Context. The Extreme Ultraviolet Imager (EUI) on board the Solar Orbiter (SO) spacecraft observed small extreme ultraviolet (EUV) bursts, termed campfires, that have been proposed to be brightenings near the apexes of low-lying loops in the quiet-Sun atmosphere. The underlying magnetic processes driving these campfires are not understood. Aims. During the cruise phase of SO and at a distance of 0.523 AU from the Sun, the Polarimetric and Helioseismic Imager on Solar Orbiter (SO/PHI) observed a quiet-Sun region jointly with SO/EUI, offering the possibility to investigate the surface magnetic field dynamics underlying campfires at a spatial resolution of about 380 km. Methods. We used co-spatial and co-temporal data of the quiet-Sun network at disc centre acquired with the High Resolution Imager of SO/EUI at 17.4 nm (HRI_EUV, cadence 2 s) and the High Resolution Telescope of SO/PHI at 617.3 nm (HRT, cadence 2.5 min). Campfires that are within the SO/PHI−SO/EUI common field of view were isolated and categorised according to the underlying magnetic activity. Results. In 71% of the 38 isolated events, campfires are confined between bipolar magnetic features, which seem to exhibit signatures of magnetic flux cancellation. The flux cancellation occurs either between the two main footpoints, or between one of the footpoints of the loop housing the campfire and a nearby opposite polarity patch. In one particularly clear-cut case, we detected the emergence of a small-scale magnetic loop in the internetwork followed soon afterwards by a campfire brightening adjacent to the location of the linear polarisation signal in the photosphere, that is to say near where the apex of the emerging loop lays. The rest of the events were observed over small scattered magnetic features, which could not be identified as magnetic footpoints of the campfire hosting loops. Conclusions. The majority of campfires could be driven by magnetic reconnection triggered at the footpoints, similar to the physical processes occurring in the burst-like EUV events discussed in the literature. About a quarter of all analysed campfires, however, are not associated to such magnetic activity in the photosphere, which implies that other heating mechanisms are energising these small-scale EUV brightenings.

Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA–PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively). Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA–PDE5i combination therapy compared with initial monotherapy.

Background: A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in other PAH forms remains uncertain. We present the distribution of mutations across PAH genes identified at the largest German referral centre for genetic diagnostics in PAH over a course of > 3 years. Methods: Our PAH-specific gene diagnostics panel was used to sequence 325 consecutive PAH patients from March 2017 to October 2020. For the first year the panel contained thirteen PAH genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4.These were extended by the three genes ATP13A3, AQP1 and SOX17 from March 2018 onwards following the genes’ discovery. Results: A total of 79 mutations were identified in 74 patients (23%). Of the variants 51 (65%) were located in the gene BMPR2 while the other 28 variants were found in ten further PAH genes. We identified disease-causing variants in the genes AQP1, KCNK3 and SOX17 in families with at least two PAH patients. Mutations were not only detected in patients with heritable and idiopathic but also with associated PAH. Conclusions: Genetic defects were identified in 23% of the patients in a total of 11 PAH genes. This illustrates the benefit of the specific gene panel containing all known PAH genes.

CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-regulated chloride (Cl(-)) channel that plays an important role in salt and fluid movement across epithelia. Cystic fibrosis (CF), the most common genetic disease among Caucasians, is caused by mutations in the gene encoding CFTR. The most predominant mutation, F508del, disturbs CFTR protein trafficking, resulting in a reduced number of CFTR in the plasma membrane. Recent studies indicate that CFTR is not only found in epithelia but also in human erythrocytes. Although considerable attempts have been made to quantify CFTR in cells, conclusions on numbers of CFTR molecules localized in the plasma membrane have been drawn indirectly. AFM has the power to provide the needed information, since both sub-molecular spatial resolution and direct protein recognition via antibody-antigen interaction can be observed. We performed a quantification study of the CFTR copies in erythrocyte membranes at the single molecule level, and compared the difference between healthy donors and CF patients. We detected that the number of CFTR molecules is reduced by 70% in erythrocytes of cystic fibrosis patients.