Discovery of a Novel Mutant-Selective Epidermal Growth Factor Receptor Inhibitor Using an Enabled Drug Discovery Platform.

Despite the success of first, second, and third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer with classical EGFR mutations (L858R or Exon 19 deletions), disease progression occurs due to the acquisition of T790M and C797S resistance. Herein, we report a physics-based computationally driven lead identification approach that identified structurally unique imidazo[3.2-]pyrazoles as reversible and wild-type-sparing EGFR TKIs of classical mutations bearing both T790M and C797S.

Men's empathy toward children's emotions across the transition to fatherhood.

We investigated whether men's affective and cognitive empathy toward children's emotions changes across the transition to fatherhood. Specifically, we were interested in whether empathy increases with fathering experience. In two preregistered online studies ( = 1,046, primarily from the United Kingdom and the United States), participants' task was to rate their affective responses to emotional pictures of children (affective empathy) and to recognize children's emotions from pictures of the eye area (cognitive empathy).

Tickling induces a unique type of spontaneous laughter.

Laughing is ubiquitous in human life, yet what causes it and how it sounds is highly variable. Considering this diversity, we sought to test whether there are fundamentally different kinds of laughter. Here, we sampled spontaneous laughs ( = 887) from a wide range of everyday situations (e.

Genicular artery embolisation versus sham embolisation for symptomatic osteoarthritis of the knee: a randomised controlled trial.

Objective: To determine the efficacy of genicular artery embolisation (GAE) compared with sham GAE for pain reduction in patients with symptomatic mild-to-moderate knee osteoarthritis (KOA).

Design: Double-blind randomised sham-controlled clinical trial conducted from June 2019 to December 2021. The follow-up period was 4 months.

Proteomic analysis of dorsal root ganglia in a mouse model of paclitaxel-induced neuropathic pain.

Paclitaxel is a chemotherapy drug widely used for the treatment of various cancers based on its ability to potently stabilize cellular microtubules and block division in cancer cells. Paclitaxel-based treatment, however, accumulates in peripheral system sensory neurons and leads to a high incidence rate (over 50%) of chemotherapy induced peripheral neuropathy in patients. Using an established preclinical model of paclitaxel-induced peripheral neuropathy (PIPN), we examined proteomic changes in dorsal root ganglia (DRG) of adult male mice that were treated with paclitaxel (8 mg/kg, at 4 injections every other day) relative to vehicle-treated mice.

Containment Measures and Alcohol Consumption Among Drinking Higher Education Students Before and During the COVID-19 Pandemic: A Multilevel Analysis in 25 Countries.

Hazardous alcohol use tends to be more prominent among higher education students. The COVID-19 pandemic severely altered student life, raising questions on its impact on students' alcohol use patterns. The current study examined cross-country variations in drinking behaviors (weekly drinking and binge drinking), and the extent to which these variations were associated with containment measures implemented during the first wave of the COVID-19 pandemic.

The Innate Immune System and the TRAIL-Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females.

There is a significant sex bias in lung cancer, with males showing increased mortality compared with females. A better mechanistic understanding of these differences could help identify therapeutic targets to personalize cancer therapies to each sex. After observing a clear sex bias in humanized mice, with male patient-derived xenograft lung tumors being more progressive and deadlier than female patient-derived xenograft lung tumors, we identified mouse tumor models of lung cancer with the same sex bias.

Latent profile analysis of biopsychosocial measures in older patients with (un)explained persistent somatic symptoms.

Patients with persistent somatic symptoms (PSS) often receive either somatic or psychiatric care, depending on whether symptoms are respectively medically explained (MES) or unexplained (MUS). This separation may not be as clinically relevant as previously assumed; however, research on data-driven subgroups within cohorts of older patients with PSS is not available. Our goal is to identify more clinically relevant homogeneous subgroups beyond the distinction of MUS and MES among older patients with PSS by using a data-driven approach.

Intraoperative application of three-dimensional printed guides in total hip arthroplasty: A systematic review.

Background: Acetabular component positioning in total hip arthroplasty (THA) is of key importance to ensure satisfactory post-operative outcomes and to minimize the risk of complications. The majority of acetabular components are aligned freehand, without the use of navigation methods. Patient specific instruments (PSI) and three-dimensional (3D) printing of THA placement guides are increasingly used in primary THA to ensure optimal positioning.

Facing infant cuteness: How nurturing care motivation and oxytocin system gene methylation are associated with responses to baby schema features.

Baby schema features are a specific set of physical features-including chubby cheeks, large, low-set eyes, and a large, round head-that have evolutionary adaptive value in their ability to trigger nurturant care. In this study among nulliparous women (N = 81; M age = 23.60, SD = 0.

Revealed masks: Facial mimicry after oxytocin administration in forensic psychopathic patients.

Facial mimicry serves as an evolutionarily rooted important interpersonal communication process that touches on the concepts of socialization and empathy. Facial electromyography (EMG) of the corrugator muscle and the zygomaticus muscle was recorded while male forensic psychopathic patients and controls watched morphed angry or happy facial expressions. We tested the hypothesis that psychopathic patients would show weaker short latency facial mimicry (that is, within 600 ms after stimulus onset) than controls.

Time trends in case-mix and risk of revision following hip and knee arthroplasty in public and private hospitals: a cross-sectional analysis based on 476,312 procedures from the Dutch Arthroplasty Register.

Background And Purpose: This study aims to assess time trends in case-mix and to evaluate the risk of revision and causes following primary THA, TKA, and UKA in private and public hospitals in the Netherlands.

Methods: We retrospectively analyzed 476,312 primary arthroplasties (public: n = 413,560 and private n = 62,752) implanted between 2014 and 2023 using Dutch Arthroplasty Register data. We explored patient demographics, procedure details, trends over time, and revisions per hospital type.

Unravelling the Belgian cascade of hypertension care and its determinants: insights from a cross-sectional analysis.

Background: Hypertension is a major risk factor for cardiovascular disease and all-cause mortality worldwide. Despite the widespread availability of effective antihypertensives, blood pressure (BP) control rates remain suboptimal, even in high-income countries such as Belgium. In this study, we used a cascade of care approach to identify where most patients are lost along the continuum of hypertension care in Belgium, and to assess the main risk factors for attrition at various stages of hypertension management.

Quantification of cefuroxime and flucloxacillin in synovial tissue and bone using ultra-performance convergence chromatography-tandem mass spectrometry.

After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery.

Evaluating the Clinical Relevance of Routine Sonication for Periprosthetic Hip or Knee Joint Infection Diagnosis.

Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. PJI screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique for PJI diagnosis.

Effect of optical diagnosis training on recognition and treatment of submucosal invasive colorectal cancer in community hospitals: a prospective multicenter intervention study.

Background:  Recognition of submucosal invasive colorectal cancer (T1 CRC) is difficult, with sensitivities of 35 %-60 % in Western countries. We evaluated the real-life effects of training in the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals.

Methods:  In this prospective multicenter study (OPTICAL II), 383 endoscopists from 40 hospitals were invited to follow an e-learning program on the OPTICAL model, to increase sensitivity in detecting T1 CRC in nonpedunculated polyps.

Reciprocal self-disclosure makes children feel more loved by their parents in the moment: A proof-of-concept experiment.

Feeling loved by one's parents is critical for children's health and well-being. How can such feelings be fostered? A vital feature of loving interactions is reciprocal self-disclosure, where individuals disclose intimate information about themselves. In a proof-of-concept experiment, we examined whether encouraging reciprocal self-disclosure in parent-child dyads would make children feel more loved during the conversation.

Low revision rate throughout the adoption of the direct superior approach in primary total hip arthroplasty: an analysis based on 1551 total hip arthroplasties from the Dutch Arthroplasty Register.

Background: Recently, surgeons introduced a minimally invasive modification on the classic posterolateral approach (PLA) in total hip arthroplasty (THA): the direct superior approach (DSA). We investigated the association between surgeon's experience and the risk of early revision of the DSA in primary THA, using data from the Dutch Arthroplasty Register (LROI).

Methods: We retrieved all primary THAs performed using the DSA in 4 hospitals between 2016 and 2022 ( = 1551).

Multimorbidity healthcare expenditure in Belgium: a 4-year analysis (COMORB study).

Background: The complex management of health needs in multimorbid patients, alongside limited cost data, presents challenges in developing cost-effective patient-care pathways. We estimated the costs of managing 171 dyads and 969 triads in Belgium, taking into account the influence of morbidity interactions on costs.

Methods: We followed a retrospective longitudinal study design, using the linked Belgian Health Interview Survey 2018 and the administrative claim database 2017-2020 hosted by the Intermutualistic Agency.

Femoral Neck Design Does Not Impact Revision Risk After Primary Total Hip Arthroplasty Using a Dual Mobility Cup.

Background: The use of dual mobility (DM) cups has increased quickly. It is hypothesized that femoral neck taper geometry may be involved in the risk of prosthetic impingement and DM cup revision. We aim to (1) explore the reasons for revision of DM cups or head/liners and (2) explore whether certain femoral neck characteristics are associated with a higher risk of revision of DM cups.

Standardised training for endoscopic mucosal resection of large non-pedunculated colorectal polyps to reduce recurrence (*STAR-LNPCP study): a multicentre cluster randomised trial.

Objective: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals.

Design: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group.

Full-color optical combiner with good imaging quality and a wide angle of incident light acceptance.

This work demonstrates a full-color optical image combiner for augmented reality head-up displays. In this device, the angle of the incident light of the computer-generated image reflected by it can vary over a large range. It achieves improved performance by using a combination of polarization interference filters (PIFs), quarter-wave retarders (QWRs), and polarization volume holograms (PVHs).

The Prediction of Biological Features Using Magnetic Resonance Imaging in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Magnetic resonance imaging (MRI) is an indispensable, routine technique that provides morphological and functional imaging sequences. MRI can potentially capture tumor biology and allow for longitudinal evaluation of head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis evaluates the ability of MRI to predict tumor biology in primary HNSCC.