Age-specific SARS-CoV-2 transmission differed from human rhinovirus in households during the early COVID-19 pandemic.

Objectives: Children are generally considered main drivers of transmission for respiratory viruses, but the emergence of SARS-CoV-2 challenged this paradigm. Human rhinovirus (RV) continued to co-circulate throughout the pandemic, allowing for direct comparison of age-specific infectivity and susceptibility within households between these viruses during a time of low SARS-CoV-2 population immunity.

Methods: Households with children were prospectively monitored for ≥23 weeks between August 2020 and July 2021.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of susceptibility and infectivity by person-type. A main inclusion criterion in such studies is usually the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household.

Development and validation of a fully automated laboratory-developed test for detection of HSV-1/2 and VZV in clinical samples run on the Panther Fusion® system.

The purpose of this study was to develop a laboratory developed test (LDT) for HSV1/2 and VZV to run on fully automated Hologic Panther Fusion® System. The Panther Fusion System is a fully automated walkaway system, providing end-to-end workflow from sample input to DNA/RNA extraction, amplification, automated analysis, and reporting to a laboratory information system (LIS). The LDT was developed and validated on 230 clinical and 20 reference samples (n = 250) and compared to a commercially available kit.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of individual susceptibility and infectivity. A main inclusion criterion in such studies is often the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household.

Comparative effectiveness of β-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study.

Objectives: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia.

Methods: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia.

Positive Impact of [18F]FDG-PET/CT on Mortality in Patients With Staphylococcus aureus Bacteremia Explained by Immortal Time Bias.

Background: Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias.

Methods: Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB.

Similar Sensitivity of SARS-CoV-2 Detection in Oropharyngeal/Nasopharyngeal and Saliva Samples on the Hologic Panther Platform.

Background: Oropharyngeal (OP) and nasopharyngeal (NP) sampling has historically been considered the reference specimen type used for respiratory virus detection. Saliva could be a less invasive alternative for SARS-CoV-2 detection, but limited evidence is available.

Methods: The technical and clinical performance of saliva was compared to OP/NP on the Hologic Panther platform with two Aptima assays, the End-Point Transcription-Mediated Amplification assay (EP-TMA) and Real-Time Transcription-Mediated Amplification assay (RT-TMA).

All-Cause and Infection-Related Mortality in Bacteremia, a Multicenter Prospective Cohort Study.

Background: bacteremia (SAB) is a heterogeneous disease with changing epidemiology due to changing demographics and evolving clinical management. SAB is associated with high mortality, but the current fraction of infection-related mortality is less well quantified.

Methods: In a multicenter prospective cohort study of consecutive patients with SAB, we determined clinical features of SAB and determined 90-day mortality and risk factors of all-cause and infection-related mortality.

Longitudinal Household Assessment of Respiratory Illness in Children and Parents During the COVID-19 Pandemic.

Importance: In the early COVID-19 pandemic, SARS-CoV-2 testing was only accessible and recommended for symptomatic persons or adults. This restriction hampered assessment of the true incidence of SARS-CoV-2 infection in children as well as detailed characterization of the SARS-CoV-2 disease spectrum and how this spectrum compared with that of other common respiratory illnesses.

Objective: To estimate the community incidence of SARS-CoV-2 infection in children and parents and to assess the symptoms and symptom severity of respiratory illness episodes involving SARS-CoV-2-positive test results relative to those with SARS-CoV-2-negative test results.

Mouse organoids as an in vitro tool to study the in vivo intestinal response to cytotoxicants.

Cross-species comparison of drug responses at the organoid level could help to determine the human relevance of findings from animal studies. To this end, we first need to evaluate the in vitro to in vivo translatability of preclinical organoids. Here, we used 5-fluorouracil (5-FU) as an exemplar drug to test whether the in vivo gut response to this cytotoxicant was preserved in murine intestinal organoids.

Initial Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load Is Associated With Disease Severity: A Retrospective Cohort Study.

Background: We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and hospital admission, intensive care unit (ICU) admission, and in-hospital mortality.

Methods: All SARS-CoV-2-positive persons with a combined nasopharyngeal and oropharyngeal swab that was collected between 17 March 2020 and 31 March 2021 in public health testing facilities were included.

Results: From 20 207 SARS-CoV-2-positive persons, 310 (1.

Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors.

Patient-derived organoids (PDOs) recapitulate tumor architecture, contain cancer stem cells and have predictive value supporting personalized medicine. Here we describe a large-scale functional screen of dual-targeting bispecific antibodies (bAbs) on a heterogeneous colorectal cancer PDO biobank and paired healthy colonic mucosa samples. More than 500 therapeutic bAbs generated against Wingless-related integration site (WNT) and receptor tyrosine kinase (RTK) targets were functionally evaluated by high-content imaging to capture the complexity of PDO responses.

Linker-Improved Chimeric Endolysin Selectively Kills Staphylococcus aureus , on Reconstituted Human Epidermis, and in a Murine Model of Skin Infection.

Staphylococcus aureus causes a broad spectrum of diseases in humans and animals. It is frequently associated with inflammatory skin disorders such as atopic dermatitis, where it aggravates symptoms. Treatment of S.

The Effect of Varying Interval Definitions on the Prevalence of SARS-CoV-2 Reinfections: A Retrospective Cross-Sectional Cohort Study.

Background: We assessed the SARS-CoV-2 reinfection rate in a large patient cohort, and evaluated the effect of varying time intervals between two positive tests on assumed reinfection rates using viral load data.

Methods: All positive SARS-CoV-2 samples collected between 1 March 2020 and 1 August 2021 from a laboratory in the region Kennemerland, the Netherlands, were included. The reinfection rate was analyzed using different time intervals between two positive tests varying between 2 and 16 weeks.

A Transcriptomic Approach to Elucidate the Mechanisms of Gefitinib-Induced Toxicity in Healthy Human Intestinal Organoids.

Gefitinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits the epidermal growth factor receptor (EGFR), hampering cell growth and proliferation. Due to its action, gefitinib has been used in the treatment of cancers that present abnormally increased expression of EGFR. However, side effects from gefitinib therapy may occur, among which diarrhoea is most common, that can lead to interruption of the planned therapy in the more severe cases.

Unravelling Mechanisms of Doxorubicin-Induced Toxicity in 3D Human Intestinal Organoids.

Doxorubicin is widely used in the treatment of different cancers, and its side effects can be severe in many tissues, including the intestines. Symptoms such as diarrhoea and abdominal pain caused by intestinal inflammation lead to the interruption of chemotherapy. Nevertheless, the molecular mechanisms associated with doxorubicin intestinal toxicity have been poorly explored.

[Staphylococcus aureus osteomyelitis in children].

Osteomyelitis is an infectious disease of the bone that primarily affects children. Here we discuss three patients, aged 11-13 years that were diagnosed with osteomyelitis. Despite the fact that in all three patients the infection was caused by the Staphylococcus Aureus bacteria, the clinical presentation and diagnostic results in all three was different.

Clinical Sensitivity, Specificity and Epidemiology of SARS-CoV-2 Serological Testing Using the Biozek COVID-19 Test.

Background: Clinical validation using the Biozek COVID-19 test including sensitivity and specificity and associated patient-reported symptoms with SARS-CoV-2 seropositivity.

Methods: 316 sera were analyzed including 47 hospitalized cases, 50 mild cases and 219 negative controls. Results were read visually by two technicians and in case of discrepancy by a third.

SARS-CoV-2 viral-load distribution reveals that viral loads increase with age: a retrospective cross-sectional cohort study.

Background: Describing the SARS-CoV-2 viral-load distribution in different patient groups and age categories.

Methods: All results from first nasopharyngeal (NP) and oropharyngeal (OP) swabs from unique patients tested via SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) collected between 1 January and 1 December 2020 predominantly in the Public Health Services regions Kennemerland and Hollands Noorden, province of North Holland, the Netherlands, were included in this study. SARS-CoV-2 PCR crossing-point (Cp)-values were used to estimate viral loads.

Butyrate and propionate restore interleukin 13-compromised esophageal epithelial barrier function.

Background: Eosinophilic esophagitis (EoE) is a food allergen driven disease that is accompanied by interleukin (IL) 13 overexpression and esophageal barrier dysfunction allowing transepithelial food allergen permeation. Nutraceuticals, such as short-chain fatty acids (SCFAs) that restore barrier function and increase immune fitness may be a promising tool in the management of EoE. Here, we investigated the effects of the SCFAs acetate, propionate, and butyrate on an IL-13-compromised human esophageal epithelial barrier, including the mechanisms involved.

Prediction Rules for Ruling Out Endocarditis in Patients With Staphylococcus aureus Bacteremia.

Background: Staphylococcus aureus bacteremia (SAB) is in 10% to 20% of cases complicated by infective endocarditis. Clinical prediction scores may select patients with SAB at highest risk for endocarditis, improving the diagnostic process of endocarditis. We compared the accuracy of the Prediction Of Staphylococcus aureus Infective endocarditiseTime to positivity, Iv drug use, Vascular phenomena, preExisting heart condition (POSITIVE), Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT), and VIRSTA scores for classifying the likelihood of endocarditis in patients with SAB.

New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids.

5-Fluorouracil (5-FU) is a widely used chemotherapeutical that induces acute toxicity in the small and large intestine of patients. Symptoms can be severe and lead to the interruption of cancer treatments. However, there is limited understanding of the molecular mechanisms underlying 5-FU-induced intestinal toxicity.

Hherisomes, Hedgehog specialized recycling endosomes, are required for high level Hedgehog signaling and tissue growth.

In metazoans, tissue growth and patterning is partly controlled by the Hedgehog (Hh) morphogen. Using immuno-electron microscopy on Drosophila wing imaginal discs, we identified a cellular structure, the Hherisomes, which contain the majority of intracellular Hh. Hherisomes are recycling tubular endosomes, and their formation is specifically boosted by overexpression of Hh.

Temporal Variation in Staphylococcus aureus Protein A Genotypes from Nose and Skin in Atopic Dermatitis Patients.

Background: Staphylococcus aureus colonization is associated with disease severity in patients with atopic dermatitis (AD).

Objective: To investigate temporal variation in S. aureus protein A gene (spa)-types isolated from the nose and lesional skin and the correlation of spa-types with disease severity.

Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy.

Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs.