Parallel EEG-fNIRS assessments of covert cognition in behaviorally non-responsive ICU patients: A multi-task feasibility study in a case of acute motor sensory axonal neuropathy.

Background: Repeat neurological assessment is standard in cases of severe acute brain injury. However, conventional measures rely on overt behavior. Unfortunately, behavioral responses may be difficult or impossible for some patients.

Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.

Purpose: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.

Methods: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS).

Regional scale diversity and distribution of soil inhabiting Tetracladium.

The genus Tetracladium has historically been regarded as an aquatic hyphomycete. However, sequencing of terrestrial ecosystems has shown that Tetracladium species might also be terrestrial soil and plant-inhabiting fungi. The diversity of Tetracladium species, their distribution across ecosystems, and the factors that shape community composition remain largely unknown.

A qualitative study of perceptions of the care pathway for familial hypercholesterolemia: screening, diagnosis, treatment, and family cascade screening.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic condition that carries increased risk for premature atherosclerotic cardiovascular disease, cardiovascular events, and death. Due to low uptake of evidence-based practices, up to 80% of FH patients remain undiagnosed and most are undertreated. This project aimed to understand patient and clinician perceptions across the care pathway of evidence-based diagnosis and treatment of FH, to inform implementation strategy design for two clinical trials seeking to increase evidence-based care.

Normal tissue transcriptional signatures for tumor-type-agnostic phenotype prediction.

Cancer transcriptional patterns reflect both unique features and shared hallmarks across diverse cancer types, but whether differences in these patterns are sufficient to characterize the full breadth of tumor phenotype heterogeneity remains an open question. We hypothesized that these shared transcriptomic signatures reflect repurposed versions of functional tasks performed by normal tissues. Starting with normal tissue transcriptomic profiles, we use non-negative matrix factorization to derive six distinct transcriptomic phenotypes, called archetypes, which combine to describe both normal tissue patterns and variations across a broad spectrum of malignancies.

Global Health Priority Box─Proactive Pandemic Preparedness.

The coronavirus pandemic outbreak of 2019 highlighted the critical importance of preparedness for current and future public health threats (https://www.mmv.org/mmv-open/global-health-priority-box/about-global-health-priority-box).

Predictors of response to CDK4/6i retrial after prior CDK4/6i failure in ER+ metastatic breast cancer.

After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution.

Design and rationale of penn medicine healthy heart, a randomized trial of effectiveness of a centrally organized approach to blood pressure and cholesterol improvement among patients at elevated risk of atherosclerotic cardiovascular disease.

Rationales: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of nonclinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies.

Resistance to high-fat diet-induced weight gain in transgenic mice overexpressing human wild-type α-synuclein: A model for metabolic dysfunction in Parkinson's disease.

Unintentional weight loss, primarily due to the loss of fat mass rather than muscle mass, is common among patients with Parkinson's disease (PD) and is associated with poor quality of life and accelerated disease progression. Since transgenic mice overexpressing human wild-type α-synuclein (α-Syn mice) are modestly leaner than control mice, and since diabetes, a metabolic disorder, is a major risk factor for PD, we reasoned that high-fat diet-induced diabetes/metabolic dysregulation in α-Syn mice may serve as a robust tool for exploring how early α-synuclein pathology contributes to metabolic dysregulation, leading to weight loss in PD. Thus, α-Syn and age-matched controls were fed a high-fat diet (HFD) chow (60% fat calories) for four months.

Tumor suppressor heterozygosity and homologous recombination deficiency mediate resistance to front-line therapy in breast cancer.

The co-occurrence of germline and somatic oncogenic alterations is frequently observed in breast cancer, but their combined biologic and clinical significance has not been evaluated. To assess the role of germline-somatic interactions on outcomes in routine practice, we developed an integrated clinicogenomic pipeline to analyze the genomes of over 4,500 patients with breast cancer. We find that germline (g) -associated tumors are enriched for loss-of-function mutations and manifest poor outcomes on standard-of-care, front-line CDK4/6 inhibitor (CDK4/6i) combinations.

Early Circulating Tumor DNA Shedding Kinetics for Prediction of Platinum Sensitivity in Patients With Small Cell Lung Cancer.

Purpose: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity.

Materials And Methods: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions.

Functional near-infrared spectroscopy: A novel tool for detecting consciousness after acute severe brain injury.

Recent advancements in functional neuroimaging have demonstrated that some unresponsive patients in the intensive care unit retain a level of consciousness that is inconsistent with their behavioral diagnosis of awareness. Functional near-infrared spectroscopy (fNIRS) is a portable optical neuroimaging method that can be used to measure neural activity with good temporal and spatial resolution. However, the reliability of fNIRS for detecting the neural correlates of consciousness remains to be established.

Investigating racial and gender disparities in virtual randomized clinical trial enrollment: Insights from the BE ACTIVE study.

Randomized clinical trials (RCTs) often suffer from a lack of representation from historically marginalized populations, and it is uncertain whether virtual RCTs (vRCTs) enhance representativeness or if elements of their consent and enrollment processes may instead contribute to underrepresentation of these groups. In this study, we aimed to identify disparities in enrollment demographics in a vRCT, the BE ACTIVE study, which recruited patients within a single health system. We discovered that the proportions of eligible patients who were randomized differed significantly by gender and race/ethnicity (men 1.

The mitochondrial pyruvate carrier regulates adipose glucose partitioning in female mice.

Objective: The mitochondrial pyruvate carrier (MPC) occupies a critical node in intermediary metabolism, prompting interest in its utility as a therapeutic target for the treatment of obesity and cardiometabolic disease. Dysregulated nutrient metabolism in adipose tissue is a prominent feature of obesity pathophysiology, yet the functional role of adipose MPC has not been explored. We investigated whether the MPC shapes the adaptation of adipose tissue to dietary stress in female and male mice.

FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.

Acquired resistance to PARP inhibitors (PARPi) remains a treatment challenge for BRCA1/2-mutant breast cancer that drastically shortens patient survival. Although several resistance mechanisms have been identified, none have been successfully targeted in the clinic. Using new PARPi-resistance models of Brca1- and Bard1-mutant breast cancer generated in-vivo, we identified FLT1 (VEGFR1) as a driver of resistance.

6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking.

A transdiagnostic examination of cognitive heterogeneity in children and adolescents with neurodevelopmental disorders.

Children and adolescents with neurodevelopmental disorders demonstrate extensive cognitive heterogeneity that is not adequately captured by traditional diagnostic systems, emphasizing the need for alternative assessment and classification techniques. Using a transdiagnostic approach, a retrospective cohort study of cognitive functioning was conducted using a large heterogenous sample ( = 1529) of children and adolescents 7 to 18 years of age with neurodevelopmental disorders. Measures of short-term memory, verbal ability, and reasoning were administered to participants with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), comorbid ADHD/ASD, and participants without neurodevelopmental disorders (non-NDD) using a 12-task, web-based neurocognitive testing battery.

Dose dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple negative breast cancer.

The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included.

Sex-dependent adipose glucose partitioning by the mitochondrial pyruvate carrier.

Objective: The mitochondrial pyruvate carrier (MPC) occupies a critical node in intermediary metabolism, prompting interest in its utility as a therapeutic target for the treatment of obesity and cardiometabolic disease. Dysregulated nutrient metabolism in adipose tissue is a prominent feature of obesity pathophysiology, yet the functional role of adipose MPC has not been explored. We investigated whether the MPC shapes the adaptation of adipose tissue to dietary stress in female and male mice.