Mild-Temperature Catalyzed Hydrosilylation for Simplified Carbohydrate Functionalization of Porous Silicon Nanoparticles.

Porous silicon is one of the most explored nanostructured materials in various biomedical applications owing to its remarkable properties. However, its inherent chemical instability mandates a robust surface modification procedure, and proper surface bioengineering is essential to ensure its effectiveness in the biomedical field. In this study, we introduce a one-pot functionalization strategy that simultaneously stabilizes porous silicon nanoparticles and decorates their surface with carbohydrates through hydrosilylation chemistry, combining mild temperatures and a Lewis acid catalyst.

A systematic review of microneedles technology in drug delivery through a bibliometric and patent overview.

The transdermal drug delivery (TDD) route has gathered considerable attention for its potential to improve therapeutic efficacy while minimizing systemic side effects. Among transdermal technologies, microneedle (MN) devices have proven to be a promising approach that combines the advantages of traditional needle injections and non-invasive topical applications. This review provides a comprehensive analysis of progress in transdermal drug delivery systems (TDDS) via MN from 2000 to 2023, integrating bibliometric analysis and patent landscape to present a multi-faceted perspective on the evolution of this technology.

Results from a Double-Blind, Randomized, Placebo-Controlled, Single-Dose, Crossover Trial of Lovastatin or Minocycline in Fragile X Syndrome.

Treatment studies in knockout rodent models have found that minocycline and lovastatin each improve synaptic, neurological, and behavioral functioning, and open-label chronic dosing studies in human patients with fragile X syndrome (FXS) have demonstrated modest clinical improvements. Findings from blinded studies are mixed, and there is a limited understanding of electrophysiological target engagement that would facilitate cross-species translational studies. Smaller-scale, acute (e.

Iron deficiency negatively affects behavioral measures of learning, indirect neural measures of dopamine, and neural efficiency.

Iron deficiency (ID) is the most prevalent nutrient deficiency in the world, with a growing literature documenting the negative effects of ID on perception, attention, and memory. Animal models of ID suggest that dysregulation of dopamine is responsible for the deficits in memory. However, evidence that ID affects dopamine in humans is extremely limited.

Flexible 3D nanofiber-based SERS biosensor for detection of miRNA-223-3p in early Laryngeal Cancer diagnosis.

MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nucleotides) that regulate gene expression and are associated with various diseases, including Laryngeal Cancer (LCa), which has a high mortality rate due to late diagnosis. Traditional methods for miRNA detection present several drawbacks (time-consuming steps, high cost and high false positive rate). Early-stage diagnosis and selective detection of miRNAs remain challenging.

A novel inner-branched stent-graft to overcome narrowed lumen in branched endovascular aneurysm repair.

A narrowed patent aortic lumen (<25 mm) represents a challenging scenario frequently observed during thoraco-abdominal and abdominal aortic pathologies involving the visceral vessels. The paper aims to describe the characteristics of a novel tapered-shape inner-branched custom-made stent-graft designed to specifically address the narrowed patent aortic lumen and its applicability in a wider spectrum of aortic scenarios at the reno-visceral segment.

Myxinidin-analogs able to sequester Fe(III): Metal-based gun to combat Pseudomonas aeruginosa biofilm.

Bacteria have developed a tendency to form biofilms, where bacteria live in organized structures embedded in a self-produced matrix of DNA, proteins, and polysaccharides. Additionally, bacteria need iron(III) as an essential nutrient for bacterial growth and secrete siderophore groups that sequester it from the environment. To design a molecule able both to inhibit the bacteria and to sequester iron, we developed two hydroxamate-based peptides derived from an analog (WMR-4), previously developed in our lab, of the antimicrobial peptide myxinidin.

Feasibility and Safety of Using Carbon Dioxide Exclusively in Regular Endovascular Aortic Aneurysm Repair: Results of a Multicentre, Prospective, Zero Iodine Contrast Endovascular Aneurysm Repair Study.

Objective: Carbon dioxide (CO) angiography has emerged as a viable alternative to regular iodinated contrast medium (ICM) for guiding endovascular aneurysm repair (EVAR) procedures. This study aimed to evaluate the feasibility and safety of a standardised EVAR procedure using only CO angiography.

Methods: A prospective, multicentre, national study enrolled consecutive patients between January 2023 and January 2024 with asymptomatic abdominal aortic aneurysms measuring ≥ 55 mm and for whom a standard endovascular graft (instructions for use) was anatomically feasible.

Timely escalation to second-line therapies after failure of methotrexate in patients with early rheumatoid arthritis does not reduce the risk of becoming difficult-to-treat.

Background: To investigate the frequency of difficult-to-treat (D2T) rheumatoid arthritis (RA) in patients early escalated to biologic/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) after failure of treat-to-target with methotrexate (MTX).

Methods: From a prospective cohort of early RA, all patients with their first access in the years 2005-2018, and eventually starting a b/tsDMARD before the end of 2022, were included and followed-up until April 2024. Study outcomes included drug survival on each consecutive b/tsDMARDs, development of D2T (according to the EULAR definition and subsequent modifications), and its predictors.

Combined intraocular and intravenous gene delivery for therapy of gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina (GACR) is due to ornithine aminotransferase (OAT) deficiency, which causes hyperornithinemia, leading to retinal pigment epithelium, followed by choroidal and retinal degeneration. Adeno-associated virus serotype 8 (AAV8) vector-mediated OAT (AAV8-OAT) liver gene transfer reduces ornithinemia in the Oat mouse model of GACR and improves retinal function and structure. Since OAT is expressed in various tissues including the retina, we investigated the efficacy of restoration of OAT expression in either retina or liver or both tissues on the retinal phenotype of Oat mice.

High serum levels of CXCL13 predict lower response to csDMARDs in both ACPA-positive and ACPA-negative early rheumatoid arthritis.

Objectives: Increased circulating levels of CXCL13 reflect synovial production and indicate immune dysregulation in patients with rheumatoid arthritis (RA). Here we tested whether CXCL13 predicts response to first-line treatment with methotrexate (MTX) in patients with early RA, independently and in association with anti-citrullinated protein antibodies (ACPA) and IgM-rheumatoid factor (RF).

Methods: A prospective cohort of 243 early RA patients undergoing treat-to-target with MTX was evaluated.

Validating brain activity measures as reliable indicators of individual diagnostic group and genetically mediated sub-group membership Fragile X Syndrome.

Recent failures translating preclinical behavioral treatment effects to positive clinical trial results in humans with Fragile X Syndrome (FXS) support refocusing attention on biological pathways and associated measures, such as electroencephalography (EEG), with strong translational potential and small molecule target engagement. This study utilized guided machine learning to test promising translational EEG measures (resting power and auditory chirp oscillatory variables) in a large heterogeneous sample of individuals with FXS to identify best performing EEG variables for reliably separating individuals with FXS, and genetically-mediated subgroups within FXS, from typically developing controls. Best performing variables included resting relative frontal theta power, all combined posterior-head resting power bands, posterior peak alpha frequency (PAF), combined PAF across all measured regions, combined theta, alpha, and gamma power during the chirp, and all combined chirp oscillatory variables.

Neural shape completion for personalized Maxillofacial surgery.

In this paper, we investigate the effectiveness of shape completion neural networks as clinical aids in maxillofacial surgery planning. We present a pipeline to apply shape completion networks to automatically reconstruct complete eumorphic 3D meshes starting from a partial input mesh, easily obtained from CT data routinely acquired for surgery planning. Most of the existing works introduced solutions to aid the design of implants for cranioplasty, i.

A structural peculiarity of Antarctic fish IgM drives the generation of an engineered mAb by CRISPR/Cas9.

IgM is the major circulating Ig isotype in teleost fish, showing in Antarctic fish unique features such as an extraordinary long hinge region, which plays a crucial role in antibody structure and function. In this work, we describe the replacement of the hinge region of a murine monoclonal antibody (mAb) with the peculiar hinge from Antarctic fish IgM. We use the CRISPR/Cas9 system as a powerful tool for generating the engineered mAb.

Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003).

Tuning Peptide-Based Nanofibers for Achieving Selective Doxorubicin Delivery in Triple-Negative Breast Cancer.

Introduction: The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with poor prognosis and limited effective therapeutic options.

Purpose: In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects.

Exosomes multiplex profiling, a promising strategy for early diagnosis of laryngeal cancer.

Background: Exosomes are nanosized vesicles released from all cells into surrounding biofluids, including cancer cells, and represent a very promising direction in terms of minimally invasive approaches to early disease detection. They carry tumor-specific biological contents such as DNA, RNA, proteins, lipids, and sugars, as well as surface molecules that are able to pinpoint the cellular source. By the above criteria, exosomes may be stratified according to the presence of tissue and disease-specific signatures and, due to their stability in such biofluids as plasma and serum, they represent an indispensable source of vital clinical insights from liquid biopsies, even at the earliest stages of cancer.

Liver gene transfer for metabolite detoxification in inherited metabolic diseases.

Inherited metabolic disorders (IMDs) are a growing group of genetic diseases caused by defects in enzymes that mediate cellular metabolism, often resulting in the accumulation of toxic substrates. The liver is a highly metabolically active organ that hosts several thousands of chemical reactions. As such, it is an organ frequently affected in IMDs.

Neural Disparity Refinement.

We propose a framework that combines traditional, hand-crafted algorithms and recent advances in deep learning to obtain high-quality, high-resolution disparity maps from stereo images. By casting the refinement process as a continuous feature sampling strategy, our neural disparity refinement network can estimate an enhanced disparity map at any output resolution. Our solution can process any disparity map produced by classical stereo algorithms, as well as those predicted by modern stereo networks or even different depth-from-images approaches, such as the COLMAP structure-from-motion pipeline.

Glucose transporter-1 deficiency syndrome with extreme phenotypic variability in a five-generation family carrying a novel SLC2A1 variant.

Background And Purpose: Glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1-DS) is a metabolic disorder due to reduced expression of GLUT1, a glucose transporter of the central nervous system. GLUT1-DS is caused by heterozygous SLC2A1 variants that mostly arise de novo. Here, we report a large family with heterogeneous phenotypes related to a novel SLC2A1 variant.

Field evaluation of validity and feasibility of Pan-Lassa rapid diagnostic test for Lassa fever in Abakaliki, Nigeria: a prospective diagnostic accuracy study.

Background: Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria.

Higher-order G-quadruplex structures and porphyrin ligands: Towards a non-ambiguous relationship.

Herein, we evaluated the interaction of the tetracationic porphyrin HTCPPSpm4 with three distinct DNA G-quadruplex (G4) models, i.e., the tetramolecular G4 d(TGGGGT) (Q), the 5'-5' stacked G4-dimer [d(CGGAGGT)] (Q), and a mixture of 5'-5' stacked G-wires [d(5'-CGGT-3'-3'-GGC-5')] (Q).

Changes in Brain Activity Immediately Post-Exercise Indicate a Role for Central Fatigue in the Volitional Termination of Exercise.

Electroencephalography (EEG) allows for the evaluation of real time changes in brain (electrocortical) activity during exercise. A few studies have examined changes in electrocortical activity using stationary cycling, but the findings have been mixed. Some of these studies have found increases in brain activity following exercise, while others have found decreases in brain activity following exercise.