Systematic conservation prioritization with the prioritizr R package.

Plans for expanding protected area systems (prioritizations) need to fulfill conservation objectives. They also need to account for other factors, such as economic feasibility and anthropogenic land-use requirements. Although prioritizations are often generated with decision support tools, most tools have limitations that hinder their use for decision-making.

Exploring Diagnostic and Therapeutic Odyssey in Pulmonary Arterial Hypertension: Insights from In-Depth Semi-Structured Interviews.

Introduction: Establishing a diagnosis is paramount in medical practice as it shapes patients' experiences and guides treatment. Patients grappling with rare diseases face a triple challenge: prolonged diagnostic journeys, limited responses to existing therapies, and the absence of effective monitoring tools. Genetic diagnosis often provides crucial diagnostic and prognostic information, opening up possibilities for genotype-targeted treatments and facilitating counselling and relative testing.

Reversal of pulmonary veno-occlusive disease phenotypes by inhibition of the integrated stress response.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension arising from EIF2AK4 gene mutations or mitomycin C (MMC) administration. The lack of effective PVOD therapies is compounded by a limited understanding of the mechanisms driving vascular remodeling in PVOD. Here we show that administration of MMC in rats mediates activation of protein kinase R (PKR) and the integrated stress response (ISR), which leads to the release of the endothelial adhesion molecule vascular endothelial (VE) cadherin (VE-Cad) in complex with RAD51 to the circulation, disruption of endothelial barrier and vascular remodeling.

Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.

Background: Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.

Methods: We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics.

Results: We identified 2 potentially protective gene network modules associated with vascular cells, and we validated , coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH.

The Effect of Palatoplasty on Growth.

Objectives: To assess the effect of palatoplasty on growth velocity in undernourished and nourished orally fed children with cleft palate.

Methods: A retrospective chart review was conducted using a data query with cleft-associated ICD-10 and ICD-9 codes to identify children who underwent cleft palate repair between 2006 and 2022 at a tertiary pediatric hospital. Data gathered included demographics, admission variables, weight gain, and weight percentile as per the WHO growth chart data.

Fluorinated perhexiline derivative attenuates vascular proliferation in pulmonary arterial hypertension smooth muscle cells.

Increased proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs) is recognised as a universal hallmark of pulmonary arterial hypertension (PAH), in part related to the association with reduced pyruvate dehydrogenase (PDH) activity, resulting in decreased oxidative phosphorylation of glucose and increased aerobic glycolysis (Warburg effect). Perhexiline is a well-recognised carnitine palmitoyltransferase-1 (CPT1) inhibitor used in cardiac diseases, which reciprocally increases PDH activity, but is associated with variable pharmacokinetics related to polymorphic variation of the cytochrome P450-2D6 (CYP2D6) enzyme, resulting in the risk of neuro and hepatotoxicity in 'slow metabolisers' unless blood levels are monitored and dose adjusted. We have previously reported that a novel perhexiline fluorinated derivative (FPER-1) has the same therapeutic profile as perhexiline but is not metabolised by CYP2D6, resulting in more predictable pharmacokinetics than the parent drug.

SEMA3G regulates BMP9 inhibition of VEGF-mediated migration and network formation in pulmonary endothelial cells.

Aims: Bone morphogenetic protein-9 (BMP9) is critical for bone morphogenetic protein receptor type-2 (BMPR2) signalling in pulmonary vascular endothelial cells. Furthermore, human genetics studies support the central role of disrupted BMPR2 mediated BMP9 signalling in vascular endothelial cells in the initiation of pulmonary arterial hypertension (PAH). In addition, loss-of-function mutations in BMP9 have been identified in PAH patients.

Newly formed dust within the circumstellar environment of SN Ia-CSM 2018evt.

Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line.

ATP13A3 variants promote pulmonary arterial hypertension by disrupting polyamine transport.

Aims: Potential loss-of-function variants of ATP13A3, the gene encoding a P5B-type transport ATPase of undefined function, were recently identified in patients with pulmonary arterial hypertension (PAH). ATP13A3 is implicated in polyamine transport but its function has not been fully elucidated. In this study, we sought to determine the biological function of ATP13A3 in vascular endothelial cells (ECs) and how PAH-associated variants may contribute to disease pathogenesis.

A magnetic massive star has experienced a stellar merger.

Massive stars (those ≥8 solar masses at formation) have radiative envelopes that cannot sustain a dynamo, the mechanism that produces magnetic fields in lower-mass stars. Despite this, approximately 7% of massive stars have observed magnetic fields, the origin of which is debated. We used multi-epoch interferometric and spectroscopic observations to characterize HD 148937, a binary system of two massive stars.

Unlocking the potential of genetic research in pulmonary arterial hypertension: Insights from clinicians, researchers, and study team.

Genetic research and testing are increasingly important for understanding and treating pulmonary arterial hypertension. We aimed to explore how attitudes toward genetic research among clinical and research teams impacted the engagement in genetic research and the integration of genetic insights into clinical practice. We conducted 53 semistructured interviews and focus groups with patients, clinicians, and researchers from nine UK Pulmonary Hypertension centers, who had genetic research experience.

Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism.

Chronic thromboembolic pulmonary hypertension involves the formation and nonresolution of thrombus, dysregulated inflammation, angiogenesis, and the development of a small-vessel vasculopathy. We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors. We conducted a genome-wide association study on 1,907 European cases and 10,363 European control subjects.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community.

Seasonal profile of common pharmaceuticals in edible bivalve molluscs.

Pharmaceuticals are recognised as environmental contaminants of emerging concern (CECs) due to their increasing presence in the aquatic environment, along with high bioactivity linked to their therapeutic use. Therefore, information on environmental levels is urgently required. This study examined the presence of a range of common pharmaceuticals in oysters and mussels intended for human consumption from England and Wales using stable isotope dilution tandem mass spectrometry.

Understanding what drives genetic study participation: Perspectives of patients, carers, and relatives.

Genetic research's growing importance in understanding pulmonary arterial hypertension (PAH) and developing effective treatments prompted the RAPID-PAH study. This study sought feedback from stakeholders who participated in two genomic studies to enhance genetic study delivery and clinical integration. Stakeholders from nine UK PH centres, representing various roles, ages, genders, and mutation statuses, took part in 53 semi-structured interviews and focus groups.

Timing of First Set of Pressure Equalization Tubes in Pediatric Patients With Cleft Deformities.

Objectives: Children with cleft palates often have comorbid eustachian tube dysfunction requiring pressure equalization tubes (PETs). PETs can relieve middle ear effusions that impede hearing. Ideal PET placement timing in this population is controversial.

A Case for Acute Proximal Row Carpectomy for Perilunate Injuries.

Background: Perilunate injuries are complex injuries typically arising from high-energy injuries to the wrist. Standard treatment involves open reduction and internal fixation with ligamentous reconstruction; however, outcomes are fraught with complications including pain, stiffness, and arthrosis. Several case reports have demonstrated the role of proximal row carpectomy as a salvage procedure for complex carpal trauma in the setting of significant cartilage injury or bone loss.

Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling causing premature death from right heart failure. Established DNA variants influence PAH risk, but susceptibility from epigenetic changes is unknown. We addressed this through epigenome-wide association study (EWAS), testing 865,848 CpG sites for association with PAH in 429 individuals with PAH and 1226 controls.

Adolescent, parent, and provider attitudes toward a machine learning based clinical decision support system for selecting treatment for youth depression.

Background: Machine learning based clinical decision support systems (CDSSs) have been proposed as a means of advancing personalized treatment planning for disorders, such as depression, that have a multifaceted etiology, course, and symptom profile. However, machine learning based models for treatment selection are rare in the field of psychiatry. They have also not yet been translated for use in clinical practice.

Protocol for a hybrid type 3 effectiveness-implementation trial of a pragmatic individual-level implementation strategy for supporting school-based prevention programming.

Background: For approximately one in five children who have social, emotional, and behavioral (SEB) challenges, accessible evidence-based prevention practices (EBPPs) are critical. In the USA, schools are the primary setting for children's SEB service delivery. Still, EBPPs are rarely adopted and implemented by front-line educators (e.