Transplantation of a genetically modified porcine heart into a live human.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.

Single-nucleus transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration.

Bone regeneration is mediated by skeletal stem/progenitor cells (SSPCs) that are mainly recruited from the periosteum after bone injury. The composition of the periosteum and the steps of SSPC activation and differentiation remain poorly understood. Here, we generated a single-nucleus atlas of the periosteum at steady state and of the fracture site during the early stages of bone repair (https://fracture-repair-atlas.

Exploring and describing alcohol harm reduction interventions: a scoping review of literature from the past decade in the western world.

Context: Regular alcohol use is a predominant risk factor for disease, injury, and social harm. While robust evidence is advocating for implementing interventions to reduce the harms of illegal substance use, less literature is dedicated to identifying and understanding interventions aiming at reducing the various harms associated with alcohol.

Objectives: This review describes how alcohol harm reduction (AHR) interventions are currently conducted and analyzes the facilitators and barriers identified by the studies on their efficacy.

Clinician attitudes towards adoption of evidence-based practice: a nationwide multiprofessional cross-sectional study of child and adolescent mental health services in Sweden.

Background: Implementation of evidence-based practice (EBP) in child and adolescent mental health services (CAMHS) is a priority to improve service delivery and outcomes. Clinicians' EBP attitudes are likely to play a crucial role in implementation but are poorly understood. This study aimed to assess variation in EBP attitudes in a large national sample of CAMHS clinicians in Sweden, and to compare these findings to findings from the United States of America (USA).

Women, gender and drugs: between research and action.

This article is part of Harm Reduction Journal's special issue on harm reduction research in the francophone context and specifically the Harm Reduction Network (HARENE). After highlighting the history and current context of harm reduction for women in France, we present the results of four research studies addressing the links between gender and drugs which were presented in the book Espaces genrés des drogues. Parcours dans la fête, l'intimité et la réduction des risques ('Gendered Spaces of Drugs.

Evanescent point sources: application to microsphere-assisted super-resolution microscopy.

In the rigorous electromagnetic simulation of an imaging system, the evanescent waves from a point source or from a sample are naturally mixed with the propagative waves. Therefore, their contributions are difficult to distinguish. We present a point-source model made of only the evanescent waves.

Effectiveness evaluation of an organisational intervention, targeting pregnancy and addiction care professionals, among women who have just given birth in maternity wards and smoked tobacco during pregnancy (5A-QUIT-N): study protocol for a stepped-wedge cluster randomised trial.

Introduction: In 2021, among French women who smoked when they knew they were pregnant, 59% still smoked at the end of pregnancy. Support for pregnant women to stop smoking must include a structured organisational perspective. The main objective of the study is to evaluate the effectiveness of the 5A-QUIT-N organisational intervention on smoking cessation at delivery among pregnant women who smoke during pregnancy.

Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.

Background: The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS).

A new class of capsid-targeting inhibitors that specifically block HIV-1 nuclear import.

HIV-1 capsids cross nuclear pore complexes (NPCs) by engaging with the nuclear import machinery. To identify compounds that inhibit HIV-1 nuclear import, we screened drugs in silico on a three-dimensional model of a CA hexamer bound by Transportin-1 (TRN-1). Among hits, compound H27 inhibited HIV-1 with a low micromolar IC.

Multimodal analyses of immune cells during bone repair identify macrophages as a therapeutic target in musculoskeletal trauma.

Musculoskeletal traumatic injuries (MTI) involve soft tissue lesions adjacent to a bone fracture leading to fibrous nonunion. The impact of MTI on the inflammatory response to fracture and on the immunomodulation of skeletal stem/progenitor cells (SSPCs) remains unknown. Here, we used single-nucleus transcriptomic analyses to describe the immune cell dynamics after bone fracture and identified distinct macrophage subsets with successive pro-inflammatory, pro-repair and anti-inflammatory profiles.

Management of Patients With Cardiac Arrest Requiring Interfacility Transport: A Scientific Statement From the American Heart Association.

People who experience out-of-hospital cardiac arrest often require care at a regional center for continued treatment after resuscitation, but many do not initially present to the hospital where they will be admitted. For patients who require interfacility transport after cardiac arrest, the decision to transfer between centers is complex and often based on individual clinical characteristics, resources at the presenting hospital, and available transport resources. Once the decision has been made to transfer a patient after cardiac arrest, there is little direct guidance on how best to provide interfacility transport.

Multilevel barriers to guideline implementation: a nationwide multi-professional cross-sectional study within child and adolescent psychiatry.

Background: Despite efforts to promote guideline use, guideline adoption is often suboptimal due to failure to identify and address relevant barriers. Barriers vary not only between guidelines but also between settings, intended users, and targeted patients. Multi-professional guidelines are often used in child and adolescent mental health services (CAMHS), making the implementation process more difficult.

Single nuclei transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration.

Bone regeneration is mediated by skeletal stem/progenitor cells (SSPCs) that are mainly recruited from the periosteum after bone injury. The composition of the periosteum and the steps of SSPC activation and differentiation remain poorly understood. Here, we generated a single-nuclei atlas of the periosteum at steady-state and of the fracture site during early stages of bone repair ( https://fracture-repair-atlas.

Climate change vulnerability of Arctic char across Scandinavia.

Climate change is anticipated to cause species to shift their ranges upward and poleward, yet space for tracking suitable habitat conditions may be limited for range-restricted species at the highest elevations and latitudes of the globe. Consequently, range-restricted species inhabiting Arctic freshwater ecosystems, where global warming is most pronounced, face the challenge of coping with changing abiotic and biotic conditions or risk extinction. Here, we use an extensive fish community and environmental dataset for 1762 lakes sampled across Scandinavia (mid-1990s) to evaluate the climate vulnerability of Arctic char (Salvelinus alpinus), the world's most cold-adapted and northernly distributed freshwater fish.

Roadmap on Label-Free Super-Resolution Imaging.

Label-free super-resolution (LFSR) imaging relies on light-scattering processes in nanoscale objects without a need for fluorescent (FL) staining required in super-resolved FL microscopy. The objectives of this Roadmap are to present a comprehensive vision of the developments, the state-of-the-art in this field, and to discuss the resolution boundaries and hurdles which need to be overcome to break the classical diffraction limit of the LFSR imaging. The scope of this Roadmap spans from the advanced interference detection techniques, where the diffraction-limited lateral resolution is combined with unsurpassed axial and temporal resolution, to techniques with true lateral super-resolution capability which are based on understanding resolution as an information science problem, on using novel structured illumination, near-field scanning, and nonlinear optics approaches, and on designing superlenses based on nanoplasmonics, metamaterials, transformation optics, and microsphere-assisted approaches.

VR-assisted aggression treatment in forensic psychiatry: a qualitative study in patients with severe mental disorders.

Introduction: Improvements in virtual reality (VR) have made it possible to create realistic, virtual settings for behavioral assessment and skills training that cannot otherwise be accessed in a safe way in forensic psychiatric settings. VR interventions are under development but little is known how forensic psychiatric patients with severe mental disorders experience VR-assisted assessments or treatments.

Methods: The present study aimed to help fill this knowledge gap via qualitative interviews with seven patients with severe mental disorders at a high-security forensic psychiatric clinic who had completed the newly revised Virtual Reality Aggression Prevention Training (VRAPT).

Multimodal analyses of immune cells during bone repair identify macrophages as a therapeutic target in musculoskeletal trauma.

Unlabelled: Musculoskeletal traumatic injuries (MTI) involve soft tissue lesions adjacent to a bone fracture leading to fibrous nonunion. The impact of MTI on the inflammatory response to fracture and on the immunomodulation of skeletal stem/progenitor cells (SSPCs) remains unknown. Here, we used single cell transcriptomic analyses to describe the immune cell dynamics after bone fracture and identified distinct macrophage subsets with successive pro-inflammatory, pro-repair and anti-inflammatory profiles.

Access to psychological treatment for chronic cancer-related pain in Sweden.

Objectives: Cancer-related pain (CRP) is among the most frequent collateral effects of cancer, with chronic CRP, lasting at least 3 months, affecting >40% of cancer survivors. Evidence-based treatments, including pain-focused cognitive behavioral therapy (CBT), are available, but it appears that cancer patients/survivors are often poorly informed about CRP or the potential benefits of CBT for such pain. This study examined current experience of Swedish cancer patients/survivors in relation to CRP.

PERK modulation, with GSK2606414, Sephin1 or salubrinal, failed to produce therapeutic benefits in the SOD1G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) has been linked to overactivity of the protein kinase RNA-like ER kinase (PERK) branch of the unfolded protein response (UPR) pathway, both in ALS patients and mouse models. However, attempts to pharmacologically modulate PERK for therapeutic benefit have yielded inconsistent and often conflicting results. This study sought to address these discrepancies by comprehensively evaluating three commonly used, CNS-penetrant, PERK modulators (GSK2606414, salubrinal, and Sephin1) in the same experimental models, with the goal of assessing the viability of targeting the PERK pathway as a therapeutic strategy for ALS.

ψ(2S) Suppression in Pb-Pb Collisions at the LHC.

The production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.

Moderators of short- and long-term outcomes in panic control treatment and panic-focused psychodynamic psychotherapy.

Objective: The objective was to test the hypothesis that externalizing and internalizing helpfulness beliefs and learning styles at baseline moderate panic severity and overall mental illness as short-term and long-term outcomes of two panic-focused psychotherapies, Panic Control Treatment (PCT) and Panic-Focused Psychodynamic Psychotherapy (PFPP).

Method: Participants were 108 adults with DSM-IV Panic Disorder with or without Agoraphobia (PD/A) who were randomized to treatment in a trial of PCT and PFPP. Piece-wise/segmented multilevel modeling was used to test three-way interactions (Treatments × Moderator × Time), with participants and therapists as random factors.

Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H.

The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process).