Exploring Immune-Mediated Brain Function Abnormalities in Systemic Lupus Erythematosus: Neuroimaging Evidence of the Impact of Anti-Ribosomal P Protein Antibodies.

Rationale And Objectives: Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most severe complications of systemic lupus erythematosus (SLE), and its early biomarkers and immune mechanisms remain unclear. This study utilizes Resting-State functional magnetic resonance imaging (rs-fMRI) to explore early neuroimaging biomarkers and potential immune mechanisms of brain injury in SLE, with a particular focus on anti-ribosomal P protein antibody (ARPA).

Materials And Methods: A total of 47 SLE patients and 33 healthy controls (HCs) underwent rs-fMRI.

Using magnetic resonance relaxometry to evaluate the safety and quality of induced pluripotent stem cell-derived spinal cord progenitor cells.

Background: The emergence of induced pluripotent stem cells (iPSCs) offers a promising approach for replacing damaged neurons and glial cells, particularly in spinal cord injuries (SCI). Despite its merits, iPSC differentiation into spinal cord progenitor cells (SCPCs) is variable, necessitating reliable assessment of differentiation and validation of cell quality and safety. Phenotyping is often performed via label-based methods including immunofluorescent staining or flow cytometry analysis.

Extensive Biotransformation Profiling of AZD8205, an Anti-B7-H4 Antibody-Drug Conjugate, Elucidates Pathways Underlying Its Stability .

What happens to macromolecules ? What drives the structure-activity relationship and stability for antibody-drug conjugates (ADCs)? These interrelated questions are increasingly relevant due to the re-emerging importance of ADCs as an impactful therapeutic modality and the gaps that exist in our understanding of ADC structural determinants that underlie ADC stability. Complex macromolecules, such as ADCs, may undergo changes due to their intricate structure as biotransformations may occur on the linker, the payload, and/or at the modified conjugation site. Furthermore, the dissection of ADC metabolism presents a substantial analytical challenge due to the difficulty in the identification or quantification of minor changes on a large macromolecule.

Association between protein intake, diet quality, and obesity in Australian adults: a comparison of measurement units.

Previous investigations on protein associations with diet quality and obesity still have inconclusive findings, possibly due to how protein intake was expressed. This study aimed to compare how different ways of expressing total protein intake may influence its relationships with diet quality and obesity. Usual protein intake was estimated from the 2011-12 Australian National Nutrition and Physical Activity Survey ( = 7637 adults, ≥19 years), expressed in grams (g/d), percent energy (%EI), and grams per actual kilogram body weight (g/kgBW/d).

Therapeutic application of extracellular vesicular EGFR isoform D as a co-drug to target squamous cell cancers with tyrosine kinase inhibitors.

Targeting wild-type epidermal growth factor receptor (EGFR) using tyrosine kinase inhibitors (TKIs) never achieved its purported success in cancers such as head and neck squamous cell carcinoma, which are largely EGFR-dependent. We had previously shown that exceptional responders to TKIs have a genetic aberration that results in overexpression of an EGFR splice variant, isoform D (IsoD). IsoD lacks an integral transmembrane and kinase domain and is secreted in extracellular vesicles (EVs) in TKI-sensitive patient-derived cultures.

Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

Background: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone.

Efficacy of Traditional Acupuncture Compared to Biofeedback Therapy in Fecal Incontinence: A Randomized Controlled Trial.

Background: Fecal incontinence has a devastating impact on quality of life and imposes a substantial socioeconomic burden. Best medical therapy, including biofeedback therapy, improves mild symptoms with minimal impact on moderate to severe symptoms. Surgical management for incontinence carries a degree of morbidity, resulting in low uptake and acceptability.

Optimization of Graft Position at the Tibia Footprint in Anterior Cruciate Ligament Revision-Lasso Technique.

In anterior cruciate ligament (ACL) revision cases, the resultant bigger aperture at the tibia footprint can cause graft instability. The increased movement hinders bone-graft integration and leads to graft abrasion. This article describes a technique to optimize graft stability when using a soft tissue graft for ACL revision.

In situ anchored ternary hierarchical hybrid nickel@cobaltous sulfide on poly(3,4-ethylenedioxythiophene)-reduced graphene oxide for highly efficient non-enzymatic glucose sensing.

A ternary hierarchical hybrid Ni@CoS/poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@CoS/PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@CoS/PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@CoS/PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

Background: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

Objective: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting.

Study Design: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated.

Hydrogel dressings with intrinsic antibiofilm and antioxidative dual functionalities accelerate infected diabetic wound healing.

Chronic wounds are often infected with biofilm bacteria and characterized by high oxidative stress. Current dressings that promote chronic wound healing either require additional processes such as photothermal irradiation or leave behind gross amounts of undesirable residues. We report a dual-functionality hydrogel dressing with intrinsic antibiofilm and antioxidative properties that are synergistic and low-leaching.

Umbilical Cord Plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles.

Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes.

Field-free switching of perpendicular magnetization by two-dimensional PtTe/WTe van der Waals heterostructures with high spin Hall conductivity.

The key challenge of spin-orbit torque applications lies in exploring an excellent spin source capable of generating out-of-plane spins while exhibiting high spin Hall conductivity. Here we combine PtTe for high spin conductivity and WTe for low crystal symmetry to satisfy the above requirements. The PtTe/WTe bilayers exhibit a high in-plane spin Hall conductivity σ ≈ 2.

Coronary CT Angiography-based Morphologic Index for Predicting Hemodynamically Significant Coronary Stenosis.

Purpose To develop a new coronary CT angiography (CCTA)-based index, α×LL/MLD, that considers lesion entrance angle (α) in addition to lesion length (LL) and minimal lumen diameter (MLD) and to evaluate its efficacy in predicting hemodynamically significant coronary stenosis compared with invasive coronary angiography (ICA)-derived fractional flow reserve (FFR). Materials and Methods This prospective study enrolled participants (September 2016-March 2020) from two centers who underwent CCTA followed by ICA (ClinicalTrials.gov identifier: NCT03054324).

Associations of cord plasma per- and polyfluoroakyl substances (PFAS) with neonatal and child body composition and adiposity: The GUSTO study.

Background: The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS.

Methods: In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age.

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI.

Background: Existing literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots.

Design and testing of a humanized porcine donor for xenotransplantation.

Recent human decedent model studies and compassionate xenograft use have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model.

The Structural Layers of the Porcine Iris Exhibit Inherently Different Biomechanical Properties.

Purpose: The purpose of this study was to isolate the structural components of the ex vivo porcine iris tissue and to determine their biomechanical properties.

Methods: The porcine stroma and dilator tissues were separated, and their dimensions were assessed using optical coherence tomography (OCT). The stroma underwent flow test (n = 32) to evaluate for permeability using Darcy's Law (ΔP = 2000 Pa, A = 0.

Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization.

Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection.

Ocular Manifestations and Outcomes in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients.

Purpose: To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Design: Retrospective comparative case series.

Methods: This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020.

Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer.

KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of KAT6A to achieve therapeutic benefit has been a challenge. Here we describe identification of a highly potent, selective, and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from a benzisoxazole series, which demonstrates anti-tumor activity in correlation with H3K23Ac inhibition in KAT6A over-expressing breast cancer.

Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease.

The biological basis of the neurodegenerative movement disorder, Parkinson's disease (PD), is still unclear despite it being 'discovered' over 200 years ago in Western Medicine. Based on current PD knowledge, there are widely varying theories as to its pathobiology. The aim of this article was to explore some of these different theories by summarizing the viewpoints of laboratory and clinician scientists in the PD field, on the biological basis of the disease.