Reflection to enhance dental students´ awareness of and comfort with uncertainty - an experimental study.

Background: Uncertainty is present in many situations in dental practice, but must not prevent wise clinical decision-making. Dental education should acknowledge uncertainty and teach useful management strategies. This study explored if dental students are aware of, and comfortable with uncertainty.

Airway MMP-12 and DNA methylation in COPD: an integrative approach.

Background: In COPD, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] is shifted towards excessive degradation, reflected in bronchoalveolar lavage (BAL) as increased MMP concentrations. Because of their critical role in lung homeostasis, MMP activity is tightly regulated, but to what extent this regulation occurs through epigenetic mechanisms remains unknown.

Methods: To explore the interplay between MMPs, TIMPs, and DNA methylation (DNAm) we (1) analysed MMP-9, -12, and TIMP-1 concentrations in BAL fluid, and profiled DNAm in BAL cells from 18 COPD and 30 control subjects, (2) estimated protein-COPD relationships using multivariable regression, (3) identified protein quantitative trait methylation loci (pQTMs) with COPD as a potential modifier in a separate interaction model, and (4) integrated significant interactions with a previous COPD GWAS meta-analysis.

BiomiX, a user-friendly bioinformatic tool for democratized analysis and integration of multiomics data.

Background: Interpreting biological system changes requires interpreting vast amounts of multi-omics data. While user-friendly tools exist for single-omics analysis, integrating multiple omics still requires bioinformatics expertise, limiting accessibility for the broader scientific community.

Results: BiomiX tackles the bottleneck in high-throughput omics data analysis, enabling efficient and integrated analysis of multiomics data obtained from two cohorts.

Prognostic Testing for Prostate Cancer-A Cost-Effectiveness Analysis Comparing a Prostatype P-Score Biomarker Approach to Standard Clinical Practice.

Background: The Prostatype score (P-score) is a prognostic biomarker that integrates a three-gene (IGFBP3, F3, and VGLL3) signature derived from prostate biopsy samples, with key clinical parameters, including prostate-specific antigen (PSA) levels, Gleason grade, and tumor stage at diagnosis. The test has demonstrated superior predictive accuracy for prostate cancer outcomes compared with traditional risk categorization systems such as D'Amico. Notably, it reclassifies a higher proportion of patients into the low-risk category, making them eligible for active surveillance.

AI image analysis as the basis for risk-stratified screening.

Artificial intelligence (AI) has emerged as a transformative tool in breast cancer screening, with two distinct applications: computer-aided cancer detection (CAD) and risk prediction. While AI CAD systems are slowly finding its way into clinical practice to assist radiologists or make independent reads, this review focuses on AI risk models, which aim to predict a patient's likelihood of being diagnosed with breast cancer within a few years after negative screening. Unlike AI CAD systems, AI risk models are mainly explored in research settings without widespread clinical adoption.

High prevalence of atrial conduction abnormalities in Lewy body disease - a marker of cardiac complications?

Increasing evidence suggests that Lewy body disease (LBD) is associated with clinically important cardiac complications, including sick sinus syndrome, atrial fibrillation and sudden cardiac death. The high prevalence of sick sinus syndrome and atrial fibrillation in LBD suggests the presence of disease-related atrial conduction disorders. To explore whether LBD is associated with atrial conduction disorders, electrocardiographic (ECG) P wave parameters were analyzed in a cohort of LBD patients (n = 74), using age-matched Alzheimer's disease (AD) patients (n = 25) as controls.

Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease.

In Alzheimer's disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau determined in the cerebrospinal fluid (CSF).

Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis.

Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid.

Leisure-Time Physical Activity, Sedentary Behavior, and Biological Aging: Evidence From Genetic Correlation and Mendelian Randomization Analyses.

Physical inactivity and sedentary behavior are associated with higher risks of age-related morbidity and mortality. However, whether they causally contribute to accelerating biological aging has not been fully elucidated. Utilizing the largest available genome-wide association study (GWAS) summary data, we implemented a comprehensive analytical framework to investigate the associations between genetically predicted moderate-to-vigorous leisure-time physical activity (MVPA), leisure screen time (LST), and four epigenetic age acceleration (EAA) measures: HannumAgeAccel, intrinsic HorvathAgeAccel, PhenoAgeAccel, and GrimAgeAccel.

The power of caring touch: from survival to prosocial cooperation.

Cooperation is a pivotal biological phenomenon that occurs in diverse forms. In species that engage in helping, individuals vary in the time they spend together and the degree of their physical proximity, which affects the extent of physical touch between individuals. Here, we propose that touch activates a hormonal feedback loop that supports bond formation and maintenance in mating, parenting, and social contexts.

The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.

The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ("seed") to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined.

Clinical trials for implantable neural prostheses: understanding the ethical and technical requirements.

Neuroprosthetics research has entered a stage in which animal models and proof-of-concept studies are translated into clinical applications, often combining implants with artificial intelligence techniques. This new phase raises the question of how clinical trials should be designed to scientifically and ethically address the unique features of neural prostheses. Neural prostheses are complex cyberbiological devices able to acquire and process data; hence, their assessment is not reducible to only third-party safety and efficacy evaluations as in pharmacological research.

Long-term outcome for neoadjuvant versus adjuvant chemotherapy in early breast cancer and the prognostic impact of nodal therapy response: A population-based study.

Introduction: Although neoadjuvant systemic treatment for non-metastatic breast cancer has gained ground during the past decade, there is no compelling evidence that it improves overall survival compared to primary tumor resection and adjuvant treatment. At the same time, the approach to responders to neoadjuvant treatment in the axilla is evolving.

Materials And Methods: This is a retrospective analysis of a prospectively collected population-based registry.

Neutropenic event incidence in women with early-stage breast cancer receiving neoadjuvant or adjuvant chemotherapy: a retrospective study.

Objectives: To assess the incidence of neutropenia, febrile neutropenia, documented infection with neutropenia and fever associated with early-stage breast cancer (BC) in a real-life setting.

Methods: A retrospective study that includes 88 women with BC who received a first dose of Epirubicin plus Cyclophosphamide with or without 5-Fluorouracil, in the county hospital of Ryhov, Sweden. The patients were included continuously from May 2017 to November 2020 and were ≥18 years old.

An integrative and translational PKPD modelling approach to explore the combined effect of polymyxin B and minocycline against Klebsiella pneumoniae.

Objectives: To expand a translational pharmacokinetic-pharmacodynamic (PKPD) modelling approach for assessing the combined effect of polymyxin B and minocycline against Klebsiella pneumoniae.

Methods: A PKPD model developed based on in vitro static time-kill experiments of one strain (ARU613) was first translated to characterize that of a more susceptible strain (ARU705), and thereafter to dynamic time-kill experiments (both strains) and to a murine thigh infection model (ARU705 only). The PKPD model was updated stepwise using accumulated data.

Pneumatic tube transport of trastuzumab in IV bags -effect of headspace and surfactant on subvisible particle formation.

In hospitals, IV bags can be prepared in advance for logistical and microbial safety reasons in a compounding unit and then transported to wards. Transport of protein drugs using a pneumatic tube system has been reported to result in high particle levels. In this study, pneumatic tube transport of trastuzumab in saline polyolefin bags was compared to delivery by hospital porters using an electric platform truck in an underground tunnel system.

Unveiling the role of artificial intelligence applied to clear aligner therapy: A scoping review.

Objectives: To conduct a scoping review on the application of artificial intelligence (AI) in clear aligner therapy and to assess the extent of AI integration and automation in orthodontic software currently available to orthodontists.

Data And Sources: A systematic electronic literature search was performed in the following databases: PubMed, Embase, Web of Science, Cochrane Library, and Scopus. Also, grey literature resources up to March 2024 were reviewed.

A Distinct Alternative mRNA Splicing Profile Identifies the Oncogenic CD44 Transcript Variant 3 in KMT2A-Rearranged Pediatric T-cell Acute Lymphoblastic Leukemia Cells.

T-cell acute lymphoblastic leukemia (T-ALL), which constitutes of 10-15% of all pediatric ALL cases, is known for its complex pathology due to pervasive genetic and chromosomal abnormalities. Although most children are successfully cured, chromosomal rearrangements involving the KMT2A gene is considered a poor prognostic factor. In a cohort of 171 pediatric T-ALL samples we have studied differences in gene and splice variant patterns in KMT2A rearranged (KMT2A-r) T-ALL compared to KMT2A negative (KMT2A-wt) T-ALL samples.

A novel panel of peptides with diagnostic potential for serological identification of Borrelia burgdorferi sensu stricto, B. garinii and B. afzelii in human sera.

A novel panel of peptide for serological identification of Borrelia burgdoferi sensu stricto, Borrelia garinii and Borrelia afzelii was developed and assessed in this study. The diagnostic algorithm of the novel test was initially trained testing 10 US human sera including 3 early-stage and 3 late-stage Lyme disease positive sera, 2 sera positive for Babesia and 2 sera positive for Syphilis, all purchased from a private biorepository. Findings were then corroborated testing (a) 33 additional EU follow-up positive sera from seroconverted patients bitten by ticks that tested positive for B.