A new approach to off-gas analysis for shaken bioreactors showing high CTR and RQ accuracy.

Background: Shake flasks are essential tools in biotechnological development due to their cost efficiency and ease of use. However, a significant challenge is the miniaturization of process analytical tools to maximize information output from each cultivation. This study aimed to develop a respiration activity online measurement system via off-gas analysis, named "Transfer rate Online Measurement" (TOM), for determining the oxygen transfer rate (OTR), carbon dioxide transfer rate (CTR), and the respiration quotient (RQ) in surface-aerated bioreactors, primarily targeting shake flasks.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Semi-mechanistic efficacy model for PARP + ATR inhibitors-application to rucaparib and talazoparib in combination with gartisertib in breast cancer PDXs.

Background: Promising cancer treatments, such as DDR inhibitors, are often challenged by the heterogeneity of responses in clinical trials. The present work aimed to build a computational framework to address those challenges.

Methods: A semi-mechanistic pharmacokinetic-pharmacodynamic model of tumour growth inhibition was developed to investigate the efficacy of PARP and ATR inhibitors as monotherapies, and in combination.

A morphometric signature to identify ductal carcinoma in situ with a low risk of progression.

Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early breast cancer, many women with harmless DCIS face overtreatment. To identify features associated with progression, we developed an artificial intelligence-based DCIS morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections.

Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis.

Under stress, bacteria display selective growth propensities on solid and liquid media. For Mycobacterium tuberculosis (Mtb), differentially culturable bacteria have been found in tuberculosis (TB) patient sputa. We hypothesized that antibiotic treatment can induce selective culturability in Mtb.

Different keratoconus definitions can lead to substantial prevalence disparities in population-based studies.

This report explores the prevalence of keratoconus in a population-based cohort of adults aged 40 or older according to ten different definitions. All Rotterdam Study participants with reliable Pentacam scans and no prior corneal refractive surgery were cross-sectionally analysed (n = 2660). First, we applied a novel evidence-based definition.

Comparative analysis of salivary cytokine profiles in newly diagnosed pediatric patients with cancer and healthy children.

Salivary cytokines have the potential to serve as biomarkers for evaluating cancer progression and treatment response in specific cancer types. This study explored salivary cytokine profiles in pediatric cancer patients and healthy controls, examining changes during chemotherapy. We conducted a prospective study involving newly diagnosed cancer patients and healthy controls under 19 years old.

High prevalence of veterinary drugs in bird's nests.

The environmental impact of insecticides used as ectoparasitic treatments for companion animals is not well understood, since they are not subject to detailed environmental risk assessment. Many of these treatments include active ingredients such as fipronil and imidacloprid that are banned from agricultural use in the EU. These treatments are applied topically and can remain on the animal's fur for an extended period of time.

Oncogenic competence: balancing mutations, cellular state, and microenvironment.

Cancer development is driven by mutations, yet tumor-causing mutations only lead to tumor formation within specific cellular contexts. The reasons why certain mutations trigger malignant transformation in some contexts but not others remain often unclear. Both intrinsic and extrinsic factors play a key role in driving carcinogenesis by leading the cells toward a state of 'oncogenic competence'.

'I wish I had been better prepared': a mixed-methods study of psychological reactions, perceptions and opinions of cardiovascular preparticipation screening among young competitive athletes.

Objective: To evaluate the psychological reactions, perceptions and opinions of cardiovascular preparticipation screening (PPS) among young competitive athletes.

Methods: This convergent parallel mixed-methods study recruited 222 athletes (mean age: 18.7 years) who underwent PPS at a Canadian university.

Parsimonious versus extensive bleeding score: can we simplify risk stratification after percutaneous coronary intervention and reduce bleeding events by de-escalation of the antiplatelet strategy?

Background And Aims: Due to the multitude of risk factors outlined in the guidelines, personalised dual antiplatelet therapy (DAPT) guidance after percutaneous coronary intervention (PCI) is complex. A simplified method was created to facilitate the use of risk stratification. We aimed to compare the predictive and prognostic value of the 'Zuidoost Nederland Hart Registratie' (ZON-HR) classification for bleeding risk with the PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent DAPT (PRECISE-DAPT) score and to determine the effect of ticagrelor monotherapy versus DAPT in patients with or without high bleeding risk (HBR).

The Impact of Changing Physicians on Compliance with Management of Myopia Progression.

Background: The global incidence of high myopia is increasing, with projections indicating a rise from 3 to 10% of the global population by 2050. Effective treatment options exist to reduce myopia progression, but their success is contingent on patient adherence. This study assesses the impact of changes in treating physicians on adherence to therapy to control myopia progression.

Formulation screening of lyophilized mRNA-lipid nanoparticles.

Lipid nanoparticles (LNPs) have demonstrated their therapeutic potential as safe and effective drug delivery systems for nucleic acids during the COVID-19 pandemic. However, one of the main challenges during technical CMC (Chemistry, Manufacturing, and Controls) development is their long-term stability at temperatures of 2-8 °C or higher, which may be improved by the removal of water by lyophilization. In this study, we identified lyo-/cryo-protectants for freeze-dried mRNA-LNP formulations beyond conventional excipients such as sucrose and trehalose as T-modifiers using polyA as a surrogate.

Acute effect of aerobic exercise on inhibitory control and task-related heart rate variability in preadolescent children.

Objectives: To investigate whether a single session of aerobic exercise improves inhibitory control in preadolescent children and whether this effect is mediated by changes in parasympathetic activity.

Design: In this experimental study, an intervention and control group were pair-matched by age, sex and moderate-to-vigorous physical activity.

Method: 114 participants either completed a 20-min moderately-intense exercise bout on a cycling ergometer or watched a 20-min video.

Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.

Has the documentation of chest injuries and the development of systemic complications in patients with long bone fractures changed over time?-A systematic literature review and meta-analysis by the IMPACT expert group.

Introduction: Blunt chest trauma represents a major risk factor for complications in polytrauma patients. Various scoring systems have emerged, but their impact is not fully appreciated. This review evaluates changes in chest trauma scoring over time and potential shifts in complication rates linked to modified surgical approaches in long bone fractures.

Towards contrast-agnostic soft segmentation of the spinal cord.

Spinal cord segmentation is clinically relevant and is notably used to compute spinal cord cross-sectional area (CSA) for the diagnosis and monitoring of cord compression or neurodegenerative diseases such as multiple sclerosis. While several semi and automatic methods exist, one key limitation remains: the segmentation depends on the MRI contrast, resulting in different CSA across contrasts. This is partly due to the varying appearance of the boundary between the spinal cord and the cerebrospinal fluid that depends on the sequence and acquisition parameters.

Fibrosis in PCLS: comparing TGF-β and fibrotic cocktail.

Introduction: Fibrotic cocktail (FC) is a combination of pro-fibrotic and pro-inflammatory mediators that induces early fibrotic changes in organotypic lung models. We hypothesised that transforming growth factor beta 1 (TGF-β1) alone induces a pro-fibrotic effect similar to FC. Our aim was to compare the pro-fibrotic effects of TGF-β1 with FC in human precision-cut lung slices (PCLS).

A human metabolic map of pharmacological perturbations reveals drug modes of action.

Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.

Small changes of femoral torsion in varus or valgus distal femoral osteotomy using patient-specific instruments.

Purpose: Hinge fractures show a relatively high incidence in varus and valgus distal femoral osteotomy (DFO) and can lead to delayed- or non-union. Another observed complication of a hinge fracture is an unintentional change of the postoperative femoral torsion of up to + 9.5° in conventionally performed DFO.

fMRI data acquisition and analysis for task-free, anesthetized rats.

Templates for the acquisition of large datasets such as the Human Connectome Project guide the neuroimaging community to reproducible data acquisition and scientific rigor. By contrast, small animal neuroimaging often relies on laboratory-specific protocols, which limit cross-study comparisons. The establishment of broadly validated protocols may facilitate the acquisition of large datasets, which are essential for uncovering potentially small effects often seen in functional MRI (fMRI) studies.

The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow.

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing.

A large synthetic dataset for machine learning applications in power transmission grids.

With the ongoing energy transition, power grids are evolving fast. They operate more and more often close to their technical limit, under more and more volatile conditions. Fast, essentially real-time computational approaches to evaluate their operational safety, stability and reliability are therefore highly desirable.

Exploring when to exploit: the cognitive underpinnings of foraging-type decisions in relation to psychopathy.

Impairments in reinforcement learning (RL) might underlie the tendency of individuals with elevated psychopathic traits to behave exploitatively, as they fail to learn from their mistakes. Most studies on the topic have focused on binary choices, while everyday functioning requires us to learn the value of multiple options. In this study, we evaluated the cognitive correlates of naturalistic foraging-type decision-making and their electrophysiological signatures in a community sample (n = 108) with varying degrees of psychopathic traits.

Abiraterone acetate fixed-dosed combinations with ibuprofen-based therapeutic eutectic and deep eutectic solvents.

In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent.