Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

Elevating Dermatology Beyond Aesthetics: Perinatal-Derived Advancements for Rejuvenation, Alopecia Strategies, Scar Therapies, and Progressive Wound Healing.

Dermatologists have been interested in recent advancements in regenerative therapy. Current research is actively investigating the possibility of placental tissue derivatives to decelerate the skin aging process, enhance skin regeneration, reduce scarring, and prevent hair loss. Amniotic membranes (AM) play a crucial role in regenerative medicine as they serve as a suitable means of transporting stem cells, growth hormones, cytokines, and other essential compounds.

Pancreatic Ductal Adenocarcinoma with Medullary Features and a Complete Pathological Response After Neoadjuvant FOLFIRINOX: A Case Report and Literature Review.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor response to chemotherapy. High-frequency microsatellite instability (MSI-H) is a rare biological phenomenon in conventional PDAC, being more frequently described in tumors with medullary or mucinous features.

Methods And Results: In this manuscript, we report the case of a patient with an MSI-H pancreatic carcinoma with medullary features (medullary carcinoma of the pancreas-MCP) that achieved a complete pathological response after neoadjuvant modified FOLFIRINOX.

Artificial Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure: Systematic Review and Meta-Analysis.

Objectives: To systematically review the safety and efficacy of nonbiological (NBAL) or biological artificial liver support systems (BAL) and whole-organ extracorporeal liver perfusion (W-ECLP) systems, in adults with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF).

Data Sources: Eligible NBAL/BAL studies from PubMed/Embase searches were randomized controlled trials (RCTs) in adult patients with ALF/ACLF, greater than or equal to ten patients per group, reporting outcomes related to survival, adverse events, transplantation rate, and hepatic encephalopathy, and published in English from January 2000 to July 2023. Separately, we searched for studies evaluating W-ECLP in adult patients with ALF or ACLF published between January1990 and July 2023.

Characterization and genomic insights into bacteriophages Kpph1 and Kpph9 against hypervirulent carbapenem-resistant .

The increasing incidence of infections attributed to hypervirulent carbapenem-resistant (Hv-CRKp) is of considerable concern. Bacteriophages, also known as phages, are viruses that specifically infect bacteria; thus, phage-based therapies offer promising alternatives to antibiotic treatments targeting Hv-CRKp infections. In this study, two isolated bacteriophages, Kpph1 and Kpph9, were characterized for their specificity against the Hv-CRKp NUHL30457 strain that possesses a K2 capsule serotype.

Construction of a predictive model for the effectiveness of plastic surgery and repair in patients with facial basal cell carcinoma.

This study aims to identify factors influencing aesthetic outcomes following facial basal cell carcinoma (BCC) plastic surgery to enhance post-operative satisfaction and cosmetic results. A retrospective cohort study was conducted on 303 patients who underwent facial BCC plastic surgery between June 2021 and June 2023. Data on demographics, blood tests, SF-12, and Skindex-16 scores were analyzed.

Evaluation of Biomaterials in Periodontal Regeneration: A Literature Review.

The field of periodontal regeneration focuses on restoring the form and function of periodontal tissues compromised due to diseases affecting the supporting structures of teeth. Biomaterials have emerged as a vital component in periodontal regenerative therapy, offering a variety of properties that enhance cellular interactions, promote healing, and support tissue reconstruction. This review explores current advances in biomaterials for periodontal regeneration, including ceramics, polymers, and composite scaffolds, and their integration with biological agents like growth factors and stem cells.

Overcoming drug resistance through extracellular vesicle-based drug delivery system in cancer treatment.

Drug resistance is a major challenge in cancer therapy that often leads to treatment failure and disease relapse. Despite advancements in chemotherapeutic agents and targeted therapies, cancers often develop drug resistance, making these treatments ineffective. Extracellular vesicles (EVs) have gained attention for their potential applications in drug delivery because of their natural origin, biocompatibility, and ability to cross biological barriers.

Mitochondria-Targeting Type-I Photodynamic Therapy Based on Phenothiazine for Realizing Enhanced Immunogenic Cancer Cell Death via Mitochondrial Oxidative Stress.

Purpose: Photo-immunotherapy faces challenges from poor immunogenicity and low response rate due to hypoxic microenvironment. This study presents Rh-PTZ, a small organic molecule with a D-π-A structure, that simultaneously amplifies mitochondria-targeted type-I PDT-dependent immune stimulation for the treatment of hypoxic cancer.

Methods: The hydrophobic Rh-PTZ was encapsulated into F127 to prepare Rh-PTZ nanoparticles (Rh-PTZ NPs).

Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials.

Background: Cardiogenic shock (CS) is a heterogeneous clinical syndrome, making it challenging to predict patient trajectory and response to treatment. This study aims to identify biological/molecular CS subphenotypes, evaluate their association with outcome, and explore their impact on heterogeneity of treatment effect (ShockCO-OP, NCT06376318).

Methods: We used unsupervised clustering to integrate plasma biomarker data from two prospective cohorts of CS patients: CardShock (N = 205 [2010-2012, NCT01374867]) and the French and European Outcome reGistry in Intensive Care Units (FROG-ICU) (N = 228 [2011-2013, NCT01367093]) to determine the optimal number of classes.

Advances in the Assessment and Treatment of Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases primarily cause inflammation of small blood vessels. Renal involvement occurs frequently and often leads to end-stage renal disease (ESRD), which significantly impacts patient health and survival. Early diagnosis and appropriate treatment are essential to improving patient outcomes.

Relationship Between Patient Demographics and Biologic Therapy Use in Inflammatory Bowel Disease. A Single Center Cross-Sectional Study.

Introduction: Biologic therapies treat patients with moderate to severe inflammatory bowel disease (IBD). This study aims to investigate the demographics of biologic therapy use and its association with patient characteristics, a topic that has not yet been thoroughly assessed in our region.

Methods: Electronic health record data from June 1, 2021, to May 31, 2023, were collected at a tertiary care IBD center in Kuwait.

Single and repeated-dose toxicity studies by intravaginal administration of ATG-K2 powder in female rats.

Bacterial vaginosis (BV) is a microbial dysbiosis that shifts the paradigms of vaginal flora from lactobacilli to opportunistic pathogens. Globally, BV is treated with antibiotic therapy and recurrence rates are > 70% occurring within 6 months due to antibiotic resistance against pathogenic bacteria. An incorporation of orally or intravaginally for the recolonization of healthy microbes in vagina is the suggested course of treatment.

A new fluorescent oxaliplatin(iv) complex with EGFR-inhibiting properties for the treatment of drug-resistant cancer cells.

Platinum chemotherapy is part of every second anticancer treatment regimen. However, its application is limited by severe side effects and drug resistance. The combination of platinum-based chemotherapeutics with EGFR inhibitors has shown remarkable synergism in clinical treatment.

MHCI trafficking signal-based mRNA vaccines strengthening immune protection against RNA viruses.

The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines.

Sphingosylphosphorylcholine Promotes Th9 Cell Differentiation Through Regulation of Smad3, STAT5, and β-Catenin Pathways.

Sphingosylphosphorylcholine (SPC) is one of sphingomyelin-derived sphingolipids. SPC levels are increased in ascitic fluids of ovarian cancer patients and stratum corneum of atopic dermatitis (AD) patients. SPC has antitumor activity against several cancer cells by reducing proliferation and migration and increasing apoptosis .

Finely Tailored Conjugated Small Molecular Nanoparticles for Near-Infrared Biomedical Applications.

Near-infrared (NIR) phototheranostics (PTs) show higher tissue penetration depth, signal-to-noise ratio, and better biosafety than PTs in the ultraviolet and visible regions. However, their further advancement is severely hindered by poor performances and short-wavelength absorptions/emissions of PT agents. Among reported PT agents, conjugated small molecular nanoparticles (CSMNs) prepared from D-A-typed photoactive conjugated small molecules (CSMs) have greatly mediated this deadlock by their high photostability, distinct chemical structure, tunable absorption, intrinsic multifunctionality, and favorable biocompatibility, which endows CSMNs with more possibilities in biological applications.

Templated self-organization of polymer-tethered gold nanoparticles into freestanding superlattices at the liquid-air interface.

Programmable organization of uniform organic/inorganic functional building blocks into large-scale ordered superlattices has attracted considerable attention since the bottom-up self-organization strategy opens up a robust and universal route for designing novel and multifunctional materials with advanced applications in memory storage devices, catalysis, photonic crystals, and biotherapy. Despite making great efforts in the construction of superlattice materials, there still remains a challenge in the preparation of organic/inorganic hybrid superlattices with tunable dimensions and exotic configurations. Here, we report the spontaneous self-organization of polystyrene-tethered gold nanoparticles (AuNPs@PS) into freestanding organic/inorganic hybrid superlattices templated at the diethylene glycol-air interface.

Trends in nanobody radiotheranostics.

As the smallest antibody fragment with specific binding affinity, nanobody-based nuclear medicine has demonstrated significant potential to revolutionize the field of precision medicine, supported by burgeoning preclinical investigations and accumulating clinical evidence. However, the visualization of nanobodies has also exposed their suboptimal biodistribution patterns, which has spurred collaborative efforts to refine their pharmacokinetic and pharmacodynamic profiles for improved therapeutic efficacy. In this review, we present clinical results that exemplify the benefits of nanobody-based molecular imaging in cancer diagnosis.

Integration of clinical, pathological, radiological, and transcriptomic data improves prediction for first-line immunotherapy outcome in metastatic non-small cell lung cancer.

Immunotherapy is improving the survival of patients with metastatic non-small cell lung cancer (NSCLC), yet reliable biomarkers are needed to identify responders prospectively and optimize patient care. In this study, we explore the benefits of multimodal approaches to predict immunotherapy outcome using multiple machine learning algorithms and integration strategies. We analyze baseline multimodal data from a cohort of 317 metastatic NSCLC patients treated with first-line immunotherapy, including positron emission tomography images, digitized pathological slides, bulk transcriptomic profiles, and clinical information.

The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria.

Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through the continuous accumulation of misfolded proteins and damaged organelles. This review delineates the roles of two complementary and synergistic degradation systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system, in the degradation of misfolded proteins and damaged organelles for intracellular recycling. We emphasize the interconnected decision-making processes of degradation systems in maintaining cellular homeostasis, such as the biophysical state of substrates, receptor oligomerization potentials (e.

Developing novel Lin28 inhibitors by computer aided drug design.

Lin28 is a key regulator of cancer stem cell gene network that promotes therapy-resistant tumor progression in various tumors. However, no Lin28 inhibitor has been approved to treat cancer patients, urging exploration of novel compounds as candidates to be tested for clinical trials. In this contribution, we applied computer-aided drug design (CADD) in combination with quantitative biochemical and biological assays.

Preparation of novel chiral stationary phases based on chiral metal-organic cages enable extensive HPLC enantioseparation.

Background: The metal organic cages (MOCs) are an emerging type of porous material that has attracted considerable research interest due to their unique properties, including good stability and well-defined intrinsic cavities. The chiral MOCs with porous structures have broad application prospects in enantiomeric recognition and separation. However, there are almost no relevant reports on chiral MOCs as chiral stationary phases (CSPs) for enantioseparation by high-performance liquid chromatography (HPLC).

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction.

Background: The efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor immune microenvironment (TIME), with a preference for a T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered the exploration of non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics with T cell-inflamed gene-expression profiles.