Low-dose intranasal deferoxamine modulates memory, neuroinflammation, and the neuronal transcriptome in the streptozotocin rodent model of Alzheimer's disease.

Introduction: Intranasal (IN) deferoxamine (DFO) has emerged over the past decade as a promising therapeutic in preclinical experiments across neurodegenerative and neurovascular diseases. As an antioxidant iron chelator, its mechanisms are multimodal, involving the binding of brain iron and the consequent engagement of several pathways to counter pathogenesis across multiple diseases. We and other research groups have shown that IN DFO rescues cognitive impairment in several rodent models of Alzheimer Disease (AD).

Revolutionising oral organoids with artificial intelligence.

The convergence of organoid technology and artificial intelligence (AI) is poised to revolutionise oral healthcare. Organoids - three-dimensional structures derived from human tissues - offer invaluable insights into the complex biology of diseases, allowing researchers to effectively study disease mechanisms and test therapeutic interventions in environments that closely mimic in vivo conditions. In this review, we first present the historical development of organoids and delve into the current types of oral organoids, focusing on their use in disease models, regeneration and microbiome intervention.

Comparative dissection of transcriptional landscapes of human iPSC-NK differentiation and NK cell development.

Clinical and preclinical research has demonstrated that iPSC-derived NK (iNK) cells have a high therapeutic potential, yet poor understanding of the detailed process of their differentiation and their counterpart cell development has hindered therapeutic iNK cell production and engineering. Here we dissect the crucial differentiation of both fetal liver NK cells and iNK cells to enable the rational design of advanced iNK production protocols. We use a comparative analysis of single-cell RNA-seq (scRNA-seq) to pinpoint key factors lacking in the induced setting which we hypothesized would hinder iNK differentiation and/ or functionality.

Seminoma Diagnosed by Multicancer Detection Testing: A Case Report.

A 67-year-old male with positive signals for neuroendocrine and head/neck cancer on a commercially available multicancer detection test underwent an extensive negative diagnostic workup at a local hospital. Referred to our medical center for advanced imaging and endoscopic procedures ultimately led to the diagnosis of an early-stage seminoma with eventual orchiectomy. This case highlights challenges in evaluating positive multicancer detection results, emphasizing the need for a broader understanding of how to interpret these testing results to fully evaluate complex cases, as well as the need for protocolized follow-up approaches to a positive multicancer detection test.

Cement-within-cement technique in revision reverse total shoulder arthroplasty: complications, reoperations, and revision rates at 5-year mean follow-up.

Background: Revision reverse total shoulder arthroplasty (rTSA) of a previously cemented humeral component is challenging. In hip arthroplasty, the cement-within-cement (CwC) technique has been well described as an effective option. However, for shoulder arthroplasty there remains a paucity of data investigating this technique.

Obinutuzumab in Difficult to Treat Phospholipase A2 Receptor Positive Membranous Nephropathy: Our Experience at a Tertiary Care Center in North India.

Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody with superior B cell cytotoxicity compared to rituximab. Various case reports suggest that in refractory phospholipase A2 receptor (PLA2R) positive membranous nephropathy (MN) patients, Obinutuzumab led to immunologic remission and improvement in proteinuria. In the present case series, we present six cases of difficult-to-treat PLA2R-associated MN refractory to prednisolone, calcineurin inhibitor (CNI), cyclophosphamide, and rituximab but subsequently responded to Obinutuzumab.

Insights into Therapeutic Strategies and Longitudinal Outcomes: A Retrospective Analysis of NELL1 Positive Membranous Nephropathy Cohort.

Membranous nephropathy (MN) is a rare autoimmune disease, in which the circulating autoantibodies against antigens attack podocytes. Neural Epidermal Growth Factor like 1 (NELL1) 1-associated MN is the second most common antigen, following phospholipase A2 receptor. Complementary and alternative medicine and malignancies play a pivotal role in the development of NELL1-MN.

Viral Infection Associated Membranous Nephropathy: Clinical Presentation and Outcomes.

Background: Viral infections can increase the likelihood of an individual developing membranous nephropathy (MN). Limited information is available regarding the treatment approaches for such cases. We conducted a review focusing on hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV)-associated MN.

Environment scan of generative AI infrastructure for clinical and translational science.

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers.

Geochemical signatures and nanomechanical properties of echinoid tests from nearshore habitats of Florida: environmental and physiological controls on echinoid biomineralization.

The mechanisms that regulate minor and trace element biomineralization in the echinoid skeleton can be primarily controlled biologically (, by the organism and its vital effects) or by extrinsic environmental factors. Assessing the relative role of those controls is essential for understanding echinoid biomineralization, taphonomy, diagenesis, and their potential as geochemical archives. In this study, we (1) contrast geochemical signatures of specimens collected across multiple taxa and environmental settings to assess the effects of environmental and physiological factors on skeletal biomineralogy; and (2) analyze the nanomechanical properties of the echinoid skeleton to assess potential linkages between magnesium/calcium (Mg/Ca) ratios and skeletal nanohardness.

Impact of liver cirrhosis on morbidity and mortality of patients admitted to the hospital with necrotizing fasciitis.

Background: Necrotizing fasciitis (NF) is a potentially fatal bacterial infection of the soft tissues. Liver cirrhosis appears to be a contributing factor to higher morbidity and mortality in patients with NF. This research article explores the relationship between these two conditions.

Elucidating Thermal Decomposition Kinetic Mechanism of Charged Layered Oxide Cathode for Sodium-Ion Batteries.

The safety of the P2-type layered transition metal oxides (P2-NaTMO), a promising cathode material for sodium-ion batteries (SIBs), is a prerequisite for grid-scale energy storage systems. However, previous thermal runaway studies mainly focused on morphological changes resulting from gas production detection and thermogravimetric analysis, while the structural transition and chemical reactions underlying these processes are still unclear. Herein, a comprehensive methodology to unveil an interplay mechanism among phase structures, interfacial microcrack, and thermal stability of the charged P2-NaNiMnO (NNMO) and the P2-NaNiLiMnO (NNMO-Li) at elevated temperatures is established.

Self-assembled Gap-Rich PdMn Nanofibers with High Mass/Electron Transport Highways for Electrocatalytic Reforming of Waste Plastics.

Innovating nanocatalysts with both high intrinsic catalytic activity and high selectivity is crucial for multi-electron reactions, however, their low mass/electron transport at industrial-level currents is often overlooked, which usually leads to low comprehensive performance at the device level. Herein, a Cl/O etching-assisted self-assembly strategy is reported for synthesizing a self-assembled gap-rich PdMn nanofibers with high mass/electron transport highway for greatly enhancing the electrocatalytic reforming of waste plastics at industrial-level currents. The self-assembled PdMn nanofiber shows excellent catalytic activity in upcycling waste plastics into glycolic acid, with a high current density of 223 mA cm@0.

Activating Reversible V/V Redox Couple in NASICON-Type Phosphate Cathodes by High Entropy Substitution for Sodium-Ion Batteries.

Vanadium-based Na superionic conductor (NASICON) type materials (NaVM(PO), M = transition metals) have attracted extensive attention when used as sodium-ion batteries (SIBs) cathodes due to their stable structures and large Na diffusion channels. However, the materials have poor electrical conductivity and mediocre energy density, which hinder their practical applications. Activating the V/V redox couple (V/V≈4.

Divergent Synthesis of Polysubstituted 1,2-Dihydropyridines and Pyridines through Manganese-Mediated Radical Cascade Cyclization of Tertiary Enamides.

A Mn(III)-mediated radical cascade cyclization of -propargyl enamides with sodium sulfinates was developed. Mechanistic studies indicated that this cascade process is mainly composed of the chemoselective addition of sulfonyl radical to C≡C bond and the regioselective intramolecular 6--trig cyclization. This protocol provided a powerful method for the divergent synthesis of diverse polysubstituted -sulfonylpyridines or 1,2-dihydropyridines just by varying solvent and temperature featuring good functional group compatibility and simple operation.

Continuous risk monitoring and management of heart failure: Rationale and design of the ALLEVIATE-HF trial.

Aims: Early identification and management of worsening heart failure (HF) is necessary to prevent disease progression and hospitalizations. The ALLEVIATE-HF (Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure) trial is a prospective, randomized, controlled, double-blind, multicentre trial that aims to assess the safety and efficacy of using the Reveal LINQ™ insertable cardiac monitor (ICM) in patients with HF to continuously monitor and evaluate HF risk status and guide timely interventions.

Methods: The ICM algorithm uses parameters derived from electrocardiogram (atrial fibrillation [AF], ventricular rate during AF, heart rate variability, and night heart rate), three-axis accelerometer (patient activity duration), and subcutaneous bioimpedance (fluid volume, respiration rate).

Enhanced Sodium Storage and Thermal Safety of NaNiFeMnO Cathode via Incorporation of TiN and WO.

This study proposes an efficient, cost-effective, and industrially scalable electrode modulation strategy, which involves directly adding a small amount of high thermal and high conductance TiN and well interface compatible WO to NaNiFeMnO (NaNFMO-TW) cathode slurry, to effectively reduce electrode polarization and interface side reactions, reduce the Ohmic heat and polarization heat of the battery, and ultimately to significantly improve the sodium-ion storage and thermal safety performance of the battery. At room temperature (RT) and 1C rate, the modified NaNFMO-TW electrode exhibits a reversible capacity of ∼95 mAh g after 300 cycles, with a capacity retention rate of 82.6%, being higher than the 50.

Study on the Preparation and Electrochemical Properties of LiFeMnPO Coated with Bamboo Shaving-Based Carbon.

LiFeMnPO (0 < < 1) has a high operating voltage range and theoretical energy density, but its actual capacity decreased due to its low electronic conductivity. To overcome this problem, we successfully prepared LiFeMnPO/C (LFMP/C) with a uniform carbon coating by a one-step solvothermal method using bamboo shavings as the carbon source. The results showed that heating at a reaction temperature of 180 °C for 18 h was the optimal synthesis condition to obtain LFMP/C.

Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.

Alzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to the involvement of lipid dysregulation in the development of AD. Nevertheless, the precise lipidomic landscape and the mechanistic roles of lipids in disease pathology remain poorly understood.

Effectiveness of room-of-error interventions for healthcare providers: a systematic review.

Background: Patient safety incidents are recognized as significant contributors to patient mortality, thus demanding immediate attention and strategic interventions in healthcare systems. The room-of-error education program serves as a solution, as it provides a case-based learning platform allowing nursing students to identify and resolve medical errors within a controlled environment systematically. This study aimed to identify the context, mechanisms, and outcomes of room-of-error training programs.

Scalable information extraction from free text electronic health records using large language models.

Background: A vast amount of potentially useful information such as description of patient symptoms, family, and social history is recorded as free-text notes in electronic health records (EHRs) but is difficult to reliably extract at scale, limiting their utility in research. This study aims to assess whether an "out of the box" implementation of open-source large language models (LLMs) without any fine-tuning can accurately extract social determinants of health (SDoH) data from free-text clinical notes.

Methods: We conducted a cross-sectional study using EHR data from the Mass General Brigham (MGB) system, analyzing free-text notes for SDoH information.

Glucocorticoid therapy in classic congenital adrenal hyperplasia: traditional and new treatment paradigms.

Introduction: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition characterized by cortisol deficiency and excess adrenal androgens. CAH treatment is a lifelong balancing act between the need to reduce excess androgens, typically with supraphysiologic glucocorticoid (GC) doses, and concerns about potentially serious GC-related adverse events. Tradeoffs between the consequences of excess androgens versus GCs must be constantly reassessed throughout each patient's lifetime, based on current clinical needs and treatment goals.