Dental and oral health assessments in the German National Cohort (NAKO).

Background: Despite considerable improvements in oral health in recent decades, caries and periodontitis are still widespread, ranking among the most prevalent diseases worldwide and requiring future research. The German National Cohort (NAKO Gesundheitsstudie, NAKO) is a large-scaled, multidisciplinary, nationwide, multi-centre, population-based, prospective cohort study with oral examinations that aims to provide a resource to study risk factors for major diseases. The aim of the present article is to provide the methodological background, to report on the data quality, and to present initial results of the oral examinations.

Segment specific loss of NFAT5 function in the kidneys is sufficient to induce a global kidney injury like phenotype.

Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor known for its role in osmotic stress adaptation in the renal inner medulla, due to the osmotic gradient that is generated between the renal cortex and renal inner medulla. However, its broader implications in kidney injury and chronic kidney disease (CKD) are less understood. Here we used two different Cre deleter mice (Ksp1.

Assessing Preferences of Patients with Chronic Spontaneous Urticaria for Injectable Treatment Profiles.

Background: In the context of injectable biologic products approved or in development for chronic spontaneous urticaria (CSU), it is important to capture which treatment attributes matter most to patient and what trade-offs patients are willing to make.

Objectives: The CHOICE-CSU study aimed to quantify patient preferences toward injectable treatment attributes among patients with CSU, inadequately controlled by H1-antihistamines.

Methods: This was a two-phase cross-sectional patient preference study in adult patients with a diagnosis of CSU, inadequately controlled by H1-antihistamines.

Modality-, feature-, and strategy-dependent organization of low-level working memory.

Previous research has shown that, when multiple similar items are maintained in working memory, recall precision declines. Less is known about how heterogeneous sets of items across different features within and between modalities impact recall precision. In two experiments, we investigated modality (Experiment 1, n = 79) and feature-specific (Experiment 2, n = 154) load effects on working memory performance.

Effective eradication of acute myeloid leukemia stem cells with FLT3-directed antibody-drug conjugates.

Refractory disease and relapse are major challenges in acute myeloid leukemia (AML) therapy attributed to survival of leukemic stem cells (LSC). To target LSCs, antibody-drug conjugates (ADCs) provide an elegant solution, combining the specificity of antibodies with highly potent payloads. We aimed to investigate if FLT3-20D9h3-ADCs delivering either the DNA-alkylator duocarmycin (DUBA) or the microtubule-toxin monomethyl auristatin F (MMAF) can eradicate quiescent LSCs.

Empathy During Crises: Investigating Attitudes, Tolerance, and Ingroup-Outgroup Dynamics in Response to Refugee Movements.

Objective: In times of societal crises, it is pivotal to understand and share others' feelings. Yet, the role of empathy in fostering prosocial responses during societal crises has not gained enough attention. Our study uses the onset of Russia's war on Ukraine to examine three key questions: (1) Is empathy related to attitudes toward pro-refugee policies? (2) Does empathy correlate with a higher tolerance for diverse opinions on refugee policies? (3) Is empathy linked to perceived interpersonal closeness toward social in- and outgroups, including refugees?

Methods And Results: Using observational data from online surveys conducted with a largely representative quota sample from Germany (N = 1199-1631) during the initial months of the war, we found that empathy was associated with significantly higher support of pro-refugee policies, driven primarily by empathic concern.

White matter connections within the central sulcus subserving the somato-cognitive action network.

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network.

New and Emerging Biological Therapies for Myasthenia Gravis: A Focussed Review for Clinical Decision-Making.

Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured.

Multicenter validation of secondary hemophagocytic lymphohistiocytosis diagnostic criteria.

Background: Five fulfilled hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, and the HScore are widely used and recommended by international expert consensus to diagnose secondary HLH. Both diagnostic scores have never been validated in heterogeneous patient cohorts of secondary HLH patients. We aimed to systematically optimize and validate diagnostic criteria of secondary HLH using a multicenter approach.

Linking higher amyloid beta 1-38 (Aβ(1-38)) levels to reduced Alzheimer's disease progression risk.

Introduction: The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.

Methods: Cognitive function and diagnostic change were assessed annually for 3 years in 177 Aβ-positive participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia from the German Center for Neurodegenerative Diseases (DZNE) longitudinal cognitive impairment and dementia study (DELCODE) cohort using the Mini-Mental State Examination (MMSE), Preclinical Alzheimer's Cognitive Composite (PACC), Clinical Dementia Rating (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

Predicting the impact of targeted fence removal on connectivity in a migratory ecosystem.

Fencing is one of the most widely utilized tools for reducing human-wildlife conflict in agricultural landscapes. However, the increasing global footprint of fencing exceeds millions of kilometers and has unintended consequences for wildlife, including habitat fragmentation, movement restriction, entanglement, and mortality. Here, we present a novel and quantitative approach to prioritize fence removal within historic migratory pathways of white-bearded wildebeest (Connochaetes taurinus) across Kenya's Greater Masai Mara Ecosystem.

Roads to remission: evolving treatment concepts in type 2 inflammatory diseases.

Unlabelled: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases.

The role of Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in MS and AQP4-NMOSD: Advancing clinical applications.

Fluid biomarkers such as Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light (NfL) play important roles in the diagnosis, monitoring, and evaluation of therapeutic responses in conditions such as Multiple Sclerosis (MS) and Aquaporin-4 Neuromyelitis Optica Spectrum Disorder (AQP4-NMOSD). These biomarkers offer key insights into the underlying pathophysiological mechanisms of these diseases, enabling effective follow-up and personalized treatment approaches, which are essential for improving patient outcomes. Herein, we synthesize the structural attributes, functional roles, and clinical significance of GFAP and NfL in the context of MS and AQP4-NMOSD.

Efficacy, Safety, Pharmacokinetics, and Immunogenicity of ABBV-154 in Adults With Glucocorticoid-Dependent Polymyalgia Rheumatica: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: An unmet need exists for glucocorticoid-sparing treatments for patients with polymyalgia rheumatica (PMR). The antibody-drug conjugate ABBV-154 comprises adalimumab conjugated to a glucocorticoid receptor modulator. We evaluated ABBV-154 versus placebo in patients with glucocorticoid-dependent PMR.

Copy Number Variant Does Not Influence Stroke Severity in 2 C57BL/6J Mouse Models nor in Humans: An Exploratory Study.

Background: Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory.

Myocardial Inflammation in Cardiac Transthyretin Amyloidosis: Prevalence and Potential Prognostic Implications.

Background: Despite previous histopathologic evidence for its presence, the role of myocardial inflammation in the development and progression of cardiac transthyretin amyloidosis (ATTR-CA) remains insufficiently understood. Thus, this study sought to characterize the prevalence and potential prognostic implications of myocardial inflammation in ATTR-CA.

Methods: A retrospective observational study including patients with ATTR-CA diagnosed by endomyocardial biopsy was conducted.

Influence of frailty status on the incidence of intraoperative hypotensive events in elective surgery: Hypo-Frail, a single-centre retrospective cohort study.

Background: Frailty is a predictor of morbidity and mortality in older patients. This study aimed to investigate the influence of frailty status on likelihood, rate, duration, and severity of intraoperative hypotension (IOH), which can lead to severe organ dysfunction.

Methods: Surgical patients (≥70 yr old) with preoperative frailty assessment were analysed retrospectively.

Genetically attenuated parasites show promise as a next-generation malaria vaccine.

Metabolically active, genetically attenuated Plasmodium falciparum parasite lines are promising second-generation malaria vaccine candidates. Lamers et al. and Roozen et al.

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

Hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life.

People with aphasia show stable Cumulative Semantic Interference (CSI) when tested repeatedly in a web-based paradigm: A perspective for longitudinal assessment.

Retrieving words quickly and correctly is an important language competence. Semantic contexts, such as prior naming of categorically related objects, can induce conceptual priming but also lexical-semantic interference, the latter likely due to enhanced competition during lexical selection. In the continuous naming (CN) paradigm, such semantic interference is evident in a linear increase in naming latency with each additional member of a category out of a seemingly random sequence of pictures being named (cumulative semantic interference/CSI effect).

Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites.

Background/objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs of the known anticancer active and antileishmanial 2',4',6'-trimethoxychalcone SU086 were prepared and investigated.

Methods: The chalcones were prepared according to the Claisen-Schmidt condensation protocol and analyzed.

Preventive Effects of Botulinum Neurotoxin Long-Term Therapy: Comparison of the 'Experienced' Benefits and 'Suspected' Worsening Across Disease Entities.

Repetitive intramuscular injections of botulinum neurotoxin (BoNT) have become the treatment of choice for a variety of disease entities. But with the onset of BoNT therapy, the natural course of a disease is obscured. Nevertheless, the present study tries to analyze patients' "suspected" course of disease severity under the assumption that no BoNT therapy had been performed and compares that with the "experienced" improvement during BoNT treatment.

Meeting Cancer Detection Benchmarks in MRI/Ultrasound Fusion Biopsy for Prostate Cancer: Insights from a Retrospective Analysis of Experienced Urologists.

Background: The relationship between case volume and clinical outcomes is well established for most urological procedures but remains underexplored in prostate ultrasound/MRI fusion biopsy (UMFB). UMFB aims to detect clinically significant prostate cancer (csPCa) by adhering to cancer detection benchmarks for PI-RADS lesions identified via multiparametric MRI (mpMRI). These benchmarks, defined by Ahmed et al.

Lidocaine Shows Significant Antimicrobial Effects Against Species: An In-Vitro Study Comparing Different Combinations of Lidocaine and Clinically Used Injectables, like Steroids and Hyaluronan, in the Context of Arthritis Management.

Introduction: Intra-articular injections, commonly used in osteoarthritis treatment, are debated due to their potential link to septic arthritis, though its incidence remains low. Lidocaine, used as a "carrier" for therapeutic substances like hyaluronan or triamcinolone, has pain-relieving and antimicrobial properties. This study investigates the concentration-dependent antimicrobial effects of lidocaine in combination with hyaluronan and triamcinolone in both standard and synovial fluid cultures.