Influence of germline variations in drug transporters ABCB1 and ABCG2 on intracerebral osimertinib efficacy in patients with non-small cell lung cancer.

Background: Central nervous system (CNS) metastases are present in approximately 40% of patients with metastatic epidermal growth factor receptor-mutated (m+) non-small cell lung cancer (NSCLC). The EGFR-tyrosine kinase inhibitor osimertinib is a substrate of transporters ABCB1 and ABCG2 and metabolized by CYP3A4. We investigated relationships between single nucleotide polymorphisms (SNPs) 3435C>T, 421C>A and 34G>A, and and CNS treatment efficacy of osimertinib in m+ NSCLC patients.

Invited review: Selective treatment of clinical mastitis in dairy cattle.

Treatment of clinical mastitis (CM) and use of antimicrobials for dry cow therapy are responsible for the majority of animal-defined daily doses of antimicrobial use (AMU) on dairy farms. However, advancements made in the last decade have enabled excluding nonsevere CM cases from antimicrobial treatment that have a high probability of cure without antimicrobials (no bacterial causes or gram-negative, excluding Klebsiella spp.) and cases with a low bacteriological cure rate (chronic cases).

Prevalence of extended-spectrum and AmpC β-lactamase-producing Escherichia coli in young calves on Dutch dairy farms.

In young calves on dairy farms the animal prevalence of extended-spectrum and AmpC β-lactamase-producing Escherichia coli (ESBL/AmpC-EC) is significantly higher compared with the animal prevalence in young stock and dairy cows. Hitherto it was unknown at what age antimicrobial resistant bacteria appear for the first time in the gut of calves on dairy farms, and how long these infections persist. The aim of this study was to examine the prevalence of ESBL/AmpC-EC, the number of excreted ESBL/AmpC-EC (in cfu/g of feces), as well as the ESBL/AmpC genotypes in young dairy calves (0-21 d of age) and the variation of these parameters between calves of different ages.

Additional Value of 3-Month Cranial Magnetic Resonance Imaging in Infants with Neonatal Encephalopathy following Perinatal Asphyxia.

Objective: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia.

Methods: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore.

Identification of Z-Tyr-Ala-CHN, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses, including SARS-CoV-2.

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partly under control by vaccination. However, highly potent and safe antiviral drugs for SARS-CoV-2 are still needed to avoid development of severe COVID-19. We report the discovery of a small molecule, Z-Tyr-Ala-CHN, which was identified in a cell-based antiviral screen.

Hyperlipidaemia elicits an atypical, T helper 1-like CD4 T-cell response: a key role for very low-density lipoprotein.

Aims: Hyperlipidemia and T cell driven inflammation are important drivers of atherosclerosis, the main underlying cause of cardiovascular disease. Here, we detailed the effects of hyperlipidemia on T cells.

Methods And Results: In vitro, exposure of human and murine CD4+ T cells to very low-density lipoprotein (VLDL), but not to low-density lipoprotein (LDL) resulted in upregulation of Th1 associated pathways.

Prediction of outcome after ligation or thin film banding of extrahepatic shunts, based on plasma albumin concentration and hematologic expression of 8 target genes in 85 dogs.

Background: In dogs with a congenital extrahepatic portosystemic shunt (EHPSS), outcome after surgical attenuation is difficult to predict.

Objectives: Develop a minimally invasive test to predict outcome after surgical EHPSS attenuation and establish risk factors for postattenuation seizures (PAS).

Animals: Eighty-five client-owned dogs referred for surgical attenuation of a single EHPSS.

OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction (OPTICORE): study protocol of a multicentre, retrospective cohort study.

Introduction: Early-onset fetal growth restriction (FGR) requires timely, often preterm, delivery to prevent fetal hypoxia causing stillbirth or neurologic impairment. Antenatal corticosteroids (CCS) administration reduces neonatal morbidity and mortality following preterm birth, most effectively when administered within 1 week preceding delivery. Optimal timing of CCS administration is challenging in early-onset FGR, as the exact onset and course of fetal hypoxia are unpredictable.

A Systematic Review of Chest Imaging Findings in Long COVID Patients.

Long COVID is the persistence of one or more COVID-19 symptoms after the initial viral infection, and there is evidence supporting its association with lung damage. In this systematic review, we provide an overview of lung imaging and its findings in long COVID patients. A PubMed search was performed on 29 September 2021, for English language studies in which lung imaging was performed in adults suffering from long COVID.

Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.

Background And Purpose: Medullary tegmental cap dysplasia is a rare brainstem malformation, first described and defined by James Barkovich in his book from 2005 as an anomalous mass protruding from the posterior medullary surface. We describe the neuroimaging, clinical, postmortem, and genetic findings defining this unique malformation.

Materials And Methods: This is a multicenter, international, retrospective study.

Universal beta-diversity-functioning relationships are neither observed nor expected.

Widespread evidence shows that local species richness (α-diversity) loss hampers the biomass production and stability of ecosystems. β-Diversity, namely the variation of species compositions among different ecological communities, represents another important biodiversity component, but studies on how it drives ecosystem functioning show mixed results. We argue that to better understand the importance of β-diversity we need to consider it across contexts.

Unraveling Amazon tree community assembly using Maximum Information Entropy: a quantitative analysis of tropical forest ecology.

In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies.

What are the needs of frail older patients in the emergency department? A qualitative study.

Background: There is an increase in the number of frail elderly patients presenting to the emergency department. Diagnosis and treatment for this patient group is challenging due to multimorbidity, a-typical presentation and polypharmacy and requires specialised knowledge and competencies from healthcare professionals. We aim to explore the needs and preferences regarding emergency care in frail older patients based on their experiences with received care during Emergency Department admission.

The Value of Current Meat Inspection and Food Chain Information of Dairy Cows in Relation to Findings and the Protection of Public Health: A Case for a More Risk-Based Meat Inspection.

In this study, the contribution of the (AM) inspection and the food chain information (FCI) to ensuring meat safety and public health was investigated, by evaluating the slaughterhouse findings of 223,600 slaughtered dairy cows in the Netherlands. The outcome of this study was that the (AM) and (PM) inspections have a substantial overlap, and that with regard to food safety and public health in over 99% of cases the PM could even be omitted on the basis of the AM. In this study, the data provided by the dairy farmers on the current FCI forms contributed little to nothing with regard to the outcomes of AM and PM inspection.

Moving forward to achieve the ambitions of the European Water Framework Directive: Lessons learned from the Netherlands.

The restoration and preservation of freshwater ecosystems is one of the prerequisites for a sustainable and fair future for all and therefore part of the United Nations Sustainable Development Goals (SDG 6). However, countries worldwide are facing a challenge to achieve this ambition by 2030. This paper focuses on the legal and governance challenges faced in the European context with regard to achieving water quality ambitions, using experiences from the Netherlands as a case study.

Design of OSMI-4 Analogs Using Scaffold Hopping: Investigating the Importance of the Uridine Mimic in the Binding of OGT Inhibitors.

β-N-Acetylglucosamine transferase (OGT) inhibition is considered an important topic in medicinal chemistry. The involvement of O-GlcNAcylation in several important biological pathways is pointing to OGT as a potential therapeutic target. The field of OGT inhibitors drastically changed after the discovery of the 7-quinolone-4-carboxamide scaffold and its optimization to the first nanomolar OGT inhibitor: OSMI-4.