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OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

Immune responses of the epithelia of the upper respiratory tract are likely crucial in early inhibition of the viral replication and finally clearance of SARS-CoV-2. We aimed to compare the expression profiles of antimicrobial peptides/proteins (AMPs) and related cytokines observed in the nasopharynx of SARS-CoV-2-infected patients and non-infected controls and to assess the associations between these parameters and COVID-19 patients' outcomes. We included 45 subjects who had tested positive for SARS-CoV-2 and 22 control subjects who had tested negative for SARS-CoV-2. Biomaterial for SARS-CoV-2 detection, as well as gene and protein expression studies, was obtained from all subjects using nasopharyngeal swabs which were performed a maximum of 7 days before inclusion in the study. Univariable and multivariable statistics were performed. When compared to the controls, the mRNA expression levels of human β-defensin 1 (hBD-1), LL-37, and trappin-2 were significantly higher in specimens of nasopharyngeal swabs from COVID-19 patients. Protein expression of hBD-1 was also increased in the COVID-19 group. mRNA expression levels of interferon-ɣ (IFN-ɣ), tumor necrosis factor- ɑ (TNF-ɑ), and interleukin-6 (IL-6) measured in SARS-CoV-2-infected patients were significantly higher than those observed in the controls, which could also be confirmed in the protein levels of IFN-ɣ and IL-6. A significant correlation between mRNA and protein levels could be observed only for IL-6. Univariable analysis revealed that low IFN-ɣ mRNA levels were associated with severe/fatal outcomes. The occurrence of COVID-19 pneumonia was significantly associated with lower expression levels of IL-6 mRNA, IFN-ɣ mRNA, and TNF-ɑ mRNA. Concerning the severe/fatal outcomes, the multivariable logistic regression model revealed that none of the aforementioned parameters remained significant in the model. However, the logistic regression model revealed that higher TNF-ɑ mRNA expression was a significant independent predictor of absence of pneumonia [odds ratio: 0.35 (95% CI 0.14 to 0.88, p = 0.024)]. In conclusion, nasopharyngeal expression of AMPs (hBD-1, LL-37, and trappin-2) and cytokines (IL-6, IFN-ɣ, and TNF-ɑ) is upregulated in response to early SARS-CoV-2 infection, indicating that these AMPs and cytokines play a role in the local host defense against the virus. Upregulated nasopharyngeal TNF-ɑ mRNA expression during the early phase of SARS-CoV-2 infection was a significant independent predictor of the absence of COVID-19 pneumonia. Hence, high TNF-ɑ mRNA expression in the nasopharynx appears to be a protective factor for lung complications in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Rheumatologists are increasingly utilizing ultrasound for suspected giant cell arteritis (GCA) or Takayasu arteritis (TAK). This enables direct confirmation of a suspected diagnosis within the examination room without further referrals. Rheumatologists can ask additional questions and explain findings to their patients while performing ultrasound, preferably in fast-track clinics to prevent vision loss. Vascular ultrasound for suspected vasculitis was recently integrated into rheumatology training in Germany. New European Alliance of Associations for Rheumatology recommendations prioritize ultrasound as the first imaging tool for suspected GCA and recommend it as an imaging option for suspected TAK alongside magnetic resonance imaging, positron emission tomography and computed tomography. Ultrasound is integral to the new classification criteria for GCA and TAK. Diagnosis is based on consistent clinical and ultrasound findings. Inconclusive cases require histology or additional imaging tests. Robust evidence establishes high sensitivities and specificities for ultrasound. Reliability is good among experts. Ultrasound reveals a characteristic non-compressible 'halo sign' indicating intima-media thickening (IMT) and, in acute disease, artery wall oedema. Ultrasound can further identify stenoses, occlusions and aneurysms, and IMT can be measured. In suspected GCA, ultrasound should include at least the temporal and axillary arteries bilaterally. Nearly all other arteries are accessible except the descending thoracic aorta. TAK mostly involves the common carotid and subclavian arteries. Ultrasound detects subclinical GCA in over 20% of polymyalgia rheumatica (PMR) patients without GCA symptoms. Patients with silent GCA should be treated as GCA because they experience more relapses and require higher glucocorticoid doses than PMR patients without GCA. Scores based on intima-thickness (IMT) of temporal and axillary arteries aid follow-up of GCA, particularly in trials. The IMT decreases more rapidly in temporal than in axillary arteries. Ascending aorta ultrasound helps monitor patients with extracranial GCA for the development of aneurysms. Experienced sonologists can easily identify pitfalls, which will be addressed in this article. Plain language summary: Diagnosing vasculitis with ultrasound Rheumatologists use ultrasound to diagnose two types of blood vessel inflammation: giant cell arteritis (GCA) or Takayasu arteritis (TAK). They can do this right in their office during the examination, without sending patients elsewhere. During the ultrasound, rheumatologists can talk with patients about what they see. This is especially helpful in fast-track clinics to prevent vision loss. In Germany, doctors training to become rheumatologists learn how to use ultrasound to check for problems like these. An organization called 'European Alliance of Associations for Rheumatology (EULAR)' recommends using ultrasound as the main way to look for GCA and, if needed, for TAK. Ultrasound is also an important part of the new classification criteria for GCA and TAK. However, doctors do not rely on ultrasound alone. They also look what patients are feeling and do other medical tests. If ultrasound is not clear enough, doctors might need to do more tests like taking a small piece of tissue (biopsy) or using other kinds of imaging like MRI or CT scans. Ultrasound can show some characteristic signs of blood vessel inflammation, like a 'halo sign,' which tells doctors that the blood vessel walls are thicker than normal. It can also spot other problems like blockages or bulges in the blood vessels. When doctors suspect GCA, they should at least examine the arteries at the forehead and at the armpit. Most of the time, these areas are easy to see with ultrasound, but some areas might be harder to reach. Sometimes, people can have blood vessel inflammation without feeling any typical symptoms. Ultrasound can still find this silent inflammation in more than 20% of people with a condition called polymyalgia rheumatica (PMR). Even though these patients do not have typical symptoms of GCA, it is important to treat them the same way as those with GCA. Otherwise, they may have more flare-ups and need higher doses of glucocorticoids. Doctors may measure the thickness of the artery walls over time in research studies. This helps them to see if treatments are working well. The wall thickness decreases faster in arteries of the head than in larger arteries outside the head. Ultrasound of the aorta close to heart helps to find out if a widening of the aorta develops. This can be dangerous because of rupture. [ABSTRACT FROM AUTHOR]

Crispr/CAS9‐enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context‐dependent promoter activity that complicate analysis of gene expression and protein accumulation patterns. However, there have been few reports examining whether such gene targeting/gene tagging (GT) can alter expression of the target gene. The enzyme encoded by Δ1‐pyrroline‐5‐carboxylate synthetase 1 (P5CS1) is key for stress‐induced proline synthesis and drought resistance, yet its expression pattern and protein localisation have been difficult to assay. We used GT to insert YFP in frame with the 5′ or 3′ ends of the endogenous P5CS1 and At14a‐Like 1 (AFL1) coding regions. Insertion at the 3′ end of either gene generated homozygous lines with expression of the gene‐YFP fusion indistinguishable from the wild type allele. However, for P5CS1 this occurred only after selfing and advancement to the T5 generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT‐generated P5CS1‐YFP plants revealed new information about P5CS1 localisation and tissue‐specific expression. In contrast, insertion of YFP at the 5′ end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene. Summary statement: Gene tagging (GT) of Arabidopsis thaliana P5CS1 and AFL1 shows the potential of GT for functional analysis of stress‐related genes, but also provides examples of how GT can dramatically disrupt expression of the target gene. [ABSTRACT FROM AUTHOR]

Climate change effects on tree reproduction are poorly understood, even though the resilience of populations relies on sufficient regeneration to balance increasing rates of mortality. Forest‐forming tree species often mast, i.e. reproduce through synchronised year‐to‐year variation in seed production, which improves pollination and reduces seed predation. Recent observations in European beech show, however, that current climate change can dampen interannual variation and synchrony of seed production and that this masting breakdown drastically reduces the viability of seed crops. Importantly, it is unclear under which conditions masting breakdown occurs and how widespread breakdown is in this pan‐European species. Here, we analysed 50 long‐term datasets of population‐level seed production, sampled across the distribution of European beech, and identified increasing summer temperatures as the general driver of masting breakdown. Specifically, increases in site‐specific mean maximum temperatures during June and July were observed across most of the species range, while the interannual variability of population‐level seed production (CVp) decreased. The declines in CVp were greatest, where temperatures increased most rapidly. Additionally, the occurrence of crop failures and low seed years has decreased during the last four decades, signalling altered starvation effects of masting on seed predators. Notably, CVp did not vary among sites according to site mean summer temperature. Instead, masting breakdown occurs in response to warming local temperatures (i.e. increasing relative temperatures), such that the risk is not restricted to populations growing in warm average conditions. As lowered CVp can reduce viable seed production despite the overall increase in seed count, our results warn that a covert mechanism is underway that may hinder the regeneration potential of European beech under climate change, with great potential to alter forest functioning and community dynamics. [ABSTRACT FROM AUTHOR]

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5–8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid—the spin supersolid—in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.Evidence for a quantum magnetic analogue of a supersolid appears in a recently synthesized antiferromagnet showing a strong magnetocaloric effect of the spin supersolid phase with potential for applications in sub-kelvin refrigeration. [ABSTRACT FROM AUTHOR]

This article presents a case study of a patient with severe hidradenitis suppurativa (HS) who developed secondary haemophagocytic lymphohistiocytosis (HLH) caused by varicella zoster virus (VZV) infection following treatment with upadacitinib. The patient experienced a severe reaction to the VZV infection, including polymorphous exanthema, sepsis, pneumonia, and generalized seizures. The diagnosis of secondary HLH associated with VZV infection was made based on clinical and laboratory findings. The patient was treated with antiviral therapy, immunoglobulins, and glucocorticoids, and underwent radical resection of HS lesions. The article highlights the potential risk of severe adverse events, such as VZV infection and HLH, in patients receiving upadacitinib treatment and emphasizes the importance of close monitoring for herpes zoster complications in these patients. [Extracted from the article]

Objective: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR)., Methods: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated., Results: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care., Conclusions: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR., Competing Interests: Competing interests: KKK: Research grants from Independent Research Fund Denmark, Danish Rheumatic Association and Central Denmark Region unrelated to this project. SES: Research grants from Rheumatology Research Foundation, Bristol Myers Squibb Foundation. Clinical trial support from AstraZeneca, GlaxoSmithKline; Consulting fees from Sanofi (funds toward research support); Data Safety Monitoring Board on MINT trial, Advisory Board for Sanofi (funds toward research support). E-MH: Has received grants unrelated to this manuscript from Novo Nordic Foundation, Roche, Novartis; Personal fees from AbbVie, Sanofi, SOBI, Merck Sharp & Dohme and Union Chimique Belge. AD: Consulting fees from Sanofi; Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi; Board member Vasculitis Foundation. LN: Has received Honorarium from Abbvie; Trustee of the charity PMR-GCA Scotland. SM: Consulting fees from Astrazeneca; Honoraria from Vifor. KJW: Grants from Eli Lilly, Kiniksa, BMS; Consulting fees from Amgen, Sanofi. Honoraria from Amgen. CP: Consulting fee from Pfizer. MP: Consulting fee from Novartis; Clinical trial participant for Abbvie, Amgen, AstraZeneca. HIK: Honoraria from Roche, eTherapeutic Guidelines Australia; Board member Australian Rheumatology Association; Clinical trials for Roche, Abbvie, Sun, Emerald, Novartis, Biogen, Sanofi, Syneos. CEO: Consultancy for Abbvie; Speaking honoraria from Abbvie, Janssen, Novartis and Roche; Advisory board for Abbvie. WAS: Has received honoraria from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi ; Support for attending meetings/travel from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi; Participated in advisory board from Abbvie, GlaxoSmithKline, Novartis, Sanofi; Principle investigator of phases 2 and 3 studies sponsored by Abbvie, GlaxoSmithKlinie, Novartis and Sanofi. EBrouwer: As an employee of the UMCG received a speaker fee for a talk on GCA at a post EULAR symposium in the Netherlands in 2023 which was paid to the UMCG; As an employee of the UMCG received grants from the Dutch Arthritis Society DAS and the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking Immune-Image grant no 831514 which were paid to the UMCG. SM: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SM is supported in part by the NIHR Leeds Biomedical Research Centre. VD-P has received honorarium from Abbvie, Chugai, Novartis, BMS, Support for attending meetings/travel from Novartis; Participated in advisory borad from Abbvie, Novartis. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Biological nitrogen fixation is a fundamental part of ecosystem functioning. Anthropogenic nitrogen deposition and climate change may, however, limit the competitive advantage of nitrogen-fixing plants, leading to reduced relative diversity of nitrogen-fixing plants. Yet, assessments of changes of nitrogen-fixing plant long-term community diversity are rare. Here, we examine temporal trends in the diversity of nitrogen-fixing plants and their relationships with anthropogenic nitrogen deposition while accounting for changes in temperature and aridity. We used forest-floor vegetation resurveys of temperate forests in Europe and the United States spanning multiple decades. Nitrogen-fixer richness declined as nitrogen deposition increased over time but did not respond to changes in climate. Phylogenetic diversity also declined, as distinct lineages of N-fixers were lost between surveys, but the "winners" and "losers" among nitrogen-fixing lineages varied among study sites, suggesting that losses are context dependent. Anthropogenic nitrogen deposition reduces nitrogen-fixing plant diversity in ways that may strongly affect natural nitrogen fixation.

Climate change is commonly assumed to induce species' range shifts toward the poles. Yet, other environmental changes may affect the geographical distribution of species in unexpected ways. Here, we quantify multidecadal shifts in the distribution of European forest plants and link these shifts to key drivers of forest biodiversity change: climate change, atmospheric deposition (nitrogen and sulfur), and forest canopy dynamics. Surprisingly, westward distribution shifts were 2.6 times more likely than northward ones. Not climate change, but nitrogen-mediated colonization events, possibly facilitated by the recovery from past acidifying deposition, best explain westward movements. Biodiversity redistribution patterns appear complex and are more likely driven by the interplay among several environmental changes than due to the exclusive effects of climate change alone.

Currently, only 25% of all polymyalgia rheumatica (PMR) patients are referred to specialists. An expert committee has recently recommended confirmation of diagnosis by specialist care. This can help to avoid misdiagnoses and hospital stays and can result in lower glucocorticoid doses.Using ultrasound, magnetic resonance imagining (MRI), or positron emission tomography-computed tomography (PET-CT), typical periarticular inflammatory changes are observed, especially in the shoulder and pelvic girdle area. However, for clinical use, ultrasound is usually sufficient.In 20-25% of newly diagnosed PMR patients without symptoms of giant cell arteritis (GCA), GCA can be detected through vascular ultrasound. These patients require higher glucocorticoid doses in analogy to GCA therapy. There is growing awareness of a joint GCA-PMR spectrum disease.Glucocorticoids remain the primary treatment. The interleukin-6 inhibitor Sarilumab has recently been approved in the USA for patients with recurrent PMR. Studies have also demonstrated the effectiveness of Tocilizumab in PMR., Competing Interests: Berater von Abbvie, Amgen, Bristol Myers Squibb, Chugai, Fresenius Kabi, GlaxoSmithKline, Novartis, Sanofi; Vortragshonorare von Abbvie, Amgen, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Lilly, Johnson & Johnson, Medac, Novartis, Pfizer, Roche, Sanofi, UCB. Forschungsgelder für Arbeitgeber als Principal Investigator in Studien, gesponsert durch Abbvie, GlaxoSmithKline, Novartis, and Sanofi., (Thieme. All rights reserved.)

Clinical guidelines for COPD and asthma recommend inhaled β-adrenergic agonists, muscarinic antagonists, and, for frequent exacerbators, inhaled corticosteroids, with the challenge of combining them into a single device. The MABA (muscarinic antagonist and β 2 agonist) concept has the potential to simplify this complexity while increasing the efficacy of both pharmacologies. In this article, we report the outcome of our solid-state driven back-up program that led to the discovery of the MABA compound CHF-6550 . A soft drug approach was applied, aiming at high plasma protein binding and high hepatic clearance, concurrently with an early stage assessment of crystallinity through a dedicated experimental workflow. A new chemotype was identified, the diphenyl hydroxyacetic esters, able to generate crystalline material. Among this class, CHF-6550 demonstrated in vivo efficacy, suitability for dry powder inhaler development, favorable pharmacokinetics, and safety in preclinical settings and was selected as a back-up candidate, fulfilling the desired pharmacological and solid-state profile.

Objectives: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV)., Methods: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes., Results: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation., Conclusions: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV., Competing Interests: Competing interests: CDejaco has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow and Sanofi; grant support from AbbVie and Novartis, all unrelated to this manuscript. He is an editorial board member of ARD. SR has received research grants and/or consultancy fees From AbbVie, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sanofi, UCB. MB: consultancy fees from AbbVie PB has received speaker fees by Janssen and project grants by Pfizer. CP has received research grants and/or consultancy fees from AbbVie, Vifor, Roche, GlaxoSmithKline and AstraZeneca, all unrelated to this manuscript. SLM reports: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer and Novartis; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SLM is supported in part by the NIHR Leeds Biomedical Research Centre. TAB reports research grants from Deutsche Forschungsgemeinschaft (DFG) and Siemens Healthineers on behalf of his Department. He has received consulting/speaker’s fees from BioTel Research, Chugai, Guerbet, Novartis, Roche, Sanofi and Siemens Healthineers. DB consultancy fees from Roche and GSKSara Brolin: Grant from Novartis. MCC has received consulting fees from GSK, SCL-Vifor, AbbVie, AstraZeneca and Janssen, and a research grant form Kiniksa Pharmaceuticals. JM-C has received consulting/speaker’s fees from Abbvie, Lilly, Janssen, Novartis, Pfizer, UCB, MSD, all unrelated to this manuscript. BD has received consultancies and educational grants from Novartis, Abbvie, Roche, Chugai, Sanofi. BDN has received consulting/speaker’s fees from Roche and Novartis all unrelated to this manuscript. EDM Research funding/consulting and conferences fees from: Abbvie, Novartis, Pfizer, Roche, Janssen, Lilly, MSD, BMS, UCB, Grunental and Sanofi. CDuftner has received consulting/speaker’s fees from Abbvie, AOP Orphan, Astra-Zeneca, Bristol-Myers-Squibb, Eli-Lilly, Janssen, Galapagos, Merck-Sharp-Dohme, Novartis, Pfizer, Roche, Sandoz, UCB, Vifor, and grant/research support from Eli-Lilly, Pfizer, UCBHaner Direskeneli is investigator in clinical trials for Abbvie and Novartis, had educational support from Pfizer, Amgene, Celltrion, UCB and Roche unrelated to this manuscript. AM has received research grants and/or consultancy fees From AbbVie, BMS, Biogen, Eli Lilly, Galapagos, Janssen, MSD, Novartis and UCB. LS has received grant support from the Swiss Society of Rheumatology, iQone and Sandoz and support for travel expenses from Sanofi; all unrelated to this manuscript. RHJAS has received independent research grants of Siemens Healtineers and WAS has received consultancy fees, honoraria and travel expenses from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, and Sanofi and is principal investigator in trials sponsored by Abbvie, GlaxoSmithKline, Novartis and Sanofi., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Global change has accelerated local species extinctions and colonizations, often resulting in losses and gains of evolutionary lineages with unique features. Do these losses and gains occur randomly across the phylogeny? We quantified: temporal changes in plant phylogenetic diversity (PD); and the phylogenetic relatedness (PR) of lost and gained species in 2672 semi-permanent vegetation plots in European temperate forest understories resurveyed over an average period of 40 yr. Controlling for differences in species richness, PD increased slightly over time and across plots. Moreover, lost species within plots exhibited a higher degree of PR than gained species. This implies that gained species originated from a more diverse set of evolutionary lineages than lost species. Certain lineages also lost and gained more species than expected by chance, with Ericaceae, Fabaceae, and Orchidaceae experiencing losses and Amaranthaceae, Cyperaceae, and Rosaceae showing gains. Species losses and gains displayed no significant phylogenetic signal in response to changes in macroclimatic conditions and nitrogen deposition. As anthropogenic global change intensifies, temperate forest understories experience losses and gains in specific phylogenetic branches and ecological strategies, while the overall mean PD remains relatively stable., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

Plant communities are being exposed to changing environmental conditions all around the globe, leading to alterations in plant diversity, community composition, and ecosystem functioning. For herbaceous understorey communities in temperate forests, responses to global change are postulated to be complex, due to the presence of a tree layer that modulates understorey responses to external pressures such as climate change and changes in atmospheric nitrogen deposition rates. Multiple investigative approaches have been put forward as tools to detect, quantify and predict understorey responses to these global-change drivers, including, among others, distributed resurvey studies and manipulative experiments. These investigative approaches are generally designed and reported upon in isolation, while integration across investigative approaches is rarely considered. In this study, we integrate three investigative approaches (two complementary resurvey approaches and one experimental approach) to investigate how climate warming and changes in nitrogen deposition affect the functional composition of the understorey and how functional responses in the understorey are modulated by canopy disturbance, that is, changes in overstorey canopy openness over time. Our resurvey data reveal that most changes in understorey functional characteristics represent responses to changes in canopy openness with shifts in macroclimate temperature and aerial nitrogen deposition playing secondary roles. Contrary to expectations, we found little evidence that these drivers interact. In addition, experimental findings deviated from the observational findings, suggesting that the forces driving understorey change at the regional scale differ from those driving change at the forest floor (i.e., the experimental treatments). Our study demonstrates that different approaches need to be integrated to acquire a full picture of how understorey communities respond to global change., (© 2023 John Wiley & Sons Ltd.)

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5μm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly)., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)