Induction of MASH in three-dimensional bioprinted human liver tissue.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (MASH), is a major risk factor for cirrhosis and hepatocellular carcinoma (HCC) and a leading cause of liver transplantation. MASH is caused by an accumulation of toxic fat molecules in the hepatocyte which leads to inflammation and fibrosis. Inadequate human "MASH in a dish" models have limited our advances in understanding MASH pathogenesis and in drug discovery.

Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.

Phase II Study of Defactinib (VS6063) in Patients With Tumors With Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U.

Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.

Phase II Study of Sunitinib in Tumors With Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V.

Purpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.

Methods: EAY131-V, is an open-label, single-arm, phase II study.

Advanced Granulosa Cell Tumors of the Ovary: A Review with a Focus on Current and Novel Therapeutic Approaches.

Granulosa cell tumor (GCT) is the most common nonepithelial ovarian malignancy. Still, it is considered rare, with a paucity of high-level evidence guiding management, particularly in the metastatic setting. Advancements in molecular pathology allowed the identification of several targetable mutations that play an important role in GCT pathogenesis.

Laboratory validation of a clinical metagenomic next-generation sequencing assay for respiratory virus detection and discovery.

Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in <24 h. The mNGS assay achieved mean limits of detection of 543 copies/mL, viral load quantification with 100% linearity, and 93.

Wastewater Surveillance for Norovirus, California, USA.

Norovirus is a leading cause of acute gastroenteritis and imposes a substantial disease burden. In California, USA, norovirus surveillance is limited. We evaluated correlations between wastewater norovirus concentrations and available public health surveillance data.

Phase II Study of Palbociclib in Patients with Tumors with CDK4 or CDK6 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C.

Purpose: Amplification of cyclin-dependent kinase 4 (CDK4) and CDK6 is a feature of a variety of malignancies, and preclinical evidence suggests that inhibition of CDK4/6 is a plausible treatment strategy in these tumors. Subprotocol Z1C of the NCI-Molecular Analysis for Therapy Choice trial was designed to evaluate the CDK4/6 inhibitor palbociclib in CDK4- or CDK6-amplified tumors.

Patients And Methods: Patients had a solid malignancy or lymphoma with progression on at least one systemic therapy for advanced disease or with no standard-of-care therapy available.

Paying for advance care planning in medicare: Impacts on care and spending near end of life.

Spending at end of life (EOL) accounts for a large and growing share of healthcare expenditures in the US, and often reflects aggressive care with questionable value for dying patients. Using a novel instrumental variables approach, we conduct the first study on the causal effect of Medicare reimbursement for advance care planning (ACP)-the process of discussing and recording patient preferences for goals of care-on care utilization, spending, and mortality outcomes for critically ill Medicare patients. We find that billed ACP services substantially increase hospice use and hospice spending within a year, accompanied by corresponding increase in one-year mortality.

Plasma ctDNA as a Treatment Response Biomarker in Metastatic Cancers: Evaluation by the RECIST Working Group.

Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease.

Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells.

During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development.

The Clinical, Morphologic, and Molecular Spectrum of BRAF Fusion Spitz Tumors.

BRAF fusion Spitz neoplasms along with MAP3K8 fusions are among the subtypes of Spitz most likely to be diagnosed as Spitz melanoma. However, the current literature has only limited amounts of clinical follow-up on these cases. In this study, we share our experience with 39 BRAF fusion Spitz neoplasms and provide the greatest number of cases with available clinical follow-up.

Phase II Trial of Afatinib in Patients With -Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A.

Purpose: National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring mutations.

Methods: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable mutations were offered participation in Arm A.

Fitting in? Physician practice style after forced relocation.

Objective: This study aims to examine how variation in physicians' treatment decisions for newborn deliveries responds to changes in the hospital-level norms for obstetric clinical decision-making.

Data Sources: All hospital-based births in Florida from 2003 through 2017.

Study Design: Difference-in-differences approach is adopted that leverages obstetric unit closures as the source of identifying variation to exogenously shift obstetricians to a new, nearby hospital with different propensities to approach newborn deliveries less intensively.

PRKC Fusion Melanocytic Tumors, a Subgroup of Melanocytic Tumors More Closely Aligned to Blue Nevi Than to PRKAR1A-inactivated Pigmented Epithelioid Melanocytomas.

Tumors morphologically classified as pigmented epithelioid melanocytomas (PEMs) are genomically diverse, with the 2 most common genomic subtypes being PRKC fusions or PRKAR1A inactivating mutations. PRKC fusions activate the Gα q/11 pathway similar to blue nevi. Conversely, inactivating mutations in PRKAR1A activate the Gα s pathway.

Dopamine β-hydroxylase shapes intestinal inflammation through modulating T cell activation.

Background: Inflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-immune interaction are thought to contribute to the initiation and progression of IBD. However, the role of dopamine beta-hydroxylase (DBH), an enzyme converting dopamine into norepinephrine, in modulating intestinal inflammation is not well defined.

The Community As A Full Partner: A New Model For Public Health.

The COVID-19 pandemic demonstrated a need to strengthen the US public health system by shifting toward much greater community engagement and leadership. In November and December 2023, we conducted separate online surveys of community-based organizations and large metropolitan health departments to identify barriers and opportunities for building a public health system with strong community partnerships. Identified barriers included mistrust, siloed health departments with structural challenges in funding community-based organizations, and insufficient shared decision making.

The scope of practice of geriatric dentistry in British Columbia (Canada): An exploratory study.

Aims: The oral health needs of frail older adults are increasing with an aging population in Canada. The objective of this study was to explore the perceptions of dentists in British Columbia regarding their view of geriatric dentistry as a distinct scope of practice and in relation to special needs dentistry.

Methods And Results: Qualitative data were gathered thorough semi guided interviews of a purposeful sample of dental clinicians, educators and members of organized dentistry with specialized knowledge of oral health for frail older adults.

Application of Statistical Analysis and Machine Learning to Identify Infants' Abnormal Suckling Behavior.

Objective: Identify infants with abnormal suckling behavior from simple non-nutritive suckling devices.

Background: While it is well known breastfeeding is beneficial to the health of both mothers and infants, breastfeeding ceases in 75 percent of mother-child dyads by 6 months. The current standard of care lacks objective measurements to screen infant suckling abnormalities within the first few days of life, a critical time to establish milk supply and successful breastfeeding practices.

Diagnostic performance of [Ga]DOTATATE PET/CT, [F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma.

Objective: To compare the diagnostic performance of [Ga]DOTATATE PET/CT, [F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases.

Materials And Methods: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [Ga]DOTATATE PET/CT, [F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRI), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRI), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CT). Per-patient and per-lesion detection rates were calculated.

Phase II Study of Erdafitinib in Patients With Tumors With Amplifications: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol K1.

Purpose: Despite fibroblast growth factor receptor () inhibitors being approved in tumor types with select rearrangements or gene mutations, amplifications of represent the most common alteration across malignancies. Subprotocol K1 (EAY131-K1) of the National Cancer Institute-MATCH platform trial was designed to evaluate the antitumor efficacy of the oral inhibitor, erdafitinib, in patients with tumors harboring amplification.

Methods: EAY131-K1 was an open-label, single-arm, phase II study with central confirmation of presence of amplification in tumors.

Phase II Study of Erdafitinib in Patients With Tumors With Fibroblast Growth Factor Receptor Mutations or Fusions: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol K2.

Purpose: Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 mutations or fusions.

Methods: Central confirmation of tumor FGFR1-4 mutations or fusions was required for outcome analysis. Patients with urothelial carcinoma were excluded.

Phase II Study of Osimertinib in Patients With Epidermal Growth Factor Receptor Mutations: Results From the NCI-MATCH ECOG-ACRIN (EAY131) Trial Subprotocol E.

Purpose: The National Cancer Institute Molecular Analysis for Therapy Choice trial is a signal-finding genomically driven platform trial that assigns patients with any advanced refractory solid tumor, lymphoma, or myeloma to targeted therapies on the basis of next-generation sequencing results. Subprotocol E evaluated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with mutations.

Methods: Eligible patients had mutations (T790M or rare activating) and received osimertinib 80 mg once daily.