Random forest algorithm identifies miRNA signatures for breast cancer detection and classification from patient urine samples.

Background And Objectives: Breast cancer is the most common cancer in women, with one in eight women suffering from this disease in her lifetime. The implementation of centrally organized mammography screening for women between 50 and 69 years of age was a major step in the direction of early detection. However, the participation rate reaches approximately 50% of the eligible women, one reason being the painful compression of the breast, cited as a major issue for not participating in this very important program.

plaque formation model to unravel biofilm formation dynamics on implant abutment surfaces.

Background: Biofilm formation on implant-abutment surfaces can cause inflammatory reactions. Ethical concerns often limit intraoral testing, necessitating preliminary in vitro or animal studies. Here, we propose an in vitro model using human saliva and hypothesize that this model has the potential to closely mimic the dynamics of biofilm formation on implant-abutment material surfaces in vivo.

Lack of detection of Porcine circovirus 3 (PCV-3) in formalin-fixed, paraffin- embedded tissues from porcine abortions in Switzerland.

The novel Porcine circovirus 3 (PCV-3) has been associated in the past years to different porcine diseases, including reproductive failure. The potential occurrence of PCV-3 in abortions from Swiss pig herds has not been investigated so far. Thus, we conducted a retrospective study on pig aborted cases submitted to our laboratory in the University of Bern during the last 10 years with the main aim of investigating the possible presence of PCV-3 in foetal and/or placental tissue.

Electron-rich pyridines with -N-heterocyclic imine substituents: ligand properties and coordination to CO, SO, BCl and Pd complexes.

Electron-rich pyridines with π donor groups at the position play an important role as nucleophiles in organocatalysis, but their ligand properties and utilization in coordination chemistry have received little attention. Herein, we report the synthesis of two electron-rich pyridines 1 and 2 bearing N-heterocyclic imine groups at the position and explore their coordination chemistry. Experimental and computational methods were used to assess the donor ability of the new pyridines showing that they are stronger donors than aminopyridines and guanidinyl pyridines, and that the nature of the N-heterocyclic backbone has a strong influence on the pyridine donor strength.

TLR9 agonism differentially impacts human NK cell-mediated direct killing and antibody-dependent cell-mediated cytotoxicity.

There are two known mechanisms by which natural killer (NK) cells recognize and kill diseased targets: (i) direct killing and (ii) antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated an indirect NK cell activation strategy for the enhancement of human NK cell killing function. We did this by leveraging the fact that toll-like receptor 9 (TLR9) agonism within pools of human peripheral blood mononuclear cells (PBMCs) results in a robust interferon signaling cascade that leads to NK cell activation.

Pharmacist-Led Medication Management in Acute Geriatric Medicine and Its Associations with Rehospitalizations: A Cohort Study.

Introduction: Hospitalization and discharge in older patients are critical and clinical pharmacists have shown to ameliorate risks. Our objective was to assess their benefit as part of the geriatric team regarding rehospitalizations and related outcomes after discharge focusing on general practitioners' decision to continue or change discharge medication (GPD).

Methods: Prospective implementation study with 6-month follow-up in an acute geriatric clinic.

Automated classification of cellular expression in multiplexed imaging data with Nimbus.

Multiplexed imaging offers a powerful approach to characterize the spatial topography of tissues in both health and disease. To analyze such data, the specific combination of markers that are present in each cell must be enumerated to enable accurate phenotyping, a process that often relies on unsupervised clustering. We constructed the Pan-Multiplex (Pan-M) dataset containing 197 million distinct annotations of marker expression across 15 different cell types.

Gender Difference in sidE eFfects of ImmuNotherapy: a possible clue to optimize cancEr tReatment (G-DEFINER): study protocol of an observational prospective multicenter study.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited.

Detection of and an unknown -like nematode in raccoon ().

The raccoon (Carnivora: Procyonidae) is an invasive species of growing importance for the introduction of alien pathogens or as additional hosts for autochthonous pathogens in Europe, including zoonotic parasites. As the population is steadily increasing and outcompeting the red fox () in Germany, the consumption of raccoon meat raises concerns about pathogens they may transmit. Therefore the presence of larvae was here investigated in muscle samples (n = 904) of raccoons from northern Germany.

Neural extracellular matrix regulates visual sensory motor integration.

Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components, brevican, neurocan, tenascin-C, and tenascin-R, in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing .

Designing peptide amphiphiles as novel antibacterials and antibiotic adjuvants against gram-negative bacteria.

Gram-negative strains are intrinsically resistant to most antibiotics due to the robust and impermeable characteristic of their outer membrane. Self-assembling cationic peptide amphiphiles (PAs) have the ability to disrupt bacteria membranes, constituting an excellent antibacterial alternative to small molecule drugs that can be used alone or as antibiotic adjuvants to overcome bacteria resistance. PA1 (CKHKHK), self-assembled into micelles, which exhibited low antibacterial activity against all strains tested, and showed strong synergistic antibacterial activity in combination with Vancomycin with a Fractional Inhibitory Concentration index (FICi) of 0.

Culture expansion of CAR T cells results in aberrant DNA methylation that is associated with adverse clinical outcome.

Chimeric antigen receptor (CAR) T cells provide new perspectives for treatment of hematological malignancies. Manufacturing of these cellular products includes culture expansion procedures, which may affect cellular integrity and therapeutic outcome. In this study, we investigated culture-associated epigenetic changes in CAR T cells and found continuous gain of DNAm, particularly within genes that are relevant for T cell function.

Timing of rectal cancer surgery after short-course radiotherapy: national database study.

Background: Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4-8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database.

Methods: Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)-) N0 M0 and T1-3(MRF-) N1 M0) treated with either SCRT-delay (4-12 weeks) or SCRT-direct surgery in 2018-2021 were selected from a Dutch national colorectal cancer database.

Epithelial membrane antigen-reactive feline chordoid meningioma in a European wildcat (Felis silvestris).

Meningioma is the most frequent intracranial neoplasm in cats. Here we describe the first case of chordoid meningioma (CM), a rare grade II meningioma subtype, in a 5.5-year-old European wildcat (Felis silvestris) from a Swiss zoo.

Cytoprotective Effects of Human Platelet Lysate during the Xeno-Free Culture of Human Donor Corneas.

We evaluated the suitability of 2% human platelet lysate medium (2%HPL) as a replacement for 2% fetal bovine serum medium (2%FBS) for the xeno-free organ culture of human donor corneas. A total of 32 corneas from 16 human donors were cultured in 2%FBS for 3 days (TP1), then evaluated using phase contrast microscopy (endothelial cell density (ECD) and cell morphology). Following an additional 25-day culture period (TP2) in either 2%FBS or 2%HPL, the pairs were again compared using microscopy; then stroma and Descemet membrane/endothelium (DmE) were processed for next generation sequencing (NGS).

Cannabidiol attenuates fear memory expression in female rats via hippocampal 5-HT but not CB1 or CB2 receptors.

Growing evidence from male rodent and human studies suggests that cannabidiol (CBD) modulates the expression of aversive memories and anxiety-related responses. The limited data on whether and how CBD influences these aspects in females could have therapeutic implications given the increased susceptibility of women to anxiety- and stress-related disorders relative to men. Female studies are also essential to examine inherent aspects that potentially contribute to differences in responsiveness to CBD.

The steady state and response to a periodic stimulation of the firing rate for a theta neuron with correlated noise.

The stochastic activity of neurons is caused by various sources of correlated fluctuations and can be described in terms of simplified, yet biophysically grounded, integrate-and-fire models. One paradigmatic model is the quadratic integrate-and-fire model and its equivalent phase description by the theta neuron. Here we study the theta neuron model driven by a correlated Ornstein-Uhlenbeck noise and by periodic stimuli.

Characterization of an outbreak of equine coronavirus infection in adult horses in Switzerland.

Outbreaks of equine coronavirus (ECoV) infections have been described in different parts of the world including Europe. The aim of this report was to describe clinical signs, diagnostic work-up and outcome of the first documented outbreak of ECoV in Switzerland in order to raise the awareness for the disease and its various clinical presentations. The outbreak occurred on a farm with 26 horses.

Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction.

Women present increased susceptibility to anxiety- and stress-related disorders compared to men. A potentially promising pharmacological-based strategy to regulate abnormal aversive memories disrupts their reconsolidation stage after reactivation and destabilization. Male rodent findings indicate that cannabidiol (CBD), a relatively safe and effective treatment for several mental health conditions, can impair the reconsolidation of aversive memories.

DNA methylation changes associated with cannabis use and verbal learning performance in adolescents: an exploratory whole genome methylation study.

The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents (n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders.

Atrophic gastritis is inversely associated with gastroesophageal reflux disease in a twin register based study.

Background: The association between atrophic gastritis (AG) and symptomatic gastroesophageal reflux disease (GERD) needs to be better assessed.

Objective: We aimed to study this association in a twin setting, controlling for genetic and familial factors, in addition to a range of known covariates.

Methods: We performed a co-twin control study based on the Swedish Twin Registry, including confirmed monozygotic (MZ) and dizygotic (DZ) twins.

Hematopoietic differentiation persists in human iPSCs defective in de novo DNA methylation.

Background: DNA methylation is involved in the epigenetic regulation of gene expression during developmental processes and is primarily established by the DNA methyltransferase 3A (DNMT3A) and 3B (DNMT3B). DNMT3A is one of the most frequently mutated genes in clonal hematopoiesis and leukemia, indicating that it plays a crucial role for hematopoietic differentiation. However, the functional relevance of Dnmt3a for hematopoietic differentiation and hematological malignancies has mostly been analyzed in mice, with the specific role for human hematopoiesis remaining elusive.

Patterns in the Pandemic: Disproportionate Patient Burdens Among Regional Hospitals.

Study Objective: To examine the distribution of hospitalized COVID-19 patients among adult acute care facilities in the Greater Philadelphia area and identify factors associated with hospitals carrying higher burdens of COVID-19 patients.

Methods: In this observational descriptive study, we obtained self-reported daily COVID-19 inpatient censuses from 28 large (>100 beds) adult acute care hospitals in the Greater Philadelphia region during the initial wave of the COVID-19 pandemic (March 23, 2020, to July 28, 2020). We examined hospitals based on their size, location, trauma certification, median household income, and reliance on public insurance.