Blueprint of ethics content in undergraduate education: A workshop-research study.

Background: Ethics is a fundamental component of nursing education to increase students' moral competence and moral reasoning abilities. However, the core ethics content that should be included in undergraduate education has not been established to date at the international level.

Aim: To identify the core contents required in formal undergraduate education to ensure morally competent nurses.

Discovery of (3-Phenylcarbamoyl-3,4-dihydro-2-pyrrol-2-yl)phosphonates as Imidazoline Receptor Ligands with Anti-Alzheimer and Analgesic Properties.

Imidazoline receptors (I-IRs) are altered in Alzheimer's disease (AD) patients and are associated with analgesia. I-IRs are not structurally described, and their pharmacological characterization relies on their modulation by highly affine ligands. Herein, we describe the synthesis of (3-phenylcarbamoyl-3,4-dihydro-2-pyrrol-2-yl)phosphonates endowed with relevant affinities for I-IRs in human brain tissues.

Improved Ammonia Synthesis and Energy Output from Zinc-Nitrate Batteries by Spin-State Regulation in Perovskite Oxides.

Electrocatalytic nitrate reduction to ammonia (eNRA) is a promising route toward environmental sustainability and clean energy. However, its efficiency is often limited by the slow conversion of intermediates due to spin-forbidden processes. Here, we introduce a novel A-site high-entropy strategy to develop a new perovskite oxide (LaPrNdBaSr)CoO (LPNBSC) for eNRA.

Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Pathological diagnosis of central nervous system tumours in adults: what's new?

In the course of the last decade, the pathological diagnosis of many tumours of the central nervous system (CNS) has transitioned from a purely histological to a combined histological and molecular approach, resulting in a more precise 'histomolecular diagnosis'. Unfortunately, translation of this refinement in CNS tumour diagnostics into more effective treatment strategies is lagging behind. There is hope though that incorporating the assessment of predictive markers in the pathological evaluation of CNS tumours will help to improve this situation.

Structure-Based Optimization of Pyridone α-Ketoamides as Inhibitors of the SARS-CoV-2 Main Protease.

The main protease M is a clinically validated target to treat infections by the coronavirus SARS-CoV-2. Among the first reported M inhibitors was the peptidomimetic α-ketoamide , whose cocrystal structure with M paved the way for multiple lead-finding studies. We established structure-activity relationships for the series by modifying residues at the P1', P3, and P4 sites.

The Benefit of Evolution of Pesticide Tolerance Is Overruled under Combined Stressor Exposure due to Synergistic Stressor Interactions.

Despite pleas to consider both evolutionary and multistressor climate change perspectives to improve ecological risk assessment, the much needed combination of both perspectives is largely missing. This is especially important when evaluating the costs of the evolution of genetic tolerance to pollutants as these costs may become visible only under combined exposure to the pollutant and warming due to energetic constraints. We investigated the costs of chlorpyrifos tolerance in when sequentially exposed to 4-day pesticide treatments and 4-day heat spike treatments.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert.

Tuberous sclerosis complex-associated kidney disease in children.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder which can have manifestations in the kidneys, along with other organ systems. Children with TSC may develop kidney lesions at any point during childhood, and typically these are angiomyolipomata (AML) and/or kidney cysts. Children may also have hypertension associated with TSC-associated kidney disease, and rarely reduced kidney function.

Validation of mixed reality in planning orbital reconstruction with patient-specific implants.

This study aims to evaluate and compare the usability and performance of mixed reality (MR) technology versus conventional methods for preoperative planning of patient-specific reconstruction plates for orbital fractures. A crossover study design was used to compare MR technology with conventional three-dimensional (3D) printing approaches in the planning of maxillofacial traumatology treatments. The primary focus was on user-friendliness and the accuracy of patient-specific reconstruction planning.

Flexible micromachined ultrasound transducers (MUTs) for biomedical applications.

The use of bulk piezoelectric transducer arrays in medical imaging is a well-established technology that operates based on thickness mode piezoelectric vibration. Meanwhile, advancements in fabrication techniques have led to the emergence of micromachined alternatives, namely, piezoelectric micromachined ultrasound transducer (PMUT) and capacitive micromachined ultrasound transducer (CMUT). These devices operate in flexural mode using piezoelectric thin films and electrostatic forces, respectively.

Pitfalls in gut single-cell eukaryote research.

Gut single-celled eukaryotes (GSCEs) are found in billions of people worldwide, but we still know little about their functions and relationships in human gut ecology. Lately, retrospective analysis of bacterial data obtained by next-generation sequencing (NGS) methods has been used to identify links between GSCEs, gut bacteria, host metabolism, and host phenotypical traits, suggesting possible direct or indirect associations to favorable gut microbiome features and other health parameters. Here, we highlight some of the pitfalls related to the research strategy typically used so far and propose action points that could pave the way for a more accurate understanding of GSCEs in human health and disease.

UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia.

T-cell receptor recognition of cognate peptide-MHC leads to the formation of signalling domains and the immunological synapse. Because of the close membrane apposition, there is rapid exclusion of CD45, and therefore LCK activation. Much less is known about whether spatial regulation of the intracellular face dictates LCK activity and TCR signal transduction.

Larger sample sizes are needed when developing a clinical prediction model using machine learning in oncology: methodological systematic review.

Background: Having a sufficient sample size is crucial when developing a clinical prediction model. We reviewed details of sample size in studies developing prediction models for binary outcomes using machine learning (ML) methods within oncology and compared the sample size used to develop the models with the minimum required sample size needed when developing a regression-based model (N).

Methods: We searched the Medline (via OVID) database for studies developing a prediction model using ML methods published in December 2022.

A randomised phase III study of bevacizumab and carboplatin-pemetrexed chemotherapy with or without atezolizumab, as first-line treatment for advanced pleural mesothelioma: results of the ETOP 13 18 BEAT-meso trial.

Background: The currently approved frontline treatments for diffuse pleural mesothelioma (DPM) are ipilimumab-nivolumab or platinum-pemetrexed. The addition of bevacizumab to chemotherapy improves overall survival (OS). While single-agent immunotherapy or chemotherapy-immunotherapy combinations are superior to chemotherapy monotherapy, there is a potential for synergistic triple combination of chemotherapy, bevacizumab, and immunotherapy.

Structure-based discovery of novel diarylpyrimidines as potent and selective Non-Nucleoside reverse transcriptase inhibitors: From CH(CN)-Biphenyl-Diarylpyrimidines to CNNH-Biphenyl-Diarylpyrimidines.

In order to enhance the anti-HIV-1 potency and selectivity of the previously reported compound 3 (EC = 27 nM, SI = 1361), a series of novel biphenyl-diarylpyrimidine derivatives were developed by employing structure-based drug design strategy. Among these derivatives, compound M44 demonstrated the most potent inhibitory activity against wild-type (WT) HIV-1 as well as five drug-resistant mutants (EC = 5-148 nM), which were 5-173 times more potent than that of 3 (EC = 27-9810 nM). Furthermore, this analogue exhibited approximately 11-fold lower cytotoxicity (CC = 54 μM) than that of etravirine and rilpivirine.

N-glycan shielded CUB domains of ADAMTS13 prevent binding of C-terminal antibodies in patients with immune-mediated TTP.

In Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP), patients develop antibodies against ADAMTS13. The majority of patients exhibit inhibitory anti-spacer antibodies. Non-inhibitory antibodies binding to the carboxy-terminal CUB domains have been suggested to enhance the clearance of ADAMTS13 in iTTP.

Clinical and imaging spectrum of non-congenital dominant ACTN2 myopathy.

Background: Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy.

Methods: Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium.

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Data fusion by T3-PCA: A global model for the simultaneous analysis of coupled three-way and two-way real-valued data.

In various areas of science, researchers try to gain insight into important processes by jointly analysing different datasets containing information regarding common aspects of these processes. For example, to explain individual differences in personality, researchers collect, for the same set of persons, data regarding behavioural signatures (i.e.