Basic Science and Pathogenesis.

Background: The bi-directional autophagy and inflammation network becomes progressively dysregulated with age, with systemic inflammation as a biomarker of this dysregulation including in Alzheimer's Disease (AD). We hypothesize that interventions which target the shared feature of systemic inflammation in the biology of aging and AD, via regulation of the autophagy-inflammation network, will prevent the conversion to disease pathogenesis in AD as well as improve healthspan and longevity in aging populations. While previous studies report benefits of mTOR inhibition including rapamycin in transgenic mouse models of familial AD, the present studies aim to evaluate this pathway in a model of sporadic, late onset AD (LOAD) and test the contribution of AMP-activated protein kinase (AMPK) as a critical regulator of the mTOR pathway.

Basic Science and Pathogenesis.

Background: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically-engineered marmosets that carry knock-in (KI) point mutations in the presenilin-1 (PSEN1) gene that can be studied from birth throughout lifespan.

Method: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1.

Proton radiography inversions with source extraction and comparison to mesh methods.

Proton radiography is a central diagnostic technique for measuring electromagnetic (EM) fields in high-energy-density, laser-produced plasmas. In this technique, protons traverse the plasma where they accumulate small EM deflections which lead to variations in the proton fluence pattern on a detector. Path-integrated EM fields can then be extracted from the fluence image through an inversion process.

Clonal hematopoiesis of indeterminate potential (CHIP) and its association with treatment outcomes and adverse events in patients with solid tumours.

Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of hematopoietic stem cells from somatic mutations. It is a common incidental finding in cell-free DNA (cfDNA). We investigated the incidence of CHIP in cfDNA from patients with solid tumours and explored its association with treatment outcomes and adverse events.

Communicative health literacy and associated variables in nine European countries: results from the HLS survey.

Our study aimed to report on variables associated with communicative health literacy (COM-HL) in European adults. The HLS survey was conducted in 2019-2021 including nine countries which measured COM-HL by using a validated questionnaire (HLS-COM-P-Q6 with a score ranging from 0 to 100). Linear regression models were used to study variables associated with COM-HL globally (multilevel model with random intercepts and slopes and at country level) and in each country.

Correction: Titmuss et al. Immune Activation Following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study. 2023, , 5869.

The journal's Editorial Office and Editorial Board are jointly issuing a resolution and removal of the linked to this article [...

Pancreatic cancer tumor organoids exhibit subtype-specific differences in metabolic profiles.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease characterized by complex metabolic rewiring that enables growth in changing nutrient availability and oxygen conditions. Transcriptome-based prognostic PDAC tumor subtypes, known as 'basal-like' and 'classical' subtypes are associated with differences in metabolic gene expression including genes involved in glycolysis. Tumor subtype-specific metabolism phenotypes may provide new targets for treatment development in PDAC, but their functional relevance has not been fully elucidated.

Inflammatory bowel disease uncovered in fecal immunochemical test positive patients in a Canadian provincial colon cancer screening program.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition that usually affects younger adults but has a second incidence peak in the older population. Although diagnosis of IBD is driven by symptoms, some patients are asymptomatic and incidentally discovered while participating in colon screening program (CSP). We aimed to identify the incidence and outcome of IBD in fecal immunochemical test (FIT) positive patients in the British Columbia CSP.

A Deep Learning Approach for the Identification of the Molecular Subtypes of Pancreatic Ductal Adenocarcinoma Based on Whole Slide Pathology Images.

Delayed diagnosis and treatment resistance result in high pancreatic ductal adenocarcinoma (PDAC) mortality rates. Identifying molecular subtypes can improve treatment, but current methods are costly and time-consuming. In this study, deep learning models were used to identify histologic features that classify PDAC molecular subtypes based on routine hematoxylin-eosin-stained histopathologic slides.

[Professional Health Literacy of General Practitioners - Results of the HLS-PROF].

Aim: To date, there are only a few studies analyzing health professionals' health literacy (HL). Mostly, the focus has been on personal rather than professional HL. To bridge this gap, a new concept and an associated survey instrument have been developed in a three-country consortium.

Proton deflectometry analysis in magnetized plasmas: Magnetic field reconstruction in one dimension.

Proton deflectometry is used in magnetized high-energy-density plasmas to observe electromagnetic fields. We describe a reconstruction algorithm to recover the electromagnetic fields from proton fluence data in 1-D. The algorithm is verified against analytic solutions and applied to example data.

Acvr1b Loss Increases Formation of Pancreatic Precancerous Lesions From Acinar and Ductal Cells of Origin.

Background & Aims: Pancreatic ductal adenocarcinoma can develop from precursor lesions, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN). Previous studies indicated that loss of Acvr1b accelerates the Kras-mediated development of papillary IPMN in the mouse pancreas; however, the cell type predominantly affected by these genetic changes remains unclear.

Methods: We investigated the contribution of cellular origin by inducing IPMN associated mutations (KRAS expression and Acvr1b loss) specifically in acinar (Ptf1a;Kras;Acvr1b mice) or ductal (Sox9CreER;Kras;Acvr1b mice) cells in mice.

Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma.

Purpose: Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic-initiated testing (HCT) pathway and a new oncology clinic-initiated testing (OCT) pathway.

Methods: Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022.

Implementation and evaluation of a national quality improvement initiative in cancer surgery.

Background: In 2017, the Canadian Partnership Against Cancer, a Canadian federally sponsored organisation, initiated a national multijurisdictional quality improvement (QI) initiative to maximise the use of synoptic data to drive cancer system improvements, known as the Evidence for Surgical Synoptic Quality Improvement Programme. The goal of our study was to evaluate the outcomes, determinants and learning of this nationally led initiative across six jurisdictions in Canada, integrating a mix of cancer surgery disease sites and clinicians.

Methods: A mixed-methods evaluation (surveys, semistructured interviews and focus groups) of this initiative was focused on the ability of each jurisdiction to use synoptic reporting data to successfully implement and sustain QI projects to beyond the completion of the initiative and the lessons learnt in the process.

Evidence for and against manganese deficiency as causal for congenital joint deficiency disease or death in fetal and neonatal cattle.

Measures of manganese (Mn) status in cattle vary among studies, and no single criterion accurately predicts or diagnoses Mn deficiency and pathologic outcomes. Mn deficiency causes congenital joint laxity and dwarfism (CJLD) when total dietary intake is <20 ppm Mn dry matter (DM) for most of the pregnancy. However, the recommended dietary intake of 40 ppm DM can also result in clinical Mn deficiency.

An open-source MRI compatible frame for multimodal presurgical mapping in macaque and capuchin monkeys.

Background: High-precision neurosurgical targeting in nonhuman primates (NHPs) often requires presurgical anatomical mapping with noninvasive neuroimaging techniques (MRI, CT, PET), allowing for translation of individual anatomical coordinates to surgical stereotaxic apparatus. Given the varied tissue contrasts that these imaging techniques produce, precise alignment of imaging-based coordinates to surgical apparatus can be cumbersome. MRI-compatible stereotaxis with radiopaque fiducial markers offer a straight-forward and reliable solution, but existing commercial options do not fit in conformal head coils that maximize imaging quality.

Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations.

Introduction: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan.

Methods: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1.

Molecular confirmation of alpha 1-antitrypsin deficiency in liver transplant setting: A province-wide experience.

Background And Aim: Patients suspected of Alpha 1-Antitrypsin (A1AT) abnormality based on low serum concentration are routinely confirmed through polymerase chain reaction (PCR) testing of peripheral blood. Genotyping formalin-fixed paraffin-embedded (FFPE) tissue is a novel approach that could aid in detecting variant A1AT. We performed qPCR on FFPE liver explants with Periodic Acid Schiff after Diastase (PASD)- and A1AT-positive globules to confirm and estimate the frequency of A1AT deficiency in transplant cases.

[Professional health literacy among nurses in Germany: Results of a quantitative, cross-sectional survey].

Professional health literacy among nurses in Germany: Results of a quantitative, cross-sectional survey Little is known about the professional health literacy (HL) of nurses, i.e., how well they are able to promote patients' HL.

Noninvasive focal transgene delivery with viral neuronal tracers in the marmoset monkey.

We establish a reliable method for selectively delivering adeno-associated viral vectors (AAVs) across the blood-brain barrier (BBB) in the marmoset without the need for neurosurgical injection. We focally perturbed the BBB (∼1 × 2 mm) in area 8aD of the frontal cortex in four adult marmoset monkeys using low-intensity transcranial focused ultrasound aided by microbubbles. Within an hour of opening the BBB, either AAV2 or AAV9 was delivered systemically via tail-vein injection.

Complete genome sequences of five that infect hosts.

This announcement contains the whole genome sequences of five that infect members of the family of bacteria. Four of the five phages were isolated using serovar Typhimurium as a bacterial host: AR2819, Sajous1, SilasIsHot, and FrontPhageNews. ChubbyThor was isolated using .

[Digital health literacy in Germany: current status, concepts, and challenges].

A key prerequisite for the successful digital transformation of the healthcare system is a well-developed level of digital health literacy (DHL) among the population. DHL is the ability to deal with health-relevant digital information and information options with the aim of promoting and maintaining health and well-being for oneself and one's environment. This article examines the discussions about digital health literacy, the existing studies and measurement tools used in them, the data situation in Germany, and current challenges.