Patient-Reported Outcomes in the Phase III OASIS-HAE Study of Donidalorsen for Hereditary Angioedema.

Background: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, frequently severe swelling that negatively impacts patients' quality of life (QoL). In the phase III OASIS-HAE study (NCT05139810), donidalorsen reduced HAE attack rate, increased disease control, and improved QoL. Here, we report further analysis of donidalorsen's impact on QoL and other patient-reported outcomes (PROs).

Self-Adhesive and Reprocessable Ionogel Sensor from Controllable Ionized Corncob Cellulose.

In recent years, the disposal of agricultural lignocellulosic residues has been accompanied by problems such as resource waste and environmental pollution. Therefore, the development of valorization technologies has emerged as a strategic priority in sustainable materials science. This study pioneered the use of corncob cellulose as the substrate (a representative agricultural lignocellulosic residue) and transformed it into ionized cellulose by grafting methacryloxyethyl trimethyl ammonium chloride (DMC) via atom transfer radical polymerization (ATRP) and UV-initiated polymerization.

A preclinical state of Graves' ophthalmopathy characterized by hypoxia of T-cells identified via multi-omics analysis.

Context: A preclinical state of Graves' ophthalmopathy (pre-GO) exists during the progression from Graves' hyperthyroidism (GH) to GO.

Objective: To distinguish the pre-GO state and identify key pathways of T-cell immunity.

Methods: 24 GH (without ophthalmopathy within 6-month follow-up), 10 pre-GO (ophthalmopathy occurred within 6-month follow-up) and 21 GO patients were enrolled, and the transcription and DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) were generated.

Intensification of Ethylene Carbonate Synthesis via Microwave-Induced Phase-Change Cycles.

This study reports for the first time on the application of microwave (MW) heating under ambient pressure reflux conditions to intensify the transesterification reaction of ethylene glycol with dimethyl carbonate (DMC) for the synthesis of ethylene carbonate (EC), a relevant industrial compound for polycarbonate products, lubricants and li-ion batteries. Conventional heating (CH) methods often require high-temperature autoclave systems to achieve elevated temperatures and suppress vaporization of the reactant DMC (bp ≈ 90 °C). However, these systems usually entail extended reaction times and significant process cost.

ROCC/GOG-3043: a randomized controlled trial of robotic versus open surgery for early-stage cervical cancer.

Background: The Laparoscopic Approach to Cervical Cancer trial is the only randomized trial to date addressing the role of surgical approach in cervical cancer; however, this non-inferiority trial of minimally invasive surgery vs an open approach in patients undergoing radical hysterectomy for early-stage cervical cancer did not meet its primary end point of 4.5-year disease-free survival and was terminated early because of significantly worse disease-specific survival, overall survival, and locoregional recurrence in the minimally invasive surgery cohort.

Primary Objective: Our trial compares 3-year disease-free survival after robotic-assisted or abdominal radical or simple (in select cases) hysterectomy in early-stage cervical cancer.

Cooperative role of PACT and ADAR1 in preventing aberrant PKR activation by self-derived double-stranded RNA.

Double-stranded RNAs (dsRNAs) produced during viral infections are recognized by the innate immune sensor protein kinase R (PKR), triggering a host translation shutoff that inhibits viral replication and propagation. Given the harmful effects of uncontrolled PKR activation, cells must tightly regulate PKR to ensure that its activation occurs only in response to viral infections, not endogenous dsRNAs. Here, we use CRISPR-Translate, a FACS-based genome-wide CRISPR-Cas9 knockout screening method that exploits translation levels as a readout and identifies PACT as a key inhibitor of PKR during viral infection.

Outcomes Following Minimally Invasive Surgery for Intracerebral Hemorrhage in the AHA Get With The Guidelines-Stroke Registry.

Background: The efficacy of minimally invasive surgery (MIS) in improving outcomes after nontraumatic intracerebral hemorrhage (ICH) remains uncertain, with inconsistent findings from randomized clinical trials. Our objective was to evaluate the real-world impact of MIS on ICH outcomes using a nationally representative cohort.

Methods: We performed a retrospective cohort study of patients with a nontraumatic ICH enrolled in the American Heart Association Get With The Guidelines-Stroke Registry between January 1, 2011, and December 31, 2021.

Promoting Intermediate Stabilization and Coupling for Dimethyl Carbonate Electrosynthesis.

The electrocatalytic coupling of methanol and CO to produce dimethyl carbonate (DMC) is an attractive strategy for converting C resources into value-added products, while the controlled adsorption and coupling of two key intermediates, CO and OCH, have not been demonstrated yet. Herein, a heterointerface engineering strategy is developed to modulate intermediate adsorption and facilitate the C─O bond formation. By constructing a Pd and PdO heterostructure catalyst with abundant interfaces (designated as Pd/PdO-r), the Pd sites serve to stabilize CO and the electrophilic Pd sites can promote the OCH adsorption, thereby optimizing their spatial proximity and reactivity.

Olfaction, Eating Preference, and Quality of Life in Cystic Fibrosis Chronic Rhinosinusitis.

Objectives: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF) and chronic rhinosinusitis (CRS). OD is associated with impaired quality of life (QOL) and dietary alterations in certain non-CF populations. This study explored relationships between OD, QOL, and modulator use in PwCF.

Impact of adding palbociclib on treatment adherence to ongoing adjuvant endocrine treatment in the global randomized PALLAS randomized trial in patients with early breast cancer.

Purpose: Using patient-reported outcomes (PROs) and more objective measures, we evaluated adherence to adjuvant palbociclib and ET in the PALLAS trial, and the impact of palbociclib on ET adherence.

Methods: The open-label, global, phase 3 PALLAS trial randomized patients with hormone receptor-positive (HR+), HER2-negative stage II-III breast cancer (1:1) to either 26 cycles of palbociclib (125 mg/day for 21 days and then 7 days off) plus adjuvant ET, versus ET alone. After 23.

Preventing Cardiomyopathy in Duchenne Muscular Dystrophy: Long-Term Follow-Up of Patients in the Randomised, Placebo-Controlled Drug-Trial of Perindopril and Bisoprolol.

Introduction: It is uncertain whether using cardiac drugs prophylactically in combinations for DMD is better than ACE-inhibitor alone. Our previous study showed no differences in left ventricular function between perindopril-bisoprolol and matched placebo after 36 months.

Methods: This study aimed to determine whether heart measures diverged after 60-month total follow-up.

DMC-BH derivative DMC-GF inhibits the growth of glioma stem cells by targeting the TRIM33/SLC25A1/mitochondrial oxidative phosphorylation pathway.

Glioma stem cells (GSCs) exhibit significant resistance to conventional radiotherapy and chemotherapy, contributing to high recurrence rates in gliomas. Addressing this critical clinical need, we developed DMC-GF, a novel GLUT1-based curcumin derivative, to enhance brain specificity and metabolic stability compared to its predecessor DMC-BH. Pharmacokinetic studies in rats demonstrated that DMC-GF achieved an 8.

Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies.

Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infusion (300 mg IV) versus placebo. We present final safety and laboratory outcomes; primary outcomes were previously reported.

Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Purpose: To investigate the safety, tolerability, and efficacy of intravitreal injection of galegenimab, an anti-HtrA1 FAb, in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Phase 2, single-masked, randomized clinical trial.

Methods: Eligible GA patients with BCVA letter scores of ≥ 24 letters and baseline GA lesion size 2.

Selecting patients with sickle cell disease for gene addition or gene editing-based therapeutic approaches: Report on behalf of a joint EHA Specialized Working Group and EBMT Hemoglobinopathies Working Party consensus conference.

Sickle cell disease (SCD) remains associated with reduced life expectancy and poor quality of life despite improvements observed in the last decades mostly related to comprehensive care, use of hydroxycarbamide, screening to identify patients at risk of strokes, and implementation of safe transfusion protocols. The course of the disease is highly variable, making it difficult to predict severity and response to therapy. Allogeneic hematopoietic stem cell transplantation potentially provides a cure with a relatively low rate of complications, but few patients have an HLA-identical sibling.

A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study.

Introduction: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC).

Methods: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression.

Hereditary Angioedema with Normal C1 Inhibitor: an Updated International Consensus Paper on Diagnosis, Pathophysiology, and Treatment.

Hereditary angioedema (HAE) has been recognized for almost 150 years. The newest form of HAE, where C1 inhibitor levels are normal (HAE-nC1INH), was first described in 2000. Over the last two decades, new types of apparent non-mast cell-mediated angioedema with normal quantity and activity of C1INH have been described, in some cases with proven genetic pathogenic variants that co-segregate with angioedema expression within families.

Expert opinion on the integration of combination therapy into the treatment algorithm for the management of dyslipidaemia: the integration of ezetimibe and bempedoic acid may enhance goal attainment.

The clinically important link between LDL cholesterol (LDL - C) lowering and cardiovascular (CV) risk reduction is well-established and reflected in the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidaemia. They recommend a stepwise approach to reaching LDL - C goals, beginning with statin monotherapy at the highest tolerated dose. However, real-world data show a large gap between guideline LDL - C goal recommendations and their achievement in clinical practice.

Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial.

Historically, the treatment of patients with advanced stage or recurrent endometrial cancer included paclitaxel plus carboplatin. Immunotherapy in combination with chemotherapy resulted in improved clinical outcomes in several solid tumors. In the phase 3 NRG GY018 study, pembrolizumab plus chemotherapy significantly improved investigator-assessed progression-free survival (PFS; primary endpoint) versus placebo plus chemotherapy in patients with advanced/metastatic/recurrent endometrial cancer regardless of mismatch repair status.

Prediction of quality traits in packaged mango by NIR spectroscopy.

Packaging with paper bags is essential for protecting mangoes during growth, but strongly berries near infrared (NIR) spectral signals used for non-invasive analysis of their internal quality. This study focused on eliminating or minimizing the interference of paper bags on the NIR spectra of mangoes and developed innovative solutions to accurately assess mango firmness (FI), dry matter content (DMC), soluble solids content (SSC), and titratable acidity (TA). Specific NIR signals at around 1150-1250 nm and 2100-2400 nm were highlighted, which significantly reduced the precision of NIR predictions for these quality traits.

Impact of Multimorbidity on Mortality in Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

Background: How different combinations of comorbidities influence risk at the patient level and population level in patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction is unknown. We aimed to investigate the prevalence of different combinations of cardiovascular and noncardiovascular comorbidities (ie, multimorbidity) and associated risk of death at the patient level and population level.

Methods: Using patient-level data from the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) and PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction), we investigated the 5 most common cardiovascular and noncardiovascular comorbidities and the resultant 45 comorbidity pairs.

Use and safety of corticosteroid injections in joints and musculoskeletal soft tissue: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, and the International Pain and Spine Intervention Society.

Background: Intra-articular corticosteroid (IACS) injection and peri-articular corticosteroid injection are commonly used to treat musculoskeletal conditions. Results vary by musculoskeletal region, but most studies report short-term benefit with mixed results on long-term relief. Publications showed adverse events from single corticosteroid injections.

The Paratyphi A O-Antigen Glycoconjugate Vaccine Is Able to Induce Antibodies with Bactericidal Activity Against a Panel of Clinical Isolates.

Background: Typhoid and paratyphoid fevers represent a global health burden, especially in Southern Asia, exacerbated by the increase in antimicrobial resistance. While vaccines against Typhi have been successfully introduced, a vaccine against Paratyphi A is not available, yet. Efforts to develop an effective vaccine targeting both serovars are currently ongoing.

Reproductive Potential and Population Growth of the Worm (Clitellata: Enchytraeidae) Under Laboratory Conditions as Well as Regression Models.

The worm is a new pest injuring American ginseng . To explore its reproductive potential and then estimate its population dynamics, the authors conducted two related experiments: (1) measuring individual fecundity in its lifetime by rearing each of the parent adults alone in a wet sandy dish at 18 and 21 °C indoors; (2) testing population growth by rearing each of the parent adults together with its offspring for a time longer than two generations at 21 °C. In Experiment I, five dependent variables, namely daily mean cocoons (), cumulative cocoons (), eggs per cocoon (), daily mean eggs () and cumulative eggs (), were extracted, with each of them subject to a stepwise regression analysis on rearing time () and its power series as independent variables.