Efficacy and safety of guselkumab in patients with active lupus nephritis: results from a Phase 2, randomized, placebo-controlled study.

Objective: Evaluate the efficacy and safety of guselkumab, an interleukin (IL)-23 inhibitor, in a Phase 2, multicentre, randomized, double-blind, placebo-controlled study of patients with active lupus nephritis (LN).

Methods: Adults (18-75 years) with active LN (Class III-IV proliferative nephritis [kidney biopsy] and urine protein-to-creatinine ratio [UPCR)] of ≥ 1 mg/mg despite standard-of-care therapy) were randomized (1:1; planned sample = 60) to receive intravenous infusions of guselkumab 400 mg or placebo at Weeks 0, 4, and 8, then subcutaneous injections (guselkumab 200 mg or placebo) at Week12 and every 4 weeks through Week48 in addition to their background therapy. The primary end point was achievement of ≥ 50% decrease in proteinuria from baseline at Week24.

Oral health care pathways for patients with epidermolysis bullosa: A position statement from the European reference network for rare skin diseases.

Background: Inherited epidermolysis bullosa (EB) comprises a group of genetic disorders characterized by skin fragility and unique oral features. It requires interdisciplinary care from several health professionals, including oral health teams. Modern dentistry encompasses a wide range of therapeutic options performed by specialists from different fields.

Prospective clinical study of enamel wear caused by monolithic zirconia resin-bonded inlay-retained and wing-retained fixed partial dentures over 5 years.

Objectives: To prospectively evaluate the wear of posterior zirconia resin-bonded fixed partial dentures (RBFPDs) with polished occlusal surfaces and their natural enamel antagonists compared to contralateral controls in an enamel-enamel contact over 5 years.

Materials And Methods: In six patients with either an inlay- or wing-retained RBFPD made of monolithic 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP), wear was evaluated indirectly using baseline and annual polyvinyl siloxane impressions. Resulting gypsum models were digitized and aligned by unchanged surface areas.

-related disorder in 87 adults: Natural history and self-sustainability.

Purpose: is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with -related disorder have been described, which limits our understanding of the disease's natural history and our ability to counsel patients and their families.

Methods: Data on patients aged 18+ years with -related disorder were collected through an online questionnaire completed by clinicians and parents.

Diving into RNAi Therapy: An Inhalable Formulation Based on Lipid-Polymer Hybrid Systems for Pulmonary Delivery of siRNA.

Here, a pulmonary formulation based on lipid-polymer hybrid nanoparticles carrying small interfering RNA (siRNA) was developed to realize a RNA interference-based therapy to treat respiratory diseases. Toward this aim, a new copolymer was synthesized, by functionalization of the α,β-poly(-2-hydroxyethyl)-d,l-aspartamide with 35 mol % of 1,2-bis(3-aminopropylamino)ethane, 0.4 mol % of fluorescent dye, and 4.

The oldest monofenestratan pterosaur from the Queso Rallado locality (Cañadón Asfalto Formation, Toarcian) of Chubut Province, Patagonia, Argentina.

As the first group of tetrapods to achieve powered flight, pterosaurs first appeared in the Late Triassic. They proliferated globally, and by the Late Jurassic through the Cretaceous, the majority of these taxa belonged to the clade Monofenestrata (which includes the well-known Pterodactyloidea as its major subclade), typified by their single undivided fenestra anterior to the orbit. Here, a new taxon gen.

Enduring effects of psychotherapy, antidepressants and their combination for depression: a systematic review and meta-analysis.

Introduction: Although depressive disorders are frequently associated with relapses, the sustained efficacy of therapies after their termination has been insufficiently investigated.

Objective: The aim of this study was to evaluate the current evidence of enduring effects of psychotherapy, antidepressants and their combination after the end of treatment.

Methods: PubMed and PsychINFO were systematically screened according to PRISMA guidelines (except for preregistration).

DNA methylation-based analysis reveals accelerated epigenetic aging in giant cell-enriched adult-type glioblastoma.

Background: Giant cell (gc)-enriched glioblastoma (gcGB) represents a distinct histological variant of isocitrate dehydrogenase wild-type adult-type glioblastoma with notable enlarged mono- or multinuclear tumor cells. While some studies suggest a survival advantage for gcGB patients, the underlying causes remain elusive. GcGBs are associated with TP53 mutations, and gcs were shown to accumulate DNA double-strand breaks and show deficient mitosis, potentially triggering cellular senescence programs.

Psychological interventions for improvement of symptoms of post-stroke depression - study protocol of the depression-intervention study for optimization of reconvalesence after stroke (DISCOVER).

Introduction: Besides functional outcomes, mental health and health-related quality of life (HRQoL) are significant measures in chronic diseases, such as stroke. Post-stroke depression (PSD) is an important complication affecting up to one in three stroke survivors. So far, specific programs to screen, detect and treat these patients are lacking but might be a crucial component in stroke aftercare.

Tertiary lymphoid structures in pancreatic cancer are structurally homologous, share gene expression patterns and B-cell clones with secondary lymphoid organs but show increased T-cell activation.

Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Impact of fixation duration on messenger RNA detectability in human formalin-fixed paraffin-embedded brain tissue.

Technologies to study mRNA in post-mortem human brain samples have greatly advanced our understanding of brain pathologies. With ongoing improvements, particularly in formalin-fixed paraffin-embedded tissue, these technologies will continue to enhance our knowledge in the future. Despite various considerations for tissue and mRNA quality, such as pre-mortem health status and RNA integrity, the impact of the tissue fixation time has not been addressed in a systemic fashion yet.

Focus on patient perspectives in climate action policies for healthcare. A German survey analysis on what patients are willing to do.

Background: The healthcare sector, while dedicated to improving health, paradoxically contributes significantly to global carbon emissions, accounting for approximately 4.9% of global emissions. Despite growing public concern about climate change, few studies have explored patients' awareness and attitudes toward the environmental impact of healthcare.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

Clinical results of autologous fat transfer for basal thumb arthritis with a minimum of three years' follow-up.

Aims: In the treatment of basal thumb osteoarthritis (OA), intra-articular autologous fat transplantation has become of great interest within recent years as a minimally invasive and effective alternative to surgical intervention with regard to pain reduction. This study aims to assess its long-term effectiveness.

Methods: Patients diagnosed with stage one to three OA received a single intra-articular autologous fat transplantation.

EPA guidance on lifestyle interventions for adults with severe mental illness: A meta-review of the evidence.

There is growing interest in lifestyle interventions as stand-alone and add-on therapies in mental health care due to their potential benefits for both physical and mental health outcomes. We evaluated lifestyle interventions focusing on physical activity, diet, and sleep in adults with severe mental illness (SMI) and the evidence for their effectiveness. To this end, we conducted a meta-review and searched major electronic databases for articles published prior to 09/2022 and updated our search in 03/2024.

Differential energetic profile of signal processing in central vestibular neurons.

Background: Energetic aspects of neuronal activity have become a major focus of interest given the fact that the brain among all organs dominates the oxygen consumption. At variance with the importance of neuroenergetics, the knowledge about how electrical activity and metabolism is correlated in defined neuronal populations is still rather scarce.

Results: We have estimated the ATP consumption in the two physiologically well characterized populations of frog central vestibular neurons, with tonic and phasic firing patterns, respectively.

Time as a significant factor in the release of potassium from lithium heparin plasma and serum.

Objectives: In most countries the majority of patients are in outpatient care. In difference to hospitalized patients, their blood samples often take hours after collection to centrifugation. The study investigates the release of potassium and the development of pseudohyperkalemia in lithium heparin (Li-Hep) and serum blood collection tubes over time.

Heterogeneity and Penumbra of White Matter Hyperintensities in Small Vessel Diseases Determined by Quantitative MRI.

Background: White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.

Correlation of Anti-Müllerian hormone serum concentration measured in proestrus and estrus with the litter size as a fertility marker in bitches.

The use of the anti-Müllerian hormone (AMH) serum concentration as a fertility marker has been shown in cows, sheep and mares and has been indicated in one study in female dogs. The aim of this study was to investigate the connection between the AMH serum concentration, taken at two defined time points during the bitch`s heat, and the litter size to investigate whether AMH can be used as a practical measurement for the individual breeding bitch to predict litter size. The study was carried out on 27 healthy female dogs presented for pre-breeding examination, considering all previously known influencing factors on AMH in the bitch such as age, body weight and estrous cycle phase at the time the sample was taken.

Modified CD15/CD16-CLL1 inhibitory CAR-T cells for mitigating granulocytopenia toxicities in the treatment of acute myeloid leukemia.

CLL1 Chimeric antigen receptor T-cell (CAR-T) therapy, as a promising immunotherapeutic approach, has demonstrated its potential to enhance the prognosis of patients diagnosed with acute myeloid leukemia (AML). However, due to the overexpression of CLL1 on neutrophils, CAR-T cells not only eliminated tumor cells but also eradicated neutrophils simultaneously, resulting in severe granulocytopenia and subsequent infections. Considering the distinct expression levels of CD15/CD16 on neutrophils and AML blasts, we have devised novel modified CD15 /CD16-CLL1 iCAR structures incorporating diverse inhibitory elements.