different Papillary Thyroid Cancer Patient Population? A Comparison Between Dutch and U.S. T1-T3 Patient Population.

Introduction: The 2015 American Thyroid Association guidelines recommend de-escalating surgical treatment for papillary thyroid cancer (PTC). We hypothesize that the Dutch PTC population might differ due to a restrictive diagnostic policy that mainly selects symptomatic and palpable thyroid nodules for further diagnostics, potentially selecting relatively more aggressive tumors. We aimed to describe the Dutch PTC population because differences in populations can have consequences for the adoption of foreign guidelines.

Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms.

Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce.

Real-time shrimp freshness detection by anthocyanin-enriched wheat gluten/gelatin electrospun nanofiber films.

Electrospun nanofiber films exhibited significant potential as food freshness indicators (FFI) due to their structural advantages. Herein, a novel electrospinning film based on wheat gluten (WG), gelatin, and anthocyanins was fabricated to detect the freshness of shrimp. Compared with pure WG, an adjusted ratio of the WG to gelatin (W16E9, 16:9) improved physicochemical properties, reducing viscosity from 3.

Summer CH ebullition strongly determines year-round greenhouse gas emissions from agricultural ditches despite frequent dredging.

Recent studies indicate that greenhouse gas (GHG) emissions from agricultural drainage ditches can be significant on a per-unit area basis, but spatiotemporal investigations are still limited. Additionally, the impact of dredging - a common management in such environments - on ditch GHG emissions is largely unknown. This study presents year-round GHG emissions from nine ditches on a dairy farm in the center of the Netherlands, where each year, approximately half of the ditches are dredged in alternating cycles.

An update on access to novel treatment for metastatic melanoma in Europe - A 2024 survey of the European melanoma registry and the European association of dermato-oncology.

Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.

Manure odor profiling for flock-level monitoring on commercial layer pullet farms: Vaccination events as a model stressor.

Continuous, non-invasive, and objective methods to detect flock-level responses to stressors, including intestinal health deviations, are currently lacking in poultry. This proof of principle study investigated the potential of manure odor profiling in monitoring stress responses in Lohmann Brown Classic, Lohmann LSL Classic and Lohmann LSL Lite layer pullets. Stressors were represented by a Salmonella vaccination given to the pullets at wk 3 of age (Dataset 1 and Dataset 2) and wk 16 of age (Dataset 4) and a viral/bacterial vaccine cocktail given at wk 12 of age (Dataset 3).

Molecular responses to clove and oregano essential oils are associated with reduced inflammation and improved gut barrier function in broiler chickens.

In vitro tests were conducted to characterize the host-mediated responses of chickens to Clove Essential Oil (CEO) and Oregano Essential Oil (OEO). Chicken macrophage cells (CMCs), chicken intestinal epithelial cells (IECs), quail muscle cells (QMCs), and chicken embryonic muscle cells (EMCs) were utilized in these assays. EMCs were collected from the 13-day-old embryo during egg incubation and all cell lines were seeded at 2 × 10/mL in a 24-well plate.

Digital approaches to chronic pain: A brief meta-review of eHealth interventions - Current evidence and future directions.

Digital approaches to chronic pain are emerging worldwide and rapidly gaining increased empirical support. This brief meta-review aims at providing a comprehensive overview of evidence and recommendations reported in recent reviews (2023-2024) on eHealth interventions for chronic pain promoting self-management. A systematic search provided 2041 records, of which 225 reviews were screened and 20 were synthesized.

Examining the nonlinear effects of traffic and built environment factors on the traffic safety of cyclist from different age groups.

In the Netherlands and all over the world, traffic safety problem has been growing particularly for cyclists over the last decades with more people shifting to cycling as a healthy and sustainable mode of transport. Literature shows that age is an important factor in crash involvement and consequences; however, few studies identify the risk factors for cyclists from across different age groups. Therefore, this study aims to identify and understand the effects of traffic, infrastructure, and land use factors on vehicle-to-bike injury and fatal crashes involving cyclists from different age groups.

Beat gestures and prosodic prominence interactively influence language comprehension.

Face-to-face communication is not only about 'what' is said but also 'how' it is said, both in speech and bodily signals. Beat gestures are rhythmic hand movements that typically accompany prosodic prominence in conversation. Yet, it is still unclear how beat gestures influence language comprehension.

Sample size estimation for task-related functional MRI studies using Bayesian updating.

Task-related functional MRI (fMRI) studies need to be properly powered with an adequate sample size to reliably detect effects of interest. But for most fMRI studies, it is not straightforward to determine a proper sample size using power calculations based on published effect sizes. Here, we present an alternative approach of sample size estimation with empirical Bayesian updating.

Developing a comprehensive framework for evaluating public health emergency management program implementation: A scoping review.

Objectives: Public health emergencies and disasters highlight gaps in health systems' emergency preparedness capabilities. Developing robust public health emergency management (PHEM) programs is crucial yet challenging. Existing assessment tools are limited in scope or lack standardized measurement.

Genomic structural equation modeling of reward-related traits: exploring the genetic factor structure and its relationship with psychopathology.

Reward sensitivity has a partial genetic background, and extreme levels may increase vulnerability to psychopathology. This study explores the genetic factor structure underlying reward-related traits and examines how genetic variance links to psychopathology. We modeled GWAS data from ten reward-related traits: risk tolerance (N = 975,353), extraversion (N = 122,886), sensation seeking (N = 132,395), (lack of) premeditation (N = 132,667), (lack of) perseverance (N = 133,517), positive urgency (N = 132,132), negative urgency (N = 132,559), attentional impulsivity (N = 124,739), motor impulsivity (N = 124,104), and nonplanning impulsivity (N = 123,509) to derive their genetic factor structure.

Evaluating growth-factor release in leukocyte- and platelet-rich fibrin, advanced platelet-rich fibrin, and injectable platelet-rich fibrin protocols: a narrative review.

Since its introduction in 2001, multiple platelet-rich fibrin (PRF) centrifugation protocols have emerged, but the variations in growth factor release that result from these protocols remain unclear. This review aimed to evaluate growth factor release across three PRF protocols: leukocyte-PRF (L-PRF), advanced-PRF (A-PRF/+), and injectable-PRF (i-PRF). A comprehensive search was conducted using the MEDLINE and Embase databases, identifying 14 studies that met the inclusion criteria.