Pediatric Advance Care Planning and Adolescent Preparedness and Quality of Life: An RCT.

Background And Objective: To evaluate the efficacy of Family-Centered Advance Care Planning for Teens With Cancer (FACE-TC) on adolescents' quality of life.

Methods: A clinical trial randomized adolescent-family dyads at a 2:1 ratio to either FACE-TC or control. FACE-TC dyads received 3 weekly 60-minute sessions: Lyon Pediatric Advance Care Planning Survey; Next Steps: Respecting Choices; and Five Wishes.

Psychosocial Support Needs and Preferences Among Family Caregivers of ICU Patients with Severe Acute Brain Injury: A Qualitative Thematic Analysis.

Background: Family caregivers of patients with severe acute brain injury (SABI) are at risk for clinically significant chronic emotional distress, including depression, anxiety, and posttraumatic stress. Existing psychosocial interventions for caregivers of intensive care unit (ICU) patients are not tailored to the unique needs of caregivers of patients with SABI, do not demonstrate long-term efficacy, and may increase caregiver burden. In this study, we explored the needs and preferences for psychosocial services among SABI caregivers to inform the development and adaptation of interventions to reduce their emotional distress during and after their relative's ICU admission.

The role of dynamic shape cues in the recognition of emotion from naturalistic body motion.

Human observers can often judge emotional or affective states from bodily motion, even in the absence of facial information, but the mechanisms underlying this inference are not completely understood. Important clues come from the literature on "biological motion" using point-light displays (PLDs), which convey human action, and possibly emotion, apparently on the basis of body movements alone. However, most studies have used simplified and often exaggerated displays chosen to convey emotions as clearly as possible.

Piloting total perioperative telemedicine for elective cholecystectomies for symptomatic cholelithiasis.

Background: Telemedicine has the potential to increase healthcare access while decreasing the environmental impact associated with providing care. We piloted total perioperative telemedicine (TPT) visits for evaluating patients with symptomatic cholelithiasis. We aimed to evaluate the feasibility and environmental impact of TPT by comparing the perioperative and environmental outcomes of patients participating in TPT to those undergoing traditional in-person preoperative evaluations.

Head and Neck Paraganglioma in Pacak-Zhuang Syndrome.

Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Brain Age Modeling and Cognitive Outcomes in Young Adults With and Without Sickle Cell Anemia.

Importance: Both sickle cell anemia (SCA) and socioeconomic status have been associated with altered brain structure and cognitive disability, yet precise mechanisms underlying these associations are unclear.

Objective: To determine whether brains of individuals with and without SCA appear older than chronological age and if brain age modeling using brain age gap (BAG) can estimate cognitive outcomes and mediate the association of socioeconomic status and disease with these outcomes.

Design, Setting, And Participants: In this cross-sectional study of 230 adults with and without SCA, individuals underwent brain magnetic resonance imaging (MRI) and cognitive assessment.

Delivering Guideline-Concordant Care for Patients With High-Risk HPV and Normal Cytologic Findings.

Importance: As US health care systems shift to human papillomavirus (HPV)-based cervical cancer screening, more patients are receiving positive high-risk non-16/18 genotype HPV results and negative for intraepithelial lesion or malignancy (NILM) cytological findings. Risk-based management guidelines recommend 2 consecutive negative annual results to return to routine screening.

Objective: To quantify patterns of surveillance testing and associated outcomes for patients after an HPV-positive results and NILM cytologic findings.

Lived Experiences of Patients Hospitalized With Acute Decompensated Heart Failure and Kidney Dysfunction.

Importance: For patients hospitalized with acute decompensated heart failure (ADHF), the presence of kidney dysfunction can substantially shape prognosis and treatment options. Yet little is known about the lived experiences of these medically vulnerable patients.

Objective: To elicit accounts of the illness and care experiences of patients currently or recently hospitalized with ADHF and kidney dysfunction in order to identify potential opportunities to improve care.

Pediatric erythromelalgia from multidisciplinary perspectives: a scoping review.

Erythromelalgia is a rare, chronic pain disorder characterized by the triad of intense burning sensation, warmth, and redness, primarily involving the hands and feet, and usually alleviated by cold and worsened by heat. The objective of this scoping review was to: 1) map the existing literature on erythromelalgia in youth, 2) identify knowledge gaps, and 3) inform directions for future research in pediatric erythromelalgia. One hundred and sixty-seven studies reporting 411 cases of childhood-onset erythromelalgia were identified.

Distinct molecular and clinical features of specific variants of KRAS codon 12 in pancreatic adenocarcinoma.

PURPOSE Oncogenic mutations in KRAS have been identified in > 85% of pancreatic ductal adenocarcinoma (PDAC) cases. G12D, G12V, and G12R are the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRAS G12D and G12R.

The differential impacts of equivalent gating-charge mutations in voltage-gated sodium channels.

Voltage-gated sodium (Nav) channels are pivotal for cellular signaling, and mutations in Nav channels can lead to excitability disorders in cardiac, muscular, and neural tissues. A major cluster of pathological mutations localizes in the voltage-sensing domains (VSDs), resulting in either gain-of-function, loss-of-function effects, or both. However, the mechanism behind this functional diversity of mutations at equivalent positions remains elusive.

Pasteurized waste milk vs. milk replacer at the same crude protein:metabolizable energy ratio with different energy sources (fat vs. lactose) to pre-weaning Holstein calves: Effects on growth performance, feeding behavior, and health.

The improved growth performance of calves at weaning results from an effective pre-weaning feeding strategy. The type and pasteurization process of liquid feed are among the most variable feeding practices affecting calves' growth and health. In previous studies that compared waste milk (WM) vs.

Decreasing miR-433-3p activity in the osteoblast lineage blunts glucocorticoid-mediated bone loss.

Glucocorticoid excess causes bone loss due to decreased bone formation and increased bone resorption; miR-433-3p is a miRNA that negatively regulates bone formation in male mice by targeting Runx2 as well as RNAs involved in Wnt, protein kinase A and endogenous glucocorticoid signaling. To examine the impact of miR-433-3p on glucocorticoid-mediated bone loss, transgenic mice expressing a miR-433-3p tough decoy inhibitor in the osteoblast lineage were administered prednisolone via slow-release pellets. Bone loss was greater in control mice treated with prednisolone compared with miR-433-3p tough decoy mice due to higher osteoclast activity in the controls.

Cost-Effectiveness of Noninvasive Colorectal Cancer Screening in Community Clinics.

Importance: Several noninvasive tests for colorectal cancer screening are available, but their effectiveness in settings with low adherence to screening and follow-up colonoscopy is not well documented.

Objective: To assess the cost-effectiveness of and outcomes associated with noninvasive colorectal cancer screening strategies, including new blood-based tests, in a population with low adherence to screening and ongoing surveillance colonoscopy.

Design, Setting, And Participants: The validated microsimulation model used for the decision analytical modeling study projected screening outcomes from 2025 to 2124 for a simulated cohort of 10 million individuals aged 50 years in 2025 and representative of a predominantly Hispanic or Latino patient population served by a Federally Qualified Health Center in Southern California.

Novel T Cell reactivities to Hybrid Insulin Peptides in Islet Autoantibody-Positive At-Risk Subjects.

Type 1 Diabetes (T1D) is an autoimmune disease mediated by autoreactive T cells. Our studies indicate that CD4 T cells reactive to Hybrid Insulin Peptides (HIPs) play a critical role in T cell-mediated beta-cell destruction. We have shown that HIPs form in human islets between fragments of the C-peptide and cleavage products of secretory granule proteins.

CooccurrenceAffinity: An R package for computing a novel metric of affinity in co-occurrence data that corrects for pervasive errors in traditional indices.

1. Analysis of co-occurrence data with traditional indices has led to many problems such as sensitivity of the indices to prevalence and the same value representing either a strong positive or strong negative association across different datasets. In our recent study (Mainali et al 2022), we revealed the source of the problems that make the traditional indices fundamentally flawed and unreliable-namely that the indices in common use have no target of estimation quantifying degree of association in the non-null case-and we further developed a novel parameter of association, alpha, with complete formulation of the null distribution for estimating the mechanism of affinity.

Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Genome-wide association study of urinary cadmium levels in current smokers from the multiethnic cohort study.

Background: Cadmium (Cd), classified as an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, is present in cigarette smoke. Recent studies have illustrated the potential role of genetics in influencing Cd biomarker levels.

Methods: We conducted a genome-wide association study (GWAS) of urinary Cd levels in 1977 current smokers from the Multiethnic Cohort Study, comprising participants from five different racial and ethnic groups.

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.

Growth of Private Equity and Hospital Consolidation in Primary Care and Price Implications.

Importance: Consolidation of physician practices by hospitals and private equity (PE) firms has increased rapidly. This trend is of particular importance within primary care. Despite its significance, there is no systematic evidence on the emerging trends in ownership affiliation of primary care physicians (PCPs) and its association with prices paid for physician services.

RSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia.

Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation.

Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients.

CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971).

Co-occurring Change in Electronic Nicotine Delivery System (ENDS) and Cigarette Harm Perceptions and Use in Young Adults.

Introduction: Use of electronic nicotine delivery systems (ENDS) may contribute to cigarette use and nicotine addiction by shifting perceptions and norms around tobacco, but little is known about whether or how ENDS use and norms are related to cigarette use and norms, particularly among young adults. This study tested two potential mechanisms by which END use may facilitate cigarette use: decreasing tobacco harm perceptions (desensitization) and increasing favorability of tobacco use (renormalization).

Method: Analyses included data from 2187 young adults in a longitudinal panel who reported any ENDS or combustible cigarette use at ages 21, 23, or 26.