Opportunities and limitations of B cell depletion approaches in SLE.

B cell depletion with rituximab, a chimeric monoclonal antibody that selectively targets B cells by binding CD20, has been used off label in severe and resistant systemic lupus erythematosus (SLE) for over two decades. Several biological mechanisms limit the efficacy of rituximab, including immunological reactions towards the chimeric molecule, increased numbers of residual B cells, including plasmablasts and plasma cells, and a post-treatment surge in B cell-activating factor (BAFF) levels. Consequently, rituximab induces remission in only a proportion of patients, and safety issues limit its use.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert.

Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology.

Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics cancer biology in vivo. This review highlights the critical advancements facilitated by pancreatic organoid models in understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable the proper recapitulation of the cellular architecture and genetic makeup of the original tumors, providing insights into the complex molecular and cellular dynamics at various stages of pancreatic ductal adenocarcinoma (PDAC).

Methane emissions from the Nord Stream subsea pipeline leaks.

The amount of methane released to the atmosphere from the Nord Stream subsea pipeline leaks remains uncertain, as reflected in a wide range of estimates. A lack of information regarding the temporal variation in atmospheric emissions has made it challenging to reconcile pipeline volumetric (bottom-up) estimates with measurement-based (top-down) estimates. Here we simulate pipeline rupture emission rates and integrate these with methane dissolution and sea-surface outgassing estimates to model the evolution of atmospheric emissions from the leaks.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Validation of mixed reality in planning orbital reconstruction with patient-specific implants.

This study aims to evaluate and compare the usability and performance of mixed reality (MR) technology versus conventional methods for preoperative planning of patient-specific reconstruction plates for orbital fractures. A crossover study design was used to compare MR technology with conventional three-dimensional (3D) printing approaches in the planning of maxillofacial traumatology treatments. The primary focus was on user-friendliness and the accuracy of patient-specific reconstruction planning.

Influence of spousal educational disparities on intimate partner violence (IPV) against pregnant women: a study of 30 countries.

Intimate Partner Violence (IPV) during pregnancy poses a serious threat to maternal health, particularly in low- and lower-middle-income countries (LMICs). Despite these known risks, the role of spousal educational differences in IPV during pregnancy remains poorly understood. This study aimed to examine this influence, analyzing data from multiple countries across five continents.

A preliminary evaluation of a fast, low-cost, and high-throughput nucleic acid extraction method for bacterial microbiota profiling in low-microbial biomass samples.

The respiratory tract is colonized with low-density microbial communities, which have been shown to impact human respiratory health through microbiota-host interactions. However, a lack of fast and cost-effective nucleic acid extraction method for low-microbial biomass samples hinders investigation of respiratory microbiota. Here, we performed a pilot study to assess the suitability of the NAxtra nucleic acid extraction protocol for profiling bacterial microbiota in respiratory samples.

The role of fluid friction in streamer formation and biofilm growth.

Biofilms constitute one of the most common forms of living matter, playing an increasingly important role in technology, health, and ecology. While it is well established that biofilm growth and morphology are highly dependent on the external flow environment, the precise role of fluid friction has remained elusive. We grew Bacillus subtilis biofilms on flat surfaces of a channel in a laminar flow at wall shear stresses spanning one order of magnitude (τ = 0.

Airborne observations reveal the fate of the methane from the Nord Stream pipelines.

The Nord Stream pipeline leaks on 26 September 2022 released 465 ± 20 kt of methane into the atmosphere, which is the largest recorded transient anthropogenic methane emission event. While most of the gas escaped directly to the atmosphere, a fraction dissolved in the water. So far, studies on the fate of this dissolved methane rely on pipeline volumetric estimates or spatially sparse concentration measurements and ocean models.

Nord Stream methane leaks spread across 14% of Baltic waters.

A suspected 443-486 kt of methane escaped from the Nord Stream pipelines in September 2022 at four explosion sites across three pipelines. Much of this methane rapidly escaped to the atmosphere, while an unknown amount was dissolved. We use sustained high-resolution observations of methane concentrations from autonomous gliders and an instrumented ship of opportunity to reveal the timing and spread of dissolved methane across different Baltic regions and marine protected areas.

Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use.

As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic.

A Systematic Review of Evaluated Labor Market Initiatives Addressing Precarious Employment: Findings and Public Health Implications.

Precarious employment (PE) is a major determinant of population health and contributor to health and social inequities. The purpose of this article is to synthesize and critically appraise available evidence on labor market initiatives addressing PE identified through a systematic review. Of the 21 initiatives reviewed, grouped into four categories-labor market policies, legislation, and reforms; union strategies; apprenticeships and other youth programs; social protection programs-10 showed consistently positive outcomes and 11 a combination of negative, mixed, or inconclusive outcomes.

Explainable deep neural networks for predicting sample phenotypes from single-cell transcriptomics.

Recent advances in single-cell RNA-Sequencing (scRNA-Seq) technologies have revolutionized our ability to gather molecular insights into different phenotypes at the level of individual cells. The analysis of the resulting data poses significant challenges, and proper statistical methods are required to analyze and extract information from scRNA-Seq datasets. Sample classification based on gene expression data has proven effective and valuable for precision medicine applications.

Migraine and its major subtypes - with and without aura are associated with polygenic scores for autism.

Background: Individuals with autism spectrum disorder (ASD) experience a wide array of neurological, psychiatric and medical comorbidities, yet little attention has been given to the potential link between ASD and migraine, one of the most prevalent neurological disorders worldwide. This study aimed to investigate whether a genetic predisposition for ASD is linked to migraine and its major subtypes, with and without aura. Additionally, potential moderator and mediators of the association between ASD and migraine were explored.

Therapist-Guided Internet-Delivered Acceptance-Enhanced Behavior Therapy for Skin-Picking Disorder: A Randomized Controlled Trial.

Despite its high prevalence, individuals suffering from skin-picking disorder (SPD) face limited access to treatment due to several factors, including geographical and economic barriers, as well as a shortage of properly trained therapists. Offering Internet-delivered therapy could be a solution to these barriers. This study aimed to evaluate the efficacy of therapist-guided Internet-delivered acceptance-enhanced behavior therapy (iBT) for SPD compared to a wait-list control condition.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Adverse Outcomes After Cemented and Cementless Primary Elective Total Hip Arthroplasty in 60,064 Matched Patients: A Study of Data From the Swedish Arthroplasty Register.

Introduction: The choice between cemented and cementless fixation in primary elective total hip arthroplasty (THA) remains a subject of ongoing debate. However, comparisons between the two are subject to limited adjustments for patient characteristics, diagnoses, and surgical factors, as well as by limited outcome time endpoints. Our study aimed to compare the effect of femoral fixation on safety and implant survival outcomes in matched patients.

Heterogeneous entity representation for medicinal synergy prediction.

Motivation: Forecasting the synergistic effects of drug combinations facilitates drug discovery and development, especially regarding cancer therapeutics. While numerous computational methods have emerged, most of them fall short in fully modeling the relationships among clinical entities including drugs, cell lines, and diseases, which hampers their ability to generalize to drug combinations involving unseen drugs. These relationships are complex and multidimensional, requiring sophisticated modeling to capture nuanced interplay that can significantly influence therapeutic efficacy.

Association between dairy products intake and frailty transitions in older adults: The InCHIANTI cohort study.

Objective: To evaluate the association between dairy products consumption and the probability of frailty transitions in community-dwelling older adults.

Design: Longitudinal study.

Setting And Participants: We included 863 community-dwelling participants ≥65 years from the Chianti region in Italy.

Interventions to Maintain HIV/AIDS, Tuberculosis, and Malaria Service Delivery During Public Health Emergencies in Low- and Middle-Income Countries: Protocol for a Systematic Review.

Background: Although existing disease preparedness and response frameworks provide guidance about strengthening emergency response capacity, little attention is paid to health service continuity during emergency responses. During the 2014 Ebola outbreak, there were 11,325 reported deaths due to the Ebola virus and yet disruption in access to care caused more than 10,000 additional deaths due to measles, HIV/AIDS, tuberculosis, and malaria. Low- and middle-income countries account for the largest disease burden due to HIV, tuberculosis, and malaria and yet previous responses to health emergencies showed that HIV, tuberculosis, and malaria service delivery can be significantly disrupted.