Inhibiting triggering receptor expressed on myeloid cells 1 signaling to ameliorate skin fibrosis.

Systemic sclerosis (SSc) is characterized by immune system failure, vascular insult, autoimmunity, and tissue fibrosis. TGF-β is a crucial mediator of persistent myofibroblast activation and aberrant extracellular matrix production in SSc. The factors responsible for this are unknown.

In situ observations of large-amplitude Alfvén waves heating and accelerating the solar wind.

After leaving the Sun's corona, the solar wind continues to accelerate and cools, but more slowly than expected for a freely expanding adiabatic gas. Alfvén waves are perturbations of the interplanetary magnetic field that transport energy. We use in situ measurements from the Parker Solar Probe and Solar Orbiter spacecraft to investigate a stream of solar wind as it traverses the inner heliosphere.

Closed magnetic topology in the Venusian magnetotail and ion escape at Venus.

Venus, lacking an intrinsic global dipole magnetic field, serves as a textbook example of an induced magnetosphere, formed by interplanetary magnetic fields (IMF) enveloping the planet. Yet, various aspects of its magnetospheric dynamics and planetary ion outflows are complex and not well understood. Here we analyze plasma and magnetic field data acquired during the fourth Venus flyby of the Parker Solar Probe (PSP) mission and show evidence for closed topology in the nightside and downstream portion of the Venus magnetosphere (i.

Mediation of collisionless turbulent dissipation through cyclotron resonance.

The dissipation of turbulence in astrophysical systems is fundamental to energy transfer and heating in environments ranging from the solar wind and corona to accretion disks and the intracluster medium. Although turbulent dissipation is relatively well understood in fluid dynamics, astrophysical plasmas often exhibit exotic behaviour, arising from the lack of interparticle collisions, which complicates turbulent dissipation and heating in these systems. Recent observations by NASA's Parker Solar Probe mission in the inner heliosphere have shed new light on the role of ion cyclotron resonance as a potential candidate for turbulent dissipation and plasma heating.

The impact of leadership style in team-based primary care - staff satisfaction and motivation.

Background: Leadership styles, beliefs, and behaviours are an important and critical component to the delivery of quality care in any primary care organisation. The human resource crisis in health care has resulted in greater investments in team-based care; however, some leaders may not have experience working in team-based settings.

Aim: To explore what leadership characteristics, styles, and behaviours were most conducive to employee satisfaction, motivation, and delivery of care in a team-based primary care setting.

Comparison of ultrasound-guided paravertebral block versus erector spinae plane block for postoperative analgesia after percutaneous nephrolithotomy - A randomised, double-blind, controlled study.

Background And Aims: Paravertebral block (PVB) is the regional anaesthesia of choice for percutaneous nephrolithotomy (PCNL). Erector spinae plane block (ESPB) is also effective for the same. This study aims to compare the analgesic efficacy and ease of performing PVB or ESPB for PCNL surgery.

Erratum: In situ Signature of Cyclotron Resonant Heating in the Solar Wind [Phys. Rev. Lett. 129, 165101 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.

Energy transfer of imbalanced Alfvénic turbulence in the heliosphere.

Imbalanced Alfvénic turbulence is a universal process playing a crucial role in energy transfer in space,  astrophysical, and laboratory plasmas. A fundamental and long-lasting question about the imbalanced Alfvénic turbulence is how and through which mechanism the energy transfers between scales. Here, we show that the energy transfer of imbalanced Alfvénic turbulence is completed by coherent interactions between Alfvén waves and co-propagating anomalous fluctuations.

A prospective radiostereometric analysis of the stability of a metal-backed glenoid component/autograft composite in reverse shoulder arthroplasty.

Aims: Reverse total shoulder arthroplasty (rTSA) can be used in complex cases when the glenoid requires reconstruction. In this study, a baseplate with composite bone autograft and a central trabecular titanium peg was implanted, and its migration was assessed for two years postoperatively using radiostereometric analysis (RSA).

Methods: A total of 14 patients who underwent a rTSA with an autograft consented to participate.

Extracellular Matrix-Derived Damage-Associated Molecular Patterns (DAMP): Implications in Systemic Sclerosis and Fibrosis.

Damage-associated molecular patterns (DAMPs) are intracellular molecules released under cellular stress or recurring tissue injury, which serve as endogenous ligands for toll-like receptors (TLRs). Such DAMPs are either actively secreted by immune cells or passively released into the extracellular environment from damaged cells or generated as alternatively spliced mRNA variants of extracellular matrix (ECM) glycoproteins. When recognized by pattern recognition receptors (PRRs) such as TLRs, DAMPs trigger innate immune responses.

Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis.

Multiorgan fibrosis in systemic sclerosis (SSc) accounts for substantial mortality and lacks effective therapies. Lying at the crossroad of TGF-β and TLR signaling, TGF-β-activated kinase 1 (TAK1) might have a pathogenic role in SSc. We therefore sought to evaluate the TAK1 signaling axis in patients with SSc and to investigate pharmacological TAK1 blockade using a potentially novel drug-like selective TAK1 inhibitor, HS-276.

Interchange reconnection as the source of the fast solar wind within coronal holes.

The fast solar wind that fills the heliosphere originates from deep within regions of open magnetic field on the Sun called 'coronal holes'. The energy source responsible for accelerating the plasma is widely debated; however, there is evidence that it is ultimately magnetic in nature, with candidate mechanisms including wave heating and interchange reconnection. The coronal magnetic field near the solar surface is structured on scales associated with 'supergranulation' convection cells, whereby descending flows create intense fields.

Fusion of the molecular adjuvant C3d to cleavage-independent native-like HIV-1 Env trimers improves the elicited antibody response.

An effective HIV vaccine likely requires the elicitation of neutralizing antibodies (NAbs) against multiple HIV-1 clades. The recently developed cleavage-independent native flexibly linked (NFL) envelope (Env) trimers exhibit well-ordered conformation and elicit autologous tier 2 NAbs in multiple animal models. Here, we investigated whether the fusion of molecular adjuvant C3d to the Env trimers can improve B- cell germinal center (GC) formation and antibody responses.

Survivorship of Allologous Structural Bone Graft at a Minimum of 2 Years When Used to Address Significant Glenoid Bone Loss in Revision Shoulder Arthroplasty: A Computed Tomographic and Clinical Review.

Background: This study assesses outcomes in revision shoulder replacements where the glenoid bone loss was managed using a structural allograft (donated femoral head) in combination with a trabecular titanium (TT) implant.

Methods: We contacted patients who had undergone revision shoulder arthroplasty using the Lima Axioma TT metal-backed glenoid with an allologous bone graft as a composite who were over 2 years since surgery. Patients underwent computerd tomography evaluation, clinical review, and scoring preoperatively, at 6 months and the latest follow-up.

Future Exploration of the Outer Heliosphere and Very Local Interstellar Medium by Interstellar Probe.

A detailed overview of the knowledge gaps in our understanding of the heliospheric interaction with the largely unexplored Very Local Interstellar Medium (VLISM) are provided along with predictions of with the scientific discoveries that await. The new measurements required to make progress in this expanding frontier of space physics are discussed and include in-situ plasma and pick-up ion measurements throughout the heliosheath, direct sampling of the VLISM properties such as elemental and isotopic composition, densities, flows, and temperatures of neutral gas, dust and plasma, and remote energetic neutral atom (ENA) and Lyman-alpha (LYA) imaging from vantage points that can uniquely discern the heliospheric shape and bring new information on the interaction with interstellar hydrogen. The implementation of a pragmatic Interstellar Probe mission with a nominal design life to reach 375 Astronomical Units (au) with likely operation out to 550 au are reported as a result of a 4-year NASA funded mission study.

In Situ Signature of Cyclotron Resonant Heating in the Solar Wind.

The dissipation of magnetized turbulence is an important paradigm for describing heating and energy transfer in astrophysical environments such as the solar corona and wind; however, the specific collisionless processes behind dissipation and heating remain relatively unconstrained by measurements. Remote sensing observations have suggested the presence of strong temperature anisotropy in the solar corona consistent with cyclotron resonant heating. In the solar wind, in situ magnetic field measurements reveal the presence of cyclotron waves, while measured ion velocity distribution functions have hinted at the active presence of cyclotron resonance.

Deficiency of inhibitory TLR4 homolog RP105 exacerbates fibrosis.

Activation of TLR4 by its cognate damage-associated molecular patterns (DAMPs) elicits potent profibrotic effects and myofibroblast activation in systemic sclerosis (SSc), while genetic targeting of TLR4 or its DAMPs in mice accelerates fibrosis resolution. To prevent aberrant DAMP/TLR4 activity, a variety of negative regulators evolved to dampen the magnitude and duration of the signaling. These include radioprotective 105 kDa (RP105), a transmembrane TLR4 homolog that competitively inhibits DAMP recognition of TLR4, blocking TLR4 signaling in immune cells.

Parker Solar Probe Observations of Solar Wind Energetic Proton Beams Produced by Magnetic Reconnection in the Near-Sun Heliospheric Current Sheet.

We report observations of reconnection exhausts in the Heliospheric Current Sheet (HCS) during Parker Solar Probe Encounters 08 and 07, at 16 and 20 , respectively. Heliospheric current sheet (HCS) reconnection accelerated protons to almost twice the solar wind speed and increased the proton core energy by a factor of ∼3, due to the Alfvén speed being comparable to the solar wind flow speed at these near-Sun distances. Furthermore, protons were energized to super-thermal energies.

Gut microbe-derived metabolite trimethylamine N-oxide activates PERK to drive fibrogenic mesenchymal differentiation.

Intestinal dysbiosis is prominent in systemic sclerosis (SSc), but it remains unknown how it contributes to microvascular injury and fibrosis that are hallmarks of this disease. Trimethylamine (TMA) is generated by the gut microbiome and in the host converted by flavin-containing monooxygenase (FMO3) into trimethylamine N-oxide (TMAO), which has been implicated in chronic cardiovascular and metabolic diseases. Using cell culture systems and patient biopsies, we now show that TMAO reprograms skin fibroblasts, vascular endothelial cells, and adipocytic progenitor cells into myofibroblasts via the putative TMAO receptor protein R-like endoplasmic reticulum kinase (PERK).

Assessing the required glenoid peg penetration in native scapula when bone graft is used during primary and revision shoulder arthroplasty.

Aims: Achieving purchase in native glenoid bone is essential for the stability of the glenoid baseplate when bone graft is used to address bone loss in both primary and revision shoulder arthroplasty procedures. The aim of this study is to assess the required depth of the baseplate peg in native bone when bone graft is used to result in satisfactory integration.

Patients And Methods: The CT scans of patients who underwent either primary or revision arthroplasty procedures with bone graft using the SMR Axioma Trabecular Titanium (TT) Metal Backed glenoid system were assessed.

Eugene N. Parker (1927-2022).

Pioneer of theoretical solar and plasma astrophysics.