Histamine H receptor blockade alleviates neuropathic pain through the regulation of glial cells activation.

Neuropathic pain is a disorder affecting the somatosensory nervous system. However, this condition is also characterized by significant neuroinflammation, primarily involving CNS-resident non-neuronal cells. A promising target for developing new analgesics is histamine H receptor (HR); thus, we aimed to determine the influence of a novel HR antagonist/inverse agonist, E-98 (1-(7-(4-chlorophenoxy)heptyl)-3-methylpiperidine), on pain symptoms and glia activation in model of neuropathic pain in male mice (chronic constriction injury to the sciatic nerve).

Guaranteed efficient energy estimation of quantum many-body Hamiltonians using ShadowGrouping.

Estimation of the energy of quantum many-body systems is a paradigmatic task in various research fields. In particular, efficient energy estimation may be crucial in achieving a quantum advantage for a practically relevant problem. For instance, the measurement effort poses a critical bottleneck for variational quantum algorithms.

The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.

Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1 kinase and inhibits autophagy flux.

Cerebral vasculitis related to neurosarcoidosis: a case series and systematic literature review.

Cerebral vasculitis is a rare but severe manifestation of neurosarcoidosis (NS) that has received little attention. The aim of the present study was to characterize clinical and diagnostic features as well as potential treatment strategies of cerebral vasculitis related to NS. We assessed 29 patients with cerebral vasculitis related to NS (15 female, mean age at time of diagnosis 45 years, SD = 11.

Subacute thyroiditis - Is it really linked to viral infection? Retrospective hospital patient registry study.

Objective: Subacute thyroiditis (SAT) is a painful inflammatory disorder of the thyroid gland, which - after a phase of thyrotoxicosis - leads to transient, or less frequently permanent hypothyroidism. Apart from a strong association with specific HLA alleles, the causes are uncertain. Viral disease has been hypothesised as a trigger, with Enteroviruses, namely Echoviruses and Coxsackieviruses, showing a seasonal distribution that coincides with the incidence of SAT.

Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth and metastasis, partly driven by fibroblast-mediated stromal interactions. Using RNA sequencing of fibroblasts from early-stage KPC mouse models, we identified significant upregulation of genes involved in adipogenesis, fatty acid metabolism, and the ROS pathway. ANGPTL4, a key adipogenesis regulator, was highly expressed in fibroblasts and promoted pancreatic cancer cell proliferation and migration through paracrine signaling.

Expanding the Chemical Space of Reverse Fosmidomycin Analogs.

Multidrug-resistant pathogens pose a major threat to human health, necessitating the identification of new drug targets and lead compounds that are not susceptible to cross-resistance. This study demonstrates that novel reverse thia analogs of the phosphonohydroxamic acid antibiotic fosmidomycin inhibit 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme for , , and that is absent in humans. Some novel analogs with large α-phenyl substituents exhibited strong inhibition across these three DXR orthologues, surpassing the inhibitory activity of fosmidomycin.

Effects on impulsivity and delay discounting of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: a randomized, sham-controlled pilot trial.

Background: Dialectical behavioral therapy (DBT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating borderline personality disorder (BPD). Impulsivity and impaired decision-making are prominent features of BPD, and therapeutic interventions targeting these symptoms could lead to significant improvements.

Objective/hypothesis: We hypothesized that intermittent theta burst stimulation (iTBS), a modified rTMS protocol that targets the left dorsolateral prefrontal cortex, would enhance the therapeutic effects of DBT, leading to greater improvements in impulsivity and decision-making compared with sham stimulation.

Deep-Learning-based Automated Identification of Ventriculoperitoneal-Shunt Valve Models from Skull X-rays.

Introduction: Ventriculoperitoneal shunts (VPS) are an essential part of the treatment of hydrocephalus, with numerous valve models available with different ways of indicating pressure levels. The model types often need to be identified on X‑rays to assess pressure levels using a matching template. Artificial intelligence (AI), in particular deep learning, is ideally suited to automate repetitive tasks such as identifying different VPS valve models.

Engineering organoids as cerebral disease models.

Cerebral organoids pioneered in replicating complex brain tissue architectures in vitro, offering a vast potential for human disease modeling. They enable the in vitro study of human physiological and pathophysiological mechanisms of various neurological diseases and disorders. The trajectory of technological advancements in brain organoid generation and engineering over the past decade indicates that the technology might, in the future, mature into indispensable solutions at the horizon of personalized and regenerative medicine.

Temporal Lobe Epilepsy Perturbs the Brain-Wide Excitation-Inhibition Balance: Associations with Microcircuit Organization, Clinical Parameters, and Cognitive Dysfunction.

Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with ample research focusing on elucidating its cellular manifestations. However, few studies investigate E/I imbalance at the macroscale, whole-brain level, and its microcircuit-level mechanisms and clinical significance remain incompletely understood. Here, the Hurst exponent, an index of the E/I ratio, is computed from resting-state fMRI time series, and microcircuit parameters are simulated using biophysical models.

Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches.

Atherosclerosis is a disease of large and medium arteries that can lead to life-threatening cardiovascular and cerebrovascular consequences, such as myocardial infarction and stroke. Moreover, atherosclerosis is a major contributor to cardiovascular-related mortality in individuals with diabetes mellitus. Diabetes aggravates the pathobiological mechanisms that underlie the development of atherosclerosis.

Type 1 diabetes incidence curves differ by age for girls and boys between 1996 and 2022: Results from the North Rhine-Westphalia diabetes Registry, Germany.

Type 1 diabetes incidence was analyzed in 0- to 14-year-old children in North Rhine-Westphalia, Germany, from 1996 to 2022. The data revealed an overall increasing trend, with variations by age and sex. The incidence increased in boys across age groups but peaked in girls in the 5-9-year age group.

Assessment of pandemic-related pregnancy stress from seven western countries using Rasch analyses.

Introduction: This study examined psychometric properties of the Pandemic-Related Pregnancy Stress Scale (PREPS) using a Rasch Model (RM) in a large sample of pregnant women from Germany, Israel, Italy, Poland, Spain, Switzerland and the United States of America (USA).

Material And Methods: Rasch analyses were used to analyze a sample of 7185 pregnant women who completed the PREPS during the COVID-19 pandemic onset from April to August 2020. Psychological, sociodemographic, and obstetric factors were also collected and analyzed.

Assembly and Quantification of Co-Cultures Combining Heterotrophic Yeast with Phototrophic Sugar-Secreting Cyanobacteria.

With the increasing demand for sustainable biotechnologies, mixed consortia containing a phototrophic microbe and heterotrophic partner species are being explored as a method for solar-driven bioproduction. One approach involves the use of CO2-fixing cyanobacteria that secrete organic carbon to support the metabolism of a co-cultivated heterotroph, which in turn transforms the carbon into higher-value goods or services. In this protocol, a technical description to assist the experimentalist in the establishment of a co-culture combining a sucrose-secreting cyanobacterial strain with a fungal partner(s), as represented by model yeast species, is provided.

The predictive power of baseline metabolic and volumetric [F]FDG PET parameters with different thresholds for early therapy failure and mortality risk in DLBCL patients undergoing CAR-T-cell therapy.

Objective: [F]FDG imaging is an integral part of patient management in CAR-T-cell therapy for recurrent or therapy-refractory DLBCL. The calculation methods of predictive power of specific imaging parameters still remains elusive. With this retrospective study, we sought to evaluate the predictive power of the baseline metabolic parameters and tumor burden calculated with automated segmentation via different thresholding methods for early therapy failure and mortality risk in DLBCL patients.

Time is Confidence: Monetary Incentives Metacognitive Profile on Duration Judgment.

The question we addressed in the current study is whether the mere prospect of monetary reward gain affects subjective time perception. To test this question, we collected trial-based confidence reports in a task where participants made categorical decisions about probe durations relative to the reference duration. When there was a potential to gain a monetary reward, the duration was perceived to be longer than in the neutral condition.

Evaluating the impact of a hand-crafted 3D-Printed head Model and virtual reality in skull base surgery training.

Introduction: While cadaveric dissections remain the cornerstone of education in skull base surgery, they are associated with high costs, difficulty acquiring specimens, and a lack of pathology in anatomical samples. This study evaluated the impact of a hand-crafted three-dimensional (3D)-printed head model and virtual reality (VR) in enhancing skull base surgery training.

Research Question: How effective are 3D-printed models and VR in enhancing training in skull base surgery?

Materials And Methods: A two-day skull base training course was conducted with 12 neurosurgical trainees and 11 faculty members.

Three-year course of clinical high-risk symptoms for psychosis in the community: a latent class analysis.

Aims: Clinical high-risk for psychosis (CHR-P) states exhibit diverse clinical presentations, prompting a shift towards broader outcome assessments beyond psychosis manifestation. To elucidate more uniform clinical profiles and their trajectories, we investigated CHR-P profiles in a community sample.

Methods: Participants ( = 829; baseline age: 16-40 years) comprised individuals from a Swiss community sample who were followed up over roughly 3 years.

Associations between biomarkers of inflammation and depressive symptoms-potential differences between diabetes types and symptom clusters of depression.

Inflammation is a probable biological pathway underlying the relationship between diabetes and depression, but data on differences between diabetes types and symptom clusters of depression are scarce. Therefore, this cross-sectional study aimed to compare associations of a multimarker panel of biomarkers of inflammation with depressive symptoms and its symptom clusters between people with type 1 diabetes (T1D) and type 2 diabetes (T2D). This cross-sectional study combined data from five studies including 1260 participants (n = 706 T1D, n = 454 T2D).

Molecular basis for the enzymatic inactivity of class III glutaredoxin ROXY9 on standard glutathionylated substrates.

Class I glutaredoxins (GRXs) are nearly ubiquitous proteins that catalyse the glutathione (GSH)-dependent reduction of mainly glutathionylated substrates. In land plants, a third class of GRXs has evolved (class III). Class III GRXs regulate the activity of TGA transcription factors through yet unexplored mechanisms.

C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis.

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients.