The Role of Cross-Institutional and Interdisciplinary Collaboration in Defining and Executing a Quantitative Systems Pharmacology Strategy.

The application of quantitative systems pharmacology (QSP) has enabled substantial progress and impact in many areas of therapeutic discovery and development. This new technology is increasingly accepted by industry, academia, and solution providers, and is enjoying greater interest from regulators. In this chapter, we summarize key aspects regarding how effective collaboration among institutions and disciplines can support the growth of QSP and expand its application domain.

MOMENT registry: Patients with advanced non-small-cell lung cancer harboring exon 14 skipping treated with systemic therapy.

exon 14 ex14) skipping occurs in 3-4% of non-small-cell lung cancer (NSCLC) cases. Low frequency of this alteration necessitated open-label, single-arm trials to investigate MET inhibitors. Since broad MET biomarker testing was only recently introduced in many countries, there is a lack of historical real-world data from patients with ex14 skipping NSCLC receiving conventional therapies.

The affective iconicity of lexical tone: Evidence from standard Chinesea).

Previous studies suggested that pitch characteristics of lexical tones in Standard Chinese influence various sensory perceptions, but whether they iconically bias emotional experience remained unclear. We analyzed the arousal and valence ratings of bi-syllabic words in two corpora (Study 1) and conducted an affect rating experiment using a carefully designed corpus of bi-syllabic words (Study 2). Two-alternative forced-choice tasks further tested the robustness of lexical tones' affective iconicity in an auditory nonce word context (Study 3).

Bibliometric Analysis of Research on Lip Prints.

Lip prints, or cheiloscopy, are unique patterns of grooves and wrinkles, gaining prominence in forensic science as reliable tools for personal identification, akin to fingerprints and DNA profiling. Advances in imaging techniques have enhanced their forensic applicability. This study conducts a bibliometric analysis to explore global research trends, key contributors, and thematic developments in lip print research.

Clinically interpretable multiclass neural network for discriminating cardiac diseases.

Background: Deep-learning applications in cardiology typically perform trivial binary classification and are able to discriminate between subjects affected or not affected by a specific cardiac disease. However, this working scenario is very different from the real one, where clinicians are required to recognize the occurrence of one cardiac disease among the several possible ones, performing a multiclass classification. The present work aims to create a new interpretable deep-learning tool able to perform a multiclass classification and, thus, discriminate among several different cardiac diseases.

Histone deacetylase inhibition with givinostat: a multi-targeted mode of action with the potential to halt the pathological cascade of Duchenne muscular dystrophy.

Muscle repair and regeneration are complex processes. In Duchenne muscular dystrophy (DMD), these processes are disrupted by the loss of functional dystrophin, a key part of the transmembrane dystrophin-associated glycoprotein complex that stabilizes myofibers, indirectly leading to progressive muscle wasting, subsequent loss of ambulation, respiratory and cardiac insufficiency, and premature death. As part of the DMD pathology, histone deacetylase (HDAC) activity is constitutively increased, leading to epigenetic changes and inhibition of muscle regeneration factors, chronic inflammation, fibrosis, and adipogenesis.

How cells align to structured collagen fibrils: a hybrid cellular Potts and molecular dynamics model with dynamic mechanosensitive focal adhesions.

Many mammalian cells, including endothelial cells and fibroblasts, align and elongate along the orientation of extracellular matrix (ECM) fibers in a gel when cultured . During cell elongation, clusters of focal adhesions (FAs) form near the poles of the elongating cells. FAs are mechanosensitive clusters of adhesions that grow under mechanical tension exerted by the cells' pulling on the ECM and shrink when the tension is released.

Prognostic performance of bedside tests for predicting ulcer healing and wound healing after minor amputation in patients prone to medial arterial calcification: A systematic review.

Foot ulceration is a significant and growing health problem worldwide, particularly due to rises in diabetes mellitus (DM) and peripheral artery disease. The prediction of ulcer healing remains a major challenge. In patients with foot ulcers, medial arterial calcification (MAC) can be present as a result of concomitant DM or chronic kidney disease and is a prognostic factor for unfavorable outcome.

Pupillometry and perceived listening effort for cochlear implant users-a comparison of three speech-in-noise tests.

Objective: Measuring listening effort using pupillometry is challenging in cochlear implant (CI) users. We assess three validated speech tests (Matrix, LIST, and DIN) to identify the optimal speech material for measuring peak-pupil-dilation (PPD) in CI users as a function of signal-to-noise ratio (SNR).

Design: Speech tests were administered in quiet and two noisy conditions, namely at the speech recognition threshold (0 dB re SRT), i.

Large simple randomized controlled trials-from drugs to medical devices: lessons from recent experience.

Randomized controlled trials (RCTs) are the cornerstone of modern evidence-based medicine. They are considered essential to establish definitive evidence of efficacy and safety for new drugs, and whenever possible they should also be the preferred method for investigating new high-risk medical devices. Well-designed studies robustly inform clinical practice guidelines and decision-making, but administrative obstacles have made it increasingly difficult to conduct informative RCTs.

Mixed vulnerabilities: the biological risk of high parity is aggravated by emergency referral in Benin, Malawi, Tanzania and Uganda.

Identification of interacting vulnerabilities is essential to reduce maternal and perinatal mortality in sub-Saharan Africa (SSA). High parity (≥ 5 previous births) is an underemphasized biological vulnerability linked to poverty and affecting a sizeable proportion of SSA births. Despite increased risk, high parity women rarely use hospitals for childbirth.

Cesarean section in Suriname using robson classification: a two-year nationwide cross-sectional study on rates, risk factors and perinatal outcomes of cesarean section.

Background: Optimizing CS performance is a global health priority, given the maternal and perinatal morbidity and mortality associated with both underuse and overuse. This study aims to (1) determine the facility-based CS rate in Suriname and explore which women are most likely to undergo a CS and (2) classify all CS by the WHO Robson classification and analyze the perinatal outcomes.

Methods: An observational, cross-sectional study in Suriname, using nationwide birth registry data that included all hospital births in 2020 and 2021 (≥ 27 weeks of gestation).

Triadic balance and network evolution in predictive models of signed networks.

This paper introduces a novel approach for identifying dynamic triadic transformation processes, applied to five networks: three undirected and two directed. Our method significantly enhances the prediction accuracy of network ties. While balance theory offers insights into evolving patterns of triadic structures, its effects on overall network dynamics remain underexplored.

Optimizing emergency response systems in urban health crises: A project management approach to public health preparedness and response.

Effective management of health crises requires public health preparedness and response, especially in urban settings where the complexity and scope of catastrophes provide considerable challenges. The integration of project management frameworks with public health policies is highlighted in this review, which investigates the optimization of emergency response systems using a project management methodology. The adoption of cutting-edge technologies that improve real-time monitoring, predictive analytics, and resource allocation such as artificial intelligence (AI), big data, and the Internet of Things (Io-T) is one of the main topics covered.

Effects of improved partner notification on the transmission of HIV and among men who have sex with men: a modelling study.

Men who have sex with men (MSM) are disproportionally affected by HIV in the Netherlands. Partner notification (PN) is an important element in controlling the transmission of sexually transmitted infections (STIs) and HIV. We investigated the effects of improving PN on the transmission of HIV and (NG) among MSM in the Netherlands.

Plasma transfusions in neonatal intensive care units: a prospective observational study.

Objective: Despite lack of evidence supporting efficacy, prophylactic fresh frozen plasma and Octaplas transfusions may be administered to very preterm infants to reduce bleeding risk. International variation in plasma transfusion practices in neonatal intensive care units (NICUs) is poorly understood, therefore, we aimed to describe neonatal plasma transfusion practice in Europe.

Design: Prospective observational study.

Symptomatic early coronary graft failure in bypass surgery patients: incidence, predictors and clinical impact.

Objectives: Coronary graft failure (CGF) may occur early after coronary bypass graft surgery (CABG). The study aimed to identify clinical and perioperative risk factors and to evaluate the long-term clinical impact of symptomatic early CGF.

Methods: Patients who underwent clinically indicated coronary angiography (CAG) prior to post-CABG discharge between 2012 and 2022 were included.

Androgens differentially modulate glucocorticoid effects on adipose tissue and lean mass.

Glucocorticoids and androgens affect each other in several ways. In metabolic organs such as adipose tissue and the liver, androgens enhance glucocorticoid-induced insulin resistance and promote fat accumulation in male mice. However, the direct contribution of the androgen receptor (AR) to these effects is unknown.

Excess mortality during the first 2 years of the COVID-19 pandemic (2020-2021) in the Netherlands: Overall and across demographic subgroups.

Objectives: The overall impact of the COVID-19 pandemic on mortality can be estimated by the assessment of excess deaths from all causes because the reported number of deaths due to COVID-19 do not accurately reflect the true death toll. We assessed excess mortality in 2020 and 2021 in the Netherlands.

Methods: All analyses were performed on data from comprehensive nationwide registers provided by Statistics Netherlands (Centraal Bureau voor de Statistiek), including demographic characteristics and mortality.

The Clinical Significance of HLA Compatibility Scores in Lung Transplantation.

Lung transplantation is a life-saving therapeutic option for many chronic end-stage pulmonary diseases, but long-term survival may be limited by rejection of the transplanted organ. Since HLA disparity between donor and recipient plays a major role in rejection, we performed a single center, retrospective observational cohort analysis in our lung transplant cohort (n = 128) in which we calculated HLA compatibility scores for B-cell epitopes (HLAMatchmaker, HLA-EMMA), T-cell epitopes (PIRCHE-II) and missing self-induced NK cell activation (KIR Ligand Calculator). Adjusted Cox proportional hazards model was used to investigate the association between mismatched scores and time to development of donor-specific antibodies (DSA) post-transplant, time to first biopsy-proven acute rejection episode, freedom from CLAD, graft survival and overall survival.

Soil Microbiome Inoculation for Resilient and Multifunctional New Forests in Post-Agricultural Landscapes.

Afforestation is increasingly recognized as a critical strategy to restore ecosystems and enhance biodiversity on post-agricultural landscapes. However, agricultural legacies, such as altered soil structure, nutrient imbalances, and depleted microbial diversity, can slow down forest establishment or cause ecosystems to deviate from expected successional trajectories. In this opinion paper, we explore the potential of soil inoculations as a tool to overcome these challenges by introducing beneficial microbial communities that can accelerate ecosystem recovery and forest development.

Ideal outcome after pancreatic resection for neuroendocrine tumors: a nationwide study.

Background: Pancreatic resections for pancreatic neuroendocrine tumors (pNET) may experience a higher complication rate than for pancreatic ductal adenocarcinoma (PDAC). This study aimed to determine the rate of the novel composite "Ideal Outcome" measure after resection for pNET, using PDAC as reference.

Methods: This observational cohort study included all consecutive patients after pancreatic resection for pNET and PDAC using the nationwide Dutch Pancreatic Cancer Audit (2014-2021).

Screening instruments to detect problematic alcohol use among adults in hospitals and their diagnostic test accuracy: A systematic review.

Issues: Alcohol consumption can cause physical, psychological and social problems that can result in hospitalisations. Screening in hospitals helps to determine which patients should be given interventions. In this review, we aimed to summarise the diagnostic test accuracy (DTA) of screening instruments for problematic alcohol use among adults in hospitals.

Fibrinogen genotypes and their impact on recurrence of venous thromboembolism and family history: A prospective population-based study.

Venous thromboembolism (VTE) involves blood clot formation in veins, resulting in serious health issues. Fibrinogen, a crucial clotting protein, consists of three polypeptides encoded by the fibrinogen genes: alpha (FGA), beta (FGB) and gamma (FGG). We genotyped most common missense variants in the fibrinogen genes in relation to VTE, recurrence and family history in Malmö Thrombophilia Study, including 1465 VTE patients followed for ~10 years and 429 healthy donors.