Precuneus activity during retrieval is positively associated with amyloid burden in cognitively normal older carriers.

The precuneus is a site of early amyloid-beta (Aβ) accumulation. Previous cross-sectional studies reported increased precuneus fMRI activity in older adults with mild cognitive deficits or elevated Aβ. However, longitudinal studies in early Alzheimer's disease (AD) are lacking and the relationship to the Apolipoprotein-E () genotype is unclear.

Neurocan regulates axon initial segment organization and neuronal activity.

The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, perisynaptically, and at the nodes of Ranvier and the AIS, highlighting its potential role in regulating axonal excitability.

LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro.

For the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs such as natalizumab in animal stroke models have not been translated into clinical practice.

Activation and Reactivity of the Deubiquitinylase OTU Cezanne-2 from MD Simulations and QM/MM Calculations.

Cezanne-2 (Cez2) is a deubiquitinylating (DUB) enzyme involved in the regulation of ubiquitin-driven cellular signaling and selectively targets Lys11-linked polyubiquitin chains. As a representative member of the ovarian tumor (OTU) subfamily DUBs, it performs cysteine proteolytic isopeptide bond cleavage; however, its exact catalytic mechanism is not yet resolved. In this work, we used different computational approaches to get molecular insights into the Cezanne-2 catalytic mechanism.

Training and validating a treatment recommender with partial verification evidence.

Background: Current clinical decision support systems (DSS) are trained and validated on observational data from the clinic in which the DSS is going to be applied. This is problematic for treatments that have already been validated in a randomized clinical trial (RCT), but have not yet been introduced in any clinic. In this work, we report on a method for training and validating the DSS core before introduction to a clinic, using the RCT data themselves.

Environmental enrichment is associated with favorable memory-related functional brain activity patterns in older adults.

Background: In humans, environmental enrichment (EE), as measured by the engagement in a variety of leisure activities, has been associated with larger hippocampal structure and better memory function. The present cross-sectional study assessed whether EE during early life (13-30 years) and midlife (30-65 years) is associated with better preserved memory-related brain activity patterns in older age.

Methods: In total, 372 cognitively unimpaired older adults (aged ≥60 years old) of the DZNE-Longitudinal Study on Cognitive Impairment and Dementia (DELCODE; DRKS00007966) were investigated.

Finerenone in Heart Failure-A Novel Therapeutic Approach.

This review will discuss heart failure, introduce a new drug finerenone, and discuss clinical studies with a focus on its effects on heart failure. Heart failure is a condition or syndrome characterized by an impairment of the pumping ability of the heart, thus no longer keeping up with the demands of the body. There are several types of heart failure; among them are heart failure with reduced ejection fraction, with mildly reduced ejection fraction and with preserved ejection fraction.

Endoscopic Ultrasonography-Guided Drainage of the Pancreatic Duct (EUS-PD)-Indications and Results with a Literature Review.

: Drawing upon over twenty years of clinical experience in endoscopic and endosonographic procedures, along with comprehensive literature research, we present an overview on EUS-guided pancreatography and pancreatic duct drainage (EUS-PD) as an alternative approach, encompassing indications, procedural methods, and outcomes, including complications and the success rate. Narrative review. (corner points): EUS-PD is indicated for cases, for which conventional methods are ineffective due to altered abdominal anatomy of the upper gastrointestinal (GI) tract, such as congenital or postoperative conditions that prevent access to the papilla or pancreatoenteric anastomosis.

Decoding Salience: A Functional Magnetic Resonance Imaging Investigation of Reward and Contextual Unexpectedness in Memory Encoding and Retrieval.

The present study investigated the neuromodulatory substrates of salience processing and its impact on memory encoding and behaviour, with a specific focus on two distinct types of salience: reward and contextual unexpectedness. 46 Participants performed a novel task paradigm modulating these two aspects independently and allowing for investigating their distinct and interactive effects on memory encoding while undergoing high-resolution fMRI. By using advanced image processing techniques tailored to examine midbrain and brainstem nuclei with high precision, our study additionally aimed to elucidate differential activation patterns in subcortical nuclei in response to reward-associated and contextually unexpected stimuli, including distinct pathways involving in particular dopaminergic modulation.

Follow-up care needs and motivational factors for childhood cancer survivors and their parents in Germany.

This study aims to explore the long-term follow-up needs and motivations of childhood and adolescent cancer survivors and their parents to attend follow-up care in Germany, given the inconsistent adherence to national follow-up guidelines. We developed interview guidelines based on the Theory of Planned Behavior and the stereotype priming model to explore motivations and barriers related to follow-up care. We conducted a total of 36 episodic narrative interviews with adolescent (ages 13-17) and adult (ages 18-45) survivors of pediatric cancer, as well as their parents.

Higher physical activity levels are related to faecal microbiota diversity and composition in young adults.

Increasing physical activity (PA) is recognised as an efficacious approach for preventing and treating cardiometabolic diseases. Recently, the composition of microorganisms living within the gut has been proposed as an important appropriate target for treating these diseases. Whether PA is related to faecal microbiota diversity and composition in humans remains to be ascertained.

More micrometastases, more recurrence? The role of qPCR of PSA mRNA in lymph nodes during prostatectomy.

Background And Objectives: Radical prostatectomy is a standard treatment for prostate cancer, yet about 30% of patients experience rising biochemical markers within a decade post-surgery. Pelvic lymph node sampling during prostatectomy assesses potential lymph node metastases, but standard histological assessments, which typically examine only 2-3 tissue sections, often miss occult metastases. This study assesses the effectiveness of qPCR in detecting PSA coding KLK3 mRNA for identifying lymph node metastases post-prostatectomy and explores the correlation between PSA-mRNA and biochemical recurrence.

Toward structured abdominal examination training using augmented reality.

Purpose: Structured abdominal examination is an essential part of the medical curriculum and surgical training, requiring a blend of theory and practice from trainees. Current training methods, however, often do not provide adequate engagement, fail to address individual learning needs or do not cover rare diseases.

Methods: In this work, an application for structured Abdominal Examination Training using Augmented Reality (AETAR) is presented.

Pharmacological targeting of caspase-8/c-FLIP heterodimer enhances complex II assembly and elimination of pancreatic cancer cells.

Extrinsic apoptotic network is driven by Death Ligand (DL)-mediated activation of procaspase-8. Recently, we have developed the first-in class small molecule, FLIPinB, which specifically targets the key regulator of extrinsic apoptosis, the protein c-FLIP, in the caspase-8/c-FLIP heterodimer. We have shown that FLIPinB enhances DL-induced caspase-8 activity and apoptosis.

Synaptoneurolipidomics: lipidomics in the study of synaptic function.

The brain is an exceptionally lipid-rich organ with a very complex lipid composition. Lipids are central in several neuronal processes, including membrane formation and fusion, myelin packing, and lipid-mediated signal transmission. Lipid diversity is associated with the evolution of higher cognitive abilities in primates, is affected by neuronal activity, and is instrumental for synaptic plasticity, illustrating that lipids are not static components of synaptic membranes.

Compromising tyrosine hydroxylase function extends and blunts the temporal profile of reinforcement by dopamine neurons in .

For a proper representation of the causal structure of the world, it is adaptive to consider both evidence for and evidence against causality. To take punishment as an example, the causality of a stimulus is unlikely if there is a temporal gap before punishment is received, but causality is credible if the stimulus immediately precedes punishment. In contrast, causality can be ruled out if the punishment occurred first.

Prefrontal dimension change-related activation differs for visual search in sparse and dense displays.

Changes of the target-defining feature dimension have previously been shown to elicit anterior prefrontal activation increases. In the majority of studies, this change-related activation was observed in the left lateral frontopolar cortex. In at least one study, however, right anterior prefrontal activation was observed.

Experimental economics for machine learning-a methodological contribution on lie detection.

In this paper, we investigate how technology has contributed to experimental economics in the past and illustrate how experimental economics can contribute to technological progress in the future. We argue that with machine learning (ML), a new technology is at hand, where for the first time experimental economics can contribute to enabling substantial improvement of technology. At the same time, ML opens up new questions for experimental research because it can generate previously impossible observations.

Olfactory deficits in aging and Alzheimer's-spotlight on inhibitory interneurons.

Cognitive function in healthy aging and neurodegenerative diseases like Alzheimer's disease (AD) correlates to olfactory performance. Aging and disease progression both show marked olfactory deficits in humans and rodents. As a clear understanding of what causes olfactory deficits is still missing, research on this topic is paramount to diagnostics and early intervention therapy.

Tracing active members in microbial communities by BONCAT and click chemistry-based enrichment of newly synthesized proteins.

A comprehensive understanding of microbial community dynamics is fundamental to the advancement of environmental microbiology, human health, and biotechnology. Metaproteomics, defined as the analysis of all proteins present within a microbial community, provides insights into these complex systems. Microbial adaptation and activity depend to an important extent on newly synthesized proteins (nP), however, the distinction between nP and bulk proteins is challenging.

- a large-scale dataset of 3D medical shapes for computer vision.

Objectives: The shape is commonly used to describe the objects. State-of-the-art algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from the growing popularity of ShapeNet (51,300 models) and Princeton ModelNet (127,915 models).

The Effects of Reverse Nordic Exercise Training on Measures of Physical Fitness in Youth Karate Athletes.

In karate, the ability to execute high-velocity movements, particularly kicks and punches, is heavily dependent on the strength and power of the lower limb muscles, especially the knee extensors. As such, this study aimed to evaluate the effects of an 8-week eccentric training program utilizing the reverse Nordic exercise (RNE) integrated into karate training compared with regular karate training only on measures of physical fitness in youth karate athletes. Twenty-seven youth karatekas were recruited and allocated to either RNE group (n = 13; age = 15.

First Clinical Application of Aztreonam-Avibactam in Treating Carbapenem-Resistant Enterobacterales: Insights from Therapeutic Drug Monitoring and Pharmacokinetic Simulations.

: A novel fixed combination of aztreonam (ATM) and avibactam (AVI) offers promising potential to treat infections with carbapenem-resistant (CRE) producing metallo-β-lactamases (MBL). This study aimed to assess the accuracy of population pharmacokinetic (PK) models for ATM-AVI in predicting in vivo concentrations in a critically ill patient with CRE infection during its first clinical use. : A 70-year-old male with septic shock due to hospital-acquired pneumonia (HAP) caused by MBL-producing was treated with ATM-AVI.

Advanced Wearable Devices for Monitoring Sweat Biochemical Markers in Athletic Performance: A Comprehensive Review.

Wearable technology has advanced significantly, offering real-time monitoring of athletes' physiological parameters and optimizing training and recovery strategies. Recent developments focus on biosensor devices capable of monitoring biochemical parameters in addition to physiological ones. These devices employ noninvasive methods such as sweat analysis, which reveals critical biomarkers like glucose, lactate, electrolytes, pH, and cortisol.