Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Introducing and Validating the Multiphasic Evidential Decision-Making Matrix (MedMax) for Clinical Management in Patients with Intrahepatic Cholangiocarcinoma.

Despite the significant advancements of liver surgery in the last few decades, the survival rate of patients with liver and pancreatic cancers has improved by only 10% in 30 years. Precision medicine offers a patient-centered approach, which, when combined with machine learning, could enhance decision making and treatment outcomes in surgical management of ihCC. This study aims to develop a decision support model to optimize treatment strategies for patients with ihCC, a prevalent primary liver cancer.

Generation of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells.

Placentation disorders, including severe preeclampsia and fetal growth restriction, have their origins in early pregnancy, whereas symptoms typically present later on. To investigate the pathogenesis of these diseases, there is a need for a reliable in vitro model system of early placenta development with known pregnancy outcomes. Therefore, we optimized the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord, enabling non-invasive collection of patient-derived material immediately after birth.

A cellulosic fibre foam as a bicycle helmet impact liner for brain injury mitigation in oblique impacts.

Bulky cellulosic network structures (BRC) with densities between 60 and 130 g/l were investigated as a sustainable alternative to fossil-based foams for impact liners in bicycle helmets. The mechanical properties of BRC foams were characterized across a wide range of strain rates and incorporated into a validated finite element model of a hardshell helmet. Virtual impact tests simulating both consumer information and certification scenarios were conducted to compare BRC-lined helmets against conventional expanded polystyrene (EPS) designs.

Climate change mitigation potential and economic evaluation of selected technical adaptation measures and innovations in conventional arable farming in Germany.

Agriculture accounts for a large proportion of global greenhouse gas (GHG) emissions. It is therefore crucial to identify effective and efficient GHG mitigation potentials in agriculture, but also in related upstream sectors. However, previous studies in this area have rarely undertaken a cross-sectoral assessment.

Reinventing type 2 immunity in cancer.

Our understanding of type 2 immunity has undergone a substantial transformation in recent years, revealing previously unknown functions. Beyond its canonical role in defence against parasitic helminth infections, type 2 immunity safeguards the host through additional mechanisms, including the suppression of excessive type 1 immune responses, regulation of tissue repair and maintenance of adipose tissue homeostasis. However, unlike type 1 immune responses, type 2 immunity is perceived as a potential promoter of tumorigenesis.

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.

Modifiable Health Behaviours in Children with HCM: Lessons from the Heart Health Survey.

Obesity factors into hypertrophic cardiomyopathy (HCM)-related risk as a disease modifying environmental factor. Behaviours such as diet and sleep are seldom reported upon in children with HCM. It was our aim to report on these factors in this population.

Impact of T Cell Exhaustion and Stroma Senescence on Tumor Cell Biology and Clinical Outcome of Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinomas (HNSCC) have an overall poor prognosis, especially in locally advanced and metastatic stages. In most cases, multimodal therapeutic approaches are required and show only limited cure rates with a high risk of tumor recurrence. Anti-PD-1 antibody treatment was recently approved for recurrent and metastatic cases but to date, response rates remain lower than 25%.

Proteomic Sensors for Quantitative, Multiplexed and Spatial Monitoring of Kinase Signaling.

Understanding kinase action requires precise quantitative measurements of their activity . In addition, the ability to capture spatial information of kinase activity is crucial to deconvolute complex signaling networks, interrogate multifaceted kinase actions, and assess drug effects or genetic perturbations. Here we developed a proteomic kinase activity sensor platform (ProKAS) for the analysis of kinase signaling using mass spectrometry.

Deep learning enabled near-isotropic CAIPIRINHA VIBE in the nephrogenic phase improves image quality and renal lesion conspicuity.

Background: Deep learning (DL) accelerated controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE), provides high spatial resolution T1-weighted imaging of the upper abdomen. We aimed to investigate whether DL-CAIPIRINHA-VIBE can improve image quality, vessel conspicuity, and lesion detectability compared to a standard CAIPIRINHA-VIBE in renal imaging at 3 Tesla.

Methods: In this prospective study, 50 patients with 23 solid and 45 cystic renal lesions underwent MRI with clinical MR sequences, including standard CAIPIRINHA-VIBE and DL-CAIPIRINHA-VIBE sequences in the nephrographic phase at 3 Tesla.

Distribution of TRPC1, TRPC3, and TRPC6 in the human thyroid.

Background: Little is known about the protein expression of the transient receptor potential canonical (TRPC) channels 1, 3, and 6 in the thyroid. Research in human tissue is insufficient. Our aim was to investigate the distribution of TRPC1, 3, and 6 in the healthy human thyroid.

RICTOR variants are associated with neurodevelopmental disorders.

RICTOR is a key component of the mTORC2 signaling complex which is involved in the regulation of cell growth, proliferation and survival. RICTOR is highly expressed in neurons and is necessary for brain development. Here, we report eight unrelated patients presenting with intellectual disability and/or development delay and carrying variants in the RICTOR gene.

Defining the role of Hmu and Hus systems in Porphyromonas gingivalis heme and iron homeostasis and virulence.

Iron and heme are essential nutrients for all branches of life. Pathogenic members of the Bacteroidota phylum, including Porphyromonas gingivalis, do not synthesize heme and rely on host hemoproteins for heme as a source of iron and protoporphyrin IX. P.

Claudins in vulvar cancer - from epithelial barrier to potential tumor-agnostic cancer therapy.

The immunohistochemical expression of various members of the claudin family has already been studied in pathological affections of the vulva whether to differentiate precancerous lesions from vulvar squamous cell carcinoma or in inflammatory conditions such as lichen sclerosus. From an oncological perspective, however, immunohistochemical analysis of claudin 18.2 protein expression has become increasingly clinically relevant nowadays since the impressive therapeutic benefits of the claudin 18.

Psychological and behavioral dimensions in cardiac arrest survivors and their families: A state-of-the-art review.

This article aims to highlight high-quality observational and intervention studies focused on promoting psychological well-being among cardiac arrest (CA) survivors and their families. Following CA, many patients experience significant psychological distress, including depression, generalized anxiety, and post-traumatic stress. Recent studies indicate that this distress can narrow patients' focus, resulting in heightened awareness of cardiac signals-such as fluctuations in heart rate or blood pressure-that lead to constant monitoring and increased anxiety.

pH-FISH: coupled microscale analysis of microbial identity and acid-base metabolism in complex biofilm samples.

Background: Correlative structural and chemical imaging of biofilms allows for the combined analysis of microbial identity and metabolism at the microscale. Here, we developed pH-FISH, a method that combines pH ratiometry with fluorescence in situ hybridization (FISH) in structurally intact biofilms for the coupled investigation of microbial acid metabolism and biofilm composition. Careful biofilm handling and modified sample preparation procedures for FISH allowed preservation of the three-dimensional biofilm structure throughout all processing and imaging steps.

Mild-to-moderate psoriasis is associated with subclinical inflammation in the duodenum and a tendency of disturbed intestinal barrier.

Psoriasis is a chronic skin disease occasionally associated with abdominal symptoms and IBD. We aimed to characterize intestinal immune cells and the integrity of the intestinal barrier in psoriasis. Biopsies from the duodenum and colon were analyzed by flow cytometry and immunohistochemistry for the presence and activation status of different immune cell populations.

Generating 3D brain tumor regions in MRI using vector-quantization Generative Adversarial Networks.

Medical image analysis has significantly benefited from advancements in deep learning, particularly in the application of Generative Adversarial Networks (GANs) for generating realistic and diverse images that can augment training datasets. The common GAN-based approach is to generate entire image volumes, rather than the region of interest (ROI). Research on deep learning-based brain tumor classification using MRI has shown that it is easier to classify the tumor ROIs compared to the entire image volumes.

Listeria monocytogenes colonises established multispecies biofilms and resides within them without altering biofilm composition or gene expression.

Listeria (L.) monocytogenes can survive for extended periods in the food producing environment. Here, biofilms possibly provide a niche for long-term survival due to their protective nature against environmental fluctuations and disinfectants.

Subnormothermic Machine Perfusion of Neonatal and Small-Sized Pediatric Donor Hearts.

Donor heart machine perfusion enables avoidance of prolonged cold ischemia, however the optimal temperature is yet to be elucidated. Given that maintenance of temperature beyond ambient levels demands significant energy, we sought to determine the suitability of room-temperature perfusion preservation of neonatal/pediatric-sized (5-20 kg) piglet donor hearts. A custom device was fabricated suitable for this purpose, with continuous readout of perfusion pressure, flow rate, temperature, and oxygen saturation.

A Robust High-Pressure RO Technology to Overcome the Barriers to Full Circularity in Cr(III) Electroplating Operations.

Electroplating is a widely used technology for anticorrosion materials and decorative coatings. In view of the transition to a circular economy, the current electroplating wastewater treatment disposing of heavy metal sludge and wastewater severely lacks sustainability. Authors recently reported the successful recycling of electroplating agents using hybrid semibatch/batch reverse osmosis technology (hybrid RO).

Does needle clogging change the spatial distribution of injected drug in tissue? New insights by X-ray computed tomography.

Prefilled syringes (PFS) are primary packaging materials that offer convenience and safety for subcutaneous injection of parenteral drug solutions. However, an increasingly common problem with the trend towards higher drug concentrations is the clogging of the needle during storage due to evaporative water loss and consequent solidification of the drug. In contrast to all previous studies on this topic, this work focuses on pharmacokinetically relevant aspects and investigates the effects of needle clogging on the spatial distribution of the injected drug in the tissue.

Evaluation of immunohistochemical TRPC3 and TRPC6 expression patterns in human endometriosis.

Background: Although to date the pathogenesis of endometriosis remains largely unexplained, it is known that processes of migration, proliferation and revascularization and thus calcium as a messenger substance play an important role. Consecutively, the present study examines the immunohistochemical expression of the calcium transient receptor potential channels 3 and 6 (TRPC3 and TRPC6) in ectopically located (outside the uterine cavity) endometrial tissue.

Methods: Laparoscopically collected and histomorphologically verified endometriosis tissues from several different intraabdominal locations were examined (n = 20) and immunohistochemical stainings were performed with anti-TRPC3 and anti-TRPC6 antibodies (Alomone Labs, Jerusalem).