Light-Dependent Chemoselective Amide or Thioamide Ligation of Acylsilanes with Amines using Elemental Sulfur.

Due to the diverse chemical and physical properties of functional groups, mild and controllable ligation methods are often required to construct complex drugs and functional materials. To make diverse sets of products with tunable physicochemical properties, it is also useful to employ complimentary ligation methods that adopt the same starting materials. Here, we disclose the efficient and modular synthesis of amides or thioamides through the chemical ligation of acyl silanes with amines, simply by turning a light on or off.

GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth.

Background: Granzyme B (GrB) is a key effector molecule, delivered by cytotoxic T lymphocytes and natural killer cells during immune surveillance to induce cell death. Fusion proteins and immunoconjugates represent an innovative therapeutic approach to specifically deliver a deadly payload to target cells. Epithelial membrane protein-2 (EMP2) is highly expressed in invasive breast cancer (BC), including triple-negative BC (TNBC), and represents an attractive therapeutic target.

Clinical outcomes of a digital musculoskeletal women's pelvic health program: an observational, longitudinal study with comparison group.

Background: Chronic pelvic pain is a common yet undertreated condition that significantly impacts quality of life for women worldwide. Digital exercise therapy designed to target pelvic pain can improve symptomology while reducing time and cost-related barriers to in-person clinical care.

Methods: This longitudinal, observational study of a digital women's pelvic health program examined pelvic pain, anxiety, and depression at 4 and 12 weeks in female adults experiencing chronic pelvic pain.

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels.

A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

Brief Report: Stated Preferences for Long-Acting Injectable ART Among Mobile Men Living With HIV in Malawi: A Qualitative Study.

Background: Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV).

Methods: We conducted a qualitative substudy within two parent trials in 24 health facilities in Malawi that enrolled MLHIV ≥15 years not on ART.

Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles.

In this study, we designed a nanoscale platform for sustained amino acid delivery to support transplanted pancreatic islets. The platform features mesoporous silica nanoparticles (MSNPs) loaded with glutamine (G), an essential amino acid required for islet survival and function, and coated with polydopamine (PD). We investigated various PD concentrations (0.

Population dynamics modeling reveals that myeloid bias involves both HSC differentiation and progenitor proliferation biases.

Aging and chronic inflammation are associated with overabundant myeloid-primed multipotent progenitors (MPPs) amongst hematopoietic stem and progenitor cells (HSPCs). While HSC differentiation bias has been considered a primary cause of myeloid bias, whether it is sufficient has not been quantitatively evaluated. Here, we analyzed bone marrow data from the IκB- (Nfkbia+/-Nfkbib-/-Nfkbie-/-) mouse model of inflammation with elevated NFκB activity, which shows increased myeloid-biased MPPs.

A Malleable Collagen-Mimic that Undergoes Moisture-Induced Hardening for Gluing Hydrophilic Surfaces.

A collagen-inspired helical protein-mimic has been synthesized via topochemical polymerization of a designed tripeptide monomer. In the monomer crystal, molecules arrange in a head-to-tail manner, forming supramolecular helices. The azide and alkyne of adjacent molecules in the supramolecular helix are proximally preorganized in a ready-to-react arrangement.

Utility of word embeddings from large language models in medical diagnosis.

Objective: This study evaluates the utility of word embeddings, generated by large language models (LLMs), for medical diagnosis by comparing the semantic proximity of symptoms to their eponymic disease embedding ("eponymic condition") and the mean of all symptom embeddings associated with a disease ("ensemble mean").

Materials And Methods: Symptom data for 5 diagnostically challenging pediatric diseases-CHARGE syndrome, Cowden disease, POEMS syndrome, Rheumatic fever, and Tuberous sclerosis-were collected from PubMed. Using the Ada-002 embedding model, disease names and symptoms were translated into vector representations in a high-dimensional space.

Characteristics of Patients Experiencing Opioid Overdose and Eligibility for Prehospital Treatment with Buprenorphine.

Objectives: Opioids kill tens of thousands of patients each year. While only a fraction of people with opioid use disorder (OUD) have accessed treatment in the last year, 30% of people who died from an overdose had an Emergency Medical Services (EMS) encounter within a year of their death. Prehospital buprenorphine represents an important emerging OUD treatment, yet limited data describe barriers to this treatment.

A Hitchhiker's Guide Toward CSF Biomarkers for Neuro-Oncology.

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection.

Outcomes of Immunotherapy Treatment in Sinonasal Mucosal Melanoma.

Background: Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous melanoma is well-defined, there are relatively little data on sinonasal mucosal melanoma.

Objective: We sought to define immunotherapy outcomes in patients with sinonasal mucosal melanoma.

Morphological Features Influence the Drug Loading and Delivery Efficacy of Photoactivatable Gold Nanocarriers for Antitumor Photo/Chemotherapy.

Photoactivatable gold nanocarriers are transforming antitumor therapies by leveraging their distinctive physicochemical properties, enabling targeted drug delivery and enhanced therapeutic efficacy in cancer treatment. This study systematically investigates how surface topography and morphology of gold nanocarriers influence drug loading capacity, light-to-heat conversion efficiency, and overall therapeutic performance in photo/chemotherapy. We synthesized four distinct morphologies of gold nanoparticles: porous gold nanocups (PAuNCs), porous gold nanospheres (PAuNSs), solid gold nanocups (SAuNCs), and solid gold nanospheres (SAuNSs).

Task relevant autoencoding enhances machine learning for human neuroscience.

In human neuroscience, machine learning can help reveal lower-dimensional neural representations relevant to subjects' behavior. However, state-of-the-art models typically require large datasets to train, and so are prone to overfitting on human neuroimaging data that often possess few samples but many input dimensions. Here, we capitalized on the fact that the features we seek in human neuroscience are precisely those relevant to subjects' behavior rather than noise or other irrelevant factors.

Small variant benchmark from a complete assembly of X and Y chromosomes.

The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets.

Diuretic Potentiation Strategies in Acute Heart Failure.

Several trials have evaluated diuretic-based strategies to improve symptoms and outcomes in patients with acute heart failure (AHF). The authors sought to summarize the effect of different combination strategies on symptoms, physical signs, physiological variables, and outcomes in patients with AHF. Twelve trials were identified that assessed the addition of thiazide diuretics, sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, vasopressin receptor antagonists, carbonic anhydrase inhibitors, or loop diuretic intensification to conventional therapy for AHF.

Practice Intention: Addressing the Needs of Diverse Underserved Communities in Medical Education.

Background And Objectives: The US physician workforce is at a critical juncture, with a projected shortage and misdistribution of primary care physicians. Culturally and linguistically diverse states, such as California, are challenged to search for innovative approaches in medical education to address the physician needs of diverse underserved communities. The University of California recognizes this imperative and supports Programs in Medical Education (PRIME), including PRIME Leadership and Advocacy (PRIME-LA) at University of California Los Angeles (UCLA).

Application of machine learning to identify risk factors for outpatient opioid prescriptions following spine surgery.

Introduction: Spine surgery is a common source of narcotic prescriptions and carries potential for long-term opioid dependence. As prescription opioids play a role in nearly 25 % of all opioid overdose deaths in the United States, mitigating risk for prolonged postoperative opioid utilization is crucial for spine surgeons.

Purpose: The aim of this study was to employ six ML algorithms to identify clinical variables predictive of increased opioid utilization across spinal surgeries, including anterior cervical discectomy and fusion (ACDF), posterior thoracolumbar fusion (PTLF), and lumbar laminectomy.

Alternative Formulations of Job Strain and Sleep Disturbances: A Longitudinal Study in the United States.

Background: Sleep disturbances are a major public health concern in the United States, leading to adverse health outcomes. In the working population, job strain has been identified as an important risk factor for sleep disturbances, but evidence from the United States remained limited. This study aimed to examine longitudinal associations between job strain and sleep disturbances in the United States, with a focus on the alternative formulations of job strain.

Medicare Part D: Major Shifts With the Inflation Reduction Act and a Way Forward.

The Inflation Reduction Act (IRA) of 2022 introduced major changes in the Part D benefit that aim to improve medication access and correct several of the financial misalignments in the current Part D benefit. The changes address financial obligations of Medicare beneficiaries, the federal government, Part D plan sponsors (i.e.