New therapies to treat cardiac amyloidosis.

Purpose Of Review: Review advancements in therapies for transthyretin (ATTR-CM) and immunoglobulin light chain (AL-CM) cardiac amyloidosis.

Recent Findings: In ATTR-CM, tafamidis remains the cornerstone therapy, with Food and Drug Administration (FDA) approval for over 5 years. Acoramidis, another transthyretin stabilizer, has very recently been FDA-approved following positive results in the ATTRibute-CM trial.

Electrical impedance tomography meets reduced order modelling: a framework for faster and more reliable electrical conductivity estimations.

Inclusion of individualised electrical conductivities of head tissues is crucial for the accuracy of electrical source imaging techniques based on electro/magnetoencephalography and the efficacy of transcranial electrical stimulation. Parametric electrical impedance tomography (pEIT) is a method to cheaply and non-invasively estimate them using electrode arrays on the scalp to apply currents and measure the resulting potential distribution. Conductivities are then estimated by iteratively fitting a forward model to the measurements, incurring a prohibitive computational cost that is generally lowered at the expense of accuracy.

Nasal CPAP increases alveolar number in a rhesus monkey model of moderate prematurity.

Rationale: Most premature human infants are born in the moderate to late preterm (MLP) range, ≥30 to <37 weeks gestation and demonstrate increased incidence of wheeze and respiratory illness as they age. Animal models suggest that mechanical lung distention stimulates lung growth and alveolar development. To determine if nasal continuous positive airway pressure (nCPAP) influences MLP infant lung development, we developed a rhesus monkey model of moderate prematurity, randomized to 9 days of nCPAP or sham nCPAP.

Two-year outcomes using fast-acting sub-perception therapy for spinal cord stimulation: results of a real-world multicenter study in the United States.

Background: Fast-acting Sub-perception Therapy (FAST) is a novel spinal cord stimulation (SCS) modality delivering paresthesia-free pain relief. Our study evaluated the longer-term, real-world impact of FAST on chronic pain.

Research Design And Methods: As part of a multicenter, real-world, consecutive case series, we retrospectively identified patients who used FAST-SCS and analyzed their data.

A power dependence model of the impact of leader impostorism on supervisor support and undermining: The moderating role of power distance.

Leaders, often perceived as possessing exceptional confidence and competence, are not immune to feelings of self-doubt. Leader impostorism describes the experience that one's attributes, experiences, skills, and abilities fall short of the standards expected in the leadership role, resulting in a sense of deception in fulfilling leadership responsibilities. While existing research has examined the antecedents and individual outcomes of leader impostorism, its implications for leaders' treatment of subordinates remain largely unexplored.

Nonbonded Molecular Interaction Controls Aggregation Kinetics of Hydrophobic Molecules in Water.

Molecular aggregation frequently occurs during material synthesis, cellular processes, and drug delivery systems, often resulting in decreased performance and efficiency. One major reason for such aggregation in an aqueous solution is hydrophobicity. While the basic understanding of the aggregation process of hydrophobic molecules from a thermodynamic standpoint is known, the present literature lacks a connection between the aggregation kinetics and the molecular basis of hydrophobicity.

Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Trifunctional lipid derivatives: PE's mitochondrial interactome.

Phosphatidylethanolamine (PE) is a ubiquitous lipid species in higher eukaryotes. Here, we synthesized a multifunctionalized PE derivative (1) designed to identify PE-binding proteins in intact cells through photo-crosslinking and subsequent isolation and proteomic analysis of the PE-protein conjugates. We show that the tool is also useful for tracking PE translocation to mitochondria after uncaging.

Coexisting Calcific Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Real-World Evaluation of Clinical Characteristics and Outcomes.

Background: The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and aortic stenosis (AS) is increasingly recognized, but the clinical consequences are unclear. We aimed to characterize clinical outcomes in AS plus ATTR-CA compared with only AS or ATTR-CA.

Methods And Results: In a retrospective cohort study, patients with AS only, ATTR-CA only, or AS plus ATTR-CA were identified using all-payer claims data (2015-2021).

Welfare Status in Dairy Cows during Confined and Grazing Periods in the North American Pacific Northwest using Blood Parameters and Visual Assessments.

Grazing is usually associated with higher well-being in dairy cows. However, current research on the welfare of grazing cows lacks validation via blood profiling. We monitored four dairy farms that seasonally graze in the temperate North American Pacific Northwest, USA, to address this gap.

Electrical Heterogeneity in Hispanic Background Subpopulations: The HCHS/SOL.

Background: The Hispanic/Latino population is not uniform. Prevalence and clinical outcomes of cardiac arrhythmias in ethnic background subgroups are variable, but the reasons for differences are unclear. Vectorcardiographic Global Electrical Heterogeneity (GEH) has been shown to be associated with adverse cardiovascular outcomes.

Ground Reaction Forces and Joint Moments Predict Metabolic Cost in Physical Performance: Harnessing the Power of Artificial Neural Networks.

Understanding metabolic cost through biomechanical data, including ground reaction forces (GRFs) and joint moments, is vital for health, sports, and rehabilitation. The long stabilization time (2-5 min) of indirect calorimetry poses challenges in prolonged tests. This study investigated using artificial neural networks (ANNs) to predict metabolic costs from the GRF and joint moment time series.

Divergent Transport Dynamics of Alkylated versus Unsubstituted Polycyclic Aromatic Hydrocarbons at the Air-Water and Sediment-Water Interfaces at a Legacy Creosote Site.

Alkylated polycyclic aromatic hydrocarbons (PAHs) are abundant constituents of many PAH mixtures and contribute to risk at contaminated sites. Despite their abundance, the movement of alkylated PAHs remains understudied relative to unsubstituted PAHs. In the present study, passive sampling devices were deployed in the air, water, and sediments at 11 locations across multiple seasons to capture spatial and temporal variability in the abundance and movement of alkylated PAHs at a Brownsfield creosote site in Oregon, USA.

The potential role of tumor deposits in the prognosis and TNM staging for colorectal cancer.

Background: Tumor deposits (TDs) can impact proper staging of cancer, which is crucial for discussing prognosis and determining the appropriate treatment plan. Our study aimed to correlate how TDs influence prognosis of resected colorectal cancer (CRC) and how to optimize tumor-node-metastasis (TNM) staging with respect to TDs for clinical decision-making.

Methods: A retrospective analysis was performed on 611 patients with CRC treated in Jiangsu Cancer Hospital from January 1, 2010 to December 31, 2020 among whom 197 had TDs.

Cognitive Remediation to Facilitate Independent Living in Persons With Serious Mental Illness.

Many people with serious mental illness (SMI) experience cognitive disabilities and poor independent living skills which limit their ability to live independently in the community. This study examined the feasibility and initial effectiveness of integrating a new cognitive remediation program, Thinking Skills for Life (TSL), into independent living skills training programs in four secure residential treatment facilities (SRTFs) to facilitate discharge to more independent living situations. Participants were 30 individuals in the SRTF, of whom 11 were forensically committed to the SRTF.

An Expert Consensus Statement for Implementing Cognitive Behavioral Therapy for Nightmares in Adults.

Objectives: Research supports cognitive behavioral therapies for nightmares (CBT-N) in adults. However, the nuances of implementation and unstandardized nomenclature for treatment components has created confusion in the field. To provide clarification, an expert consensus panel convened to review treatment manual components and to develop guidelines for the standardized implementation and terminology of CBT-N.

Causal analysis for multivariate integrated clinical and environmental exposures data.

Electronic health records (EHRs) provide a rich source of observational patient data that can be explored to infer underlying causal relationships. These causal relationships can be applied to augment medical decision-making or suggest hypotheses for healthcare research. In this study, we explored a large-scale EHR dataset on patients with asthma or related conditions (N = 14,937).

The human and non-human primate developmental GTEx projects.

Many human diseases are the result of early developmental defects. As most paediatric diseases and disorders are rare, children are critically underrepresented in research. Functional genomics studies primarily rely on adult tissues and lack critical cell states in specific developmental windows.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Addition of an NK1 receptor antagonist to standard antiemetic prophylaxis in patients with B-cell lymphoma receiving EPOCH.

Introduction: Data on the optimal management of patients with hematologic malignancies and chemotherapy-induced nausea and vomiting (CINV) are lacking, particularly for multiday chemotherapy regimens. We report our institutional experience in patients with B-cell lymphoma receiving multiday dose-adjusted R-EPOCH chemotherapy utilizing two CINV prophylaxis strategies.

Methods: We performed a retrospective, single-center, cohort study evaluating hospitalized patients with aggressive non-Hodgkin B-cell lymphoma receiving DA-R-EPOCH (April 2016 to October 2022).