Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.

Nanoscale Viscometry Reveals an Inherent Mucus Defect in Cystic Fibrosis.

The abnormally viscous and thick mucus is a hallmark of cystic fibrosis (CF). How the mutated CF gene causes abnormal mucus remains an unanswered question of paramount interest. Mucus is produced by the hydration of gel-forming mucin macromolecules that are stored in intracellular granules prior to release.

Generating allogeneic CAR-NKT cells for off-the-shelf cancer immunotherapy with genetically engineered HSP cells and feeder-free differentiation culture.

The clinical potential of current chimeric antigen receptor-engineered T (CAR-T) cell therapy is hampered by its autologous nature that poses considerable challenges in manufacturing, costs and patient selection. This spurs demand for off-the-shelf therapies. Here we introduce an ex vivo feeder-free culture method to differentiate gene-engineered hematopoietic stem and progenitor (HSP) cells into allogeneic invariant natural killer T (NKT) cells and their CAR-armed derivatives (CAR-NKT cells).

T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice.

Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance.

Single Na- and K-Ion-Conducting Sulfonated -NH-Linked Covalent Organic Frameworks.

Highly ion-conductive solid electrolytes of nonlithium ions (sodium or potassium ions) are necessary for pursuing a more cost-effective and sustainable energy storage. Here, two classes of sulfonated -NH-linked covalent organic frameworks (COFs), specifically designed for sodium or potassium ion conduction (named i-COF-2 (Na or K) and i-COF-3 (Na or K)), were synthesized through a straightforward, one-step process using affordable starting materials. Remarkably, these COFs demonstrate high ionic conductivity at room temperature─3.

Implications of scale up flexible plastic packaging recycling in the United States.

Flexible plastic packaging (FPP) is a growing waste source in the United States. Currently, FPP has a recycling rate of only 2% in the U.S.

The presence of clonal isotype switch after autologous stem cell transplantation as a prognostic biomarker for long-term survival in patients with multiple myeloma.

Clonal isotype switch (CIS) in multiple myeloma (MM) refers to the emergence of new immunoglobulin bands distinct from those present at diagnosis. CIS often appears after high-dose chemotherapy and autologous stem cell transplantation (ASCT), reflecting post-transplant immune recovery. However, its prognostic significance remains unclear.

An evolutionarily conserved cation channel tunes the sensitivity of gustatory neurons to ephaptic inhibition in .

In ephaptic coupling, physically adjacent neurons influence one another's activity via the electric fields they generate. To date, the molecular mechanisms that mediate and modulate ephaptic coupling's effects remain poorly understood. Here, we show that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel lateralizes the potentially mutual ephaptic inhibition between gustatory receptor neurons (GRNs).

Chronic Kidney Disease-Associated Pruritus Burden: A Patient Survey Study.

Rationale & Objective: Chronic kidney disease-associated pruritus (CKD-aP) is a common, underrecognized condition in patients with chronic kidney disease (CKD), especially those receiving hemodialysis (HD). The present study analyzed the clinical treatment journey and overall burden of pruritus among patients with CKD-aP.

Study Design: Cross-sectional, patient-reported online survey.

Impact of Halide (Cl vs I) Identity on the Preferred Positioning of Substituents between Al and M (M = Co, Rh, Ir) in PAlP Pincer Complexes.

Protolysis of AlMe or AlEt with 2-diisopropylphosphinopyrrole () resulted in alane/bis(phosphine) pincer ligands containing two flanking phosphines and a central Al-Me (), Al-Et () unit. Reactions of with [(COD)MI] (COD = 1,5-cyclooctadiene; M = Rh or Ir) in the presence of pyridine produced pincer complexes ( and ) with M supported by the PAlP tridentate ligand, and pyridine, methyl, and iodide as monodentate ligands for Al or M. The analogous reaction of with [(COD)MI] and pyridine resulted in the formation of the analogous compounds and with hydride in place of methyl.

Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

Background: The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine.

Methods: The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6 months to 16 years with estimated glomerular filtration rate (eGFR) 30-89 ml/min/1.

Phase I study of adavosertib with radiation therapy and temozolomide in newly diagnosed glioblastoma and intratumoral drug levels in recurrent glioblastoma.

Purpose: Adavosertib is an oral small molecular inhibitor of Wee1. The Adult Brain Tumor Consortium performed a phase I study of adavosertib, radiation (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) as well as a surgical window of opportunity study in recurrent GBM.

Patients And Methods: The maximum tolerated dose (MTD) of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in 2 separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ.

Developing an alternative medium for in-space biomanufacturing.

In-space biomanufacturing provides a sustainable solution to facilitate long-term, self-sufficient human habitation in extraterrestrial environments. However, its dependence on Earth-supplied feedstocks renders in-space biomanufacturing economically nonviable. Here, we develop a process termed alternative feedstock-driven in-situ biomanufacturing (AF-ISM) to alleviate dependence on Earth-based resupply of feedstocks.

Identification of Key Amino Acids in the A Domains of Polymyxin Synthetase Responsible for 2,4-Diaminobutyric Acid Adenylation in NBRC3020 Strain.

Developing novel nonribosomal peptides (NRPs) requires a comprehensive understanding of the enzymes involved in their biosynthesis, particularly the substrate amino acid recognition mechanisms in the adenylation (A) domain. This study focused on the A domain responsible for adenylating l-2,4-diaminobutyric acid (l-Dab) within the synthetase of polymyxin, an NRP produced by NBRC3020. To date, investigations into recombinant proteins that selectively adenylate l-Dab─exploring substrate specificity and enzymatic activity parameters─have been limited to reports on A domains found in enzymes synthesizing l-Dab homopolymers (pldA from USE31 and pddA from NBRC15115), which remain exceedingly rare.

Multidimensional sleep health and cognitive function across adulthood.

Study Objectives: Sleep is essential for proper function of the mind and body. Studies report the effect of sleep problems on cognition but focus on only a single or limited number of sleep indicators or on clinical populations (e.g.

Predictors of mortality among sepsis patients transferred from a rural, low-volume ED to an urban, high-volume hospital.

Introduction: We investigated the extent to which demographic characteristics, clinical care aspects, and relevant biomarkers predicted sepsis-related mortality among patients transferred from a rural, low-volume emergency department (ED) to an urban, high-volume, level-2 trauma center.

Methods: We conducted an observational study among adult severe sepsis patients (N = 242) who, within a community-based regional healthcare system, presented to one of the four rural, low-volume EDs and were subsequently transferred to the urban, high-volume, level-2 trauma center, and were identified as septic at either location. We evaluated in-hospital and 30 days after discharge mortality.

T-Shaped Wedge Resection of the Upper Eyelid: An Alternative to the Pentagonal Wedge.

Purpose: To report the experience with an alternative to the upper eyelid pentagonal wedge resection technique which results in improved cosmesis due to a greater alignment of incisions with relaxed skin tension lines.

Methods: A retrospective review of all patients who underwent the T-shaped wedge resection by the authors from 2009 to 2017. A horizontal eyelid crease incision is made across the upper eyelid skin.

The Impact of Storage Conditions on Stool Smellprints as Assessed by an Electronic Nose.

Necrotizing enterocolitis (NEC) is a devastating disease of the neonatal gastrointestinal tract. Volatile organic compounds (VOCs), odoriferous compounds released as a byproduct of bacterial metabolism, can be used as a proxy for gut health. We hypothesized that patients with NEC would have different microbial profiles and elicit different VOC signatures as assessed by gas chromatography/mass spectrometry (GC/MS) or an electronic nose compared to controls.

Outer hair cells stir cochlear fluids.

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery.

Atmospheric Deposition of Microplastics in South Central Appalachia in the United States.

Due to the increased prevalence of plastic pollution globally, atmospheric deposition of microplastics (MPs) is a significant issue that needs to be better understood to identify potential consequences for human health. This study is the first to quantify and characterize atmospheric MP deposition in the Eastern United States. Passive sampling was conducted at two locations within the Eastern United States, specifically in remote South Central Appalachia, from March to September 2023.

Gastrointestinal bleed mortality disparities in patients with atrial fibrillation: A cross-sectional analysis 1999-2020.

Introduction: Gastrointestinal bleeding (GIB) is often encountered among patients with atrial fibrillation (AF) due to the use of anticoagulation. This study assesses disparities in GIB-related mortality among decedents with AF in the United States.

Methods: GIB mortality data in patients with AF from 1999 to 2020 was queried from the CDC database.

Lead Adsorption and Desorption at the Barite (001) Surface in the Presence of EDTA.

Scaling minerals, such as barite, can cause detrimental consequences for oil/gas pipelines and water systems, but their formation can be inhibited by organic chelators such as ethylenediaminetetraacetic acid (EDTA). Here, we resolve how EDTA affects sorption and desorption of Pb at the barite (001) surface using a combination of X-ray scattering and microscopy measurements. In the presence of EDTA, Pb incorporated in the topmost part of the barite surface and adsorbed as inner-sphere complexes on the surface.

The percentage of sacroiliac fusions done in the U.S. by non-surgical specialties has increased.

Background: Surgical fusion of the sacroiliac (SI) joint is often performed to manage chronic lower back or buttock pain. When Current Procedural Terminology (CPT) codes were introduced, SI joint fusion procedures were done primarily by orthopaedic surgeons and neurosurgeons. The purpose of this study was to examine the utilization of SI joint fusion CPT codes by physician specialty over time.

An implantable system for opioid safety.

Naloxone can effectively rescue victims from opioid overdose, but less than 5% survive due to delayed or absent first responder intervention. Current overdose reversal systems face key limitations, including low user adherence, false positive detection, and slow antidote delivery. Here, we describe a subcutaneously implanted robotic first responder to overcome these challenges.