Generative Artificial Intelligence Use in Healthcare: Opportunities for Clinical Excellence and Administrative Efficiency.

Generative Artificial Intelligence (Gen AI) has transformative potential in healthcare to enhance patient care, personalize treatment options, train healthcare professionals, and advance medical research. This paper examines various clinical and non-clinical applications of Gen AI. In clinical settings, Gen AI supports the creation of customized treatment plans, generation of synthetic data, analysis of medical images, nursing workflow management, risk prediction, pandemic preparedness, and population health management.

Endometrial scratching before euploid embryo transfer: a case-control study.

Purpose: To evaluate the effect of endometrial scratching on in vitro fertilization (IVF) success rates in women undergoing frozen embryo transfer with preimplantation genetic testing for aneuploidy (PGT-A).

Methods: Biopsy was performed at oocyte retrieval in cases and compared to those who did not undergo scratching (controls). Endpoints included pregnancy loss, total pregnancy, clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR), and the incidence of chronic endometritis (CE).

Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8 T-cell infiltration while reducing neutrophils.

Vibrational weak and strong coupling modify a chemical reaction via cavity-mediated radiative energy transfer.

Controlling reaction outcomes through external influences is a central goal in chemistry. Vibrational coupling between molecular vibrations and cavity modes is rapidly emerging as a distinct strategy compared with conventional thermochemical and photochemical methods; however, insight into the fundamental mechanisms remains limited. Here we investigate how vibrational weak and strong coupling in plasmonic nanocavities modifies the thermal dehydration of copper sulfate pentahydrate.

ATXN10 Gene Expansions in Mexican Patients with Ataxia Without Epilepsy.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant (AD) neurodegenerative disorder prevalent in the Americas, particularly in Mexico. Clinical manifestations include progressive ataxia and epilepsy. However, it can exhibit wide phenotypic variability and even reduced penetrance.

Hepcidin, Incident Heart Failure and Cardiac Dysfunction in Older Adults: the ARIC Study.

Aims: Hepcidin regulates plasma and tissue iron levels. We studied the association of hepcidin levels with the risk of incident heart failure (HF) and cardiac dysfunction in older adults.

Methods: We included adults from the ongoing, longitudinal Atherosclerosis Risk in Communities (ARIC) study who were free from prevalent anemia and HF at Visit 5 (2011-2013) and had available hepcidin and covariate data.

PRDM1 is a key regulator of the natural killer T-cell central memory program and effector function.

Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR/Cas9-based mutagenesis screen that employs a guide RNA (gRNA) library targeting 1,118 immune-related genes. Unmodified NKTs and NKTs expressing a GD2-specific chimeric antigen receptor (GD2.

Carbohydrate and wound healing in critically ill burn patients: A retrospective cohort study.

Two randomized controlled trials conducted in acutely burned patients found clinical benefits with higher carbohydrate (60-65% of total energy), lower fat (12-15%) nutrition, to include faster wound healing, fewer wound infections, decreased hospital stay, and less pneumonia. The primary purpose of this study was to assess whether our change in practice to a higher proportion of carbohydrates (60%) with 25% of energy from protein, and 15% of energy from fat was associated with improved wound healing rates. Secondary outcomes evaluated included invasive fungal wound infections, ischemic bowel, sepsis, and mortality.

An exosome-based liquid biopsy predicts depth of response and survival outcomes to cetuximab and panitumumab in metastatic colorectal cancer: The EXONERATE Study.

PURPOSE EXONERATE (EXOsome and cell-free micro-RNAs of anti-EGFR ResistAnce) was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with newly diagnosed RAS-WT, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in 2-nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRC to predict PFS, OS, and ORR.

A Lambda-evo (λ) phage platform for Zika virus E protein display.

One of the most significant bacteriophage technologies is phage display, in which heterologous peptides are exhibited on the virion surface. This work describes the display of λ decorative protein D linked to the E protein domain III of Zika virus (D-ZE), to the GFP protein (D-GFP), or to different domain III epitopes of the E protein (D-TD), exhibited on the surface of an in vitro evolved lambda phage (λ). This phage harbors a gene D deletion and was subjected to directed evolution using Escherichia coli W3110/pD-ZE as background.

Torsion-Induced Traumatic Optic Neuropathy (TITON): A physiologically relevant animal model of traumatic optic neuropathy.

Traumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone.

Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial.

Aims/hypothesis: COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications.

Methods: This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions.

Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer.

Sirtuin 7 (SIRT7), a member of the sirtuin family of NAD+-dependent deacetylases, plays a vital role in cancer, exhibiting context-dependent functions across various malignancies. Our study investigates the role of SIRT7 depletion in head and neck squamous cell carcinoma (HNSCC) progression. In vitro and 3D organotypic models demonstrated that SIRT7 knock-out attenuates cancer cell viability, proliferation, and motility as well as induces downregulation of migration- and epithelial-mesenchymal transition (EMT)-related gene expression.

Three-dimensional linkage analysis with digital PCR for genome integrity and identity of recombinant adeno-associated virus.

Recombinant adeno-associated virus (rAAV) has emerged as the vector of choice for in vivo gene delivery, with numerous clinical trials underway for the treatment of various human diseases. Utilizing rAAV in gene therapy requires a highly precise quantification method to determine the viral genome titer and further establish the optimal therapeutic dosage for a rAAV product. The conventional single-channel droplet digital PCR (1D ddPCR) method offers only partial information regarding the viral vector genome titer, lacking insights into its integrity.

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.

Development, review, and activation of thoracic oncology investigator-initiated trials.

Background: Investigator-initiated trials (IITs) may address important biological and clinical questions that may not be prioritized by pharmaceutical sponsors. However, little is known about the process by which IIT proposals are evaluated and activated.

Methods: We performed a retrospective study of IIT concepts submitted through the Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC), which comprises 13 institutions in the U.

Functional test of a naturally occurred tumor modifier gene provides insights to melanoma development.

Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness in most animal systems. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus, is used to study hybrid dysfunction, and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids.

Amino acids and CART distinguish A-β+ Ketosis-Prone Diabetes from type 1 and type 2 diabetes during hyperglycemic crises.

Context: When clinically stable, patients with A-β+ Ketosis-Prone Diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

Objective: Compare serum metabolomics of KPD, T1D and T2D patients during hyperglycemic crises, and utilize Classification and Regression Tree (CART) modeling to distinguish these forms of diabetes.

Operation Baby Drop: Lessons Learned From Military International Air Transport of Critically Ill Neonate.

Military medical transport is unique due to its frequent long-distance travel with limited supplies and capabilities. Military neonatal transport is perhaps even more niche, and descriptions in the literature are rare. A military neonatal team transported a 1-month-old former 26-week infant from a forward-deployed non-combat setting.

Digital humanistic program to manage premature frailty in young breast cancer survivors with gender perspective.

Premature frailty is a critical challenge for young breast cancer survivors (YBCSs), impacting their health and perpetuating gender inequality through heightened vulnerability and marginalization. While digital health shows promise in frailty screening, its effectiveness for comprehensively managing frailty remains inconclusive. This randomized controlled trial, registered at the Chinese Clinical Trial Registry (ChiCTR2200058823), tests the "AI-TA" program's efficacy on premature frailty and quality of life in YBCSs.

Early Versus Late Atrial Fibrillation Recurrence After Pulsed Field Ablation: Insights From the admIRE Trial.

Background And Aims: Studies have shown correlations between early recurrence (ER) and late recurrence (LR) of atrial arrhythmia after ablation with thermal technologies. This admIRE trial (NCT05293639) subanalysis aims to analyze ER versus LR in patients with paroxysmal atrial fibrillation (PAF) undergoing pulsed field ablation (PFA).

Methods: Patients with symptomatic paroxysmal atrial fibrillation and ≥1 transtelephonic monitoring transmission during the blanking period were included (n=169).

Safety and efficacy of trifluridine/tipiracil +/- bevacizumab plus XB2001 (anti-IL-1α antibody): a single-center phase 1 trial.

In the tumour microenvironment, IL-1α promotes neoangiogenesis, matrix remodelling, tumour proliferation, chemoresistance, and metastases. Highly expressed in human colorectal cancers, IL-1α is associated with poor prognosis. XB2001, a fully human monoclonal antibody neutralizing IL-1α, was evaluated for safety and preliminary efficacy with trifluridine/tipiracil (FTD/TPI) and bevacizumab in metastatic colorectal cancer patients previously treated with oxaliplatin- and irinotecan-based chemotherapies.

The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis.

The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation.