Predictive, integrative, and regulatory aspects of AI-driven computational toxicology - Highlights of the German Pharm-Tox Summit (GPTS) 2024.

The 9th German Pharm-Tox Summit (GPTS) and the 90th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) took place in Munich from March 13-15, 2024. The event brought together over 700 participants from around the world to discuss cutting-edge developments in the fields of pharmacology and toxicology as well as scientific innovations and novel insights. A key focus of the conference was on the rapidly increasing role of computational toxicology, artificial intelligence (AI), and machine learning (ML) into the field, marking a shift away from traditional methods and allowing the reduction of animal testing as primary tool for toxicological risk assessment.

Mutation of , encoding homogentisate 1,2-dioxygenase, is responsible for pyomelanin production but does not impact the virulence of in a chronic granulomatous disease mouse lung infection.

The complex (Bcc) is a group of Gram-negative opportunistic bacteria often associated with fatal pulmonary infections in patients with impaired immunity, particularly those with cystic fibrosis (CF) and chronic granulomatous disease (CGD). Some Bcc strains are known to naturally produce pyomelanin, a brown melanin-like pigment known for scavenging free radicals; pigment production has been reported to enable Bcc strains to overcome the host cell oxidative burst. In this work, we investigated the role of pyomelanin in resistance to oxidative stress and virulence in strains J2315 and K56-2, two epidemic CF isolates belonging to the ET-12 lineage.

Investigating the application of "Guttmann Cognitest" in older adults and people with acquired brain injury.

Introduction: Digital solutions for cognitive assessment are currently not only widely used in experimental contexts but can also be useful in clinical practice for efficient screening and longitudinal follow-up. The "Guttmann Cognitest", which includes seven computerized tasks designed to assess main cognitive functions, revealed in a previous validation study to be a potential useful tool to assess cognitive functioning in healthy middle-aged adults.

Method: Here, we present results from a validation in two different populations: one consisting of older adults, and the other comprising young and middle-aged individuals, some of them affected by acquired brain injury.

Epicardial adipose tissue dispersion at CT and recurrent atrial fibrillation after pulmonary vein isolation.

Objectives: Epicardial adipose tissue (EAT) remodeling is associated with atrial fibrillation (AF). Left atrial (LA) EAT dispersion on cardiac CT is a non-invasive imaging biomarker reflecting EAT heterogeneity. We aimed to investigate the association of LA EAT dispersion with AF recurrence after pulmonary vein isolation (PVI).

The Relationship between Enhancing Left Atrial Adipose Tissue at CT and Recurrent Atrial Fibrillation.

Background The association of epicardial adipose tissue (EAT) and its metabolic activity with atrial fibrillation (AF) is an area of active investigation. Left atrial (LA) enhancing EAT (e-EAT) at cardiac CT may be a noninvasive surrogate marker for the metabolic activity of EAT. Purpose To determine the relationship between LA e-EAT and recurrence after AF ablation.

No Science Fair? No Problem. Engaging Students in Science Communication through Peer Review and Publication in a Remote World.

Since March 2020, in-person science competitions have been cancelled or moved to a virtual space. This reality has encouraged teachers and students to find alternative ways to disseminate student research and participate in a scientific community. Participating in the peer review and publication of one's research offers one such alternative.

What next for local government climate emergency declarations? The gap between rhetoric and action.

The UK, like other countries, has seen a proliferation of declarations of local climate emergencies. While these declarations have been interpreted as a demonstration of ambition, little is known about how and why they actually came about when they did and the implications this will have for what happens next. Focusing on London, UK, we present evidence collected via semi-structured interviews with experts and practitioners involved in the propagation of climate emergency declarations to critically explore how and why these declarations emerged, and the various different roles they are perceived to play for different local actors.

Saponins from Saffron Corms Inhibit the Gene Expression and Secretion of Pro-Inflammatory Cytokines.

Corms are obtained as a byproduct during the cultivation of saffron (). In a project aimed at the valorization of this waste product, we observed that a 70% EtOH extract of the corms and a sugar-depleted MeOH fraction of the extract inhibited the TNF-α/IFN-γ-induced secretion and gene expression of the chemokines IL-8, MCP-1, and RANTES in human HaCaT cells. The effects were in part stronger than those of the positive control hydrocortisone.

Building a Social Mandate for Climate Action: Lessons from COVID-19.

The COVID-19 imposed lockdown has led to a number of temporary environmental side effects (reduced global emissions, cleaner air, less noise), that the climate community has aspired to achieve over a number of decades. However, these benefits have been achieved at a massive cost to welfare and the economy. This commentary draws lessons from the COVID-19 crisis for climate change.

Characterizing changes in soil microbiome abundance and diversity due to different cover crop techniques.

Soil-based microorganisms assume a direct and crucial role in the promotion of soil health, quality and fertility, all factors known to contribute heavily to the quality and yield of agricultural products. Cover cropping, used in both traditional and organic farming, is a particularly efficient and environmentally favorable tool for manipulating microbiome composition in agricultural soils and has had clear benefits for soil quality and crop output. Several long-term investigations have evaluated the influence of multi-mix (multiple species) cover crop treatments on soil health and microbial diversity.

A FLIPR Assay for Discovery of GABAA Receptor Modulators of Natural Origin.

A fluorometric imaging plate reader (FLIPR) assay utilizing Chinese hamster ovary (CHO) cells stably transfected with GABA receptors of subunit composition was evaluated and validated for rapid screening of plant extract libraries and efficient localization of active compounds in extracts. Validation was performed with pure compounds and extracts known to contain allosteric GABA receptor modulators. Plants extracts that had been previously reported as active in an assay using oocytes transiently expressing GABA receptors of subunit composition were also active in the FLIPR assay.

Overcoming public resistance to carbon taxes.

Carbon taxes represent a cost-effective way to steer the economy toward a greener future. In the real world, their application has however been limited. In this paper, we address one of the main obstacles to carbon taxes: public opposition.

Engaging in the Publication Process Improves Perceptions of Scientific Communication, Critique, and Career Skills Among Graduate Students.

Reading and critiquing primary scientific literature is an important skill for graduate students, as reviewing literature is critical to advancing science. Prior research indicates that graduate students lack understanding of effective communication as well as basic experimental design, but also that graduate students are capable of growth in their experimental design abilities when given proper opportunities. The provides graduate students with the opportunity to review and edit original research papers submitted by middle and high school student-authors.

[Assessing Change of Depressive Symptoms and Severity of Depression in an Inpatient Setting : Performance of the HoNOS (Health of the Nation Outcome Scales)].

This study investigates the assessment of change of depressive symptoms and severity of depression with the "Health of the Nation Outcome Scales" (HoNOS) in an inpatient setting. Participants were 132 adults diagnosed with depressive disorder (F32: n=102; F33: n=30). Bivariate correlations were used to determine the correlation of the HoNOS with self-reported (BDI) and observer-rated depressive symptoms (HAMD).

Social network and cognitive functioning in old age : Self-efficacy as a mediator?

This study investigated self-efficacy (self-perceived and rated by an informant) as a mediator of the relationship between social network variables (including network size, frequency of social contacts, satisfaction with social contacts and social support) and cognitive impairment. Participants were 189 adults with a mean age of 75 years, 32 of whom suffered from mild cognitive impairment (MCI), 39 from early stage Alzheimer's disease (AD) and 118 who had no cognitive impairment. Binary logistic regression and linear regression models were used to assess the association between the predictor variables and cognitive impairment, controlling for several confounders.

Using Scavenger Hunts to Familiarize Students with Scientific Journal Articles.

Primary scientific literature can be difficult to navigate for anyone unfamiliar with its foreign, formal structure. We sought to create a fun, easy learning tool to help familiarize students of all ages with the structure of a scientific article. Our main learning objective was for the student to realize that science writing is formulaic-that specific information is found in predictable locations within an article-and that, with an understanding of the formula, anyone can comfortably navigate any journal article and accurately predict what to expect to find in each section.

Incorporating Primary Scientific Literature in Middle and High School Education.

Primary literature is the most reliable and direct source of scientific information, but most middle school and high school science is taught using secondary and tertiary sources. One reason for this is that primary science articles can be difficult to access and interpret for young students and for their teachers, who may lack exposure to this type of writing. The Journal of Emerging Investigators (JEI) was created to fill this gap and provide primary research articles that can be accessed and read by students and their teachers.

Identification of heart rate dynamics during moderate-to-vigorous treadmill exercise.

Background: Heart rate can be used to prescribe exercise intensity for development and maintenance of cardiorespiratory fitness. The aim of this study was to identify the dynamics of heart rate response during moderate-to-vigorous treadmill exercise and to explore parameter dependencies with respect to time, intensity level and step-change direction. The focus was on simple approximate models for subsequent design of heart rate control systems.

Risk of dementia in older adults with low versus high occupation-based motivational processes: differential impact of frequency and proximity of social network.

Objectives: This study investigates the impact of occupation-based motivational processes and social network variables on the incidence of dementia over 8 years.

Method: Data were derived from the Leipzig Longitudinal Study of the Aged (LEILA75+), a population-based longitudinal study of individuals aged 75 years and older (n=1692 at baseline). Motivational processes were estimated based on the main occupation using the Occupational Information Network database.

Single amino acid substitution in homogentisate 1,2-dioxygenase is responsible for pigmentation in a subset of Burkholderia cepacia complex isolates.

The Burkholderia cepacia complex (Bcc) is a group of Gram-negative bacilli that are ubiquitous in the environment and have emerged over the past 30 years as opportunistic pathogens in immunocompromised populations, specifically individuals with cystic fibrosis (CF) and chronic granulomatous disease. This complex of at least 18 distinct species is phenotypically and genetically diverse. One phenotype observed in a subset of Burkholderia cenocepacia (a prominent Bcc pathogen) isolates is the ability to produce a melanin-like pigment.

Depressive symptoms in later life: differential impact of social support and motivational processes on depression in individuals with and without cognitive impairment.

This study investigates the role of a motivational process based on a composite of four subcomponents (self-efficacy, decision regulation, activation regulation and motivation regulation), as a mediator of the relationship between social support and depression assessed with the Geriatric Depression Scale in cognitively impaired and unimpaired individuals. Participants were 229 adults with a mean age of 74 years (range: 52-94 years). The sample comprised 64 participants diagnosed with mild cognitive impairment (MCI), 47 participants diagnosed with early-stage Alzheimer's disease (AD), and a group of 118 participants without any cognitive impairment.

PD-L1 limits the mucosal CD8+ T cell response to Chlamydia trachomatis.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease in the United States. Repeated infections with C. trachomatis lead to serious sequelae, such as infertility.

Caregiver rating bias in mild cognitive impairment and mild Alzheimer's disease: impact of caregiver burden and depression on dyadic rating discrepancy across domains.

Background: Caregivers of individuals with dementia are biased in their rating of mental health measures of the care receiver. This study examines caregiver burden and depression as predictors of this bias for mild cognitive impairment and mild Alzheimer's disease in different domains.

Methods: The sample consisted of 202 persons: 60 with mild cognitive impairment, 41 with mild Alzheimer's disease, and 101 caregivers.