Accumulation of Oncogenic Mutations During Progression from Healthy Tissue to Cancer.

Cancers are typically fueled by sequential accumulation of driver mutations in a previously healthy cell. Some of these mutations, such as inactivation of the first copy of a tumor suppressor gene, can be neutral, and some, like those resulting in activation of oncogenes, may provide cells with a selective growth advantage. We study a multi-type branching process that starts with healthy tissue in homeostasis and models accumulation of neutral and advantageous mutations on the way to cancer.

Quantitative and comparative assessment of dyes and protocols for rapid ex vivo microscopy of fresh tissues.

Using ex vivo microscopy, virtual pathology can improve histological procedures by providing pathology images in near real-time without tissue destruction. Several emerging and promising approaches leverage fast-acting small-molecule fluorescent stains to replicate traditional pathology structural contrast, combined with rapid optical sectioning microscopes. However, several vital challenges must be addressed to translate virtual pathology into the clinical environment.

Spatiotemporal dynamics of tumor - CAR T-cell interaction following local administration in solid cancers.

The success of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic malignancies has generated widespread interest in translating this technology to solid cancers. However, issues like tumor infiltration, the immunosuppressive tumor microenvironment, and tumor heterogeneity limit its efficacy in the solid tumor setting. Recent experimental and clinical studies propose local administration directly into the tumor or at the tumor site to increase CAR T-cell infiltration and improve treatment outcomes.

Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy.

Modern electroconvulsive therapy (ECT) and the approval of nasal esketamine for clinical use have significantly improved the approach to treatment-resistant depression (TRD), which is defined as non-response to at least two different courses of antidepressants with verified adherence to treatment, adequate dosage, and duration of treatment. The goal of this literature review is to present the newest evidence regarding efficacy and safety. Furthermore, we aim to provide an overview of future perspectives in this field of research, for example, regarding structural and molecular effects.

Assessment of Gallbladder Drainage Methods in the Treatment of Acute Cholecystitis: A Literature Review.

Gallbladder drainage is a treatment option in high-risk surgical patients with moderate or severe acute cholecystitis. It may be applied as a bridge to cholecystectomy or a definitive treatment option. Apart from the simple and widely accessible percutaneous cholecystostomy, new attractive techniques have emerged in the previous decade, including endoscopic transpapillary gallbladder drainage and endoscopic ultrasound-guided gallbladder drainage.

Thiamine and benfotiamine: Focus on their therapeutic potential.

Thiamine, also known as vitamin B1, is an essential nutrient that plays a crucial role in energy metabolism and overall health. It is a water-soluble vitamin that plays an important role in the conversion of carbohydrates into energy in the body. Thiamine is essential for the proper functioning of the nervous system, heart and muscles.

Stochastic model for cell population dynamics quantifies homeostasis in colonic crypts and its disruption in early tumorigenesis.

The questions of how healthy colonic crypts maintain their size, and how homeostasis is disrupted by driver mutations, are central to understanding colorectal tumorigenesis. We propose a three-type stochastic branching process, which accounts for stem, transit-amplifying (TA) and fully differentiated (FD) cells, to model the dynamics of cell populations residing in colonic crypts. Our model is simple in its formulation, allowing us to estimate all but one of the model parameters from the literature.

Effects of Social Media Social Comparisons and Identity Processes on Body Image Satisfaction in Late Adolescence.

One of the important developmental tasks in adolescence and emerging adulthood is the questioning of identity issues, with body image being a prominent concern. In the age of modern technology, many processes of social comparison take place on social media, which serve as an ideal platform for comparison with others. The aim of this study was to examine the effects of identity dimensions, social media use, and social media social comparison, on different domains of body image satisfaction (i.

A multidisciplinary evaluation, exploration, and advancement of the concept of a traumatic birth experience.

Background: Understanding a woman's traumatic birth experience benefits from an approach that considers perspectives from various fields of healthcare and social sciences.

Aim: To evaluate and explore the multidisciplinary perspectives surrounding a traumatic birth experience to form a theory and to capture its structure.

Methods: A multidisciplinary advanced principle-based concept analysis was conducted, including the following systematic steps: literature review, assessment of concept maturity, principle-based evaluation, concept exploration and advancement, and formulating a multidisciplinary concept theory.

The Croatian Primary Sjögren's Disease Oral Health Study: Oral Status and Oral Health-Related Quality of Life.

To determine salivary flow rate, oral and periodontal status, oral health-related quality of life (OHRQoL), objective and subjective indexes, and serum antibody reactivity in patients with primary Sjögren's disease (pSD). Thirty-one patients with pSD and 31 control subjects participated in this cross-sectional, single-center study. The unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index (DMFT = D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, OHRQoL, objective European League Against Rheumatism (EULAR) SS Disease Activity Index (ESSDAI) and subjective (EULAR SS Patient Reported Index (ESSPRI), 6-items-VAS-SS (Visual Analog Scale), Profile of Fatigue) indexes were analyzed.

Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer's disease.

Early Alzheimer's disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in App mice, but that this mechanism fails in older mice. Spatial transcriptomics analysis identifies Pmch as part of the adaptive response in App mice.

Waiting times in a branching process model of colorectal cancer initiation.

We study a multi-stage model for the development of colorectal cancer from initially healthy tissue. The model incorporates a complex sequence of driver gene alterations, some of which result in immediate growth advantage, while others have initially neutral effects. We derive analytic estimates for the sizes of premalignant subpopulations, and use these results to compute the waiting times to premalignant and malignant genotypes.

Clonal interactions in cancer: Integrating quantitative models with experimental and clinical data.

Tumors consist of different genotypically distinct subpopulations-or subclones-of cells. These subclones can influence neighboring clones in a process called "clonal interaction." Conventionally, research on driver mutations in cancer has focused on their cell-autonomous effects that lead to an increase in fitness of the cells containing the driver.

Salivary Flow Rate and Oral Status in Patients with Primary Sjögren's Syndrome and Diffuse Cutaneous Systemic Sclerosis: A Cross-Sectional Study.

Determination of salivary flow rate and oral status in patients with primary Sjögren's Syndrome (pSS) and diffuse cutaneous systemic sclerosis (dcSSc) and comparison with control subjects. Thirty-one pSS patients, 28 dcSSc patients, and 28 control subjects participated in this single-center, cross-sectional study. Unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index (D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, and OHRQoL (oral health-related quality of life) were analyzed in all three groups of subjects.

Time in Range in Children with Type 1 Diabetes before and during a Diabetes Camp-A Ceiling Effect?

Background: The aim of this study was to assess and compare the time in range (TIR) of children with type 1 diabetes (T1D) before and during a diabetes summer camp using different therapy modalities. Methods: A retrospective analysis of continuous glucose monitoring (CGM) data collected from 26 children with T1D (mean age: 11.0 ± 1.

In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities.

Unlabelled: Transformation to aggressive disease histologies generates formidable clinical challenges across cancers, but biological insights remain few. We modeled the genetic heterogeneity of chronic lymphocytic leukemia (CLL) through multiplexed in vivo CRISPR-Cas9 B-cell editing of recurrent CLL loss-of-function drivers in mice and recapitulated the process of transformation from indolent CLL into large cell lymphoma [i.e.

Inferring parameters of cancer evolution in chronic lymphocytic leukemia.

As a cancer develops, its cells accrue new mutations, resulting in a heterogeneous, complex genomic profile. We make use of this heterogeneity to derive simple, analytic estimates of parameters driving carcinogenesis and reconstruct the timeline of selective events following initiation of an individual cancer, where two longitudinal samples are available for sequencing. Using stochastic computer simulations of cancer growth, we show that we can accurately estimate mutation rate, time before and after a driver event occurred, and growth rates of both initiated cancer cells and subsequently appearing subclones.

Coupling between the prelimbic cortex, nucleus reuniens, and hippocampus during NREM sleep remains stable under cognitive and homeostatic demands.

The interplay between the medial prefrontal cortex and hippocampus during non-rapid eye movement (NREM) sleep contributes to the consolidation of contextual memories. To assess the role of the thalamic nucleus reuniens (Nre) in this interaction, we investigated the coupling of neuro-oscillatory activities among prelimbic cortex, Nre, and hippocampus across sleep states and their role in the consolidation of contextual memories using multi-site electrophysiological recordings and optogenetic manipulations. We showed that ripples are time-locked to the Up state of cortical slow waves, the transition from UP to DOWN state in thalamic slow waves, the troughs of cortical spindles, and the peaks of thalamic spindles during spontaneous sleep, rebound sleep and sleep following a fear conditioning task.

A mechanistic mathematical model of initiation and malignant transformation in sporadic vestibular schwannoma.

Background: A vestibular schwannoma (VS) is a relatively rare, benign tumour of the eighth cranial nerve, often involving alterations to the gene NF2. Previous mathematical models of schwannoma incidence have not attempted to account for alterations in specific genes, and could not distinguish between nonsense mutations and loss of heterozygosity (LOH).

Methods: Here, we present a mechanistic approach to modelling initiation and malignant transformation in schwannoma.

Alterations in TRN-anterodorsal thalamocortical circuits affect sleep architecture and homeostatic processes in oxidative stress vulnerable Gclm mice.

Schizophrenia is associated with alterations of sensory integration, cognitive processing and both sleep architecture and sleep oscillations in mouse models and human subjects, possibly through changes in thalamocortical dynamics. Oxidative stress (OxS) damage, including inflammation and the impairment of fast-spiking gamma-aminobutyric acid neurons have been hypothesized as a potential mechanism responsible for the onset and development of schizophrenia. Yet, the link between OxS and perturbation of thalamocortical dynamics and sleep remains unclear.

Estimating the transfer rates of bacterial plasmids with an adapted Luria-Delbrück fluctuation analysis.

To increase our basic understanding of the ecology and evolution of conjugative plasmids, we need reliable estimates of their rate of transfer between bacterial cells. Current assays to measure transfer rate are based on deterministic modeling frameworks. However, some cell numbers in these assays can be very small, making estimates that rely on these numbers prone to noise.