Crystal Lattice Analysis for 2D Nanomorphology Prediction of Phase-Separated Materials.

Spontaneous phase separation of materials is a powerful strategy to generate highly defined 2D nanomorphologies with novel properties and functions. Exemplary are such morphologies in block copolymers or amphiphilic systems, whose formation can be well predicted based on parameters such as volume fraction and shape factor. In contrast, the formation of 2D nanomorphologies is currently unpredictable in materials perfectly defined at the molecular level, in which crystallinity plays a significant role.

The [2Fe-2S] cluster of mitochondrial outer membrane protein mitoNEET has an O-regulated nitric oxide access tunnel.

The mitochondrial outer membrane iron-sulphur ([Fe-S]) protein mitoNEET has been extensively studied as a target of the anti-inflammatory and type-2 diabetes drug pioglitazone and as a protein affecting mitochondrial respiratory rate. Despite these extensive past studies, its molecular function has yet to be discovered. Here, we applied an interdisciplinary approach and discovered an explicit nitric oxide (NO) access site to the mitoNEET [2Fe-2S] cluster.

Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation.

Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age-linked lung inflammation.

Myotilin gene duplication causing late-onset myotilinopathy.

Background: myotilinopathy is a very rare inherited muscle disease that belongs to the group of myofibrillar myopathies. These diseases share a common alteration of the sarcomere organization at the level of the Z disk resulting in pathological protein aggregation, autophagic abnormalities, and ultimately muscle degeneration. Most reported cases are due to dominant missense mutations in the MYOT gene, two of which are largely recurrent.

Parenteral nutrition and bioelectrical impedance analysis estimated fat-free mass in adult patients with chronic intestinal failure: A descriptive cohort study.

Background: In patients with chronic intestinal failure, the content and type of parenteral nutrition are individually determined based on various factors, including body composition. In clinical practice, bioelectrical impedance analysis is used to assess body composition using standardized protocols. However, these protocols lack specific recommendations for patients receiving parenteral nutrition.

Carbapenemase-Producing Enterobacterales from Patients Arriving from Ukraine in Poland, March 2022-February 2023.

Introduction: Despite a scarcity of data, before 2022 Ukraine was already considered a high-prevalence country for carbapenemase-producing Enterobacterales (CPE), and the situation has dramatically worsened during the full-scale war with Russia. The aim of this study was to analyse CPEs isolated in Poland from victims of war in Ukraine.

Methods: The study included 65 CPE isolates from March 2022 till February 2023, recovered in 36 Polish medical centres from 57 patients arriving from Ukraine, differing largely by age and reason for hospitalisation.

Spatiotemporal Control Over Circadian Rhythms With Light.

Circadian rhythms are endogenous biological oscillators that synchronize internal physiological processes and behaviors with external environmental changes, sustaining homeostasis and health. Disruption of circadian rhythms leads to numerous diseases, including cardiovascular and metabolic diseases, cancer, diabetes, and neurological disorders. Despite the potential to restore healthy rhythms in the organism, pharmacological chronotherapy lacks spatial and temporal resolution.

Assessment of Coronary Microcirculation with High Frame-Rate Contrast-Enhanced Echocardiography.

Objective: Assessing myocardial perfusion in acute myocardial infarction is important for guiding clinicians in choosing appropriate treatment strategies. Echocardiography can be used due to its direct feedback and bedside nature, but it currently faces image quality issues and an inability to differentiate coronary macro- from micro-circulation. We previously developed an imaging scheme using high frame-rate contrast-enhanced ultrasound (HFR CEUS) with higher order singular value decomposition (HOSVD) that provides dynamic perfusion and vascular flow visualization.

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.

Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).

Exploring intra- and intergenomic variation in haplotype-resolved pangenomes.

With advances in long-read sequencing and assembly techniques, haplotype-resolved (phased) genome assemblies are becoming more common, also in the field of plant genomics. Computational tools to effectively explore these phased genomes, particularly for polyploid genomes, are currently limited. Here we describe a new strategy adopting a pangenome approach.

Prenatal polycyclic aromatic hydrocarbons exposure and child growth and adiposity: A longitudinal study.

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) during childhood has been associated with altered growth and adiposity in children. The effects of prenatal exposure to PAHs on developmental programming of growth and adiposity are still unknown.

Objective: To study the association of prenatal exposure to PAHs with early childhood growth and adiposity measures.

Combating cisplatin-resistant lung cancer using a coiled-coil peptides modified membrane fused drug delivery system.

Drug resistance to chemotherapy in treating cancers becomes an increasingly serious challenge, which leads to treatment failure and poor patient survival. Drug-resistant cancer cells normally reduce intracellular accumulation of drugs by controlling drug uptake and promoting drug efflux, which severely limits the efficacy of chemotherapy. To overcome this problem, a membrane fused drug delivery system (MF-DDS) was constructed to treat cisplatin (DDP)-resistant lung cancer (A549-DDP) by delivering DDP via membrane fusion using a complementary coiled-coil forming peptides (CPK/CPE).

Revising EU pharmaceutical legislation: will it foster drug repurposing?

Repurposing off-patent drugs can be a potential source of low-cost treatments for patients with unmet medical needs. Here, we review the proposed new European Union (EU) pharmaceutical legislation in which two articles address drug repurposing. We find certain barriers hindering the adoption of these new incentives by academic and not-for-profit stakeholders, including lack of knowledge on regulatory aspects, pharmacovigilance, and restrictions in data protection.

Pre-Hospital ECPR cost analysis and cost effectiveness modelling study.

Background: The use of extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) is increasing. Prehospital ECPR (PH-ECPR) for out-of-hospital cardiac arrest (OHCA) may improve both equity of access and outcomes but its cost effectiveness has yet to be determined.

Methods: Cost analyses of PH-ECPR was performed utilizing current PH-ECPR trial, NSW Ambulance Cardiac Arrest Registry (CAR), geospatial modelling and in-hospital costings data.

Pregnancy With a Stoma is Feasible, Though Associated With Manageable Complications.

Background: Inflammatory bowel disease (IBD) is often diagnosed in young adults, and therefore frequently coincides with pregnancy. Patients may require surgery that includes (temporary) stoma placement. Literature on the occurrence of stoma-complications during pregnancy and the effect on pregnancy outcomes is limited.

Vanzacaftor-tezacaftor-deutivacaftor for children aged 6-11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial.

Background: In phase 2 trials in people with cystic fibrosis aged 18 years and older, vanzacaftor-tezacaftor-deutivacaftor has been shown to be a safe and effective, once-daily cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Restoring normal CFTR function early in life has the potential to prevent manifestations of cystic fibrosis. We aimed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of vanzacaftor-tezacaftor-deutivacaftor in children with cystic fibrosis aged 6-11 years.

Evidence Supports the Validity and Reliability of Response Times from a Brief Survey as a Digital Biomarker for Processing Speed in a Large Panel Study.

Survey response times (RTs) have hitherto untapped potential to allow researchers to gain more detailed insights into the cognitive performance of participants in online panel studies. We examined if RTs recorded from a brief online survey could serve as a digital biomarker for processing speed. Data from 9,893 adults enrolled in the nationally representative Understanding America Study were used in the analyses.

Exploring Health Literacy among Adults with Hidradenitis Suppurativa.

Background: Health literacy plays an important role in the management of chronic and debilitating skin diseases like hidradenitis suppurativa (HS). Adequate health literacy empowers patients to understand their disease, manage it effectively, and make informed decisions about their health. Exploring the interplay between health literacy and HS is essential to improve healthcare outcomes in this population.

Estimation of potential denitrification and its spatiotemporal dynamics in seasonally inundated geomorphic units of a large tropical river using satellite data.

Denitrification in large tropical river systems is likely important for nitrogen retention estimates, but is limited by the need for measurements and the ability to scale these estimates to relate seasonal changes to river geomorphology and discharge. Geomorphic units (GUs), that describe the structure of a river system based on their inundation frequency and vegetation cover, may be useful to characterise features that influence denitrification rates. In this study, we tested the hypothesis that measurements of potential denitrification rate (PDR) using denitrification enzyme assays from different GUs could be used to1) relate PDR to soil, vegetation and different land use and land-cover (LULC) types as controlling factors and 2) that these characteristics could be assessed using remote sensing data to model PDR over a large spatial scale (along a 50 km reach) for the Padma River (Bangladesh).