The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response.

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment.

Defining the Optimal Dose for 3-Dimensional Conformal Accelerated Partial Breast Irradiation: 15-Year Follow-Up of a Dose-Escalation Trial.

Purpose: Randomized trials have demonstrated similar local tumor control in patients treated with accelerated partial-breast irradiation (APBI) compared with whole-breast irradiation. However, the optimal APBI dose for maximizing tumor control and minimizing toxicity is uncertain.

Methods And Materials: We enrolled patients ≥18 years of age with grade 1 or 2 ductal carcinoma in situ or stage I invasive breast cancer and resection margins ≥2 mm between 2003 and 2011 to a sequential dose-escalation trial using 3-dimensional conformal external beam APBI giving twice daily 4 Gy fractions with total doses of 32 Gy, 36 Gy, and 40 Gy.

Growth Differentiation Factor-15 Is Associated With Congestion-Related Anorexia and Weight Loss in Advanced Heart Failure.

Background: Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy.

Objectives: This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF).

Methods: In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with Heart Failure Questionnaire, and right heart catheterization.

Variations in Revascularization Strategies for Chronic Limb-Threatening Ischemia: A Nationwide Analysis of Medicare Beneficiaries.

Background: Recent data support both surgical-first and endovascular-first revascularization approaches for chronic limb-threatening ischemia (CLTI), but hospital-based practices are poorly described.

Objectives: This aim of this study was to characterize contemporary variations and outcomes associated with each strategy among U.S.

Inpatient Hospitalizations for COVID-19 Among Patients With Prader-Willi Syndrome: A National Inpatient Sample Analysis.

Prader-Willi syndrome (PWS) is a genetic disorder associated with baseline respiratory impairment caused by multiple contributing etiologies. While this may be expected to increase the risk of severe COVID-19 infections in PWS patients, survey studies have suggested paradoxically low disease severity. To better characterize the course of COVID-19 infection in patients with PWS, this study analyses the outcomes of hospitalizations for COVID-19 among patients with and without PWS.

Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study.

Objective: To compare the effectiveness and safety of budesonide-glycopyrrolate-formoterol, a twice daily metered dose inhaler, and fluticasone-umeclidinium-vilanterol, a once daily dry powder inhaler, in patients with chronic obstructive pulmonary disease (COPD) treated in routine clinical practice.

Design: New user cohort study.

Setting: Longitudinal commercial US claims data.

Physical and neurophysiological maturation associated with ADHD among previously institutionalized children: a randomized controlled trial.

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental outcome among children with a history of early institutional care. Prior research on institutionalized children suggested that accelerated physical growth in childhood is a risk factor for ADHD outcomes.

Methods: The current study examined physical and neurophysiological growth trajectories among institutionalized children randomized to foster care treatment (n = 59) or care as usual (n = 54), and never institutionalized children (n = 64) enrolled in the Bucharest Early Intervention Project (NCT00747396, clinicaltrials.

Injectable Estradiol Use in Transgender and Gender-Diverse Individuals in the U.S.: A Multicenter Retrospective Study.

Context: Guidelines for use of injectable estradiol esters (valerate [EV] and cypionate [EC]) among transgender and gender diverse (TGD) individuals designated male at birth vary considerably, with many providers noting supraphysiologic serum estradiol concentrations based on current dosing recommendations.

Objectives: 1. Determine dose of injectable estradiol (subcutaneous [SC] and intramuscular [IM]) needed to reach guideline-recommended estradiol concentrations for TGD adults using EC/EV.

WS/MHS PdTe/Si Mixed-Dimensional Heterojunction as Ultra-Broadband Photodetector for Health and Safety Monitoring.

Ultra-broadband photodetectors (UB-PDs) are essential in medical applications, public safety monitoring, and various other fields. However, developing UB-PDs covering multiple bands from ultraviolet to medium infrared remains a challenge due to material limitations. Here, a mixed-dimensional heterojunction composed of 2D WS/monodisperse hexagonal stacking (MHS) 3D PdTe particles on 3D Si is proposed, capable of detecting light from 365 to 9600 nm.

Endothelial Glycocalyx Damage and Arterial Thickness in Patients with Retinal Vein Occlusion (RVO).

: Retinal vein occlusion (RVO) is a relatively uncommon condition with a complex pathophysiology. However, its association with traditional cardiovascular risk factors is well established. In this study, we compared arterial stiffness and endothelial function between patients with RVO and healthy controls.

A Digital Phenotypic Assessment in Neuro-Oncology (DANO): A Pilot Study on Sociability Changes in Patients Undergoing Treatment for Brain Malignancies.

Background: The digital phenotyping tool has great potential for the deep characterization of neurological and quality-of-life assessments in brain tumor patients. Phone communication activities (details on call and text use) can provide insight into the patients' sociability.

Methods: We prospectively collected digital-phenotyping data from six brain tumor patients.

Association of Serum Polyunsaturated Fatty Acids (PUFAs) and Children's Dietary Inflammatory Index (C-DII) with Recurrent Respiratory Infections in Children: A Cross-Sectional Study.

To assess the associations between serum and dietary polyunsaturated fatty acids (PUFAs), as well as the inflammatory potential of diet measured by the Children's Dietary Inflammatory Index (C-DII), and recurrent respiratory infections (RRIs) in children. We enrolled 44 children aged 3-16 years with RRIs and 44 healthy controls. Dietary intake was assessed using a 7-day food record from which PUFA intake and C-DII were calculated.

Metabolic Adaptation and Its Determinants in Adolescents Two Years After Sleeve Gastrectomy.

Weight loss is associated with reductions in resting energy expenditure (REE), which are impacted by changes in body composition following sleeve gastrectomy (SG). Current data regarding changes in measured REE (mREE) and metabolic adaptation in adolescents after SG are limited. We evaluated changes in mREE, metabolic adaptation, and body composition in youths after SG vs.

Targeting CD200 in Breast Cancer: Opportunities and Challenges in Immunotherapeutic Strategies.

One of the key factors that contribute to tumor progression and resistance is the immunosuppressive microenvironment of the tumor. CD200 is a recently identified cell surface glycoprotein recognized as an important molecule in breast cancer for its versatile modulation of the immune response via its receptor, CD200R. The interaction between CD200 and CD200R suppresses the immune activities against tumor cells and allows them to be undetected and, in doing so, to escape from the destructive capability of the immune cells.

Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.

Prime editing (PE) is a CRISPR-based tool for genome engineering that can be applied to generate human induced pluripotent stem cell (hiPSC)-based disease models. PE technology safely introduces point mutations, small insertions, and deletions (indels) into the genome. It uses a Cas9-nickase (nCas9) fused to a reverse transcriptase (RT) as an editor and a PE guide RNA (pegRNA), which introduces the desired edit with great precision without creating double-strand breaks (DSBs).

Orphanhood and caregiver death among children in the United States by all-cause mortality, 2000-2021.

Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and prevalence among US children aged 0-17 years between 2000 and 2021 by cause, child age, race and ethnicity, sex of deceased parent and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate that 2.

Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms.

Three monoclonal antibodies directed against specific forms of the amyloid-β (Aβ) peptide have been granted accelerated or traditional approval by the FDA as treatments for Alzheimer disease, representing the first step towards bringing disease-modifying treatments for this disease into clinical practice. Here, we review the detection, underlying pathophysiological mechanisms and clinical implications of amyloid-related imaging abnormalities (ARIA), the most impactful adverse effect of anti-Aβ immunotherapy. ARIA appears as regions of oedema or effusions (ARIA-E) in brain parenchyma or sulci or as haemorrhagic lesions (ARIA-H) in the form of cerebral microbleeds, convexity subarachnoid haemorrhage, cortical superficial siderosis or intracerebral haemorrhage.

The genomic architecture of circulating cytokine levels points to drug targets for immune-related diseases.

Circulating cytokines orchestrate immune reactions and are promising drug targets for immune-mediated and inflammatory diseases. Exploring the genetic architecture of circulating cytokine levels could yield key insights into causal mediators of human disease. Here, we performed genome-wide association studies (GWAS) for 40 circulating cytokines in meta-analyses of 74,783 individuals.

Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.

Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim.

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.

Recent developments in myeloid immune modulation in cancer therapy.

Myeloid cells play a crucial dual role in cancer progression and response to therapy, promoting tumor growth, enabling immune suppression, and contributing to metastatic spread. The ability of these cells to modulate the immune system has made them attractive targets for therapeutic strategies aimed at shifting their function from tumor promotion to fostering antitumor immunity. Therapeutic approaches targeting myeloid cells focus on modifying their numbers, genetics, metabolism, and interactions within the tumor microenvironment.

Frontal Paraventricular Cysts: Refined Definitions and Outcomes.

Background And Purpose: Frontal paraventricular cystic changes have a varied etiology that includes connatal cysts, subependymal pseudocysts, necrosis, and enlarged perivascular spaces. These may be difficult to distinguish by neuroimaging and have a variety of associated prognoses. We aim to refine the neuroimaging definition of frontal horn cysts and correlate it with adverse clinical conditions.

Clinically significant hemoptysis and all-cause mortality in patients with nontuberculous mycobacterial pulmonary disease.

Background: Hemoptysis is one of the major symptoms in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its prevalence, incidence, and impact on long-term prognosis remain uncertain. We evaluated the incidence of clinically significant hemoptysis, and determined its association with mortality in patients with NTM-PD.