Pragmatic Algorithm for Visual Assessment of 4-Repeat Tauopathies in [F]PI-2620 PET Scans.

Aim: Standardized evaluation of [F]PI-2620 tau-PET scans in 4R-tauopathies represents an unmet need in clinical practice. This study aims to investigate the effectiveness of visual evaluation of [F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility.

Methods: A total of 83 individuals with [F]PI-2620 PET scans were included.

Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort.

High-throughput proteomic platforms are crucial to identify novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan 7k) and antibody-based (Olink Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan assays analyzing the same samples, and between SomaScan and Olink results.

The α- and β-Subunits of Nitric Oxide-Sensitive Guanylyl Cyclase in Pericytes of Healthy Human Dental Pulp.

Nitric oxide-sensitive guanylyl cyclase (NO-GC) is a heterodimeric enzyme with an α- and a β-subunit. In its active form as an αβ-heterodimer, NO-GC produces cyclic guanosine-3',5'-monophophate (cGMP) to regulate vasodilation and proliferation of vascular smooth muscle cells (VSMCs). In contrast to VSMCs, only a few studies reported on the expression of the NO-GC αβ-heterodimer in human pericytes.

Structure-Activity Relationship Studies of Tetracyclic Pyrrolocarbazoles Inhibiting Heterotetrameric Protein Kinase CK2.

The serine/threonine kinase CK2 (formerly known as casein kinase II) plays a crucial role in various CNS disorders and is highly expressed in various types of cancer. Therefore, inhibiting this key kinase could be promising for the treatment of these diseases. The CK2 holoenzyme is formed by the recruitment of two catalytically active CK2α and/or CK2α' subunits by a regulatory CK2β dimer.

Safety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.

Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.

Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.

Predicting the risk of intensive care unit admission in patients with COVID-19 presenting in the emergency room: Development and evaluation of the CROSS score.

Background: Existing risk evaluation tools underperform in predicting intensive care unit (ICU) admission for patients with the Coronavirus Disease 2019 (COVID-19). This study aimed to develop and evaluate an accurate and calculator-free clinical tool for predicting ICU admission at emergency room (ER) presentation.

Methods: Data from patients with COVID-19 in a nationwide German cohort (March 2020-January 2023) were analyzed.

A creatine efflux transporter in oligodendrocytes.

Creatine is essential for ATP regeneration in energy-demanding cells. Creatine deficiency results in severe neurodevelopmental impairments. In the brain, creatine is synthesized locally by oligodendrocytes to supply neighboring neurons.

Bridging health registry data acquisition and real-time data analytics.

The number of clinical studies and associated research has increased significantly in the last few years. Particularly in rare diseases, an increased effort has been made to integrate, analyse, and develop new knowledge to improve patient stratification and wellbeing. Clinical databases, including digital medical records, hold significant amount of information that can help understand the impact and progression of diseases.

A systematic review of the blockchain application in healthcare research domain: toward a unified conceptual model.

Recently, research on blockchain applications in the healthcare research domain has attracted increasing attention due to its strong potential. However, the existing literature reveals limited studies on defining use cases of blockchain in clinical research, categorizing and comparing available studies. Therefore, this study aims to explore the significant potential and use cases of blockchain in clinical research through a comprehensive systematic literature review (SLR).

Neglect symptoms are related to a prediction-hypersensitivity in ipsilesional space.

The precise cognitive mechanisms underlying spatial neglect are not fully understood. Recent studies have provided the first evidence for aberrant behavioral and electrophysiological prediction and prediction error responses in patients with neglect, but also in right-hemispheric (RH) stroke patients without neglect. For prediction-dependent attention, as assessed with Posner-type cueing paradigms with volatile cue-target contingencies, studies in healthy volunteers point to a crucial role of the right temporo-parietal junction (rTPJ) - as part of a network commonly disrupted in neglect.

Approach to anaemia in gastrointestinal disease: A position paper by the ESPGHAN Gastroenterology Committee.

Anaemia is a frequent consequence of many gastrointestinal (GI) diseases in children and it can even be the initial presenting symptom of underlying chronic GI disease. The definition of anaemia is age and gender-dependent and it can be classified based on pathophysiology, red cell morphology, and clinical presentation. Although nutritional deficiencies, including GI malabsorption of nutrients and GI bleeding, play a major role, other pathophysiologic mechanisms seen in chronic GI diseases, whether inflammatory (e.

The role of the left primary motor cortex in apraxia.

Background: Apraxia is a motor-cognitive disorder that primary sensorimotor deficits cannot solely explain. Previous research in stroke patients has focused on damage to the fronto-parietal praxis networks in the left hemisphere (LH) as the cause of apraxic deficits. In contrast, the potential role of the (left) primary motor cortex (M1) has largely been neglected.

C3aR1-Deletion Delays Retinal Degeneration in a White-Light Damage Mouse Model.

Purpose: In the aging retina, persistent activation of microglia is known to play a key role in retinal degenerative diseases like age-related macular degeneration (AMD). Furthermore, dysregulation of the alternative complement pathway is generally accepted as the main driver for AMD disease progression and microglia are important producers of local complement and are equipped with complement receptors themselves. Here, we investigate the involvement of anaphylatoxin signaling, predominantly on Iba1+ cell activity, in light-induced retinal degeneration as a model for dry AMD, using anaphylatoxin receptor knockout (KO) mice.

Association of Molecular Detections of Microsporidia in Stool Samples with Clinical and Immunological Parameters in Ghanaian HIV Patients.

Although the etiological relevance of the detection of microsporidia in human stool samples remains uncertain, the immunological status of patients has been posited as an important determinant of potential clinical impact of these parasites. To further assess the interplay between the epidemiology of microsporidia and immunological markers, we conducted a study utilizing real-time PCR targeting , , , and , combined in a single fluorescence channel. The study involved a cohort of 595 clinically and immunologically well-characterized Ghanaian HIV patients, alongside 82 HIV-negative control individuals from Ghana.

Matrix-mediated activation of murine fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLS) are key cells promoting cartilage damage and bone loss in rheumatoid arthritis (RA). They are activated to assume an invasive and migratory phenotype. While mechanisms of FLS activation are unknown, evidence suggests that pre-damaged extracellular matrix (ECM) of the cartilage can trigger FLS activation.

Trends in smoking-attributable cardiovascular mortality in Germany.

We quantified the fraction of cardiovascular deaths attributable to smoking in Germany over time, accounting for population ageing. We calculated population-attributable fractions to quantify cardiovascular deaths attributable to smoking for 1992 to 2021, and compared actual with age-standardized figures. We found a significant decline in the number of cardiovascular deaths attributable to smoking: from about 71 900 cases in 1992 to around 42 000 cases in 2021, with a steeper decline in men.

Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons.

Cell polarity is crucial in neurons, characterized by distinct axonal and dendritic structures. Neurons generally have one long axon and multiple shorter dendrites, marked by specific microtubule (MT)-associated proteins, e.g.

Progress in Nanotechnology for Treating Ocular Surface Chemical Injuries: Reflecting on Advances in Ophthalmology.

Ocular surface chemical injuries often result in permanent visual impairment and necessitate complex, long-term treatments. Immediate and extensive irrigation serves as the first-line intervention, followed by various therapeutic protocols applied throughout different stages of the condition. To optimize outcomes, conventional regimens increasingly incorporate biological agents and surgical techniques.

Transcriptome and DNA methylation profiling during the NSN to SN transition in mouse oocytes.

Background: During the latter stages of their development, mammalian oocytes under dramatic chromatin reconfiguration, transitioning from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) stage, and concomitant transcriptional silencing. Although the NSN-SN transition is known to be essential for developmental competence of the oocyte, less is known about the accompanying molecular changes. Here we examine the changes in the transcriptome and DNA methylation during the NSN to SN transition in mouse oocytes.

"We are doing it together, don't worry" - A qualitative study on the implementation of electronic medical records in German hospitals.

Background: The ongoing implementation of electronic medical records (EMRs) in German hospitals is currently slow. Implementation science widely acknowledges the barriers and facilitators to implementation. Thus, specific preconditions are necessary to address the former and to support an effective EMR implementation.

Optimising (re-)irradiation for locally recurrent head and neck cancer: impact of dose-escalation, salvage surgery, PEG tube and biomarkers on oncological outcomes-a single centre analysis.

Introduction: Locoregional recurrence (LR) is common in locally advanced head and neck cancer (HNSCC), posing challenges for treatment. We analysed outcome parameters and toxicities for patients being treated with radiotherapy (RT) for LR-HNSCC and investigated patient and disease related prognostic factors in this prognostically unfavourable group.

Methods: This analysis includes 101 LR-HNSCC patients treated with RT, radio-chemotherapy (RCT) or radio-immunotherapy (RIT) between 2010 and 2018 at a high-volume tertiary centre.

Risk factors analysis and nomogram for predicting recurrence in periocular basal cell carcinoma.

Objectives: Aim to develop a nomogram to effectively predict the potential for recurrence after surgical resection in patients with periocular basal cell carcinoma (BCC).

Methods: We conducted a retrospective study involving 329 patients with eyelid BCC. Univariate and multivariate Cox proportional risk regression was used to screen for independent factors affecting BCC recurrence.

Evaluation of early metabolic changes following vorasidenib using FET PET in patients with -mutant gliomas.

The phase-3 INDIGO trial demonstrated that the isocitrate dehydrogenase () inhibitor vorasidenib significantly prolonged progression-free survival and delayed intervention in patients with CNS WHO grade 2 gliomas. However, conventional MRI showed limited response, with only 11% of patients having objective responses. Studies suggest that serial PET imaging with radiolabeled amino acids, such as -(2-[ F]-fluoroethyl)-L-tyrosine (FET) PET, may provide earlier and more informative assessments of treatment response than MRI.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.