Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) progressing to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly.

Combined matrix-assisted laser desorption/ionisation-mass spectrometry imaging with liquid chromatography-tandem mass spectrometry for observing spatial distribution of lipids in whole Caenorhabditis elegans.

Rationale: Matrix-assisted laser desorption/ionisation-mass spectrometry imaging (MALDI-MSI) is a powerful label-free technique for biomolecule detection (e.g., lipids), within tissue sections across various biological species.

Spatial omics reveals molecular changes in focal cortical dysplasia type II.

Focal cortical dysplasia (FCD) represents a group of diverse localized cortical lesions that are highly epileptogenic and occur due to abnormal brain development caused by genetic mutations, involving the mammalian target of rapamycin (mTOR). These somatic mutations lead to mosaicism in the affected brain, posing challenges to unravel the direct and indirect functional consequences of these mutations. To comprehensively characterize the impact of mTOR mutations on the brain, we employed here a multimodal approach in a preclinical mouse model of FCD type II (Rheb), focusing on spatial omics techniques to define the proteomic and lipidomic changes.

Standardized item selection for alternate computerized versions of Rey Auditory Verbal Learning Test(-based) word lists.

Introduction: Despite an increasing need for new Rey Auditory Verbal Learning Test (RAVLT)-based word lists in computerized testing, no criteria or standardized procedures exist for its development. To lay a foundation for future development of new and alternate computerized RAVLT(-based) word lists, we present cross-lingual word criteria, developed new lists using the criteria and evaluated performance on the lists using online assessment.

Method: Based on psycholinguistic literature, we identified relevant word selection criteria.

Subgroups of cognitively affected and unaffected breast cancer survivors after chemotherapy: a data-driven approach.

Purpose: It is assumed that a segment of breast cancer survivors are cognitively affected after chemotherapy. Our aim is to discover whether there is a qualitatively different cognitively affected subgroup of breast cancer survivors, or whether there are only quantitative differences between survivors in cognitive functioning.

Methods: Latent profile analysis was applied to age-corrected neuropsychological data -measuring verbal memory, attention, speed, and executive functioning- from an existing sample of 62 breast cancer survivors treated with chemotherapy.

Binary classification threatens the validity of cognitive impairment detection.

Objective: Neuropsychological literature reports varying prevalence of cognitive impairment within patient populations, despite assessment with standardized neuropsychological tests. Within the domain of oncology, the International Cognition and Cancer Task Force (ICCTF) proposed standard cutoff points to harmonize the operationalization of cognitive impairment. We evaluated how this binary classification affects agreement between two highly comparable test batteries.

Multimodal molecular imaging in drug discovery and development.

In addition to individual imaging techniques, the combination and integration of several imaging techniques, so-called multimodal imaging, can provide large amounts of anatomical, functional, and molecular information accelerating drug discovery and development processes. Imaging technologies aid in understanding the disease mechanism, finding new pharmacological targets, and assessment of new potential drug candidates and treatment response. Here, we describe how different imaging techniques can be used in different phases of drug discovery and development and highlight their strengths, related innovations, and future potential with a focus on the implementation of artificial intelligence (AI) and radiomics for imaging technologies.

Effect of Source Type and Protective Message on the Critical Evaluation of News Messages on Facebook: Randomized Controlled Trial in the Netherlands.

Background: Disinformation has become an increasing societal concern, especially due to the speed that news is shared in the digital era. In particular, disinformation in the health care sector can lead to serious casualties, as the current COVID-19 crisis clearly shows.

Objective: The main aim of this study was to experimentally examine the effects of information about the source and a protective warning message on users' critical evaluation of news items, as well as the perception of accuracy of the news item.

Continued influence of misinformation in times of COVID-19.

Health-related misinformation, especially in times of a global health crisis, can have severe negative consequences on public health. In the current studies, we investigated the persuasive impact of COVID-19-related misinformation, and whether the valence of the misinformation and recipients' degree of overconfidence affect this impact. In two pre-registered experimental studies, participants (N = 403; N = 437) were exposed to either a positive or a negative news article describing a fictional hospital's high COVID-19 recovery/mortality rates.

Computational Modeling of Neuropsychological Test Performance to Disentangle Impaired Cognitive Processes in Cancer Patients.

There is a need to better identify impaired cognitive processes to increase our understanding of cognitive dysfunction caused by cancer and cancer treatment and to improve interventions. The Trail Making Test is frequently used for evaluating information-processing speed (part A) and executive function (part B), but interpretation of its outcomes is challenging because performance depends on many cognitive processes. To disentangle processes, we collected high-resolution data from 192 non-central nervous system cancer patients who received systemic therapy and 192 cancer-free control participants and fitted a Shifted-Wald computational model.

Translation of HDAC6 PET Imaging Using [F]EKZ-001-cGMP Production and Measurement of HDAC6 Target Occupancy in Nonhuman Primates.

Histone deacetylase 6 (HDAC6) is a multifunctional cytoplasmic enzyme involved in diverse cellular processes such as intracellular transport and protein quality control. Inhibition of HDAC6 can alleviate defects in cell and rodent models of certain diseases, particularly neurodegenerative disorders, including Alzheimer's disease and amyotrophic lateral sclerosis. However, while HDAC6 represents a potentially powerful therapeutic target, development of effective brain-penetrant HDAC6 inhibitors remains challenging.

How to Correct for Computer Experience in Online Cognitive Testing?

Since computerized cognitive test performance may be influenced by computer experience, correction for this measure might be needed. This study examined how to correct for computer experience by examining its influence on online and traditional tests. 248 healthy adults completed an online neuropsychological test battery and 70 adults completed traditional equivalents of the tests.

Online Self-Administered Cognitive Testing Using the Amsterdam Cognition Scan: Establishing Psychometric Properties and Normative Data.

Background: Online tests enable efficient self-administered assessments and consequently facilitate large-scale data collection for many fields of research. The Amsterdam Cognition Scan is a new online neuropsychological test battery that measures a broad variety of cognitive functions.

Objective: The aims of this study were to evaluate the psychometric properties of the Amsterdam Cognition Scan and to establish regression-based normative data.

Reliability and validity of a self-administered tool for online neuropsychological testing: The Amsterdam Cognition Scan.

Introduction: To facilitate large-scale assessment of a variety of cognitive abilities in clinical studies, we developed a self-administered online neuropsychological test battery: the Amsterdam Cognition Scan (ACS). The current studies evaluate in a group of adult cancer patients: test-retest reliability of the ACS and the influence of test setting (home or hospital), and the relationship between our online and a traditional test battery (concurrent validity).

Method: Test-retest reliability was studied in 96 cancer patients (57 female; M = 51.

Correction: Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

[This corrects the article DOI: 10.1371/journal.pone.

Mycolates of modulate the flow of cholesterol for bacillary proliferation in murine macrophages.

The differentiation of macrophages into lipid-filled foam cells is a hallmark of the lung granuloma that forms in patients with active tuberculosis (TB). Mycolic acids (MAs), the abundant lipid virulence factors in the cell wall of (Mtb), can induce this foam phenotype possibly as a way to perturb host cell lipid homeostasis to support the infection. It is not exactly clear how MAs allow differentiation of foam cells during Mtb infection.

Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

Background: The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release.

Methods: Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche).

Online cognition: factors facilitating reliable online neuropsychological test results.

Objective: Online neuropsychological test batteries could allow for large-scale cognitive data collection in clinical studies. However, the few online neuropsychological test batteries that are currently available often still require supervision or lack proper psychometric evaluation. In this paper, we have outlined prerequisites for proper development and use of online neuropsychological tests, with the focus on reliable measurement of cognitive function in an unmonitored setting.

Female rats are resistant to developing the depressive phenotype induced by maternal separation stress.

Many stress-related psychiatric disorders are more common in women than in men. We aimed to determine how female rats respond to maternal separation (MS; removal of the dam from the litter for 3 h/day from postnatal day (P) 2-14)). A subset of MS females were also exposed to chronic constant light for 3 weeks during adolescence (P42-63) to investigate whether the antidepressant effect of light treatment, previously observed in male rats, could be seen in female rats.

Anonymity versus privacy: selective information sharing in online cancer communities.

Background: Active sharing in online cancer communities benefits patients. However, many patients refrain from sharing health information online due to privacy concerns. Existing research on privacy emphasizes data security and confidentiality, largely focusing on electronic medical records.

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients.

In first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA(+) , GADA(+) , IA-2A(+) and/or ZnT8A(+) relatives (6·1%).

HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody-positive first-degree relatives of type 1 diabetic patients.

We investigated whether HLA-A*24 typing complements screening for HLA-DQ and for antibodies (Abs) against insulin, GAD, IA-2 (IA-2A), and zinc transporter-8 (ZnT8A) for prediction of rapid progression to type 1 diabetes (T1D). Persistently Ab(+) siblings/offspring (n = 288; aged 0-39 years) of T1D patients were genotyped for HLA-DQA1-DQB1 and HLA-A*24 and monitored for development of diabetes within 5 years of first Ab(+). HLA-A*24 (P = 0.

Playing in or out of character: user role differences in the experience of interactive storytelling.

Interactive storytelling (IS) is a promising new entertainment technology synthesizing preauthored narrative with dynamic user interaction. Existing IS prototypes employ different modes to involve users in a story, ranging from individual avatar control to comprehensive control over the virtual environment. The current experiment tested whether different player modes (exerting local vs.

Exploring replay value: shifts and continuities in user experiences between first and second exposure to an interactive story.

While replay value is a common term in interactive entertainment, psychological research on its meaning in terms of user experiences is sparse. An exploratory experiment using the interactive drama "Façade" was conducted (n=50) to examine shifts and continuities in entertainment-related user experiences between first and second exposure to the same system. A questionnaire with brief scales measuring various user-experience dimensions (interaction-related facets such as usability, flow, and presence, as well as narrative-related facets such as suspense and curiosity) was administered after the first and the second round of exposure.

Environmental impact of incineration of calorific industrial waste: rotary kiln vs. cement kiln.

Rotary kiln incinerators and cement kilns are two energy intensive processes, requiring high temperatures that can be obtained by the combustion of fossil fuel. In both processes, fossil fuel is often substituted by high or medium calorific waste to avoid resource depletion and to save costs. Two types of industrial calorific waste streams are considered: automotive shredder residue (ASR) and meat and bone meal (MBM).