Multi-layered proteomics identifies insulin-induced upregulation of the EphA2 receptor via the ERK pathway which is dependent on low IGF1R level.

Insulin resistance impairs the cellular insulin response, and often precedes metabolic disorders, like type 2 diabetes, impacting an increasing number of people globally. Understanding the molecular mechanisms in hepatic insulin resistance is essential for early preventive treatments. To elucidate changes in insulin signal transduction associated with hepatocellular resistance, we employed a multi-layered mass spectrometry-based proteomics approach focused on insulin receptor (IR) signaling at the interactome, phosphoproteome, and proteome levels in a long-term hyperinsulinemia-induced insulin-resistant HepG2 cell line with a knockout of the insulin-like growth factor 1 receptor (IGF1R KO).

Cervical cancer screening activity in the Capital Region of Denmark before, during and after the COVID-19 pandemic.

Objective: Denmark went through various COVID-19 pandemic restrictions including periodic lockdowns from March 2020 to January 2022. All cancer screening programs were kept operational, yet access to clinicians for cervical screening was at times limited. We assessed the impact of the pandemic on cervical cancer screening activity in the Capital Region of Denmark.

Subacute prognosis of oral nutrition (SPOON): Development of a multivariable prognostic model for complete oral intake in tube-fed subjects with acquired brain injury.

Background & Aims: Enteral feeding is very common following an acquired brain injury. However, no prognostic models for oral food intake have been developed for subacute rehabilitation. The aim of this study was to develop a prognostic model and online tool, coined "subacute prognosis of oral nutrition" (SPOON), for complete oral intake in tube-fed subjects with acquired brain injury.

Operational experiences from the general implementation of HPV self-sampling to Danish screening non-attenders.

The Danish cervical cancer screening program is a cost-free cancer prevention program for all Danish resident women aged 23-64 years. The coverage is 73%, but screening attendance is slowly declining. Notwithstanding, almost half of all newly diagnosed cervical cancers are found amongst screening non-attenders.

Clinical Performance of the Full Genotyping Agena MassARRAY HPV Assay Using SurePath Screening Samples within the VALGENT4 Framework.

The clinical performance evaluation of the novel MassARRAY human papillomavirus (MA-HPV) assay was performed using Danish SurePath cervical cancer screening samples under the fourth Validation of HPV Genotyping Tests (VALGENT) framework. The MA-HPV assay is a mass array-based assay that individually detects 14 oncogenic HPV genotypes and five nononcogenic types. The MA-HPV assay was validated using the VALGENT4 panel, which constitutes 997 consecutive samples from a screening population in addition to 297 disease-enriched samples with abnormal cytology findings.

The Effect of Normobaric Intermittent Hypoxia Therapy on Bone in Normal and Disuse Osteopenic Mice.

Bromer, Frederik Duch, Mikkel Bo Brent, Michael Pedersen, Jesper Skovhus Thomsen, Annemarie Brüel, and Casper Bindzus Foldager. The effect of normobaric intermittent hypoxia therapy on bone in normal and disuse osteopenic mice. .

Methylation markers FAM19A4 and miR124-2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study.

In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID-SCREEN is a EU-multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4/miR124-2 methylation-based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4/miR124-2 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV-positive cervical screening samples, from women 29-76 years of age, derived from four EU countries.

Clinical validation of full genotyping CLART® HPV4S assay on SurePath and ThinPrep collected screening samples according to the international guidelines for human papillomavirus test requirements for cervical screening.

Background: To ensure the highest quality of human papillomavirus (HPV) testing in primary cervical cancer screening, novel HPV assays must be evaluated in accordance with the international guidelines. Furthermore, HPV assay with genotyping capabilities are becoming increasingly important in triage of HPV positive women in primary HPV screening. Here we evaluate a full genotyping HPV assay intended for primary screening.

Sodium fluorescein shows high surgeon-reported usability in glioblastoma surgery.

Introduction: Glioblastoma has a high mortality rate. Current treatment includes largest possible surgical resection of the tumour using neuronavigation and fluorescence to better identify tumour tissue. In recent years, sodium fluorescein has been reintroduced in neurosurgery as a fluorescence to increase the resection rate.

Clinical and Analytical Performance of the BD Onclarity HPV Assay with SurePath Screening Samples from the Danish Cervical Screening Program Using the VALGENT Framework.

The idation of HPV otyping ests (VALGENT) framework is an international cooperation designed to evaluate human papillomavirus (HPV) assays with genotyping capabilities. Here, we assessed the performance of the BD Onclarity assay using Danish SurePath cervical screening samples collected under the fourth VALGENT installment, consisting of 998 consecutive samples from a screening population and 297 enriched samples with abnormal cytology (100 with atypical squamous cells of undetermined significance [ASCUS], 100 with low-grade squamous intraepithelial lesions [LSIL], and 97 with high-grade squamous intraepithelial lesions [HSIL]). The Onclarity assay detects six HPV genotypes individually (genotypes 16, 18, 31, 45, 51, and 52) and eight genotypes in three bulks (genotypes 33 and 58; genotypes 56, 59, and 66; and genotypes 35, 39, and 68).

Barthel Index at hospital admission is associated with mortality in geriatric patients: a Danish nationwide population-based cohort study.

Purpose: The Barthel Index (BI)-100 is used to measure geriatric patients' activities of daily living (ADL). The aim of this study was to explore whether BI at hospital admission is associated with mortality.

Patients And Methods: In a nationwide population-based cohort study, patients aged ≥65 years admitted during 2005-2014 to Danish geriatric departments were assessed with BI at admission.

Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma.

Oncogenic anaplastic lymphoma kinase (ALK) is one of the few druggable targets in neuroblastoma, and therapy resistance to ALK-targeting tyrosine kinase inhibitors (TKIs) comprises an inevitable clinical challenge. Therefore, a better understanding of the oncogenic signaling network rewiring driven by ALK is necessary to improve and guide future therapies. Here, we performed quantitative mass spectrometry-based proteomics on neuroblastoma cells treated with one of three clinically relevant ALK TKIs (crizotinib, LDK378, or lorlatinib) or an experimentally used ALK TKI (TAE684) to unravel aberrant ALK signaling pathways.

Lung cancer screening: national consensus is an important step toward implementation.

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Prevalence of Human Papillomavirus in Self-Taken Samples from Screening Nonattenders.

The Copenhagen Self-Sampling Initiative (CSi) has shown how human papillomavirus (HPV)-based self-sampling can be used to increase screening participation among 23,632 nonattenders in the Capital Region of Denmark. In this study, we describe HPV prevalence and genotype frequency in 4,824 self-samples as determined by three HPV assays (the CLART, Onclarity, and Hybrid Capture 2 [HC2] assays) and compare the results with those for physician-taken follow-up samples. The HPV self-sample findings were also compared to the findings for a reference population of 3,347 routinely screened women from the Horizon study, which had been undertaken in the same screening laboratory.

Self-Sampling for Human Papillomavirus Testing among Non-Attenders Increases Attendance to the Norwegian Cervical Cancer Screening Programme.

Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus (HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance. To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25-69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited to be part of the intervention group.

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment.

Aim: To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendroflumethiazide (BFTZ), amiloride and placebo.

Methods: In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fluid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.

Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation.

SH-SY5Y neuroblastoma cells respond to nerve growth factor (NGF)-mediated activation of the tropomyosin-related kinase A (TrkA) with neurite outgrowth, thereby providing a model to study neuronal differentiation. We performed a time-resolved analysis of NGF-TrkA signaling in neuroblastoma cells using mass spectrometry-based quantitative proteomics. The combination of interactome, phosphoproteome, and proteome data provided temporal insights into the molecular events downstream of NGF binding to TrkA.

Long-term Oncologic and financial implications of lung cancer screening.

Benefits and risks of computed tomography lung cancer screening are discussed with specific focus on oncologic and financial issues. Earlier disease stage at diagnosis implies that more patients are treated surgically, but the changes in oncologic treatment will not be dramatic. The crucial issue for implementation of screening will be that it is cost effective.

Graft rejection and graft failure after penetrating keratoplasty or posterior lamellar keratoplasty for fuchs endothelial dystrophy.

Purpose: To compare the frequency of rejection episodes and graft failure because of surgical complications or rejection after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for Fuchs endothelial dystrophy.

Methods: A total of 201 eyes of 201 consecutive patients with Fuchs endothelial dystrophy undergoing keratoplasty were included. One hundred two patients underwent DSAEK and 99 PK in the period January 1, 2000, to December 31, 2010.

Sound exposure of symphony orchestra musicians.

Background: Assessment of sound exposure by noise dosimetry can be challenging especially when measuring the exposure of classical orchestra musicians where sound originate from many different instruments. A new measurement method of bilateral sound exposure of classical musicians was developed and used to characterize sound exposure of the left and right ear simultaneously in two different symphony orchestras.

Objectives: To measure binaural sound exposure of professional classical musicians and to identify possible exposure risk factors of specific musicians.

The Danish randomized lung cancer CT screening trial--overall design and results of the prevalence round.

Introduction: Lung cancer screening with low dose computed tomography (CT) has not yet been evaluated in randomized clinical trials, although several are underway.

Methods: In The Danish Lung Cancer Screening Trial, 4104 smokers and previous smokers from 2004 to 2006 were randomized to either screening with annual low dose CT scans for 5 years or no screening. A history of cigarette smoking of at least 20 pack years was required.

Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response?

Background: Anti-inflammatory treatment affects ischemic damage and neurogenesis in rodent models of cerebral ischemia. We investigated the potential benefit of COX-2 inhibition with parecoxib in spontaneously hypertensive rats (SHRs) subjected to transient middle cerebral artery occlusion (tMCAo).

Methods: Sixty-four male SHRs were randomized to 90 min of intraluminal tMCAo or sham surgery.

Mathematical models behind advanced simulators in medicine.

The paper presents as an example the types of mathematical models that are used in a full scale anesthesia simulator. The models vary from detailed reference models, based on fundamental physiological laws and principles, to simple script based models. A few considerations on the implementation of the models are also given.